Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and mechanistic analysis of the membrane-embedded glycosyltransferase WaaA required for lipopolysaccharide synthesis

WaaA is a key enzyme in the biosynthesis of LPS, a critical component of the outer envelope of Gram-negative bacteria. Embedded in the cytoplasmic face of the inner membrane, WaaA catalyzes the transfer of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) to the lipid A precursor of LPS. Here we present crystal structures of the free and CMP-bound forms of WaaA from Aquifex aeolicus, an ancient Gram-negative hyperthermophile. These structures reveal details of the CMP-binding site and implicate a unique sequence motif (GGS/TX5GXNXLE) in Kdo binding. In addition, a cluster of highly conserved amino acid residues was identified which represents the potential membrane-attachment and acceptor-substrate binding site of WaaA. A series of site-directed mutagenesis experiments revealed critical roles for glycine 30 and glutamate 31 in Kdo transfer. Our results provide the structural basis of a critical reaction in LPS biosynthesis and allowed the development of a detailed model of the catalytic mechanism of WaaA.
Surgical Treatment of Developmental Dysplasia of the Hip in Adults: I. Nonarthroplasty Options

&NA; Hip dysplasia is a developmental disorder that results in anatomic abnormalities leading to increased contact pressure in the joint and, eventually, coxarthrosis. However, many patients with hip dysplasia become symptomatic before the development of severe degenerative changes because of abnormal hip biomechanics, mild hip instability, impingement, or associated labral pathology. Several nonarthroplasty treatment options are available. Because the primary deformity is mostly acetabular, for many patients, a reconstructive osteotomy that restores more nearly normal pelvic anatomy is preferable. The Bernese periacetabular osteotomy is presently favored because it provides good correction while creating little secondary pelvic deformity or destabilizing the pelvis. Proximal femoral osteotomy is occasionally needed as a complement to pelvic osteotomy and may also be indicated as an isolated procedure when most deformity is located on the femoral side (coxa valga subluxans). Arthroscopy can be beneficial when symptoms seem to be related only to labral tears or loose bodies in the absence of severe structural abnormalities about the hip. Fusion and resection arthroplasty are rarely indicated and are reserved for occasional patients who are not candidates for total hip replacement or other procedures but who complain of refractory hip pain.
Vaginal Yeast Colonization in Nonpregnant Women: A Longitudinal Study

OBJECTIVE: We sought to investigate the prevalence and risk factors for vaginal yeast colonization over a 1-year period. METHODS: We conducted a longitudinal cohort study of 1,248 asymptomatic young women by collecting demographic and behavioral data at baseline, 4, 8, and 12 months. RESULTS: Seventy percent of women were colonized by vaginal yeast at one or more visits, but only 4% were colonized at all 4 visits. Using an adjusted generalized estimating equation model, factors associated with vaginal yeast colonization were marijuana use in the previous 4 months, depomedroxyprogesterone acetate use in the past 4 months, sexual intercourse in the previous 5 days, and concurrent colonization with lactobacilli and group B streptococcus. Symptoms of pruritus and vulvovaginal burning were associated with yeast colonization, but antifungal use was not. CONCLUSION: Recent sexual intercourse and use of injection contraceptives are risk factors for yeast colonization. Rates of antifungal use did not show an association with yeast colonization. The reporting of antifungal use by women lacking yeast colonization suggests that self-diagnosis is inaccurate. LEVEL OF EVIDENCE: II-2
Overexpression of Wild-Type Aspartokinase Increases l-Lysine Production in the Thermotolerant Methylotrophic Bacterium Bacillus methanolicus

