Miracle-dz/UniFAR-FTUs huggingface dataset:
A Crosstalk Between Castration-Resistant Prostate Cancer Cells, M2 Macrophages, and NK Cells: Role of the ATM-PI3K/AKT-PD-L1 Pathway

ABSTRACT Castration-resistant prostate cancer (CRPC) in males is associated with a poor prognosis and a higher risk of treatment-related adverse effects, with high mortality among cancers globally. It is thus imperative to explore novel potential molecules with dual therapeutic and biomarker functions. Based on the recent research findings, the expression levels of ataxia telangiectasia mutant kinase (ATM) in prostate cancer (PC) tissues collected from CRPC patients were higher than hormone-dependent PC patients. Using CRPC cell lines (C4–2 and CWR22Rv1), the transwell chamber experiments revealed ATM promoted macrophage recruitment in CRPC cells in vitro via C-X-C motif chemokine ligand 12 (CXCL12). Further in vitro investigations demonstrated that polarized macrophages prevented NK cell recruitment and reduced the immunocidal activity of NK cells against CRPC cell lines. Moreover, ATM boosted programmed death receptor ligand 1 (PD-L1) expression while inhibiting NK group 2D (NKG2D) ligand expression in selected cell lines via PI3K/AKT signaling pathway. The in vivo investigations revealed ATM induced proliferation of CRPC and macrophage recruitment, while the NK cell recruitment was found to suppress ATM expression and CRPC proliferation. In conclusion, it could be demonstrated that inhibiting ATM increased the susceptibility of CRPC to NK cell inhibitors by dampening the CXCL12 and PI3K/AKT-PD-L1 pathways, thereby offering a novel and individualized treatment protocol for treating CRPC.
The Influence of Hydrological Patterns on Brook Trout ( Salvelinus fontinalis ) and Rainbow Trout ( Oncorhynchus mykiss ) Population Dynamics in the Great Smoky Mountains National Park.

I am submitting herewith a thesis written by Joseph Michael Parker entitled “The Influence of Hydrological Patterns on Brook Trout (Salvelinus fontinalis) and Rainbow Trout (Oncorhynchus mykiss) Population Dynamics in the Great Smoky Mountains National Park. ” I have examined the final electronic copy of this thesis for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Master of Science, with a major in Civil Engineering.
He must be mad; she might be sad: perceptual and decisional aspects of emotion recognition in ambiguous faces

ABSTRACT While the recognition of ambiguous emotions is crucial for successful social interactions, previous work has shown that they are perceived differently depending on whether they are viewed on male or female faces. The present paper aims to shed light on this phenomenon by exploring two hypotheses: the confounded signal hypothesis, which posits the existence of perceptual overlaps between emotions and gendered morphotypes, and the social role hypothesis, according to which the observer's responses are biased by stereotypes. Participants were asked to categorise blended faces (i.e. artificial faces made ambiguous by mixing two emotions) in a forced-choice task. Six emotions were used to create each blend (neutral, surprise, sadness, fear, happiness, anger), for a total of 15 expressions. We then applied signal detection theory – considering both the morphotype of the stimuli and the participants’ gender – to distinguish participants’ perceptual processes from their response biases. The results showed a perceptual advantage for anger on male faces and for sadness on female faces. However, different strategies were deployed when labelling emotions on gendered morphotypes. In particular, a response bias towards angry male faces establishes their special status, as they resulted in both excellent detection and a tendency to be over-reported, especially by women.
Retrograde peripheral nerve regeneration from sensory to motor pathways in rats: a new experimental concept in nerve repair

ABSTRACT Background The polarity of nerve grafts does not interfere with axon growth. Our goal was to investigate whether axons can regenerate in a retrograde fashion within sensory pathways and then extend into motor pathways, leading to muscle reinnervation. Methods Fifty-four rats were randomized into four groups. In Group 1, the ulnar nerve was connected end-to-end to the superficial radial nerve after neurectomy of the radial nerve in the axilla. In Group 2, the ulnar nerve was connected end-to-end to the radial nerve distal to the humerus; the radial nerve then was divided in the axilla. In Group 3, the radial nerve was divided in the axilla, but no nerve reconstruction was performed. In Group 4, the radial nerve was crushed in the axilla. Over 6 months, we behaviorally assessed the recovery of toe spread in the right operated-upon forepaw by lifting the rat by its tail and lowering it onto a flat surface. Six months after surgery, rats underwent reoperation, nerve transfers were tested electrophysiologically, and the posterior interosseous nerve (PIN) was removed for histological evaluation. Results Rats in the crush group recovered toe spread between 5 and 8 days after surgery. Rats with nerve transfers demonstrated electrophysiological and histological findings of nerve regeneration but no behavioral recovery. Conclusions Ulnar nerve axons regrew into the superficial radial nerve and then into the PIN to reinnervate the extensor digitorum communis. We were unable to demonstrate behavioral recovery because rats cannot readapt to cross-nerve transfer.
ESTIMATION AND OPTIMAL PLANS OF MULTIPLE RAMP-STRESS ACCELERATED LIFE TESTS FOR THE GENERALIZED HALF-NORMAL DISTRIBUTION

Abstract Accelerated life tests are commonly utilized in manufacturing industries to induce early failures of highly reliable products. In this paper, estimation and optimal design issues of multiple ramp-stress accelerated life tests are discussed for the generalized half-normal distribution. Assuming inverse power model as a life-stress relationship, the maximum likelihood estimates of the parameters, as well as Fisher information matrix are derived. In addition, the methods of least square, moments, Bayes are used for estimating the model parameters. The optimal proportion of test units allocated to each stress level is obtained under D and A-optimality criteria. A sensitivity analysis of the optimal allocation to misspecification of the model parameters is carried out. Furthermore, a real data set is used to show the application of the generalized half-normal distribution in reliability studies. Finally, a Monte Carlo simulation study is carried out to examine the performance of the estimation methods and the optimality criteria.
Arteriosclerosis, Thrombosis

BACKGROUND: VWF (von Willebrand factor) is an endothelial-specific procoagulant protein with a major role in thrombosis. Aging is associated with increased circulating levels of VWF, which presents a risk factor for thrombus formation. METHODS: Circulating plasma, cellular protein, and mRNA levels of VWF were determined and compared in young and aged mice. Major organs were subjected to immunofluorescence analyses to determine the vascular pattern of VWF expression and the presence of platelet aggregates. An in vitro model of aging, using extended culture time of endothelial cells, was used to explore the mechanism of age-associated increased VWF levels. RESULTS: Increased circulating plasma levels of VWF with elevated levels of larger multimers, indicative of VWF functional activity, were observed in aged mice. VWF mRNA and cellular protein levels were significantly increased in the brains, lungs, and livers but not in the kidneys and hearts of aged mice. Higher proportion of small vessels in brains, lungs, and livers of aged mice exhibited VWF expression compared with young, and this was concomitant with increased platelet aggregate formation. Prolonged culture of endothelial cells resulted in increased cell senescence that correlated with increased VWF expression; VWF expression was specifically detected in senescent cultured endothelial cells and abolished in response to p53 knockdown. A significantly higher proportion of VWF expressing endothelial cells in vivo exhibited senescence markers SA-β -Gal (senescence-associated β -galactosidase) and p53 in aged mouse brains compared with that of the young. CONCLUSIONS: Aging elicits a heterogenic response in endothelial cells with regard to VWF expression, leading to organ-specific increase in VWF levels and alterations in vascular tree pattern of expression. This is concomitant with increased platelet aggregate formation. The age-associated increase in VWF expression may be modulated through the process of cell senescence, and p53 transcription factor contributes to its regulation. GRAPHIC ABSTRACT: A graphic abstract is available for this article.
Prostaglandin E2 contributes to L. braziliensis survival and therapeutic failure in cutaneous leishmaniasis

ABSTRACT Patients with cutaneous leishmaniasis (CL) present an exacerbated inflammatory response associated with tissue damage and ulcer development. In recent years, higher rates of failure to pentavalent antimoniate therapy have been observed, yet the underlying reason remains poorly understood. We hypothesize that the eicosanoid PGE2 favours the establishment of infection by L. braziliensis, which contributes to therapeutic failure. The aim of the present study was to investigate the influence of PGE2 on the survival of L. braziliensis in macrophages and rates of therapeutic failure in CL patients. PGE2, an eicosanoid derived from the metabolism of arachidonic acid by the COX-2 enzyme, plays several roles in immune response. We found that increased PGE2 decreases the microbicidal function of macrophages and is associated with disease severity and therapeutic failure. Additionally, the neutralization of COX-2 by NS398, a selective NSAID, increases the ability of macrophages to kill L. braziliensis and protects against the pathological inflammatory response. Our data suggest that NS398 may serve as an adjunct treatment for CL patients.
Do bacteriophages have activity in synovial fluid and against synovial fluid induced bacterial aggregates?

Bacteriophage therapy is a promising adjuvant therapy for the treatment of periprosthetic joint infections. However, there is a paucity of knowledge about the activity of bacteriophages in synovial fluid. Therefore, this study evaluated the activity of a clinically used bacteriophage in synovial fluid as well as the ability of that bacteriophage to prevent the formation of and eradicate bacteria in synovial fluid induced aggregates. The results of this study reinforce that synovial fluid induced aggregates form rapidly in numerous synovial fluid concentrations. More importantly, there was a statistically significant reduction in bacteriophage activity in synovial fluid compared to tryptic soy broth (p < 0.05) and the bacteriophage could not prevent the formation synovial fluid induced aggregates. Also the bacteriophage could not significantly reduce the amount of bacteria in the synovial fluid induced aggregates when compared to controls, and this was not secondary to resistance. Rather the reduced activity seems to be caused by bacteriophages being hindered in the ability to attach to bacterial receptors. We hypothesize this occurred because the viscosity of synovial fluid slowed bacteriophage interactions with planktonic bacteria and the synovial fluid polymers obstructed the bacteriophage attachment receptors thereby preventing attachment to bacteria in the aggregates. These findings have clinical ramifications, supporting the use of bacteriophage therapy as an adjunct to surgical interventions and not in isolation, at the nascent stage. While these findings show a shortcoming of bacteriophage therapy in periprosthetic joint infections, the knowledge gained should spearhead further research to ultimately devise effective and reproducible bacteriophage therapeutics.
Factores relevantes en la adopción de tecnologías de la información por la Pyme española

This study, based on a broad scope, measures the intensity of adoption of Information Technology (IT) in Spanish small businesses and identifies its determinants. Although its limited applicability makes it difficult to extrapolate results, it is argued that the extent of use of IT will be determined by variables such as (1) current knowledge of IT(2) a flexible firm logic and (3) serious problems affecting the firm.
Variability and trends in the wave climate of the North Atlantic : A review

Measurements of wave height away from the coast only became possible during the 1950's, and studies of wave climate from measured data only commenced in the late 1950's. Analysis of visual estimates and measurements over the next 20 years indicated a significant increase in wave height in parts of the North Atlantic. By the late 1980's there were sufficient years of wave measurements at a few locations in the NE Atlantic to suggest a statistically significant increase in mean wave heights. This suggestion, together with a widespread feeling that winter storms were getting more severe in the Atlantic and concerns about 'global warming', provoked considerable research into wave climate during the past ten years. Global measurements from satellites and estimates from numerical wave models have provided a growing database for detailed studies of decadal trends, and of spatial variability, as well as of temporal variability. This paper reviews these activities over the past few decades.
A novel bacterial sulfite dehydrogenase that requires three c-type cytochromes for electron transfer

ABSTRACT c-type Cytochromes (c-Cyts), primarily as electron carriers and oxidoreductases, play a key role in energy transduction processes in virtually all living organisms. Many bacteria, such as Shewanella oneidensis, are particularly rich in c-Cyts, supporting respiratory versatility not seen in eukaryotes. Unfortunately, a large number of c-Cyts are underexplored, and their biological functions remain unknown. In this study, we identify SorCABD of S. oneidensis as a novel sulfite dehydrogenase (SDH), which catalyzes the oxidation of sulfite to sulfate. In addition to catalytic subunit SorA, this enzymatic complex includes three c-Cyt subunits, which all together carry out electron transfer. The electrons extracted from sulfite oxidation are ultimately delivered to oxygen, leading to oxygen reduction, a process relying on terminal oxidase cyt cbb3. Genomic analysis suggests that the homologs of this SDH are present in a small number of bacterial genera, Shewanella and Vibrio in particular. Because these bacteria are generally capable of reducing sulfite under anaerobic conditions, the co-existence of a sulfite oxidation system implies that they may play especially important roles in the transformation of sulfur species in natural environments. Importance c-type Cytochromes (c-Cyts) endow bacteria with high flexibility in their oxidative/respiratory systems, allowing them to extracellularly transform diverse inorganic and organic compounds for survival and growth. However, a large portion of the bacterial c-Cyts remain functionally unknown. Here, we identify three c-Cyts that work together as essential electron transfer partners for the catalytic subunit of a novel SDH in sulfite oxidation in Shewanella oneidensis. This characteristic makes S. oneidensis the first organism known to be capable of oxidizing and reducing sulfite. The findings suggest that Shewanella, along with a small number of other aquatic bacteria, would serve as a particular driving force in the biogeochemical sulfur cycle in nature. c-type Cytochromes (c-Cyts) endow bacteria with high flexibility in their oxidative/respiratory systems, allowing them to extracellularly transform diverse inorganic and organic compounds for survival and growth. However, a large portion of the bacterial c-Cyts remain functionally unknown. Here, we identify three c-Cyts that work together as essential electron transfer partners for the catalytic subunit of a novel SDH in sulfite oxidation in Shewanella oneidensis. This characteristic makes S. oneidensis the first organism known to be capable of oxidizing and reducing sulfite. The findings suggest that Shewanella, along with a small number of other aquatic bacteria, would serve as a particular driving force in the biogeochemical sulfur cycle in nature.
Analyzing Evacuation Behavior of Transportation-Disadvantaged Populations in Northern New Jersey

In the post-Katrina period, researchers and federal agencies involved in evacuation planning have expressed serious concern about the failure of conventional, automobile-oriented evacuation approaches in serving the needs of transportation-disadvantaged populations during times of disaster. This paper provides empirical evidence documenting significant differences between the general population and transportation-disadvantaged groups in their evacuation behavior. The empirical evidence is based on an analysis of household survey data on stated evacuation response to a series of hypothetical disaster scenarios in a seven-county region of northern New Jersey. Discrete choice and regression models demonstrate that potential evacuation behavior among disadvantaged populations could be significantly different from others in terms of evacuation rate, mode choice and destination choice. This evidence highlights the importance of incorporating multi-modal approaches in evacuation plans that fully address the transportation and shelter needs of transportation-disadvantaged populations.
Mitochondrial disease in New Zealand: a nationwide prevalence study.

BACKGROUND The complexities of mitochondrial disease make epidemiological studies challenging, yet this information is important in understanding the healthcare burden and addressing service and educational needs. Existing studies are limited to quaternary centres or focus on a single genotype or phenotype and estimate disease prevalence at 12.5 per 100 000. New Zealand's (NZ) size and partially integrated national healthcare system make it amenable to a nationwide prevalence study. AIM To estimate the prevalence of molecularly confirmed and suspected mitochondrial disease on 31 December 2015 in NZ. METHODS Cases were identified from subspecialists and laboratory databases and through interrogation of the Ministry of Health National Minimum Dataset with a focus on presentations between 2000 and 2015. Patient records were reviewed, and those with a diagnosis of 'mitochondrial disease' who were alive and residing in NZ on the prevalence date were included. These were divided into molecularly confirmed and clinically suspected cases. Official NZ estimated resident population data were used to calculate prevalence. RESULTS Seven hundred twenty-three unique national health index numbers were identified. Five hundred five were excluded. The minimum combined prevalence for mitochondrial disease was 4.7 per 100 000 (95% confidence interval (CI): 4.1-5.4). The minimum prevalence for molecularly confirmed and suspected disease was 2.9 (95% CI 2.4-3.4) and 1.8 (95% CI 1.4-2.2) cases per 100 000 respectively. CONCLUSIONS Within the limitations of this study, comparison to similar prevalence studies performed by specialist referral centres suggests mitochondrial disease is underdiagnosed in NZ. This highlights a need for improved education and referral pathways for mitochondrial disease in NZ.
A daily diary study of primary appraisals, emotional exhaustion, and turnover intentions in sport coaches

ABSTRACT Cognitive-motivational-relational theory asserts that stress is a dynamic process, during which daily fluctuations in mediating processes (primary appraisals) can explain a range of ill-being and performance related outcomes. We tested this idea using a daily diary study to examine the relationships between primary appraisals, emotional exhaustion, and turnover intentions in sport coaches. Forty-four sport coaches (61% male; M age = 34.98 years) completed an online questionnaire twice per day for five days. The findings of within-person analyses indicated that hourly harm appraisals positively predicted momentary emotional exhaustion over the diary period (β = .30, p < .05). Additionally, emotional exhaustion positively predicted coaches’ job turnover intentions (β = .18, p < .05). The findings offer unique insight into the cognitive-motivational-relational theory of stress and emotion by illustrating how exhaustion and turnover intentions may be intensified as a function of primary appraisals experienced during the working day.
Potential of aerobic granular sludge membrane bioreactor (AGMBR) in wastewater treatment

ABSTRACT This investigation is a review of the potential of aerobic granular sludge membrane bioreactor (AGMBR) in wastewater treatment due to the advantage of combination of membrane and aerobic granules for reducing membrane fouling and enhancing removal performance. The AGMBR is the same as the membrane bioreactor (MBR), but the activated sludge is replaced by aerobic granular sludge. This technology combines the advantages of aerobic granular sludge, such as good settleability, strong ability to withstand shock-loadings and high organic loading rate, and capacity of simultaneous chemical oxygen demand (COD) and nitrogen removal, and advantages of membrane bioreactor (MBR) such as excellent effluent quality, high biomass content, low excess sludge production, and small land requirement. Therefore, it can be considered a promising option for efficient wastewater treatment. Most studies have shown that aerobic granules could control membrane fouling, which often occurs in MBR. The main fouling mechanism was determined to be surface fouling by floccular sludge in MBR but pore fouling by colloids and solutes in AGMBR. Aerobic granular sludge also removed COD and nitrogen simultaneously, with more than 60% total nitrogen removal efficiency. The formation and stability of aerobic granules in AGMBR with various operational modes are discussed in this study.
Prediction and design of protease enzyme specificity using a structure-aware graph convolutional network

Significance Enzymes that can precisely and selectively read, write, and edit DNA have revolutionized biochemical sciences and technologies. The availability of similar enzymes for site-selectively "editing" proteins would have broad impact. Proteases are a large class of enzymes that have the ability to site-selectively cleave target proteins and therefore serve as examples to learn the rules of site-specific recognition, and as starting points for designing targeted cleavage. We present a geometric machine learning approach that uses protein structure and energetics to enable protease–substrate specificity prediction and design targeting alternative substrates. These studies set the stage for the large-scale prediction and design of tailor-made proteases that can site-selectively edit (cut) any chosen target protein, associated, for example, with a disease state.