Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Studies of Lac Repressor: 4000 Single Amino Acid Substitutions and Analysis of the Resulting Phenotypes on the Basis of the Protein Structure

Each amino acid from position 2 to 329 of Lac repressor was replaced by 12 or 13 of the 20 natural occurring amino acids. The resulting phenotypes are discussed on the basis of (1) the recently published structure of the Lac repressor core complexed with the inducer IPTG and (2) a model of the dimeric Lac repressor built by homology modelling from the X-ray structure of the purine repressor-corepressor-operator complex. This phenotype analysis, based on 4000 well-defined mutants, yields a functional description of each amino acid position of Lac repressor. In most cases, mutant effects can be directly correlated with the structure and function of the protein. This connection between the amino acid position and the structure and function of the protein is in most cases direct and not complicated: amino acids which are directly involved in sugar binding are affected in Lac repressor mutants of the Is type; small amino acids which can only be replaced by other small acids are located in the core of the protein; positions at which nearly all amino acids are tolerated are in most cases located on the surface of the protein. Amino acids which are highly conserved throughout the LacI family of repressors, and not directly involved in specific functions of the protein like DNA recognition or sugar binding, form a network of contacts with other amino acids. Such amino acids are either located inside one subunit, mostly at the interface between secondary structure elements, or are involved in the dimerisation interface.
Precautionary Saving and Social Learning Across Generations: An Experiment

We use experimental methods to study how individuals solve life cycle 'precautionary savings' tasks. Some results resemble previous experimental work on dynamic optimisation tasks. Within our experiment, however, opportunities exist for subjects to learn from one another. Subjects participated in three-member 'families'. Second and third 'generation' subjects observe and/or communicate with their 'antecedent' first or second generation subject. We find that later generations perform significantly better than earlier generations. The results speak to questions concerning the precautionary model of consumption, the modelling of dynamic decision behaviour more generally, and the possible importance of social learning to individual decision-making. Copyright 2003 Royal Economic Society.
Randomized unregulated step descent for limited precision synaptic elements

Training neural networks with low-resolution synaptic weights raised much interest recently and inference in neural networks with binary activation and binary weights has been shown to be able to achieve near state-of-the-art performance in a wide range of tasks. However, the current methods for training such networks rely on high-resolution gradients or update probabilities. Low resolution training methods would be useful for neuromorphic architectures that support lower power hardware implementations as well as emerging memory technologies based on memristive devices that do not always support fine-grained state changes. In this paper, we propose a training method, Randomized Unregulated Step Descent (RUSD), as an alternative to gradient descent that uses only a single bit of information about the gradient; we show how it is compatible with low-resolution integer arithmetic platforms and is resilient to some of the prominent non-idealities of memristive memories. We verify the performance of RUSD several standard machine-learning benchmarks.
Regulation of Inducible Nitric Oxide Synthase Expression by p300 and p50 Acetylation 1

To determine whether p300 is involved in inducible NO synthase (iNOS) transcriptional regulation, we evaluated the effect of p300 overexpression on iNOS expression and characterized p300 binding to iNOS promoter in RAW 264.7 cells. p300 overexpression increased iNOS expression which was abrogated by deletion of the histone acetyltransferase (HAT) domain (Δ1472–1522). DNA-binding and chromatin immunoprecipitation assays revealed binding of p300 to several DNA-bound transactivators at basal state. Following stimulation with LPS plus IFN-γ, binding of p300, p50/p65 NF-κB, and IFN-regulatory factor-1 was increased by ∼2-fold. Nuclear p50 was complexed with and acetylated by p300 at the basal binding state which was increased by LPS and IFN-γ stimulation. p300 overexpression resulted in increased p50 acetylation which was reduced by HAT mutation. p50 acetylation correlated with increased NF-κB binding and enhanced p300 recruitment. Co-overexpression of E1A abolished the augmentation of p50 acetylation and p50 binding induced by p300 overexpression, and a correlative suppression of p300 recruitment to the complex. We conclude that p300 is essential for iNOS transcription. Our results suggest that p300 HAT acetylates the p50 subunit of NF-κB, thereby increasing NF-κB binding and NF-κB mediated transactivation.
New tools for mass isotopomer data evaluation in 13C flux analysis: Mass isotope correction, data consistency checking, and precursor relationships

