The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

The function of the endoplasmic reticulum (ER) can be impaired by the alternation of the extra- and intracellular environment such as disruption of calcium homeostasis, expression of mutated proteins and oxidative stress. In response to disruptions to ER homeostasis, eukaryotic cells activate canonical branches of signal transduction cascades, collectively termed the unfolded protein response (UPR). The UPR attempts to recover the protein folding capacity and avoid irreversible cellular damage. Additionally, the UPR has been shown to play unique physiological roles in the regulation of diverse cellular events, including cell differentiation and development and lipid biosynthesis. Recent studies have indicated that these important cellular events are also regulated by contact and communication among organelles. These reports suggest strong involvement among the UPR, organelle communication and regulation of cellular homeostasis. However, the precise mechanisms for the formation of contact sites and the regulation of its dynamics by UPR remain unresolved. In this review, we summarized the current understanding of how the UPR regulates morphological changes to the ER and the formation of contact sites between the ER and other organelles. We also review how UPR-dependent connections between the ER and other organelles affect cellular and physiological functions.

The research is focusing on analyzing the concentrations of particulate matter (PM) next to a highly congested road section, with 39,900 as a maximum number of vehicles per 24 h, in the vicinity of Timisoara, Romania. Concentrations have been measured in multiple episodes using two different measurement methods, gravimetric and dynamic light scattering, showing a disperse range of PM concentrations. Presence of metal particles in the samples have been analyzed using an electron microscope. Additionally, impact on human health is described by evaluating results for inhalable, thoracic, and alveolar sized particles.

in this paper, the optical channel performance with respect to varying scintillation index parameters is studied. Where different channel effects are studied and analyzed. In free-space optical (FSO) communication, the major drawback of the optical communication system is the atmospheric turbulence (AT). This effect is nonlinear with optical channel altitude being changed. Therefore, the power margenal (PM) required for such a channel is also inconstant respectively. In this thesis, we analyze AT effect on the optical channel with different altitudes. Such that we found the difference in the range of PM required for such optical link distance. In our result, the Bit Error Rate (BER) VS. PM required is measured. The optical channel model is Log-Normal considered and the BER threshold BER^th = 10^-10 is taken.

The objective of this research is to analyze metal elements like Na (sodium), Mg (magnesium), Al (aluminum), Si (silicon), Pb (lead), K (potassium), Ca (calcium), and Fe (iron) found in dust particles within two distinct areas from which the sampling has been done. First sampling was taken from the road verge of a highly trafficked road section, while the second sampling was done in a residential garden area 90 m away from the road. Several metal elements have been detected, with a high difference for Silicon Si, which present higher concentrations in the dust sampled from the road verge area. Pb has only been detected in the samples taken from the road verge, which could be explained by residual remnants from old lead gasoline, and wheel weights. Additionally, airborne particulate matter (PM) concentrations have been measured, during the same episode, in comparison between the road verge and the garden area, presenting a substantial difference in the concentration levels, deducing that dense vegetation is protecting and blocking a majority of airborne PM. A literature highlight of health effects of different metal elements and PM concentrations is presented.

This paper makes a theoretical contribution by exploring the integration of sustainability principles into project management. It compares two recent methodologies, PM² and PRiSM^TM, and provides a practical contribution by advocating for the adoption of these sustainability-driven practices among practitioners. Sustainability remains relatively unknown in the realm of project management, and this research aims to bridge that gap. The study follows an interpretivist philosophy and employs a combination of interviews and archival data analysis. PM², created by the European Commission, provides a project management methodology free to organizations and includes best practices from other bodies of knowledge. However, it doesn't include sustainability, because it aims to be generic. PRiSM^TM, based on the P5™, aims to make the project management process more sustainable. PRiSM^TM has P5 Impact Analysis and Sustainability Management Plan as the main differentiating deliverables and is an extension of the Triple Bottom Line, also including product and process. The PM² Alliance CEO believes that PM² aims to be generic, so a focus on sustainability would remove the methodology's "elasticity". However, users wishing to use PM² and consider sustainability can include it in the additional objectives and use PRiSM^TM differentiating deliverables.

Air pollution has become a growing invisible killer in recent years and is major cause of morbidity and mortality globally. India stands 10th among the highly polluted countries with an average PM10 level of 134μg/m3 per year. It is also reported that 99% of India's population comes across air pollution level that exceed the World Health Organization Air Quality Guideline (AQG), PM2.5 permissible levels of 10 μg/m3. Maternal exposure to air pollution has a serious health outcome to the offspring because it can affect embryonic phases of development during the gestation period. Fetus is more prone to air pollution effect during embryonic developmental phases due to oxidative stress as antioxidant mechanisms are lacking at that stage. Any injury during this vulnerable period (embryonic phase) will have long-term impact on offspring health both in early and later in life. Epidemiological studies have revealed that maternal exposure to air pollution increases the risk of developing airways disease in offspring due to impaired lung development in utero. In this review, we discuss cellular mechanisms involved in maternal exposure to air pollution and how it can impact development of airways disease in offspring. Better understanding of these mechanisms in context of maternal exposure to air pollution can offer newer avenue to prevent development of airways disease in offspring.

The variations of visibility, PM mass concentration and mixing layer height (MLH) at four major urban-industry regions (Shenyang, Anshan, Benxi and Fushun) in multi-cities of central Liaoning over northeast China were evaluated from 2009-2012 to characterize the dynamics effect on air pollution. The annual mean visibilities were about 13.7±7.8km, 13.5±6.5km, 12.8±6.1km and 11.5±6.8km in Shenyang, Anshan, Benxi and Fushun, respectively. The pollution load (PM×MLH) shown a weaker vertical diffusion in Anshan with a higher PM concentration in the near-surface. High concentrations of fine mode particles may be partially attributed to the biomass burning emissions from September in Liaoning Province and surrounding regions in Northeast China as well as the coal burning during the heating period with lower MLH in winter. The increasing wind speed has a similar change as the increasing of mixing layer height to make the effect on the aerosol vertical diffusion. The visibility on the non haze-fog days was about 2.5-3.0 times higher than that on hazy and fog days. The fine particle concentrations of PM2.5 and PM1.0 on the haze and fog days were ~1.8-1.9 times and ~1.5 times higher than that on no hazy-fog days. The MLH during fog pollution showed more declining trend than haze pollution compared with non haze-fog days. The results of this study could provide the useful information to better recognize the effects of vertical pollutants diffusion on air quality in the multi-cities of central Liaoning over Northeast China.

Particulate matter (PM) is one of the problems faced in environmental science. It has health effects on man and animals in both developed and developing countries. Research and efforts have been on it several years back. Policy statements and efforts have been published. This review paper is an added information on air pollution. In it, efforts were made in discussing these: classification, effects, methodology, case studies and source apportionment. It is hoped that this paper would contribute to existing knowledge on PM.

Despite accumulating evidence for the pro-apoptotic role for X-linked inhibitor of apoptosis-associated factor 1 (XAF1), its involvement in endoplasmic reticulum (ER) stress response remains undefined. Here, we report that XAF1 enhances cell sensitivity to ER stress and acts as a switch in unfolded protein response (UPR)-mediated cell-fate decisions favoring apoptosis over adaptive autophagy. XAF1 interacts with and destabilizes ER stress sensor GRP78 through the assembly of zinc finger protein 313-mediated destruction complex. Moreover, XAF1 gene transcription is activated by ER stress through PERK-Nrf2 signaling to direct an adaptive to apoptotic switch of stress response by blocking C-terminus of Hsc70-interacting protein (CHIP)-mediated K63-linked ubiquitination and subsequent phosphorylation of inositol-required enzyme-1α (IRE1α). In tumor xenograft assays, XAF1-/- tumors display substantially lower regression compared to XAF1+/+ tumors in response to cytotoxic dose of ER stress inducer. XAF1 and GRP78 expression show an inverse correlation in human cancer cell lines and primary breast carcinomas. Collectively this study uncovers an important role for XAF1 as a linchpin to govern the sensitivity to ER stress and the outcomes of UPR signaling, illuminating the mechanistic consequence of XAF1 inactivation in tumorigenesis.

The study aimed to estimate the prevalence of respiratory symptoms and to assess respiratory health risks associated with Particulate Matter (PM) exposure among the residents of Windhoek, Namibia. Objectives: To measure particulate pollution concentration in Windhoek through monitoring of particulate matter concentration and to identify any associations between particulate pollution, individual location and respiratory health among the Windhoek resident’s. Methods: an adapted standardized self-administered questionnaire was used to collect respiratory health related data as well as previous exposure, while PM monitoring was done using ASTM D1739 reference method. Results: A high prevalence was observed for cough (43%), breathlessness (25%), and Asthma (11.2%). PM was found to be a significant risk factor for episode of cough and phlegm, while high PM exposure category had increased odds ratio for episode of phlegm and cough (OR: 2.5, 95% CI: 0.8-8.0). No association was observed between location and respiratory health outcomes. Conclusion: The study found high levels of PM concentration across all Windhoek suburbs which were above the German, American and EPA. Enactment of legislation relating to the control and monitoring of PM related emissions at point of generation is required at country and city level.

Cellular Integrated Stress Response (ISR), the mitochondrial Unfolded Protein Response (UP-Rmt) and the IFN signaling are associated with viral infections. The Activating transcription fac-tor 4 (ATF4) plays a pivotal role in these pathways and controls the expression of many genes involved in redox processes, amino acid metabolism, protein misfolding, autophagy and apop-tosis. The precise role of ATF4 during viral infection is unclear and depends on cell hosts, viral agents and models. Furthermore, ATF4 signaling can be hijacked by pathogens to favor viral in-fection and replication. In this review, we summarize the ATF4-mediated signaling pathways in response to viral infections, focusing on human immunodeficiency virus (HIV). We examine the consequences of ATF4 activation for HIV replication and reactivation. The role of ATF4 in au-tophagy and apoptosis is explored as in the context of HIV infection programmed cell deaths contribute to the depletion of CD4 T cells. Furthermore, ATF4 can also participate in the estab-lishment of innate and adaptive immunity that are essential for the host to control viral infec-tions. We finally discuss the putative role of the ATF4 paralogue, named ATF5, in HIV infection. This review underlines the role of ATF4 at the crossroads of multiple processes reflecting host-pathogen interactions.

Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the kidney proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week old and the subsequent development of polycystic kidneys at three week old. As the damaged proximal tubular cells with intracellular vacuoles later form cysts, autophagy may play a role in their survival. We examined the autophagy activity before and after the development of cysts in AQP11(-/-) kidneys. We first observed an enhanced expression of LC3 gene (Map1lc3b) as well as other autophagy-related genes in AQP11(-/-) mice by quantitative PCR analysis. We then examined the formation of autophagosomes visualized by a green fluorescent fusion protein, GFP–LC3 in its transgenic mice. The expression of GFP-LC3 puncta was increased in the proximal tubule of AQP11(-/-) mice before the cyst formation. Interestingly, they were also observed in the cyst-lining epithelial cell. Further PCR analyses revealed the enhanced expression of apoptosis- and ER stress-related caspase genes before and after the cyst formation suggesting that ER stress may have enhanced autophagy. We conclude that autophagy will play an important role in the development and the survival of the kidney cysts in AQP11(-/-) mice.

Inhaled particulate matter (PM) is a key player in the millions of yearly deaths worldwide related to air pollution. The oxidative potential of PM provides an indication of its ability to promote an oxidative environment. When the human lungs are exposed to PM, the reactive oxygen species (ROS) generated in such oxidative environment, if excessive, may lead to cell damage via oxidative stress. Inflammation, endoplasmic reticulum stress, airway remodeling, and many different cell death modes (apoptosis, ferroptosis, pyroptosis, among others) can be triggered by oxidative stress via complex molecular pathways, which also involve the adaptive cellular response. But ROS can also directly interact with macromolecules such as proteins and lipids, as well as nucleic acids, having been reported to induce DNA damage and epigenetic modifications, which jeopardizes homeostasis. These facts have been extensively studied in in vitro models and confirmed in in vivo models.In this review, we delve beyond conventional assessments of airborne particles, discussing their oxidative potential and the PM-induced ROS-mediated cellular damage observed in in vitro models. The close link between oxidative stress and inflammation, and the manifestation of different cell death modes is highlighted by reviewing the latest literature. The effects of ROS on the balance of DNA damage and repair, carcinogenicity and epigenetics interplay are then analyzed. Finally, we expand on the latest reports on the antioxidants’ potential to counteract the deleterious effects of ROS, and disclose future perspectives for the topic.

Air conditioning system of electric vehicles has new change as the internal combustion engine is being replaced with electrified AC motor. With large amount of batteries installed at the bottom of frame, the conventional compressor which is belt-driven can be removed and another AC motor can play the role for air conditioning in electric vehicles. From this change, the system efficiency would be improved since it is possible to control the electrified compressor independently from traction system in contrast with the belt-driven compressor. As a result, by applying the electrified compressor for air conditioning system, the whole system can achieve better efficiency and longer driving distance, which is most important in electric vehicles. In this paper, 3-phase interior permanent magnet synchronous motor (IPMSM) was designed using lumped-parameter model and finite element method.

Air quality has been a major concern throughout the world, Nigeria inclusive. The monitoring of air quality involves indoor and outdoor air quality. In this study, our concern was on indoor air quality. The aim of this study was to assess the air quality of residential homes (17), classrooms (3), hospitals (2), offices (5), Shops (2), and laboratories (5) in Akure, Nigeria in terms of formaldehyde (HCHO), total volatile organic compound (TVOC), Particulate matter (PM_1.0; PM_2.5, and PM₁₀). A Multifunction Air Detector was used for the assessment using the manufacturers’ procedures and the locations were identified using a Mini GPS. The results revealed as follows: HCHO (0.001-0.030 mg/m³), TVOC (0.003-362 mg/m³), PM_1.0 (004-014 µg/m³), PM_2.5 (006-020 µg/m³), and PM₁₀ (006-022 µg/m³). The results obtained were below the 24 h pollution recommended standards (0.1 mg/m³- HCHO; TVOC; 10-20 μ/m³ PM) of EPA and WHO. Statistically, there were correlations within the pollutants and weather. The Indoor air quality (IAQ) depicted the areas as ‘good,’ and toxicity potential (TP) were below unity. Although the locations looked safe, it is recommended that constant monitoring of the indoors should be ensured and proper ventilation should be provided.

Acute HSV-1 infection is associated with mild symptom, such as fever and lesions of the mouth, face and skin. This phase is followed by a latency period before reactivation which is associated with symptoms ranging from ulcers to encephalitis. Despite available anti-HSV-1 drugs, the development of new antiviral agents is sought due to the presence of resistant viruses. Melatonin, a molecule secreted by the pineal gland, has been shown to be an antioxidant, inducer of antioxidant enzymes, and regulator of various biological processes. Clinical trials have explored its therapeutic utility in conditions including infections. This study focuses on melatonin's role in HSV-1 replication and the underlying mechanisms. Melatonin was found to decrease the synthesis of HSV-1 proteins in infected Vero cells measured by inmunofluorescence indicating an inhibition of HSV-1 replication. Additionally, it regulates the activities of antioxidant enzymes and affects proteasome activity. Melatonin activates the unfolded protein response (UPR) and autophagy and suppresses apoptosis in HSV-1-infected cells. In summary, melatonin demonstrates an inhibitory role in HSV-1 replication by modulating various cellular responses, suggesting its potential utility in the treatment of viral infections.

This paper aims to contribute to the advancement of scientific knowledge about the impact of the COVID-19 pandemic on social workers and the social work profession in Romania. Research has shown that social work is a profession at high risk for developing the burnout syndrome, which has many detrimental effects on both social workers and the clients that they serve. Two conceptual models are used to frame the discussion: the theoretical framework of VUCA (volatility, uncer-tainty, complexity, and ambiguity) to discuss the challenges of the unprecedented context the COVID-19 pandemic has created for social workers; stress and burnout to explain the negative impact of this period of time. Based on convergent mixt methods, the study sample consisted of 83 social workers employed in statutory and private social services in Romania, from different fields of intervention. Results show that 25,3% of respondents suffer from a high level of burnout and 44.6% scored in a range that indicate a medium level of burnout. A group of 31.1% have managed to handle stress factors in a healthy manner. Main stressors found are especially personal (fear of contamination, personal and family) and work-related factors (workload, new legislative rules and decisions, inconsistency, instability, ambiguity of managerial decisions, or even their absence or non-assumption, lack of clarity of working procedures, limited managerial and supervisory support, limited financial resources), less than client related factors (lack of direct contact, risk of contami-nation in two ways, managing beneficiaries fears, difficulties related to technology and digital skills). Study results point to the importance of organizational support and developing a self-care plan that help protect against occupational stress and burnout. Recommendations are made putting forward the voice of fieldworkers and managers fostering initiatives and applications of sustainability-based measures and activities designed to deal with the challenges of the VUCA environment.

