gebhart/patrepeval huggingface dataset:
Slippage synthesis of simple sequence DNA (1992)

The analysis of slippage synthesis of simple sequence DNA in vitro sheds some light on the question of how simple sequences arise in vivo. We show that it is possible to synthesize all types of repetitious di- and trinucleotide motifs starting from short primers and a polymerase in vitro. The rate of this synthesis depends on a sequence specific slippage rate, but is independent of the length of the fragments being synthesized. This indicates that only the ends of the DNA fragments are involved in determining this rate and that slippage is accordingly a short range effect. Slippage synthesis occurs also on a fixed template where only one strand is free to move, a situation which resembles chromosome replication in vivo. It seems therefore likely that slippage during replication is the cause of the observed length polymorphism of simple sequence stretches between individuals of a population.
Adaptive surface-related multiple elimination (1992)

Abstract The major amount of multiple energy in seismic data is related to the large reflectivity of the surface. A method is proposed for the elimination of all surface-related multiples by means of a process that removes the influence of the surface reflectivity from the data. An important property of the proposed multiple elimination process is that no knowledge of the subsurface is required. On the other hand, the source signature and the surface reflectivity do need to be provided. As a consequence, the proposed process has been implemented adaptively, meaning that multiple elimination is designed as an inversion process where the source and surface reflectivity properties are estimated and where the multiple-free data equals the inversion residue. Results on simulated data and field data show that the proposed multiple elimination process should be considered as one of the key inversion steps in stepwise seismic inversion.
Lessons from People with Nonprogressive HIV Infection (1995)

Infectious diseases can be extremely variable in their manifestations, but human immunodeficiency virus (HIV) infection is notorious for its protean manifestations. One of these, the absence of any apparent progression of disease over a decade or more, is particularly intriguing. The average time from HIV infection to death is 10 years, but clinical and immunologic decline is generally evident much earlier. About 5 percent of infected people are characterized as having nonprogressive infection because they remain healthy and do not have the declining CD4+ lymphocyte counts that are evident in people with progressive disease.1 Although we remain uncertain of their eventual fate, people with long-term nonprogressive infection nonetheless have especially favorable outcomes of an otherwise fatal disease. From these patients we may be able to learn important lessons that could improve the treatment of those with progressive disease. In this issue of the Journal there are three reports of investigations into the possibility that people with long-term nonprogressive infection represent some special circumstance of the virus–host interaction.
Fecal Microbiota Transplantation for Clostridium difficile Infection: Systematic Review and Meta-Analysis (2013)

FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated.
Immunopurified Mammalian Target of Rapamycin Phosphorylates and Activates p70 S6 Kinase α in Vitro (1999)

p70 S6 kinase alpha (p70alpha) is activated in vivo through a multisite phosphorylation in response to mitogens if a sufficient supply of amino acids is available or to high concentrations of amino acids per se. The immunosuppressant drug rapamycin inhibits p70alpha activation in a manner that can be overcome by coexpression of p70alpha with a rapamycin-resistant mutant of the mammalian target of rapamycin (mTOR) but only if the mTOR kinase domain is intact. We report here that a mammalian recombinant p70alpha polypeptide, extracted in an inactive form from rapamycin-treated cells, can be directly phosphorylated by the mTOR kinase in vitro predominantly at the rapamycin-sensitive site Thr-412. mTOR-catalyzed p70alpha phosphorylation in vitro is accompanied by a substantial restoration in p70alpha kinase activity toward its physiologic substrate, the 40 S ribosomal protein S6. Moreover, sequential phosphorylation of p70alpha by mTOR and 3-phosphoinositide-dependent protein kinase 1 in vitro resulted in a synergistic stimulation of p70alpha activity to levels similar to that attained by serum stimulation in vivo. These results indicate that mTOR is likely to function as a direct activator of p70 in vivo, although the relative contribution of mTOR-catalyzed p70 phosphorylation in each of the many circumstances that engender p70 activation remains to be defined.
A Simplified Electroencephalogram Monitoring System in the Emergency Room (2017)

For the ER physician, the simple EEG, such as eEEG, is useful as a biological monitor because it enables quick assessment of lethal abnormal brain waves in the ER. The clinical usefulness and limitations of our eEEG method should be investigated further in a large population.
Medical Backgrounder: Psoriasis (2002)

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European populations. Psoriatic lesions are extremely characteristic of the disease, which allows for simple diagnosis. A clear understanding of the pathogenesis of psoriasis does not yet exist. Hyperproliferation of keratinocytes is a further characteristic feature. Studies have depicted that the epidermal cell cycle of psoriatic lesions is shortened by approximately eight-fold more than normal. The lesions are classified as erythrosquamous, due to the erythema which develops asa result of involvement of the vasculature, and the involvement of the epidermis with scale formation. The diagnosis of psoriasis can usually be established on clinical grounds. If the clinician is in doubt, a small cutaneous punch biopsy and subsequent histopathological examination can be performed. There are multiple therapeutic options for psoriasis. First-line therapy for patients with moderate to severe psoriasis is the application of topical agents, followed by phototherapy (UVB) for more extensive disease. If extensive disease does not respond to UVB, second-line agents include psoralen plus UVA (PUVA), methotrexate, cyclosporine or other systemic agents, including novel biologic therapies. New psoriasis treatment regimens have been developed and include combination, rotational and sequential therapy.
Diagnosis, Epidemiology and Outcomes of Acute Kidney Injury (2008)

Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. Early observational studies from the 1980s and 1990s established the general epidemiologic features of acute kidney injury: the incidence, prognostic significance, and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g., in the setting of intravenous contrast, sepsis, and major surgery) have provided further details into this heterogeneous syndrome. Despite our sophisticated understanding of the epidemiology and pathobiology of acute kidney injury, current prevention strategies are inadequate and current treatment options outside of renal replacement therapy are nonexistent. This failure to innovate may be due in part to a diagnostic approach that has stagnated for decades and continues to rely on markers of glomerular filtration (blood urea nitrogen and creatinine) that are neither sensitive nor specific. There has been increasing interest in the identification and validation of novel biomarkers of acute kidney injury that may permit earlier and more accurate diagnosis. This review summarizes the major epidemiologic studies of acute kidney injury and efforts to modernize the approach to its diagnosis.
Optimal Planning of Robotically Assisted Heart Surgery: First Results on the Transfer Precision in the Operating Room (2004)

The aim of this work is to quantify the errors introduced at different levels of applying results planned using a computer integrated surgery system in the operating room, and to make use of these errors to adapt the transfer and rethink the planning. In particular, we address the registration between preoperative imaging and the intraoperative patient model, as well as between the patient and the robot. Two different registration methods are used and their accuracies compared. Moreover, augmented reality trials are conducted to assess the difficulty of adapting preoperative data to intraoperative models in order to deliver useful information to the surgeon during the intervention. The experimental work in this paper is conducted on a dog for a coronary bypass intervention using the da Vinci™ surgical system.
Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs (2003)

Coactivator recruitment by activation function 2 (AF2) in the steroid receptor ligand binding domain takes place through binding of an LXXLL amphipathic alpha-helical motif at the AF2 hydrophobic surface. The androgen receptor (AR) and certain AR coregulators are distinguished by an FXXLF motif that interacts selectively with the AR AF2 site. Here we show that LXXLL and FXXLF motif interactions with steroid receptors are modulated by oppositely charged residues flanking the motifs and charge clusters bordering AF2 in the ligand binding domain. An increased number of charged residues flanking AF2 in the ligand binding domain complement the two previously characterized charge clamp residues in coactivator recruitment. The data suggest a model whereby coactivator recruitment to the receptor AF2 surface is initiated by complementary charge interactions that reflect a reversal of the acidic activation domain-coactivator interaction model.
An efficient multilevel placement technique using hierarchical partitioning (1992)

Ratio cut hierarchical partitioning, which enables efficient multilevel simulated annealing, is applied to the row placement problem for large circuits. An overlapping moving window scheme is used to compensate for the effect of partitioning on the placement quality. Through the use of hierarchical partitioning, the asymptotic run time complexity of this algorithm grows linearly as the function of the circuit size. The system is called placement by ratio cut partitioning (PRC). The results from several benchmark tests are presented demonstrating PRC to be 2.49% on average better than TimberWolfSC Ver5.6. Furthermore, the run time for PRC is 18.3% on average less than that required for TimberWolfSC Ver5.6 for large test cases with more than 2000 cells. For a 100-K sea of gates test case, a 7.09% reduction in total wire length over TimberWolfSC Ver5.6 and a 51.7% saving in CPU time were achieved.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Glutamic acid decarboxylase T lymphocyte responses associated with susceptibility or resistance to type I diabetes: analysis in disease discordant human twins, non-obese diabetic mice and HLA-DQ transgenic mice. (1998)

