Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibiotic efficacy is linked to bacterial cellular respiration

Significance The global burden of antibiotic resistance has created a demand to better understand the basic mechanisms of existing antibiotics. Of significant interest is how antibiotics may perturb bacterial metabolism, and how bacterial metabolism may influence antibiotic activity. Here, we study the interaction of bacteriostatic and bactericidal antibiotics, the two major phenotypic drug classes. Interestingly, the two classes differentially perturb bacterial cellular respiration, with major consequences for their intrinsic activity both alone and in combination. Of note, bacteriostatic antibiotics decelerate cellular respiration, generating a metabolic state that is prohibitive to killing. Further, we show that the efficacy of bactericidal drugs can be improved by increasing basal respiration, and we identify a respiration-related drug target that potentiates the activity of bactericidal antibiotics. Bacteriostatic and bactericidal antibiotic treatments result in two fundamentally different phenotypic outcomes—the inhibition of bacterial growth or, alternatively, cell death. Most antibiotics inhibit processes that are major consumers of cellular energy output, suggesting that antibiotic treatment may have important downstream consequences on bacterial metabolism. We hypothesized that the specific metabolic effects of bacteriostatic and bactericidal antibiotics contribute to their overall efficacy. We leveraged the opposing phenotypes of bacteriostatic and bactericidal drugs in combination to investigate their activity. Growth inhibition from bacteriostatic antibiotics was associated with suppressed cellular respiration whereas cell death from most bactericidal antibiotics was associated with accelerated respiration. In combination, suppression of cellular respiration by the bacteriostatic antibiotic was the dominant effect, blocking bactericidal killing. Global metabolic profiling of bacteriostatic antibiotic treatment revealed that accumulation of metabolites involved in specific drug target activity was linked to the buildup of energy metabolites that feed the electron transport chain. Inhibition of cellular respiration by knockout of the cytochrome oxidases was sufficient to attenuate bactericidal lethality whereas acceleration of basal respiration by genetically uncoupling ATP synthesis from electron transport resulted in potentiation of the killing effect of bactericidal antibiotics. This work identifies a link between antibiotic-induced cellular respiration and bactericidal lethality and demonstrates that bactericidal activity can be arrested by attenuated respiration and potentiated by accelerated respiration. Our data collectively show that antibiotics perturb the metabolic state of bacteria and that the metabolic state of bacteria impacts antibiotic efficacy.
Responsive Microgels through RAFT-HDA Dynamic Covalent Bonding Chemistry

This paper developed a method for preparing ultrasound-responsive microgels based on reversible addition fragmentation chain transfer-hetero Diels–Alder (RAFT-HAD) dynamic covalent bonding. First, a styrene cross-linked network was successfully prepared by a Diels–Alder (DA) reaction between phosphoryl dithioester and furan using double-ended diethoxyphosphoryl dithiocarbonate (BDEPDF) for RAFT reagent-mediated styrene (St) polymerization, with a double-ended dienophile linker and copolymer of furfuryl methacrylate (FMA) and St as the dienophile. Subsequently, the microgel system was constructed by the HDA reaction between phosphoryl disulfide and furan groups using the copolymer of polyethylene glycol monomethyl ether acrylate (OEGMA) and FMA as the dienophore building block and hydrophilic segment and the polystyrene pro-dienophile linker as the cross-linker and hydrophobic segment. The number of furans in the dienophile chain and the length of the dienophile linker were regulated by RAFT polymerization to investigate the effects of the single-molecule chain functional group degree, furan/dithioester ratio, and hydrophobic cross-linker length on the microgel system. The prepared microgels can achieve the reversible transformation of materials under force responsiveness, and their preparation steps are simple and adaptive to various potential applications in biomedical materials and adaptive electrical materials.
Retailer-Supplier Flexible Commitments Contracts: A Robust Optimization Approach

