Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro and In Vivo Antibacterial Evaluation of Cadazolid, a New Antibiotic for Treatment of Clostridium difficile Infections

ABSTRACT Clostridium difficile is a leading cause of health care-associated diarrhea with significant morbidity and mortality, and new options for the treatment of C. difficile-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone-type antibiotic that is currently in clinical development for treatment of CDAD. Here, we report the in vitro and in vivo antibacterial evaluation of cadazolid against C. difficile. Cadazolid showed potent in vitro activity against C. difficile with a MIC range of 0.125 to 0.5 μg/ml, including strains resistant to linezolid and fluoroquinolones. In time-kill kinetics experiments, cadazolid showed a bactericidal effect against C. difficile isolates, with >99.9% killing in 24 h, and was more bactericidal than vancomycin. In contrast to metronidazole and vancomycin, cadazolid strongly inhibited de novo toxin A and B formation in stationary-phase cultures of toxigenic C. difficile. Cadazolid also inhibited C. difficile spore formation substantially at growth-inhibitory concentrations. In the hamster and mouse models for CDAD, cadazolid was active, conferring full protection from diarrhea and death with a potency similar to that of vancomycin. These findings support further investigations of cadazolid for the treatment of CDAD.
Multiple CO lines in SMM J16359+6612 -- Further evidence for a merger

Using the IRAM 30 m telescope, we report the detection of the CO(3–2), CO(4–3), CO(5–4) and CO(6–5) lines in the gravitational lensed submm galaxy SMM J16359+6612 at $z=2.5$. The CO lines have a double peak profile in all transitions. From a Gaussian decomposition of the spectra we show that the CO line ratios, and therefore the underlying physical conditions of the gas, are similar for the blue and the redshifted component. The CO line Spectral Energy Distribution (SED; i.e. flux density vs. rotational quantum number) turns over already at the CO 5–4 transition which shows that the molecular gas is less excited than in nearby starburst galaxies and high- z QSOs. This difference mainly arises from a lower average H 2 density, which indicates that the gas is less centrally concentrated than in nuclear starburst regions in local galaxies. We suggest that the bulk of the molecular gas in SMM J16359+6612 may arise from an overlap region of two merging galaxies. The low gas density and clear velocity separation may reflect an evolutionary stage of the merger event that is in between those seen in the Antennae and in the more evolved ultraluminous infrared galaxies (ULIRGs) like e.g. Mrk 231.
Long-Term Memory Updating: The Reset-of-Encoding Hypothesis in List-Method Directed Forgetting

People’s memory for new information can be enhanced by cuing them to forget older information, as is shown in list-method directed forgetting (LMDF). In this task, people are cued to forget a previously studied list of items (list 1) and to learn a new list of items (list 2) instead. Such cuing typically enhances memory for the list 2 items and reduces memory for the list 1 items, which reflects effective long-term memory updating. This review focuses on the reset-of-encoding (ROE) hypothesis as a theoretical explanation of the list 2 enhancement effect in LMDF. The ROE hypothesis is based on the finding that encoding efficacy typically decreases with number of encoded items and assumes that providing a forget cue after study of some items (e.g., list 1) resets the encoding process and makes encoding of subsequent items (e.g., early list 2 items) as effective as encoding of previously studied (e.g., early list 1) items. The review provides an overview of current evidence for the ROE hypothesis. The evidence arose from recent behavioral, neuroscientific, and modeling studies that examined LMDF on both an item and a list level basis. The findings support the view that ROE plays a critical role for the list 2 enhancement effect in LMDF. Alternative explanations of the effect and the generalizability of ROE to other experimental tasks are discussed.
Imported Intermediate Inputs and Domestic Product Growth: Evidence from India

New goods play a central role in many trade and growth models. We use detailed trade and firm-level data from India to investigate the relationship between declines in trade costs, imports of intermediate inputs, and domestic firm product scope. We estimate substantial gains from trade through access to new imported inputs. Moreover, we find that lower input tariffs account on average for 31% of the new products introduced by domestic firms. This effect is driven to a large extent by increased firm access to new input varieties that were unavailable prior to the trade liberalization.
Containment Problems for Polytopes and Spectrahedra