Glutamic acid decarboxylase (GAD65) has been implicated as a targeted self antigen in the immune destruction of pancreatic beta cells. T cell responses to GAD65 peptides have been detected in both patients with type I diabetes and in the non-obese diabetic (NOD) mouse. To establish which GAD65 epitopes are important in the immunopathogenesis of disease we initially compared T cell responses to GAD65 epitopes in conditions of disease susceptibility and protection. T cell responses to GAD65 peptides were measured in monozygotic twin pairs selected on the basis of disease discordance and T cell recognition of immunogenic regions of GAD65. Peptides of interest were then used to immunize susceptible NOD mice and H2-E transgenic NOD mice which are protected from diabetes. A differential response to the epitope GAD65 521-535 discriminated diabetic from non-diabetic human twins as well as susceptible from protected mice. This epitope as well as GAD 505-519 induces T cell responses despite binding the type I diabetes associated HLA-DQA1*0301/DQB1*0302 product with low affinity. Since DQ-restricted T cell responses are difficult to study in humans, HLA-DQ8 transgenic mice were then used: GAD epitopes 521-535 and 505-519 induced responses in DQ8 transgenic mice and T cell lines were established. Long-term T cell lines against GAD 505-519 were HLA-DQ restricted, and responded to peptide with a strong IFN-gamma and IL-10 response. The findings implicate GAD 521-535 as a possible target peptide in pathogenesis and are compatible with a model whereby self-reactive T cells specific for low-affinity peptide-MHC complexes may escape thymic negative selection.
A novel low-loss Terahertz waveguide: Polymer tube (2010)

We propose a kind of novel low-loss Terahertz (THz) waveguide, a polymer tube with a cross section of ring structure. Low-loss property of the polymer tube for THz guiding is achieved due to the effect of the air core inside the polymer tube which traps a large part of mode power and, at the same time, enlarges the mode area of the fundamental mode. Both the polymer tube and a solid polymer fiber are comparatively investigated, considering effective indexes, mode area, power fraction, relative absorption loss and mode profile. Simulation results show that the proposed polymer tube exhibits better loss property and confinement property than the solid polymer fiber. As an example, we finally show the experimentally measured property of a Polytetrafluoroethylene (PTFE) tube.
The phenotypic and functional consequences of tumour necrosis factor receptor type 2 expression on CD4+ FoxP3+ regulatory T cells (2011)

Cytokine receptors expressed by CD4(+) FoxP3(+) regulatory T cells (Treg cells) not only serve as a phenotypic marker for the identification of this important population of immunosuppressive cells, they also promote the function of Treg cells. CD25, the α-chain of interleukin-2 receptor, is a prototype of such a receptor, which enables Treg cells to be activated by interleukin-2. We and others have found that tumour necrosis factor receptor type 2 (TNFR2) is another important cytokine receptor preferentially expressed by Treg cells with important phenotypic and functional roles. TNFR2 is preferentially expressed by highly functional human and mouse Treg cells, and mediates the activating effect of TNF on Treg cells. We review here the studies of the regulation of expression of TNFR2 on functional Treg cells as well as on CD4(+) FoxP3(-) effector T cells (Teff cells). We document the critical role of this receptor in the activation, proliferative expansion and survival of Treg cells. The contribution of TNFR2 expression on Treg and Teff cells to the beneficial and detrimental effects of anti-TNF treatment in autoimmune disorders will also be discussed.
Transcriptional Regulation of the Interferon- γ-inducible Tryptophanyl-tRNA Synthetase Includes Alternative Splicing (1995)

We have investigated the transcriptional control elements of the human interferon (IFN)-gamma-induced tryptophanyl-tRNA synthetase (hWRS) gene and characterized the transcripts. Transcription leads to a series of mRNAs with different combinations of the first exons. The full-length mRNA codes for a 55-kDa protein (hWRS), but a mRNA lacking exon II is present in almost as high amounts as the full-length transcript. This alternatively spliced mRNA is probably translated into a 48-kDa protein starting from Met48 in exon III. The predicted 48-kDa protein corresponds exactly to an IFN-gamma-inducible protein previously detected by two-dimensional gel electrophoresis. By isolation of genomic clones and construction of plasmids containing hWRS promoter fragments fused to the secreted alkaline phosphatase reporter gene we have mapped a promoter region essential for IFN-mediated gene activation. This region contains IFN-stimulated response elements (ISRE) as well as a Y-box and a gamma-activated sequence (GAS) element. IFN-gamma inducibility of hWRS depends on ongoing protein synthesis, suggesting that so far undescribed transcription factors apart from the latent GAS-binding protein p91 contribute to gene activation. This could be interferon-regulatory factor-1, which binds ISRE elements.
Adhesion preventive effect of hyaluronic acid after intraperitoneal surgery in mice (1999)

Prevention of intraperitoneal adhesion after gynaecological surgery is essential for maintaining postoperative fertility. In this study, the adhesion prevention effect was examined of a hyaluronic acid (HA) solution obtained from the fermentation method and having a molecular weight of 1.9×106 with high viscosity. Laparotomy was conducted on female mice 7 weeks old, whose menstrual periods were synchronized by pregnant mare serum gonadotrophin (PMSG) to injure the uterine horn surface. Intraperitoneal adhesions were favourably formed in 91.7% of cases induced with iodine abrasion, compared with 50% induced by electrosurgery. Intraperitoneal administration of HA was evaluated for its effect on the prevention of adhesions made by iodine abrasion. Adhesion prevention effects of HA were observed at concentrations of 0.3, 0.5, 0.75 and 1.0%, among which the most pronounced effect was with the use of a 0.3% solution (92.3% of cases). Compared with the control group adhesion score of 2.0 ± 0.8, significant decreases in adhesion scores were observed at all concentrations. HA with a molecular weight of 1.9×106 was recognized to have a definitive prevention effect on postoperative adhesions in mice after laparotomy and is considered to be a prospective material for future clinical use.
The worldwide Protein Data Bank (wwPDB): ensuring a single, uniform archive of PDB data (2006)

The worldwide Protein Data Bank (wwPDB) is the international collaboration that manages the deposition, processing and distribution of the PDB archive. The online PDB archive is a repository for the coordinates and related information for more than 38 000 structures, including proteins, nucleic acids and large macromolecular complexes that have been determined using X-ray crystallography, NMR and electron microscopy techniques. The founding members of the wwPDB are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan) [H.M. Berman, K. Henrick and H. Nakamura (2003) Nature Struct. Biol., 10, 980]. The BMRB group (USA) joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single archive of macromolecular structural data that are freely and publicly available to the global community. Additionally, the wwPDB provides a variety of services to a broad community of users. The wwPDB website at http://www.wwpdb.org/ provides information about services provided by the individual member organizations and about projects undertaken by the wwPDB.
A biparatopic anti‐EGFR nanobody efficiently inhibits solid tumour growth (2011)

The epidermal growth factor receptor (EGFR) has been shown to be a valid cancer target for antibody-based therapy. At present, several anti-EGFR monoclonal antibodies have been successfully used, such as cetuximab and matuzumab. X-ray crystallography data show that these antibodies bind to different epitopes on the ecto-domain of EGFR, providing a rationale for the combined use of these two antibody specificities. We have previously reported on the successful isolation of antagonistic anti-EGFR nanobodies. In our study, we aimed to improve the efficacy of these molecules by combining nanobodies with specificities similar to both cetuximab and matuzumab into a single biparatopic molecule. Carefully designed phage nanobody selections resulted in two sets of nanobodies that specifically blocked the binding of either matuzumab or cetuximab to EGFR and that did not compete for each others' binding. A combination of nanobodies from both epitope groups into the biparatopic nanobody CONAN-1 was shown to block EGFR activation more efficiently than monovalent or bivalent (monospecific) nanobodies. In addition, this biparatopic nanobody potently inhibited EGF-dependent cell proliferation. Importantly, in an in vivo model of athymic mice bearing A431 xenografts, CONAN-1 inhibited tumour outgrowth with an almost similar potency as the whole mAb cetuximab, despite the fact that CONAN-1 is devoid of an Fc portion that could mediate immune effector functions. Compared to therapy using bivalent, monospecific nanobodies, CONAN-1 was clearly more potent in tumour growth inhibition. These results show that the rational design of biparatopic nanobody-based anticancer therapeutics may yield potent lead molecules for further development.
Field-dependence of the area-density of ‘cold’ electron emission sites on broad-area CVD diamond films (1993)

A high area density of field-induced electron emission sites has been observed on broad-area (12 mm in diameter) CVD diamond films deposited on molybdenum substrates. Furthermore, it was found that the density increased with the electric field applied to the surface of the films. These findings indicate that the CVD diamond film has to be seen as a potentially favoured candidate among electronic materials for the development of new types of cold cathode electron source.
Selective Chemical Vapor Deposition of Manganese Self-Aligned Capping Layer for Cu Interconnections in Microelectronics (2010)

In modern Cu interconnections in microelectronics, weak adhesion between the chemical-mechanical polished copper surface and the dielectric capping material can lead to rapid electromigration of Cu and early failure of the wiring. A self-aligned chemical vapor deposition (CVD) Mn capping process is introduced to strengthen the interface between Cu and dielectric insulators without increasing the resistivity of Cu. In this CVD process, a vapor mixture of Mn precursor and molecular hydrogen deposits Mn selectively on copper and not at all on the adjacent, previously deactivated surfaces of insulators. Deactivation of the insulator surfaces is accomplished by exposure to vapors containing reactive alkylsilyl groups. The presence of Mn at the Cu/insulator interface greatly increases the strength of the bonding between Cu and the insulator. The debonding energy increases approximately linearly with the amount of Mn at the interface, up to values so large that the interface could not be broken apart. This Mn-enhanced binding strength of Cu to insulators is observed for all insulators tested, including plasma-enhanced chemical vapor deposited , SiCNOH, , and low- SiCOH, as well as thermal and atomic-layer-deposited . This selective CVD Mn capping process should increase the lifetime of advanced copper interconnections.