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). The replication rate generates a high polyprotein integration that can contribute to ER stress. Therefore, the host cell can develop an Unfolded Protein Response (UPR) to this protein accumulation which will stimulate appropriate cellular responses in the infectious context (Adaptation, autophagy or cell death). These different stress responses can help to overcome the virus and usually support antiviral strategies initiated by infected cells. In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in epithelial A549 cells with a special focus on the causal factors behind it. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway but surprisingly without activation of the ATF6 branch. When we examined the effects of modulating the ER stress response we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV can altered the UPR in order to escape to the host cell defense system.

A classical origin for the Bohmian quantum potential, as that potential term arises in the quantum mechanical treatment of black holes and Einstein-Rosen (ER) bridges, can be based on 4th-order extensions of Einstein's equations. In Bohm's ontological interpretation, black hole radiation, and the analogous tunneling process of quantum transmission through an ER bridge, are classically allowed if the dynamics are modified to include such a quantum potential. The 4th-order extension of general relativity required to generate the quantum potential is given by adding quadratic curvature terms with coefficients that maintain a fixed ratio, as their magnitudes approach zero. Quantum transmission through the classically non-traversable bridge is replaced by classical transmission through a traversable wormhole. If entangled particles are connected by a Planck-width ER bridge, as conjectured by Maldacena and Susskind, then the classical wormhole transmission effect gives the ontological nonlocal connection between the particles posited in Bohm's interpretation of their entanglement. It is hypothesized that higher-derivative extensions of classical gravity can account for the nonlocal part of the quantum potential generally.

Introduction: Patients’ satisfaction was extensively researched over the last decades, given its role in building loyalty, compliance to treatment, prevention, and eventually higher levels of wellbeing and improved health status. Patients’ feedback on the perceived quality of health services can be incorporated into practice; therefore, understanding factors and mechanisms responsible for patients’ satisfaction allows providers to tailor targeted interventions. Method: A questionnaire assessing patients’ perception of the quality of health services was administered to a country-representative sample of 1500 Romanian patients. Using a partial least squares—path modeling approach (PLS-PM), with cross-sectional data, we developed a variance-based structural model, emphasizing the mediating role of trust and satisfaction with various categories of health services. Results: We confirmed the mediating role of trust in shaping the relationship between the procedural accuracy of health professionals, along with the perceived intensity of their interaction with patients, and patients’ experienced quality of the health services. We confirmed the mediating role of satisfaction by the categories of services in the relationship between waiting time on the premises, attention received, and the perceived reliability of the information received, as predictors, and the experienced quality of the health services. In addition, indirect assessment of patients’ satisfaction is a good predictor for direct assessment, thereby affirming the idea that the results of the two types of evaluations converge. Discussions: One of the most efficient solutions to increase both patients’ satisfaction and their compliance is to empower the communication dimension between patients and health practitioners. Given the non-linear relationships among variables, we advocate that, unless the nature of the relationships between satisfaction and its predictors is understood, practical interventions could fail. The most relevant variable for intervention is the degree of attention patients perceive they received. We suggest three methods to turn waiting time into attention given to patients.

Iron powders having average particle sizes of ~40µm are mechanically mixed thoroughly with aluminum powders ranging from 1 to 10 in wt.% with an average particle size of ~10µm. Two different powder metallurgical techniques cold and hot pressing are used to study the effect of the additive element powder on the mechanical properties, wear properties and the microstructure of the iron based alloys. The hot pressing technique was performed at a temperature up to 500°C at 445.6 MPa. The cold pressing technique was performed at 909 MPa in room temperature. By increasing the Al content to 10 wt. % in the base Fe-based matrix, the hardness was decreased from 780 to 690 MPa and the radial strength was decreased from 380 to 202 MPa with reductions of 11.5% and 40%, respectively. Improvement of the wear resistance with the increase addition of the Al powder to the Fe matrix up to 5 times was achieved compared to the alloy without Al addition for different wear parameters namely; wear time and sliding speed.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus considered as a threat to human health due to large epidemics and serious clinical outcomes such as microcephaly in newborns. Like all flaviviruses, ZIKV relies on the cellular machinery to complete its viral cycle, with the endoplasmic reticulum (ER) being the critical site of viral replication factories. The sudden high protein load in the ER induces an ER stress to which the cell responds with an appropriate unfolded protein response (UPR) in an attempt to restore its disturbed homeostasis. When the restoration fails, the cell signaling leads to a programmed cell death by apoptosis with the upregulation of the UPR-induced C/EBP homologous protein (CHOP) which acts as the main trigger for this fatal outcome. Our previous studies have shown the ability of ZIKV to manipulate various cellular responses in order to optimize virus production. ZIKV is able to delay apoptosis to its benefit and although ER stress is induced, the UPR is not complete. Here we discovered that ZIKV impairs the expression of CHOP/DDIT3, the main factor responsible of ER-stress driven apoptosis. Surprisingly, the mechanism does not take place at the transcriptional level but at the translational level.

(1) Background: Prefabricated zirconia crowns are used to restore teeth in children. The purpose of this study was to evaluate the removal of these crowns with the erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser; (2) Methods: Twelve primary and 13 permanent teeth were prepared and prefabricated zirconia crowns were passively fitted and cemented with two resin modified glass-ionomer cements. Surface areas of prepared teeth and crowns were calculated. Crowns were removed using two laser settings: 4.5 Watts, 15 Hertz, 20 water/ 20 air, and 5 Watts, 15 Hertz, 50 water/50 air. The retrieval time and temperature changes were tested recorded. Data were analyzed using ANOVA with Tuckey’s adjusted post hoc pairwise comparison t-test; (3) Results: The average time for crown removal was: 3 minutes, 47.7 seconds for permanent; and 2 minutes 5 seconds for primary teeth. The mean temperature changes were 2.48℃ (SD=1.43) for permanent; and 3.14℃ (SD=1.88) for primary teeth. The time to debond was significantly positively correlated with tooth inner surface area and volume, outer crown volume, and the cement volume; (4) Conclusions: Use of the Er,Cr:YSGG laser is an effective, safe and non-invasive method to remove prefabricated zirconia crowns cemented with RMGI cements from permanent and primary teeth.

Translation is spatiotemporally regulated and ER-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, suggesting that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, suggesting that PARN may play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. By promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy, the ER-anchored PARN modulated DNA damage response and thereby cell viability. These findings revealed that a highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and that PARN may contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies.

Environment pollution is the major problem for all the sectors. In environment pollution there are different types of pollution is included such as air pollution, water pollution, soil pollution etc. In these types of pollution most of it is air pollution. There are many reasons for pollution of air. Human advance in science but one of the major draw backs of science is the pollution of air rapidly. Air pollution is injurious to health. Every year a large number of people died for the effects of air pollution. It can be improved in many ways among these ways technology upgradation plays a major role here. There are various method that prevent air pollution. Many researchers tried and is trying to prevent the air pollution in many ways. In this review paper I summarise the existing research on different ways for preventing air pollution in addition I will discuss the gaps and future aspect on this topic.

The construction industry is notable contributors to atmospheric dust particulate emissions. The particulate matter (PM) produced in construction processes contains a range of chemically hazardous substances, posing significant health risks (HR) to individuals. The occupational health hazards research in construction has become a focal point of interest internationally. Initiated in the early 2000s, there has been a growing demand within the construction research community for the creation of a unified PM database that encapsulates a wide array of construction activities. Previous studies have endeavored to establish a PM database for various construction contexts, yet they have fallen short in thoroughly addressing the diversity of construction materials and the levels of toxic substances (TS) within the PM. This study validates the proof of value that HR associated with construction processes can be measured using PM and TS datasets generated from various work processes using a variety of construction materials. This was accomplished through a semi-automated Building Information Modeling (BIM)-based plugin, which streamlines the assessment of occupational HR in construction projects alongside ongoing work processes. To validate the practicality of the Health Risk Index (HRI) determination via this BIM plugin, a case study on a real renovation project was executed. This system provides construction supervisors with a tool to visually assess the HR of daily operations, thereby facilitating the adoption of preemptive measures to protect the health of construction workers.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (>12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Endoplasmic reticulum (ER) is an important organelle responsible as protein synthesis regulator in plant. High salinity can also lead to the activation of ER stress, caused by the accumulation of misfolded protein. This could lead to a stress response mechanism, unfolded protein response (UPR). Failure of UPR to reverse the effect of protein misfolding will activate Programmed Cell Death (PCD). Metacaspase genes regulate programmed cell death (PCD) in plants. The present study was focused on comprehensive gene analyses of the expression patterns of type II rice metacaspase (OsMC) genes in response to the endoplasmic reticulum (ER) and salinity stress in rice leaf and OsMC4 in callus. A strong evidence of unfolded protein response (UPR) during tolerance to both ER and salinity stress was found in the present study. Overexpression of OsMC4 in rice callus as a fusion protein with TagRFP and controlled by the CaMV35 promoter caused major changes in the expression of the stress ER-marker genes, protein disulfide isomerase (PDI) and Binding immunoglobulin Protein (BiP), and OsMC4 in overexpressing calli. These expression analyses of the OsMC family provide valuable information for further functional studies on the biological roles of OsMCs in PCD related to ER and salinity stress responses.

The microstructure of Al-5Fe-1.5Er alloy was characterized and analyzed by using XRD, SEM, TEM and EDS. The effect of microstructure on the behavior of crack initiation and propagation was investigated by in situ tensile testing. Results show that the microstructure consists of α-Al matrix, Al₃Fe, Al₄Er, eutectic phase Al₃Fe + Al₄Er, while the 1.5 wt.% Er was added in Al-5Fe alloy. The twin structure of the Al₃Fe phase was observed, and the twin plane is {001}. Moreover, a continuous concave and convex interface structure of the Al₄Er has been found. Al₃Fe is in the form of a sheet with a clear gap inside.In situ tensile tests of the alloy at room temperature show that the crack initiation occured mainly in the Al₃Fe phase, and that the crack propagation modes include intergranular and transgranular expansion. Crack transgranular expansion is due to the strong binding ability between Al₄Er phases and surrounding organization, and the continuous concave and convex interface structure of the Al₄Er provides a significant meshing effect on the matrix and eutectic structure.

Endo-reticular stress induces the unfolded protein response including a highly conserved set of genes crucial for cell survival against a variety of onslaughts. Among the activated stress response genes is Ire1, which undergoes auto-phosphorylation and acquires a regulated Ire1-dependent mRNA decay activity. Ire1P non-canonically splices the mRNA for Xbp1 in the cytoplasm. This spliced Xbp1 serves as mRNA encoding a transcription factor for unfolded protein response genes. Meanwhile the mRNA decay function of Ire1P degrades other cellular mRNAs and can cause changes to the translation machinery by altering regulators in a cell specific manner. Naïve splenic B cells differentiate into Antibody Secreting Cells and activate Ire1 phosphorylation early on after LPS stimulation, within 18 hrs. When Ire1 is activated in B cells, in addition to Xbp1 splicing, there are large-scale changes in mRNA; inhibition of the mRNA degradation function of Ire1 both reduces the number and changes the type of genes involved in altered splicing patterns, including factors for snRNA transcription. Some of the splicing changes seen at 18 hrs after LPS persist into the late stages of antibody secretion, up to 72 hrs, while others are supplanted by new splicing changes introduced by the induction of ELL2, a transcription elongation factor. ELL2 changes mRNA processing patterns and is necessary for Immunoglobulin secretion. RNA splicing patterns in antibody secreting cells are thus shaped by endo-reticular stress, ELL2 induction, and are associated with changes in the levels of snRNAs.

Both fibrosis and cirrhosis of the liver are the end results of most kinds of chronic liver damage and present a common but difficult clinical challenge throughout the world. The inhibition of the fibrogenic, proliferative, and migratory effects of hepatic stellate cells (HSCs) has become an experimental therapy for preventing and even reversing hepatic fibrosis. Furthermore, a complete understanding of the function of non-coding RNA-mediated epigenetic mechanisms in HSC activation may improve our perception of liver fibrosis pathogenesis. This review focuses on an evolving view of molecular mechanisms in which HSC activation by miR-29a signaling may moderate their profibrogenic phenotype, thus supporting the use of miR-29a agonists as a potential therapy for treating liver fibrosis in the future.

Spectacularly, particulate matter pollution influences human health by aggravating numerous diseases and causing premature deaths. In order to eliminate its concentration in the ambient air, plant species can act as natural bio-filters and capture, degrade, and metabolize air pollutants inside their foliage. In a study carried out at three sites with different pollution levels and plant types. The immobilization efficiency of Particulate Matter (PM) was investigated in the leaves of three species (shrub, climber, and herb) in the southwestern of Japan with a time gap of 14 days. Two healthy mature leaf samples of each specimen were carefully collected and analyzed using the gravimetric analytical method. A significant quantity of PM in three-size fractions with aerodynamic diameters ranging between (0.1-100 μm) was captured inside the leaf foliage of the analyzed species. Fine particles (2.5 -10 μm) dominated the highest portion of the PM deposition captured by the analyzed species with 70.6 μg.cm-2(39.5%). Shrub species represented with Elaeagnus pungens proved to be the most efficient species among the analyzed species. Leaf traits such as grooves, trichomes, roughness, and margin are considered key factors associated with positive PM deposition, whereas the total surface area of the leaves had no direct correlation to PM deposition.

The lockdown implemented to tackle the spread of the COVID-19 pandemic had a positive impact on air quality. Globally, studies have shown that the air pollutants levels reduced temporally during the restriction measures. In this study, we evaluated the impact of COVID-19 restrictions on the air quality of Western Macedonia, Greece, using the hourly concentrations of PM2.5 and PM10 along with meteorological data from the Air Quality Monitoring Stations (AQMS) operated by the Lignite Center of Western Macedonia. In Western Macedonia, previous studies have identified that there is a general reduction in air pollutants levels during the last decade due to coal phase-out plan for power generation. During the lockdown the levels of PM2.5 and PM10 decreased further. However, reduced emissions from the local mining activities and lignite-fired power plant electricity generation, as well as the weather conditions seems to contribute to improving air quality.

The economic downturn caused by the financial crisis of 2008-2009 and the intensifying glob-al climate policy trends forced changes in the energy management of the European Union. The study examined how the most relevant energy economic variables affected the economic growth of the EU between 2010-2019. The study examined the relationship between GDP (dependent variable) and energy consumption, greenhouse gas emissions, the average energy price, and renewable energy use (independent variables) using the PSL-PM methodology. The results show an asymmetric picture because the independent variables influenced the eco-nomic growth of the EU in the examined period with different correlations and with different strengths. One of the significances of the study is that the presented and analyzed variables, as well as the results of the relationships between them, can contribute to the optimization of the EU's currently critical energy management and economic growth.

The air is not the same as thousands and hundreds of years ago. In the air, suspended particles originate from natural phenomena like dust storms or volcanic activities, as well as anthropogenic pollutants such as fuel engine exhaust and everyday activities at home. The total particles in the air can be classified by sizes, such as PM10, PM2.5 or ultrafine particles. However, there are many other important factors in addition to the particle size, influencing the particle behavior and affecting our health. The surface area, chemical and biological composition, aspect ratio, and the charge are all factors characteristic of particles. OoC microfluidic chips are very useful for the pollutant toxicity measurements on various body tissues. A better understanding of pollutants will help to trace these to the potential sources. The data from the on-the-ground and satellite monitoring can be integrated into models, helping to predict and prevent pollution exposure.

The cast grains of the 7055 aluminum alloy were refined by adding Sm + Er, and the proper heat treatment procedure was utilized to further precipitate the rare earth phase in order to increase the alloy's strength and toughness. The grain size, microstructure and phase were characterized by optical microscopes (OM), Scanning electron microscopy - energy spectrum (SEM-EDS), XRD diffractometer (XRD). The macroscopic hardness, yield strength and tensile strength of alloy materials were measured by hardness meter and universal electronic tensile machine. The results shown that the as-cast sample and the heat treatment sample all exist Al10Cu7Sm2 and Al8Cu4Er rare earth phase; But after heat treatment, the volume percentage of the rare earth phase dramatically increased and the dispersion was more unified. When 0.3wt.%Sm and 0.1wt.%Er were added, the grain size could be refined to 53μm. With the increase of the total content of rare earth elements, the refining effect first increased and then decreased. Under 410 oC solid solution for 2h + 150oC aging for 12h, the macroscopic hardness, yield strength, tensile strength and elongation of 0.3wt.%Sm + 0.1wt.%Er+7055 as-cast sample were 155.8HV, 620.5Mpa, 658.1Mpa, and 11.90%, respectively.