We study the computational question whether a given polytope or spectrahedron $S_A$ (as given by the positive semidefiniteness region of a linear matrix pencil $A(x)$) is contained in another one $S_B$. First we classify the computational complexity, extending results on the polytope/polytope-case by Gritzmann and Klee to the polytope/spectrahedron-case. For various restricted containment problems, NP-hardness is shown. We then study in detail semidefinite conditions to certify containment, building upon work by Ben-Tal, Nemirovski and Helton, Klep, McCullough. In particular, we discuss variations of a sufficient semidefinite condition to certify containment of a spectrahedron in a spectrahedron. It is shown that these sufficient conditions even provide exact semidefinite characterizations for containment in several important cases, including containment of a spectrahedron in a polyhedron. Moreover, in the case of bounded $S_A$ the criteria will always succeed in certifying containment of some scaled spectrahedron $\nu S_A$ in $S_B$.
Relationship between immune response to melanoma vaccine immunization and clinical outcome in stage II malignant melanoma

The authors investigated whether there was a relationship between the induction of a delayed‐type hypersensitivity (DTH) response to melanoma vaccine immunization and disease recurrence. They studied prospectively 94 evaluable patients with surgically resected Stage II malignant melanoma who were immunized to a partially purified, polyvalent, melanoma antigen vaccine. The DTH response to skin tests to the vaccine was measured before treatment and at the fourth vaccine immunization. Vaccine treatment induced a strong DTH response in 29 (31%) patients, an intermediate response in 24 (25%), and no response in 41 (44%). The median disease‐free survival (DFS) of patients with a strong, intermediate, and no DTH response to vaccine immunization was more than 72 months, 24 months, and 15 months, respectively. The relationship between an increase in the DTH response and a prolonged DFS was statistically significant (P = 0.02); clinically meaningful (the median DFS of patients with a strong DTH response was 4.7 years longer than that of nonresponders); and, by multivariate analysis, independent of disease severity or overall immune competence. These findings suggest, but do not prove, that vaccine treatment can slow the progression of melanoma in some patients.
Effect of Partial Martensite Transformation on Bainite Reaction Kinetics in Different 1%C Steels

Isothermal bainitizing of high carbon steel is used to obtain exceptionally high mechanical characteristics together with near zero distortion during heat-treating. Such heat-treatments are often carried out at temperatures close to but above the martensite start temperature, where transformation kinetics are unfortunately very sluggish. The formation of a small amount of martensite prior to isothermal holding is known to accelerate transformation kinetics. However, the influence of the amount transformed remains to clarify, and the consequence on final properties have not been explored. In the following, the influence of partial martensite formation on the kinetics of bainite formation is investigated in 100Cr6 (AISI 52100) and similar grades. It is shown that, although the formation of martensite allows for shorter heat-treatment durations, it does not seem to affect the bainite kinetics, inasmuch as the bainite formation kinetics after formation of X% martensite are identical to that which would be expected if the first X% transformation had been obtained through isothermal bainitic transformation.
Classification-based strategies for combining multiple 5-w question answering systems

We describe and analyze inference strategies for combining outputs from multiple question answering systems each of which was developed independently. Specifically, we address the DARPA-funded GALE information distillation Year 3 task of finding answers to the 5-Wh questions (who, what, when, where, and why) for each given sentence. The approach we take revolves around determining the best system using discriminative learning. In particular, we train support vector machines with a set of novel features that encode systems’ capabilities of returning as many correct answers as possible. We analyze two combination strategies: one combines multiple systems at the granularity of sentences, and the other at the granularity of individual fields. Our experimental results indicate that the proposed features and combination strategies were able to improve the overall performance by 22% to 36% relative to a random selection, 16% to 35% relative to a majority voting scheme, and 15% to 23% relative to the best individual system. Index Terms: Question answering, Systems for spoken language understanding
Analysis of Spike Electrogenesis of Eel Electroplaques with Phase Plane and Impedance Measurements

