Miracle-dz/UniFAR-FTUs huggingface dataset:
Visual Information Present in Infragranular Layers of Mouse Auditory Cortex

The cerebral cortex is a major hub for the convergence and integration of signals from across the sensory modalities; sensory cortices, including primary regions, are no exception. Here we show that visual stimuli influence neural firing in the auditory cortex of awake male and female mice, using multisite probes to sample single units across multiple cortical layers. We demonstrate that visual stimuli influence firing in both primary and secondary auditory cortex. We then determine the laminar location of recording sites through electrode track tracing with fluorescent dye and optogenetic identification using layer-specific markers. Spiking responses to visual stimulation occur deep in auditory cortex and are particularly prominent in layer 6. Visual modulation of firing rate occurs more frequently at areas with secondary-like auditory responses than those with primary-like responses. Auditory cortical responses to drifting visual gratings are not orientation-tuned, unlike visual cortex responses. The deepest cortical layers thus appear to be an important locus for cross-modal integration in auditory cortex. SIGNIFICANCE STATEMENT The deepest layers of the auditory cortex are often considered its most enigmatic, possessing a wide range of cell morphologies and atypical sensory responses. Here we show that, in mouse auditory cortex, these layers represent a locus of cross-modal convergence, containing many units responsive to visual stimuli. Our results suggest that this visual signal conveys the presence and timing of a stimulus rather than specifics about that stimulus, such as its orientation. These results shed light on both how and what types of cross-modal information is integrated at the earliest stages of sensory cortical processing.
Engineering global regulator Hha of Escherichia coli to control biofilm dispersal

The global transcriptional regulator Hha of Escherichia coli controls biofilm formation and virulence. Previously, we showed that Hha decreases initial biofilm formation; here, we engineered Hha for two goals: to increase biofilm dispersal and to reduce biofilm formation. Using random mutagenesis, Hha variant Hha13D6 (D22V, L40R, V42I and D48A) was obtained that causes nearly complete biofilm dispersal (96%) by increasing apoptosis without affecting initial biofilm formation. Hha13D6 caused cell death probably by the activation of proteases since Hha‐mediated dispersal was dependent on protease HslV. Hha variant Hha24E9 (K62X) was also obtained that decreased biofilm formation by inducing gadW, glpT and phnF but that did not alter biofilm dispersal. Hence, Hha may be engineered to influence both biofilm dispersal and formation.
Multimodel ensembles of streamflow forecasts: Role of predictor state in developing optimal combinations

A new approach for developing multimodel streamflow forecasts is presented. The methodology combines streamflow forecasts from individual models by evaluating their skill, represented by rank probability score (RPS), contingent on the predictor state. Using average RPS estimated over the chosen neighbors in the predictor state space, the methodology assigns higher weights for a model that has better predictability under similar predictor conditions. We assess the performance of the proposed algorithm by developing multimodel streamflow forecasts for Falls Lake Reservoir in the Neuse River Basin, North Carolina (NC), by combining streamflow forecasts developed from two low‐dimensional statistical models that use sea‐surface temperature conditions as underlying predictors. To evaluate the proposed scheme thoroughly, we consider a total of seven multimodels that include existing multimodel combination techniques such as combining based on long‐term predictability of individual models and by simple pooling of ensembles. Detailed nonparametric hypothesis tests comparing the performance of seven multimodels with two individual models show that the reduced RPS from multimodel forecasts developed using the proposed algorithm is statistically significant from the RPSs of individual models and from the RPSs of existing multimodel techniques. The study also shows that adding climatological ensembles improves the multimodel performance resulting in reduced average RPS. Contingency analyses on categorical (tercile) forecasts show that the proposed multimodel combination technique reduces average Brier score and total number of false alarms, resulting in improved reliability of forecasts. However, adding multiple models with climatology also increases the number of missed targets (in comparison to individual models' forecasts) which primarily results from the reduction of increased resolution that is exhibited in the individual models' forecasts under various forecast probabilities.
Building an evidence base on mental health interventions for children affected by armed conflict