We propose the use of robust optimization (RO) as a powerful methodology for multiperiod stochastic operations management problems. In particular, we study a two-echelon multiperiod supply chain problem, known as the retailer-supplier flexible commitment (RSFC) problem with uncertain demand that is only known to reside in some uncertainty set. We adopt a min-max criterion, whereby the cost function is minimized against the worst case demand occurrence. To solve the min-max RSFC problem we employ a recent extension of the RO method adapted to dynamic decision problems and known as the affinely adjustable robust counterpart (AARC) methodology. The AARC solution is tested by a large simulation study and found to provide excellent results.
A Clinical Practice Update on the Latest AAOS/ADA Guideline (December 2012) on Prevention of Orthopaedic Implant Infection in Dental Patients

The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA), along with 10 other academic associations and societies recently (December 2012) published their mutual clinical practice guideline “Prevention of Orthopaedic Implant Infection in Patients Undergoing Dental Procedures. ” This evidence-based guideline ,detailed in 325 pages, has three recommendations and substitutes the previous AAOS guideline. The new published clinical guideline is a protocol to prevent patients undertaking dental procedures from orthopaedic implant infection. The guideline is developed on the basis of a collaborative systematic review to provide practical advice for training clinicians, dentists and any qualified physicians who need to consider prevention of orthopaedic implant (prosthesis) infection in their patients. This systematic review found no explicit evidence of cause-and-effect relationship between dental procedures and periprosthetic joint infection (PJI). This LTTE wishes to present a vivid summary of AAOS/ADA clinical practice guideline as a clinical update and an academic implementation to inform and assist Iranian competent clinicians and dentists in the course of their treatment decisions, to enrich the value and quality of health care on the latest international basis.
Precise Haptic Device Co-Location for Visuo-Haptic Augmented Reality

Visuo-haptic augmented reality systems enable users to see and touch digital information that is embedded in the real world. PHANToM haptic devices are often employed to provide haptic feedback. Precise co-location of computer-generated graphics and the haptic stylus is necessary to provide a realistic user experience. Previous work has focused on calibration procedures that compensate the non-linear position error caused by inaccuracies in the joint angle sensors. In this article we present a more complete procedure that additionally compensates for errors in the gimbal sensors and improves position calibration. The proposed procedure further includes software-based temporal alignment of sensor data and a method for the estimation of a reference for position calibration, resulting in increased robustness against haptic device initialization and external tracker noise. We designed our procedure to require minimal user input to maximize usability. We conducted an extensive evaluation with two different PHANToMs, two different optical trackers, and a mechanical tracker. Compared to state-of-the-art calibration procedures, our approach significantly improves the co-location of the haptic stylus. This results in higher fidelity visual and haptic augmentations, which are crucial for fine-motor tasks in areas such as medical training simulators, assembly planning tools, or rapid prototyping applications.
A numerical representation of fracturing granular materials

This paper describes the computer algorithms used in a numerical simulation of the compression of an aggregate of crushable grains. It has been used in a model for the evolution of a granular medium under one-dimensional compression, in which the probability of fracture for individual particles is a function of applied stress, particle-size and co-ordination number. The information relating to the particles is represented in a compact way on the computer which allows the number of particles produced to become sufficiently large for satisfactory comparisons to be made with experimental data and which allows information, such as the positions and sizes of the particles, to be easily extracted. An algorithm based on the representation is used to locate neighbouring particles in a way which does not deteriorate unacceptably in terms of speed as the number of particles increases. © 1997 by John Wiley & Sons, Ltd.
The Nemours database of dysarthric speech

The Nemours database is a collection of 814 short nonsense sentences; 74 sentences spoken by each of 11 male speakers with varying degrees of dysarthria. Additionally, the database contains two connected-speech paragraphs produced by each of the 11 speakers. The database was designed to test the intelligibility of dysarthric speech before and after enhancement by various signal processing methods, and is available on CD-ROM. It can also be used to investigate general characteristics of dysarthric speech such as production error patterns. The entire database has been marked at the word level and sentences for 10 of the 11 talkers have been marked at the phoneme level as well. The paper describes the database structure and techniques adopted to improve the performance of a Discrete Hidden Markov Model (DHMM) labeler used to assign initial phoneme labels to the elements of the database. These techniques may be useful in the design of automatic recognition systems for persons with speech disorders, especially when limited amounts of training data are available.
Food and time: dietary plasticity of different sources of a generalist insect herbivore