13C metabolic flux analysis (MFA) is based on carbon‐labeling experiments where a specifically 13C labeled substrate is fed. The labeled carbon atoms distribute over the metabolic network and the label enrichment of certain metabolic pools is measured by using different methods. Recently, MS methods have been dramatically improved—large and precise datasets are now available. MS data has to be preprocessed and corrected for natural stable mass isotopes. In this article we present (1) a new elegant method to correct MS measurement data for natural stable mass isotopes by infinite dimensional matrix calculus and (2) we statistically analyze and discuss a reconstruction of labeling pattern in metabolic precursors from biosynthesis molecules. Moreover, we establish a new method for consistency checking of MS spectra that can be applied for automatic error recognition in high‐throughput flux analysis procedures. Preprocessing the measurement data changes their statistical properties which have to be considered in the subsequent parameter fitting process for 13C MFA. We show that correcting for stable mass isotopes leads to rather small correlations. On the other hand, a direct reconstruction of a precursor labeling pattern from an aromatic amino acid measurement turns out to be critical. Reasonable results are only obtained if additional, independent information about the labeling of at least one precursor is available. A versatile MatLab tool for the rapid correction and consistency checking of MS spectra is presented. Practical examples for the described methods are also given. ©2004 Wiley Periodicals, Inc.
Priority setting in kidney transplantation: A qualitative study evaluating Swedish practices

Background: Transplantation is the treatment of choice for end-stage renal disease; it increases survival and quality of life, while being more cost-effective than dialysis. It is, however, limited by the scarcity of kidneys. The aim of this paper is to investigate the fairness of the priority setting process underpinning Swedish kidney transplantation in reference to the Accountability for Reasonableness (A4R) framework. Methods: Fifteen semi-structured interviews were carried out with transplant surgeons (7), nephrologists (6) and coordinators (2) representing centers nationwide. Collected data was analysed using thematic analysis. To assess fairness in the priority setting process, identified factors were assessed in the reference to the four conditions (publicity, relevance, revision and appeal, enforcement) forming the accountability for reasonableness framework. Results: Decision-making in assessment and allocation is based on clusters of factors. The factors appeal to various values, which are balanced against each other throughout the kidney allocation process: maximizing benefit, priority to the worst off and equality. The factors described by subjects and the values on which they rest satisfy the relevance condition of the accountability for reasonableness framework. However, two potential sources for unfair inequalities in access to treatment are identified: clinical judgment and institutional policies. Conclusions: The development of national guidelines both for assessing transplant candidacy, and for the allocation of kidneys from deceased donors, would contribute to standardize practices across centres; it will also help to better meet the conditions of fairness in reference to Accountability for Reasonableness. The benefits of this policy proposal in Swedish kidney transplantation merits consideration.
Learning-Based Computation Offloading for IoT Devices With Energy Harvesting

Internet of Things (IoT) devices can apply mobile edge computing (MEC) and energy harvesting (EH) to provide high-level experiences for computational intensive applications and concurrently to prolong the lifetime of the battery. In this paper, we propose a reinforcement learning (RL) based offloading scheme for an IoT device with EH to select the edge device and the offloading rate according to the current battery level, the previous radio transmission rate to each edge device, and the predicted amount of the harvested energy. This scheme enables the IoT device to optimize the offloading policy without knowledge of the MEC model, the energy consumption model, and the computation latency model. Further, we present a deep RL-based offloading scheme to further accelerate the learning speed. Their performance bounds in terms of the energy consumption, computation latency, and utility are provided for three typical offloading scenarios and verified via simulations for an IoT device that uses wireless power transfer for energy harvesting. Simulation results show that the proposed RL-based offloading scheme reduces the energy consumption, computation latency, and task drop rate, and thus increases the utility of the IoT device in the dynamic MEC in comparison with the benchmark offloading schemes.
[The Anopheles gambiae complex in Guinea Bissau].

