Measurement-Device-Independent Quantum Key Distribution (MDI-QKD) is a two-photon protocol devised to eliminate eavesdropping attacks that interrogate or control the detector in realized quantum key distribution systems. In MDI-QKD, the measurements are carried out by an untrusted third party, and the measurement results are announced openly. Knowledge or control of the measurement results gives the third party no information about the secret key. Error-free implementation of the MDI-QKD protocol requires the crypto-communicating parties, Alice and Bob, to independently prepare and transmit single photons that are physically indistinguishable, with the possible exception of their polarization states. In this paper, we apply the formalism of quantum optics and Monte Carlo simulations to quantify the impact of small errors in wavelength, bandwidth, polarization and timing between Alice's photons and Bob's photons on the MDI-QKD quantum bit error rate (QBER). Using published single-photon source characteristics from two-photon interference experiments as a test case, our simulations predict that the finite tolerances of these sources contribute (4.04+/-20/N_sifted) to the QBER in an MDI-QKD implementation generating an N_sifted-bit sifted key.

In this work, we derive the spectral efficiency, secrecy outage probability, and bit error rate of a communication system assisted by a large intelligent surface (LIS). We consider a single-antenna user and an array of antennas at the transmitter side and the possibility of a direct link between transmitter and receiver. Additionally, there is a single-antenna eavesdropper with a direct link to the transmitter, which is modeled as a Nakagami-m distributed fading coefficient. The channels from transmitter to the LIS and from the LIS to the user may or may not have the line-of-sight (LoS) and are modeled by the Nakagami- m distribution. Moreover, we assume that the LIS elements perform non-ideal phase cancellation leading to a residual phase error that assumes a Von Mises distribution. We show that the resulting channel can be accurately approximated by a Gamma distribution whose parameters are analytically estimated using the moments of the equivalent signal-to-noise ratio. We also provide an upper bound for the error probability for M-QAM modulations. With the derived formulas, we analyze the effect of the strength of the LoS link by varying the Nakagami parameter, m.

This paper deals with experimental study of the influence of conductive (Fe₃O₄) and insulating (Al₂O₃) nanostructured particles at various concentrations on the dielectric strength of transformer mineral oil. The method of preparation and characterization of these nanofluids (NFs) through the measurements of zeta potential, the real and imaginary parts of dielectric constant as well as the concentration and size of nanoparticles using Scanning Electron Microscope (SEM) images of nanoparticles powders and Dispersive x-ray Spectroscopy (EDS) analysis are presented. Experimental findings reveal that these two types of nanoparticles materials significantly improve AC breakdown voltage and the magnitude of this improvement depends on the concentration, size and nature (material) of nanoparticles. For a given type of nanoparticles, the effect is more marked with the smallest nanoparticles. The conductive nanoparticles offer higher enhancement of dielectric strength compared with insulating nanoparticles based nanofluids. With Fe₃O₄, the breakdown voltage (BDV) can exceed twice that of mineral oil and it increases by more than 76% with Al₂O₃. The physicochemical mechanisms implicated in this improvement are discussed.

In this paper, we study the symmetry between the supersingular prime number according to smallest sphenic number. With this symmetry, we show that the elements of sporadic group generates all prime numbers with the order by a simple application.

Despite the continued growth of the sport, particularly among recreational athletes, very little is known about how triathletes prepare for an event. The aim of this study was to identify the training characteristics of recreational-level triathletes and assess how their preparation for a triathlon influences their health and fatigue. During the 6 weeks prior to an Olympic distance triathlon, and the 2 weeks after the event, ten (5 males, 5 females) recreational athletes completed a daily training log to provide information on every training session. In addition, participants answered the Daily Analysis of Life Demands Questionnaire (DALDA), the Training Distress Scale (TDS), and the Alberta Swim Health Questionnaire weekly. Training loads were calculated using session-based rating of perceived exertion (sRPE) and training impulse (TRIMP). Every week of training was compared to week 1 to determine how athletes’ training and health changed throughout the study. In the 6 weeks leading up to the event, training loads, total minutes trained, and time spent in each training zone did not differ significantly. Significant reductions in training duration (Z=2.39, p=0.017, ES = 0.90), training strain (Z=2.59, p=0.009, 0.98), and number of sessions (Z=2.49, p=0.012, ES = 0.94) were seen on week 6. Training intensity distribution favored a threshold approach with athletes spending 56% of their training time at zone 1, 40% at zone 2, and 4% at zone 3. No significant changes were seen in the DALDA or TDS questionnaires. The results show that while the training intensity distribution of recreational-level triathletes does not follow a polarized model, these athletes were able to maintain their health while preparing for an Olympic distance triathlon.

A descriptive epidemiological study has been conducted using hospital database of Teaching Veterinary Hospital (TVH) at Jhenaidah Government Veterinary College (JGVC) from July 2018 to June 2019. The study aimed to estimate the proportionate prevalence of different livestock and poultry diseases along with their spatiotemporal distribution and drug prescribing pattern. A total of 960 clinical cases were recorded during the study period. Ectoparasitic cases were proportionately higher in cattle (25.2%), whereas Peste des Petits Ruminants (PPR) cases were more frequent in goat (53.4%). The proportionate prevalence of other cases in cattle was Fascioliasis (14.3%), Myiasis (11.2%) and Foot and Mouth Disease (FMD) (7.2%). The proportionate prevalence of other cases in goats were vitamin and mineral deficiency (12.3%), bloat (5.2%), abscess (4.7%), and dog bite (1.2%). Again, the proportionate prevalence of poultry diseases was Infectious Bursal Disease (41.2%), salmonellosis (33.4%), fowl cholera (13.7%) and pox (7.8%). Most of the cattle cases were highly prevalent during the summer season except fascioliasis. In goat, PPR was predominated in the rainy season whereas myiasis was in the winter. Around 92% of disease cases were spatially located within the 2.5 km radius of the TVH of JGVC where only 0.9% of disease cases came from >10km away from TVH of JGVC. Simple linear regression identified a significant relation (p=0.01) with the distance and number of diseased animals came to the hospital. Antimicrobials belonging to b-Lactam group were most frequently prescribed for both poultry (48.6%), cattle (32.5%) followed by goat (9.2%), however sulfar drugs (34.8%) were commonly prescribed for goat cases. This type of study is very novel in Jhenaidah region of Bangladesh that might contribute to the researchers for further investigation.

This paper presents the results of hot smoke tests, conducted in a real road tunnel. The tunnel is located within the expressway S69 in southern Poland between cities Żywiec and Zwardoń. Its common name is Laliki tunnel. It is a bi-directional non-urban tunnel. The length of the tunnel is 678 m and it is inclined by 4%. It is equipped with the longitudinal ventilation system. Two hot smoke tests have been carried out according to Australian Standard AS 4391-1999. Hot smoke tests corresponded to a HRR (Heat Release Rate) equal to respectively 750 kW and 1500 kW. The fire source was located in the middle of the road lane imitating an initial phase of a car fire (respectively 150 m and 265 m from S portal). The temperature distribution was recorded during both tests using a set of fourteen thermocouples mounted at two stand poles located at the main axis of the tunnel on windward. The stand poles were placed at distances of 5 m and 10 m. The recorded data were applied to validate of a numerical model built and solved using Ansys Fluent. The calculated temperature distribution matched the measured values.

Long non-coding RNA (lncRNA) aberrant expression have been found in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped in transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated in pediatric ALL and uc.112 expression was higher in T-ALL compared to patients with B-ALL and in patients with hyperdiploid karyotype. These findings suggest a potential role of this uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

The management of existing water distribution system (WDS) is challenged by ageing of infrastructure, population growth, increasing of urbanization, climate change impacts and environmental pollution. Therefore, there is a need for integrated solutions that support decision makers to plan today, while taking into account the effect of these factors in the mid and long term. The paper is part of a more comprehensive project, where advanced hydraulic analysis for WDS is coupled with a dynamic resources input-output analysis model. The proposed modeling solution can be used to optimize the performance of a water supply system while considering also the energy consumption and consequently the environmental impacts. Therefore, as a support tool in the management of a water supply system also in the intervention planning. Here a possible application is presented for rehabilitation/replacement planning while maximizing the network mechanical reliability and minimizing risk of unsupplied demand and pressure deficit, under given economic constraints.

Many systems in nature and laboratories are far from equilibrium and exhibit significant fluc- tuations, invalidating the key assumptions of small fluctuations and short memory time in or near equilibrium. A full knowledge of Probability Distribution Functions (PDFs), especially time- dependent PDFs, becomes essential in understanding far-from-equilibrium processes. We consider a stochastic logistic model with multiplicative noise, which has gamma distributions as stationary PDFs. We numerically solve the transient relaxation problem, and show that as the strength of the stochastic noise increases the time-dependent PDFs increasingly deviate from gamma distributions. For sufficiently strong noise a transition occurs whereby the PDF never reaches a stationary state, but instead forms a peak that becomes ever more narrowly concentrated at the origin. The addition of an arbitrarily small amount of additive noise regularizes these solutions, and re-establishes the existence of stationary solutions. In addition to diagnostic quantities such as mean value, standard deviation, skewness and kurtosis, the transitions between different solutions are analyzed in terms of entropy and information length, the total number of statistically distinguishable states that a system passes through in time.

A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds (3a-3i) exhibited significant clot lysis with respect to negative control and reference drug streptokinase (30,000 IU) while enhanced clotting time (CT) values were observed (130-342 sec) for these tested compounds than the standard drug heparin (110 sec.). High affinity towards 1NFY with greater docking score was observed for the compounds (3a, 3i, 3e, 3d and 3h) than the control ligand RPR200095. In addition, very good inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612-6270) with ACE values (–189.68 to –352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE –197.81 kcal/mol. In vitro, in vivo and in silico results proposed that these newly synthesized compounds can be used as anti-coagulant agents.

This paper introduces an approach that chooses the fault detection by calculating probabilities using probability mass function (pmf) and cumulative distribution function (CDF). This work used a method for multiple stuck-at faults by producing a new test pattern in combinational circuits. We assumed that existence of all multiple faults is only because of one single component that is faulty. A complete test set can be created by all possible single stuck-at faults in a combinational circuit using some combination of gates. The test set generation fault detection method is applied on two different 3-bit input variable and 4-bit input variable circuits. The probability of error occurrence is calculated at both 3-bit and 4-bit input variable circuits. The resulting feature is used to obtain maximum error occurrence probability to detect faults by the logic used that the complexity of the circuit is inversely proportional to the fault occurrence probability. Then again, undetectability is directly proportional to the complexity of the circuit. Therefore, finest feasible circuit should have large input variable components with less complexity to reduce the fault occurrence probability.