Secretory and membrane proteins are vital for cell activities, including intra- and intercellular communication. Therefore, protein quality control in the endoplasmic reticulum (ER) is an essential and crucial process for eukaryotic cells. Endoplasmic reticulum-associated degradation (ERAD) targets misfolded proteins during the protein maturation process in the ER and leads to their disposal. This process maintains the ER productive function and prevents misfolded protein stress (i.e., ER stress). The ERAD-stimulating factor ER degradation-enhancing α mannosidase-like 1 protein (EDEM1) acts on misfolded proteins to accelerate ERAD, thereby maintaining the productivity of the ER. However, the detail mechanism underlying the function of EDEM1 in ERAD is not completely understood due to lack of established physiological substrate proteins. In this study, we attempted to identify substrate proteins for EDEM1 using siRNA. The matrix component thrombospondin-1 (TSP1) and epidermal growth factor receptor (EGFR) were identified as candidate targets of EDEM1. Their protein maturation status and cellular localization were markedly affected by knockdown of EDEM1. We also showed that EDEM1 physically associates with EGFR and enhances EGFR degradation via ERAD. Our data highlight the physiological role of EDEM1 in maintaining specific target proteins and provide a potential approach to the regulation of expression of clinically important proteins.

The endomembrane system in plant cells enables the cell to manage and coordinate a variety of membranous compartments so that they and their contents arrive at the right location. The secretory pathway takes part in this complex network and has its gateway at the Endoplasmic Reticulum. Therefore, alterations at the Endoplasmic reticulum level could condition how protein trafficking takes place or, at least, influence how such cargo leaves this organelle. With this work, we intended to assess how abnormalities at the Endoplasmic Reticulum would interfere with protein sorting and trafficking. Thus, we used a novel Arabidopsis mutant - leb-2 GFP-h -, presenting ER morphology alterations. Our results show that alterations in the leb-2 GFP-h mutant did not disrupt PSI A/B–mCherry transport to the vacuole but influences the expression of endogenous aspartic proteinases. Furthermore, the study of key-endomembrane genes expression revealed an upregulation of the SNAREs AtVAMP722 and AtVAMP723. As a whole, the leb-2 mutant seems not to interfere with vacuolar routes but may be implicated in secretion events.

PM-Gati-Shakti Initiative, integration of ministries, including railways, ports, waterways, logistic infrastructure, mass transport, airports, and roads. Aimed at enhancing connectivity and bolstering the competitiveness of Indian businesses, the initiative focuses on six pivotal pillars known as "Connectivity for Productivity": comprehensiveness, prioritization, optimization, synchronization, analytical, and dynamic. In this study, we explore the application of these pillars to address the problem of "Maximum Demand Forecasting in Delhi." Electricity forecasting plays a very significant role in the power grid as it is required to maintain a balance between supply and load demand at all times, to provide a quality electricity supply, for Financial planning, generation reserve, and many more. Forecasting helps not only in Production Planning but also in Scheduling like Import / Export which is very often in India and mostly required by the rural areas and North Eastern Regions of India. As Electrical Forecasting includes many factors which cannot be detected by the models out there, We use Classical Forecasting Techniques to extract the seasonal patterns from the daily data of Maximum Demand for the Union Territory Delhi. This research contributes to the power supply industry by helping to reduce the occurrence of disasters such as blackouts, power cuts, and increased tariffs imposed by regulatory commissions. The forecasting techniques can also help in reducing OD and UD of Power for different regions. We use the Data provided by a department from the Ministry of Power and use different forecast models including Seasonal forecasts for daily data.

A large core size and bending resistance are very important properties of mid-infrared energy transfer fibers, but large core sizes usually lead to a deterioration of bending properties. A negative-curvature nested node-free anti-resonant hollow-core fiber (AR-HCF) based on quartz is proposed. It was made by adding a nested layer to a previous AR-HCF design to provide an additional anti-resonance region while keeping the gap between adjacent tubes strictly correlated to the core diameter to produce a node-free structure. These features improve the fiber’s bending resistance while achieving a larger core diameter. The simulation results show that the radial air-glass anti-resonant layer is increased by the introduction of the nested anti-resonant tube, and the weak interference overlap between the fiber core and the cladding mode is reduced, so the fiber core’s limiting loss and the sensitivity to bending are effectively reduced. When the capillary wall thickness t of the fiber is 0.71 μm, the core diameter D is 70 μm, the ratio of the inner diameter of the cladding capillary to the core diameter d/D is 0.62, and the diameter of the nested tube is d0=29 μm, the fiber has a lower limiting loss at the wavelength of 2.79 μm, and the limiting loss is 3.28×10-4 dB/m. At the same time, the optimized structure also has good bending resistance. When the bending radius is 30 mm, the bending loss is only 4.72×10-2 dB/m. To our knowledge, this is the first research to achieve an anti-bending low-loss micro-structure hollow fiber with a bending radius of less than 30 mm in the 2.79 μm band. An anti-bending low-loss anti-resonant hollow-core fiber with this structure constitutes a reliable choice for the light guiding system of a 2.79 μm band erbium laser therapy instrument.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

To assess AR’s role in TNBC treatment, various existing and completed clinical trials targeting AR or co-targeting AR with other pertinent signaling molecules were analyzed. Cyclin-dependent kinase 4/6 (CDK4/6), cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17 lyase), and the phosphatidylinositol 3kinase (PI3K)/protein kinase B (AKT) signaling pathway were some of the most prevalent biomarkers used in combination therapy with AR inhibitors in these trials. Studying how AR functions in tandem with these molecules can have increasing breakthroughs in the treatment options for TNBC. Previous studies have been largely unsuccessful in utilizing AR as the sole drug target for systemic targeted treatment in TNBC. However, there is a lack of other commonly used drug target biomarkers in the treatment of this disease, as well. Thus, analyzing the clinical benefit rate (CBR) within clinical trials that are using combination therapy can prove to be imperative to the progression of improving treatment options and prognoses.

Flaviviruses replicate in membrane factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus viral protein accumulation contribute to ER stress. As a consequence, the host cell exhibits an Unfolded Protein Response (UPR), subsequently stimulating appropriate cellular responses such as adaptation, autophagy or apoptosis. The correct redox conditions of this compartment are essential to form native disulfide bonds in proteins. ZIKA virus (ZIKV) has ability to induce persistent ER stress leading to activation of UPR pathways. In this study, we wondered whether ZIKV affects the redox balance and consequently the oxidative protein folding in the ER. We found that ZIKV replication influences redox state leading to aggregation of viral envelope protein as amyloid-like structures in the infected cells.

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

Neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyloidal lateral sclerosis (ALS), and Huntington disease (HD) are the most concerned disorders due to the lack of effective therapeutics and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, yet they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and ER-stress, which combats with stress conditions, but the overwhelming cellular stress response induces cell damage. Small molecules such as flavonoids could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the mechanistic ways of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

The APIS Breast Cancer Subtyping Kit is an mRNA-based assessment of the three biomarkers routinely assessed in all newly diagnosed breast cancers (BC), estrogen receptor (ER), progesterone receptor (PR), and HER2 as well as an additional four genes that create a novel proliferation signature, MKI67, PCNA, CCNA2, KIF23. Taken together the data is used to produce a molecular sub-type for every sample. The kit was evaluated against the current standard protocol of immunohistochemistry (IHC) and/or in situ hybridization (ISH) in breast cancer patients. The data was presented at the weekly breast Multidisciplinary Team (MDT) meeting. 98 consecutive cases of pre-operative breast cancer core biopsies and two core biopsy of nodal metastases yielding 100 cases were assessed. IHC and APIS Results were available for 100 and 99 cases. ER was concordant in 97% cases, PR in 89% and HER2 results were concordant with IHC/ISH in 100% of the cases. Ki-67 IHC was discordant in 3% cases when compared with MK167 alone but discordant in 24% when compared with the four gene proliferation signature. In conclusion, our study, indicates that the APIS Breast Cancer Subtyping Kit is highly concordant when compared to the results produced for ER/PR/HER2 by IHC and/or ISH. The assay could play a role in the routine assessment of newly diagnoses Breast Cancer (BC) specimens.