Three species of the Anopheles gambiae complex were identified in Guinea Bissau (West Africa) by chromosomal analysis. They were An. melas, An. arabiensis and An. gambiae s.s. An melas was observed in coastal and insular zones of the study area as well as in areas where the rivers are tidal and brackish and bordered by mangroves. For this reason, the species occurs also in inland riverine localities such as Farim and Bissorà. An. arabiensis apparently occurs only in low numbers in a very limited inland area during the dry season. An gambiae s.s. was observed nearly everywhere in the study area. In the samples of An. melas three inversion polymorphisms occurred: one on the chromosomal arm 2R (2Rn) and two on the arm 3R (3Rc and 3Re). It was observed that the frequencies of the inverted arrangements 2Rn and 3Re were significantly higher in the islands as compared to the continental sampling localities. The An. arabiensis sample was characterized by the presence of three inversion polymorphisms: 2Ra, 2Rb and 3Ra. A very high degree of polymorphism was shown by the An. gambiae s.s. samples. Four inversion polymorphisms were observed (three on chromosomal arm 2R and one on arm 2L) with very different frequencies of the alternative arrangements in different zones of the study area. From these data it seemed possible to split the species into three populations, each of them apparently linked with a peculiar ecological situation. The first population, characterized by high frequencies of 2Rd arrangement, is present on the coastal zones and in the islands; the second one is present in the northern inland areas particularly during the dry season and it is characterized by high frequencies of 2Rb and 2La arrangements. The third population is present only in the inland zones and it is characterized by high frequencies of 2Rjb, 2Rjd and 2Rjbd arrangements.
Utilization of ribonucleotides and RNA primers by Tetrahymena telomerase.

Telomerase is a ribonucleoprotein (RNP) DNA polymerase involved in telomere synthesis. A short sequence within the telomerase RNA component provides a template for de novo addition of the G‐rich strand of a telomeric simple sequence repeat onto chromosome termini. In vitro, telomerase can elongate single‐stranded DNA primers processively: one primer can be extended by multiple rounds of template copying before product dissociation. Telomerase will incorporate dNTPs or ddNTPs and will elongate any G‐rich, single‐stranded primer DNA. In this report, we show that Tetrahymena telomerase was able to incorporate a ribonucleotide, rGTP, into product polynucleotide. Synthesis of the product [d(TT)r(GGGG)]n was processive, suggesting that the chimeric product remained associated with the enzyme both at the active site and at a second, previously characterized, template‐independent product binding site. As predicted by this finding, RNA‐containing oligonucleotides served as primers for elongation. More than 3 nt of RNA at a primer 3′ end decreased the quantity of product synthesis but increased the affinity of the primer for telomerase. Thus, RNA‐containing primers were effective as competitive inhibitors of DNA primer elongation by telomerase. These results support the possible evolutionary origin of telomerase as an RNA‐dependent RNA polymerase.
Examining the effects of customer service management (CSM) on perceived business performance via structural equation modelling

Structural equation modelling (SEM) is a useful multivariate technique to investigate the causal relationships between variables. This paper uses SEM to model the relationships between critical success factors (CSFs) of business process reengineering (BPR) implementations, customer service management (CSM) and perceived business performance (PBP) in Malaysian banking institutions. SEM results show that Management Competence has significant positive effects on PBP and CSM. Information technology (IT) infrastructure capabilities has significant effects on CSM but statistically insignificant (but positive) effect on PBP. Similarly Effective Process Redesign has statistically insignificant (but positive) effect on CSM and PBP. Results also show that CSM has a positive and significant association with PBP. Copyright © 2006 John Wiley & Sons, Ltd.
PAX3 across the spectrum: from melanoblast to melanoma

The PAX3 transcription factor is critical for the proper development of neural crest lineages including melanocytes. These cells show continued PAX3 expression from formation to differentiation. While many expression, misexpression and mutation studies clarify the importance of PAX3 in melanocyte development, less well understood, and more perplexing, is the continued PAX3 expression in the adult skin. In this article we explore the multiple roles of PAX3 in melanocyte genesis, and draw on evidence from expression in developing melanoblasts, adult melanocytes and melanocyte stem cells. From this, we present a more encompassing theory that PAX3 is a key regulator of the myriad steps in melanocytic cell determination. These roles may be accomplished by differential association with cofactors, via alternate transcripts or posttranslational protein modification(s). In light of the plethora of information gleaned from development we then consider its roles in melanoma and provide here a comprehensive consideration of the significance of PAX3 expression in melanoma. PAX3 and Pax3 indicate human and mouse transcription factors respectively.
UHF and SHF Fading Analysis Using Wavelets in Tunnel Environments

The propagation of electromagnetic waves in tunnel- like environments differs from other scenarios, basically because tunnels can act as a waveguide, allowing the communication range to be extended. Nevertheless, phenomena such as strong fadings appear. In this context, our research group has been performing multi-robot navigation under communication constraints in this kind of environments. It is clear that fadings greatly affect communication among robots, and an in-depth study of these phenomena is required. In this paper, we present the results of a measuring campaign carried out in the Somport tunnel (in Spain) at 433 MHz, 868 MHz, 2.4 GHz and 5.2 GHz. Slow and fast fadings, as well as near and far sectors are analyzed using wavelets, a tool never used before to study propagation in tunnels. Results obtained from the wavelets and from classic filtering techniques are compared, showing that the former have the advantage of condensing most of the useful and valid information in a single graph.
The distribution of Belbin team roles among UK managers

Ascertains the preferred team roles of a substantial sample of UK managers using Belbin’s model. Finds that co‐ordinators and resource investigators are present in great numbers, but few completers, monitor evaluators, plants and shapers are encountered. Highlights the significance of this finding for firms seeking to create balanced and, hopefully, optimally‐structured teams. Adduces some evidence for the validity of the Belbin team role construct.
Helicobacter pylori and Gastric Cancer: Factors That Modulate Disease Risk

SUMMARY Helicobacter pylori is a gastric pathogen that colonizes approximately 50% of the world's population. Infection with H. pylori causes chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. Infection with H. pylori is the strongest known risk factor for gastric cancer, which is the second leading cause of cancer-related deaths worldwide. Once H. pylori colonizes the gastric environment, it persists for the lifetime of the host, suggesting that the host immune response is ineffective in clearing this bacterium. In this review, we discuss the host immune response and examine other host factors that increase the pathogenic potential of this bacterium, including host polymorphisms, alterations to the apical-junctional complex, and the effects of environmental factors. In addition to host effects and responses, H. pylori strains are genetically diverse. We discuss the main virulence determinants in H. pylori strains and the correlation between these and the diverse clinical outcomes following H. pylori infection. Since H. pylori inhibits the gastric epithelium of half of the world, it is crucial that we continue to gain understanding of host and microbial factors that increase the risk of developing more severe clinical outcomes.
Extending Model-based Policy Gradients for Robots in Heteroscedastic Environments

In this paper, we consider the problem of learning robot control policies in heteroscedastic environments, whose noise properties vary throughout a robot’s state and action space. We consider reinforcement learning algorithms that evaluate policies using learned models of the environment, and we extend this class of algorithms to capture heteroscedastic effects with two enchained Gaussian processes. We explore the capabilities and limitations of this approach, and demonstrate that it reduces model bias across a variety of simulated robotic systems.
Loss of Tuberous Sclerosis Complex 2 (TSC2) Is Frequent in Hepatocellular Carcinoma and Predicts Response to mTORC1 Inhibitor Everolimus

