cssi/SciSciGPT-SciSciNet huggingface dataset:
A tight link between orthologs and bidirectional best hits in bacterial and archaeal genomes

Orthologous relationships between genes are routinely inferred from bidirectional best hits (BBH) in pairwise genome comparisons. However, to our knowledge, it has never been quantitatively demonstrated that orthologs form BBH. To test this "BBH-orthology conjecture," we take advantage of the operon organization of bacterial and archaeal genomes and assume that, when two genes in compared genomes are flanked by two BBH show statistically significant sequence similarity to one another, these genes are bona fide orthologs. Under this assumption, we tested whether middle genes in "syntenic orthologous gene triplets" form BBH. We found that this was the case in more than 95% of the syntenic gene triplets in all genome comparisons. A detailed examination of the exceptions to this pattern, including maximum likelihood phylogenetic tree analysis, showed that some of these deviations involved artifacts of genome annotation, whereas very small fractions represented random assignment of the best hit to one of closely related in-paralogs, paralogous displacement in situ, or even less frequent genuine violations of the BBH-orthology conjecture caused by acceleration of evolution in one of the orthologs. We conclude that, at least in prokaryotes, genes for which independent evidence of orthology is available typically form BBH and, conversely, BBH can serve as a strong indication of gene orthology.
In memory of a legendary athlete: measured success in diabetic nephropathy.

Historically diabetic nephropathy has been a devastating complication of both type I and type II diabetes. The past 2 decades have seen enormous conceptual advances in understanding the pathogenesis of diabetic nephropathy. The genetic determinants of diabetic renal disease have also been elucidated as well as biochemical events and cytokine interactions. Most importantly, key clinical trials have identified therapeutic interventions which can slow or halt the progression of diabetic nephropathy, specifically the therapeutic use of angiotensin-converting enzyme inhibition and intensive blood sugar control. Multiple treatment modalities for patients once they reach end-stage renal disease are also available and great strides have been improving outcomes in these areas as well.
TOBACCO SMOKING AND LONGEVITY.

Analysis of the effect of tobacco upon human longevity after age 30 using a random sample of 6813 men (grouped as nonusers of tobacco moderate smokers and heavy smokers) showed a significant impairment of survivorship among smokers with the impairment increasing as frequency of smoking increased. Beyond age 70 however differences in the mortality rates of the 3 groups practically disappeared possibly because of the immunity developed by resistent specimens against the harmful effects of tobacco.
Predicting academic problems in college from freshman alcohol involvement.

Objective: The present article examines the relation of problematic alcohol use to collegiate academic problems based on a systematic assessment of problematic alcohol use and college transcript data. The degree to which this prospective association can be explained by reference to third variables is also explored. These third variables include: students' high school academic achievement and aptitude, concurrent drug use, participation in deviant behaviors and students' investment or participation in the college experience. Method: A sample of 444 (240 female) college freshman recruited for a longitudinal study of alcohol use was followed for 6 years. Alcohol and drug involvement, general deviance, academic investment, campus involvement and several background variables were assessed during the freshman year. Additional measures of high school aptitude and achievement as well as collegiate performance were calculated based on college transcript data from all institutions attended. Results: A latent variab...
Mass spectrometric and computational analysis of cytokine-induced alterations in the astrocyte secretome

The roles of astrocytes in the CNS have been expanding beyond the long held view of providing passive, supportive functions. Recent evidence has identified roles in neuronal development, extracellular matrix maintenance, and response to inflammatory challenges. Therefore, insights into astrocyte secretion are critically important for understanding physiological responses and pathological mechanisms in CNS diseases. Primary astrocyte cultures were treated with inflammatory cytokines for either a short (1 day) or sustained (7 days) exposure. Increased interleukin-6 secretion, nitric oxide production, cyclooxygenase-2 activation, and nerve growth factor (NGF) secretion confirmed the astrocytic response to cytokine treatment. MS/MS analysis, computational prediction algorithms, and functional classification were used to compare the astrocyte protein secretome from control and cytokine-exposed cultures. In total, 169 secreted proteins were identified, including both classically and nonconventionally secreted proteins that comprised components of the extracellular matrix and enzymes involved in processing of glycoproteins and glycosaminoglycans. Twelve proteins were detected exclusively in the secretome from cytokine-treated astrocytes, including matrix metalloproteinase-3 (MMP-3) and members of the chemokine ligand family. This compilation of secreted proteins provides a framework for identifying factors that influence the biochemical environment of the nervous system, regulate development, construct extracellular matrices, and coordinate the nervous system response to inflammation.
Paradoxical persistence through mixed-system dynamics: towards a unified perspective of reversal behaviours in evolutionary ecology