Elevation of the intermediate amino acid metabolite Homocysteine (Hcy) causes Hyperhomocysteinemia (HHcy), a metabolic disorder frequently associated with mutations in the methionine-cysteine metabolic cycle as well as with nutritional deficiency and aging. Previous literature suggest that HHcy is a strong risk factor for cardiovascular diseases. Severe HHcy is well established to correlate with vascular pathologies primarily via endothelial cell death. Though moderate HHcy is more prevalent and associated with an increased risk of cardiovascular abnormalities in later part of life, its precise role in endothelial physiology is largely unknown. In this study, we report that moderate elevation of Hcy causes endothelial dysfunction through impairment of their migration and proliferation. We established that unlike severe elevation of Hcy, moderate HHcy is not associated with suppressed endothelial VEGF/VEGFR signaling and oxidative stress induction. We further showed that moderate HHcy induces a sub-lethal ER stress that causes defective endothelial migration through abnormal actin cytoskeletal remodeling. We also found that sub-lethal increase of Hcy causes endothelial proliferation defect by suppressing mitochondrial respiration and concomitantly increases glycolysis to compensate the consequential ATP loss and maintain overall energy homeostasis. Finally, analyzing an available microarray dataset, we confirmed that these hallmarks of moderate HHcy are conserved in adult endothelial cells as well. Thus, we identified adaptive UPR and metabolic rewiring as two key mechanistic signatures in moderate HHcy-associated endothelial dysfunction. As HHcy is clinically associated with enhanced vascular inflammation and hypercoagulability, identifying these mechanistic pathways may serve as future targets to regulate endothelial function and health.

The emergence of chemoresistance in neoplastic cells is one of the major obstacles in cancer therapy. Autophagy was recently reported as one of the mechanisms that promote chemoresistance in cancer cells by protecting from apoptosis and driving senescence. Thus, understanding the role of autophagy and its underlying signaling pathways is crucial for the development of new therapeutic strategies to overcome chemoresistance. We have previously reported that PKCη is a stress-induced kinase that confers resistance in breast cancer cells against chemotherapy by inducing senescence. Here we show that PKCη promotes autophagy induced by ER and oxidative stress and facilitates the transition from autophagy to senescence. We demonstrate that PKCη knockdown reduces both the autophagic flux and markers of senescence. Additionally, using autophagy inhibitors, such as chloroquine and 3-methyladenine, we show that PKCη and autophagy are required for establishing senescence in MCF-7 in response to oxidative stress. Different drugs used in the clinic are known to induce autophagy and senescence in breast cancer cells. Our study proposes PKCη as a target for therapeutic intervention, acting in synergy with autophagy-inducing drugs, to overcome resistance and enhance cell death in breast cancer.

Dehydrodiisoeugenol (DEH), a novel lignan component extracted from the Nutmeg seeds, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anti-cancer activity in gastrointestinal cancer is still to be investigated. Here, the anti-cancer effect of DEH to human colorectal cancer and its underlying mechanism were evaluated. The DEH treatment arrests the cell cycle of colorectal cancer cells at G1/S phase, which leading to a significant cell growth inhibition. Moreover, it can induce strong cellular autophagy and the autophagy would be inhibited through autophagic inhibitors with reducing EDH-induced inhibition of cell growth in colorectal cancer cells. Further studies indicated that DEH can also induce endoplasmic reticulum (ER) stress, and could subsequently stimulating autophagy through activating PERK/eIF2α and IRE1α/XBP-1s/CHOP pathways. Knockdown of PERK or IRE1α can significantly decrease the DEH-induced autophagy and retrieve cell viability in cells treated with DEH. What’s more, DEH exhibits significant anti-cancer activities through CDX- and PDX-model as well. Taken together, our studies strongly suggest that DEH might be a potential anti-cancer agent against colorectal cancer via activating ER stress-induced autophagy inhibition.

An elevated level of endoplasmic reticulum (ER) stress is considered an aggravating factor for inflammatory bowel disease (IBD). To develop an ER stress attenuator that is effective against colitis, 4-phenylbutyric acid (4-PBA), a chemical chaperone that alleviates ER stress, was conjugated with acidic amino acids to yield a 4-PBA-glutamic acid conjugate (PBA-GA) and a 4-PBA-aspartic acid conjugate (PBA-AA). The PBA derivatives were converted to 4-PBA in the cecal contents, where the conversion was greater with PBA-GA. After oral administration of PBA-GA (oral PBA-GA), millimolar levels of PBA were accumulated in the cecum, whereas 4-PBA was not detected in the blood, indicating the targeting of PBA-GA to the large intestine. At concentrations in the cecum achievable by oral PBA-GA, 4-PBA effectively attenuated ER stress in human colon epithelial cells. In 2,4-dinitrobenzenesulfonic acid-induced colitis in rats, oral PBA-GA alleviated the damage and inflammation in the colon. Moreover, oral PBA-GA substantially reduced the elevated levels of ER stress marker proteins in the inflamed colon. Moreover, PBA-GA was as effective as the currently used anti-IBD drug, sulfasalazine. In conclusion, PBA-GA is a colon-targeted prodrug of 4-PBA and is effective against rat colitis probably through the attenuation of ER stress in the inflamed colon.

Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus polyprotein integration contribute to ER stress and the host cell may exhibit an Unfolded Protein Response (UPR) to this protein accumulation, stimulating appropriate cellular responses such as adaptation, autophagy or cell death. These different stress responses support other antiviral strategies initiated by infected cells and can help to overcome viral infection. In epithelial A549 cells, a model currently used to study the flavivirus infection cycle and the host cell responses, all three pathways leading to UPR are activated during infection by Dengue virus (DENV), Yellow Fever virus (YFV) or West Nile virus (WNV). In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in A549 cells. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway without activation of the ATF6 branch. By modulating the ER stress response, we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV could manipulate the UPR to escape this host cell defence system. Since incomplete UPR could lead to unresolved and persistent ER stress, we found that ZIKV infection was associated with an abnormal accumulation of viral envelope proteins, which were aggregated with non-native disulfide bridges. As the presence of these “amyloid like” protein polymers may be cytopathic, our observations provide new insights into specific neuropathologies associated with ZIKA virus infections.

This contribution deals with the assessment of air pollution caused by atmospheric aerosol particulate matter fraction PM10 and benzo[a]pyrene (BaP) in the urban agglomeration of Ostrava, located in the Czech Republic in Central Europe. The motivation for this research was the need to identify the sources of air pollution in the area, particularly in locations where the contribution of different sources to concentrations of pollutants of concern has not been elucidated yet. In this study, source apportionment in the vicinity of the industrial hot-spot was performed by statistically evaluating measured pollutant concentrations as a function of meteorological variables and using the Positive Matrix Factorization (PMF) receptor model. A significant methodological innovation and improvement over previous assessments was the higher monitoring resolution of benzo[a]pyrene, with samples collected at three-hour intervals instead of the standard 24-hour collection period. The key findings indicate that in the cold part of the year, secondary particles - specifically sulphates and ammonium nitrates - were responsible for the most significant portion of PM10 air pollution throughout the area of interest. The contribution of these particles ranged from one third to two fifths of the total concentration, except at the industrial site of Ostrava-Radvanice (TORE), where they accounted for approximately one fifth of the measured pollution concentration level. Emissions from individual household heating were identified as the main source of this type of pollution. With regards to benzo[a]pyrene air pollution, the study found that in the whole area of interest, except for the Ostrava-Radvanice site, it mainly originated from individual heating with coal (90%). In contrast, at the Ostrava-Radvanice site, two-thirds of the benzo[a]pyrene pollution came from the premises of Liberty Ostrava a.s., primarily from coke production, and less than one-third from local domestic heating. This study also determined the spatial extent of the occurrence of extremely high benzo[a]pyrene concentrations (above 5 ng/m3), which are estimated to affect nearly 10,000 inhabitants. The results confirm that the data from the TORE station are only representative of its immediate surroundings and are not applicable to the assessment of air quality and causes of air pollution in the whole city of Ostrava or the urban area of Ostrava-Radvanice as a whole. After years of research, these findings provide the Ministry of the Environment of the Czech Republic and the government with an accurate basis for implementing measures to address the identified pollution sources in the area of interest. The success of this study was made possible by the adoption of a more detailed sampling approach, which involved a resolution of 3 hours instead of 24 hours. This methodological improvement is a significant finding and will be useful for future source apportionment studies.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate genes involved in the biogenesis of cholesterol, fatty acids, and triglycerides. SREBPs are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). We review the mechanisms by which SREBPs regulate lipogenesis, the alterations in these processes associated with liver diseases, and therapeutic strategies to target these pathways.

During the last century, entanglement was the bone of contention between the two main pillars of Physics: General Relativity (GR) and Quantum Mechanics (QM). This began in 1935 with the Einstein-Podolsky-Rosen paradox (EPR paradox) which concluded that although Quantum Mechanics is not wrong, it is an incomplete theory to represent physical reality. In this paper it is demonstrated that some byproducts resulting from entanglement and which we will call avatars act as a hinge that link both theories making the completeness of QM clear. Moreover, a thorough analysis of the non-locality of this effect will be carried out. Besides, it is demonstrated that entanglement is an instantaneous phenomenon and that it does not require the use of a superluminal signaling for this purpose. Finally, the avatars will also appear in each wormhole resulting from an entanglement process (WREP) demonstrating that they are traversable with an equivalent path of null length which can be crossed in a null time with all that this implies in Quantum Communications.

We propose a wave-like design on the surface of cathode channels (wave form cathode channels) to improve oxidant delivery to gas diffusion layers (GDLs) [1-2]. We performed experiments using PEMFCs combined with wave form surface design on cathodes. We varied the factors of the distance between wave-bumps (the Adhesive distance, AD), and the size of the wave-bumps (the Expansion ratio, ER). The ADs are 3, 4, and 5 times the size of the half-circle bump’s radius, and the ERs are 1/1.5, 1/2, and 1/3 times the channel’s height. We evaluated the performances of the fuel cells, and compared the current-voltage (I-V) relations. For comparison, we prepared PEMFCs with conventional flat-surfaced oxygen channels. Our aim in this work is to identify fuel cell operation by modifying the surface design of channels, and ultimately to find the optimal design of cathode channels that will maximize fuel cell performance.

Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed potentiating or inhibiting viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.

Congenital Disorders of Glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid linked oligosaccha-rides and their transfer to proteins. CDGs affect multiple organ systems and vary in presentation, even within families. Here we describe a chemically induced mouse mutant, tvrm76, with early onset photoreceptor degeneration. The recessive mutation was mapped to Chromosome 9 and as-sociated with a missense mutation in the Dpagt1 gene encoding UDP-N-acetyl-D-glucosamine:dolichyl-phosphate N-acetyl-D-glucosaminephosphotransferase (EC 2.7.8.15). The mutation is predicted to cause a substitution of aspartic acid with glycine at residue 166 of DPAGT1. Increased expression of Ddit3, and elevated levels of HSPA5 (BiP) sug-gest the presence of early-onset endoplasmic reticulum (ER) stress. These changes were associated with induction of photoreceptor apoptosis in tvrm76 retinas. Mutations in human DPAGT1 cause Myasthenic Syndrome 13 and severe forms of Congenital Disorder of Glycosylation Type Ij. In contrast, Dpagt1tvrm76 homozygous mice present with congenital photoreceptor degeneration without overt muscle or muscular junction involvement. Our results suggest the possibility of DPAGT1 mutations in human patients that present primarily with retinitis pigmentosa with little or no muscle disease. Variants in DPAGT1 should be considered when evaluating cases of non-syndromic retinal degeneration.

This review documents an emerging body of evidence concerning the neurological effect of polycyclic aromatic hydrocarbon (PAH) exposure, with regard to cognitive function and increased risk of neurodegeneration. Two electronic databases PubMed and Web of Science were systematically searched. The 37/428 studies selected included outcomes measuring cognitive function, neurobehavioral symptoms of impaired cognition, and pathologies associated with neurodegeneration from prenatal (21/37 studies), childhood (14/37 studies), and adult (8/37 studies) PAH exposure. Sufficient evidence surrounding prenatal exposure negatively impacting child intelligence, mental development, average overall development, verbal IQ, memory impairment, externalizing, internalizing, anxious, depressed behaviours, behavioural development and child attentiveness was found. Evidence concerning exposure during childhood and as an adult was scarce and highly heterogeneous, however presence of neurodegenerative biomarkers and increased concentrations of cryptic “self” antigens in serum and cerebrospinal fluid samples suggest a higher risk of neurodegenerative disease. Associations with lowered cognitive ability, and impaired attentiveness were found in children and memory disturbances, specifically auditory memory, verbal learning and general memory in adults. Although evidence is not yet conclusive and further research is needed the studies included supported the hypothesis that PAH exposure negatively impacts cognitive function and increases the risk of neurodegeneration in humans, and recommends considering the introduction of a variable “rural vs. urban” as covariate for adjusting analyses where the neurological functions affected (as result of our review) are outcome variables.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress was determined by qRT-PCR, TNF-α protein by ELISA, ROS by DCFH-DA assay, HIF-1α/p38/ERK-1,2/NF-κB phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed by qRT-PCR/IHC and plasma TNF-α/hs-CRP/MDA/OX-LDL by ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CHOP, ATF6, SOD2, and NRF2 expression (P≤0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α/p38/NF-κB phosphorylation, while MAPK/NF-κB inhibitors and antioxidants/ROS scavengers attenuated TNF-α production (P≤0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (P≤0.05). Our findings support a cooperative interaction between metabolic and ER stresses, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also shows the therapeutic potential of ROS scavengers/anti-oxidants in inflammatory conditions involving metabolic/ER stresses.

The endoplasmic reticulum (ER) is the major site of membrane biogenesis in most eukaryotic cells. As the entry point to the secretory pathway, it handles more than 10.000 different secretory and membrane proteins. The membrane insertion of proteins, their folding, and ER exit are affected by the lipid composition of the ER membrane and its collective membrane stiffness. The ER is also a hotspot of lipid metabolism for membrane lipids including sterols, glycerophospholipids, ceramides and neural storage lipids. The unfolded protein response (UPR) bears an evolutionary conserved, dual sensitivity to both protein folding-imbalances in the ER lumen and aberrant compositions of the ER membrane, referred to as lipid bilayer stress (LBS). Through transcriptional and non-transcriptional mechanisms, the UPR upregulates the protein folding capacity of the ER and balances the production of proteins and lipids to maintain a functional secretory pathway. In this review, we discuss how UPR transducers sense unfolded proteins and LBS with a particular focus on their role as guardians of the secretory pathway.

In the paper, the authors generalize the notion "k-Mittag-Leffler function'', establish some integral transforms of the generalized k-Mittag-Leffler function, and derive several special and known conclusions in terms of the generalized Wright function and the generalized k-Wright function.

Abstract: The frequency and intensity of air pollution are two of most critical issues the world faces in dealing with global environmental problems. They are both important areas that need to be improved. Our previous research [20] examines the assessment of fine dust pollution in Baekryeong island by statistical reasoning through one specific example of inland city (Yanggu) in Republic of Korea; however, given that Baekryeong Island is a remote island, there has been little focus on in-depth examination of its effect on the high density of fine dust in Baekryeong Island. The purpose of this article is twofold: (i) to examine the effect of a remote island on the high density of fine dust on Baekryeong Island using statistical reasoning and to provide a more specific statistical basis for the claim that one of the non-negligible factors influencing the high density of fine dust on Baekryeong Island is the geographic proximity to China; and (ii) to present brief discussion of fundamental cause of fine dust and global air pollution issues, which are not discussed in [20].

Chronic Mesenteric Ischemia (CMI) arises from the inability to achieve adequate intestinal blood flow after meals, leading to an imbalance between oxygen and metabolite supply and demand. The true incidence of CMI remains uncertain. However, the occurrence of mesenteric artery occlusive disease (MAOD) is relatively common among the elderly population. Delays in diagnosing CMI can often be attributed to several factors, including the variability of patient symptoms, the range of potential causes for chronic abdominal pain with weight loss. Mikkelson pioneered the introduc-tion of a surgical treatment for occlusive lesions of the superior mesenteric artery (SMA) in 1957. The inaugural performance of endovascular revascularization (ER) for visceral vessels took place in 1980. The literature has documented two types of endovascular revascularization (ER) methods: percutaneous transluminal angioplasty (PTA) and primary stenting (PMAS). Despite the limited quality of available evidence, the consensus among experts is strongly in favor of PMAS over PTA alone for the treatment of atherosclerotic mesenteric artery stenosis. There are several key areas of focus for chronic mesenteric ischemia (CMI) treatment. Randomized controlled trials comparing different stent types, such as covered stents versus bare metal stents, are needed to evaluate effi-cacy, patency rates, and long-term outcomes in CMI patients.

Susceptibility to photoimmune suppression and photocarcinogenesis is greater in male than in female humans and mice and is exacerbated in female estrogen receptor-beta knockout (ER-β-/-) mice. We previously reported that the active vitamin D hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D) applied topically protects against ultraviolet radiation (UV)-induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and suppression of contact hypersensitivity (CHS) in female mice. Here we compare these responses in female versus male Skh:hr1 mice, in ER-β-/- versus wild type C57BL/6 mice, and in female ER-blockaded Skh:hr1 mice. Induction of CPDs was significantly greater in male than female Skh:hr1 mice and was more effectively reduced by 1,25(OH)2D in female Skh:hr1 and C57BL/6 mice, than in male Skh:hr1 or ER-β-/- mice respectively. This correlated with reduced sunburn inflammation by 1,25(OH)2D in female but not male Skh:hr1 mice. Furthermore, although 1,25(OH)2D alone dose-dependently suppressed basal CHS responses in male Skh:hr1 and ER-β-/- mice, UV-induced immunosuppression was universally observed. In female Skh:hr1 and C57BL/6 mice, the immunosuppression was decreased by 1,25(OH)2D dose-dependently, but not in male Skh:hr1, ER-β-/- or ER-blockaded mice. These results reveal a sex bias in genetic, inflammatory and immune photoprotection by 1,25(OH)2D favoring female mice, that is dependent on the presence of ER-β.

This paper analyses the viability of different solutions to passively augment the axial stiffness of a horizontal axis radial levitation passive magnetic bearing (PMB) with topology previously studied. The zero-field cooling (ZFC) of high-temperature superconductor (HTS) bulks promotes higher magnetic impulsion and levitation forces and lower electromagnetic losses than with the field-cooling (FC), but on the other hand, the guiding stability is much lower than with FC. Because of stability reasons, FC was adopted in most superconducting maglev systems. The trend of this research group has been to develop an HTS ZFC horizontal axis radial levitation PMB presenting notable levitation forces with reduced electromagnetic losses, defined by a topology that creates guiding stability. Previous work has shown that even optimizing the bearing geometry to maximize magnetic guidance forces, could not be enough to guarantee the axial stiffness required for many applications. First, the extent to which guidance forces are augmented by increasing the number of HTS bulks in the stator is evaluated. Then, the axial stiffness augmentation by passively adding two limiting permanent magnet (PM) rings is evaluated. Results show that the axial stiffness is highly augmented by adding limiting PM rings with no significant additional investment. This change enables using the studied ZFC superconducting PMB in high-precision axial stability applications, such as precision gyroscopes, horizontal axis propellers and turbines.

In the evolving landscape of Portfolio Management (PM), the fusion of advanced machine 1 learning techniques with traditional financial methodologies has opened new avenues for innovation. 2 Our study introduces a cutting-edge model combining Deep Reinforcement Learning (DRL) with 3 a Non-stationary Transformer architecture. This model is specifically designed to decode complex 4 patterns in financial time series data, enhancing portfolio management strategies with deeper insights 5 and robustness. It effectively tackles the challenges of data heterogeneity and market uncertainty, 6 key obstacles in PM. Our approach integrates key macroeconomic indicators and targeted news 7 sentiment analysis into its framework, capturing a comprehensive picture of market dynamics. This 8 amalgamation of varied data types addresses the multifaceted nature of financial markets, enhancing 9 the model’s ability to navigate through the complexities of asset management. Rigorous testing 10 demonstrates the model’s efficacy, highlighting the benefits of blending diverse data sources and 11 sophisticated algorithmic approaches in mastering the nuances of PM.12

Plants offer a simpler and cheaper alternative to mammalian animal models for the study of Endoplasmic Reticulum glycoprotein folding Quality Control (ERQC). In particular, the Arabidopsis thaliana (At) innate immune response to bacterial peptides provides an easy means of assaying ERQC function in vivo. A number of mutants that are useful to study ERQC in planta have been described in the literature, but only for a subset of these mutants the innate immune response to bacterial elicitors has been measured beyond monitoring plant weight and some physio-pathological parameters related to the plant immune response. In order to probe deeper into the role of ERQC in the plant immune response, we monitored expression levels of the PHI-1 and RET-OX genes in the At ER α-Glu II rsw3 and the At UGGT uggt1-1 mutant plants, in response to bacterial peptides elf18 and flg22. The elf18 response was impaired in the rsw3 but not completely abrogated in the uggt1-1 mutant plants, raising the possibility that the latter enzyme is partly dispensable for ERF signalling. In the rsw3 mutant, seedling growth was impaired only by concomitant application of the At ER α-Glu II NB-DNJ inhibitor at concentrations above 500 nM, suggesting residual activity in this mutant. The study highlights the need for extending plant innate immune response studies to assays sampling EFR signalling at the molecular level.

Alzheimer’s Disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with small molecule CP2 induces adaptive stress response activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, improved synaptic and mitochondrial functions, and blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model of AD. Here, using serial block-face scanning electron microscopy (SBFSEM) and three-dimensional (3D) EM reconstructions combined with Western blot analysis and next-generation RNA sequencing, we demonstrate that CP2 treatment also restores mitochondrial morphology and mitochondria-endoplasmic reticulum (ER) communication in the APP/PS1 mouse brain. Using 3D EM volume reconstructions, we show that mitochondria in AD dendrites exist primarily as mitochondria-on-a-string (MOAS). Compared to other morphological phenotypes, MOAS are extensively enveloped in the ER membranes forming multiple mitochondria-ER contact sites (MERCS) known to contribute to abnormal lipid and calcium homeostasis. CP2 treatment specifically reduced MOAS formation, consistent with improved energy homeostasis in the brain, with concomitant reduction in MERCS, ER stress, and improved lipid homeostasis. These data provide novel information on the role MOAS play in AD and additional support for further development of partial MCI inhibitors as disease modifying strategy for AD.

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

The broad emission bump in the electromagnetic spectra observed following the detection of gravitational waves created during the kilonova event of merger of two neutron stars in August 2017, GW170817, has been linked to the heavy elements of lanthanides (Z=57-71), and a new understanding of creation of heavy elements in the r-process. The initial spectral emission bump has a wavelength range of 3000 - 7000 \AA, thus covering the region of ultraviolet (UV) to optical (O) wavelengths, and is similar to those seen for lanthanides. Most lanthanides have large number of closely lying energy levels which introduce extensive sets of radiative transitions which often form broad region of lines of significant strength. The current study explores these broad features through photoabsorption spectroscopy of 25 lanthanides ions, Ho I-III, Er I-IV, Tm I-V, Yb I-VI and Lu I-VII. With excitations only to a few orbitals up beyond the ground configurations, we find most of these ions cover large number of bound levels with open $4f$ orbital and produce tens to about hundred thousands lines that may form one or multiple broad features in X-ray to UV, O, and infrared (IR) regions. Spectrum of each of 25 ions is presented indicating presence, shape and wavelength region of the features. Accuracy of atomic data to interpret the merger spectra has been a outstanding problem. The present study aims at providing improved atomic data for energies and transition parameters obtained using relativistic Breit-Pauli approximation implemented in the atomic structure code SUPERSTRUCTURE. The present data have been benchmarked with available experimental data for energies and transition parameters. The study finds that number of ions under the present study are possible contributors of the emission bump of GW170817. All atomic data will be made available online at NORAD-Atomic-Data database.

Recently, due to the miniaturization of electronic products, printed circuit boards (PCBs) have also become smaller. This trend has led to the need for high-precision electrical test equipment to check PCBs for disconnections and short circuits. The purpose of this study is to improve the position repeatability of the platform unit up to ±2.5 μm in a linear stage type test equipment. For this purpose, the causes of position errors of the platform unit are analyzed. The platform unit holding the PCB is driven by a single-axis linear ball screw drive system offset from its geometric center due to design constraints. The yaw rotation of the platform is found to have a dominant effect on position repeatability. To address this problem, the methods of adding balancing weights to the platform unit and adjusting the stiffness of LM Guides are proposed. This reduces the yaw rotation by moving the centers of mass and stiffness closer to the linear ball screw actuator. In the verification tests, the position repeatability was decreased to less than ±1.0 μm.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.