Abstract Painted lady butterflies (Vanessa cardui L., Nymphalidae) are generalist herbivores and serve as a model system across several fields of biology. While it has been demonstrated that V. cardui caterpillars can develop on different host plants, much of this work has been done on commercially sourced caterpillars, which could limit our understanding of wild V. cardui populations. In this study, we sought to explore possible differences in how commercial and wild V. cardui caterpillars may respond to feeding on different host plants, and subsequently, how their diet impacts immune response and survival. Here, we analyzed performance, survival, and immune response of wild and commercially sourced V. cardui caterpillars over several generations on diets that consisted of either 1 of 4 different host plant species or a mixed diet including all 4 species. Qualitatively, we observed that wild larvae had a better larval performance and hemocyte counts compared to the commercial larvae. The results demonstrate that both wild and commercially sourced caterpillars grew and survived best on the same diet treatments (mallow, narrowleaf plantain, and a mixed diet) during development across generations. Immune responses showed similar patterns across host plants between wild and commercial populations, with individuals showing lowered immune responses on dandelion and lupine and higher ones on mallow, plantain and the mixed diet; although the relative rankings on those 3 diets varied. Survival also demonstrated similar patterns, in that individuals reared on dandelion and lupine had the lowest survival.
CD4+ T Lymphocytes from Calves Immunized withAnaplasma marginale Major Surface Protein 1 (MSP1), a Heteromeric Complex of MSP1a and MSP1b, Preferentially Recognize the MSP1a Carboxyl Terminus That Is Conserved among Strains

ABSTRACT Native major surface protein 1 (MSP1) of the ehrlichial pathogenAnaplasma marginale induces protective immunity in calves challenged with homologous and heterologous strains. MSP1 is a heteromeric complex of a single MSP1a protein covalently associated with MSP1b polypeptides, of which at least two (designated MSP1F1 and MSP1F3) in the Florida strain are expressed. Immunization with recombinant MSP1a and MSP1b alone or in combination fails to provide protection. The protective immunity in calves immunized with native MSP1 is associated with the development of opsonizing and neutralizing antibodies, but CD4+ T-lymphocyte responses have not been evaluated. CD4+ T lymphocytes participate in protective immunity to ehrlichial pathogens through production of gamma interferon (IFN-γ), which promotes switching to high-affinity immunoglobulin G (IgG) and activation of phagocytic cells to produce nitric oxide. Thus, an effective vaccine for A. marginaleand related organisms should contain both T- and B-lymphocyte epitopes that induce a strong memory response that can be recalled upon challenge with homologous and heterologous strains. This study was designed to determine the relative contributions of MSP1a and MSP1b proteins, which contain both variant and conserved amino acid sequences, in stimulating memory CD4+ T-lymphocyte responses in calves immunized with native MSP1. Peripheral blood mononuclear cells and CD4+ T-cell lines from MSP1-immunized calves proliferated vigorously in response to the immunizing strain (Florida) and heterologous strains of A. marginale. The conserved MSP1-specific response was preferentially directed to the carboxyl-terminal region of MSP1a, which stimulated high levels of IFN-γ production by CD4+ T cells. In contrast, there was either weak or no recognition of MSP1b proteins. Paradoxically, all calves developed high titers of IgG antibodies to both MSP1a and MSP1b polypeptides. These findings suggest that in calves immunized with MSP1 heteromeric complex, MSP1a-specific T lymphocytes may provide help to MSP1b-specific B lymphocytes. The data provide a basis for determining whether selected MSP1a CD4+ T-lymphocyte epitopes and selected MSP1a and MSP1b B-lymphocyte epitopes presented on the same molecule can stimulate a protective immune response.
Emotion Detection using Lexical Chains