Eel electroplaques provide experimental conditions in which registration of phase plane trajectories (dV/dt vs. V) and impedance measurements with an AC Wheatstone bridge, in conjunction with spike electrogenesis describe quantitatively the ionic processes of the electrogenesis. Thus, these data employing as they do measurements of transients, permit an independent test of the validity of the assumptions which underlie the Hodgkin-Huxley equivalent circuit: independent ionic channels with fixed ionic batteries and exhibiting time-variant conductance changes with different kinetics for the different channels. The analysis accords with earlier findings on voltage-clamped electroplaques and this agreement confirms the validity of the equivalent circuit despite the fact that the current-voltage characteristics of the axons and electroplaques differ profoundly. As for squid axons, the equivalent circuit of the electroplaques has four branches: a capacity and three ionic channels. One of the latter is an invariant leak channel (GL) of high conductance. A K channel (G K) is fully open at rest, but rapidly undergoes inactivation when the cell is depolarized by more than 40 mv. GL and G K have a common inside negative emf (E K). A Na channel (G Na) with an inside positive emf (E Na) is closed at rest, but opens transiently upon depolarization.
Ridge push, mantle plumes and the speed of the Indian plate

SUMMARY The buoyancy of lithospheric slabs in subduction zones is widely thought to dominate the torques driving plate tectonics. In late Cretaceous and early Paleogene times, the Indian plate moved more rapidly over the mantle than freely subducting slabs sink within it. This signal event has been attributed to arrival of the Deccan-Rmantle plume beneath the plate, but itisunknowninwhichproportionstheplumeactedtoalterthebalanceofexistingplatedriving torques and to introduce torques of its own. Our plate kinematic analysis of the Mascarene Basin yields a detailed Indian plate motion history for the period 89-60Ma. Plate speed initially increases steadily until a pronounced acceleration in the period 68-64Ma, after which it abruptly returns to values much like those beforehand. This pattern is unlike that suggested to result from the direct introduction of driving forces by the arrival of a thermal plume at the base of the plate. A simple analysis of the gravitational force related to the Indian plate's thickening away from its boundary with the African plate suggests instead that the sudden acceleration and deceleration may be related to uplift of part of that boundary during a period when it was located over the plume head. In this instance, torques related to plate accretion and subduction may have contributed in similar proportions to drive plate motion.
Clinical presentation, complications and treatment of infection with verocytotoxin‐producing Escherichia coli. Challenges for the clinician

Seventeen years after its recognition, outbreaks and sporadic infections attributed to Escherichia coli O157 continue to increase. Acute gastrointestinal, and the systemic complications haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), are frequent and severe. Current challenges that face clinicians are the early recognition of infection, identification of risk factors for poor prognosis, determination of appropriate monitoring for the development of complications, establishment of a therapeutic strategy and, finally, advice for patients about their long‐term prognosis. Clinical features which, in combination, have been shown to distinguish E. coli O157 infection from other enteric pathogens are a history of bloody diarrhoea, visibly bloody stools, absence of fever, a leucocyte count greater than 10 × 109 1−1 and abdominal tenderness on physical examination. The most consistent risk factors for the development of HUS/TTP are the extremes of age and a raised leucocyte count. Bloody diarrhoea and ‘antimotility’ drugs are also likely to be important risk factors. Recent evidence from the central Scotland outbreak suggests that individuals who are taking drugs that reduce gastric acidity or antibiotics at the time of infection with E. coli O157, or who have a short incubation period, may also be at increased risk of progression to HUS/TTP. Clinical management, in particular the role of antibiotics in gastrointestinal infection, remains controversial, and retrospective assessment of the 1996 outbreaks from central Scotland and Japan only adds to this controversy. Therapeutic plasma exchange is a promising treatment for adults who develop HUS/TTP, but its role has yet to be determined definitively, either in a randomized controlled trial or by an international register of cases. Significant chronic sequelae of infection occur, particularly irritable bowel syndrome after uncomplicated gastrointestinal infection, and renal failure after HUS/TTP. Their frequency and severity are likely to become evident over the next decade.
DNA Binding by the Coliphage 186 Repressor Protein CI (*)