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

The world is now undergoing through a global emergency due to COVID-19 which needs immediate remedies in order to strengthen the healthcare facility to save the nations. Looking towards to the remedies, research on different aspects including the genomic and proteomic level characterizations of the SARS-CoV2 are necessarily important. In this present study, the spatial representation/composition of twenty amino acids across the primary protein sequences of SARS-CoV2 have been looked into through different parameters viz. Shannon entropy, Hurst exponent in order to fetch the autocorrelation and amount of information over the spatial representations. Also frequency distribution of each of the amino acids over the protein sequences have been chalked out.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

Multiple Myeloma (MM) is one of the incurable types of cancer in plasma cells. While immense progress has been made in the treatment of this malignancy, a large percentage of patients were unable to adapt to such therapy. Additionally, these therapies might be associated with significant diseases and are not always tolerated well in all patients. Since cancer in plasma cells has no cure, patients develop resistance to treatments, resulting in R/R MM. BCMA is primarily produced on mature B cells. Its up-regulation and activation are associated with multiple myeloma in both murine and human models, indicating that this might be an effective therapeutic target for this type of malignancy. Additionally, BCMA's predictive value, association with effective clinical trials, and capacity to be utilized in previously difficult to observe patient populations, imply that it might be used as a biomarker for multiple myeloma. Numerous kinds of BCMA-targeting medicines have demonstrated antimyeloma efficacy in individuals with refractory/relapsed MM, including CAR T-cell treatments, ADCs, bispecific antibody constructs. Among these medications, CART cell-mediated BCMA therapy has shown significant outcomes in multiple myeloma clinical trials. This review article outlines CAR T cell mediated BCMA medicines have the efficiency to change the therapeutic pattern for multiple myeloma significantly.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

A Wireless Body Area Sensor Network (WBASN) is combination of numerous sense nodes, positioned onto/close or inside a person body. Wireless Body Area Sensor Networks (WBASN) is a developing automation trend that exploits wireless sensor nodes to put instantaneous wearable well-being of ill person to improve individual’s existence. The sensor nodes might be used outwardly to observe abundant health parameters (like heart activity, blood pressure and cholesterol) of an ill person at a vital site within hospital. Hence the goal of WBASN is much crucial, enhancing the lifetime of nodes is compulsory to sustain many issues such as utility and efficiency. It is essential to evaluate time that when the first node will die it we want to refresh or change the battery reason is that loss of crucial information is not tolerable. The lifetime is termed as the time interval when a first node dies out due to battery exhaustion. In our proposed protocol life time of a network is the main concern as well other protocol related issues such as throughput, path loss, and residual energy. Bio-sensors are used for deployment on human body. Poisson distribution and equilibrium model techniques have been used for attaining the required results. Multi-hop network topology and random network node deployment used to achieve minimum energy consumption and longer network lifetime.

This article evaluates the macroeconomic implications of commercial bank seigniorage, which emerges from the commercial banks’ power to create money in a fractional reserves regime. After evaluating the impact on aggregate output of commercial bank money relative to alternative exchange arrangements, the article identifies the determinants of commercial bank seigniorage and analyzes how equilibrium prices are determined in an economy where commercial banks extract seigniorage. The article also identifies the conditions under which commercial banks extract seigniorage, clarifies the relationship between seigniorage from commercial bank money creation and profits from pure financial intermediation, and shows how commercial bank seigniorage changes with different types of interbank payments settlement.

Electric power systems are experiencing relevant changes involving the growing penetration of distributed generation and energy storage systems, the introduction of electric vehicles, the management of responsive loads, the proposals for new energy markets and so on. Such evolution is pushing for a paradigm shift: the management must move from traditional planning and manual intervention to full “smartization” of medium and low voltage networks. Peculiarities and criticalities of future power distribution networks originate from the complexity of the system that includes both the physical aspects of electric networks and the cyber aspects, like data elaboration, feature extraction, communication, supervision and control; only fully integrated advanced monitoring systems can foster this transition towards network automation. The design and development of such future networks require distinct kinds of expertise in the industrial and information engineering fields. In this context, this paper provides a comprehensive review of current challenges and multidisciplinary interactions in the development of smart distribution networks.

Linear state estimation (SE) formulation under a rectangular coordinate system has been proved to be applicable for real-time distribution network management. Micro phasor measurements’ model can be accommodated into this kind of SE easily. However, voltage magnitude, active power and reactive power measurements are transformed to linear measurements with large node voltage error. To cope with this issue, a linear state estimation under a polar coordinate system is adopted at the first stage to obtain accurate enough complex node voltage, and then nonlinear measurements are transformed to be linear with complex node voltage. At the second stage, linear SE under a rectangular coordinate system can be adopted to satisfy more strict network constraints. The proposed two-stage linear SE is validated on balanced 14, 33, 70,84, 119, 135 nodes network and IEEE 13, 34, 37,123 unbalanced test feeders.

Based on the cloud platform of Google Earth Engine (GEE), this study selected Landsat 5/8 and Sentinel-2 remote sensing images and used Support Vector Machine (SVM) classification method to classify the 35 years of intertidal salt marshes in China, and verified the classification results in combination with field survey. Finally, combining with various driving factors, the reasons and laws affecting the changes of salt marshes species and area were discussed and analyzed. The main results of the study are as follows:The main types of salt marshes plants in China include Phragmites australis, Spartina alterniflora, Suaeda salsa, Scirpus mariquete, Tamarix chinensis, Cyperus malaccensis and Sesuvium portulacastrum. The results salt marshes classification indicated that 166999.32 ha in 1985, 172893.87 ha in 1990, 174952.29 ha in 1995, 125567.51 ha in 2000, 93257.97 ha in 2005, 102539.04 ha in 2010, 96302.92 ha in 2015, and 115722.75 ha in 2019. The main driving factors of salt marsh change from 1985 to 2015 are reclamation, mudflat aquaculture, climate change, coastal zone erosion, invasion of alien species, and natural competition and succession among salt marshes species. The results can be used to quantitatively analyze the salt marshes carbon storage in space and time, and provide data support for the protection of salt marsh wetlands, the restoration of ecological functions and the implementation of "carbon neutral".

Inflammatory bowel disease (IBD) has evoked a significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising of Crohn’s disease and Ulcerative colitis manifest as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes, elicits both innate and adaptive immune responses in the gut culminating in aberrant intestinal inflammation. Interestingly, IBD leukocyte repertoire is significantly entwined with chemokine assisted chemotactic navigation into the sites of inflammation which is also thought to generate favourable immune suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims at critically examining the CCR6 driven immune pathways; T_H1/T_H2, T_H1/T_H17, T_H17/ T_reg, IL-23/IL-17, Akt/ERK-1 /2, ILC3 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD aetiopathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

This research focuses on the customer orientation of insurance brokers, whose activity is regulated by the Law of 26/2006 of July 17 on the mediation of private insurances and reinsurances. The goal is to ascertain whether the intermediation inherent in the insurance broker’s activity, which implies a customer-oriented service, entails a positive behaviour that transcends the immediate environment, reaching society. This study presents a comparative analysis between the insurance brokerage society, characterised by providing a personalised customer service, and banks’ advisory services on insurance. To this end, we study the evolution of the total volume of business and new production, compared for a portfolio of insurance products. The results presented in this research suggest that the customer values the advisory service provided by the broker. However, for a particular business segment in standardised insurance products and products related to banking assets, customers are more likely to resort to the bank’s services. In addition, the results indicate that the commission percentages applied by the entities operating in the banking insurance channel exceed those perceived by the insurance broker. With all this, intermediation in the development of the insurer’s activity can entail an ethical and social behaviour that involves customer-orientation and, possibly, social service, which does not always benefit the insurer.

This paper examines the regional changes of corn production and the relationship between ethanol production and corn production. The underlying hypothesis is that the rapid growth in ethanol production causes regional expansion of corn production outside the traditional regions. This paper introduces the information approach developed by entropy theory to describe these regional changes. The results support the hypothesis that ethanol production leads to expansion of corn production outside traditional corn producing regions.

The concept of DC power distribution has gained interest within the research community in the past years; especially due to rapid prevalence of solar PVs as a tool for distributed generation in DC microgrids. Various efficiency analyses have been presented for the DC distribution paradigm, in comparison to the AC counterpart, considering a variety of scenarios. However, even after a number of such comparative efficiency studies, there seems to be a disparity in the results of research efforts - wherein a definite verdict is still unavailable: 'Is DC distribution a more efficient choice as compared to the conventional AC system?' A final verdict is absent primarily due to conflicting results. In this regard, system modeling and the assumptions made in different studies play a significant role in affecting the results of the study. The current paper is an attempt to critically observe the modeling and assumptions used in the efficiency studies related to the DC distribution system. Several research efforts will be analyzed for their approach towards the system upon which they have performed efficiency studies. Subsequently, the paper aims to propose a model that may alleviate the shortcomings in earlier research efforts and be able to give a definite verdict regarding the comparative efficiency of DC and AC networks for residential power distribution.

In this paper we present the measurement of charged pion two-particle femtoscopic correlation functions in $\sqrt{S_{NN}}$= 200 GeV Au+Au collisions, in 31 average transverse mass bins, separately for positive and negative pion pairs. Lévy-shaped source distributions yield a statistically acceptable description of the measured correlation functions, with three physical parameters: correlation strength parameter λ , Lévy index α and Lévy scale parameter R. The transverse mass dependence of these Lévy parameters is then investigated. Their physical interpretation is also discussed, and the appearance of a new scaling variable is observed.

This study presents an analysis of the spatial and temporal distribution of the two large destructive earthquakes that occurred in Lake Van area on October 23, and November 9, 2011, together with the azimuth-dependent distribution of the seismic activity and microseismicity clusters after the mainshocks, associated with the complex rupture processes of their aftershock sequence. The sequence began with the magnitude Mw 7.1 earthquake of 23 October and a second destructive earthquake of Mw 5.6. The aftershock sequences of the two mainshocks were linked to the local crustal faults beneath Lake Van area, followed successively and produced unusually intense activity and significant damage in the area. The main purposes of this study are to document the spatial and temporal distribution and evolution of the October 23, 2011 aftershock hypocenters and the azimuth-dependent distribution of seismic activity, and to understand the spatial and temporal character of the aftershock sequence using the distributional and evolutional patterns of the aftershock hypocenters. A total of 10,000 aftershocks were obtained from seismic data with a high signal-to-noise ratio over collected over three years from October 23, 2011 to March 2014. These aftershocks were plotted for the time periods from November 2011 through March 2012 to March 2014 and ≈ 5000 aftershocks were retained in the depth versus distance cross-sections to detect the clusters in the first step of study (November 2011–March 2012). The focal depth distribution of the aftershock clusters, the migration of hypocenter activity and microseismicity clusters were analyzed and the distributional patterns of the detected clusters were assessed using the geometric distribution of the aftershock hypocenters. The spatial and temporal distribution of aftershocks reveal interesting key features of the deep rupture complexity of the Van earthquake: (1) most prominent aftershocks have been located in the upper crust at depths shallower than 10 km beneath ruptured area, indicating that the upper crust is brittle and seismogenic; (2) two spatial clusters have been detected at 8-10 km depths and the upward extrapolation of these clusters intersects with faults; the main cluster (60 km wide) bounded by inferred reverse faults (f3 and f4) and the central cluster (25–30 km wide) bounded by faults (f1 and f2); (3) these spatial clusters form the largest volumetric pattern of the conical-shaped cluster at depths of about 25–30 km of the azimuth-dependent rotational projections, suggesting azimuthal distributions of deep rupture characteristics; and (4) the strongest temporal cluster of microseismicity derived from temporal distribution of aftershocks has been detected within an area of about 2.5–3.0 km² and it is spatially observed at 20 km depth within the central cluster, suggesting progressive failure of the adjacent patches of possible fault.

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood-brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure-activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, q²_CV = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

Reliability analysis techniques are customary standard tools that are used for evaluating the performance of different equipment and devices in order to minimize their downtime. To predict the reliability, life data from a sample that is satisfactorily representative of the equipment should be fitted to the suitable statistical distribution. The parameterized distribution may be used to estimate essential characteristics such as failure rate; and probability at a precise time, as well as system reliability. In the current study, Weibull++/ALTA software package is used as a novel tool to fit the available data set to estimate the best fitted probability density function (PDF) using Maximum Likelihood (MLE) for parameter estimation. The determined distributions are then assessed using goodness-of-fit test to define how well it fits the available data set. There are multiple methods for determining goodness-of-fit. Weibull distributions and their special cases’ parameters have an effect on life times.

Developments of new probability models for data analysis are keen interest of importance for all fields. The log-Dagum distribution has a prominent role in the theory and practice of statistics. In this article, a new family of continuous distributions generated from a log Dagum random variable called the log-Dagum Weibull distribution is proposed. The key properties of the proposed distribution are derived. Its density function can be symmetrical, left-skewed, right-skewed and reversed-J shaped and can have increasing, decreasing, bathtub hazard rates shaped. The model parameters are estimated by the method of maximum likelihood and illustrate its importance by means of applications to real data sets.

Transient receptor potential vanilloid (TRPV) channels act as sensors of pain, temperature, and other external stimuli. We have recently shown that DPV576, an aqueous mixture of nanodiamond (ND) and nanoplatinum (NP), can modulate the activity of TRPV on human primary keratinocytes, suggesting their potential as a possible pain modulator [1]. CD4+ T lymphocytes also express TRPV channels, and we sought with special interest to examine the effect of DPV576 in modulating the functions of TRPV channel expression and secretion of cytokines on human CD4+ T lymphocytes. Human primary CD4+ T cells were activated with anti CD3/CD28 with and without DPV576 at 1:25 and 1:100 dilutions for 24 hours in vitro. TRPV Receptor expression (TRPV1 and TRPV4) on CD4+ T cells was examined by flow cytometry. The capacity of DPV576 to modulate the activity of TRPV1 agonist capsaicin in CD4+ T cells was also determined. Activation of CD4+ T cells was determined by production of cytokines TNF-α, IFN-γ, and IL-10 using specific ELISA kits. DPV576 treatment of CD4+ T cells that were activated with anti CD3/CD28, resulted in increased expression of TRPV1 channel but had no effect on TRPV4. This was accompanied by increased secretion of IFN-g and reduced expression of TRPV1 in capsaicin activated CD4+ T cells. In addition, DPV576 inhibited the capsaicin, induced the production of both IFN-g and TNF-α, and enhanced the secretion of IL-10. We conclude that short term exposure to DPV576 inhibits the activity of TRPV1 channels in CD4+ T lymphocytes, which may suggest its possible beneficial use for pain management.

Thymic stromal lymphopoietin (TSLP) is a cytokine and is closely related to Interleukin (IL) - 7, and hTSLP can activation through the human thymus dendritic cell in thymic to indirectly promote the differentiation of natural Regulatory T cells (Tregs) of the thymus. In this study, we focused on recombinant TSLP to determine its effects on the differentiation of CD4+CD25-T cells separated from the thymus of myasthenia gravis (MG) patients. Our results demonstrated that exogenous TSLP could increase CD4+CD25+T/CD4+T cells ratio, up-regulate the expression of Foxp3 mRNA and protein expression in CD4+CD25+Treg cells. Furthermore, we found that CD4+CD25+ Treg cells induced by exogenous TSLP could secrete IL - 10, Transforming growth factor (TGF) - β and the ability to inhibit CD4+T cell proliferation improved. These results indicate that TSLP may promote the differentiation of thymic CD4+CD25-T cells of MG patient to CD4+CD25+Foxp3+ regulatory T cells and enhance the function of immune suppression.

C-C Chemokine receptor type 5 (CCR5) is expressed on the CD4 T cell surface where CXCR4 and CCR5 expressions are controlled differently during the activation of T cells and with the binding of interleukin type-2 (IL-2). IL-2 can upregulate CCR1 and CCR2 in CD45R01 T cells and increase the T lymphocyte chemotaxis toward CC-chemokines. CD4+ T cells are either apart of the T helper 1 or Th1 lymphocytes that release interferon gamma (IFNγ) and lymphotoxin that provide cellular immunity to internal pathogens and T helper cells type 2 (Th2), which secrete interleukins 4 and 5 (IL-4 and IL-5). IL-4 and IL-5 cause an allergic and humoral immune response to parasites. Th2 lymphocytes use CCR3 chemokine receptors. CCR5 and CXCR3 chemokine receptors are specific for CD4+ Th1 and Th2 lymphocytes. CCR5Δ32 is a 32-base-pair deletion of the CCR5 gene. CCR5 is a co-receptor for the entrance of the human immunodeficiency virus-1 (HIV-1). CCR5Δ32 creates a malfunction of the CCR5 protein that can prevent HIV-1 infection. However, the CCR5Δ32 32-base-pair deletion is not prevalent and predominant in many populations worldwide and there also exist more genetic variations of CCR5 known as CCR5-SNPs. An alternative polymorphism was identified based on the CCR5 gene that was identified as a A to G (A/G) point mutation. This point mutation is located at the 59029 locus on the promoter that lowers the expression rate of CCR5. Gurdol et al. found activity at the promoter of CCR5/590029G was 45% lesser than the CCR5/59029A. The genetic variations of CCR5 SNPs also include: 2459G>SNP of CCR5, C101X, CCR5 gene position at -2273, and the A to G SNP mutation found in two South African blacks. Therefore, more studies are needed to find more and varied chemokine polymorphisms that are present in many diverse populations in the world. The aim of this literature review is to describe the immense impact of CCR5 SNP mutations on viral infection susceptibility, on the pathogenesis of chronic conditions, to endorse the increased discovery of more novel CCR5 SNPs, and to show the significant potential of anti-CCR5 therapies to treat multiple diseased conditions.

The thymus hosts the development of a specific type of adaptive immune cells called T cells. T cells orchestrate the adaptive immune response through recognition of antigen by the highly variable T-cell receptor (TCR). T-cell development is a tightly coordinated process comprising lineage commitment, somatic recombination of Tcr gene loci and selection for functional, but non-self-reactive TCRs, all interspersed with massive proliferation and cell death. Thus, the thymus produces a pool of T cells throughout life capable of responding to virtually any exogenous attack while preserving the body through self-tolerance. The thymus has been of considerable interest to both immunologists and theoretical biologists due to its multiscale quantitative properties, bridging molecular binding, population dynamics and polyclonal repertoire specificity. Here, we review mathematical modelling strategies that were reported to help understand the flexible dynamics of the highly dividing and dying thymic cell populations. Furthermore, we summarize the current challenges to estimating in vivo cellular dynamics and to reaching a next-generation multiscale picture of T-cell development.

Hamacher operation which is generalization of the Algebraic and Einstein operation, can widely provide a large number of arithmetical operation with respect to uncertainty information, and Heronian mean can deal with correlations of the input arguments or different criteria and don’t make calculation redundancy, meanwhile, the normal intuitionistic fuzzy numbers (NIFNs) can depict distinctively normal distribution information in practical decision making. In this paper, a multi-criteria group decision-making (MCGDM) problem is researched under the NIFNs environment, and a new MCGDM approach is introduced on the basis of the Hamacher operation. Firstly, according to Hamacher t-conorm and t-norm, some operational laws of NIFNs are presented. Secondly, it is noticed that Heronian mean can’t only once take into account mutual relation between attribute values once, but also consider the correlation between input argument and itself. Therefore, we develop some operators and study their properties in order to aggregate normal intuitionistic fuzzy numbers information, these operators include Hamacher Heronian mean (NIFHHM), Hamacher weighted Heronian mean (NIFHWHM), Hamacher geometric Heronian mean (NIFHGHM) and Hamacher weighted geometric Heronian mean (NIFHWGHM). Furthermore, we apply the proposed operators to the MCGDM problem and present a new method. The main characteristics of this new method involve that: (1) it is suitable to make decision under the normal intuitionistic fuzzy numbers environment and more reliable and reasonable to aggregate the normal distribution information. (2) it utilizes Hamacher operation which can provide more reliable and flexible decision-making results and offer an effective and powerful mathematic tool for the MAGDM under uncertainty. (3) it uses the Heronian mean operator which can considers relationships between the input arguments or the attributes and don’t brings subsequently about redundancy. Lastly, an application is given for showing the feasibility and effectiveness of the presented method in this paper.