Emotion detection has become an indispensable task in Natural Language Processing (NLP) in recent times. Emotion detection has been done using various knowledge based and corpus based methods. In this paper, we propose a methodology for emotion detection using lexical chains. Lexical chains easily identify the coherent concepts present in the text and so the emotion detection is also done with much ease. We have handled six types of emotions namely happiness, sadness, anger, fear, disgust and surprise. We have evaluated our method with the existing methods and we have shown better performance. General Terms Emotion Detection, Sentiment Analysis
CYTOPLASMIC COMPONENTS IN HEPATIC CELL LYSOSOMES

De Duve and his colleagues, a few years ago, originated the concept of lysosomes based on the biochemical analysis of isolated cytoplasmic particles (1). He reported that a number of hydrolytic enzymes are concentrated in a fraction consisting of small subcellular units which sediments between the usual mitochondrial and microsomal fractions. Subsequent to this discovery, some of these properties have been demonstrated in hepatic pericanalicular dense bodies, and Essner and Novikoff (2), using the electron microscope, have shown that the enzyme product of acid phosphatase is found exclusively in these bodies. They have also found that a variety of pigment granules in human liver cells possess both the fine structure characteristic of dense bodies and the acid phosphatase activity of lysosomes (3). In this report we shall refer to polymorphic dense bodies which appear normally in peribiliary (or pericanalicular) positions in liver cells as lysosomes. This is in keeping with what is now the usual practice among cytologists. Admit tedly the identification would be more definite if parallel cytochemical studies had been done to determine the presence or absence of acid phosphatase and other acid hydrolases. The microbody, as distinct from the lysosome, is a cytoplasmic particle 0.4 to 0.6 micron in
The KACTUS View on the 'O' word

This paper describes the view taking in the ESPRIT project “KACTUS” on the notion of ontology. KACTUS is an application-driven project concerned with knowledge reuse in technical doamins. This paper discusses part of the theoretical background of the project. The use of the deﬁnitions of “ontology” and related terms is illustrated through an example in the VT elevator-design domain
A Novel Differential Privacy Approach that Enhances Classification Accuracy

In the recent past, there has been a tremendous increase of large repositories of data, examples being in healthcare data, consumer data from retailers, and airline passenger data. These data are continually being shared with interested parties, either anonymously -- for research purposes, or openly by financial or insurance companies, for decision-making purposes. When is shared anonymously, there is still the possibility of de-anonymizing the data. Privacy Preserving Data Publishing (PPDP) is a way to allow one to share secure data while ensuring protection against identity disclosure of an individual. Generalization of attributes is a technique of data anonymization where an attribute is replaced with a more generalized value. Differential privacy is a technique that ensures the highest level of privacy for a record owner while providing actual information about the data set. This research develops a framework by generalizing attributes of a data set that satisfy differential privacy principles for publishing secure data for sharing. The proposed algorithm is a non-interactive method to publish anonymize data set, and the decision tree classifier showed better results compared to other existing classification works on anonymized data set. In this paper differential privacy refers to ε-differential privacy.
Towards a taxonomy of network scanning techniques

Network scanning is a common reconnaissance activity in network intrusion. Despite this, it's classification remains vague and detection systems in current Network Intrusion Detection Systems are incapable of detecting many forms of scanning traffic. This paper presents a classification of network scanning and illustrates how complex and varied this activity is. The presented classification extends previous, well known, definitions of scanning traffic in a manner which reflects this complexity.
Evaluation of the impact of antibody fragments on aggregation of intact molecules via size exclusion chromatography coupled with native mass spectrometry

ABSTRACT Aggregates are recognized as one of the most critical product-related impurities in monoclonal antibody (mAb)-based therapeutics due to their negative impact on the stability and safety of the drugs. So far, investigational efforts have primarily focused on understanding the causes and effects of mAb self-aggregation, including both internal and external factors. In this study, we focused on understanding mAb stability in the presence of its monovalent fragment, formed through hinge cleavage and loss of one Fab unit (referred to as “Fab/c”), a commonly observed impurity during manufacturing and stability. The Fab/c fragments were generated using a limited IgdE digestion that specifically cleaves above the IgG1 mAb hinge region, followed by hydrophobic interaction chromatographic (HIC) enrichment. Two IgG1 mAbs containing different levels of Fab/c fragments were incubated under thermally accelerated conditions. A method based on size exclusion chromatography coupled with native mass spectrometry (SEC-UV-native MS) was developed and used to characterize the stability samples and identified the formation of heterogeneous dimers, including intact dimer, mAb-Fab/c dimer, Fab/c-Fab/c dimer, and mAb-Fab dimer. Quantitative analyses on the aggregation kinetics suggested that the impact of Fab/c fragment on the aggregation rate of individual dimer differs between a glycosylated mAb (mAb1) and a non-glycosylated mAb (mAb2). An additional study of deglycosylated mAb1 under 25°C accelerated stability conditions suggests no significant impact of the N-glycan on mAb1 total aggregation rate. This study also highlighted the power of SEC-UV-native MS method in the characterization of mAb samples with regard to separating, identifying, and quantifying mAb aggregates and fragments.
An Exponential Distribution Complex Network Model Constructed by Degree Sequence Length Iteration

Many real world complex networks possess exponential degree distribution with the characteristics of small length and self-similar. To better understand the formation mechanism of exponential distribution network, and make it more direct to reveal the change of degree sequence and the dynamic relationship among nodes in the process of network formation, we propose a deterministic iterative algorithm based on increasing degree sequence length and network self-replication and generate a complex network model. We analyze the main attributes of the network model by both theoretical derivation and numerical simulation. The simulation results are well consistent with the theoretical predictions and show that our network model has a low average distance, an arithmetic degree sequence and follows an exponential degree distribution.
Abnormal Features in Skeletal Muscle from Mice Lacking Mitsugumin29

Physiological roles of the members of the synaptophysin family, carrying four transmembrane segments and being basically distributed on intracellular membranes including synaptic vesicles, have not been established yet. Recently, mitsugumin29 (MG29) was identified as a novel member of the synaptophysin family from skeletal muscle. MG29 is expressed in the junctional membrane complex between the cell surface transverse (T) tubule and the sarcoplasmic reticulum (SR), called the triad junction, where the depolarization signal is converted to Ca2+ release from the SR. In this study, we examined biological functions of MG29 by generating knockout mice. The MG29-deficient mice exhibited normal health and reproduction but were slightly reduced in body weight. Ultrastructural abnormalities of the membranes around the triad junction were detected in skeletal muscle from the mutant mice, i.e., swollen T tubules, irregular SR structures, and partial misformation of triad junctions. In the mutant muscle, apparently normal tetanus tension was observed, whereas twitch tension was significantly reduced. Moreover, the mutant muscle showed faster decrease of twitch tension under Ca2+-free conditions. The morphological and functional abnormalities of the mutant muscle seem to be related to each other and indicate that MG29 is essential for both refinement of the membrane structures and effective excitation-contraction coupling in the skeletal muscle triad junction. Our results further imply a role of MG29 as a synaptophysin family member in the accurate formation of junctional complexes between the cell surface and intracellular membranes.
Unsupervised Learning of General-Specific Noun Relations from the Web

In this paper, we propose a new methodology based on d irected weighted graphs and the TextRank algorithm to automatically induce general-specific noun relations from web corpora frequency counts. Different asymmetric association measures are implemented to build the graphs upon which the TextRank algorithm is applied and produces an ordered list of nouns from the most general to the most specific. Experiments are conducted based on the WordNet noun hierarchy and a quantitative evaluation is proposed.