This paper reviews what is currently known from research about the effectiveness of interventions to address mental health problems in children and adolescents affected by armed conflict. The focus will be on interventions delivered in conflict affected countries either during active humanitarian emergencies or during the post conflict period. The paper will discuss two main paradigms of intervention dominating the field: psychosocial approaches and clinical/psychiatric approaches. The paper reviews some of the basic literature, theories and issues involved in assessment, programme planning, monitoring and evaluation of both approaches. In order to explore these issues in depth, the paper will draw from the author's field experiences with research in the Russian Federation and in northern Uganda. The paper also presents a brief review of a handful of other published evaluations of mental health interventions for war affected children. We will close with a discussion of what future research is needed to build an evidence base regarding mental health interventions for children affected by armed conflict as well as the ethical and feasibility issues associated with carrying out this work.
Integrative Conjugative Element ICE-βox Confers Oxidative Stress Resistance to Legionella pneumophila In Vitro and in Macrophages

ABSTRACT Integrative conjugative elements (ICEs) are mobile blocks of DNA that can contribute to bacterial evolution by self-directed transmission of advantageous traits. Here, we analyze the activity of a putative 65-kb ICE harbored by Legionella pneumophila using molecular genetics, conjugation assays, a phenotype microarray screen, and macrophage infections. The element transferred to a naive L. pneumophila strain, integrated site-specifically, and conferred increased resistance to oxacillin, penicillin, hydrogen peroxide, and bleach. Furthermore, the element increased survival of L. pneumophila within restrictive mouse macrophages. In particular, this ICE protects L. pneumophila from phagocyte oxidase activity, since mutation of the macrophage NADPH oxidase eliminated the fitness difference between strains that carried and those that lacked the mobile element. Renamed ICE-βox (for β-lactam antibiotics and oxidative stress), this transposable element is predicted to contribute to the emergence of L. pneumophila strains that are more fit in natural and engineered water systems and in macrophages. IMPORTANCE Bacteria evolve rapidly by acquiring new traits via horizontal gene transfer. Integrative conjugative elements (ICEs) are mobile blocks of DNA that encode the machinery necessary to spread among bacterial populations. ICEs transfer antibiotic resistance and other bacterial survival factors as cargo genes carried within the element. Here, we show that Legionella pneumophila, the causative agent of Legionnaires’ disease, carries ICE-βox, which enhances the resistance of this opportunistic pathogen to bleach and β-lactam antibiotics. Moreover, L. pneumophila strains encoding ICE-βox are more resistant to macrophages that carry phagocyte oxidase. Accordingly, ICE-βox is predicted to increase the fitness of L. pneumophila in natural and engineered waters and in humans. To our knowledge, this is the first description of an ICE that confers oxidative stress resistance to a nosocomial pathogen. Bacteria evolve rapidly by acquiring new traits via horizontal gene transfer. Integrative conjugative elements (ICEs) are mobile blocks of DNA that encode the machinery necessary to spread among bacterial populations. ICEs transfer antibiotic resistance and other bacterial survival factors as cargo genes carried within the element. Here, we show that Legionella pneumophila, the causative agent of Legionnaires’ disease, carries ICE-βox, which enhances the resistance of this opportunistic pathogen to bleach and β-lactam antibiotics. Moreover, L. pneumophila strains encoding ICE-βox are more resistant to macrophages that carry phagocyte oxidase. Accordingly, ICE-βox is predicted to increase the fitness of L. pneumophila in natural and engineered waters and in humans. To our knowledge, this is the first description of an ICE that confers oxidative stress resistance to a nosocomial pathogen.
Direct assessment in bacteria of prionoid propagation and phenotype selection by Hsp70 chaperone