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and hyperactivation of mTOR signaling plays a pivotal role in HCC tumorigenesis. Tuberous sclerosis complex (TSC), a heterodimer of TSC1 and TSC2, functions as a negative regulator of mTOR signaling. In the current study, we discovered that TSC2 loss-of-function is common in HCC. TSC2 loss was found in 4 of 8 HCC cell lines and 8 of 28 (28.6%) patient-derived HCC xenografts. TSC2 mutations and deletions are likely to be the underlying cause of TSC2 loss in HCC cell lines, xenografts, and primary tumors for most cases. We further demonstrated that TSC2-null HCC cell lines and xenografts had elevated mTOR signaling and, more importantly, were significantly more sensitive to RAD001/everolimus, an mTORC1 inhibitor. These preclinical findings led to the analysis of TSC2 status in HCC samples collected in the EVOLVE-1 clinical trial of everolimus using an optimized immunohistochemistry assay and identified 15 of 139 (10.8%) samples with low to undetectable levels of TSC2. Although the sample size is too small for formal statistical analysis, TSC2-null/low tumor patients who received everolimus tended to have longer overall survival than those who received placebo. Finally, we performed an epidemiology survey of more than 239 Asian HCC tumors and found the frequency of TSC2 loss to be approximately 20% in Asian HBV+ HCC. Taken together, our data strongly argue that TSC2 loss is a predictive biomarker for the response to everolimus in HCC patients. Mol Cancer Ther; 14(5); 1224–35. ©2015 AACR.
Distinct localization of histone H3 methylation in the vegetative nucleus of lily pollen

We analysed the distribution of histone H3 modifications in the nucleus of the vegetative cell (the vegetative nucleus) during pollen development in lily (Lilium longiflorum). Among the modifications specifically and/or abundantly present in the vegetative nucleus, dimethylation of histone H3 at lysine 9 (H3K9me2) and lysine 27 (H3K27me2) were found in heterochromatin, whereas trimethylation of histone H3 at lysine 27 (H3K27me3) was localized in euchromatin in the vegetative nucleus. Such unique localization of the histone H3 methylation marks, particularly of H3K27me3, within a nucleus was not observed in lily nuclei other than the vegetative nucleus. The level of H3K27me3 increased in the euchromatic region of the vegetative nucleus during pollen maturation. The results suggest that H3K27me3 controls the gene expression of the vegetative cell during pollen maturation.
Comparison of Rambach agar, SM-ID medium, and Hektoen Enteric agar for primary isolation of non-typhi salmonellae from stool samples

Stool samples (n = 504) were streaked simultaneously onto Rambach agar (R agar; E. Merck, Darmstadt, Germany), SM-ID medium (bioMérieux S.A., Montalieu-Vercieu, France), and Hektoen Enteric (HE) agar (BBL Becton-Dickinson, Baltimore, Md.) in order to evaluate the performances of the first two media in comparison with that of the well-established HE agar. Following overnight cultivation at 37 degrees C, 29 samples (5.8%) were positive for non-typhi salmonellae on at least one of the three media. Sensitivities and specificities were 69 and 98%, 79 and 85%, and 100 and 79% for R, SM-ID, and HE agars, respectively. On the basis of the poor sensitivities, R and SM-ID agars are not recommended as primary plating media when screening for non-typhi salmonellae. However, the high specificity of R agar may help to reduce the work load when this medium is used for plating after enrichment.
Relationship between Competitive Intensity, Internal Resources and Firm Performance: Evidence from Indian ITES Industry

The purpose of this article is to investigate how competitive intensity impacts the relationship between crucial firm resources (human capital, organizational capital, management capability) and firm performance. Using a sample of 105 service providers from the Indian Information Technology-Enabled Services (ITES) industry, I find that competitive intensity positively moderates the relationship between firm resources and firm performance such that the relationships become stronger when competitive intensity is high than when it is low. Results imply that top managers’ evaluation of the performance implications of internal firm resources are significantly shaped by the perceptions of intensity of competition encountered by their firms.