ABSTRACT Aspartokinase (AK) controls the carbon flow into the aspartate pathway for the biosynthesis of the amino acids l-methionine, l-threonine, l-isoleucine, and l-lysine. We report here the cloning of four genes (asd, encoding aspartate semialdehyde dehydrogenase; dapA, encoding dihydrodipicolinate synthase; dapG, encoding AKI; and yclM, encoding AKIII) of the aspartate pathway in Bacillus methanolicus MGA3. Together with the known AKII gene lysC, dapG and yclM form a set of three AK genes in this organism. Overexpression of dapG, lysC, and yclM increased l-lysine production in wild-type B. methanolicus strain MGA3 2-, 10-, and 60-fold (corresponding to 11 g/liter), respectively, without negatively affecting the specific growth rate. The production levels of l-methionine (less than 0.5 g/liter) and l-threonine (less than 0.1 g/liter) were low in all recombinant strains. The AK proteins were purified, and biochemical analyses demonstrated that they have similar Vmax values (between 47 and 58 μmol/min/mg protein) and Km values for l-aspartate (between 1.9 and 5.0 mM). AKI and AKII were allosterically inhibited by meso-diaminopimelate (50% inhibitory concentration [IC50], 0.1 mM) and by l-lysine (IC50, 0.3 mM), respectively. AKIII was inhibited by l-threonine (IC50, 4 mM) and by l-lysine (IC50, 5 mM), and this enzyme was synergistically inhibited in the presence of both of these amino acids at low concentrations. The correlation between the impact on l-lysine production in vivo and the biochemical properties in vitro of the individual AK proteins is discussed. This is the first example of improving l-lysine production by metabolic engineering of B. methanolicus and also the first documentation of considerably increasing l-lysine production by overexpression of a wild-type AK.
Cooperative algorithms for solving random-dot stereograms

This report examines a number of parallel . algorithms for solving random-dot stereograms. A new class of algorithms based on the Boltzmann Machine is introduced and compared to previously developed algorithms. The report includes a review of the stereo correspondence problem and of cooperative techniques for solving this problem. The use of energy functions for characterizing the computational problem, and the use of stochastic optimization techniques for solving the problem are explained.
Comparative genomics of Synechococcus and proposal of the new genus Parasynechococcus

Synechococcus is among the most important contributors to global primary productivity. The genomes of several strains of this taxon have been previously sequenced in an effort to understand the physiology and ecology of these highly diverse microorganisms. Here we present a comparative study of Synechococcus genomes. For that end, we developed GenTaxo, a program written in Perl to perform genomic taxonomy based on average nucleotide identity, average amino acid identity and dinucleotide signatures, which revealed that the analyzed strains are drastically distinct regarding their genomic content. Phylogenomic reconstruction indicated a division of Synechococcus in two clades (i.e. Synechococcus and the new genus Parasynechococcus), corroborating evidences that this is in fact a polyphyletic group. By clustering protein encoding genes into homologue groups we were able to trace the Pangenome and core genome of both marine and freshwater Synechococcus and determine the genotypic traits that differentiate these lineages.
Beyond the Hype

Colloquium in Oxford. A wide‐ranging debate about the impact of the new technologies of connectivity on Higher Education, libraries, and the publishing industry took place in the ‘parliamentary’ debating chamber of the Oxford Union on Thursday 23rd April. The event was organized by the Oxford University Computing Services Humanities Computing Unit, and was entitled ‘Beyond the Hype’. The one‐day colloquium, which was attended by about one hundred and twenty people, was the fourth in a series of colloquia hosted by the Humanities Computing Unit. In 1995 the Unit kicked the series off with the first event, entitled ‘Beyond the Book’, which appeared, paradoxically enough, in printed form (eds. Chernaik, Deegan, and Gibson, Oxford: OHC, 7, 1996). They followed this up with a look at teaching in ‘Beyond the Classroom’ (a report of which can be found on the Web at http://info.ox.ac.uk/oucs/humanities/events/beyond/). In 1997 the Unit targeted the library sector with ‘Beyond the Library’ (again a report of which can be found on the Web at http://info.ox.ac.uk/oucs/humanities/events/beyond/).
Signifying the pandemics: metaphors of AIDS, cancer, and heart disease.

This article offers a symbolic analysis of the cultural construction and signification of three of the major "pandemics" of the late 20th century: AIDS, cancer, and heart disease. It is based on unstructured interviews conducted in Israel between 1993-94 with 75 nurses and 40 physicians and between 1993-95 with 60 university students. Two key symbols, "pollution" and "transformation," are shown to constitute AIDS and cancer within a symbolic space that I suggest is "beyond culture," where body boundaries are dissolved and cultural categories are dismantled. Heart disease, in contrast, is metaphorized as a defect in the "body machinery. " The article concludes by arguing that heart attack is depicted as the pathology of the Fordist, modernist body, while AIDS/cancer are pathologies of the postmodern body in late capitalism.
The Mithramycin Gene Cluster of Streptomyces argillaceus Contains a Positive Regulatory Gene and Two Repeated DNA Sequences That Are Located at Both Ends of the Cluster

ABSTRACT Sequencing of a 4.3-kb DNA region from the chromosome ofStreptomyces argillaceus, a mithramycin producer, revealed the presence of two open reading frames (ORFs). The first one (orfA) codes for a protein that resembles several transport proteins. The second one (mtmR) codes for a protein similar to positive regulators involved in antibiotic biosynthesis (DnrI, SnoA, ActII-orf4, CcaR, and RedD) belonging to the Streptomycesantibiotic regulatory protein (SARP) family. Both ORFs are separated by a 1.9-kb, apparently noncoding region. Replacement of themtmR region by an antibiotic resistance cassette completely abolished mithramycin biosynthesis. Expression of mtmR in a high-copy-number vector in S. argillaceus caused a 16-fold increase in mithramycin production. The mtmR gene restored actinorhodin production in Streptomyces coelicolor JF1 mutant, in which the actinorhodin-specific activator ActII-orf4 is inactive, and also stimulated actinorhodin production byStreptomyces lividans TK21. A 241-bp region located 1.9 kb upstream of mtmR was found to be repeated approximately 50 kb downstream of mtmR at the other end of the mithramycin gene cluster. A model to explain a possible route for the acquisition of the mithramycin gene cluster by S. argillaceus is proposed.
Chitosan–kaolin coprecipitate as disintegrant in microcrystalline cellulose-based pellets elaborated by extrusion–spheronization

The usefulness of a coprecipitate of chitosan and kaolin as disintegrant in the pellets of microcrystalline cellulose (MCC) and hydrochlorothiazide (HCT) (as a model of poorly water-soluble drug) produced by extrusion–spheronization was evaluated in this study. The effectiveness of chitosan–kaolin coprecipitate to increase the dissolution rate was compared with that of kaolin and chitosan. A possible synergy effect was also evaluated between the coprecipitate, kaolin or chitosan and sorbitol, added to the pellets as a very water-soluble diluent. The chitosan–kaolin coprecipitate, the kaolin or the chitosan allowed pellets to be obtained of adequate size, roundness, mechanical strength and flow properties. Furthermore, the incorporation of chitosan–kaolin coprecipitate or chitosan significantly increased the dissolution rate of HCT independently of the sorbitol content. The effects on the dissolution of HCT derived from the incorporation of coprecipitate to the pellets can be attributed to its content of chitosan. However, the addition of kaolin into the pellets did not significantly affect the HCT dissolution process. The pellets incorporating coprecipitated chitosan–kaolin or chitosan and the maximum proportion of sorbitol (50%) led to the highest HCT dissolution rate and experienced a rapid and complete disintegration in the dissolution medium.
Multi-camera Topology Recovery using Lines

We present a topology estimation approach for a system of single view point (SVP) cameras using lines. Images captured by SVP cameras such as perspective, central catadioptric or fisheye cameras are mapped to spherical images using the unified projection model. We recover the topology of a multiple central camera setup by rotation and translation decoupling. The camera rotations are first recovered from vanishing points of parallel lines. Next, the translations are estimated from known rotations and line projections in spherical images. The proposed algorithm has been validated on simulated data and real images from perspective and fisheye cameras. This vision-based approach can be used to initialize an extrinsic calibration of a hybrid camera network.
Acoustic and visual survey of manganese crusts using an underwater vehicle at #5 Takuyo seamount