Most existing flexible count regression models allow only approximate inference. This work proposes a new framework to provide an exact and flexible alternative for modeling and simulating count data with various types of dispersion (equi-, under- and overdispersion). The new method, referred as “balanced discretization”, consists in discretizing continuous probability distributions while preserving expectations. It is easy to generate pseudo random variates from the resulting balanced discrete distribution since it has a simple stochastic representation in terms of the continuous distribution. For illustrative purposes, we have developed the family of balanced discrete gamma distributions which can model equi-, under- and overdispersed count data. This family of count distributions is appropriate for building flexible count regressionmodels because the expectation of the distribution has a simple expression in terms of the parameters of the distribution. Using the Jensen–Shannon divergence measure, we have shown that under equidispersion restriction, the family of balanced discrete gamma distributions is similar to the Poisson distribution. Based on this, we conjecture that while covering all types of dispersion, a count regression model based on the balanced discrete gamma distribution will allow recovering a near Poisson distribution model fit when the data is Poisson distributed.

Solar energy is a renewable resources of energy which is broadly utilized and have the least pollution impact between the available alternatives of fossil fuels. In this investigation, machine leaening approaches of neural networks (NN), neuro-fuzzy and least squares support vector machine (LSSVM) are used to build the models for prediction of the thermal performance of a photovoltaic-thermal solar collector (PV/T) by estimating its efficiency as an output of the model while inlet temperature, flow rate, heat, solar radiation, and heat of sun are input of the designed model. Experimental measurements was prepared by designing a solar collector system and 100 data extracted. Different analyses are also performed to examine the credibility of the introduced approaches revealing great performance. The suggested LSSVM model represented the best performance regarding the mean squared error (MSE) of 0.003 and correlation coefficient (R²) value of 0.99, respectively.

Species have shown their habital variations in responding to climate change, especially during the spring and summer spawning seasons. The species distribution model (SDM) is considered the most favorable tool to study the potential effects of climate change on species distribution. Therefore, we developed the ensemble SDM to predict the changes in species distribution of Portunus trituberculatus among different seasons in 2050 and 2100 under the climate scenarios RCP4.5 and RCP8.5. The results of SDM indicate that the distribution of this species will move northward and have obviouse seasonal variations. Meanwhile, the suitable habitat for the species will be significantly reduced in summer, with loses rates ranging from 45.23% (RCP4.5) to 88.26% (RCP.8.5) by 2100s. Habitat reduction will mainly occur in the East China Sea and southern part of the Yellow Sea, while there will be a small increase in the northern Bohai Sea. These findings will be important to manage the ecosystem and fishery, provide an information forecast of this species in the future, and maintain species diversity if the seawater temperature rises.

Hospital-based programs democratize mRNA therapeutics by facilitating the processes to translate a novel RNA idea from the bench to the clinic. Because mRNA is essentially biological software, therapeutic RNA constructs can be rapidly developed. The generation of small batches of clinical grade mRNA to support IND applications and first-in-man clinical trials, as well as personalized mRNA therapeutics delivered at the point-of-care, is feasible at a modest scale of cGMP manufacturing. Advances in mRNA manufacturing science and innovations in mRNA biology, are increasing the scope of mRNA clinical applications.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

In the world industry plant, solid and solid metals are always in contact even their motions not independent. Modeling of rolling die contact with slab primarily needs to describe the Tribology of contact phenomena. Consideration of continuum theory of rolling contact how a contact region is formed between rolling die and slab, and how the tangential force is distributed over the contact area with coefficient of friction is important. The central concern of numerical model is used in this work to indicate a set of equations, derived from the contact principle, that transfer the physical event into the mathematical equations including the laws of nature, such as newton’s laws, boundary conditions, state of stresses and their derivatives at particular time and locations. In this paper the elasticity stress behavior of rolling die contact with slab for number of cyclic loads is modeled. The model is including new proposed constitutive equations for discontinuity of the velocity, pressure distribution in rolling contact from the enter side to exit side of the neutral point. To verify the model, finite element simulation and experimental data from the literature are considered. The results show good agreement with finite element simulation and experimental data.

Dispersion tests based on the second order component of smooth test statistics are related to Fisher’s Index of Dispersion test, used for testing for the Poisson distribution when there are no covariates present. Such tests have been recommended in [1] to test for the Poisson distribution when covariates are present. The modified Borel-Tanner (MBT) distribution seems suited to data with extra zeroes, a monotonic decline in counts and longer tails. Here we recommend a dispersion test for the MBT distribution for both when covariates are absent and when they are present.

Historical maps constitute unique sources of retrospective geographic information. Recently, several map archives containing map series covering large spatial and temporal extents have been systematically scanned and made available to the public. The geographic information contained in such data archives allows extending geospatial analysis retrospectively beyond the era of digital cartography. However, given the large data volumes of such archives and the low graphical quality of older map sheets, the processes to extract geographic information need to be automated to the highest degree possible. In order to understand the salient characteristics, data quality variation, and potential challenges in large-scale information extraction tasks, preparatory analytical steps are required to efficiently assess spatio-temporal coverage, approximate map content, and spatial accuracy of such georeferenced map archives across different cartographic scales. Such preparatory steps are often neglected or ignored in the map processing literature but represent highly critical phases that lay the foundation for any subsequent computational analysis and recognition. In this contribution we demonstrate how such preparatory analyses can be conducted using classical analytical and cartographic techniques as well as visual-analytical data mining tools originating from machine learning and data science, exemplified for the United States Geological Survey topographic map and Sanborn fire insurance map archives.

It has been demonstrated that a decrease in cellular adenosine triphosphate (c-ATP) causes cellular dysfunction. T-cells are not an exception. One of their roles is to properly detect and eliminate cancer cells. These processes occur at the expense of ATP. Therefore, it can be concluded that a decrease in c-ATP can defect T-cell function and promote cancer evolution. In this article, we provide a hypothesis to describe the correlation between the expression of PD-1 protein on T-cells and their c-ATP levels. Moreover, we present the possible predictive factors of Anti–PD(L)-1 therapy which has not yet been determined definitely.

Location-and-scale transformation of a random variable underpins normal distribution, but it is however fundamentally incorrect for scale estimation such as relative dispersion. In this paper, a parametrized alternative to a normal distribution, called scaloc-normal distribution, is proposed that efficiently works and is fundamentally correct with absolute and relative dispersion estimators. The Monte Carlos simulation experiment was used to generate a total of 600,000 artificial datasets in 600 different simulation scenarios from loc-normal (normal) and scaloc-normal distributions. The absolute and relative dispersion were estimated and compared from the two distributions. The results show that scaloc-normal distribution is a good parametrized alternative to loc-normal distribution, fundamentally correct and efficient with both standard deviation and coefficient of variation. The key statistical advancement from loc-normal to scaloc-normal distribution is its fundamental correctness (i.e., scale-invariant property) with an efficient relative estimator of dispersion (i.e., coefficient of variation). Parametrically, the loc-normal and scaloc-normal distributions are very different, but both have linear transformations.

This report is considered different aspects of the concept of the networked distributed engine control system (DECS) of future air vehicles. These aspects include the following: the structure of multiple networks similar to NATO Generic Vehicle Architecture (NGVA), the role of Artificial Intelligence (AI) in DECS, and the use Augmented Reality (AR) as Human-Machine Interface between AI and pilots. Deployment of AI solutions for monitoring equipment in on-board infrastructure can be provided on physical or virtual servers and in the clouds. In this case, it is possible to use various methods of alerting the pilot and ground personnel on the basis of AR. The use of AI allows covering an unlimited set of scenarios, to provide an assessment of the likelihood of equipment failure, classification alarm is normal, and recognition of the development of defects. To collect Big Data from sensors and the pre-processing of this data before a machine learning (ML) procedure it is proposed to form data sets with the help of the face-splitting matrix product. To decrease the time of reaction of Neural Networks it has been suggested the implementation of advanced tensor-matrix theory on the basis of penetrating face product of matrices. Other important results of the report are a possible version of the AR data format for DECS and a proposal about the use of non-orthogonal frequency discrete multiplexing (N-OFDM) signals to data transfer via fibre optics.

We successfully designed an optimized plenum fan with a three-dimensional, smooth, curved blade. The optimized model revealed that the static pressure in the channel had been increased uniformly and stably, and the flow separation at the leading edge was significantly reduced. To conclude, the three-dimensional blade stabilized the fluid flow, and the flow friction was reduced by suppressing the flow separation as much as possible so that both the static pressure and the static efficiency were clearly improved in comparison with those of the original model. The static efficiency, as a result, was improved by 6% compared with that of the original model.

The aim of the studies was to test the hydraulic pressure losses along the length, local pressure losses, absolute and relative roughness values of the pipeline walls made of modern polymer material. The article presents the results of the experimental studies of hydraulic resistance of pipelines from modern polymer materials, the method of theoretical determination of resistance coefficients in the VALTEC ISO 21003 metal polymer pipeline, the classification and method of determining the values of local hydraulic resistance coefficients of T-Junctions are given, the dependence for determining the Darcy λ hydraulic friction coefficient associated with the value of the equivalent hydraulic roughness coefficient of the inner surface of pipes and the Reynolds number. The experimental data of the hydraulic coefficient of friction Darcy λ was compared with the known theoretical relationships of A.D. Altschul, Colbrooke for smooth pipes, Colbrooke and White, an alternative to the Colbrooke-White, Offengenden equation for low-shear pipes and pipes from polymer materials with Reynolds numbers Re>10^4. Dependence of hydraulic coefficient of friction on relative equivalent roughness of pipeline walls and Reynolds number, specific energy loss per one linear meter on total flow rate in system of hydraulically short pipeline is obtained. The empirical dependence of values of coefficients of local resistance ζ=f(Q2/Q3) from a ratio of the divided expenses of Q2/Q3 of the equal-pass T-Junction α=90 the pipeline to a branch up, on pass in the direct T-Junction and division of streams at various internal pipeline diameters of VALTEC.

Immunotherapy is an effective therapeutic option for several cancers. In the last years, the introduction of checkpoint inhibitors (ICIs) has shifted the therapeutic landscape in oncology and improved patient prognosis in a variety of neoplastic diseases. However, to date, the selection of the best patients eligible for these therapies, as well as the response assessment is still challenging. Patients are mainly stratified using immunohistochemical analysis of the expression of anti-gens on biopsy specimens, such as PD-L1 and PD-1, on tumor cells, on peritumoral immune cells, and/or in the tumor microenvironment (TME). Recently, the use and development of imaging biomarkers able to assess in-vivo cancer-related processes are becoming more important. Today, positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is used routinely to evaluate tumor metabolism, and also to predict and monitor response to immunotherapy. Although highly sensitive, FDG-PET, in general, is rather unspecific. Novel radiopharmaceuticals (immuno-PET radiotracers) able to identify specific immune system targets are under investigation in pre-clinical and clinical settings. In this review, we will provide an overview of the main new immuno-PET radiotracers in development. We will also review the main players (immune cells, tumor cells, and molecular targets) involved in immunotherapy. Furthermore, we report current applications and the evidence of using [18F]FDG PET in immunotherapy, including the use of artificial intelligence (AI).

Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Precipitation processes are technologies commonly used in hydrometallurgical plants to recover metals or to treat wastewaters. Moreover, solid-liquid separation technologies, such as thickening or filtering, are relevant unit operations, included in the precipitation technologies. These methods are strongly dependent on the characteristics of the solid precipitates formed during the specific precipitation reaction. One of these characteristics is the particle size distribution (PSD) of the solid precipitates which are fed into a solid-liquid separation process. Therefore, PSD determination is a typical practice for the characterization of the slurries generated in a precipitation plant. Furthermore, the precipitates generated in these processes have a colloidal or aggregation behavior, depending on the operational conditions. Nevertheless, the conventional methods used to estimate PSD (e.g., laser diffraction and/or ciclosizer) have not been designed to measure particles that tend to aggregate or disaggregate, since they include external forces (e.g., centrifugal, agitation, pumping and sonication). These forces affect the true size of the aggregates formed in a unit operation, thereby losing representativity in terms of aggregates particle size. This study presents an alternative method of measuring the size distribution of particles with aggregation behavior, particularly, by using non-invasive microscopy and image processing and analysis. The samples used have been obtained from an experimental precipitation process by applying sulfidization to treat the cyanide-copper complexes contained in a cyanidation solution. This method has been validated with statistical tools and compared with a conventional analysis based on laser diffraction. Our results show significant differences between the methods analyzed, demonstrating that image processing and analysis by microscopy is an excellent and non-invasive alternative to obtaining size distribution of aggregates in precipitation processes.

Cryptocurrencies like Bitcoin rely on a proof-of-work system to validate transactions and prevent attacks or double-spending. A new proof-of-work is introduced which seems to be the first number theoretic proof-of-work unrelated to primes: it is based on a new metric associated to the Collatz algorithm whose natural generalization is algorithmically undecidable: the inflation propensity is defined as the cardinality of new maxima in a developing Collatz orbit. It is numerically verified that the distribution of inflation propensity slowly converges to a geometric distribution of parameter $0.714 \approx \frac{(\pi - 1)}{3}$ as the sample size increases. This pseudo-randomness opens the door to a new class of proofs-of-work based on congruential graphs.

In this paper we discuss a problem of generalization of binomial distributed triangle, that is sequence A287326 in OEIS. The main property of A287326 that it returns a perfect cube n as sum of n-th row terms over k; 0 ≤ k ≤ n−1 or 1 ≤ k ≤ n, by means of its symmetry. In this paper we have derived a similar triangles in order to receive powers m = 5; 7 as row items sum and generalized obtained results in order to receive every odd-powered monomial n^2m+1; m ≥ 0 as sum of row terms of corresponding triangle. In other words, in this manuscript are found and discussed the polynomials D_m(n,k) and U_m(n,k), such that, when being summed up over k in some range with respect to m and n returns the monomial n^2m+1.

In this research first, a sequence of properties called delta is assigned to each prime number and then examined. Deltas are only dependent on the distribution of prime numbers, so the results obtained for the delta distribution can be considered as a proxy for the distribution of prime numbers. The first observation was that these properties are not unique and different prime numbers may have the same value of delta of a given order. It was found that a small number of deltas cover a large portion of prime numbers, so by recognizing repetitive deltas, the next prime numbers can be predicted with a certain probability, but the most important observation of this study is the normal distribution of deltas. This research has not tried to justify the obtained observations and instead of answering the questions, it seeks to ask the right question.

The power function distribution is a flexible waiting time model that may provide better fit for some failure data. This paper presents the comparison of the maximum likelihood estimates and the Bayes estimates of two-parameter power function distribution. The Bayes estimates are obtained, using conjugate priors, under five loss functions consist of square error, precautionary, weighted, LINEX and DeGroot loss function. The Gibbs sampling algorithm is proposed to generate samples from posterior distributions and in result the Bayes estimates are computed. The comparison of the maximum likelihood estimates and the Bayes estimates are done through the root mean squared errors. One real-life data set is analyzed to illustrate the evaluation of proposed methods of estimation. Finally, results from the simulation are discussed to assess the performance behavior of the maximum likelihood estimates and the Bayes estimates.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the CDC recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic ,cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an ELISA and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.

With the accelerating urbanization process, the population increasingly concentrates in urban areas. In view of the special situation in China and a series of problems in the process of rapid urbanization, there were no reasonable measures for optimizing the population pattern. This study explored the distribution pattern of the Chinese population and proposed an optimization plan for the population distribution using GIS analysis. The main findings were as follows. (1) From 2010 to 2015, the distribution of population density in China presented a pattern of high in the southeast and low in the northwest based on the county-level administrative regions. The population still showed a tendency to migrate to the southeast of the country based on the “Hu Huanyong Line”. (2) There was a great difference in the land use efficiency in terms of population and economic production in China. The economic concentration in China was higher than the population concentration. In the areas where population and economic production were aggregated, GDP per capita and land use efficiency were higher. (3) Based on the land use efficiency in terms of population and economic production, the optimized urbanization plan of “1+4+11” for China’s urbanization was put forward, namely, one national-level aggregated area of population and economic production, 4 regional-level aggregated areas of population and economic production, and 11 local regionally aggregated areas of population and economic production. This optimization plan for urbanization represents an attempt to explore the direction of China’s urbanization, and it can be used to optimize the spatial development pattern and provide scientific guidance for the new urbanization plan.

We analyzed the plant-litter-soil continuum to investigate the carbon and nitrogen distribution and ecological stoichiometry of an evergreen broad-leaved forest at Dagangshan Mountain, Jiangxi. The results showed that the average C and N contents and C:N ratios in the leaves and fine roots among 6 different tree species were 401.87g/kg, 21.41g/kg, 19.27 and 348.64g/kg, 15.73g/kg, 23.97, respectively; the average C and N contents and C:N ratios were 323.06 g/kg, 12.76 g/kg, 25.58 respectively in leaf litter, and 16.40 g/kg, 1.09 g/kg, 16.27 respectively for soil. In contrast with the C content, the total N content of the fine roots and litter had a high coefficient of variation and a high spatial heterogeneity. We ranked the six different representative tree species according to total C and N content in leaves and fine roots. The results for each species were generally consistent with each other, showing a positive correlation relationship between total C and N content in the leaves and roots. Among them, S. discolor (Champ. ex Benth.) Muell. plants displayed high carbon and nitrogen storage capacities, and on the other hand, C. fargesii Franch., C. myrsinifolia (Blume) Oersted, A. fortunei (Hemsl.) Makino, and V. fordii (Hemsl.) Airy Shaw showed a high nitrogen transfer rate. Total soil N and C decreased with depth. Soil organic carbon (SOC), soil resistant organic carbon (ROC), total N, alkali nitrogen, NH4+-N and NO3--N contents were all also negative correlated with soil depth, but the contents of the NH4+-N and NO3--N did not change significantly; The spatial distribution of soil NO3--N was significantly heterogeneous. At 0-10 cm soil depth, SOC was positively correlated with alkaline nitrogen, and at 10-20 cm soil depth, SOC was significantly positively correlated with total N. In general, when soil carbon was abundant, nitrogen supply capacity was also high.

For bounded unit interval, we propose a new Kumaraswamy generalized (G) family of distributions from a new generator which could be an alternate to the Kumaraswamy-G family proposed earlier by Cordeiro and de-Castro in 2011. This new generator can also be used to develop alternate G-classes such as beta-G, McDonald-G, Topp-Leone-G, Marshall-Olkin-G and Transmuted-G for bounded unit interval. Some mathematical properties of this new family are obtained and maximum likelihood method is used for estimating the family parameters. We investigate the properties of one special model called a new Kumaraswamy-Weibull (NKwW) distribution. Parameter estimation is dealt and maximum likelihood estimators are assessed through simulation study. Two real life data sets are analyzed to illustrate the importance and flexibility of this distribution. In fact, this model outperforms some generalized Weibull models such as the Kumaraswamy-Weibull, McDonald-Weibull, beta-Weibull, exponentiated-generalized Weibull, gamma-Weibull, odd log-logistic-Weibull, Marshall-Olkin-Weibull, transmuted-Weibull, exponentiated-Weibull and Weibull distributions when applied to these data sets. The bivariate extension of the family is proposed and the estimation of parameters is given. The usefulness of the bivariate NKwW model is illustrated empirically by means of a real-life data set.

Surface area and pore size distribution of Eucalyptus samples pretreated by different methods were determined by the Brunauer-Emmett-Teller (BET) technique. Three methods were applied to prepare cellulosic biomass samples for BET measurements: air, freeze, and critical point drying (CPD). Air and freeze drying caused severe collapse of biomass pore structures, but CPD effectively preserved biomass morphology. Surface area of CPD prepared Eucalyptus samples was determined to be 58–161 m2/g, whereas air and freeze dried samples were 0.5–1.3 and 1.0–2.4 m2/g, respectively. Average pore diameter of CPD prepared Eucalyptus samples were 61–70Å. CPD preserved Eucalyptus sample morphology by replacing water with a non-polar solvent, CO2 fluid, which prevented hydrogen bond reformation in the cellulose.

Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

Extracellular vesicles (EVs) released by different cell types play significant role in many physiological and pathophysiological processes. In physiological conditions red blood cells (RBCs) derived EVs compose 4 - 8% of all circulating EVs, and oxidative stress (OS) as a consequence of different pathophysiological conditions significantly increases the amount of circulated RBC-derived EVs, however the mechanisms of EV formation are not fully defined yet. To analyze OS-induced EV formation and RBCs transformations we used flow cytometry to evaluate cell esterase activity, caspase-3 activity, and band 3 clustering. Band 3 clustering was additionally analyzed by confocal microscopy. Two original laser diffraction-based approaches were used for analysis of cell deformability and band 3 activity. Hemoglobin species were characterized spectrophotometrically. We showed that cell viability in tert-butyl hydroperoxide-induced OS directly correlated with oxidant concentration to cell count ratio, RBCs-derived EVs contained hemoglobin oxidized to hemichrome (HbChr). OS induced caspase-3 activation and band 3 clustering in cells and EVs. Importantly, we showed that OS-induced EV formation is independent from calcium. Presented data indicated that during OS RBCs eliminate HbChr by vesiculation, in order to sacrifice the cell itself thereby prolonging lifespan and delaying the untimely clearance of in all other respects healthy RBCs.

