gebhart/patrepeval huggingface dataset:
Molecular Similarity of MDR Inhibitors (2004)

The molecular similarity of multidrug resistance (MDR) inhibitors was evaluated using the point centred atom charge approach in an attempt to find some common features of structurally unrelated inhibitors. A series of inhibitors of bacterial MDR were studied and there is a high similarity between these in terms of their shape, presence and orientation of aromatic ring moieties. A comparison of the lipophilic properties of these molecules has also been conducted suggesting that this factor is important in MDR inhibition.
Short-Channel Performance Improvement by Raised Source/Drain Extensions With Thin Spacers in Trigate Silicon Nanowire MOSFETs (2011)

We investigate the short-channel performance of trigate silicon nanowire transistors. Drain-induced barrier lowering at a gate length of 25 nm is strongly suppressed by reducing the nanowire width (W <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">NW</sub> ) down to 10 nm. We found that the parasitic resistance (R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SD</sub> ) of nanowire transistors is dominated by nanowire-shaped source/drain (S/D) regions under the gate spacer whose resistivity is higher than that in wider regions. We succeeded in significant reduction by raised S/D with thin gate spacer whose width is 10 nm. Although the parasitic capacitance (C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">para</sub> ) increases by spacer thinning, C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">para</sub> increase is much smaller than R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SD</sub> reduction, and great performance improvement is obtained for a W <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">NW</sub> of less than 15 nm.
A Common Interface on Histidine-containing Phosphocarrier Protein for Interaction with Its Partner Proteins (2000)

The bacterial phosphoenolpyruvate:sugar phosphotransferase system accomplishes both the transport and phosphorylation of sugars as well as the regulation of some cellular processes. An important component of this system is the histidine-containing phosphocarrier protein, HPr, which accepts a phosphoryl group from enzyme I, transfers a phosphoryl group to IIA proteins, and is an allosteric regulator of glycogen phosphorylase. Because the nature of the surface on HPr that interacts with this multiplicity of proteins from Escherichia coli was previously undefined, we investigated these interactions by nuclear magnetic resonance spectroscopy. The chemical shift changes of the backbone and side-chain amide (1)H and (15)N nuclei of uniformly (15)N-labeled HPr in the absence and presence of natural abundance glycogen phosphorylase, glucose-specific enzyme IIA, or the N-terminal domain of enzyme I have been determined. Mapping these chemical shift perturbations onto the three-dimensional structure of HPr permitted us to identify the binding surface(s) of HPr for interaction with these proteins. Here we show that the mapped interfaces on HPr are remarkably similar, indicating that HPr employs a similar surface in binding to its partners.
Evidence for structural heterogeneity from molecular cytogenetic analysis of dicentric Robertsonian translocations. (1996)

Most Robertsonian translocations are dicentric, suggesting that the location of chromosomal breaks leading to their formation occur in the acrocentric short arm. Previous cytogenetic and molecular cytogenetic studies have shown that few Robertsonian translocations retain ribosomal genes or beta-satellite DNA. Breakpoints in satellite III DNA, specifically between two chromosome 14-specific subfamilies, pTRS-47 and pTRS-63, have been indicated for most of the dicentric 14q21q and 13q14q translocations that have been studied. We have analyzed the structure of 36 dicentric translocations, using several repetitive DNA probes that localize to the acrocentric short arm. The majority of the translocations retained satellite III DNA, while others proved variable in structure. Of 10 14q21q translocations analyzed, satellite III DNA was undetected in 1; 6 retained one satellite III DNA subfamily, pTRS-47; and 3 appeared to contain two 14-specific satellite III DNA sub-families, pTRS-47 and pTRS-63. In 10/11 translocations involving chromosome 15, the presence of satellite III DNA was observed. Our results show that various regions of the acrocentric short arm, and, particularly, satellite III DNA sequences, are involved in the formation of Robertsonian translocations.
Direct selection of a human antibody fragment directed against the tumor T-cell epitope HLA-A1–MAGE-A1 from a nonimmunized phage-Fab library (2000)

Antitumor antibodies with the same specificity as cytotoxic T lymphocytes that recognize antigenic peptides encoded by tumor-associated genes and presented by MHC class I molecules would be valuable tools to analyze the antigenicity or target tumor cells in vivo. To obtain a human antibody directed against a peptide encoded by gene melanoma-associated antigen (MAGE)-A1 and presented by HLA-A1 molecules, we selected a large phage Fab antibody repertoire on a recombinant version of the complex HLA-A1-MAGE-A1 produced by in vitro refolding. One of the selected phage antibodies shows binding to HLA-A1 complexed with the MAGE-A1 peptide, but does not show binding to HLA-A1 complexed with a peptide encoded by gene MAGE-A3 and differing from the MAGE-A1 peptide by only three residues. Phages carrying this recombinant antibody bind to HLA-A1(+) cells only after in vitro loading with MAGE-A1 peptide. These results indicate that nonimmunized phage Fab libraries are a source of antibodies with a T cell antigen receptor-like specificity. The human anti-HLA-A1-MAGE-A1 antibody described here may prove very useful for monitoring the cell surface expression of these complexes, and eventually, as a targeting reagent for the specific immunotherapy of HLA-A1 patients bearing a MAGE-A1-positive tumor.
The beneficial effect of pozzolanas in suppressing the alkali-silica reaction (1990)

An investigation has been made of the effect of replacement of part of the ordinary Portland cement (OPC) in an OPC/silica glass (SG) mortar by pulverized fuel ash (PFA), precipitated silica (PS) and ground granulated blastfurnace slag (ggbs). The expansion of the mortar due to alkali-silica reaction is reduced, and it is found in all cases that alkali dilution due to the replacement can play only a minor role in the reduction of expansion. It is hypothesized that a major mechanism of this reduction is an increase in the effective SiO 2 /Na 2 O ratio to values in excess of the pessimum value; it is found that the greater is the deviation of this ratio from the pessimum value, the less is the expansion, the order of effectiveness of the replacements being PS &gt; PFA &gt; ggbs. The replacements are more effective in reducing the expansion due to alkali-silica reaction than they are in reducing the loss in bending strength of mortar bars. Observations by transmission electron microscopy of the microstructure of PFA/OPC/SG mortars show that the glass particle surfaces develop a layer of CSH reaction product of lower thickness than that of equivalent mortars without replacement, and that the PFA particles also develop a surface layer of CSH reaction product, but of different morphology to that of glass particle reaction product layers.
Increased Cortical Cell Loss and Prolonged Hemodynamic Depression after Traumatic Brain Injury in Mice Lacking the IP Receptor for Prostacyclin (2007)

Prostacyclin is the major arachidonic acid metabolite of the vascular endothelium and is produced mainly via the cyclooxygenase-2 pathway. By acting on the prostacyclin (IP) receptor on platelets and vascular smooth muscle cells, prostacyclin exerts vasodilatory and antiaggregative/antiadhesive effects. Previous studies have shown that prostacyclin production increases after brain trauma, but the importance of prostacyclin for posttraumatic hemodynamic alterations and neuron survival has not been investigated. This study evaluated if endogenous prostacyclin plays a role in the pathophysiologic process in the brain after brain trauma. This was performed by comparing prostacyclin (IP) receptor-deficient (IP(-/-)) mice and mice with functional IP receptor (IP(+/+)) after a controlled cortical injury regarding contusion volume, cerebral blood flow ([(14)C]iodoantipyrine autoradiography), number of perfused capillaries (fluorescein isothiocyanate-dextran fluorescence technique), the transfer constant (K(i)) for [(51)Cr]EDTA, and brain water content (wet vs dry weight) in the injured and contralateral cortex. Contusion volume was increased in IP(-/-) mice compared with IP(+/+) mice. Three hours after trauma, cortical blood flow was decreased in the injured cortex of both groups and the reduction in blood flow in the cortex of the IP(-/-) mice persisted from 3 to 24 h, whereas blood flow approached normal values in the IP(+/+) mice after 24 h. No differences could be detected between the two genotypes regarding other hemodynamic parameters. We conclude that the prostacyclin IP receptor is beneficial for neuron survival after brain trauma in mice, an effect that may be mediated by improved cortical perfusion.
Amyloid-β overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins (2008)

Mitochondrial dysfunction is a prominent feature of Alzheimer disease but the underlying mechanism is unclear. In this study, we investigated the effect of amyloid precursor protein (APP) and amyloid beta on mitochondrial dynamics in neurons. Confocal and electron microscopic analysis demonstrated that approximately 40% M17 cells overexpressing WT APP (APPwt M17 cells) and more than 80% M17 cells overexpressing APPswe mutant (APPswe M17 cells) displayed alterations in mitochondrial morphology and distribution. Specifically, mitochondria exhibited a fragmented structure and an abnormal distribution accumulating around the perinuclear area. These mitochondrial changes were abolished by treatment with beta-site APP-cleaving enzyme inhibitor IV. From a functional perspective, APP overexpression affected mitochondria at multiple levels, including elevating reactive oxygen species levels, decreasing mitochondrial membrane potential, and reducing ATP production, and also caused neuronal dysfunction such as differentiation deficiency upon retinoic acid treatment. At the molecular level, levels of dynamin-like protein 1 and OPA1 were significantly decreased whereas levels of Fis1 were significantly increased in APPwt and APPswe M17 cells. Notably, overexpression of dynamin-like protein 1 in these cells rescued the abnormal mitochondrial distribution and differentiation deficiency, but failed to rescue mitochondrial fragmentation and functional parameters, whereas overexpression of OPA1 rescued mitochondrial fragmentation and functional parameters, but failed to restore normal mitochondrial distribution. Overexpression of APP or Abeta-derived diffusible ligand treatment also led to mitochondrial fragmentation and reduced mitochondrial coverage in neuronal processes in differentiated primary hippocampal neurons. Based on these data, we concluded that APP, through amyloid beta production, causes an imbalance of mitochondrial fission/fusion that results in mitochondrial fragmentation and abnormal distribution, which contributes to mitochondrial and neuronal dysfunction.
Advanced Programming in the Unix Environment (1992)

For more than twenty years, serious C programmers have relied on one book for practical, in-depth knowledge of the programming interfaces that drive the UNIX and Linux kernels: W. Richard Stevens Advanced Programming in the UNIX Environment . Now, once again, Richs colleague Steve Rago has thoroughly updated this classic work. The new third edition supports todays leading platforms, reflects new technical advances and best practices, and aligns with Version 4 of the Single UNIX Specification. Steve carefully retains the spirit and approach that have made this book so valuable. Building on Richs pioneering work, he begins with files, directories, and processes, carefully laying the groundwork for more advanced techniques, such as signal handling and terminal I/O. He also thoroughly covers threads and multithreaded programming, and socket-based IPC. This edition covers more than seventy new interfaces, including POSIX asynchronous I/O, spin locks, barriers, and POSIX semaphores. Most obsolete interfaces have been removed, except for a few that are ubiquitous. Nearly all examples have been tested on four modern platforms: Solaris 10, Mac OS X version 10.6.8 (Darwin 10.8.0), FreeBSD 8.0, and Ubuntu version 12.04 (based on Linux 3.2). As in previous editions, youll learn through examples, including more than ten thousand lines of downloadable, ISO C source code. More than four hundred system calls and functions are demonstrated with concise, complete programs that clearly illustrate their usage, arguments, and return values. To tie together what youve learned, the book presents several chapter-length case studies, each reflecting contemporary environments. Advanced Programming in the UNIX Environment has helped generations of programmers write code with exceptional power, performance, and reliability. Now updated for todays systems, this third edition will be even more valuable.
N-terminal Processing Is Essential for Release of Epithin, a Mouse Type II Membrane Serine Protease (2001)

Epithin was originally identified as a mouse type II membrane serine protease. Its human orthologue membrane type-serine protease 1 (MT-SP1)/matriptase has been reported to be localized on the plasma membrane. In addition, soluble forms of matriptase were isolated from human breast milk and breast cancer cell-conditioned medium. In this paper, we report a processing mechanism that appears to be required for the release of epithin. CHO-K1 or COS7 cells transfected with single full-length epithin cDNA generated two different-sized proteins in cell lysates, 110 and 92 kDa. The 92-kDa epithin was found to be an N-terminally truncated form of the 110-kDa epithin, and it was the only form detected in the culture medium. The 92-kDa epithin was also found on the cell surface, where it was anchored by the N-terminal fragment. The results of in vivo cell labeling experiments indicate that the 110-kDa epithin is rapidly processed to the 92-kDa epithin. Using site-directed mutagenesis experiments, we identified Gly(149) of the GSVIA sequence in epithin as required for the processing and release of the protein. These results suggest that N-terminal processing of epithin at Gly(149) is a necessary prerequisite step for release of the protein.
Peptaibiomics: Screening for Polypeptide Antibiotics (Peptaibiotics) from Plant-ProtectiveTrichoderma Species (2006)

Eight strains of Trichoderma species (T. strigosum, T. erinaceus, T. pubescens, T. stromaticum, and T. spirale as well as T. cf. strigosum, T. cf. pubescens) were selected because of their antagonistic potential against Eutypa dieback and Esca which are fungal diseases of grapevine trunks. These isolates were screened for the production of a group of polypeptide antibiotics named peptaibiotics, including its subgroups peptaibols and lipopeptaibols. Fully-grown fungal cultures on potato-dextrose agar were extracted with CH(2)Cl(2)/MeOH, and these extracts were subjected to SPE using C(18) cartridges. The methanolic eluates were analyzed by on-line LC/ESI-MS(n) coupling--a method which is referred to as 'peptaibiomics'. New seven-, ten-, and eleven-residue lipopeptaibols, with N-terminal alkanoyl, and C-terminal leucinol or isoleucinol residues were found and named lipostrigocins and lipopubescins. Furthermore, new 18-residue peptaibols named trichostromaticins and 19-residue peptaibols named trichostrigocins were discovered. One peptaibiotic carrying a free C-terminal valine (or isovaline) named trichocompactin XII was also sequenced. These results corroborate the hypothesis that peptaibiotics might contribute to the plant-protective action of their fungal producers. The data also point out that comparison of peptaibiotic sequences is of limited relevance in order to establish chemotaxonomic relationships among species of the genus Trichoderma.
Measurement Adherence in the Blood Pressure Self-Measurement Room (2013)

Results indicate that context-aware technology may be useful for accurately modeling aspects of nonadherent patient behavior. This may be used to inform staff of the validity of the measurement and pinpoint patients in need of additional training or to design better aids to assist the patients. The developed system is generally applicable to other self-measurement environments, including the home setting and remote outpatient clinics, as it is built using telemedicine technology and thus well suited for remote monitoring and diagnosis.
Gas diffusion barriers on polymers using Al2O3 atomic layer deposition (2006)

Thin films of Al2O3 grown by atomic layer deposition (ALD) were investigated as gas diffusion barriers on flexible polyethylene naphthalate and Kapton® polyimide substrates. Al2O3 ALD films with thicknesses of 1–26nm were grown at 100–175°C. For Al2O3 ALD films with thicknesses ⩾5nm, oxygen transmission rates were below the MOCON instrument test limit of ∼5×10−3cc∕m2∕day. Applying a more sensitive radioactive tracer method, H2O-vapor transmission rates of ∼1×10−3g∕m2∕day were measured for single-sided Al2O3 ALD films with thicknesses of 26nm on the polymers. Ultrathin gas diffusion barriers grown by Al2O3 ALD may enable organic displays and electronics on permeable, flexible polymer substrates.
Translation rate is controlled by coupled trade-offs between site accessibility, selective RNA unfolding and sliding at upstream standby sites (2013)

The ribosome's interactions with mRNA govern its translation rate and the effects of post-transcriptional regulation. Long, structured 5' untranslated regions (5' UTRs) are commonly found in bacterial mRNAs, though the physical mechanisms that determine how the ribosome binds these upstream regions remain poorly defined. Here, we systematically investigate the ribosome's interactions with structured standby sites, upstream of Shine-Dalgarno sequences, and show that these interactions can modulate translation initiation rates by over 100-fold. We find that an mRNA's translation initiation rate is controlled by the amount of single-stranded surface area, the partial unfolding of RNA structures to minimize the ribosome's binding free energy penalty, the absence of cooperative binding and the potential for ribosomal sliding. We develop a biophysical model employing thermodynamic first principles and a four-parameter free energy model to accurately predict the ribosome's translation initiation rates for 136 synthetic 5' UTRs with large structures, diverse shapes and multiple standby site modules. The model predicts and experiments confirm that the ribosome can readily bind distant standby site modules that support high translation rates, providing a physical mechanism for observed context effects and long-range post-transcriptional regulation.
Biodiversity and the exotic species threat (1998)

Exotic species invasions, called by one conservation biologist the least reversible of all human impacts, cause harm to economies (e.g., fisheries, wildlife populations, tourism), the environment (e.g., in the form of broadcast of pesticides and herbicides), human health and wellbeing (e.g., allergic responses and the increase in fire severity in some landscapes), and aesthetics (e.g., the amount of mortality in vegetation). These invasions threaten biological diversity by causing population declines of native species and by altering key ecosystem processes like hydrology, nitrogen fixation, and fire regime. The earth is essentially a loaded gun of exotic species problems because (1) evolution in isolation has produced continents with a similar range of environmental conditions but a very different array of species and (2) species generally have an ability for exponential increase, particularly when removed from natural controls on their population growth. As a result, the problem is a global one-the exotic species problem is neither trivial nor transitory. The human-caused mixing of formerly isolated biota stems from a failure to base decisions on the ecological and coevolutionary setting or organisms. We must employ many methods from our management tool box: eradication, containment, biocontrol, monitoring, and, most importantly, prevention.
Provable learning of noisy-OR networks (2017)

Many machine learning applications use latent variable models to explain structure in data, whereby visible variables (= coordinates of the given datapoint) are explained as a probabilistic function of some hidden variables. Learning the model ---that is, the mapping from hidden variables to visible ones and vice versa---is NP-hard even in very simple settings. In recent years, provably efficient algorithms were nevertheless developed for models with linear structure: topic models, mixture models, hidden markov models, etc. These algorithms use matrix or tensor decomposition, and make some reasonable assumptions about the parameters of the underlying model.
Abstract 1760: Preclinical evaluation of IMGN853, an anti-FOLR1 antibody-maytansinoid conjugate, as a potential therapeutic for ovarian cancer (2011)

Abstract IMGN853 (M9346A-sulfo-SPDB-DM4) is an antibody drug-conjugate consisting of the cytotoxic maytansinoid, DM4, covalently linked to the humanized monoclonal antibody M9346A, which selectively binds to folate receptor 1 (FOLR1). FOLR1 is over-expressed on ovarian cancers (38 of 67 tumor samples positive for FOLR1 ∼ 57%) suggesting that ovarian cancer may be a primary indication for clinical development of IMGN853. FOLR1 expression was evaluated on a panel of ovarian cancer xenografts and human ovarian tumors using a calibrated immunohistochemical (IHC) staining method on formalin-fixed paraffin-embedded sections. The FOLR1 expression levels and patterns in three ovarian adenocarcinoma xenografts, OVCAR-3, IGROV-1 and OV-90, were consistent with those observed in FOLR1-positive patient ovarian tumor samples. The anti-tumor activity of IMGN853 was evaluated in the three FOLR1-positive ovarian xenograft models identified. CB.17 SCID mice bearing established subcutaneous xenograft tumors (approximately 100 mm3) were treated with a single intravenous injection of IMGN853 at 1.2, 2.5 and 5.0 mg/kg (based on antibody concentration). IMGN853 was active in all three models evaluated. In OVCAR-3 xenografts, the minimally efficacious dose (MED) of IMGN853 was 1.2 mg/kg. The higher dose levels were highly active, resulting in complete regressions (CR) in 4/6 and 6/6 mice in the 2.5 and 5.0 mg/kg treatment groups, respectively. Treatment with IMGN853 resulted in strong anti-tumor activity in both IGROV-1 and OV-90 xenograft models, with a MED of 2.5 mg/kg, single injection. The strong anti-tumor activity of IMGN853 against ovarian xenograft tumors with FOLR1 expression levels comparable to patient tumors suggests that IMGN853 may be a promising candidate for clinical development in ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1760. doi:10.1158/1538-7445.AM2011-1760