This paper describes acoustic and visual instruments developed to perform high resolution surveys of manganese crusts. The instruments consist of an acoustic device developed to perform in situ measurements of manganese crust thickness at depths of up to 3000m, and a vision based mapping system that generates three-dimensional colour reconstructions of the sea floor. The developed systems operate at low altitudes, using an underwater platform such as an autonomous underwater vehicle (AUV) or remotely operated vehicle (ROV) to maintain a close range to the sea floor. In this communication, the authors describe the acoustic probe and vision based mapping system together with the algorithms that have been implemented to process the data they obtain, and present some results from sea trials performed using the ROV Hyper-Dolphin of JAMSTEC during the NT10–11 cruise of the R/V Natsushima at #5 Takuyo seamount. During the survey, the ROV was operated at depths of between 1000 and 3000 m at low altitudes of <1.0m, with surge velocities of between 0.4 to 0.6 knots to survey the area both acoustically and visually. The results are the first time in situ measurements of manganese crust thickness have been successfully performed, and demonstrate that the proposed instruments are useful tools to enable more efficient surveys of manganese crusts.
Self-assessed health, reference levels and mortality

The article studies the relationship between self-assessed health (SAH) and subsequent mortality in the German Socio-Economic Panel. Specifically, I examine whether socio-economic characteristics of respondents have an effect on mortality, conditional on SAH. Such conditional effects are shown to exist for various covariates, including age, income and wealth. These findings question the comparability of SAH across different socio-economic groups.
Blood Rheology Aspects of the Microcirculation

To elucidate the basis for the drop in pressure from large artery to vein, Jean Leonard Marie Poiseuille (1797-1869) undertook a series of seminal studies that defined the laws of fluid flow in tubes of uniform cross-section and that identified the microcirculation as the major site of the resistance to flow [1, 2]. While best known for his meticulous experimental studies of viscous flow in glass tubes [2], he also made numerous observations in the mesentery of the frog and other microvascular preparations; these observations served to highlight the dynamics of red cell distribution, the presence of the annular plasma layer and the “skimming” of plasma by capillaries, and the adhesion of white cells to the endothelium of post-capillary venules [3]. Yet it wasn’t until almost a century later that physiologists began to methodically explore the resistance to flow within the microcirculation proper using techniques of intravital microscopy. Landis [4] pioneered many quantitative methods for describing microvascular structure and function. Using finely drawn pipettes inserted into microvessels of frog mesentery, and calculating the velocity of bolus infusions of dyes through successive microvascular divisions, Landis attempted to calculate the resistance to flow within the capillary network and concluded that Poiseulle’s law cannot be applied to the flow of blood through the capillary network except in a very limited sense. However, with the advent of sophisticated instruments for measurement of capillary pressure [5, 6] and red blood cell velocity [7], relatively precise quantitative measurements of pressure drops [8] and flow rates [9, 10] could be obtained; such measurements thus provided direct in situ flow resistance data for the hierarchy of microvessels from arteriole to venule [11]. As shown in Figure 1, measurements of pressure drops and flows in single unbranched microvessels [11] reveal that over the broad range of diameters (D) within the microcirculation proper, Poiseuille’s fourth power relationship (i.e., resistance varies inversely with D) far overshadows other determinants of resistance in the normal flow state. The significance of this relationship cannot be understated in light of the fact that control and regulation of microvascular blood flow is manifest by the ability of the vascular system to alter resistance in response to vasomotor adjustments. However, striking departures from Poiseuille’s relationship may dictate the outcome of
A Comparison of Very Fast to Very Slow Components in Degradation and Recovery Due to NBTI and Bulk Hole Trapping to Existing Physical Models

A new measuring technique with a 1mus measuring delay and a direct VT determination has been employed. The response to stress times as short as 100 mus to 105 has been studied as well as recovery over 12 decades in time. These experimental data allow a meaningful comparison to theory. Degradation data cut be precisely fitted to a simple physical model with 3 parameters thus enabling a reliable lifetime prediction from stress times below 104s.
A way of increasing stability margin of current control in VSCs connected to the grid through LCL filters

VSCs connected to the grid through LCL filters are common in the integration of renewable energies into electrical systems. Therefore, in this paper small signal stability of the current loop of this configuration is performed. The analysis includes the getting of a state-space representation of the system, the calculation of their eigenvalues and the sensitivity analysis to the variation of some relevant parameters. Real-time simulations have also been carried out in order to validate the theoretical analysis.
Are the available low-molecular-weight heparin preparations the same?