The cI gene of coliphage 186 maintains lysogeny and confers immunity to 186 infection by repressing the major early promoter, p, and the promoter for the late transcription activator gene, p. Gel mobility shift and DNase I footprinting show that CI protein binds to the DNA at p and p and also to sites 300 base pairs upstream and downstream of p, called FL and FR. Mutations which cause virulence reduce CI binding to p. The biochemical and genetic data identify three CI operators at p, two at p, and single operators at FL and FR. The operators at the p, FL, FR, and central p sites are inverted repeat sequences, separated by 5 base pairs (Type A) or, in the case of p, by 4 base pairs (Type A′). A different inverted repeat operator sequence (Type B) is proposed for the binding sites on each side of the central site at p. Thus, CI appears to recognize two distinct DNA sequences. CI binds cooperatively to adjacent operators, and binding at p is strongly dependent on these cooperative interactions. A high order CI multimer appears to be the active DNA binding species, even at single operators.
A Massive Local Rules Search Approach to the Classification Problem

An approach to the classification problem of machine learning, based on building local classification rules, is developed. The local rules are considered as projections of the global classification rules to the event we want to classify. A massive global optimization algorithm is used for optimization of quality criterion. The algorithm, which has polynomial complexity in typical case, is used to find all high--quality local rules. The other distinctive feature of the algorithm is the integration of attributes levels selection (for ordered attributes) with rules searching and original conflicting rules resolution strategy. The algorithm is practical; it was tested on a number of data sets from UCI repository, and a comparison with the other predicting techniques is presented.
Metabolic cross talk between the colon and the periphery: implications for insulin sensitivity

Until recently, a glance at a standard undergraduate textbook would have given the impression that the colon was merely a storage organ for faeces and maybe something about the absorption of electrolytes and water. In reality, the colon is a highly-metabolically-active organ, the function of which has implications not only for the remainder of the digestive tract, but also for peripheral organs such as adipose tissue (AT), liver and skeletal muscle. The present review focuses on two distinct but complementary areas: (1) the metabolic adaptation that occurs following surgical removal of colonic tissue; (2) the effect of modulating the colon in situ in terms of postprandial metabolism, insulin sensitivity and disease risk. Work in these two areas points to the colon being important in modulating normal tissue insulin sensitivity. The role of fatty acids is central to the insulin sensitivity hypothesis. AT acts as a daily ‘buffer’ for fatty acids. However, following colonic resection there is an apparent change in AT function. There is an increase in the AT lipolysis rate, resulting in the release of excess fatty acids into the circulation and consequently the take up of excess fatty acids into skeletal muscle. This resultant increase in either storage of lipid or its oxidation would result in a reduction in insulin sensitivity. The insulin-sensitising effects of high-fibre diets are also related to changes in AT function and fatty acid metabolism, but manipulating colonic tissue in situ allows the mechanisms to be elucidated. This research area is an exciting one, involving the potential role of SCFA (the absorbed by-products of colonic bacterial fermentation) acting directly on peripheral tissues, following the recent identification of G-protein-coupled receptors specific for these ligands.
Unique features of retrovirus expression in F/St mice

F/St mice are unique in producing high levels of both ecotropic and xenotropic murine leukemia virus. The high ecotropic virus phenotype is determined by three or more V (virus-inducing) loci. A single locus for inducibility of xenotropic murine leukemia virus was mapped to chromosome 1 close to, but possibly not allelic to, Bxv-1. Although the high ecotropic virus phenotype is phenotypically dominant, the high xenotropic virus phenotype was recessive in all crosses tested. Suppression of xenotropic murine leukemia virus is governed by a single gene which is not linked to the xenotropic V locus.
BLM and RMI1 Alleviate RPA Inhibition of TopoIIIα Decatenase Activity

RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIα complex. We investigated the effect of RPA on the ssDNA decatenase activity of topoisomerase IIIα. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIα. Complex formation between BLM, TopoIIIα, and RMI1 ablates inhibition of decatenation by ssDNA binding proteins. Together, these data indicate that inhibition by RPA does not involve species-specific interactions between RPA and BLM-TopoIIIα-RMI1, which contrasts with RPA modulation of double Holliday junction dissolution. We propose that topoisomerase IIIα and RPA compete to bind to single-stranded regions of catenanes. Interactions with BLM and RMI1 enhance toposiomerase IIIα activity, promoting decatenation in the presence of RPA.
Ego-motion recovery and robust tilt estimation for planar motion using several homographies

In this paper we suggest an improvement to a recent algorithm for estimating the pose and ego-motion of a camera which is constrained to planar motion at a constant height above the floor, with a constant tilt. Such motion is common in robotics applications where a camera is mounted onto a mobile platform and directed towards the floor. Due to the planar nature of the scene, images taken with such a camera will be related by a planar homography, which may be used to extract the ego-motion and camera pose. Earlier algorithms for this particular kind of motion were not concerned with determining the tilt of the camera, focusing instead on recovering only the motion. Estimating the tilt is a necessary step in order to create a rectified map for a SLAM system. Our contribution extends the aforementioned recent method, and we demonstrate that our enhanced algorithm gives more accurate estimates of the motion parameters.
SORTA: a system for ontology-based re-coding and technical annotation of biomedical phenotype data

There is an urgent need to standardize the semantics of biomedical data values, such as phenotypes, to enable comparative and integrative analyses. However, it is unlikely that all studies will use the same data collection protocols. As a result, retrospective standardization is often required, which involves matching of original (unstructured or locally coded) data to widely used coding or ontology systems such as SNOMED CT (clinical terms), ICD-10 (International Classification of Disease) and HPO (Human Phenotype Ontology). This data curation process is usually a time-consuming process performed by a human expert. To help mechanize this process, we have developed SORTA, a computer-aided system for rapidly encoding free text or locally coded values to a formal coding system or ontology. SORTA matches original data values (uploaded in semicolon delimited format) to a target coding system (uploaded in Excel spreadsheet, OWL ontology web language or OBO open biomedical ontologies format). It then semi- automatically shortlists candidate codes for each data value using Lucene and n-gram based matching algorithms, and can also learn from matches chosen by human experts. We evaluated SORTA’s applicability in two use cases. For the LifeLines biobank, we used SORTA to recode 90 000 free text values (including 5211 unique values) about physical exercise to MET (Metabolic Equivalent of Task) codes. For the CINEAS clinical symptom coding system, we used SORTA to map to HPO, enriching HPO when necessary (315 terms matched so far). Out of the shortlists at rank 1, we found a precision/recall of 0.97/0.98 in LifeLines and of 0.58/0.45 in CINEAS. More importantly, users found the tool both a major time saver and a quality improvement because SORTA reduced the chances of human mistakes. Thus, SORTA can dramatically ease data (re)coding tasks and we believe it will prove useful for many more projects. Database URL: http://molgenis.org/sorta or as an open source download from http://www.molgenis.org/wiki/SORTA
Activated factor VII–antithrombin complex predicts mortality in patients with stable coronary artery disease: a cohort study

Essentials Activated factor VII–antithrombin complex (FVIIa‐AT) in plasma may reflect tissue factor exposure. FVIIa‐AT levels were assessed in an angiographically controlled coronary artery disease (CAD) cohort. High FVIIa‐AT levels correlated with an increased thrombin generation. High FVIIa‐AT levels were associated with a greater risk of mortality in patients with stable CAD.