Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of TFIIA Function In Vivo: Evidence for a Role in TATA-Binding Protein Recruitment and Gene-Specific Activation

ABSTRACT Activation of transcription can occur by the facilitated recruitment of TFIID to promoters by gene-specific activators. To investigate the role of TFIIA in TFIID recruitment in vivo, we exploited a class of yeast TATA-binding protein (TBP) mutants that is activation and DNA binding defective. We found that co-overexpression of TOA1 and TOA2, the genes that encode yeast TFIIA, overcomes the activation defects caused by the TBP mutants. Using a genetic screen, we isolated a new class of TFIIA mutants and identified three regions on TFIIA that are likely to be involved in TBP recruitment or stabilization of the TBP-TATA complex in vivo. Amino acid replacements in only one of these regions enhance TFIIA-TBP-DNA complex formation in vitro, suggesting that the other regions are involved in regulatory interactions. To determine the relative importance of TFIIA in the regulation of different genes, we constructed yeast strains to conditionally deplete TFIIA levels prior to gene activation. While the activation of certain genes, such asINO1, was dramatically impaired by TFIIA depletion, activation of other genes, such as CUP1, was unaffected. These data suggest that TFIIA facilitates DNA binding by TBP in vivo, that TFIIA may be regulated by factors that target distinct regions of the protein, and that promoters vary significantly in the degree to which they require TFIIA for activation.
Decentralized Multisensory Information Integration in Neural Systems

How multiple sensory cues are integrated in neural circuitry remains a challenge. The common hypothesis is that information integration might be accomplished in a dedicated multisensory integration area receiving feedforward inputs from the modalities. However, recent experimental evidence suggests that it is not a single multisensory brain area, but rather many multisensory brain areas that are simultaneously involved in the integration of information. Why many mutually connected areas should be needed for information integration is puzzling. Here, we investigated theoretically how information integration could be achieved in a distributed fashion within a network of interconnected multisensory areas. Using biologically realistic neural network models, we developed a decentralized information integration system that comprises multiple interconnected integration areas. Studying an example of combining visual and vestibular cues to infer heading direction, we show that such a decentralized system is in good agreement with anatomical evidence and experimental observations. In particular, we show that this decentralized system can integrate information optimally. The decentralized system predicts that optimally integrated information should emerge locally from the dynamics of the communication between brain areas and sheds new light on the interpretation of the connectivity between multisensory brain areas. SIGNIFICANCE STATEMENT To extract information reliably from ambiguous environments, the brain integrates multiple sensory cues, which provide different aspects of information about the same entity of interest. Here, we propose a decentralized architecture for multisensory integration. In such a system, no processor is in the center of the network topology and information integration is achieved in a distributed manner through reciprocally connected local processors. Through studying the inference of heading direction with visual and vestibular cues, we show that the decentralized system can integrate information optimally, with the reciprocal connections between processers determining the extent of cue integration. Our model reproduces known multisensory integration behaviors observed in experiments and sheds new light on our understanding of how information is integrated in the brain.
Therapeutic Potential of Ex Vivo Expanded Endothelial Progenitor Cells for Myocardial Ischemia

Background —We investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization. Methods and Results —Peripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 106 EPCs labeled with 1,1′-dioctadecyl-1 to 3,3,3′,3′-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 106 EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significantly greater in the EPC group than in the control group. Moreover, the extent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells. Conclusions —Ex vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.
Factors Influencing the Success of Students’ Learning through Online Learning/Distance Education : A Bibliometric Analysis of Scopus Database

This study aims to examine the co-occurrence of several topics linked to factors that influence student learning success and explore the motor themes related to factors that influence student learning success. This study used the literature review method with data analysis using R Studio and VOSViewer software. Data analyzed were exported from the Scopus website from 2013 to 2023 of 383 documents. The research data analysis techniques used network mapping analysis of VOSviewer results (network visualization) and content analysis within the keywords and studies. The findings of this study presented the keywords (most frequent words, trending topics), co-occurrence network (thematic map and thematic evolution), and discussion of topics related to factors that influence student learning success. The basic themes identified were higher education and Covid-19. Meanwhile, gender and self-efficacy are motor themes that could be researched further as those can influence student learning performance in online learning. The findings of the bibliometric analysis were intended to reveal unique insights into the factors that determine student learning performance in distant learning and contribute to previously unexplored issues.
Modeling fault-tolerant mobile agent execution as a sequence of agreement problems

Fault tolerance is fundamental to the further development of mobile agent applications. In the context of mobile agents, fault tolerance prevents a partial or complete loss of the agent, i.e. ensures that the agent arrives at its destination. Simple approaches such as checkpointing are prone to blocking. Replication can in principle improve solutions based on checkpointing. However existing solutions in this context either assume a perfect failure detection mechanism (which is not realistic in an environment such as the Internet), or rely on complex solutions based on leader election and distributed transactions, where only a subset of solutions prevents blocking. The paper proposes a novel approach to fault tolerant mobile agent execution, which is based on modeling agent execution as a sequence of agreement problems. Each agreement problem is one instance of the well understood consensus problem. Our solution does not require a perfect failure detection mechanism, while preventing blocking and ensuring that the agent is executed exactly once.
Direction of information flow in large-scale resting-state networks is frequency-dependent

Significance A description of the structural and functional connections in the human brain is necessary for the understanding of both normal and abnormal brain functioning. Although it has become clear in recent years that stable patterns of functional connectivity can be observed during the resting state, to date, it remains unclear what the dominant patterns of information flow are in this functional connectome and how these relate to the integration of brain function. Our results are the first to describe the large-scale frequency-specific patterns of information flow in the human brain, showing that different subsystems form a loop through which information “reverberates” or “circulates. ” These results could be extended to give insights into how such flow optimizes integrative cognitive processing. Normal brain function requires interactions between spatially separated, and functionally specialized, macroscopic regions, yet the directionality of these interactions in large-scale functional networks is unknown. Magnetoencephalography was used to determine the directionality of these interactions, where directionality was inferred from time series of beamformer-reconstructed estimates of neuronal activation, using a recently proposed measure of phase transfer entropy. We observed well-organized posterior-to-anterior patterns of information flow in the higher-frequency bands (alpha1, alpha2, and beta band), dominated by regions in the visual cortex and posterior default mode network. Opposite patterns of anterior-to-posterior flow were found in the theta band, involving mainly regions in the frontal lobe that were sending information to a more distributed network. Many strong information senders in the theta band were also frequent receivers in the alpha2 band, and vice versa. Our results provide evidence that large-scale resting-state patterns of information flow in the human brain form frequency-dependent reentry loops that are dominated by flow from parieto-occipital cortex to integrative frontal areas in the higher-frequency bands, which is mirrored by a theta band anterior-to-posterior flow.
COVID-19 vaccines breakthrough infection and adverse reactions in medical students: a nationwide survey in Iran

Introduction There are different types of COVID-19 vaccines approved worldwide. Since no national studies focus on vaccine-related adverse reactions and breakthrough cases, this study aimed to investigate the rate of adverse events and COVID-19 infection in medical students in Iran. Methods This retrospective cohort study included Iranian medical students who received two doses of COVID-19 vaccines. The medical team gathered the demographic characteristics, comorbidities, type of vaccine, adverse events following vaccination, and history of COVID-19 infection data through a phone interview. The frequency of adverse events and breakthrough infection was stratified by vaccine type (ChAdOx1-S, Gam-COVID-Vac, and BIBP-CorV). Results A total of 3,591 medical students enrolled in this study, of which 57.02% were females, with a mean age of 23.31 + 4.87. A PCR-confirmed and suspicious-for-COVID-19 breakthrough infection rate of 4.51 and 7.02% was detected, respectively. There was no significant relation between breakthrough infection and gender, BMI, blood groups, and comorbidities. However, there was a significant difference in breakthrough infection rate among different types of vaccines (p = 0.001) and history of COVID-19 infection (p = 0.001). A total of 16 participants were hospitalized due to COVID-19 infection after vaccination for reasons such as dyspnea, abnormal imaging, or decreased oxygen saturation. No severe infection or death was observed in the studied population. Conclusion Vaccination prevented severe COVID-19 infection, although a high breakthrough infection rate was evident among Iranian medical students during the Delta variant’s peak. Vaccine effectiveness may be fragile during emerging new variants and in high-exposure settings. Moreover, adverse events are rare, and the benefits of vaccination outweigh the side effects. However, many limitations challenged this study, and the results should be cautious.
Characteristics and Outcomes of America's Lowest-Performing Hospitals: An Analysis of Acute Myocardial Infarction Hospital Care in the United States

Background—Studies suggest that most hospitals now have relatively high adherence with recommended acute myocardial infarction (AMI) process measures. Little is known about hospitals with consistently poor adherence with AMI process measures and whether these hospitals also have increased patient mortality. Methods and Results—We conducted a retrospective study of 2761 US hospitals reporting AMI process measures to the Center for Medicare and Medicaid Services Hospital Compare database during 2004 to 2006 that could be linked to 2005 Medicare Part A data. The main outcome measures were hospitals' combined compliance with 5 AMI measures (aspirin and β-blocker on admission and discharge and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use at discharge for patients with left ventricular dysfunction) and risk-adjusted 30-day mortality for 2005. We stratified hospitals into those with low AMI adherence (ranked in the lowest decile for AMI adherence for 3 consecutive years [2004–2006, n=105]), high adherence (ranked in the top decile for 3 consecutive years [n=63]), and intermediate adherence (all others [n=2593]). Mean AMI performance varied significantly across low-, intermediate-, and high-performing hospitals (mean score, 68% versus 92% versus 99%, P<0.001). Low-performing hospitals were more likely than intermediate- and high-performing hospitals to be safety-net providers (19.2% versus 11.0% versus 6.4%; P=0.005). Low-performing hospitals had higher unadjusted 30-day mortality rates (23.6% versus 17.8% versus 14.9%; P<0.001). These differences persisted after adjustment for patient characteristics (16.3% versus 16.0% versus 15.7%; P=0.02). Conclusion—Consistently low-performing hospitals differ substantially from other US hospitals. Targeting quality improvement efforts toward these hospitals may offer an attractive opportunity for improving AMI outcomes.
The effectiveness of intermittent pneumatic compression in long-term therapy of lymphedema of lower limbs.

BACKGROUND The manual lymphatic drainage in lymphedema has proved to be successful; however, this method cannot be applied to millions of patients around the world. The only solution is to offer inexpensive, easily accessible mechanical devices for pneumatic compression (IPC). These devices should be designed on parameters of edema fluid hydromechanics. Recent data point to high pressures and long time of compression. AIM To validate the effects of 3 years daily high pressure, long inflation time IPC therapy in terms of decrease of limb circumference/volume, tissue elasticity, histological changes, and incidental complications. METHODS A group of 18 patients with unilateral leg lymphedema stage II to IV was treated for a period of 3 years using an 8-chamber sleeve, sequential inflation of chambers to 100-120 mmHg for 50 sec (total 400 sec). Limb circumference and tissue tonicity were measured at monthly intervals. Correlation between decrease in calf and thigh circumference and increase in elasticity was done. RESULTS The treatment revealed durable permanent decrease of limb circumference and increased elasticity of tissues. The improvement was most expressed in the calf above the ankle and mid-calf. No complications as thigh ring or chronic genital edema were observed. There was no direct correlation between the decrease in limb circumference and increase in elasticity, most likely due to different mass of fibrous tissue. CONCLUSIONS IPC takes over the permanently missing function of the obliterated lymphatics by squeezing edema tissue fluid to the regions with normal lymphatic drainage. The limb circumference is decreased or at least does not further increase, elasticity of tissue is increased and maintained. No complications in limb tissues were observed. The long-term, high pressure IPC, long inflation timed therapy can be safely be recommended to patients with lower limb lymphedema.
Restoration of Antibacterial Activity of Inactive Antibiotics via Combined Treatment with AgNPs

Antimicrobial resistance poses a huge threat to human health around the world and calls for novel treatments. Combined formulations of NPs and antibiotics have emerged as a viable nanoplatform for combating bacterial resistance. The present research work was performed to investigate the effect of combined formulations of AgNPs with streptomycin, cefaclor, ciprofloxacin, and trimethoprim against multidrug-resistant (MDR) isolates of Staphylococcus aureus and Klebsiella pneumoniae. AgNPs have been synthesized by using the Nigella sativa seed extract, and their characteristics were analyzed. AgNPs depicted concentration-dependent antibacterial effects, as the highest concentration of AgNPs showed the strongest antibacterial activity. Interestingly, AgNPs in conjugation with antibiotics showed an enhanced antibacterial potential against both S. aureus and K. pneumoniae, which suggested synergism between the AgNPs and antibiotics. Against S. aureus, streptomycin and trimethoprim in conjugation with AgNPs presented a synergistic effect, while cefaclor and ciprofloxacin in combination with AgNPs showed an additive effect. However, all of the tested antibiotics depicted a synergistic effect against K. pneumoniae. The lowest value of MIC (0.78 μg/mL) was shown by AgNPs-Stp against S. aureus, whereas AgNPs-Tmp showed the lowest value of MIC (1.56 μg/mL) against K. pneumoniae. The most important point of the present study is that both organisms (S. aureus and K. pneumoniae) showed resistance to antibiotics but turned out to be highly susceptible when the same antibiotic was used in combination with AgNPs. These findings highlight the potential of nanoconjugates (the AgNPs-antibiotic complex) to mitigate the present-day crisis of antibiotic resistance and to combat antimicrobial infections efficiently.
Forest-based Tree Sequence to String Translation Model

This paper proposes a forest-based tree sequence to string translation model for syntax-based statistical machine translation, which automatically learns tree sequence to string translation rules from word-aligned source-side-parsed bilingual texts. The proposed model leverages on the strengths of both tree sequence-based and forest-based translation models. Therefore, it can not only utilize forest structure that compactly encodes exponential number of parse trees but also capture nonsyntactic translation equivalences with linguistically structured information through tree sequence. This makes our model potentially more robust to parse errors and structure divergence. Experimental results on the NIST MT-2003 Chinese-English translation task show that our method statistically significantly outperforms the four baseline systems.
Decreased Temperature Facilitates Short-Term Sea Star Wasting Disease Survival in the Keystone Intertidal Sea Star Pisaster ochraceus

An extensive 2013 mass mortality event along the West Coast of North America due to Sea Star Wasting Disease (SSWD) has affected at least 20 species of sea stars. Among environmental factors potentially contributing to the timing of the current outbreak, increased coastal water temperatures are hypothesized to have contributed to previous and current outbreaks of SSWD. With a laboratory experiment, we tested whether cooler temperatures, similar to average winter temperatures, compared to average summer temperatures could slow the progression of morbidity or prevent SSWD mortality entirely in Pisaster ochraceus. Sea stars housed in cooler water progressed through SSWD states more slowly than sea stars housed at summer temperatures. However, the cooler temperature did not prevent SSWD mortality, and all stars died of the disease. Our data are consistent with experimental studies and field observations during previous and current outbreaks, and support the hypothesis that changes in coastal water temperatures have influenced one of the largest disease related mass mortality events in our oceans.
Relative Neurotoxicity of Ivermectin and Moxidectin in Mdr1ab (−/−) Mice and Effects on Mammalian GABA(A) Channel Activity

The anthelmintics ivermectin (IVM) and moxidectin (MOX) display differences in toxicity in several host species. Entrance into the brain is restricted by the P-glycoprotein (P-gp) efflux transporter, while toxicity is mediated through the brain GABA(A) receptors. This study compared the toxicity of IVM and MOX in vivo and their interaction with GABA(A) receptors in vitro. Drug toxicity was assessed in Mdr1ab(−/−) mice P-gp-deficient after subcutaneous administration of increasing doses (0.11–2.0 and 0.23–12.9 µmol/kg for IVM and MOX in P-gp-deficient mice and half lethal doses (LD50) in wild-type mice). Survival was evaluated over 14-days. In Mdr1ab(−/−) mice, LD50 was 0.46 and 2.3 µmol/kg for IVM and MOX, respectively, demonstrating that MOX was less toxic than IVM. In P-gp-deficient mice, MOX had a lower brain-to-plasma concentration ratio and entered into the brain more slowly than IVM. The brain sublethal drug concentrations determined after administration of doses close to LD50 were, in Mdr1ab(−/−) and wild-type mice, respectively, 270 and 210 pmol/g for IVM and 830 and 740–1380 pmol/g for MOX, indicating that higher brain concentrations are required for MOX toxicity than IVM. In rat α1β2γ2 GABA channels expressed in Xenopus oocytes, IVM and MOX were both allosteric activators of the GABA-induced response. The Hill coefficient was 1.52±0.45 for IVM and 0.34±0.56 for MOX (p<0.001), while the maximum potentiation caused by IVM and MOX relative to GABA alone was 413.7±66.1 and 257.4±40.6%, respectively (p<0.05), showing that IVM causes a greater potentiation of GABA action on this receptor. Differences in the accumulation of IVM and MOX in the brain and in the interaction of IVM and MOX with GABA(A) receptors account for differences in neurotoxicity seen in intact and Mdr1-deficient animals. These differences in neurotoxicity of IVM and MOX are important in considering their use in humans.
A 3-D Coarser-Grained Computational Model for Simulating Large Protein Dynamics

: Protein dynamics is essential for gaining insight into biological functions of proteins. Although protein dynamics is well delineated by molecular model, the molecular model is computationally prohibited for simulating large protein structures. In this work, we provide the three-dimensional coarser-grained anisotropic model (CGAM), which is based on model reduction applicable to large protein structures. It is shown that CGAM achieves the fast computation on low-frequency modes, quantitatively comparable to original structural model such as elastic network model (ENM). This indicates that the CGAM by model reduction method enable us to understand the functional motion of large proteins with remarkable computational efﬁciency.