The aim of this study is (a) to develop, test, and employ a combined method of unsupervised machine learning to objectively assess the condition of sports facility in primary schools (PSSFC) and (b) examine the examine the geographical and typological association with PSSFC. Based on the Sixth National Sports Facility Census (NSFC), six PSSFC indicators (indoor and outdoor facility included) were selected as the measurements and decomposed by using the t-stochastic neighbor embedding (t-SNE). Thereafter, the Fuzzy C-mean (FCM) algorithm was used to cluster the same type of PSSFC with selecting the optimum numbers of evaluation level. Overall 845 primary schools in Shanghai, China were recruited and tested by this combined approach of unsupervised machine learning. In addition, the two-way analysis of covariance was used to examine the location and types of school associated with PSSFC variables in each level. The combined method was found to have acceptable reliability and good interpretability, differentiating PSSFC into five gradient levels. The characteristics of PSSFC differ by the location and school type of individual school. Our findings are conducive to the regionalized and personalized intervention and promotion on the children’s physical activity (PA) upon the practical situation of particular schools.

In this paper we define a continuous wavelet transform of a Schwartz tempered distribution $f \in S^{'}(\mathbb R^n)$ with wavelet kernel $\psi \in S(\mathbb R^n)$ and derive the corresponding wavelet inversion formula interpreting convergence in the weak topology of $S^{'}(\mathbb R^n)$. It turns out that the wavelet transform of a constant distribution is zero and our wavelet inversion formula is not true for constant distribution, but it is true for a non-constant distribution which is not equal to the sum of a non-constant distribution with a non-zero constant distribution.

Research Highlights: Hagenia abyssinica is geographically localized, poor regenerated and endangered species in Ethiopia. Ethiopia has been experiencing variability of rainfall and rise in temperature due to the climate change. This study has hypothesized that the suitable areas for the species will be narrowed by the year 2070. Background and Objective The prediction of species distribution models help to implement appropriate conservation actions. The aim of this research was to identify the current and likely future distribution range and suitable areas for the species, and to determine the presence of H. absyssinica in risk in a short-term future. Material and method: To this end, occurrence data, bioclim variables, soil, elevation, and land cover map of Ethiopia were used. MaxEnt was used to predict distribution. Climate change impacts on the distribution of the species was performed using bioclimatic variables of the future climate data, 2070 (average for 2061-2080) was obtained from IPPC5 (CMIP5) at 30 seconds (1km) spatial resolution. The climate data was projected from GCMs, downscaled and calibrated using rcp4.5. Results: Both current and likely future distribution models were excellent and significantly better than random performance. This study has computed 59987 km2 to be the low impact area for the species under current conditions and will remain habitat under future climates and 39025 km2 area has been identified as the possible high impact areas or declining habitat. The model has also determined that 1238724 km2 of the areas are unsuitable at present and for future climates. The current study found that 15751 km2 of the area will be modified as a new suitable area for H. abyssinica due to climate change. Conclusion: Species distribution modeling is essential for the implementation of conservation actions that are compatible with the inevitable changing climatic conditions of the country.

The landscape of therapeutic measures to treat multiple myeloma has undergone a seismic shift since the dawn of the current century. This has been driven largely by the introduction of new classes of small molecules, such as proteasome blockers (e.g., bortezomib) and immunomodulators (e.g., lenalidomide), as well as by immunotherapeutic agents starting with the anti-CD38 monoclonal antibody daratumumab in 2015. Recently, other immunotherapies have been added to the armamentarium of drugs available to fight this malignancy. These include the bispecifics teclistamab, talquetamab, and elranatamab, and the chimeric antigen receptor (CAR) T-cell products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). While the accumulated benefits of these newer agents have resulted in a more than doubling of the disease’s five-year survival rate to nearly 60% and improved quality of life, the disease remains incurable, as patients become refractory to the drugs and experience relapse. This review covers the current scope of anti-myeloma immunotherapeutic agents, both those in clinical use and in development. Included in the discussion are additional monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), bi- and multi-targeted mAbs, and CAR T-cells and emerging natural killer (NK) cells, including products intended for “off-the-shelf” (allogeneic) applications. Emphasis is placed on the benefits of each along with the challenges that need to be surmounted if MM is to be cured.

A new attack against the Kirchhoff-Law-Johnson-Noise (KLJN) key distribution system is introduced. The attack is based on 1) Utilizing the dc-voltage-source - which we put at Alice’s end in our mathematical modeling of the attack-that could exist due to errors, imbalances, Electromagnetic interference and etc.2) On studying the number of samples per bit in the security key that the measured Alice/Bob voltages exceeds or falls below a threshold voltage, respectively. The threshold voltage is the average between dc voltages across low and high resistors- generated by a dc-voltage source. We count the number of samples the voltage at Bob’s end (containing both the noise and dc components) exceeds the threshold voltage and how many times it falls below the threshold to judge whether the resistor can be guessed as low or high for every cycle. Also for a pre-specified key-length we count the number of high resistance estimations per bit –at Bob’s end-according to the previous criterion and the non-successful estimations per bit to judge the final guessed resistor value at Alice’s end and Bob’s end, where if we have more bits with most of its measured samples are above the threshold voltage then we will predict Bob’s resistance as high resistance, otherwise we predict Bob’s resistance to be low resistance. The Simulation was conducted and the attack proved that it is successful unless the temperature increased dramatically to ranges more than a threshold temperature ~ Kelvin that increases when the number of samples per bit increases.

Background: CD169 has been found overexpressed in the blood of COVID-19 patients and identified as a biomarker in the early disease. We have analysed CD169 in blood cells of COVID-19 patients to assess its role as predictive marker of the disease. Methods : The ratio of the CD169 Median median Fluorescence fluorescence Intensity intensity of CD169 between monocytes and lymphocytes (CD169 RMFI ) was analysed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HD ) and correlated with immunophenotyping, inflammatory markers, cytokines mRNA expression, pulmonary involvement and disease progression. Results: CD169 RMFI increased in COV but not in HD. CD169 RMFI correlated with T-cell differentiation and exhaustion markers as well as with B cells maturation and differentiation. In vitro stimulation of PBMCs of HD with SARS-CoV-2 Spike spike protein induced CD169 RMFI together with IL-6 and IL-10 gene expression. Likewise, CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients which that had not received any treatment at sampling. Notably, in untreated patients, CD169 RMFI reflected the respiratory outcome during hospitalization. Conclusion : Considering the immunological role of CD169 and its involvement during the infection and the progression of COVID-19, it could be considered as an early biomarker to evaluate disease progression and clinical outcome.

In this paper we describe a nonparametric maximum likelihood (NPML) method for estimating multivariate mixing distributions. Given $N$ independent observations, convexity theory shows that the NPML estimator is discrete with at most $N$ support points. The original infinite NPML problem then becomes the finite dimensional problem of finding the location and probability of the support points. The probability of the support points is found by a Primal-Dual Interior-Point method; the location of the support points is found by an Adaptive Grid method. Our method is able to handle high-dimensional and complex multivariate mixture models.An important application is discussed for the problem of population pharmacokinetics and a non-trivial example is treated.Our algorithm has been successfully applied in hundreds of published pharmacometric studies. In addition to population pharmacokinetics, this research also applies to empirical Bayes estimation and many other areas of applied mathematics.

Increasing distributed generation and intermittency, along with the increasing frequency of extreme weather events, impose a serious challenge for the electric power supply security. Understanding the costs of interruption is vital in terms of enhancing the power system infrastructure and planning the distribution grid. On the other hand, customer rights and demand response techniques are further reasons to study the worth of power reliability. In this paper, the authors make use of directional distance function and shadow pricing method for a case study from Finland. The aim is to calculate the cost of one minute of power interruption from the distribution network operator perspective. The sample consists of 78 distribution network operators from Finland with cost and network information between 2013 and 2015.

The research presents the inter-comparison of atmospheric variables measured by 9 automatic meteorological stations. This set of data was compared with the measurements of other meteorological stations in order to standardize the values that must be adjusted when taken to different areas. The data of a set of a total of 9 GMX500, which measures conventional meteorological variables, and 10 WS100 sensors, which measures precipitation parameters. The automatic stations were set up at the Huancayo Observatory (Geophysical Institute of Peru) for a period of 5 months. The data set of GMX500 were evaluated comparing with the average of the 9 sensors and the WS100 was compared with a optical disdrometer Parsivel2. The temperature, pressure, relative humidity, wind speed, rainfall rate, and drop size distribution was evaluated. A pair of GMX500 sensors presented high data dispersion, it was found found that the errors came from a bad configuration; once this problem was solved, good agreement was archived, with low RMSE and high correlation. I was found that the WS100 sensors overestimate the precipitation with a percent bias close to 100% and the differences increase with the greater intensity of rain. The DSD retrieved by WS100 have unrealistic behavior with higher concentrations in diameters of 1 mm and 5 mm, in addition to a flattened curve.

Over the last decades, cellular immunotherapy has revealed its curative potential. However, the inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death undermine adoptive cell therapies. In this review, we concentrate on how the multiple mechanisms that articulate the various forms of immune dysfunction impact cellular therapies primarily involving conventional T cells, but also other lymphoid subtypes, in addition to the various strategies put in place to circumvent these effects. The repercussions of immune cell dysfunction across the full life cycle of cell therapy, from the source material, during manufacturing, and after adoptive transfer are discussed. Applicable to cellular products prepared from native and unmodified immune cells, as well as genetically engineered therapeutics, the understanding and potential modulation of dysfunctional features is key to the development of improved cellular immunotherapies.

Microgrids can be used for securing power supply during network outages. Underground cabling of distribution networks is another effective, but conventional and expensive alternative to enhance reliability of power supply. This paper presents firstly an analysis method for the determination of microgrid power supply adequacy during islanded operation, and secondly, a comparison method for overall cost calculation of microgrids vs. underground cabling. The microgrid power adequacy during a rather long network outage is required in order to indicate high level of reliability of supply. The overall cost calculations consider the economic benefits and costs incurred combined for both the distribution network company and the consumer. Whereas the microgrid setup determines the islanded operation power adequacy and thus the reliability of supply, the economic feasibility results from the normal operations and services. The methods are illustrated by two typical, and even critical, case studies in rural distribution networks: an electric-heated detached house and a dairy farm. These case studies show that even in case of a single consumer, a microgrid option could be more economical than network renovation by underground cabling of a branch in order to increase reliability.