Protein amyloid aggregates epigenetically determine either advantageous or proteinopathic phenotypes. Prions are infectious amyloidogenic proteins, whereas prionoids lack infectivity but spread from mother to daughter cells. While prion amyloidosis has been studied in yeast and mammalian cells models, the dynamics of transmission of an amyloid proteinopathy has not been addressed yet in bacteria. Using time‐lapse microscopy and a microfluidic set‐up, we have assessed in Escherichia coli the vertical transmission of the amyloidosis caused by the synthetic bacterial model prionoid RepA‐WH1 at single cell resolution within their lineage context. We identify in vivo the coexistence of two strain‐like types of amyloid aggregates within a genetically identical population and a controlled homogeneous environment. The amyloids are either toxic globular particles or single comet‐shaped aggregates that split during cytokinesis and exhibit milder toxicity. Both segregate and propagate in sublineages, yet show interconversion. ClpB (Hsp104) chaperone, key for spreading of yeast prions, has no effect on the dynamics of the two RepA‐WH1 aggregates. However, the propagation of the comet‐like species is DnaK (Hsp70)‐dependent. The bacterial RepA‐WH1 prionoid thus provides key qualitative and quantitative clues on the biology of intracellular amyloid proteinopathies.
The theory of wedge indentation of ductile materials

The theoretical solution for the deformation produced by a rigid frictionless wedge penetrating a plastic material is presented in this paper. The solution determines the form of the lip and the deformation in the material squeezed out towards the surface. The variation with wedge angle of the force required for penetration is determined in terms of the yield stress in a tensile test. The deformation of a grid of squares on a plane normal to the axis of the wedge is shown in figure 9 for a 30° semi-angle wedge. Close agreement is obtained with experiments as shown by comparing figure 9 with the photographs in figure 10 (plate 4). Lead blocks were used with a grid of squares scribed before penetration. This investigation is a first step towards the correlation of hardness test results with the deformation properties of a material under other conditions of stress, e.g. the tensile test. The average strain due to wedge indentation is shown to correspond to an equivalent reduction of area in a tensile test which increases with increasing wedge angle.
A backward recursive algorithm for inventory lot-size models with power-form demand and shortages

In 1978, Barbosa and Friedman established a ‘general root law’ for power-form demand rate. Shortages are prohibited. However, in reality, shortages may occur and the planning time horizon is usually finite as the product life cycle is short. Therefore, the author here extends their inventory lot-size model to allow for shortages during a finite planning time horizon and propose an alternative algorithm in a backward manner to determine the optimal replenishment timing without using iterative search schemes. The study not only shows that the total relevant cost is a strictly convex function of the replenishment number, but also provides the condition for determining the optimal replenishment number. Finally, a numerical example is given for illustration.
Efficient measurement and factorization of high-order drug interactions in Mycobacterium tuberculosis

Geometrically optimized sampling of drug-dose combinations enables systematic identification of high-order drug synergies. Combinations of three or more drugs are used to treat many diseases, including tuberculosis. Thus, it is important to understand how synergistic or antagonistic drug interactions affect the efficacy of combination therapies. However, our understanding of high-order drug interactions is limited because of the lack of both efficient measurement methods and theoretical framework for analysis and interpretation. We developed an efficient experimental sampling and scoring method [diagonal measurement of n-way drug interactions (DiaMOND)] to measure drug interactions for combinations of any number of drugs. DiaMOND provides an efficient alternative to checkerboard assays, which are commonly used to measure drug interactions. We established a geometric framework to factorize high-order drug interactions into lower-order components, thereby establishing a road map of how to use lower-order measurements to predict high-order interactions. Our framework is a generalized Loewe additivity model for high-order drug interactions. Using DiaMOND, we identified and analyzed synergistic and antagonistic antibiotic combinations against Mycobacterium tuberculosis. Efficient measurement and factorization of high-order drug interactions by DiaMOND are broadly applicable to other cell types and disease models.
Comparison of Schistosoma mansoni Soluble Cercarial Antigens and Soluble Egg Antigens for Serodiagnosing Schistosome Infections

A Schistosoma mansoni cercarial antigen preparation (cercarial transformation fluid – SmCTF) was evaluated for detection of anti-schistosome antibodies in human sera in 4 collaborating laboratories. The performance of SmCTF was compared with that of S. mansoni egg antigens (SmSEA) in an indirect enzyme-immunoassay (ELISA) antigen assay, the latter being used routinely in 3 of the 4 participating laboratories to diagnose S. mansoni and S. haematobium infections. In the fourth laboratory the performance of SmCTF was compared with that of S. japonicum egg antigens (SjSEA) in ELISA for detection of anti-S. japonicum antibodies. In all 4 laboratories the results given by SmCTF in ELISA were very similar to those given by the antigen preparation routinely used in the respective laboratory to detect anti-schistosome antibodies in human infection sera. In so far as the ELISA results from SmCTF are thus so little different from those given by schistosome egg antigens and also cheaper to produce, the former is a potentially useful new diagnostic aid for schistosomiasis.
FGF21 Response to Critical Illness: Effect of Blood Glucose Control and Relation With Cellular Stress and Survival.

CONTEXT Critical illness is hallmarked by mitochondrial damage, which is attenuated by targeting normoglycemia. Mitochondrial dysfunction induces fibroblast growth factor-21 (FGF21) via the integrated stress response (ISR). OBJECTIVE We evaluated whether critical illness elevates serum FGF21 concentrations and whether targeting normoglycemia (80-110 mg/dL) with insulin vs tolerating hyperglycemia may lower serum FGF21 by attenuating mitochondrial dysfunction and the ISR. SETTING/DESIGN We quantified serum FGF21 concentrations in critically ill patients. To allow tissue analyses, including hepatic fgf21 expression in relation with mitochondrial function and ISR markers, we studied critically ill rabbits. Patients and rabbits were randomized to hyper- or normoglycemia. Patients/Other Participants: We studied 405 fed critically ill patients vs 20 matched non-critically ill control subjects as well as 26 critically ill rabbits vs 13 healthy rabbits. INTERVENTIONS Insulin was infused to control blood glucose. MAIN OUTCOME MEASURES AND RESULTS Serum FGF21 concentrations upon intensive care unit admission were 8-fold higher than in control subjects (P < .0001), decreased with time, but always remained higher in nonsurvivors than survivors (P ≤ .006). Maintaining normoglycemia lowered serum FGF21 (P = .01), statistically explaining at least part of its mortality benefit. In ill rabbits, hepatic fgf21 expression was substantially increased (P < .0001) and was tightly correlated with mitochondrial dysfunction (all R(2) ≥ 0.49; all P ≤ . 0006 for complex I and V) and ISR markers on day 3 (R(2) ≥ 0.73; P ≤ . 0001), all lowered by targeting normoglycemia. CONCLUSION Critical illness is a potent inducer of serum FGF21 and of liver fgf21 expression, possibly driven at least in part by mitochondrial damage and the ISR, which were all attenuated by targeting normoglycemia.
An Extended Quadratic Frobenius Primality Test with Average Case Error Estimates

We present an Extended Quadratic Frobenius Primality Test (EQFT), which is related to the Miller-Rabin test and the Quadratic Frobenius test (QFT) by Grantham. EQFT is well-suited for generating large, random prime numbers since on a random input number, it takes time about equivalent to 2 Miller-Rabin tests, but has much smaller error probability. EQFT extends QFT by verifying additional algebraic properties related to the existence of elements of order 3 and 4. We obtain a simple closed expression that upper bounds the probability of acceptance for any input number. This in turn allows us to give strong bounds on the average-case behaviour of the test: consider the algorithm that repeatedly chooses random odd k bit numbers, subjects them to t iterations of our test and outputs the first one found that passes all tests. We obtain numeric upper bounds for the error probability of this algorithm as well as a general closed expression bounding the error. For instance, it is at most 2^{-143} for k=500, t=2 . Compared to earlier similar results for the Miller-Rabin test, the results indicates that our test in the average case has the effect of 9 Miller-Rabin tests, while only taking time equivalent to about 2 such tests. We also give bounds for the error in case a prime is sought by incremental search from a random starting point. While EQFT is slower than the average case on a small set of inputs, we present a variant that is always fast, i.e. takes time about 2 Miller-Rabin tests. The variant has slightly larger worst case error probability than EQFT, but still improves on previous proposed tests.
Role of the major pneumococcal autolysin in the atypical response of a clinical isolate of Streptococcus pneumoniae

