Brick is widely used in construction, but it often becomes debris due to its use and lack of quality. In Ecuador, brick production is not completely industrialized, resulting in deficient properties for construction. In the city of Loja, most bricks come from artisanal factories . This research proposes the use of geopolymerization and waste bricks to create a sustainable material in construction. Geopolymerization processes were employed with sodium hydroxide as the alkaline activator. The resulting products underwent various tests to obtain the optimal formula in terms of material behavior and strength. Physical and mechanical property tests were conducted, and their application in building envelopes for low-income housing was analyzed. The results showed that the new material, when used as cladding on facades, can reduce heating and cooling demand. In a case study in Loja, a significant decrease in heating and cooling degree days was observed. This research opens new possibilities in the utilization of recycled materials in construction and can contribute to knowledge in this field.

The objective of this study was to evaluate the drying kinetics of the mass of jambu leaves and mass of jambu leaves in foam mat at different temperatures (50, 60 and 70 °C and thickness of 1.0 cm). The physicochemical characterization of the materials was performed before and after drying. Twelve different drying models were fitted to the drying kinetics data and the thermodynamic properties were calculated. The physicochemical parameters for the mass of leaves and foam after drying were moisture content from 2 to 7%, ash from 13 to 17%, protein content from 22 to 30%, lipids from 0.6 to 4% and total titratable acidity from 0.20 to 0.28% of tartaric acid. Wang & Singh and Midilli models were recommended for describing the drying kinetics. The use of foam mat promoted higher values of effective diffusion coefficient and activation energy and lower values of enthalpy and entropy, thus enhancing the reduction of drying time.

Abstract: Objective: analyze the effectiveness of the implementation of the Lean Healthcare sys-tem at the emergency room of the Clinical Hospital of the Federal University of Uberlândia (HC-UFU), based on a comparison of hospital indicators obtained over the three phases corre-sponding to the period of one year before the implementation (T1), the year during the imple-mentation (T2) and one year after implementation (T3). Material and Methods: this is applied research, classified as a case study, exploratory, descriptive that is developed in stages. Based herein on the search for hospital indicators, as occurred in the implementation process of Lean in Emergencies at the HC-UFU and a description of the implemented Lean system. Results and Discussions: during the period where it was possible to collect data relevant to the NEDOCS and LOS indicators, the motivation of the teams grew, but with a notable tension between municipal management and hospital management. It was found that, despite the fluctuations, the patient length of stay in the Emergency Room remained high. Noteworthy here is that with the excep-tion of the variable of female deaths before 24 hours of hospitalization, all other variables showed percentage increases before and after the intervention. Conclusion: the methodology followed for the implementation of Lean in Emergencies in the emergency sector of the hospital did not produce an improvement in hospital indicators.

It is shown that, for a de Sitter Universe, the Hartle-Hawking (HH) wave function can be obtained in a simple way starting from the Friedmann- Lemaitre-Robertson-Walker (FLRW) line element of cosmological equations. An oscillator having imaginary time is indeed derived starting from the Hamiltonian obtaining the HH condition. This proposes again some crucial matter on the meaning of complex time in cosmology. In order to overcome such difficulties, we propose an interpretation of the HH framework based on de Sitter Projective Holography.

In the present article, the application of an artificial neural network (ANN) model is studied, whose function is the development of plastic instability maps of a medium carbon microalloyed steel during the hot forging process. And, secondly, we proceed to create another neural network capable of providing the recrystallized grain size in the steady state phase resulting from the deformation by hot forging, thus creating a methodology that can be applied to different types of processes and materials. In order to achieve this objective, we start from the experimental data of a medium carbon microalloy steel, obtained by hot compression tests, for strain rates that vary between 10-4 and 3 s-1 and in a range of temperatures between 900 oC and 1150 oC. These experimental data will be used to train the neural network that is intended to be created in this work. Once trained, it will be verified if the results of the test correspond to the experimental data and the fluency curves will be obtained. Finally, the processing maps will be developed applying the Dynamic Materials Model (DMM), according to which the safe domains to forge the material and the plastic instability domains are delineated, to be avoided during the forging process. The maps obtained by means of RNA will be compared with the experimental ones and it will be possible to verify that the optimal regions of forging in the maps obtained by RNA coincide with those obtained by means of experimental data. In addition, a study of the influence of the microstructure on the behavior of steel during hot forming will be carried out, since the experimental tests are carried out at austenitizing temperature, so the microstructure is different in each test.

This article aimed at providing some extension of the modal square of opposition in the 1 light of Ockham’s account of the modal operators. Moreover, we shall set forth some significant 2 remarks on the de re-de dicto distinction and on the modal operator of contingency by means of a 3 Boolean algebra called Bitstring Semantics. This generalisation starting from Ockham’s account of 4 modalities will allow us to take into consideration whether Ockham’s thought on this matter holds 5 water or not, and in which case it should be changed in order to make it coherent.

A theoretical description of quantum jumps at the level of elementary particles is proposed, based on a micro-cosmological interpretation of their de Broglie phase. The third quantization formalism proposed in current literature for the description of baby universes in quantum cosmology is used here to describe the breakdown of unitarity in the transition from the pre-jump to the post-jump wave function. The corpuscular aspect manifested by the particle in the micro-interaction that originates the jump is represented by a pair of evanescent "micro-universes", respectively pre- and post-jump, connected by a wormhole. The latter represents the actual implementation of the interaction that leads to the projection on the outgoing state; this interaction is always local, even when the selected outgoing state is entangled. Therefore, the decoherence which leads to the emergence of classicality is originated by the same fundamental interactions of the Standard Model involved in the unitary evolution of the wave function. The objective nature of the reduction process admits implications on the possibility of using the formalism in the cosmological context, which are briefly discussed.

The signature of chaotic systems can be characterized either by the sensitivity of the initial conditions or by the change of its parameters. This feature can be used for manufacturing high sensitivity sensors. Sensors based on chaotic circuits have already been used for measuring water salinity, inductive effects, and both noise and weak signals. This article investigates an impedance sensor based on the Van der Pol and Duffing damped oscillators. The calibration process is a key point and therefore the folding behavior of signal periods was also explored. A sensitivity of 0.15 kΩ/Period was estimated over a range from 89.5 to 91.6 kΩ. This range can be adjusted according to the application by varying the gain of the operational amplifier used in this implementation. The development of this type of sensor might be used in medical and biological engineering for skin impedance measurements, for example. This type of chaotic sensor has the advantage of sensing small disturbances and then detect small impedance changes within biological materials which, in turn, may not be possible with other detectors.

This article aims to present the outcomes of a study focused on collaboratively developing an Innovation Management Model (IMG) tailored for Colombia's leather agro-industrial chain. The study integrates stakeholder participation, prioritization of variables, literature review, and model validation, emphasizing sustainability considerations throughout the process. Methodologically, it involved a literature review using Scopus, focusing on innovation management models, open innovation, and sustainability, particularly within the leather sector. The search identified 43 documents in Scopus, of which 15 were directly relevant; this analysis was complemented by 18 articles from Google Scholar. Three surveys were conducted to prioritize variables, utilizing Lik-ert-scale questions to assess relevance and congruence. Conceptual innovation models were validated graphically. Initial variables were identified, with 53 selected for the entry stage, 36 for the transformation stage, and 31 for the exit stage. These variables were classified for each stage, resulting in three innovation management models for validation. Key findings included 26 critical variables covering aspects such as agricultural and technological innovation in platforms and projects, capacity development, R&D activities, supply chain dynamics, innovation management processes, knowledge and technology integration, business model adaptation for sustainable development, and environmental impact assessment. The prioritized innovation model is in-tended to assist stakeholders in the leather sector's innovation system by promoting open inno-vation strategies, sustainable and regenerative innovation generation, and enhancing strategic and technological capacities. The prioritized innovation model aims to assist stakeholders in the leather sector's innovation system by promoting open innovation strategies, sustainable and re-generative innovation generation, and enhancing strategic and technological capacities.

We are using information from a paper deriving a Lorentz-violating energy-momentum relation entailing an exact mo_mentum cutof as stated by G. Salesi . Salesi in his work allegedly defines Pre Planckian physics, whereas we restrict our given application to GW generation and DE formation in the first 10^-39s to 10^-33s or so seconds in the early universe. This procedure is inacted due to an earlier work whereas referees exhibited puzzlement as to the physical mechanism for release of Gravitons in the very early universe. The calculation is meant to be complementary to work done in the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, and also a calculation for Black hole destruction as outlined by Karen Freeze, et. al. The GW generation will be when there is sufficient early universe density so as to break apart Relic Black holes but we claim that this destruction is directly linked to a Lorentz violating energy-momentum G. Salesi derived, which we adopt, with a mass m added in the G. Salesi energy momentum results proportional to a tiny graviton mass, times the number of gravitons in the first 10^-43 seconds

Background: Decision, whether to de-label patient with suspected BL hypersensitivity, is based on the risk stratification. The aim of the study was to prepare a characteristic of diagnostic risk groups and to create a model enabling the identification of the low-risk diagnostic group. Methods: We analyzed medical records of patients hospitalized due to suspected hypersensitivity to BL antibiotics. Based on the history data, patients were divided into three diagnostic risk groups, using the criteria proposed by Shenoy et al. Univariate and multivariate analysis model were used to create a diagnostic tool. Results: Among 263 patients referred for BL hypersensitivity diagnosis, 88 (33.5%) were qualified to group I, 129 (49%) to group II, and 46 (17.5%) to group III. There were significant differences between diagnostic risk groups regarding history of hypersensitivity to penicillins (p<0.001), cephalosporins (p<0.001), >1 BL (p<0.05), several episodes of BL hypersensitivity (p<0.001), medical intervention (p<0.001), documented hypersensitivity (p<0.001), time from drug intake to symptoms (p<0.001), time from hypersensitivity to diagnosis (p<0.001). 81 patients (30.8%) were de-labeled: 52 (59.8%) in group I, 27 (20.9%) in group II and 2 (4.3%) in group III. In univariate analysis, model of the low diagnostic risk group applied to the de-labeled part showed 90% specificity and 21.93% sensitivity. NPV and PPV were estimated at 72.04% and 49.53%, respectively. Multivariate model had high specificity but low sensitivity; its NPV was 76% with 68% PPV. Conclusions: The tool enabling the identification of low diagnostic risk patients based on anamnesis is not sensitive enough, to de-label patients on its basis.

The safety and reliability of structures operating in cold regions are seriously threatened by icing. This has attracted researchers to explore de-icing/anti-icing methods. In this work, a bubble de-icing system was established and investigated for the removal of ice from frozen structures using bubble pulsation energy. Traditional de-icing method face high energy consumption, environmental pollution, and secondary icing issues. To avoid this and promote the development of de-icing techniques, the massive amount of energy generated by bubble pulsation can be used for de-icing. In the present work, experimental methods have been adopted to demonstrate the possibilities of de-icing using cavitation energy. Many test cases, in which the bubble distance from the target and thickness of ice layer were varied 5 - 35 mm, were examined to determine the mechanism of ice removal by the bubble energy. This research demonstrated that bubble energy can be used effectively for de-icing. Bubble energy should be further explored for de-icing techniques and engineering application prospects.

Millet is a staple food in Northern Nigeria, widely used for the preparation of various millet‐based dishes. However, traditional processing methods, such as de‐husking, can significantly affect the grainʹs nutritional and antioxidant properties. This study evaluates the antioxidant composition and nutritional value of four millet varieties cultivated in Northern Nigeria, with a particular focus on the impact of de‐husking on these parameters. Our analysis encompasses the proximate composition, phytochemical content, antioxidant vitamins, mineral elements, amino acid profile, and antioxidant activities of the millet samples. The findings reveal that all millet varieties contain significant levels of antioxidant compounds, including phenolics, flavonoids, and vitamins, although their concentrations varied due to genetic differences and environmental factors. Notably, in the mineral composition, higher (p<0.05) levels of selenium (Se) and magnesium (Mg) were observed, while trace levels of iron (Fe), copper (Cu), and zinc (Zn) were present. The study demonstrated that de‐husking significantly (p<0.05) reduced the levels of most nutritional and antioxidant parameters, underscoring the superior nutritional value of whole grains compared to their de‐husked counterparts. This highlights the importance of consuming millets in their unprocessed form to maximise health benefits. Moreover, the presence of essential phytochemicals, amino acids, and dietary fiber in these grains, suggests their potential role in reducing the risk of chronic diseases such as cancer, cardiovascular diseases, obesity, and diabetes. These findings underscore the nutritional and functional potential of millet grains as valuable sources of essential nutrients, which can be utilised in nutraceutical formulations or as functional foods for promoting human health. This study emphasises the need to preserve the integrity of millet grains during processing to fully capitalise on their health benefits.

Introduction: The HIV/AIDS pandemic in Spanish prison institutions has led to a series of necessary changes to adapt and provide an effective response. Materials and Methods: This research was conducted from an interpretative paradigm with a phenomenological perspective, interpreting the experiences of nursing professionals in Spanish prison institutions. Focus groups were conducted with professionals who worked before and after the emergence of antiretroviral treatments through the Microsoft Teams platform, using the ATLAS Ti v.9 software. The project received approval from the Ethics Committee of the UJI university. Results: Limited dissemination of news in the press regarding HIV/AIDS and Spanish prisons was observed. Changes occurred in organizational, material, and personnel resources, requiring adaptation among nursing professionals. The available resources and difficulties are described, along with patient perspectives, the role of professionals, their environment, and their experiences, both positive and negative. Discussion and Conclusions: There is minimal visibility of the problem, and a description is provided of an adaptation process to the environment compatible with the Callista Roy´s model.

This article aims to approach the Mudejar architecture developed in Mexico during the 16th and 17th centuries. The subject has been little studied although both general and specific contributions have been made by the author’s research group. At the methodological level, this study is based on the existing bibliography as well as archive and field research which allow an accurate scientific approach and results. The article analyses the social and productive conditions in Mexico during the Viceregal period along with the systematization carried by the Viceroy Antonio de Mendoza, the guild ordinances and the architectural typologies. The perception of territory and the use of constructive models by the Viceregal authorities would justify the use of the Mudejar style as cultural and unity criteria

It is already known that a simple nonlocal de Sitter gravity model, which we denote as dS gravity, contains an exact vacuum cosmological solution which mimics dark energy and dark matter and is in very good agreement with the standard model of cosmology. This success of dS gravity motivated us to investigate how it works at lower than cosmic scale – galactic and the solar system. This paper contains our investigation of the corresponding Schwarzschild-de Sitter metric of the dS gravity model. To get exact solution, it is necessary to solve the corresponding nonlinear differential equation, what is a very complicated and difficult problem. What we obtained is a solution of linearized equation, which is related to space metric far from the massive body, where gravitational field is weak. The obtained approximate solution is of particular interest for examining the possible role of non-local de Sitter gravity dS in describing the effects in galactic dynamics that are usually attributed to dark matter. The solution has been tested on the Milky Way and the spiral galaxy M33 and is in good agreement with observational measurements.

In the same way as the realization of some of the famous gedanken experiments imagined by the founding fathers of quantum mechanics has recently led to the current renewal of the interpretation of quantum physics, it seems that the most recent progresses of observational astrophysics can be interpreted as the realization of some cosmological gedanken experiments such as the removal from the universe of the whole visible matter or the cosmic time travel leading to a new cosmological standard model. This standard model involves two dark components of the universe, dark energy and dark matter. Whereas dark energy is usually associated with the cosmological constant, we propose to explain dark matter as a pure QCD effect, namely a gluonic Bose Einstein condensate, following the transition from the quark gluon plasma phase to the colorless hadronic phase. Our approach not only allows us to assume a ratio Dark/Visible equal to 11/2 but also provides gluons and (anti-)quarks with an extra mass of vibrational nature. Such an interpretation would comfort the idea that, apart from the violation of the matter/antimatter symmetry satisfying the Sakharov’s conditions, the reconciliation of particle physics and cosmology needs not the recourse to any ad hoc fields, particles or hidden variables.

An explanation of the origin of dark matter is suggested in this work. The argument is based on symmetry considerations about the concept of mass. In the Wigner's view, the rest mass and the spin of a free elementary particle in flat space-time are the two invariants that characterize the associated unitary irreducible representation of the Poincar\'e group. The Poincar\'e group has two and only two deformations with maximal symmetry. They describe respectively the de Sitter (dS) and Anti de Sitter (AdS) kinematic symmetries. Analogously to their shared flat space-time limit, two invariants, spin and energy scale for de Sitter and rest energy for Anti de Sitter, characterize the unitary irreducible representation associated with dS and AdS elementary systems. While the dS energy scale is a simple deformation of the Poincaré rest energy and so has a purely mass nature, AdS rest energy is the sum of a purely mass component and a kind of zero-point energy derived from the curvature. An analysis based on recent estimates on the chemical freeze-out temperature marking in Early Universe the phase transition quark-gluon plasma epoch to the hadron epoch supports the guess that dark matter energy might originate from an effective AdS curvature energy.

This study offers an analysis of existing research on sustainability and its link to accounting and management control in the port sector. The existing studies do not provide a comprehensive discussion of management accounting and control tools in this context, despite recognizing the relevance of the issue. The Scoping Review was used as a methodological basis, with reference to the framework of Arksey and O’Malley [1], with the aim of mapping the literature on the role of ac-counting and management control, as well as their relationship with the Triple Bottom Line associated with the various levels of sustainability in this sector. The results point to a diversity of tools used essentially in developed countries, where the interest in efficiency, sustainability and strategic alignment stands out.

In the provinces of the region, empirical constructions reached maximum points with these practices. The effects and pathologies appear as physical, chemical and mechanical failures in pillars, walls and roofs, generating uncertainty for the user. The current powerful design can detect the interior deterioration of coatings in adobe, brick and concrete constructions, and prevent collapses, material and economic losses. Experimental methods performed affirm the serious validity. The accuracy of the simulation and design provide a pre-test reliability of 95%. Five piles constructed of various materials participate in the prototype performance test, there is a correlation (R=0.9997) between the magnetic field range "B" (cm) and density "ρ" (g/cm³), also by increasing the current (i) in transit Q1 and coil L1, the induction of the "B" increases proportionally until penetrating the density of the wall of the building, having 5% reading error.

This article focuses on the comparison and perception of the potential of water’s surface in selected parts of the waterfront in two contrasting cities. The aim is to define the potential of the water’s surface in terms of psychology and its effects on climate. The analysis was performed on the example of Prague with its waterfront on the river Vltava, and Santa Cruz de Tenerife with its Atlantic coastline. Data was sourced from maps, questionnaire surveys and interviews with waterfront users during October 2020. The research showed a higher importance of the water’s surface for users in Prague, than in Santa Cruz. The main finding is that the psychological perception of the waterfront by its the users is affected by the possibility of a visual contact with the water’s surface, the design and composition of the space, and the climate situation of a site affected by the presence of an urban heat island (UHI). The results promote an adherence to ecosystem-based approaches in future design projects and modifications of existing public spaces. The purpose of the work is to open a broader debate on the sustainability of the potential of waterfronts and their positive impact on human health.

The prevalence and incidence of cardiac pro-arrhythmic disorders are often influenced by sex due to specific effects on the QT interval. Androgens shorten QT, which may be protective against acquired long QT syndromes and their related arrhythmias in men such as torsade de pointes (TdP). On the other hand, androgens can potentiate Brugada and early repolarization syndromes, which are most prevalent in men. In this case series, we highlight four male patients with aborted SCD in the setting of abnormal testosterone status; two patients with TdP in a setting of testosterone deprivation (of which one drug-induced) and 2 patients with ventricular fibrillation associated with exogenous androgenic booster (Tribulus terrestris) intake. From this case series, we review the current available literature of the effects of androgen as a double-edged sword on the QTc interval and emphasize the importance of QTc monitoring in this subset of patients.

The origin of SARS-CoV-2 is debated, even after 18 months into the COVID-19 pandemic and a special investigation conducted by the World Health Organization. The RaTG13 sequence has been a highlight of discussions surrounding the origin of SARS-CoV-2. Here we express our opinion about the need for better reporting standards for information about sequencing data, especially for pathogens, citing our findings with the reported RaTG13 genome.

A thin-shell wormhole is crafted by the cut-and-paste method of two Bardeen de-Sitter black holes using Darmois-Israel formalism. Energy conditions are considered for different values of magnetic charge while both mass and cosmological constant are fixed. The attractive and repulsive characteristics of the throat of the thin-shell wormhole are also examined through the radial acceleration. Dynamics and stability of the wormhole are studied around the static solutions of the linearized radial perturbations at the throat of the wormhole. The regions of stability are determined by checking out the condition of concavity of the potential as a function in the throat radius for different values of magnetic charges.

This paper discusses the impact of orthographic manuals on the state of literacy, i.e. the relation of orthographic literacy and orthographic standardisation. The established hypothesis claims that frequent changes of orthographic rules during the pupils’ primary and secondary education do not have any considerable impact on their orthographic habits. In other words, the quantity of orthographic mistakes observed during a longer period of time and in conditions of changed orthographic rules would not show significant oscillations in their spelling. In order to confirm the hypothesis, a questionnaire was conducted encompassing 41 tests among 526 students of a technical study programme during four consecutive academic years, pursuant to whose results a writing uniformity index and a categorisation of orthographic controversy into six classes is established. The Croatian language has been selected for the observation due to multiple orthographic changes in the last 30 years in the three major orthographic points: writing of the covered r, writing of d and t in front of c and č in declination of words ending in -tak, -tac, -dak and -dac, and the issue of compound or separate spelling of the negation particle and the auxiliary biti (to be). Moreover, the paper methodologically and quantitatively establishes criteria according to which the second established hypothesis on evolutionary orthographic literacy can be confirmed. The conclusions are expected to be able to contribute to the better understanding of orthographic planning and application of orthographic norms in schools.

Biofilter application for treatment of stormwater containing de-icing chemicals commonly applied in airports, propylene glycol and potassium formate, was investigated. Lab-scale adsorption tests using filter media made of crushed clay (Filtralite) and granular activated carbon showed that adsorption was unsuitable for removal of propylene glycol and potassium formate. Column filtration experiment testing two different crushed clay size ranges was conducted. The results showed that DOC removal was dependent on a number of factors. This study investigated the impact of filter depth, nutrients addition, and filtration rate. DOC removal suggested that DOC degradation occurred on the top filter layer. It was shown that the most active separation occurred in the first ~20 cm of filter depth. This was confirmed by results from water quality analysis (i.e. DOC removal and ATP measurement) and calculations based on a filtration performance analysis (Iwasaki model) and filter hydraulic evaluation (Lindquist diagram). It was shown that for the highest C:N:P ratio tested (molar ratio of 24:7:1), 50-60% DOC removal was achieved. Addition of nutrients was found important and determining the biofilter performance.

Microplastics, plastic fragments smaller than 5 mm present in the environment due to the decomposition of larger plastics, can cause damage to various ecosystems and species of pollinating insects such as Apis mellifera bees. These bees play a crucial role in the ecology and production of honey and pollen, also serving as bioindicators of environmental quality as they are sensitive to contaminants such as microplastics. In this study, the presence of microplastics in these insects and their bee products, pollen, and honey, collected in August 2021 and August 2023 in rural areas (Tabio and Guasca) of Cundinamarca, Colombia, and urban areas (Universidad Nacional de Colombia) was evaluated. and Pontificia Universidad Javeriana) of Bogotá, Colombia. In each year, 24 bees, 10 grams of honey and 10 grams of pollen were collected per sampling point. Microplastics in bees and their products were identified and quantified by stereomicroscopy, with or without hydrogen peroxide digestion pretreatment. Microplastics were found in bees, pollen, and honey in both periods, with an increase in their quantity observed over time due to increasing environmental pollution. Blue fibers were the most common microplastics, with a greater amount recorded in 2023 compared to 2021.

Objectives: To investigate the etiology of amyotrophic lateral sclerosis (ALS) in an adult female patient. Methods: We conducted trio genome sequencing on a 35-year-old woman with progressive weakness in her left upper limb, as well as on her parents. Prior to sequencing, we performed a comprehensive neurological work-up on the patient, including neurological exam, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Results : The propositus experienced weakness and atrophy in her left hand 6 months before the evaluation. This was associated with brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Genome trio sequencing identified a likely pathogenic de novo variant in the propositus’s KIF1A gene (NM_001244008.2): c.574A&gt;G, p.(Ile192Val). Discussion: Pathogenic variants in the KIF1A gene have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). The present report describe a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.

A novel polymer containing β-cyclodextrin, α-cyclodextrin, γ -cyclodextrin and chitosan (cy-clodextrin-chitosan) was synthesized, characterized and used for extracting two kinds of pharmaceuticals ibuprofen and progesterone. This polymer is amorphous and porous with a high swelling capacity. The cyclodextrin-chitosan polymer exhibits high extraction capacity towards progesterone and ibuprofen. Add to that, the effect of different operator variables was studied and discussed (i.e., the effects of contact time, solute concentration, pH, ionic strength and temperature). In this study adsorption kinetic was investigated, where it follows a pseudo-second order model in case of ibuprofen and progesterone.

Introduction: Research studies have shown that workplace stress and physical immobility can have a multi-layered effect on the human body. It causes degrade our physical functioning, and also having negative effect on our performance. Yoga techniques have proved to be effective at various levels, including physical, mental, and emotional health. Objective: This study aimed to determine the efficacy of a short-term Yoga protocol – Y break, for improved well-being and resilience to stress. It is intended to working population at work to de-stress, refresh, and refocus. Methods: This study was conducted as a single-arm, multi-centric, experimental pilot trial. Prominent yoga institutes in six metropolitan cities were engaged in this study. Participants practised specific yoga techniques for 5 minutes, twice a day, for 15 days. Pre & post-intervention data was collected along with feedback about the protocol. A self-report questionnaire, based on the Pancha kosha parameters, was used to record pre- and post-data. Results: The Statistical data analysis shown significant improvement in every parameter selected for the study. Conclusion: A five-minute yoga break can do wonders for the health-related parameters of the working population; therefore, it should be introduced in all organizations to improve the quality of life and work.

We consider a real scalar field in de Sitter background and compute its thermal propagators. We propose that in a dS/CFT context, non-trivial thermal effects as seen by an `out' observer can be encoded in the anomalous dimensions of the d=3 Ising model. One of these anomalous dimensions, the critical exponent eta, fixes completely a number of cosmological observables, which we compute.

The study of phytotherapy in dentistry is relevant due to the low occurrence of research in the treatment of oral pathologies, such as caries and periodontal disease. Thus, the aim of this research was to characterize the chemical composition of extracts from the leaves of Couroupita guianensis Aubl, including toxicological evaluation and the antioxidant and antimicrobial potential against Staphylococcus aureus, Streptococcus mutans and Candida albicans. Three extracts were prepared using assisted ultrasound, originating the Crude Ultrasound Extract (CUE) and Soxhlet apparatus, originating the Crude Soxhlet Extract (CSE) and the Ethanol Soxhlet Extract (ESE). In the analysis of the chemical composition, the presence of flavonoids, tannins and saponins were detected. LC-DAD analysis revealed the presence of caffeic acid, sinapic acid, rutin, quercetin, luteolin, kaempferol and apigenin in all extracts. In the GC-MS analysis, stigmasterol and β-sitosterol were identified in CUE and CSE. The antioxidant potentials, determined by the DPPH• and ABTS•+ methods, the ESE showed higher antioxidant activity (2.98 ± 0.96 and 4.93 ± 0.90, respectively). In the evaluation of toxicity, the CUE 50µg/mL and the ESE 50 µg/mL presented growth stimulation of Allium cepa roots. At a concentration of 750µg/mL, all extracts inhibited root growth. None of the extracts showed toxicity against Artemia salina. Antibacterial action was detected in all extracts, mainly against the microorganisms S. aureus and S. mutans; however, the antifungal action against C. albicans was not detected. From the results, the extracts of C. guianensis have therapeutic potential for use in the control of microorganisms in the oral microbiota.

With the advancement of long-read sequencing technologies and their more widespread use for bacterial genomics, several methods for generating genome assemblies from error-prone long reads have been developed. These are complemented by various tools for assembly polishing using either long reads, short reads, or reference genomes. End users are therefore left with a plethora of possible combinations of programs for obtaining a final trusted assembly. Hence, there is also the need for measuring completeness and accuracy of such assemblies, for which, again, several evaluation methods implemented in various programs are available. In order to automatically run all these programs, I developed two workflows for the workflow management system Snakemake for bacterial genome assembly and evaluation of assemblies, which provide end users with an easy-to-run method for both tasks. The workflows are available as open source software under the MIT license at https://github.com/pmenzel/ont-assembly-snake and https://github.com/pmenzel/score-assemblies.

We report on the study of ultrafast laser-induced plasma expansion dynamics in a gas microjet. To this purpose, we focused femtosecond laser pulses on a nitrogen jet produced through a homemade De Laval micronozzle. The laser excitation leads to plasma excitation with a characteristic spectral line emission at 391 nm. By following the emitted signal with a detection system based on an Intensified Charge-Coupled Device (ICCD) we captured the two-dimensional spatial evolution of the photo-excited nitrogen ions with a temporal resolution on the nanosecond time scale. We fabricated the micronozzle on fused silica substrate by femtosecond laser micromachining. This technique enables high accuracy and three-dimensional capabilities, thus providing an ideal platform for developing glass-based microfluidic structures for application to plasma physics and ultrafast spectroscopy.

Philip Phenix’s (1964) book Realms of meaning started the ever growing movement concerned with how school education might help young people in their search for meaning in times of rapid social change. Today, in globalised, digital, secularised, de-traditionalised culture, the importance and urgency of this role have never been greater. Cultural change has accelerated exponentially, and for many – including students in religious/Catholic schools – traditional religious sources of meaning are no longer prominent or plausible reference points. Catholic schools, whether independent or semi-state institutions because of government funding, can make a valuable contribution young people’s spiritual/moral education, no matter what their level of religious affiliation or practice. This article argues that such a contribution requires change to the discourse or narrative of Catholic school Religious Education, with corresponding adjustments to content and pedagogy. Its present trajectory, which is excessively concerned with promoting a Catholic identity in students, needs to be modified. Both the religious and non-religious students, especially in the senior classes, would derive greater spiritual and religious benefit from the inclusion of more life-relevant and issue-related content, together with a critical, research-oriented pedagogy. Such an approach proposes that the Catholic Church’s schools should offer unconditionally a meaningful spiritual/moral education that is relevant to all students, rather than a traditional one which seemed to presume that all students are, or should be practising Catholics. This does not minimise attention to the Catholic tradition, but it allows for a study of how people negotiate the task of constructing meaning and values in a complex culture. The article also looks at the ‘headwinds’ that hinder the implementation of this approach. The article is focused specifically on the Australian context where Catholic schools are semi-state institutions because they are funded by both state and federal governments. The issues are still likely to be pertinent to Catholic education in other countries, while taking into account significant contextual differences.

As more cases of COVID-19 are studied and treated world-wide, it had become apparent that lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV, and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings point out de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a likely cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and an assay to predict the virulence of naturally circulating SARS-like animal coronaviruses.

Diopatra neapolitana (Delle Chiaje, 1841) is one of the most exploited polychaete species in European waters, particularly in Ria de Aveiro, a coastal lagoon in mainland Portugal, where the overexploitation of this resource has led to a generalized decline of local populations. In an attempt to reduce the impact of harvesting, several management actions were implemented, but, illegal poaching still fuels a parallel economy that threats the sustainable use of this marine resource. The present study evaluated the combination of fatty acid profiles and elemental fingerprints of the whole body and jaws, respectively, of D. neapolitana collected from four harvesting locations within Ria de Aveiro in order to determine if their geographic origin could be correctly assigned post-harvesting. Results showed that both fatty acid profiles and elemental fingerprints differ significantly among locations, discriminating the geographic origin with higher accuracy when combining these two natural barcodes than when employing each individually. The present work can therefore contribute for the implementation of an effective management plan for the sustainable use of this marine resource, making possible to detect if D. neapolitana was sourced from no take zones and if it was collected from the place of origin claimed by live baits traders.

The catalytic parameters describing enzyme catalysis are discussed in the context of the design of de novo enzymes. It is shown that high values of the catalytic efficiency may in some cases reflect tight substrate binding and lead to an immediate levelling-off of rates to reach a low plateau, an undesirable scenario for many industrial applications. It is argued that increasing the catalytic rate constant should be a main target in de novo enzyme engineering.

The fluid flow field at the upper airways is highly complex due to the complex structure of the airway. The inhaled particle flow, the air streamline and the interaction of the continuum and discrete phase could significantly affect the transport behaviour of the inhaled particles. A range of analytical, mathematical and computational fluid dynamics (CFD) models analyzed the airflow and particle transport in different idealized and asymmetric airway models. A precise understanding of the continuum and discrete phase interaction in realistic human airways is missing, and this study aims to develop a CFD-DEM model for particle transport in realistic airways. This study uses the CFD model for the continuum phase and the discrete element method (DEM) for the discrete phase. A soft sphere approach is used for the interaction of the discrete phase. Proper validation is performed for particle transport efficiency. The CFD-DEM model analyzed the particle transport in an idealized and realistic airway model, and different methods are used to analyze the transport behaviour. During the particle-particle interaction, a stagnation point and a high-pressure zone are observed at the airway model's carinal angle. The numerical results report higher deposition efficiency (DE) for particle-particle interaction than without interaction. The flow field becomes highly complex with the spring constant values, and higher DE is found for high spring constant values. The spring dashpot friction-dshf method shows higher deposition at the upper part of the airways than other interaction methods. The findings of this study and more case-specific analysis would improve the knowledge of aerosol transport in airways and the health risk assessment of the patient.

Alkaloids are the most diversified nitrogen-containing secondary metabolites having antioxi-dant, and antimicrobial properties and are extensively used in pharmaceuticals to treat different types of cancer. Nicotiana serves as a reservoir of anticancer alkaloids and is also used as a model plant for the de novo synthesis of various anti-cancer molecules through genetic engineering. Up to 4% of the total dry weight of Nicotiana was found to be composed of alkaloids where nicotine, nornicotine, anatabine, and anabasine are reported as the dominant alkaloids. And, among the alkaloids present in Nicotiana, β-carboline (Harmane and Norharmane), Kynurenines are found to show anti-tumor effects, especially in the case of colon and breast cancer. Creating new or shunting of existing biosynthesis pathways in different species of Nicotiana resulted in de novo or increased synthesis of different anti-tumor molecules or their derivatives or precursors includ-ing Taxadiane (~22.5 µg/g), Artemisinin (~120 μg/g), Parthenolide (~2.05 ng/g), Costunolide (~60 ng/g), Etoposide (~1 mg/g), Crocin (~400 µg/g), Catharanthine (~60 ng/g), Tabersonine (~10 ng/g), Strictosidine (~0.23 mg/g), etc. Enrich precursor pool especially Dimethylallyl Diphos-phate (DMAPP) and down-regulating of other bi-product pathways, compartmentalization or metabolic shunting, or organelle-specific reconstitution of the precursor pool might trigger the enhanced accumulation of the targeted anticancer alkaloid in Nicotiana.

QTc interval measurement is a widely used screening tool to assess the risk of cardiac diseases, arrhythmias, and is a useful biomarker for pharmacovigilance. However, interpretation of QTc is difficult in neonates due to hemodynamic maturational changes and uncertainties on reference values. To describe trends in QTc values throughout infancy (1 year of life), and to explore the impact of (non)-maturational changes and medicines exposure, a structured systematic review (PROSPERO CRD42022302296) was performed. In term neonates, a decrease was observed over the first week of life, whereafter values increased until two months of age, followed by a progressive decrease until six months. A similar pattern, with longer QTc values was observed in preterms. QTc is influenced by cord clamping, hemodynamic changes, therapeutic hypothermia, illnesses and sleep, not by sex. Cisapride, domperidone and doxapram result in QTc prolongation in neo-nates. Further research in this age category is needed to improve primary screening practices, earlier detection of risk factors and precision pharmacovigilance.

The genus Rhodotorula includes basidiomycetous oleaginous yeast species. R. babjevae can produce compounds of biotechnological interest such as lipids, carotenoids and biosurfactants from low value substrates such as lignocellulose hydrolysate. High-quality genome assemblies are needed to develop genetic tools and to understand fungal evolution and genetics. Here, we combined short- and long-read sequencing to resolve the genomes of two R. babjevae strains, CBS 7808 (type strain) and DBVPG 8058 at chromosomal level. Both genomes have a size of 21 Mbp and a GC content of 68.2%. Allele frequency analysis indicated tetraploidy in both strains. They harbor 21 putative chromosomes with sizes ranging from 0.4 to 2.4 Mb. In both assemblies, the mitochondrial genome was recovered in a single contig, which shared 97% pairwise identity. The pairwise identity between the majority of chromosomes ranges from 82% to 87%. We found indications for strain-specific extrachromosomal endogenous DNA. 7,591 protein-coding genes and 7,607 associated transcripts were annotated in CBS 7808 and 7,481 protein-coding genes and 7,516 associated transcripts in DBVPG 8058. CBS 7808 has accumulated a higher number of tandem duplications than DBVPG 8058. We identified large translocation events between putative chromosomes and a high genetic divergence between the two strains.

Docking the tail of lambs is a standard husbandry procedure and is achieved through several techniques including clamps, hot or cold knives and latex rings, the last of which is the most popular. All tail docking methods cause acute pain which can be reduced by application of local anesthetic, however precise anatomical injection for optimal efficacy requires considerable skill. This pen trial evaluated the ability of local anesthetic delivered with a dual function ring applicator / injector to alleviate acute tail docking pain. Thirty ewe lambs were assigned to one of three treatment groups (n = 10 per group): ring plus local anesthetic (Ring LA), ring only (Ring) and sham handled control (Sham). Lambs were videoed and behavior categorized every 5 minutes for the first hour and every 10 min for the subsequent 2 hours after treatment. There was a significant effect (p &lt; 0.001) of treatment on total active pain related behaviors in the first hour, with Ring lambs showing higher counts compared to Ring LA or Sham. Ring lambs also displayed a significantly higher count of combined abnormal postures (p &lt; 0.001) than Ring LA or Sham lambs. Delivery of 1.5ml of 2% lignocaine via the dual action device abolished abnormal behaviors and signs of pain in Ring LA lambs. However, lambs in the Ring LA group spent less time attempting to suckle compared to Ring and Sham lambs, suggesting that some residual discomfort remained.

Currently, with a large number of fatality rates, coronavirus disease-2019 (COVID-19) has emerged as a potential threat to human health worldwide. It has been well-known that severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and World Health Organization (WHO) proclaimed the contagious disease as a global pandemic. Researchers from different parts of the world amalgamate together inquest of remedies for this deadly virus. Recently, it has been demonstrated that the spike glycoprotein (SGP) of SARS-CoV-2 is the mediator behind the entrance into the host cells. Our group has comprehensibly analyzed the SGP of SARS-CoV-2 through multiple sequence analysis along with the phylogenetic analysis. Further, this research work predicted the most immunogenic epitopes for both B-cell and T-cell. Notably, we focused mainly on major histocompatibility complex (MHC) class I potential peptides and predicted two epitopes; WTAGAAAYY and GAAAYYVGY, that bind with the MHC class I alleles which are further validated by molecular docking analysis. Furthermore, this study also proposed that the selected epitopes were shown availability in a greater range of the population. Hence, our study comes up with a strong base for the implementation of designing novel vaccine candidates against SARS-CoV-2, however adequate laboratory works will need to be conducted for the appropriate application.

In voice analysis, the electroglottographic (EGG) signal has long been recognized as a useful complement to the acoustic signal, if only when the vocal folds are actually contacting, such that this signal has an appreciable amplitude. However, phonation can occur also without vocal fold contacting, as in breathy voice, in which case the EGG amplitude is low, but not zero. It is of great interest to identify the transition from non-contacting to contacting, because this will substantially change the nature of the vocal fold oscillations; yet that transition is not in itself audible. The magnitude of the normalized peak derivative of the EGG signal is a convenient indicator of contacting, but no current EGG hardware has a sufficient signal-to-noise ratio of the derivative. The textbook techniques of spectral thresholding and static notch filtering are straightforward to implement, can run in real time, and can mitigate several noise problems in EGG hardware.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with a distinct set of facial features, growth limitations, and limb anomalies. Its clinical spectrum is broad and presents significant challenges in pediatric diagnosis and management. The variable presentation of the disorder, due to cohesin complex mutations, requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients, alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, with an emphasis on innovations in genetic testing, including the detection of mosaicism and novel genetic variations. The aim is to synthesise case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment, and aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

The state of Veracruz has ample water resources. However, due to population and industrial growth, there has been an increase in the discharge of wastewater into surface water bodies. To analyze the water quality in the Bobos River, Veracruz, and its sustainability, researchers collected nine samples from nine different points in the reservoir. They measured various parameters such as temperature, pH, dissolved oxygen, conductivity, total nitrogen, nitrate, chemical oxygen demand, total phosphorus, phosphate, dissolved solids, and fecal coliforms. The results showed that the river's water quality is at risk. The concentration of pollutants such as chemical oxygen demand and fecal coliforms is high. Conductivity values ranged from 0.26 to 3.81 mS. If preventive and corrective measures are not taken, the river's ability to purify pollutants will be severely compromised. This study evaluates the physical, chemical, and microbiological characteristics of the water in Bobos River. It specifically investigates the influence of the nearby citrus industry on the river's water quality. The study also aims to promote environmental sustainability.

Current consensus diagnostic criteria for vestibular migraine (VM) describes this as an episodic disorder. However, a minority of patients report prolonged (>72h duration) or even persistent VM symptoms, prompting whether a chronic variant of vestibular migraine (CVM) should be introduced to the current classification and how best to define it. Here we summarize current evidence of such a potential chronic variant of VM and critically review previously published proposed definitions for CVM. Potential approaches to establish a diagnostic framework for CVM include a) following the distinction between episodic and chronic migraine headaches; namely, frequent and/or prolonged episodes of VM (but not persistent vertigo or dizziness) in the context of chronic migraine headaches or b) daily dizzy spells over more than 6 months that responded well to prophylactic anti-migraine therapy. A key challenge when defining diagnostic criteria for CVM is how to distinguish it from other chronic vestibular syndromes such as motion sickness, persistent postural-perceptual dizziness (PPPD), and mal-de-débarquement syndrome. Indeed, more than 50% of patients with PPPD and up to 46% with mal-de-débarquement syndrome fulfill diagnostic criteria for episodic migraine headaches, suggesting these disorders may all lie along a spectrum. We propose that when VM becomes persistent, it is best classified as PPPD but that VM and PPPD are not mutually exclusive, such that patients with PPPD need not have features of VM and the triggering event for persistent dizziness may be independent of migraine.

In this study we investigate the formation of dynamical energy cascades in higher order KdV-type equations. In the beginning we recall what is known about the dynamic cascades for the classical KdV (quadratic) and mKdV (cubic) equations. Then, we investigate further the mKdV case by considering a richer set of initial perturbations in order to check the validity and persistence of various facts previously established for the narrow-banded perturbations. Afterwards we focus on higher order nonlinearities (quartic and quintic) which are found to be quite different in many respects from the mKdV equation. Throughout this study we consider both the direct and double energy cascades. It was found that the dynamic cascade is always formed, but its formation is not necessarily accompanied by the nonlinear stage of the modulational instability. Direct cascade structure remains invariant regardless the size of the spectral domain. In contrast, the double cascade shape can depend on the size of the spectral domain, even if the total number of cascading modes remains invariant. Results obtained in this study can be potentially applied to plasmas, free surface and internal wave hydrodynamics.

In this study, we investigate the formation of dynamical energy cascades in higher-order KdV-type equations. In the beginning, we recall what is known about the dynamic cascades for the classical KdV (quadratic) and mKdV (cubic) equations. Then, we investigate further the mKdV case by considering a richer set of initial perturbations in order to check the validity and persistence of various facts previously established for the narrow-banded perturbations. Afterwards, we focus on higher-order nonlinearities (quartic and quintic) which are found to be quite different in many respects from the mKdV equation. Throughout this study, we consider both the direct and double energy cascades. It was found that the dynamic cascade is always formed, but its formation is not necessarily accompanied by the nonlinear stage of the modulational instability. Direct cascade structure remains invariant regardless of the size of the spectral domain. In contrast, the double cascade shape can depend on the size of the spectral domain, even if the total number of cascading modes remains invariant. Results obtained in this study can be potentially applied to plasmas, free surface and internal wave hydrodynamics.

There is crescent demand for knowledge improvement of the integrated water vapor (IWV) distribution in regions affected by heat islands that are associated with extreme rainfall events such as in the metropolitan area of Rio de Janeiro (MARJ). This work assessed the suitability and distribution of IWV in the MARJ using products from the Global Navigation Satellite Systems (GNSS), MODerate Resolution Imaging Spectroradiometer (MODIS), and radiosonde. GNSS data were collected by the tracking station named RDJN, from the cooperation of the International GNSS Monitoring and Assessment System (iGMAS) and the National Observatory of Brazil (Observatório Nacional - ON), and the tracking stations ONRJ, RIOD, and RJCG belonging to the Brazilian Network for Continuous Monitoring (RBMC) in the period of January 2015–August 2018. High variability of the near surface air temperature (T) and relative humidity (RH) were observed among eight meteorological sites considered. The mean T differences between sites, up to 4.4 °C, led to mean differences as high as 3.1 K for weighted mean temperature (Tm) and hence 0.83 mm for IWV differences. The performance of the MODIS MOD07 and MYD07 products provided a reasonably good representation of the mean spatial distribution of IWV, especially during the daylight passages of the satellites TERRA and AQUA. Local grid points of MODIS IWV estimates had relatively good agreement with the GNSS-derived IWV, with mean differences from -2.4–1.1 mm considering only daytime passages of the satellites TERRA and AQUA. During nighttime, MODIS underestimated IWV (from -9–-3 mm) with respect to GNSS, due to attenuation of IR radiation by clouds. A contrasting behavior was found in the radiosonde IWV estimates compared with the estimates from GNSS. There were dry biases of 1.4 mm (3.7% lower than expected) by radiosonde IWV during the daytime considering that all other estimates were unbiased and the differences between IWV GNSS and IWV RADS were consistent. Based on the IWV comparisons between radiosonde and GNSS at nighttime, the atmosphere over the radiosonde site is about 1.2 (2.3) mm wetter than over RIOD (RDJN) station. The long time series of the comparisons between IWVRDJN and IWVRIOD showed that the highest values of IWV occurred from the afternoon to nocturnal hours. Further, the atmosphere over the site RIOD was consistently about 1 mm wetter than over RDJN. These results showed the feasibility of the iGMAS RDJN station data compared with the RBMC, MODIS, and radiosonde data to investigate IWV in a region with occurrence of heat islands, and the peculiar physiographic and meteorological characteristics as in the MARJ. This work recommended the usage of complete meteorological station data collocated near every GNSS receiver aiming improvements of local GNSS IWV estimates and serving as additional support for operational numerical assimilation, weather forecast, and nowcast of extreme rainfall events.

99mTc is a well-known radionuclide widely used and readily available for medical imaging. Despite this, the 99mTc isotope is rarely utilized for tumour imaging due to the lack of agents that can selectively deliver it to tumours. However, the use of immunologically compatible recombinant proteins, which combine metal-binding sites and tumour-specific ligands, shows promise for utilizing 99mTc in the early detection of tumours. To illustrate this, a protein called E1b, containing a metal binding center with ELP repeats, tumour-specific ligands recognizing integrin αvβ3 and nucleolin, as well as a short Cys-rich sequence, was artificially designed. This protein was produced in E. coli and purified to homogeneity using metal-chelate chromatography. In experiments, C57Bl/6 and Balb/C mice with subcutaneously grafted lung carcinoma (LLC) or mammary gland adenocarcinoma (Ca755, EMT6, or 4T1) were used to test 99mTc-E1b selectivity and the kinetics of isotope retention. The mice were intravenously injected with approximately 80 MBq of 99mTc in complex with E1b, which had been freshly purified using gel-chromatography. The biodistribution of the labeled protein was then studied using the SPECT/CT imaging method within 24 h. The ratio of radionuclide distribution in the tumour versus the adjacent normal tissue (T/N) steadily increased over the 24-h period, reaching 15.7±4.2 for EMT6, 16.5±3.8 for Ca755, 6.7±4.2 for LLC, and 7.5±3.1 for 4T1.

Objective: To verify knowledge about HPV, promote educational action and encourage vaccination among students from 6th to 9th grade in the public school system of Campo Grande - MS. Methods: Conducting a structured interview. Results: It was pointed out that 70.1% had heard about HPV, however, 38.1% stated that it is a virus that causes cancer and 11.3% related it to the virus that causes warts. The free availability of the vaccine was known to 57.7% of participants and 62.3% were vaccinated with at least one dose. 79 students were vaccinated during the actions. Conclusion: There is a lack of knowledge, as the majority did not know how to relate HPV to the development of cervical cancer. The interaction between primary health care and schools resulted in the dissemination of knowledge about HPV, an increase in vaccine doses administered, favoring an increase in vaccination coverage among students.

Low-energy cosmic rays (LECRs) play a crucial role in the formation of planetary systems, and detecting and reconstructing the properties of early LECRs is essential for understanding the mechanisms of planetary system formation. Given that LECRs interact with the surrounding medium to produce nuclear de-excitation line emissions with energy mainly within 0.1–10 MeV, which are unaffected by stellar wind modulation, these gamma-ray emissions can accurately reflect the properties of LECRs. This study introduces an innovative method for using gamma-ray emissions to infer LECR properties. We employed the Parker transport equation to simulate the propagation and spectral evolution of LECRs in a protoplanetary disk and calculated the characteristic gamma-ray emissions resulting from interactions between LECRs and disk material. These gamma-ray emissions encapsulate the spectral information of LECRs, providing a powerful tool to reconstruct the cosmic ray environment at that time. This method, supported by further theoretical developments and observations, will fundamentally enhance our understanding of the impact of CRs on the origin and evolution of planetary systems and address significant scientific questions regarding the cosmic ray environment at the origin of life.

In developing his cosmological model of 1917, de Sitter theoretically predicted the phenomenon of cosmological redshift (the de Sitter effect), which he did long before the discovery of this phenomenon in observations. The de Sitter effect is gravitational by its nature, as it is due to differences between the coordinate systems of the observer and the distant source. However, the relationship between the redshift and distance derived from the de Sitter metric is at odds with observations, since this relationship is nonlinear (quadratic) for small redshifts, while the observed relationship between the same quantities is strictly linear. This paper discusses the possibility that cosmological redshift is gravitational by its nature, as in de Sitter’s 1917 model. At the same time, here, as in de Sitter’s model, an elliptical space is used, the main characteristic of which is the identification of its antipodal points. But, unlike de Sitter’s model, here, in order to ensure a strict linear dependence of the redshift on distance, the origin of the reference system is transferred to the observer’s antipodal point. The Schwarzschild-de Sitter metric used in this model allows you to estimate the curvature of space from observational data. To do this, a theoretical Hubble diagram is built within the framework of the model with the Schwarzschild-de Sitter metric, which is compared with observations from the Pantheon+ catalogue of type Ia supernovae and the Amati catalogue of gamma-ray bursts in the redshift range of 0&lt;z&lt;8. As a results of the comparison, the lower estimate of the radius of curvature of space turned out to be quite large: 2.3·1015 Mpc. This means that the observational data indicate a negligible curvature of space.

Currently, there is no widely accepted consensus regarding a consistent thermodynamic framework within the special relativity paradigm. However, by postulating that the inverse temperature 4-vector, denoted as β, is future-directed and timelike, intriguing insights emerge. Specifically, it is demonstrated that the q-dependent Tsallis distribution can be conceptualized as a de-Sitterian deformation of the relativistic Maxwell-Jüttner distribution. In this context, the curvature of the de Sitter space-time is characterized by Λ/3, where Λ represents the cosmological constant within the ΛCDM standard model for Cosmology. For a simple gas composed of particles with proper mass m, and within the framework of quantum statistical de Sitterian considerations, the Tsallis parameter q exhibits a dependence on the cosmological constant given by q=1+ℓcΛ/n where ℓc=ℏ/mc is the Compton length of the particle and n is a positive numerical factor. This formulation establishes a novel connection between the Tsallis distribution, quantum statistics, and the cosmological constant, shedding light on the intricate interplay between relativistic thermodynamics and fundamental cosmological parameters.

De-escalation is currently taking place both in surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor over 20 years ago was a milestone in the treatment of HER2 positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in case of small, node-negative, HER2 positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2 targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2 positive early breast cancer. Despite promising early results from these studies, combination of anti-HER2 treatment with chemotherapy backbone remains standard of care.

This study analyzes the influence of CEO types on corporate governance, focusing on de facto (substantial) CEOs. We examine how substantial CEOs impact ESG activities (Hypothesis 1) and corporate value (Hypothesis 2). Data were collected from KIS-VALUE and DART (Electronic Disclosure System) of the Financial Supervisory Service, defining substantial CEOs as highest remuneration recipients exceeding the representative director of the company pay. Results sup-port Hypothesis 1, showing companies with substantial CEOs are more engaged in ESG activities, potentially to improve public image while concealing self-serving behaviors. Hypothesis 2 is validated, indicating lower corporate value in companies with substantial CEOs due to prioritizing personal interests over long-term profit maximization. Despite limitations in exploring governance relationships beyond remuneration data, the study offers key contributions. It expands research on corporate governance and ESG activities by identifying substantial CEOs through objective remuneration data. It highlights the importance of an independent board for transparent governance and positive corporate value. Lastly, empirical evidence shows the negative impact of misdirected ESG activities on corporate value. By using remuneration as an indicator, this study illuminates substantial CEOs' influence on corporate value and ESG activities, providing insights for future research in corporate governance and ESG.

To assess the degree to which it has met its commitments under the Paris Agreement, Morocco is called upon to carry out carbon assessments and transparent evaluations. Within the forestry sector, little is known about the role of Morocco’s forests in contributing to carbon uptake. With this aim, we applied for the first time in literature the 3-PG model to Cedrus atlantica ((Endl.) Manetti ex Carrière, 1855), which represents about 131.800 ha of Morocco’s forest area (i.e. Azrou forest). Through the Differential Evolution - Markov Chains (DE-MC) we tested and assessed the sensitivity and calibrated the 3-PG model. This process-based model provided significant results regarding the carbon sequestration capacity. The results showed the following: i- Parameters related to stand properties, canopy structure, and processes, as well as biomass partitioning, are the most important or sensitive for the performance of the model; ii- The DE-MC method optimized the values of the 3-PG parameters which was confirmed by the means of Gelman-Rubin convergence test; iii- According to the predictions of the calibrated 3-PG, the Net Primary Production in the pure Azrou forest varies between 0.32 and 7.88 tC.ha−1.yr−1, it is equal in average to 4.9 tC.ha−1.yr−1, which given the total area corresponds to 7078 tC.yr−1.

Canola is the major oilseed crop of Canada. The de-oiled material is an important by-product due to its rich phenolic profile and high protein content. This co-processing stream from canola is primarily utilized as animal feed but represents an invaluable source of nutraceuticals. Microwave-assisted solvent extraction (MAE), as a green extraction method, has received considerable attention in recent times. The ease of use and application of many solvents at the same time makes the MAE one of the best methods for studying multiple solvents at the same time. The formation of canolol, from sinapine and sinapic acid, is primarily dependant on temperature which favors the decarboxylation reaction. Hence, MAE using green extractants can be used to enhance the yield of canolol. This study examined the effects of different pre-treatment temperature-time combinations of 140, 150, 160, and 170℃ for 5, 10, 15, 20 and 30 minutes on the extraction of canolol and other canola endogenous phenolic compounds. Three antioxidant assays assessed the antioxidant activity of the different extracts obtained by MAE confirming the microwave as a novel and versatile instrument for enhancing the yield of canolol. Improvements in the antioxidant activity of the different extracts further established the efficacy of the current method for isolating important natural phenolic derivatives for utilization by the nutraceutical industry.

The issue of being pro-gender is still a controversial topic to be debated in Indonesian society. However, in the 21st Century, many women have been able to break through barriers and participate in the public sphere. It is a form of self-existence as proposed by Simone de Beauvoir on existentialist feminism. Based on these problems, this study aims to find out and answer questions about how Indonesian women exist in the public sphere in the 21st Century and find out how Indonesian women exist in the public sphere through Simone de Beauvoir's existentialist feminism paradigm. The research method used is descriptive-qualitative through a literature review of 23 journal articles, websites, and data reports with a range of 2019-2021. This study found that based on Simone de Beauvoir's feminist paradigm, Indonesian women in the 21st Century are no longer a figure other than complete. Furthermore, the data collected by the researcher shows that several gender indicators have shown that Indonesian women have been able to occupy public spaces in various aspects. Based on these results, it is hoped that it can provide information about Simone de Beauvoir's existentialist feminism thought and its relevance to the existence of Indonesian women in the public sphere in the 21st Century. However, this research has limitations, those are only about women in Indonesia, and the paradigm of feminism is limited to Simone de Beauvoir's existentialist feminism.

In this paper we will show that standard physics to a large degree consists of derivatives of a deeper reality. This means standard physics is both overly complex and also incomplete. Modern physics has typically started from working with first understanding the surface of the world, that is typically the macroscopic world, and then forming theories about the atomic and subatomic world. And we did not have much of a choice, as the subatomic world is very hard to observe directly, if not impossible to observe directly at the deepest level. Despite the enormous success of modern physics, it is therefore no big surprise that we at some point have possibly taken a step in the wrong direction. We will claim that one such step came when one thought that the de Broglie wavelength represented a real matter wavelength. We will claim that the Compton wavelength is the real matter wavelength. Based on such a view we will see that many equations in modern physics are only derivatives of much simpler relations. Second, we will claim that in today’s physics one uses two different mass definitions, one mass definition that is complete or at least more complete, embedded in gravity equations without being aware of it, as it is concealed in GM, and the standard, but incomplete, kg mass definition in non-gravitational physics. First, when this is understood, and one uses the more complete mass definition that is embedded in gravity physics, not only in gravity physics, but in all of physics, then one has a chance to unify gravity and quantum mechanics. Our new theory shows that most physical phenomena when observed over a very short timescale are probabilistic for masses smaller than a Planck mass and dominated by determinism at or above Planck mass size. Our findings have many implications. For example, we show that the Heisenberg uncertainty principle is rooted in a foundation not valid for rest-mass particles, so the Heisenberg uncertainty principle can say nothing about rest-masses. When re-formulated based on a foundation compatible with a new momentum that is also compatible with rest-masses, we obtain a re-defined Heisenberg principle that seems to become a certainty principle in the special case of a Planck mass particle. Furthermore, we show that the Planck mass particle is linked to gravity and that we can easily detect the Planck scale from gravity observations. The Planck mass particle is unique as it only lasts the Planck time, and in that very short time period it can only be observed directly from itself, and it therefore closely linked to absolute rest.

Three-dimensional (3D) geological modeling technology offers intricate geological information services and technical support for the research of urban geological conditions and their evolutionary mechanisms. It further facilitates the analysis of environmental geological problems, encompassing their distinguishing features and genetic mechanisms. The precision of such three-dimensional models is predominantly influenced by the caliber of modeling data, the chosen modeling methodologies, and the intricacy of the modeled geological objects. This research, exemplified by the three-dimensional geological structure modeling of the Wuhan metropolitan development area, aims to explore a comprehensive three-dimensional modeling framework for urban geology, particularly in scenarios with large-scale and complex geological conditions. This study holds significant technical value in enhancing the application of 3D geological modeling, as well as practical importance for urban geological investigations and research.

Obstructive sleep apnea (OSA) is a prevalent source of sleep-disordered breathing, generally caused by common factors in modern life. OSA is most commonly associated with dysfunctions in the genioglossus (GG) muscles. In this study, we present the first version of a medical device that measures the electromyogram (EMG) of the GG. The prototype is composed of a (custom-made) 3D-printed mouthpiece. Impressions were taken for the lower arch and scanned with a lab scanner to be converted into digital impressions. ExoCad software was used to design the appliance. Fusion 360 software was then used to modify the design and create tubes to house the electrodes in a bilateral configuration to secure excellent and continuous contact with the GG muscle. Silver-silver chloride electrodes were incorporated within the appliance through the created tubes to record the muscle EMG. In this preliminary prototype, the EMG amplifier was placed outside the mouth, and isolated electric wires were connected to the amplifier input. Simple tests that included a group of OSA patients and a control group were done during wakefulness to check the comfort and stability of the device, understand the nature of GG EMG, and study which OSA might affect the daytime performance of the GG. The GG EMG was acquired from the participants for 60 seconds at Rest state when the participant rested his tongue without doing any activity. Then, the subject pushes his tongue against the fontal teeth with steady force while keeping the mouth closed (Active state). Several features were extracted from the acquired EMG: The results showed that mean power and standard deviation were higher in the control group than in the OSA group (p < 0.01). Regarding the wavelength during active state, the control group had a significantly longer wavelength than the OSA group (p < 0.01). Meanwhile, the mean frequency was higher in the OSA group (p < 0.01) at rest. Future research should focus on developing the device to be more user-friendly and easily used at home during wakefulness and sleep.

We discuss the consequences of the unique symmetry of the de Sitter spacetime. This symmetry leads to the specific thermodynamic properties of the de Sitter vacuum, which produces the thermal bath for matter. The de Sitter spacetime is invariant under the modified translations, ${\bf r}\rightarrow {\bf r} -e^{Ht}{\bf a}$, where $H$ is the Hubble parameter. For $H\rightarrow 0$, this symmetry corresponds to the conventional invariance of Minkowski spacetime under translations ${\bf r}\rightarrow {\bf r} -{\bf a}$. Due to this symmetry, all the comoving observers at any point of the de Sitter space perceive the de Sitter environment as the thermal bath with temperature $T=H/\pi$, which is twice larger than the Gibbons-Hawking temperature of the cosmological horizon. This temperature does not violate the de Sitter symmetry, and thus does not require the preferred reference frame, as distinct from thermal state of matter, which violates the de Sitter symmetry. This leads to the heat exchange between gravity and matter, and to instability of de Sitter state towards the creation of matter, its further heating, and finally to the decay of the de Sitter state. The temperature $T=H/\pi$ determines different processes in the de Sitter environment, which are not possible in the Minkowski vacuum, such as the process of ionization of an atom in the de Sitter environment. This temperature also determines the local entropy of the de Sitter vacuum state, and this allows us to calculate the total entropy inside the cosmological horizon. The result reproduces the Gibbons-Hawking area law, which is related to the cosmological horizon, $S_{\rm hor}=4\pi KA$, where $K=1/16\pi G$. This supports the holographic properties of the cosmological event horizon. We extend the consideration of the local thermodynamics of the de Sitter state using the $f({\cal R})$ gravity. In this thermodynamics, the Ricci scalar curvature ${\cal R}$ and the effective gravitational coupling, $K$, are thermodynamically conjugate variables. The holographic connection between the bulk entropy of the Hubble volume, and the surface entropy of the cosmological horizon remains the same, but with the gravitational coupling $K=df/d{\cal R}$. Such connection takes place only in the $3+1$ spacetime, where there is the special symmetry due to which the variables $K$ and ${\cal R}$ have the same dimensionality. We also consider the lessons from the de Sitter symmetry for the thermodynamics of black and white holes.

I argue that the main feature of elliptical space – the topological identification of its antipodal points – might be behind some observational facts on both cosmological and microscopic scales. I use calculated distance moduli of type-Ia supernovae, which are commonly regarded as “standard candles” for distance measure in cosmology. These are compared with the observational data collected in a catalogue called “Pantheon+”. On the microscopic scale I show that a physical elliptical space, in which the mathematical connectedness between antipodal points is replaced with physical connections via the Einstein-Rosen bridges (also called “wormholes”), gives rise to sub-particle structures similar to J.A. Wheeler’s geons. The interactions between these structures leading to their equilibrium configurations can explain the experimentally observed pattern of properties of elementary particles forming the standard model of particle physics. The answer to the question why we have this particular set of fundamental particles might lie in the fundamental properties of elliptical space.

The ability to simulate realistically the electronic structure of superconducting materials is important to understand and predict various properties emerging in both the superconducting topological and spintronics realms. We introduce a tight-binding implementation of the Bogoliubov-de Gennes method, parameterized from density functional theory, which we utilize to explore the bulk and thin films of Nb, known to host a significant superconducting gap. The latter is useful for various applications such as the exploration of trivial and topological in-gap states. Here, we focus on the simulations aspects of superconductivity and study the impact of temperature, Cooper-pair coupling and dimensionality on the size of the superconducting order parameter.

Resistance evolution during exposure to non-lethal levels of antibiotics is influenced by various stress responses of bacteria which are known to affect growth rate. Here, we aim to disentangle how the interplay between resistance development and associated fitness costs is affected by stress responses. We performed de novo resistance evolution of wild-type strains and single-gene knockout strains in stress response pathways using four different antibiotics. Throughout resistance development, the increase in minimum inhibitory concentration (MIC) is accompanied by a gradual decrease in growth rate, most pronounced with amoxicillin or kanamycin. By measuring biomass yield on glucose and whole-genome sequences at intermediate and final timepoints, we identified two patterns of how the stress responses affect the correlation between MIC and growth rate. First, single-gene knockout E. coli strains associated with reactive oxygen species (ROS) acquire resistance faster and mutations related to antibiotic permeability and pumping out occur earlier. This increases the metabolic burden of resistant bacteria. Second, the ΔrelA knockout strain which has reduced (p)ppGpp synthesis, is restricted in its stringent response, leading to diminished growth rates. The ROS-related mutagenesis and the stringent response are vulnerabilities within the fitness of resistant strains that can possibly be targeted to prevent development of resistance.

The gate resistance is a parasitic element in transistors for RF and millimeter-wave circuits that can negatively impact power gain and noise figure. To develop accurate device models, a reliable measurement methodology is crucial. This article reviews the standard measurement methodology used in the literature and proposes also an additional method, which is evaluated using suitable test structures in a 16nm FinFET process. The advantages and disadvantages of the two approaches are discussed along with their respective application scenarios

With the development of deep learning technology, various structures and research methods for super-resolution restoration of natural images and document images have been introduced. In particular, a number of recent studies have been conducted and developed in image restoration using generative adversarial network. Super-resolution restoration is ill-posed problem because of some complex restraints such as a lot of high-resolution images being restored for the same low-resolution image and also difficulty in restoring noises like edges, light smudging, and blurring. In this study, we utilized the spatially adaptive de-normalization (SPADE) structure for document image restoration to solve previous problems such as edge unclearness, hardness to catch features of texts, and the image color transition. Consequently, it can be confirmed that the edge of the character and the ambiguous stroke are restored more clearly when contrasting with the other previously suggested methods. Also, the proposed method’s PSNR and SSIM scores are geting 8% and 15% higher, respectively, compared to the previous methods.

The widespread integration and growing dependence among currency, stock and commodity markets make these markets often very vulnerable to shocks and at risk of collapse at the same time. As a result, these trends threaten the sustainability of the entire financial system. In this study, we explore the spillovers and nonlinear dependences between the seven major foreign ex-change rates, crude oil and gold prices, a global stock price index, and oil and stock implied volatility indices as proxy variables for global risk factors by em-ploying directional spillover network approach. We also use multi-scale de-composition method and nonlinear causality test between these variables to capture multi-level relationships at short and long horizons. Major findings are summarized as follows. First, from the multi-scale decomposition analysis, we identify that Granger causality test results and the direction and strength of return spillovers change with the level of decomposition. Second, the results of nonlinear causality tests show variation in both the significance and direction of Granger causality relationships between the decomposed currency and other series at different timescales, especially for the decomposed oil, gold, and OVX series. Third, the measured directional spillover indices identify the EUR as the largest contributor of connectedness to the other series. The central role of the EUR is a net transmitter of connectedness to gold, oil, the GBP, JPY, and CHF.

Scale invariance is expected in empty Universe models, while the presence of matter tends to suppress it. As shown recently, scale invariance is certainly absent in cosmological models with densities equal to or above the critical value ρ_c = 3(H₀)²/(8πG). For models with densities below ρc, the possibility of limited effects remains open. If present, scale invariance would be a global cosmological property. Some traces could be observable locally. For the Earth-Moon two-body system, the predicted additional lunar recession would be increased by 0.92 cm/yr, while the tidal interaction would also be slightly increased. The Earth-Moon distance is the most systematically measured distance in the Solar System, thanks to the Lunar Laser Ranging (LLR) experiment active since 1970. The observed lunar recession from LLR amounts to 3.83 (±0.009) cm/yr; implying a tidal change of the length-of-the-day (LOD) by 2.395 ms/cy. However, the observed change of the LOD since the Babylonian Antiquity is only 1.78 ms/cy, a result supported by paleontological data, and implying a lunar recession of 2.85 cm/yr. The significant difference of (3.83-2.85) cm/yr = 0.98 cm/yr, already pointed out by several authors over the last two decades, corresponds well to the predictions of the scale-invariant theory, which is also supported by several other astrophysical tests.

Formulating a relativistic equation for particles with arbitrary spin remains an open challenge in theoretical physics. In this study, the main algebraic approaches used to generalize the Dirac and Kemmer–Duffin equations for particles of arbitrary spin are investigated. It is proved that an irreducible relativistic equation formulated using spin matrices satisfying the commutation relations of the de Sitter group leads to inconsistent results, mainly as a consequence of violation of unitarity and the appearance of a mass spectrum that does not reflect the physical reality of elementary particles. However, the introduction of subsidiary conditions resolves the problem of unitarity and restores the physical meaning of the mass spectrum. The equations obtained by these approaches are solved and the physical nature of the solutions is discussed.

Autonomous weapons systems (AWS), sometimes referred to as “killer robots”, are receiving evermore attention, both in public discourse as well as by scholars and policymakers. Much of this interest is connected with emerging ethical and legal problems linked to increasing autonomy in weapons systems, but there is a general underappreciation for the ways in which existing law might impact on these new technologies. In this paper, we argue that as AWS become more sophisticated and increasingly more capable than flesh-and-blood soldiers, it will increasingly be the case that such soldiers are “in the power” of those AWS which fight against them. This implies that such soldiers ought to be considered hors de combat, and not targeted. In arguing for this point, we draw out a broader conclusion regarding hors de combat status, namely that it must be viewed contextually, with close reference to the capabilities of combatants on both sides of any discreet engagement. Given this point, and the fact that AWS may come in many shapes and sizes, and can be made for many different missions, we argue that each particular AWS will likely need its own standard for when enemy soldiers are deemed hors de combat. We conclude by examining how these nuanced views of hors de combat status might impact on meaningful human control of AWS.

The Astyanax species complex has two morphs: a blind, depigmented morph which inhabits caves in México and an eyed, pigmented surface-dwelling morph. The eyed morph can also be found in caves, sometimes hybridizing with the cave morph. This species complex has arguably become the most prominent model system among cave organisms for the study of evolutionary development and genomics. Before this study, 32 caves were known to be inhabited by the cave morph, 30 of them within the El Abra region. The purpose of this study was to conduct new surveys of the area and to assess some unconfirmed reports of caves presumably inhabited by troglomorphic fish. We describe two new localities, Sótano del Toro #2 and Sótano de La Calera. These two caves make a single hydric system together with the previously described cave of Sótano del Toro. The system is inhabited by a mixed population of troglomorphic, epigeomorphic and presumably hybrid fish. Furthermore, Astyanax cavefish and the mysid shrimp Spelaeomysis quinterensis show a phylogeographic convergence that supports the notion that the central Sierra de El Abra is a biogeographical region that has influenced the evolutionary history of its aquatic community across species. The presumptive location of its boundaries, which may limit cave-to-cave or surface-to-cave gene flow, are identified.

This paper explores the application of machine learning techniques and statistical analysis to identify patterns of victimization and the risk of gender-based violence in San Andrés de Tumaco, Nariño, Colombia. Models were developed to classify women according to their vulnerability and risk of suffering various forms of violence, which were integrated into a decision-making tool for local authorities. The algorithms employed include K-means for clustering, artificial neural networks, random forest, decision trees, and multiclass classification algorithms combined with fuzzy classification techniques to handle incomplete data. Implemented in Python and R, the models were statistically validated to ensure their reliability. Analyses based on health data revealed key patterns of victimization and risks associated with gender-based violence in the region. This study presents a data science model that uses a social determinants approach to assess the characteristics and patterns of violence against women in the Pacific region of Nariño. The research was conducted within the framework of the Orquídeas Program of the Colombian Ministry of Science, Technology, and Innovation.

This paper presents a mathematically rigorous investigation into the incompleteness of Einstein-de Sitter spacetime. The incompleteness of the spacetime is proved using results regarding isometries between connected Semi-Riemannian manifolds following the computation of the Einstein tensor of the Einstein-de Sitter spacetime. Various properties of the Einstein-de Sitter spacetime apart from its incompleteness is also discussed based on its incompleteness with the help of various results of Semi-Riemannian manifolds. Also, few properties of spacetime which cannot be concluded from the incompleteness of the spacetime is also discussed.

In this study, I will present some documentary evidence that Carlos Drummond de Andrade’s poem “A Máquina do Mundo” [The Machine of the World] (1949) was based on prior reflections contained in a forgotten newspaper article entitled “Poesia e Pesadelo” [Poetry and Nightmare] (1949). In that article, Drummond critically analyzed some of the theses of Stephen Spender's essay “What Is Modern in Modern Poetry” (1948), which had just been published in The Tiger's Eye magazine. As soon as he read Spender's text, Drummond wrote “Poetry and Nightmare” and began to elaborate a narrative poem whose protagonist would be a machine. All the documentary evidence indicates that Drummond took Spender's lessons as touchstones for the elaboration of the narrative and allegorical structure of “The Machine of the World.” According to the interpretation I am proposing here, Drummond, in writing the machine poem, put into practice at least six lessons drawn from Spender’s essay, namely: 1) the modern poet must represent the tension between the external machinelike landscape and the landscape of the inner world of the creative imagination; 2) he must also represent the machinelike, ugly, and urban world around him in a beautiful and poetic way; 3) he must avoid the misconceptions of excessive utopian visionarism, as well as creeping realism; 4) he must reject the imperative of political engagement, whose principle of action states that poetry has a transformative mission in society; 5) he must free himself from the obsession with free verse as the only form of modern poetry and start using the traditional fixed forms; 6) he must understand machines as poetic symbols of human passions, and not just as exotic objects foreign to human reality. My conclusion is that, after reading Spender’s essay, Drummond changed his aesthetic and philosophical understanding of what defines the essence of modern poetry, both in terms of form and content.

We study Einstein's gravity coupled to nonlinear electrodynamics with two parameters in Anti-de Sitter spacetime. Magnetically charged black holes in an extended phase space is investigated. We obtain the mass and metric functions, their asymptotic and corrections to the Reissner--Nordstr\"{o}m metric function when the cosmological constant vanishes. The first law of black hole thermodynamics in extended phase space is formulated and the magnetic potential and the thermodynamic conjugate to the coupling are obtained. We proved the generalized Smarr relation. The heat capacity and the Gibbs free energy are computed and phase transitions are studied. It was shown that the electric field of charged objects at the origin and electrostatic self-energy are finite within the nonlinear electrodynamics proposed.

Colletotrichum lini is a flax fungal pathogen, comprising differently virulent strains. In this work, we sequenced the genomes of three C. lini strains of different virulence: high virulent #390-1, medium virulent #757, and low virulent #771. We obtained more than 100× genome coverage with Oxford Nanopore Technologies reads and more than 50× genome coverage with Illumina data. To construct high-quality genomes, several assembly strategies were tested. The final assemblies were obtained using the Canu – Racon ×2 – Medaka – Polca scheme and were 54.0-55.3 Mb in length, contained 26-32 contigs, had an N50 > 5 Mb and the BUSCO completeness > 96%. Comparative analysis of the constructed genomes showed high similarity between mitochondrial and nuclear genomes. However, a rearrangement event and the loss of a 0.9 Mb contig were revealed. The candidate effectors were predicted in sets of proteins received after genome annotation. The obtained genome sequences of C. lini strains extend the knowledge on the genetic diversity of Colletotrichum species and are the basis for establishing molecular mechanisms of pathogenicity of the flax pathogen and effective control of flax anthracnose.

The main object of this work is to establish the existence and uniqueness of a solution to the 3D Navier-Stokes (NS) system for an incompressible fluid with viscosity. The nonlinearity of the NS system, as well as the need to estimate velocity and pressure for every value of the viscosity parameter [1] make them challenging to solve. In this regard, in the present work, we study the Navier-Stokes system, which describe the flow of a viscous incompressible fluid and the solution was obtained for velocity and pressure in an analytical form. In addition, the found pressure distribution law, which is described by a Poisson type equation and plays a fundamental role in the theory of Navier-Stokes systems in constructing analytic smooth (conditionally smooth) solutions.

Mutations, especially those at the protein-protein interaction (PPI) interface, have been associated with various diseases. Meanwhile, though de novo mutations (DNMs) have been proven important in neuropsychiatric disorders, such as developmental delay (DD), the relationship between PPI interface DMNs and DD has not been well studied. Here we curated developmental delay DNM datasets from the PsyMuKB database and showed that DD patients showed a higher rate and deleteriousness in DNM missense on the PPI interface than sibling control. Next, we identified 302 DD-related PsychiPPIs, defined as PPI harboring a statistically significant number of DNM missenses at their interface, and 42 DD candidate genes from PsychiPPI. We then observed that PsychiPPIs preferentially affected hub proteins in the human protein interactome network. When analyzing DD candidate genes using gene ontology and gene spatio-expression, we found that PsychiPPI genes carrying PPI interface mutations, such as FGFR3 and ALOX5, were enriched in development-related pathways and the development of the neocortex, and cerebellar cortex, suggesting their potential involvement in the etiology of DD. Our results demonstrated that DD patients carried an excess burden of PPI-truncating DNM, which could be used to efficiently search for disease-related genes and mutations in large-scale sequencing studies. In conclusion, our comprehensive study indicated the significant role of PPI interface DNMs in developmental delay pathogenicity.

ALDH+ H1975 lung adenocarcinoma stem cells (LSCs) are a rare cell population identified in lung adenocarcinoma (LUAD). LSCs can self-renew, drive tumor initiation, growth, metastasis, and recurrence, and are also the predominant cause of poor prognosis due to their intrinsic resistance to drugs and chemotherapy. Consequently, LSCs are a promising target for LUAD therapy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), exert many significant regulatory functions in the pathogenesis of human cancers, showing the necessity for a comprehensive understanding of the mechanisms that underlie lung carcinogenesis. Nonetheless, research on many known transcripts and messenger RNAs (mRNAs) has already generated new information. Unknown biomarkers in ncRNAs and systematic and comprehensive interrelation with unknown ncRNAs and mRNAs may provide further insights into the biology of LUAD. Herein, a set of novel ncRNAs that include miRNAs, lncRNAs, circRNAs, were identified and differentially expressed patterns of ncRNAs and mRNAs in LSCs and ALDH- H1975 LUAD tumor cells (LTCs) were obtained using stringent bioinformatics pipelines. Through a meta-analysis of the identified landscapes, novel competitive endogenous RNA (ceRNA) networks were constructed to reveal the potential molecular mechanisms that regulate the hallmarks of LSCs and LTCs. This study presents a summary of novel ncRNAs and the fundamental roles of differentially expressed ncRNAs implicated in the activity of LSCs and LTCs. In addition, the study also provides a comprehensive resource for the future identification of diagnostic, therapeutic, and prognostic biomarkers in LUAD.

To guide analysts to select the right tool and parameters in differential gene expression analysis of single-cell RNA sequencing (scRNA-seq) data, we developed a novel simulator that recapitulates the data characteristics of real scRNA-seq datasets while accounting for all the relevant sources of variation in a multi-subject, multi-condition scRNA-seq experiment: the cell-to-cell variation within a subject, the variation across subjects, the variability across cell types, the mean/variance relationship of gene expression across genes, library size effects, group effects, and covariate effects. By applying it to benchmark 12 differential gene expression analysis methods (including cell-level and pseudo-bulk methods) on simulated multi-condition, multi-subject data of the 10x Genomics platform, we demonstrated that methods originating from the negative binomial mixed model such as glmmTMB and NEBULA-HL outperformed other methods. Utilizing NEBULA-HL in a statistical analysis pipeline (https://github.com/interactivereport/scRNAseq_DE) for single cell analysis will enable scientists to better understand cell-type specific transcriptomic response to disease or treatment effects and to discover new drug targets. Further, application to two real datasets showed the outperformance of our differential expression (DE) pipeline, with unified findings of differentially expressed genes (DEG) and a pseudo-time trajectory transcriptomic result. In the end, we made recommendations of filtering strategies of cells and genes based on simulation results to achieve optimal experimental goals.

Temperature-index modeling is used to determine the magnitude of temperature depression on the Blanca Massif, Colorado, required to maintain steady-state mass balances of nine reconstructed glaciers at their extent during the Last Glacial Maximum (LGM). The mean temperature depression thus determined is ~8.6 +0.7/–0.9 °C where the uncertainties account for those inherent in the glacier reconstructions, in model parameters (e.g. melt factors), and possible modest changes in LGM precipitation. Associated equilibrium-line altitudes (ELAs) exhibit a statistically significant directional dependency being lower toward the north and east. Under the assumption that regional temperature change was uniform, required changes in precipitation vary systematically – also exhibiting a directional dependency coinciding with that in ELAs – and indicate increases (over modern) occurred on the eastern side of the massif while decreases occurred on the western side. This disparity represents a strengthening of a precipitation asymmetry, particularly winter precipitation, that exists today. The modern precipitation asymmetry may be a consequence of snow being blown over to the eastern side of the massif (advective transport) by southwesterly flow. Intensification of this flow during the LGM would have enhanced advection, and augmented snow accumulation on glaciers, thus explaining the lower ELAs and increased precipitation on that side of the massif.

In this paper we perform numerous numerical studies for the problem of low-rank matrix completion. We compare the Bayesian approaches and a recently introduced de-biased estimator which provides a useful way to build confidence intervals of interest. From a theoretical viewpoint, the de-biased estimator comes with a sharp minimax-optimal rate of estimation error whereas the Bayesian approach reaches this rate with an additional logarithmic factor. Our simulation studies show originally interesting results that the de-biased estimator is just as good as the Bayesian estimators. Moreover, Bayesian approaches are much more stable and can outperform the de-biased estimator in the case of small samples. However, we also find that the length of the confidence intervals revealed by the de-biased estimator for an entry is absolutely shorter than the length of the considered credible interval. These suggest further theoretical studies on the estimation error and the concentration for Bayesian methods as they are being quite limited up to present.

We report on the application of femtosecond laser micromachining to the fabrication of complex glass microdevices, for high-order harmonic generation in gas. The three-dimensional capabilities and extreme flexibility of femtosecond laser micromachining allow us to achieve accurate control of gas density inside the micrometer interaction channel. This device gives a considerable increase in harmonics generation efficiency if compared with traditional harmonic generation in gas jets. We propose different chip geometries that allow to control the gas density and driving field intensity inside the interaction channel to achieve quasi-phase matching conditions in the harmonic generation process. We believe that these glass micro-devices will pave the way to future downscaling of High-order Harmonic Generation beamlines.

Chile faces a serious crisis on housing affordability given that most of the population is unable to secure a house. While housing prices between 2008 increased by 70.96%, wages only increased by 20.43%. This article presents the analysis of the housing prices configuration for the main district in the country: Santiago Centro. The assessment focuses on verticalised housing buildings constructed between 2015 and 2019. The article develops an exploratory study on the price of housing in the city of Santiago de Chile, to generate a diagnosis to identify the role played by expectations of profitability when configuring that price. Based on the information generated, we seek to contribute to the discussion on public policies that advance towards the development of affordable housing for households in central communes with high urban value, as is the case of Santiago Centro. We hypothesize that profitability expectations of real estate developers play a key role in the housing prices and an adjustment in the profit ratios may increase the affordability keeping the housing market over profitable rates. The research is relevant due to the lack of data transparency in the Chilean housing market, where access to investment costs, land values, yields and house price formation are not part of the public discussion, even though this implies that many households are facing severe difficulties in paying for access to decent housing.

DNA methylation, one of the major epigenetic mechanisms, plays critical roles in regulating gene expression, genomic stability and cell lineage commitment. Establishment and maintenance of DNA methylation in mammals is achieved by two groups of DNA methyltransferases: DNMT3A and DNMT3B, which are responsible for installing DNA methylation patterns during gametogenesis and early embryogenesis, and DNMT1, which is essential for propagating DNA methylation patterns during replication. Both groups of DNMTs are multi-modular proteins, containing a large N-terminal regulatory region in addition to the C-terminal methyltransferase domain. Recent structure-function investigations of the individual domains or large fragments of DNMT1 and DNMT3A have revealed the molecular basis for their substrate recognition and specificity, intramolecular domain-domain interactions, as well as their crosstalk with other epigenetic mechanisms. These studies highlight a multifaceted regulation for both DNMT1 and DNMT3A/3B, which is essential for the precise establishment and maintenance of lineage-specific DNA methylation patterns in cells. This review summarizes current understanding of the structure and mechanism of DNMT1- and DNMT3A-mediated DNA methylation, with emphasis on the functional cooperation between the methyltransferase and regulatory domains.

Almost one fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumor and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, anti-HER2 therapy can be associated with substantial toxicities, mostly cardiac, and high cost. Over the past few years, there has been growing interest in de-escalation of anti-HER2 therapies to minimize adverse events and healthcare costs, while maintaining the efficacy of treatment. Data from clinical observations and single-arm studies have eluted to the minimal impact of anti-HER2 therapy in low-risk patients, like those with node-negative and small tumors. Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.

Here, we consider a closed composite system consisting of a primary system where the chemical reaction occurs and is located in a p, T reservoir. In the ideal isentropic case (thermodynamic process), the change in the internal energy of the composite system (due to a chemical reaction) is wholly converted into useful work - maximum useful work. Irreversibility - a measure for the degradation of useful work - in a closed system generates entropy, i.e., the thermodynamic process is no longer isentropic. Applying the principle of maximum entropy and minimum internal energy to a part of the system's total volume and applying the elements of the system's volume for which the law of local equilibrium applies useful work and irreversibility can be defined. Suppose the primary system is viewed as a set of black box volume elements in which a chemical reaction occurs. In that case, the criterion of an isentropic process or a process with entropy generation becomes the Gibbs-Duham equation. It has been proven that De Donder's equation of entropy production of a chemical reaction is a particular form of Calen's equation –TdST = dUT where dST is the differential change of total entropy and dUT is the differential change of total internal energy of the composite system.

Postoperative RT is recommended after breast conserving surgery and mastectomy (with risk factors). Consideration of pros and cons including potential side effects demands for optimization of adjuvant RT and a risk-adapted approach. There is clear de-escalation in fractionation - hypofractionation should be considered standard. For selected low risk situations PBI only or even the omission of RT might be appropriate. In contrast, tendencies in escalating RT are obvious. Preoperative RT seems attractive for patients in whom breast reconstruction is planned or for defining the tumor location more precisely with the potential of giving ablative doses. Dose escalation by a (simultaneous integrated) boost or the combination with new compounds/systemic treatments may increase antitumor efficacy but also toxicity. Despite low evidence, RT for oligometastatic disease is becoming increasingly popular. The omission of axillary dissection in node-positive disease led to an escalation of regional RT. Studies are ongoing to test if any axillary treatment can be omitted and which oligometastatic patients do really benefit from RT. Besides technical improvements the incorporation of molecular risk profiles but also the response to neoadjuvant systemic therapy have the potential to optimize the decision-making if and how local and/or regional RT should be administered.

In the quest for robust and efficient digital communication, this paper introduces cutting-edge key exchange protocols leveraging tropical semirings’ computational prowess and block matrices’ structural resilience. Moving away from the conventional use of finite fields, these protocols deliver markedly faster processing speeds and heightened security. We present two implementations of our concept, each utilizing a different platform for the set of commuting matrices: one employing tropical polynomials of matrices and the other employing Linde-de la Puente matrices. The inherent simplicity of tropical semirings leads to a decrease in operational complexity, and using block matrices enhances our protocols’ security profile. The security of these protocols relies on the Matrix Decomposition Problem. We also provide a comparative analysis of our protocols against existing matrix block-based protocols in finite fields. This research marks a significant shift in cryptographic protocol design, specifically tailored for demanding engineering applications, and sets a new standard in secure and efficient digital communication.

Intergenerational Justice entitles the maximum retention of Earth’s Biodiversity. The United Nations COP 15 committed to the protection of 30% of Earth’s terrestrial environments to provide Biospheric Sustainability. However, proactive amphibian sustainability needs support from amphibian Reproduction Technologies, Biobanking, and Conservation Breeding Programs [RBCs]. These technologies include the reliable practice of stimulation of reproduction and the collection of sperm and oocytes, refrigerated and cryopreserved sperm storage, in vitro fertilization. Emerging technologies promise the perpetuation of species solely from biobanked biomaterials. However, although exemplary national programs for amphibian RBCs are now established in the USA and Australia, these potentials are not fully realised resulting in unacceptable biodiversity loss. To fully realise these potentials an independent and democratic global organisation is proposed to, 1) focus on the bioregions with the highest amphibian biodiversity, 2) maximise regional inclusion in international initiatives, and 3) provide for maximum community engagement and financial resources. We present the first overall multidisciplinary review of amphibian RBCs, including their geopolitical, cultural, and scientific background, along with their development and application to economically, efficiently, and reliably, perpetuate amphibian biodiversity. We provide genetic models, the potential for diploid cell cryopreservation to perpetuate species, along with significant new information on methodologies and techniques, and standardise nomenclature for specificity in publications and media consistency.

Background. The molecular mechanisms underlying de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown. Materials & Methods. Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/-, HER2-), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical-pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n=32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 x 10µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR, deconvolution was performed using CIBERSORTx to assess immune cell fractions. Paired Wilcoxon test was used to compare dnMBC and eBC groups, and corrected for false discovery rate (FDR). Results. Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that CCL17 and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group. Conclusion. Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients.

Background Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular the potential to prolong cardiac repolarisation by using this combination has been discussed. Materials and methods We report a pragmatic and simple safety approach which we implemented in the first patients treated for COVID-19 in our center early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) >500 ms, hypokalaemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 hours of the initial prescription. Results Among 424 consecutive adults (mean age 46.3 ± 16.1 years; 216 women). Patients were followed in conventional wards (21.5%) or in a day-care unit (78.5%). A total of 11 patients (2.6%) had contraindications to HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after two days (p=0.003). Ten patients (2.4%) developed QTc prolongation >60 ms, and none had QTc >500 ms. Conclusions This report do not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, a simple initial assessment of patient medical history, ECG and kalaemia identifies contraindicated patients and enables the safe treatment by HCQ-AZ of COVID-19 patients. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are followed.

The acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) continues to be a public health problem. In 2020, 680,000 people died from HIV-related causes, and 1.5 million people were infected. Antiretrovirals are only a way to control HIV infection but not to cure AIDS. As such, effective treatment must be developed to control AIDS. Developing a drug is not an easy task, and there is an enormous amount of work and economic resources invested. For this reason, it is highly convenient to employ computer-aided drug design methods, which can help generate and identify novel molecules. Using the de novo design, new novel molecules can be developed using fragments as building blocks. In this work, we develop a virtual-focused compound library of HIV-1 viral protease inhibitors from natural product fragments. Natural products are characterized by a large diversity of functional groups, many sp3 atoms, and chiral centers. Pseudo-natural products are a combination of natural products fragments that keep the desired structural characteristics from different natural products. An interactive version of chemical space visualization of virtual compounds focused on HIV-1 viral protease inhibitors from natural product fragments is freely available at https://figshare.com/s/ceb58d58e8f5585ce67e.

Despite advances in algorithms and computational platforms, de-novo genome assembly remains a challenging process. Due to the constant innovation in sequencing technologies (Sanger, SOLiD, Illumina, 454, PacBio and Oxford Nanopore), genome assembly has evolved to respond to the changes in input data type. This paper includes a broad and comparative review of the most recent short-read, long-read and hybrid assembly techniques. In this review, we provide (1) an algorithmic description of the important processes in the workflow that introduces fundamental concepts and improvements; (2) a review of existing software that explains possible options for genome assembly; and (3) a comparison of the accuracy and the performance of existing methods executed on the same computer using the same processing capabilities and using the same set of real and synthetic datasets. Such evaluation allows a fair and precise comparison of accuracy in all aspects. As a result, this paper identifies both the strengths and weaknesses of each method. This comparative review is unique in providing a detailed comparison of a broad spectrum of cutting-edge algorithms and methods.

In this paper, a local meshless method (LMM) based on radial basis functions (RBFs) is utilized for the numerical solution of various types of PDEs, due to the flexibility with respect to geometry and high order of convergence rate. In case of global meshless methods, the two major deficiencies are the computational cost and the optimum value of shape parameter. Therefore, research is currently focus towards localized radial basis function approximations, as the local meshless method is proposed here. The local meshless procedures is used for spatial discretization whereas for temporal discretization different time integrators are employed. The proposed local meshless method is testified in terms of efficiency, accuracy and ease of implementation using regular and irregular domains.

The field of computational protein engineering has been transformed by recent advancements in machine learning, artificial intelligence, and molecular modeling, enabling the design of proteins with unprecedented precision and functionality. Computational methods now play a crucial role in enhancing the stability, activity, and specificity of proteins for diverse applications in bio-technology and medicine. Techniques such as deep learning, reinforcement learning, and transfer learning have dramatically improved protein structure prediction, optimization of binding affin-ities, and enzyme design. These innovations have streamlined the process of protein engineering by allowing the rapid generation of targeted libraries, reducing experimental sampling, and en-abling the rational design of proteins with tailored properties. Furthermore, the integration of computational approaches with high-throughput experimental techniques has facilitated the development of multifunctional proteins and novel therapeutics. However, challenges remain in bridging the gap between computational predictions and experimental validation, and in ad-dressing ethical concerns related to AI-driven protein design. This review provides a compre-hensive overview of the current state and future directions of computational methods in protein engineering, emphasizing their transformative potential in creating next-generation biologics and advancing synthetic biology.