Large intelligent surfaces (LIS) promises not only to improve the signal to noise ratio, and spectral efficiency but also to reduce the energy consumption during the transmission. We consider a base station equipped with an antenna array using the maximum ratio transmission (MRT), and a large reflector array sending signals to a single user. Each subchannel is affected by the Rayleigh flat fading, and the reflecting elements perform non-perfect phase correction which introduces a Von Mises distributed phase error. Based on the central limit theorem (CLT), we conclude that the overall channel has an equivalent Gamma fading whose parameters are derived from the moments of the channel fading between the antenna array and LIS, and also from the LIS to the single user. Assuming that the equivalent channel can be modeled as a Gamma distribution, we propose very accurate closed-form expressions for the bit error probability and a very tight upper bound. For the case where the LIS is not able to perform perfect phase cancellation, that is, under phase errors, it is possible to analyze the system performance considering the analytical approximations and the simulated results obtained using the well known Monte Carlo method. The analytical expressions for the parameters of the Gamma distribution are very difficult to be obtained due to the complexity of the nonlinear transformations of random variables with non-zero mean and correlated terms. Even with perfect phase cancellation, all the fading coefficients are complex due to the link between the user and the base station that is not neglected in this paper.

Hardened air void analysis provides essential information of concrete freeze-thaw durability based on the size and spacing of air voids in the material. As the physical freeze-thaw experiment is time-consuming and costly, the characteristics of concrete air voids are often deemed as a proxy of the freeze-thaw performance. This analysis is typically done by measuring the 2D air void intersections on polished samples, but the current interpretation of the 2D void characters does not accurately represent the actual void structure in 3D. To solve this problem, a 2D-to-3D unfolding technique has been proposed in the field of stereology. However, the unfolding analysis is known to be sensitive to several factors, such as void population and size along with a binning scheme, where improper unfolding can considerably bias the prediction of the actual concrete void system. This study investigates the optimal strategy of conducting the unfolding analysis for concrete. The investigation is carried out on both idealized void systems to interrogate the influence of the critical factors individually, and real concrete samples with varying levels of air entrainment to assess the concrete-specific impacts. The concrete void system is studied based on a stereological model emulating the intersected 3D air voids on the surface of polished concrete. The results highlight that, for unfolding concrete voids, logarithmic binning scheme is far more accurate to linear binning. The low unfolding error of the concrete samples indicates that the proposed methodology enables an accurate restoration of 3D void size distribution.

The central limit theorem (CLT) and its generalization to stable distributions have been widely described in literature. However, many variations of the theorem have been defined and often their applicability in practical situations is not straightforward. In particular, the applicability of the CLT is essential for a derivation of heterogeneous ensemble of Brownian particles (HEBP). Here, we analyze the role of the CLT within the HEBP approach in more detail and derive the conditions under which the existing theorems are valid.

This paper discusses and reviews the current taxonomic status and zoogeographical distribution of the mammals of Yemen. Data were collected from previous literature in addition to field observations during 2017–2018. This checklist includes 100 species of wild (terrestrial and marine) mammals currently occurring and those that went extinct within the last century in Yemen. Only wild mammals were included and domesticated species were excluded. These 100 species belong to 11 orders, 28 families, and 64 genera. In this paper, the current status and distribution of three Erinaceomorphs, seven Soricomorphs, 34 Bats, 16 Carnivores, seven Artiodactyls, one Lagomorph, 20 Rodents, one Hyracoidea, nine Cetaceans, one Sirenia, and one Primate were reported. According to the evaluation of the International Union for the Conservation of Nature and Natural Resources (IUCN): 70 species were listed as Least Concern (LC), two as Extinct (EX), one as Critically Endangered (CR), two as Endangered (EN), eight as Vulnerable (VU), five as Near Threatened (NT), and 12 as Data Deficient (DD). This paper also discusses the current main threats to the wild mammals in Yemen.

To generate a probability density function (PDF) for fitting probability distributions of real data, this study proposes a deep learning method which consists of two stages: (1) a training stage for estimating the cumulative distribution function (CDF) and (2) a performing stage for predicting the corresponding PDF. The CDFs of common probability distributions can be adopted as activation functions in the hidden layers of the proposed deep learning model for learning actual cumulative probabilities, and the differential equation of trained deep learning model can be used to estimate the PDF. To evaluate the proposed method, numerical experiments with single and mixed distributions are performed. The experimental results show that the values of both CDF and PDF can be precisely estimated by the proposed method.

Background: Strong indicators of inflammation, such as C-reactive protein (CRP), hypersensitive CRP (hs-CRP), and a series of hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT) and red blood cell distribution width (RDW), are regarded related with the incidence of contrast induced nephropathy (CIN) closely. Whereas, it remains unclear whether they can function as predictors of CIN onset. The objective of this meta-analysis was to determine the relationship between above indicators and CIN incidence among patients receiving coronary intervention. Methods: Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to June 3rd, 2020. Meta-analysis was performed on pool eligible studies. Two reviewers screened all titles and abstracts and independently assessed all articles. Results: A total of 26 studies involving 29,454 patients were included in the meta-analysis. Pooled analysis results revealed that patients with higher CRP (odds ratio [OR]=1.06, 95% confidence interval [CI]: 1.01–1.12, P=0.02), hs-CRP (OR=1.03, 95% CI: 1.01–1.06, P=0.004), NLR (OR=1.11, 95% CI: 1.01–1.20, P=0.02), RDW (OR=1.35, 95% CI: 1.19–1.53, P<0.00001), and lower HCT (OR=0.94, 95% CI: 0.92–0.97, P=0.0003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR=1.12, 95% CI: 0.99–1.26, P=0.07). Conclusion: The meta-analysis reported here demonstrates that pre-angiography CRP/hs-CRP and some hematological indices are associated with CIN.

Synthesis of zeolite T with a variety of desired characteristics necessitate extensive work in the formulation and practical experiments either by conventional hydrothermal methods or aided with different approaches and synthesis techniques such as secondary growth or microwave irradiation. The objectives of this review are to adduce the potential work in zeolite T (Offretite-Erionite) synthesis evaluating determining factors affecting the synthesis and quality of the zeolite T crystals. Attention is given to the extensive studies that interconnect with other significant findings.

Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effect to evade the immune recognition. However, clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC. Immunostaining and quantitative analysis were performed to assess CD8+ T cells infiltration, PD-L1 expression, and their relationship with CD44+/CD133+ CSCs and disease progression in PC. CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression group show high levels of CD44+/CD133+ CSCs, but patients with low CD8+ T cells infiltration/high PD-L1 expression had worse survival and higher recurrence risk than those with high CD8+ T cells infiltration/high PD-L1 expression. Moreover, CD8+ T cells infiltration could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/CD133. Our study highlights an interaction among CD8+ T cells infiltration, PD-L1 expression, and CD44+/CD133+ CSCs existence, which contributes to PC progression and immune evasion.

Abstract The last mile has to deliver the goods at the right time and at the right cost for business logistics services to enhance the customer service experience. The objective of this paper is to examine the challenges of retail omni-channel distribution influencing the effective last mile fulfilment operations processes in the apparel group (organisation phase). It further establishes the extent of how the last mile for demand-driven store replenishment influences the level of retailers’ order fulfilment (in full and on time) (environment phase). This paper, persistently assesses the contribution of integrated information systems on brick and mortar and virtual omni-channel distribution networks to improve timeousness, order accuracy and fill rate (technology phase). The mixed method has triangulated the methods from both quantitative methodology using frequencies and binomial testing and subjective thematic analysis of qualitative data from interviewees. The sample of 175 questionnaires were received with a response rate is 85 per cent (148 responses). The main findings of the paper revealed that the current order fulfilment process aligned with the last mile is effective on the basis of the fill rate, lead time and order condition of orders delivered via store economy and store express.

Immunomodulation as means of immunotherapy has been studied in major research and clinical laboratories for many years. T-Regulatory (Treg) cell therapy is one of the modulator used in immunotherapy approaches. Similarly, nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ) has extensively been shown to play a role as an immuno-modulator during inflammation. Given their mutual roles in downregulating the immune response, current study examined the influence of PPARγ ligands i.e thiazolidinedione (TZD) class of drugs on Foxp3 expression and possible crosstalk between PPARγ and nTreg cells of NOD and NOR mice. Results showed that TZD drug, ciglitazone and natural ligand of PPARγ 15d-prostaglandin downregulated Foxp3 expression in activated nTreg cells from both NOD and NOR mice. Interestingly, addition of the PPARγ inhibitor, GW9662 further downregulated Foxp3 expression in these cells from both mice. We also found that PPARγ ligands negatively regulate Foxp3 expression in activated nTreg cells via PPARγ-independant mechanism(s). These results demonstrate that both natural and synthetic PPARγ ligands capable of suppressing Foxp3 expression in activated nTreg cells of NOD and NOR mice. This may suggest that the effect of PPARγ ligands in modulating Foxp3 expression in activated nTreg cells is different from their reported effects on effector T cells. Given the capability to suppress foxp3 gene, it is possible to be tested as immunomodulators in cancer-related studies.

This study aims to model grinding of a Polish slag and evaluate the particle size distributions of the products obtained after different grinding times. Then, selected products were alkali activated in order to investigate the effect of particle size on the compressive strength of the produced alkali activated materials (AAMs). Other parameters affecting alkali activation, i.e. temperature, curing and ageing time were also examined. Among the different mathematical models used to simulate the particle size distribution, Rosin-Rammler (RR) was found to be the most suitable. When piecewise regression analysis was applied to experimental data it was found that the particle size distribution of the slag products exhibits multi fractal character. In addition, grinding of slag exhibits non-first-order behavior and the reduction rate of each size is time dependent. The grinding rate and consequently the grinding efficiency increases when the particle size increases, but drops sharply near zero after prolonged grinding periods. Regarding alkali activation, it is deduced that among the parameters studied, particle size (and the respective specific surface area) of the raw slag product and curing temperature have the most noticeable impact on the compressive strength of the produced AAMs.

Aiming at the current optimization problem of electric vehicle charging path planning, a charging path optimization strategy for electric vehicles under the "Traffic-Price-Distribution" mode is proposed. This strategy builds an electric vehicle charging and navigation system based on road traffic network model, real-time electricity price model and distribution network model. Based on Dijkstra shortest path algorithm and Monte Carlo time-space prediction method, the goal is to minimize the charging cost of electric vehicles. Optimal charging path. The simulation results of MATLAB and MATPOWER show that the electric vehicle charging path optimization strategy can better solve the local traffic congestion problem and improve the safety and stability of the distribution network on the basic of fully considering the convenience of electric vehicle charging.