Counterintuitive dynamics of various biological phenomena occur when composite system dynamics differ qualitatively from that of their component systems. Such composite systems typically arise when modelling situations with time-varying biotic or abiotic conditions, and examples range from metapopulation dynamics to population genetic models. These biological, and related physical, phenomena can often be modelled as simple financial games, wherein capital is gained and lost through gambling. Such games have been developed and used as heuristic devices to elucidate the processes at work in generating seemingly paradoxical outcomes across a spectrum of disciplines, albeit in a field-specific, ad hoc fashion. Here, we propose that studying these simple games can provide a much deeper understanding of the fundamental principles governing paradoxical behaviours in models from a diversity of topics in evolution and ecology in which fluctuating environmental effects, whether deterministic or stochastic, are an essential aspect of the phenomenon of interest. Of particular note, we find that, for a broad class of models, the ecological concept of equilibrium reactivity provides an intuitive necessary condition that must be satisfied in order for environmental variability to promote population persistence. We contend that further investigations along these lines promise to unify aspects of the study of a range of topics, bringing questions from genetics, species persistence and coexistence and the evolution of bet-hedging strategies, under a common theoretical purview.
The Rickettsia Endosymbiont of Ixodes pacificus Contains All the Genes of De Novo Folate Biosynthesis

Ticks and other arthropods often are hosts to nutrient providing bacterial endosymbionts, which contribute to their host's fitness by supplying nutrients such as vitamins and amino acids. It has been detected, in our lab, that Ixodes pacificus is host to Rickettsia species phylotype G021. This endosymbiont is predominantly present, and 100% maternally transmitted in I. pacificus. To study roles of phylotype G021 in I. pacificus, bioinformatic and molecular approaches were carried out. MUMmer genome alignments of whole genome sequence of I. scapularis, a close relative to I. pacificus, against completely sequenced genomes of R. bellii OSU85-389, R. conorii, and R. felis, identified 8,190 unique sequences that are homologous to Rickettsia sequences in the NCBI Trace Archive. MetaCyc metabolic reconstructions revealed that all folate gene orthologues (folA, folC, folE, folKP, ptpS) required for de novo folate biosynthesis are present in the genome of Rickettsia buchneri in I. scapularis. To examine the metabolic capability of phylotype G021 in I. pacificus, genes of the folate biosynthesis pathway of the bacterium were PCR amplified using degenerate primers. BLAST searches identified that nucleotide sequences of the folA, folC, folE, folKP, and ptpS genes possess 98.6%, 98.8%, 98.9%, 98.5% and 99.0% identity respectively to the corresponding genes of Rickettsia buchneri. Phylogenetic tree constructions show that the folate genes of phylotype G021 and homologous genes from various Rickettsia species are monophyletic. This study has shown that all folate genes exist in the genome of Rickettsia species phylotype G021 and that this bacterium has the genetic capability for de novo folate synthesis.
Beyond the Alternative Reform or Revolution: Post Sovereign Constitution Making and Latin America

Focusing on the Chilean case, the article proposes an alternative to governmental constitutional reform as well legal break based on the fiction of "popular sovereignty". The proposal involves a selective adaptation of forms from what the author has called the post sovereign paradigm.
Fiction and the Feminist Academic Novel

This article reviews the use of fiction as a qualitative research method. The article focuses on the feminist academic novel as a means of representing qualitative research, raising feminist consciousness, accessing hard-to-get-at dimensions of social life, opening up a multiplicity of meanings, tapping into empathy and resonance as ways of knowing and reaching diverse audiences with feminist social research knowledge. The article centers on the construction of the two lead female characters in the feminist arts-based novel, Low-Fat Love.
Selection of clearances for UHVAC overhead transmission line in China

For the needs of UHVAC project design and construction in China, it is significant to study the selection of transmission line clearance, which affects the safety operation and cost of the transmission line. Using insulation coordination guide and methods, which was used and verified by operation experience of EHV grid in China, the advised values of overhead transmission line clearances in China's UHV AC project were given. The clearances depending on switching impulse voltage were selected by using the curves of flashover voltages obtained at the switching impulses effect with long wavefront time, which is more suitable for UHV. Using this method and through calculation, the selected clearances were checked by the risk rate, that is the times of flashover in multi-clearance on the line at least one clearance with flashover when switching once. The study shows that the clearance of switching overvoltage for 'V' type suspension insulator string is selected as 6.7 m, 7.0 m and 7.3 m with 500 m, 1 000 m and 1 500 m height above sea level. The clearance is the most important for tower configuration. The results were compared with similar UHV projects in other countries, and it is feasible.
Co-culture model consisting of human brain microvascular endothelial and peripheral blood mononuclear cells.

Abstract Background Numerous systems exist to model the blood–brain barrier (BBB) with the goal of understanding the regulation of passage into the central nervous system (CNS) and the potential impact of selected insults on BBB function. These models typically focus on the intrinsic cellular properties of the BBB, yet studies of peripheral cell migration are often excluded due to technical restraints. New method This method allows for the study of in vitro cellular transmigration following exposure to any treatment of interest through optimization of co-culture conditions for the human brain microvascular endothelial cells (BMEC) cell line, hCMEC/D3, and primary human peripheral blood mononuclear cells (PBMCs). Results hCMEC/D3 cells form functionally confluent monolayers on collagen coated polytetrafluoroethylene (PTFE) transwell inserts, as assessed by microscopy and tracer molecule (FITC-dextran (FITC-D)) exclusion. Two components of complete hCMEC/D3 media, EBM-2 base-media and hydrocortisone (HC), were determined to be cytotoxic to PBMCs. By combining the remaining components of complete hCMEC/D3 media with complete PBMC media a resulting co-culture media was established for use in hCMEC/D3—PBMC co-culture functional assays. Comparison with existing methods Through this method, issues of extensive differences in culture media conditions are resolved allowing for treatments and functional assays to be conducted on the two cell populations co-cultured simultaneously. Conclusion Described here is an in vitro co-culture model of the BBB, consisting of the hCMEC/D3 cell line and primary human PBMCs. The co-culture media will now allow for the study of exposure to potential insults to BBB function over prolonged time courses.
Should Preparticipation Cardiovascular Screening of Athletes Include ECG? No: There Is Not Enough Evidence to Support Including ECG in the Preparticipation Sports Evaluation.

Although there are many reasons to conduct preparticipation sports examinations, there is insufficient evidence to support cardiac screening with ECG.
The acquired immunodeficiency syndrome.

SUMMARY AIDS is an apparently new condition that first occurred in about 1979 and is manifested primarily by profound disturbances of T-cell immunity and unusual susceptibility to either opportunistic infections (mycobacterial, fungal, parasitic, or viral) or tumors such as Kaposi's sarcoma and lymphoma. A prodrome of lymphadenopathy and wasting is also part of the spectrum of disease. The etiology is unknown, but the likely candidates are viral agents. Epidemiologic studies show that the promiscuous gay male is at particular risk, but transmission by the parenteral route and/or vertical transmission has extended the risk of acquisition to other groups. A common clinical presentation of full-blown AIDS is opportunistic infection of the lungs (especially with P. carinii), the central nervous system, or the gastrointestinal tract. Therapy against specific pathogens may be temporarily successful, but the course is frequently downhill, with relentless progressive or sequential infections or development of a tumor during continued immunodepression. Therapy for the immunologic abnormalities remains experimental. Control measures to prevent transmission are similar to those for hepatitis B.
METHOD AND LOGIC IN PRESOCRATIC EXPLANATION

Publisher Summary If there is one thing that the students of the presocratics agree upon, it is that disagreement, ranging from textual emendations to wide sweeping differences of interpretation, characterizes modern research. Within recent years, major contributions of scholars such as Harold Cherniss, F. Solmsen, and Gregory Vlastos have been studied; each of whom has added much that is new and valuable to the understanding of the presocratics. The absence of agreement, sometimes on basic matters, is a sign that further questions legitimately may be raised as to the meaning and intent of the presocratics. Most scholars have reservations about accepting Burnet's enthusiastic identification of presocratic inquiry with science. This chapter presents Burnet's thesis that may be defended with the proviso when two conditions are satisfied. The first condition is that by science means the formulation of an explanatory method. The second condition is that the sharp distinction between science and philosophy does injustice to presocratic inquiry by insisting on a distinction which is anachronistic.
The risk of shorter fasting time for pediatric deep sedation

Background: Current guidelines adopted by the American Academy of Pediatrics calls for prolonged fasting times before performing pediatric procedural sedation and analgesia (PSA). PSA is increasingly provided to children outside of the operating theater by sedation trained pediatric providers and does not require airway manipulation. We investigated the safety of a shorter fasting time compared to a longer and guideline compliant fasting time. We tried to identify the association between fasting time and sedation-related complications. Methods: This is a prospective observational study that included children 2 months to 18 years of age and had an American Society of Anesthesiologists physical status classification of I or II, who underwent deep sedation for elective procedures, performed by pediatric critical care providers. Procedures included radiologic imaging studies, electroencephalograms, auditory brainstem response, echocardiograms, Botox injections, and other minor surgical procedures. Subjects were divided into two groups depending on the length of their fasting time (4–6 h and >6 h). Complication rates were calculated and compared between the three groups. Results: In the studied group of 2487 subjects, 1007 (40.5%) had fasting time of 4–6 h and the remaining 1480 (59.5%) subjects had fasted for >6 h. There were no statistically significant differences in any of the studied complications between the two groups. Conclusions: This study found no difference in complication rate in regard to the fasting time among our subjects cohort, which included only healthy children receiving elective procedures performed by sedation trained pediatric critical care providers. This suggests that using shorter fasting time may be safe for procedures performed outside of the operating theater that does not involve high-risk patients or airway manipulation.
Stochastic-Based Deep Convolutional Networks with Reconfigurable Logic Fabric

Large-scale convolutional neural network is a fundamental algorithmic building block in many computer vision and artificial intelligence applications that follow the deep learning principle. However, a typically-sized CNN is well known to be computationally intensive. This work presents a novel stochastic-based and scalable hardware architecture and circuit design that computes a large-scale CNN with FPGA. The key idea is to implement all key components of a deep learning CNN, including multi-dimensional convolution, activation, and pooling layers, completely in the probabilistic computing domain in order to achieve high computing robustness, high performance, and low hardware usage. Our approach has three advantages. First, it can achieve significantly lower algorithmic complexity for any given accuracy requirement. For a $N$ dimensional image feature map, we have theoretically proven that a random sample size of $k^* \log (N)$ is sufficient to achieve no more than 0.05 error at 95 percent confidence level, where $k^*$ is a constant of 510. This computing complexity, when compared with that of conventional multiplier-based architecture, represents on average 8.97 $\times$ and 6.98 $\times$ performance improvement for SCNN and Deep SCNN, respectively. Second, this proposed stochastic-based architecture is highly fault-tolerant because the information to be processed is encoded with a large ensemble of random samples. As such, the local perturbations of its computing accuracy will be dissipated globally, thus becoming inconsequential to the final overall results. More interestingly, our measured results have shown that 0.1 percent degradation in computing accuracy of CNN can actually mitigate the well-known overfitting problem. Overall, being highly scalable and energy efficient, our stochastic-based convolutional neural network architecture is well-suited for a modular vision engine with the goal of performing real-time detection, recognition, and segmentation of mega-pixel images, especially those perception-based computing tasks that are inherently fault-tolerant, while still requiring high energy efficiency.
Jak/Stat signaling regulates the proliferation and neurogenic potential of Müller glia-derived progenitor cells in the avian retina

Muller glia are capable of de-differentiating and proliferating to become Muller glia-derived progenitor cells (MGPCs) with the ability to regenerate retinal neurons. One of the cell-signaling pathways that drives the reprogramming of Muller glia into MGPCs in the zebrafish retina is the Jak/Stat-pathway. However, nothing is known about the influence of Jak/Stat-signaling during the formation of MGPCs in the retinas of warm-blooded vertebrates. Accordingly, we examined whether Jak/Stat-signaling influences the formation of MGPCs and differentiation of progeny in the avian retina. We found that Jak/Stat-signaling is activated in Muller glia in response to NMDA-induced retinal damage or by CNTF or FGF2 in the absence of retinal damage. Inhibition of gp130, Jak2, or Stat3 suppressed the formation of proliferating MGPCs in NMDA-damaged and FGF2-treated retinas. Additionally, CNTF combined with FGF2 enhanced the formation of proliferating MGPCs in the absence of retinal damage. In contrast to the zebrafish model, where activation of gp130/Jak/Stat is sufficient to drive neural regeneration from MGPCs, signaling through gp130 inhibits the neurogenic potential of MGPCs and promotes glial differentiation. We conclude that gp130/Jak/Stat-signaling plays an important role in the network of pathways that drives the formation of proliferating MGPCs; however, this pathway inhibits the neural differentiation of the progeny.
“This will help your children”: Service providers’ experiences with military families during cycles of deployment

ABSTRACTMilitary families face not only the same challenges as other families, but also unique issues due to their military involvement. Parenting programs for civilian families can be helpful, but they do not generally cover the specific issues faced by military families. The purpose of this qualitative study was to gather information from a focus group of eight service providers about the types of issues that affect military families, such that content and delivery of workshops at a social service agency could be formed to specifically cater to military families. This study utilized a phenomenological approach, and analyses revealed areas for social service involvement around the cycle of deployment. Specifically, social services could be helpful by using psychoeducational and normalization techniques around the five major themes that resulted from this study: (1) the issues of servicemembers psychologically withdrawing before deployment, (2) family cohesion and connectedness during and after deployment...
Model sensitivity to spatial resolution and explicit light representation for simulation of boreal forests in complex terrain

Abstract A model is a simplification of our understanding of reality, but how much simplification is too much? We assessed model sensitivity for a new spatially-explicit individual-based gap model (IBM) SIBBORK to determine how spatial resolution (i.e., plot size) and explicit representation of light and space affect the simulated vegetation characteristics (e.g., structure and composition). The 3-dimensional (3-D) representation of light is the most computationally-expensive part of the simulation, so it is worthwhile to evaluate whether the time, resource and effort of spatial explicity improve predictive capabilities. In the simulation, gap dynamics occur at the plot-level, wherein a certain level of spatial homogeneity is assumed. Therefore, for the simulation of each ecosystem it is imperative to select the appropriate scale at which gap dynamics are simulated, i.e. the plot size. We conducted these sensitivity analyses and qualitatively compared model output to the descriptions of forest structure and composition at two different sites in central and southern Siberia. We systematically varied the plot size (100–900 m2) and found that a 100 m2 plot is most appropriate for the simulation of the central Siberian boreal forest ecosystem. Moreover, we found that the forest structure and composition simulated under the light environment generated using a 3-dimensional light ray tracing subroutine more closely resembled local and regional forest characteristics at both sites, whereas the growth and stand processes computed based on the simplified (1-D) light conditions approximated only large-scale (continental) average forest structure and biomass for the Eurasian boreal forest.
A Possible Causative Mechanism of Raton Basin, New Mexico and Colorado Earthquakes Using Recent Seismicity Patterns and Pore Pressure Modeling

The Raton Basin had the highest number of earthquakes in Colorado and New Mexico from 2008 to 2010. The rate of both wastewater injection and earthquakes in the basin increased dramatically starting in 1999 and 2001, respectively. We compare seismicity (ML 0.0–4.3) in the Raton Basin from 2008 to 2010 with the location of modeled pore pressure increases, estimated from cumulative wastewater injection volume beginning at the onset of well injection to present for all 28 injection wells in the basin. We find that modeled pore pressures in the New Mexico portion of the basin (above 0.08 MPa) reached that necessary to induce seismicity (0.01–0.1 MPa). We simulate a fault plane, 20 km long, inferred from seismicity in Vermejo Park (1355 of 1881 total earthquakes), in our model. We find that the relatively permeable fault allows pressures to migrate deeper into the basin at the onset of our study in 2008, providing an explanation for the observed seismicity in the basement. The Tercio lineament of earthquakes is similar to Vermejo Park fault in strike, but has fewer earthquakes (129) and is shorter in length (9 km). Seismicity in Vermejo Park occurs continuously, but earthquakes occur episodically in the remainder of the basin. The number of earthquakes we observe in seven seismic clusters increases as the cumulative injected volume from wells within 5 km increases. The modeled pore pressures, earthquake locations, and relationship between cumulative volume and number of earthquakes indicate that seismicity in the Raton Basin is likely induced.
The Impact of Diagnostic Code Misclassification on Optimizing the Experimental Design of Genetic Association Studies

Diagnostic codes within electronic health record systems can vary widely in accuracy. It has been noted that the number of instances of a particular diagnostic code monotonically increases with the accuracy of disease phenotype classification. As a growing number of health system databases become linked with genomic data, it is critically important to understand the effect of this misclassification on the power of genetic association studies. Here, I investigate the impact of this diagnostic code misclassification on the power of genetic association studies with the aim to better inform experimental designs using health informatics data. The trade-off between (i) reduced misclassification rates from utilizing additional instances of a diagnostic code per individual and (ii) the resulting smaller sample size is explored, and general rules are presented to improve experimental designs.
Chemical Potential of Metal Atoms in Supported Nanoparticles: Dependence upon Particle Size and Support

Metal nanoparticles supported on oxide surfaces form the basis for many industrial catalysts and promise to play an ever-increasing role in future energy and environmental technologies. The chemical potential (μ) of the metal atoms in these particles depends strongly on particle size and support and is an important factor that determines their catalytic properties, including their binding strengths to adsorbed reaction intermediates and their long-term stability against sintering. We present here a method for estimating this chemical potential as a function of particle size for different metal/oxide combinations. We show that this chemical potential for late transition metals is well approximated for a particle of diameter D by μ(D) = [(3γm – Eadh)(1 + Do/D)](2 Vm/D), where γm is the surface energy of the bulk metal, Eadh is the adhesion energy at the bulk metal/oxide interface, and Do is ∼1.5 nm, and Vm is the molar volume of the bulk metal. We further show that Eadh increases with (1) increasing heat of...
End-to-end Multilevel Hybrid Information Flow Control

We present models and soundness results for hybrid information flow, i.e. for mechanisms that enforce noninterference-style security guarantees using a combination of static analysis and dynamic taint tracking. Our analysis has the following characteristics: (i) we formulate hybrid information flow as an end-to-end property, in contrast to disruptive monitors that prematurely terminate or otherwise alter an execution upon detecting a potentially illicit flow; (ii) our security notions capture the increased precision that is gained when static analysis is combined with dynamic enforcement; (iii) we introduce path tracking to incorporate a form of termination-sensitivity, and (iv) develop a novel variant of purely dynamic tracking that ignores indirect flows; (v) our work has been formally verified, by a comprehensive representation in the theorem prover Coq.
Scalable Electric Power System Simulator

This paper describes concepts and design principles of a general scalable electric power system simulator (SEPSS). This tool is needed both for R&D in support of rapid modernization and as an advisory end-to-end computer application in on-line operation. The computer platform kernel is introduced using state-of-the-art modular multi-layered modeling of complex system dynamics affected by multi-temporal cyber signals (disturbances, market signals, control set points). Object-oriented MATLAB is used to represent components (actors) in detail, while their higher-level integration is done by interfacing them into clusters and ultimately into an interconnected system. The type and timing of information exchange are determined by communicating physical interaction variables among the modules without excessive complexity. We illustrate concepts in this paper on a small two control area system.
Radiobiological Effects of Pions

Biological studies with negative pions have been motivated almost exclusively by their therapeutic potential. There are basically two biological characteristics of negative pions which could prove useful for cancer management, 1) Negative pions have a lower oxygen enhancement ratio (OER) in the Bragg region as compared with conventional radiations, and the variation in sensitivity throughout the cell cycle is reduced with pions. In certain cases, this could produce an increased effect on malignant cells relative to normal cells. 2) The relative biological effectiveness (RBE) of pions in the Bragg region can be greater than that in the entrance region. This coupled with the good localization properties of pions could minimize the damage to normal tissues outside of the treatment volume.
Enhancing the antibacterial activity of polymyxins using a nonantibiotic drug

Purpose: The rapid emergence of multidrug-resistant (MDR) bacteria and the lack of new therapies to eliminate them poses a major threat to global health. With the alarming rise in antimicrobial resistance (AMR), focus has now shifted to the use of the polymyxin class of antibiotics as the last line of defense for treatment of Gram-negative infections. Unfortunately, the growing resistance of bacteria against polymyxins is threatening the treatment of MDR infections, necessitating the need for novel strategies. The objective of this study was to determine if combination of polymyxin (polymyxin B or colistin) with a nonantibiotic small molecule AR-12, a celecoxib derivative that is devoid of cyclooxygenase 2 (COX-2) inhibitory activities, can be an effective strategy against polymyxin-resistant MDR bacteria. Methods: Growth inhibition studies, time-kill assays and permeability assays were conducted to investigate the effect of AR-12 on the antibacterial activity of polymyxins. Results: Growth studies were performed on a panel of polymyxin-resistant MDR strains using the combination of AR-12 with either colistin or polymyxin B. The combination treatment had no effect on strains that have inherent polymyxin resistance; however, AR-12 was effective in lowering the minimal inhibitory concentration (MIC) of polymyxins by 4-60-fold in several strains that had acquired polymyxin resistance. Time-kill assays using the combination of AR-12 and colistin with select MDR strains suggest rapid killing and bactericidal activity, while the permeability assays using fluorescently labeled dansylated polymyxin and 1-N-phenylnaphthylamine (NPN) in these MDR strains suggest that AR-12 can potentiate the antibacterial activity of polymyxins by possibly altering the bacterial outer membrane via modification of lipopolysaccharide and thereby improving the uptake of polymyxins. Conclusion: Our studies indicate that the combination of AR-12 and polymyxin is effective in targeting select Gram-negative bacteria that have acquired polymyxin resistance. Further understanding of the mechanism of action of AR-12 will provide new avenues for developing narrow-spectrum antibacterials to target select Gram-negative MDR bacteria. Importantly, our studies show that the use of nonantibiotic small molecules in combination with polymyxins is an attractive strategy to counter the growing resistance of bacteria to polymyxins.
Hindsight Analysis of the Chicago Food Inspection Forecasting Model.

The Chicago Department of Public Health (CDPH) conducts routine food inspections of over 15,000 food establishments to ensure the health and safety of their patrons. In 2015, CDPH deployed a machine learning model to schedule inspections of establishments based on their likelihood to commit critical food code violations. The City of Chicago released the training data and source code for the model, allowing anyone to examine the model. We provide the first independent analysis of the model, the data, the predictor variables, the performance metrics, and the underlying assumptions. We present a summary of our findings, share lessons learned, and make recommendations to address some of the issues our analysis unearthed.
Densification and phase formation in seeded, reactively sintered Sr0.53Ba0.47Nb2O6 ceramics

Sr0.53Ba0.47Nb2O6 (SBN53) ceramics were reactively sintered from SrNb2O6 and BaNb2O6 powders. The formation temperature decreased from 1260°C for unseeded samples to 1130°C for the samples with 15.4 wt% seeds plus 0.85 mol% V2O5 at a heating rate of 4°C/min. For the V2O5-free samples, the activation energy was lowered from 554 ± 15 kJ/mol for unseeded samples to 241 ± 17 kJ/mol for the samples with 15.4 wt% seeds. In the V2O5-containing samples, densification and phase formation occurred simultaneously. In the V2O5-free samples, however, phase formation was completed before densification. In both cases, ceramics with ≥95% relative density were obtained. In all cases, SBN53 formed directly, rather than via a variety of intermediate SBN solid solutions. The microstructure evolution was also studied.
Influence of PEG on the clustering of active Janus colloids

Abstract Micrometer scale “colloidal” particles that propel in a deterministic fashion in response to local environmental cues are useful analogs to self-propelling entities found in nature. Both natural and synthetic active colloidal systems are often near boundaries or are located in crowded environments. Herein, we describe experiments in which we measured the influence of hydrogen peroxide concentration and dispersed polyethylene glycol (PEG) on the clustering behavior of 5 µm catalytic active Janus particles at low concentration. We found the extent to which clustering occurred in ensembles of active Janus particles grew with hydrogen peroxide concentration in the absence of PEG. Once PEG was added, clustering was slightly enhanced at low PEG volume fractions, but was reduced at higher PEG volumes fractions. The region in which clustering was mitigated at higher PEG volume fractions corresponded to the region in which propulsion was previously found to be quenched. Complementary agent based simulations showed that clustering grew with nominal speed. These data support the hypothesis that growth of living crystals is enhanced with increases in propulsion speed, but the addition of PEG will tend to mitigate cluster formation as a consequence of quenched propulsion at these conditions.
Brain Cholesterol The Effect of its Development on Incorporation of Acetate-2-3H and Glucose-U-14

Publisher Summary The potential of the adult brain for lipid metabolism has always been regarded as limited. Recently, the admission of newer evidence has challenged this static concept for neural metabolism. Studies with radioactive nutrients on the intact animal are difficult to interpret because of the protective mechanisms (blood-brain barrier) of the brain, which controls the movement of substances into and out of the neural tissue. Thus the unavailability of injected precursors to become incorporated into compounds of the central nervous system has been interpreted by early investigators as indicative of a limited metabolic potentiality. Through special techniques and experimental designs, recent studies have mitigated against this static metabolic picture for neural tissue, which now indicates extensive metabolic potentials. Pursuing the problems of cholesterol biosynthesis in various tissues by simultaneous use of selected 14 C- and 3 H-precursors, it has been previously reported that acetate was a poor choice for the study of the brain cholesterol formation. In this and similar studies, glucose is shown to be a better carbon source for brain cholesterol than acetate. It is of interest, therefore, to examine the contribution of a non-carbohydrate labeled substance and glucose as both became incorporated into the sterol of the developing mouse brain. Mice representing three age groups are simultaneously injected with acetate-2- 3 H and glucose-U- 14 C and the incorporation of these labeled nutrients into brain cholesterol was measured in this chapter.
Technology provides opportunities for smaller universities to improve computer science curriculum

Today, computer science graduates are well-sought by employers. A computer science education will furnish you with many skills that may be applied to a number of careers. However, as always, there are portions of the traditional curriculum that can be improved. This paper summarizes and justifies the author's opinions on how computer science curricula may evolve. She hopes to continue discussions in this area throughout her career, because discussing these issues with other interested professionals is the way to find the best path.
Coagulation driven platelet activation reduces injury and fibrosis in chronic liver disease (144.3)

Previous studies suggest that platelets and fibrin(ogen), components of the hemostatic system, reduce hepatocellular injury and inhibit liver fibrosis in models of cholestasis. However, the molecular pathways linking fibrin polymerization and platelet activation to liver injury during cholestasis are not known. We hypothesized that platelet activation by thrombin-mediated protease activated receptor (PAR)-4 signaling and fibrin engagement of the αIIBβ3 integrin on platelets are key events linked to inhibition of hepatic injury and fibrosis in a mouse model of cholestasis. To test this hypothesis, mice expressing a mutant form of fibrin(ogen) incapable of binding αIIBβ3 (FibγΔ5), mice lacking PAR-4 and wild-type (WT) mice were fed a diet containing the bile duct toxicant alpha-naphthylisothiocyanate (ANIT) (0.025%), or control diet (AIN-93M) for four weeks. Consistent with our hypothesis, PAR-4 deficiency significantly increased portal inflammation and peribiliary fibrosis in mice fed ANIT diet, but did no...
Glandular kallikrein in plasma and urine: evaluation of a direct RIA for its determination.

To determine whether there is glandular kallikrein in plasma, untreated as well as acetone-treated and heated-acidified rat plasmas together with rabbit anti-rat urinary kallikrein were used in counterimmunoelectrophoresis. Precipitation bands were observed with untreated and acetone-treated plasma, suggesting that glandular kallikrein is present in plasma. This enzyme, however, cannot be quantified in the untreated plasma by a new direct RIA since kallikrein inhibitors present in plasma appear to interfere with this assay. Destroying the inhibitors by acetone treatment or by heat and acidification of the plasma partially solves this problem. In the second part of the study, this RIA as well as a kininogenase and an esterase assay were used to measure urinary kallikrein in DOCA-salt treated rats and in control rats. There is a significant correlation between urinary kallikrein measured by the direct RIA and by a kininogenase method (r = 0.75, p 0.1). This suggests that part of the urinary esterase activity in the DOCA-salt rats is due to urinary enzymes other than kallikrein and that the esterase assay is not reliable for the determination of urinary kallikrein in pathological situations. However, the direct RIA and the kininogenase assay are suitable for this purpose.
Super-enhancers: Asset management in immune cell genomes

Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4+ T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity.
Survey: Common Knowledge in BIM for Facility Maintenance

AbstractAs building information modeling (BIM) has become more widely adopted by the architecture, engineering, construction and operations (AECO) industry, its undeveloped potential for supporting facility management (FM) has become more apparent. In order to fully release the power of BIM tools, the first step is to understand and clarify what the requirements of the facility management phase are for operations and maintenance activities. This paper proposes a process for knowledge accumulation and sharing for BIM-FM through the project life cycle. In order to collect the initial knowledge for the knowledge database, a survey questionnaire was developed and administered to collect perspectives from industry practitioners to understand existing facility management requirements and the types of maintainability problems that frequently occur that have the potential to be solved early on in the design phase. The survey results indicated that maintainability issues should be taken into consideration during t...
Amino acid transport and rubidium-ion uptake in monolayer cultures of hepatocytes from neonatal rats

Amino acid and K(+) transport during development has been investigated in hepatocyte monolayer cultures with either alpha-amino[1-(14)C]isobutyrate or (86)Rb(+) used as a tracer for K(+). Parenchymal cells from neo- and post-natal rat livers have been isolated by an improved non-perfusion technique [Bellemann, Gebhardt & Mecke (1977)Anal.Biochem.81, 408-415], and the resulting hepatocyte suspensions purified from non-hepatocytes before inoculation. In the presence of Na(+) (Na(+)-dependent component), the rates of amino acid uptake in neonatal hepatocytes were markedly enhanced compared with cells from 30-day-old rats. When Na(+) was replaced by choline (Na(+)-independent component) the accumulation of alpha-aminoisobutyrate was decreased and it was not affected by the age of the animals. Kinetic analysis of Na(+)-dependent alpha-aminoisobutyrate transport revealed the existence of a high-affinity low-K(m) component (K(m)0.91mm) with a V(max.) of 2.44nmol/mg of protein per 4min, which later declined gradually with progressive development. Rates of Rb(+) transport were concomitantly enhanced in neonatal hepatocytes and thereafter declined with postnatal age. The increased Rb(+) influx was effectively inhibited by ouabain and reflected elevated activity of the electrogenic Na(+)/K(+)-pump during early stages of development. Kinetic evaluation of the enhanced rates of Rb(+) uptake indicates multiple and co-operative binding sites of the enzyme involved in the Rb(+) uptake, and the transport system is positively co-operative (the Hill coefficient h is >1.0). In short, amino acid transport in neonatal rat hepatocytes is increased as a result of an existing low-K(m) component for the Na(+)-dependent alpha-aminoisobutyrate uptake, which endows the hepatocytes with a high capability for concentrating amino acids at low ambient values. The concomitant enhancement of K(+) transport reflects changes in the electrochemical gradient for Na(+) across the hepatocellular membrane and, along with this, presumably alterations in the membrane potential; the latter might be the driving force for the enhanced alpha-aminoisobutyrate transport in the alanine-preferring system during postnatal age.
LARVA: an integrative framework for large-scale analysis of recurrent variants in noncoding annotations

In cancer research, background models for mutation rates have been extensively calibrated in coding regions, leading to the identification of many driver genes, recurrently mutated more than expected. Noncoding regions are also associated with disease; however, background models for them have not been investigated in as much detail. This is partially due to limited noncoding functional annotation. Also, great mutation heterogeneity and potential correlations between neighboring sites give rise to substantial overdispersion in mutation count, resulting in problematic background rate estimation. Here, we address these issues with a new computational framework called LARVA. It integrates variants with a comprehensive set of noncoding functional elements, modeling the mutation counts of the elements with a β-binomial distribution to handle overdispersion. LARVA, moreover, uses regional genomic features such as replication timing to better estimate local mutation rates and mutational hotspots. We demonstrate LARVA's effectiveness on 760 whole-genome tumor sequences, showing that it identifies well-known noncoding drivers, such as mutations in the TERT promoter. Furthermore, LARVA highlights several novel highly mutated regulatory sites that could potentially be noncoding drivers. We make LARVA available as a software tool and release our highly mutated annotations as an online resource (larva.gersteinlab.org).