The autolytic enzyme (an N-acetylmuramyl-L-alanine amidase) of a clinical isolate, strain 101/87, which is classified as an atypical pneumococcus, has been studied for the first time. The lytA101 gene coding for this amidase (LYTA101) has been cloned, sequenced, and expressed in Escherichia coli. The LYTA101 amidase has been purified and shown to be similar to the main autolytic enzyme (LYTA) present in the wild-type strain of Streptococcus pneumoniae, although it exhibits a lower specific activity, a higher sensitivity to inhibition by free choline, and a modified thermosensitivity with respect to LYTA. Most important, in contrast with the LYTA amidase, the activity of the LYTA101 amidase was inhibited by sodium deoxycholate. This property is most probably responsible of the deoxycholate-insensitive phenotype shown by strain 101/87. Phenotypic curing of strain 101/87 by externally adding purified LYTA or LYTA101 amidase restored in this strain some typical characteristics of the wild-type strain of pneumococcus (e.g., formation of diplo cells and sensitization to lysis by sodium deoxycholate), although the amount of the LYTA101 amidase required to restore these properties was much higher than in the case of the LYTA amidase. Our results indicate that modifications in the primary structure or in the mechanisms that control the activity of cell wall lytic enzymes seem to be responsible for the characteristics exhibited by some strains of S. pneumoniae that have been classically misclassified and should be now considered atypical pneumococcal strains.
Universal Background Subtraction Using Word Consensus Models

Background subtraction is often used as the first step in video analysis and smart surveillance applications. However, the issue of inconsistent performance across different scenarios due to a lack of flexibility remains a serious concern. To address this, we propose a novel non-parametric, pixel-level background modeling approach based on word dictionaries that draws from traditional codebooks and sample consensus approaches. In this new approach, the importance of each background sample (or word) is evaluated online based on their recurrence among all local observations. This helps build smaller pixel models that are better suited for long-term foreground detection. Combining these models with a frame-level dictionary and local feedback mechanisms leads us to our proposed background subtraction method, coined “PAWCS. ” Experiments on the 2012 and 2014 versions of the ChangeDetection.net data set show that PAWCS outperforms 26 previously tested and published methods in terms of overall F-Measure as well as in most categories taken individually. Our results can be reproduced with a C++ implementation available online.
Unusual 1H NMR chemical shifts support (His) C(epsilon) 1...O==C H-bond: proposal for reaction-driven ring flip mechanism in serine protease catalysis.

13C-selective NMR, combined with inhibitor perturbation experiments, shows that the C(epsilon)(1)H proton of the catalytic histidine in resting alpha-lytic protease and subtilisin BPN' resonates, when protonated, at 9.22 ppm and 9.18 ppm, respectively, which is outside the normal range for such protons and approximately 0.6 to 0.8 ppm further downfield than previously reported. They also show that the previous alpha-lytic protease assignments [Markley, J. L. , Neves, D. E. , Westler, W. M. , Ibanez, I. B. , Porubcan, M. A. & Baillargeon, M. W. (1980) Front. Protein Chem. 10, 31-61] were to signals from inactive or denatured protein. Simulations of linewidth vs. pH demonstrate that the true signal is more difficult to detect than corresponding signals from inactive derivatives, owing to higher imidazole pK(a) values and larger chemical shift differences between protonated and neutral forms. A compilation and analysis of available NMR data indicates that the true C(epsilon)(1)H signals from other serine proteases are similarly displaced downfield, with past assignments to more upfield signals probably in error. The downfield displacement of these proton resonances is shown to be consistent with an H-bond involving the histidine C(epsilon)(1)H as donor, confirming the original hypothesis of Derewenda et al. [Derewenda, Z. S. , Derewenda, U. & Kobos, P. M. (1994) J. Mol. Biol. 241, 83-93], which was based on an analysis of literature x-ray crystal structures of serine hydrolases. The invariability of this H-bond among enzymes containing Asp-His-Ser triads indicates functional importance. Here, we propose that it enables a reaction-driven imidazole ring flip mechanism, overcoming a major dilemma inherent in all previous mechanisms, namely how these enzymes catalyze both the formation and productive breakdown of tetrahedral intermediates.