Low molecular weight heparins (LMWHs) are now universally accepted as drugs of choice for post-surgical prophylaxis of DVT. Currently these agents are also being developed for therapeutic and cardiovascular indications. Because of manufacturing differences, each of the LMWHs exhibit distinct pharmacologic and biochemical profiles. The specific activity of these agents in the anticoagulant assays ranges from 35 to 45 anti-IIa U/mg whereas the specific activity in terms of anti-Xa units is designated as 80 to 120 anti-Xa U/mg. These LMWHs are capable of producing product specific dose and time dependent antithrombotic effects in animal models of thrombosis. While the ex vivo effects are initially present at dosages that are antithrombotic, these agents have been found to produce sustained antithrombotic effects without any detectable ex vivo anticoagulant actions. In the experimental animal models and in various clinical trials, these agents have also been found to release tissue factor pathway inhibitor (TFPI) after both intravenous (i.v.) and subcutaneous (s.c.) administration. Repeated administration of LMWHs produces progressively stronger antithrombotic effects; however, the hemorrhagic responses vary and are largely dependent on products. The release of TFPI following i.v. and s.c. administration in a primate model also demonstrated the product individuality and the relevance of this inhibitor to the actions of LMWHs. The effect of repeated administration mimicking the post-surgical prophylaxis of DVT also exhibited product based augmentation of the antithrombotic or hemorrhagic effects. Antithrombotic and hemorrhagic studies are reported that compare the pharmacologic profile of some of the available LMWHs. Product individuality in terms of relative potency in different assays and the failure of standardization protocols to provide any guidelines for product substitution and prediction of the clinical effects is also addressed.
Analytical Aspects of the Implementation of Biomarkers in Clinical Transplantation

Abstract: In response to the urgent need for new reliable biomarkers to complement the guidance of the immunosuppressive therapy, a huge number of biomarker candidates to be implemented in clinical practice have been introduced to the transplant community. This includes a diverse range of molecules with very different molecular weights, chemical and physical properties, ex vivo stabilities, in vivo kinetic behaviors, and levels of similarity to other molecules, etc. In addition, a large body of different analytical techniques and assay protocols can be used to measure biomarkers. Sometimes, a complex software-based data evaluation is a prerequisite for appropriate interpretation of the results and for their reporting. Although some analytical procedures are of great value for research purposes, they may be too complex for implementation in a clinical setting. Whereas the proof of “fitness for purpose” is appropriate for validation of biomarker assays used in exploratory drug development studies, a higher level of analytical validation must be achieved and eventually advanced analytical performance might be necessary before diagnostic application in transplantation medicine. A high level of consistency of results between laboratories and between methods (if applicable) should be obtained and maintained to make biomarkers effective instruments in support of therapeutic decisions. This overview focuses on preanalytical and analytical aspects to be considered for the implementation of new biomarkers for adjusting immunosuppression in a clinical setting and highlights critical points to be addressed on the way to make them suitable as diagnostic tools. These include but are not limited to appropriate method validation, standardization, education, automation, and commercialization.
Providing FAQ lists based on ontology

Researchers have been fascinated in FAQ (Frequently Asked Questions) management systems in recent years. These systems have reduced the cost of supporting productions. The goal of this research is to implement a Persian FAQ generator in PC domain based on ontology. There are several steps for implementation. First, all slangs are converted into formal Persian phrases. Second, our proposed similarity method measures similarity between questions. After creating question similarity matrix, similar questions are gathered in the same clusters. FAQ lists are created based on clusters which have the most number of members. Evaluations indicates that our proposed similarity matrix generates the best results in comparison with Lin, MCS, and LSA matrices. Moreover, our proposed clustering method provides better results compared to hierarchical complete-linkage, hierarchical single-linkage, and Kmeans methods.