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of zinc fingers, and most of all the applications of CRISPR-Cas9 technology, has given researchers new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR, possibly treating more diseases such as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of HIV-1, inhibiting HIV-1 gene expression. Since 2013, several other researchers have blocked HIV replication and infection through CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells, which consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus cannot bind to T-cells, blocking the initial attachment stage, and discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improving the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission or a functional cure.

The study was done to determine the effect of supplementing different forms of L-methionine (L-Met) and acetate on protein synthesis in immortalized bovine mammary epithelial cell line (MAC-T Cell): Control, L-Met, conjugated L-Met and acetate (CMA), and non-conjugated L-Met and Acetate (NMA). Protein synthesis mechanism was determined by omics method. NMA group had the highest protein content in the media and β-casein mRNA expression levels (P < 0.05). The number of upregulated and downregulated proteins observed were 77 and 62 in CMA group and 50 and 81 in NMA group from 448 proteins, respectively (P < 0.05). NMA and CMA treatments stimulated pathways related to protein and energy metabolism (P < 0.05). Metabolomic analysis also revealed CMA and NMA treatments resulted in increases of several metabolites (P < 0.05). In conclusion, NMA treatment increased protein concentration and expression level of β-casein mRNA in MAC-T cells compared to CMA.

Results-Based Funding (RBF) for Reducing Emissions from Deforestation and Forest Degradation (REDD+) has become an important instrument for channeling financial resources to forest conservation activities. At the same time, much literature on conservation funding is ambiguous about the effectiveness of existing RBF schemes. Many effectiveness evaluations follow a simplified version of the principal-agent model, although in practice the relation between aid providers and funding recipients is much more complex. As a consequence, intermediary steps of conservation funding are often not accounted for effectiveness studies. This research paper aims to provide a nuanced understanding of conservation funding by analyzing the allocation of financial resources for one of the largest RBF schemes for REDD+ in the world: the Brazilian Amazon Fund. As part of this analysis, this study has built a dataset of information on Amazon Fund projects at unprecedented detail in order to accurately reconstruct the allocation of financial resources across different stakeholders (i.e. governments, NGOs, research institutions), geographies and activities. The results show that stakeholders seem to hold preferences with respect to the type of activities that they support, thereby suggesting that project owners exert much influence on how deforestation reduction is to be attained. There are evidences that governmental organizations lack financial additionality of their projects, which renders the growing share of funding to this type of stakeholder particularly worrisome. By contrast, the geographical distribution of financial resources seemed to follow a more focused rationale as financial support tends to concentrate in areas where deforestation threats are highest. Overall, the allocation of the financial resources from the Amazon Fund reflects an arbitrary support of different projects that adopt very diverging theories of change that are not primarily concerned with attaining further deforestation reductions. As projects owners exert influence on funding effectiveness to some extent, the Amazon Fund may either seek to regulate the allocation of financial resources more actively or adopt funding effectiveness evaluations that account for this influence more comprehensively.

As in any other plant, in the grapevine roots play a vital role in terms of anchorage, uptake of water and nutrients, as well as storage and production of chemicals. Their behaviour and development depend on various factors, namely rootstock genetics, soil physical and chemical features, field agronomic practices. Canopy management, involving techniques such as defoliation and pruning, could greatly influence root growth. To date, most of the studies on grapevine winter pruning have focused on the effects on yield and quality of grapes, achievable by using different pruning systems and techniques, while the knowledge of root distribution, development, and growth in relation to winter pruning is still not well understood. In this contest, the purpose of this study was to investigate the effect of winter pruning on the root system of field-grown Vitis vinifera cv. Pinot Gris grafted onto rootstock SO4. We compared two pruning treatments (pruning-P and no pruning-NP) and analysed the effect on root distribution and density, root index and on the root sugar reserves. Root data were analysed in relation to canopy growth and yield, to elucidate the effect of winter pruning on the root/yield ratio. Our data indicated that winter pruning stimulated the root growth and distribution without compromising canopy development, while no-pruning treatment produced less growth of roots but a larger canopy. Information regarding root growth and root canopy ratio is important as it gives us an understanding of the relationship between the aerial and subterranean parts of the plant, how they compete, and finally, offers us the possibility to ponder on cultural practices.

Objective: To investigate the effects and mechanisms of different concentrations of CCCP on mitophagy in human peripheral blood regulatory T cells. Methods: Tregs were isolated, identified and then grouped, treating with CCCP at a concentration of 2.5 μM, 5 μM, 10 μM, 20 μM and 40 μM for 24h in an incubator. Flow cytometry detected the reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial quality, and fluorescence microscopy observed the co-localization of mitochondria and lysosomes in each group. Results: The purity of CD4⁺CD25⁺Tregs was (93.36 ± 1.87) %. With the increase of CCCP concentration, the level of ROS gradually increased, while the MMP decreased gradually. About the mitochondria and lysosome fusion, the fluorescence intensity of orange (yellow) was the highest when the concentration of CCCP was in the range of 5-10 μM while decreased with the CCCP concentration continually increasing. The mitochondrial quality decreased with the increase of CCCP concentration. However, there was no significant difference between groups C, D and E. The mitochondrial quality of groups F and G were significantly lower than that of group E. Conclusions: With the concentration of CCCP gradually increased, the level of ROS in Treg cells increased, and MMP decreased, which promoted the mitophagy, mitochondrial quality maintains homeostasis; When ROS accumulated, and MMP decreased significantly, the mitophagy was inhibited, and the mitochondrial quality was significantly decreased.

The article analyzes Bernoulli 's binary sequences in representation of empirical events about the distribution of natural resources and population sizes. Considering the event as a nonlinear system, and consisting of two dependent random variables, with memory and probabilities in maximum finite or infinite lengths, constant and equal to ½ for both variables (stationary process). The expressions of the possible trajectories remain constant in sequences that are repeated alternating the presence or absence of one of the variables at each iteration (asymmetric). There are constant oscillations in the event except if the variables X₁ and X₂ are regulated as a function of time Y. It is observed that the variables X₁ and X₂ assume in time T_k → ∞ specific behaviors (geometric variable) that can be used as management tools for random systems. In this way, the article seeks to know from this analyzes, the maximum entropy of information in the system by a theoretical view and how to model resources distribution or containment in the given problem.

The objective of this study was to determine the effects of supplementing L-isoleucine (L-Ile) on milk protein synthesis, using an immortalized bovine mammary epithelial (MAC-T) cell line. In this case, the cells were treated with 0, 0.3, 0.6, 0.9, 1.2 and 1.5 mM of supplemental Isoleucine (Ile), and the most efficient time for protein synthesis for each amino acid was determined by measuring the cell, medium and total protein at 0, 24, 48, 72 and 96 h. Confirmatory tests showed that 48h incubation time and 0.6 mM dosage of L-Ile are considered as the optimal time and dosage. The mechanism of milk protein synthesis was elucidated through proteomics analysis to clarify the metabolic pathway. When the L-Ile was supplemented, extracellular protein (medium protein) reached a peak at 48h, whereas in the case of the intracellular cell protein, it was shown to have reached to its peak at 24h in all L-Ile dosage treatments. In total, it is noted that there were 63 upregulated and 52 downregulated proteins. The results of the protein pathway analysis showed that the L-Ile group stimulated insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade, insulin/IGF pathway-protein kinase B signaling cascade, p53 pathway, de novo purine biosynthesis, Wnt signaling pathway, glycolysis, pentose phosphate pathway, and ATP synthesis which are pathways involved and related to protein and energy metabolism. Together, these results demonstrate that L-Ile supplementation was effective in stimulating β-casein synthesis by stimulating genes and pathways which are significantly related to protein and energy metabolism.

The interlaminar shear behavior of a [±45°] laminated carbon fiber reinforced plastic (CFRP) specimen was investigated utilizing microscale strain mapping in a wide field of view. A three-point bending device was developed under a laser scanning microscope, and the full-field strain distributions including normal, shear and principal strains of CFRP in a three-point bending test were measured using a developed sampling Moire technique. The microscale shear strain concentrations at interfaces between each two adjacent layers were successfully detected and found to be positive-negative alternately distributed before damage occurrence. The 45° layers slipped to the right relative to the -45° layers, visualized from the revised Moire phases and shear strain distributions of the angle-ply CFRP under different loads. The absolute values of the shear strain at interfaces gradually rose with the increase of the bending load, and the sudden decrease of the shear strain peak value implied the occurrence of interlaminar damage. The evolution of the shear strain concentrations is useful in the quantitative evaluation of the potential interlaminar shear failure.

Distributed deformation based on Fiber Bragg Grating sensors or other kinds of strain sensors can be used to evaluate safety in operating periods of bridges. However, most of the published researches about distributed deformation monitoring are focused on solid rectangular beam rather than box girder—a kind of typical hollow beam widely employed in actual bridges. Considering that the entire deformation of a single-cell box girder contains not only bending deflection but also two additional deformations respectively caused by shear lag and shearing action, this paper again revises the improved conjugated beam method (ICBM) based on the LFBG sensors to satisfy the requirements for monitoring two mentioned additional deformations. The best choice for the LFBG sensor placement in box gilder is also proposed in this paper due to strain fluctuation on flange caused by shear lag effect. Results from numerical simulations show that most of the theoretical monitoring errors of the revised ICBM are 0.3%~1.5%, and the maximum error is 2.4%. A loading experiment for a single-cell box gilder monitored by LFBG sensors show that most of the practical monitoring errors are 6%~8%, and the maximum error is 11%.

This paper presents a demonstration of the feasibility of fabricating micro-cantilever harvesters with extended stress distribution and enhanced bandwidth by exploiting an M-shaped two-degrees-of-freedom design. The measured mechanical response of the fabricated device displays the predicted dual resonance peak behavior with the fundamental peak at the intended frequency. This design has the features of high energy conversion efficiency in a miniaturized environment where the available vibrational energy varies in frequency. It makes such a design suitable for future large volume production of integrated self powered sensors nodes for the Internet-of-Things.

Immunotherapy has been considered for years as a viable and attractive treatment option for patients with cancer. Among immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionized the treatment of several subtypes of tumours. These approaches aimed at restoring an effective anti-tumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells, and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because in these diseases the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and will build a projection of how the field may evolve in the near future. In particular, we will analyze the current strategies being evaluated both preclinically and clinically with the aim to foster the use of immune-checkpoint inhibitors in non-Hodgkin lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies.