gebhart/patrepeval huggingface dataset:
Using Human-Induced Pluripotent Stem Cells to Model Monogenic Metabolic Disorders of the Liver (2013)

A crucial problem in liver disease biology and a major obstacle to the development of new therapies is the inability to conduct mechanistic studies of live human hepatocytes. Liver tissue from patients is difficult to obtain and only reveals the disease aftermath, while animal models lack the significant genetic diversity of humans. Monogenic metabolic disorders of the liver are an ideal platform to explore the complex gene-environment interactions and the role of genetic variation in the onset and progression of liver disease. Human induced pluripotent stem cell (hIPSC) technology provides an unprecedented opportunity to generate live cellular models of disease for therapeutic candidate discovery and cell replacement therapy. In this review, we discuss the potential of hIPSC to increase our understanding of human disease with a focus on the current efforts to model metabolic diseases of the liver and to generate suitable populations of human hepatocytes for cell transplantation.
Double U-slot rectangular patch antenna (1998)

A rectangular microstrip antenna with two U-shaped slots on the patch is described. Using a foam layer of thickness ~9% wavelength as the supporting substrate, an impedance bandwidth of 44% is achieved. The radiation patterns are stable across the passband.
Bone matrix deposition of T1, a homologue of interleukin 1 receptors. (1995)

The mouse T1 glycoprotein is a secreted molecule of the immunoglobulin superfamily with significant homology to interleukin 1 receptors. It is expressed during bone development, and the extracellular diffusible gene product is found associated with newly formed bone but not cartilage matrix. During osteogenic differentiation of mandibular condyles of newborn mice in vitro, T1 gene expression is induced shortly after cultivation and is observed throughout the differentiation process. The temporal expression pattern of the gene is an mandibular condyles indicates that T1 expression is an early marker of osteogenic differentiation. This view is substantiated by the analysis of T1 gene regulation in continuous osteogenic cell lines. Both in differentiating osteoblast-like KM-1K cells derived from mandibular condyles and in MC3T3 cells, T1 gene activity is preferentially associated with early differentiation stages. In mandibular condyles, the secreted extracellular T1 protein is deposited into newly formed osteoid but not into cartilage matrix. This novel bone matrix protein may locally modulate the availability of its ligand.
Peptide Binding by Chaperone SecB: Implications for Recognition of Nonnative Structure (1992)

The molecular basis for recognition of nonnative proteins by the molecular chaperone SecB was investigated with an in vitro assay based on the protection of SecB from proteolysis when a ligand is bound. The SecB tetramer has multiple binding sites for positively charged peptides. When the peptide binding sites are occupied, the complex undergoes a conformational change to expose hydrophobic sites that bind the fluorescent probe 1-anilinonaphthalene-8-sulfonate. A model is proposed for interaction of nonnative polypeptides with both hydrophilic and hydrophobic sites on SecB.
Biofluid biomarkers of traumatic brain injury (2017)

The identification of biofluid biomarkers could play a vital role in identifying, diagnosing, and treating the underlying individual pathobiological changes of TBI. CNS-derived exosomes analyzed by ultra-high sensitivity detection methods have the potential to identify blood biomarkers for the range of TBI severity and time course.
Quantitative Analysis of Tat Peptide Binding to Import Carriers Reveals Unconventional Nuclear Transport Properties (2011)

A detailed study of nuclear import mediated by the HIV-1 Tat peptide (47YGRKKRRQRRR57, TatRRR) is reported. Fluorescence-based measurements, calibration of protein concentrations, and binding assays are exploited to address the physicochemical mechanisms of Tat peptide recognition by the classical importin α (Impα) and importin β (Impβ) receptors both in vitro and in intact cells. We show that TatRRR is an unconventional nuclear localization sequence that binds directly to both Impα and Impβ carriers in the absence of competitors (in vitro), whereas this property is silenced in the actual cellular environment. In the latter case, Impα/β-dependent nuclear import can be successfully restored by replacing the "RRR" stretch with "GGG". We apply a recently developed method to determine quantitatively TatGGG affinity for each receptor. Based on these results, we can rationalize previous controversial reports on the Tat peptide and provide coherent guidelines for the design of novel intracellular targeting sequences.
Enhanced Nitinol Properties for Biomedical Applications (2008)

In recent years, Nitinol producers and medical products have experienced an exponential growth, driven by advanced manufacturing techniques and the use of progressively less invasive medical procedures. Concurrently, new processing techniques have been developed to further enhance the valuable properties of Nitinol used in medical devices; recent patents on these techniques include changing the composition of nickel and titanium, alloying the nickel-titanium with other elements, improving melting practices, heat-treating the alloy, and mechanical processing of the alloy. For example, alloying the nickel-titanium with ternary elements may widen the superelastic temperature operating window, maximize/minimize the stress-strain hysteresis, and improve the radiopacity of a Nitinol intraluminal device comparable to that of a stainless steel device of the same strut pattern coated with a thin layer of gold. Limiting to less than 30% the final cold work step (after a full anneal, and before the shape-setting step) may improve the Nitinol fatigue lifetime of about 37%, the fatigue lifetime being a primary factor limiting the performances of Nitinol endoluminal prosthetic implants. Local selective and differential thermo-mechanical treatments have also been devised to achieve different physical properties in different portions of a Nitinol medical device in order to improve its performance under expected operating conditions. Keywords: Nitinol, NiTi, titanium, nickel, NiTi based alloys, superelastic, superelaticity, shape memory, processing, fatigue
Peptide aldehydes as inhibitors of HIV protease (1993)

We have recently shown that alpha-MAPI, a peptidic aldehyde of microbial origin, inhibits the HIV protease with a potency comparable to pepstatin, having, differently from pepstatin, no activity on other aspartic proteases. In this study different peptide derivatives containing a C-terminal aldehyde have been tested to assess the potential of this function for the inhibition of HIV protease. The results of our analysis correspond with the recently published subsite preferences of the viral enzyme, indicating that aldehydes bind to the active site of the HIV protease. Our data suggest that peptide aldehydes can act in their hydrated forms as transition state analogues with the most potent inhibitor having an IC50 of 0.9 microM.
Laccase and melanin in the pathogenesis of Cryptococcus neoformans (1997)

Cryptococcosis, caused by an encapsulated fungus, Cryptococcus neoformans, has emerged as a life threatening infection in HIV positive individuals and other immunocompromised hosts. The present review describes laccase and its product melanin as an important virulence factor of Cryptococcus neoformans and illustrates the approaches used in elucidating the pathogenesis of cryptococcosis. Characterization of the biochemical pathways leading to melanin synthesis is summarized using biochemical and biomolecular approaches. Melanin synthesis is dependent on a single copper-dependent enzyme, laccase. Since the mammalian host does not contain this enzyme, laccase is an attractive candidate for the study of fungal pathogenesis, as well as a drug target. The cloning of the CNLAC1 gene and construction of CNLAC1 gene knock-out strains has confirmed its role in the virulence of Cryptococcus. Also described is the role of melanin in the host-pathogen interactions. Melanin may protect Cryptococcus cells by a variety of methods including anti-oxidant or cell wall surface effects thereby offering protection against numerous effectors of cellular immunity.
Unsupervised 3D Object Recognition and Reconstruction in Unordered Datasets (2005)

This paper presents a system for fully automatic recognition and reconstruction of 3D objects in image databases. We pose the object recognition problem as one of finding consistent matches between all images, subject to the constraint that the images were taken from a perspective camera. We assume that the objects or scenes are rigid. For each image, we associate a camera matrix, which is parameterised by rotation, translation and focal length. We use invariant local features to find matches between all images, and the RANSAC algorithm to find those that are consistent with the fundamental matrix. Objects are recognised as subsets of matching images. We then solve for the structure and motion of each object, using a sparse bundle adjustment algorithm. Our results demonstrate that it is possible to recognise and reconstruct 3D objects from an unordered image database with no user input at all.
Characterization of CD4-Induced Epitopes on the HIV Type 1 gp120 Envelope Glycoprotein Recognized by Neutralizing Human Monoclonal Antibodies (2002)

The entry of human immunodeficiency virus (HIV-1) into target cells typically requires the sequential binding of the viral exterior envelope glycoprotein, gp120, to CD4 and a chemokine receptor. CD4 binding exposes gp120 epitopes recognized by CD4-induced (CD4i) antibodies, which can block virus binding to the chemokine receptor. We identified three new CD4i antibodies from an HIV-1-infected individual and localized their epitopes. These epitopes include a highly conserved gp120 beta-strand encompassing residues 419-424, which is also important for binding to the CCR5 chemokine receptor. All of the CD4i antibodies inhibited the binding of gp120-CD4 complexes to CCR5. CD4i antibodies and CD4 reciprocally induced each other's binding, suggesting that these ligands recognize a similar gp120 conformation. The CD4i antibodies neutralized laboratory-adapted HIV-1 isolates; primary isolates were more resistant to neutralization by these antibodies. Thus, all known CD4i antibodies recognize a common, conserved gp120 element overlapping the binding site for the CCR5 chemokine receptor.
Electrical Characterization of Silicon Nanogaps (2005)

We have designed and manufactured silicon nanogaps aimed at electrically interfacing molecules, utilizing the precision thickness control in an oxidation process. An insulating layer was formed on a silicon wafer, and then polysilicon was deposited on top. By using a selective etch, a vertical nanometer-sized gap was formed between the silicon electrodes.Before the etching the only current component detected is the tunneling current through the thin oxide, but after the etching large current instabilities are seen. This parasitic current can change rapidly up and down more than one order of magnitude. Measurements of the low-frequency noise show a power spectrum close to 1/f, and the current power spectrum density scales as the current squared.Stressing the etched devices by applying a constant voltage can reduce the current levels. Heating the devices in nitrogen reduces the noise levels. Storing or heating the chips in air results in oxidized electrode surfaces, and reduced currents. Comparisons to soft breakdown (a degradation mechanism for thin oxides) are made and a model based on percolation theory is presented. Another important issue addressed is the surface leakage currents after using chemical methods to deposit nanoscale objects to the electrodes. These surface leakage currents are time dependent diffusion currents, and the magnitudes are highly dependent on the chemical treatments performed. Chemical treatments leaving more conductive residuals cause time independent surface leakage currents. Simulations show that molecular resonant tunneling diodes (RTDs) are promising candidates for reducing the standby power of DRAM cells, due to the high peak-to-valley ratio displayed in the current-voltage characteristics of some molecules. Still molecules with resonance for lower applied voltages and with lower current levels in general must be developed if molecular RTDs are to be used in this application.
Effect ofBorrelia burgdorferiGenotype on the Sensitivity of C6 and 2‐Tier Testing in North American Patients with Culture‐Confirmed Lyme Disease (2008)

Lack of sensitivity of the C6 test because of strain diversity seems less likely to be a limitation of this serologic test, compared with 2-tier testing in North American patients with early Lyme disease.
Regulatory mechanisms of nucleic acid-mediated innate immune responses in the tumor microenvironment (2012)

We identified novel mechanisms whereby TIM-3 suppresses innate immunity as induced by nucleic acids. Interaction of TIM-3 with HMGB1 inhibits the recruitment of nucleic acids to the endosomal compartment of dendritic cells, impairing the transduction of innate immune signals. Thus, TIM-3 is an effective target for enhancing the immunogenicity of nucleic acids in the context of cancer therapy.
Transfer of proteins from gels to diazobenzyloxymethyl-paper and detection with antisera: a method for studying antibody specificity and antigen structure. (1979)

We describe a rapid and very sensitive method for detecting proteins as antigens after their separation in polyacrylamide/agarose composite gels, with or without sodium dodecyl sulfate. The polyacrylamide matrix is crosslinked with a reagent that can be cleaved with periodate or alkali to facilitate transfer of the protein bands to diazobenzyloxymethyl-paper, where they are coupled covalently. Specific proteins are detected by autoradiography after sequential incubation with unfractionated, unlabeled specific antiserum and 125I-labeled protein A from Staphylococcus aureus. Antibody and protein A can be removed with urea and 2-mercaptoethanol, and the same paper can be probed again with a different antiserum. An antiserum specific for the simian virus 40 virion proteins VP3 and VP2 has been prepared; it does not crossreact with VP1, as demonstrated by this method. An antiserum raised in rabbits against simian virus 40-transformed rabbit kidney cells is shown to be directed primarily against a periodate-sensitive moiety present in tumor (T) antigen from infected or transformed cells, whereas an antiserum raised in rabbits against large T antigen purified from lytically infected monkey kidney cells by electrophoresis in the presence of sodium dodecyl sulfate [Lane, D.P. & Robbins, A.K. (1978) Virology 87, 182-193] is directed primarily against determinants that are not sensitive to periodate.
Comparative, open, randomized trial of the efficacy and tolerance of slow- release 5-ASA suppositories once daily versus conventional 5-ASA suppositories twice daily in the treatment of active cryptogenic proctitis (2000)

Abstract OBJECTIVE: The efficacy and tolerance of slow-release 5-ASA suppositories (Pentasa 1 g/day) were compared with those of conventional 5-ASA suppositories (Rowasa 0.5 g b.i.d.). METHODS: Two hundred and fifty-one (251) patients presenting with an exacerbation of cryptogenic proctitis were randomized. Clinical activity and rectal lesions were measured at days 1 and 14 (and at day 21 for patients not in remission at day 14), and each patient had to fill out a daily diary card (checklist). RESULTS: Results are given for slow-release and classical suppositories, respectively. The reduction in symptoms and lesions was identical in both groups. Treatment was continued until day 21 in 36% versus 33% of the patients, and minor or moderate side effects occurred in 5.6% versus 6.3% (NS). The tolerance of the suppositories was rated as satisfactory every day by 77% versus 54% (p = 0.001), and early suppository expulsion occurred in 0.5% versus 3.4% (p = 0.001). CONCLUSIONS: The treatments were equally effective and both were well tolerated. However, the advantages of the slow-release suppositories were that patients exhibited greater tolerance and early expulsion was less frequent.
High-Q optical resonators in silicon-on-insulator-based slot waveguides (2005)

This letter describes the design, fabrication and characterization of high-Q oval resonators based on slot waveguide geometries in thin silicon-on-insulator material. Optical quality factors of up to 27 000 were measured in such filters, and we estimate losses of −10 dB/cm in the slotted waveguides on the basis of our resonator measurements. Such waveguides enable the concentration of light to very high optical fields within nanoscale dimensions, and show promise for the confinement of light in low-index material with potential applications for optical modulation, nonlinear optics and optical sensing.
Role of Basic Residues of the Autolysis Loop in the Catalytic Function of Factor Xa (2002)

The autolysis loop of factor Xa (fXa) has four basic residues (Arg(143), Lys(147), Arg(150), and Arg(154)) whose contribution to protease specificity of fXa has not been examined. Here, we substituted these basic residues individually with Ala in the fX cDNA and expressed them in mammalian cells using a novel expression/purification vector system. Following purification to homogeneity and activation by the factor X activator from Russell viper venom, the mutants were characterized with respect to their ability to assemble into the prothrombinase complex to activate prothrombin and interact with target plasma fXa inhibitors, tissue factor pathway inhibitor (TFPI) and antithrombin. We show that all mutants interacted with factor Va with normal affinities and exhibited wild-type-like prothrombinase activities toward prothrombin. Lys(147) and Arg(154) mutants were inhibited by TFPI approximately 2-fold slower than wild type; however, both Arg(143) and Arg(150) mutants were inhibited normally by the inhibitor. The reactivities of Arg(143) and Lys(147) mutants were improved approximately 2-fold with antithrombin in the absence but not in the presence of heparin cofactors. On the other hand, the pentasaccharide-catalyzed reactivity of antithrombin with the Arg(150) mutant was impaired by an order of magnitude. These results suggest that Arg(150) of the autolysis loop may specifically interact with the activated conformation of antithrombin.
Familial aggregation of lipids and lipoproteins in families ascertained through random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study. (1991)

The familial aggregation of lipids [total cholesterol (CH) and triglyceride (TG)] and lipoproteins [high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL)] was investigated in families ascertained through both random and nonrandom probands in the Minnesota Lipid Research Clinic Family Study. Nonrandom proband ascertainment was based on single selection through truncation for hyperlipidemia at an earlier screening. A path model was used to investigate the nature of familial resemblance using appropriate adjustments for ascertainment and to determine whether random and hyperlipidemic samples are heterogeneous with regard to the multifactorial model. The results suggest that parameter estimates are consistent with those from previous studies in which only random families were used and that random and nonrandom samples are homogeneous with regard to the path model for CH and LDL. However, for TG and HDL the random and hyperlipidemic samples are significantly heterogeneous. This heterogeneity would be observed if familial hypertriglyceridemia and/or familial hypoalphalipoproteinemia segregates predominantly in the hyperlipidemic rather than in the random sample, as on might expect.
HUMAN TYPE 1 DIABETES AND THE INSULIN GENE: Principles of Mapping Polygenes (1996)

▪ Abstract We review the strategy used to identify a susceptibility locus (IDDM2) for type 1 (insulin dependent) diabetes mellitus. As type 1 diabetes is becoming the paradigm for dissecting multifactorial disease genetics, the approach described provides important general guidelines for positional cloning of human disease polygenes. Main topics include: (a) historical conspectus of the mapping and identification of IDDM2—a critical survey of the work leading up to the conclusion that IDDM2 most likely corresponds to allelic variation at the insulin gene minisatellite (VNTR) locus; (b) the nature of allelic (length and sequence) variation at the VNTR locus; (c) gene interactions and disease pathogenesis; (d) mechanism of action of the INS VNTR in type 1 diabetes—insulin gene expression, parent-of-origin effects (genomic imprinting); and (e) summary and future prospects—alleles of the insulin VNTR that are protective for type 1 diabetes appear to encode susceptibility to type 2 diabetes.
802.11 with multiple antennas for dummies (2010)

The use of multiple antennas and MIMO techniques based on them is the key feature of 802.11n equipment that sets it apart from earlier 802.11a/g equipment. It is responsible for superior performance, reliability and range. In this tutorial, we provide a brief introduction to multiple antenna techniques. We describe the two main classes of those techniques, spatial diversity and spatial multiplexing. To ground our discussion, we explain how they work in 802.11n NICs in practice.
The essentiality and involvement of Streptococcus intermedius histone‐like DNA‐binding protein in bacterial viability and normal growth (2008)

Streptococcus intermedius histone-like DNA-binding protein (Si-HLP) is a homodimeric protein and, conserved with Escherichia coli HU, a well-documented nucleoid-associated protein (NAP). In E. coli, HU plays important roles as both structural and regulatory factors, but it is not essential for E. coli viability. Streptococcal HLP has been found to bind host cells and induce cytokine production, but its physiological role remains poorly defined. In the present study, using gene insertion knockout and tetracycline-regulated antisense RNA expression techniques, we determined whether Si-HLP is essential for bacterial viability and normal growth in S. intermedius. The Si-HLP-downregulated S. intermedius strain showed alterations in its morphology and surface properties. Downregulation of Si-HLP led to an expanded nucleoid to fill the intracellular space. Transcription levels of several genes, including virulence-associated factors, were found to be activated or repressed in the antisense Si-hlp RNA-expressing strain by real-time PCR and reverse-transcription PCR. Collectively, these data suggest that Si-HLP serves as an essential NAP governing the nucleoid architecture and controlling the gene transcription profile in S. intermedius.
Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies (2014)

Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and clinically important toxicity. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced nephrotoxicity. Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is still high, occurring in approximately one-third of patients who have undergone cisplatin therapy. Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity.