gebhart/patrepeval huggingface dataset:
Tak1 Selective Inhibition: State of the Art and Future Opportunities (2015)

The mitogen activated protein kinase kinase kinase transforming growth factor-β-activated kinase 1 (TAK1) has emerged as an interesting therapeutic target for inflammatory diseases and cancer. TAK1 is a tightly regulated kinase that represents a key signaling node in cellular responses to inflammatory stimuli, modulating both expression of inflammatory mediators and cell death. The first inhibitors described for TAK1 exploit the active site cysteine residue found in this kinase, but more recently both type I ATP hinge-binding inhibitors and type II DFG-out inhibitors have been described. This article will review the emerging role of TAK1 kinase in inflammation, the current state of the art for small molecule inhibitor development and opportunities for chemical biology approaches.
HBV : Entecavir Plus Tenofovir Combination Therapy in Patients with Multi-drug Resistant Chronic Hepatitis B: A Multicenter, Prospective Study-Early Experience (2013)

Background: It has been one of unsolved issues and unmet needs in chronic hepatitis B (CHB) treatment to manage multidrug resistant (MDR) hepatitis B virus. The aim of this study was to elucidate the antiviral efficacy and safety of entecavir plus tenofovir combination therapy in patients with MDR CHB. Methods: In this prospective ongoing multicenter study, patients with MDR CHB defined as detectable HBV DNA (≥ 60 IU/mL) while on any rescue treatment regimen for at least 24 weeks and prior experience of genotypic resistance to both nucleoside analogue(s) and nucleotide analogue are treated with entecavir and tenofovir combination therapy. The primary endpoint is the proportion of patients with HBV DNA < 60 IU/ml at Week 48. We present here the first 12 week interim analysis. Results: 61 patients were enrolled at the time interim analysis and 42 of these reached week 12. At baseline, mean age was 47.4 years, 83% were male, 86% were HBeAg(+), mean HBV DNA was 4.55 (±1.23) log 10IU/ml, and mean ALT was 41.3 IU/ml; 4 patients (9.5%) had documented resistance mutations to lamivudine (LAM) only, 3 (7.1%) to LAM and adefovir (ADF), 14 (33.3%) to ADF, 4 (9.5%) to LAM and entecavir, and 8 (19.0%) to all. By week 4, 9 (21.4%) patients achieved HBV DNA < 60 IU/ml and the mean reductions in HBV DNA was 1.39 ± 0.77 log 10IU/ml. By week 12, 24 (57.1%) patients achieved HBV DNA < 60 IU/ml and the mean reductions in HBV DNA was 2.11 ± 0.77 log 10IU/ml. On-treatment ALT flare was reported in 1 patient during the first 12 week. There was no serious adverse event. Conclusions: In the first 12 week interim analysis in patients with MDR CHB, entecavir plus tenofovir combination therapy early suppressed HBV replication to undetectable HBV DNA levels in the majority (57.1%) of patients.
Polyhalogenoallenes. Part VIII. Routes to tetrafluoroallene and tetra-fluoropropyne (1969)

Pyrolysis of 1,3-dibromo-1,1,3,3-tetrafluoropropane, from dibromodifluoromethane and vinylidene fluoride, over activated charcoal gives 3-bromo-1,1,3,3-tetrafluoropropene. Free-radical bromination of the propene yields 1,2,3-tribromo-1,1,3,3-tetrafluoropropane, which provides 2,3-dibromo-1,1,3,3-tetrafluoropropene when treated with aqueous potash. Debromination of the 2,3-dibromopropene with magnesium in tetrahydrofuran yields tetrafluoroallene. Tetrafluoropropyne is obtained by debromination with zinc of 1,2-dibromo-1,3,3,3-tetrafluoropropene, prepared by reaction of its isomer 2,3-dibromo-1,1,3,3-tetrafluoropropene with aluminium bromide.The n.m.r. spectra of tetrafluoroallene and tetrafluoropropyne are discussed.
Atomic Layer Deposition on Suspended Single-Walled Carbon Nanotubes via Gas-Phase Noncovalent Functionalization (2006)

Alternating exposures of nitrogen dioxide gas and trimethylaluminum vapor are shown to functionalize the surfaces of single-walled carbon nanotubes with a self-limited monolayer. Functionalized nanotube surfaces are susceptible to atomic layer deposition of continuous, radially isotropic material. This allows for the creation of coaxial nanotube structures of multiple materials with precisely controlled diameters. Functionalization involves only weak physical bonding, avoiding covalent modification, which should preserve the unique optical, electrical, and mechanical properties of the nanotubes.
A cryptographic file system for UNIX (1993)

Although cryptographic techniques are playing an increasingly important role in modern computing system security, user-level tools for encrypting file data are cumbersome and suffer from a number of inherent vulnerabilities. The Cryptographic File System (CFS) pushes encryption services into the file system itself. CFS supports secure storage at the system level through a standard Unix file system interface to encrypted files. Users associate a cryptographic key with the directories they wish to protect. Files in these directories (as well as their pathname components) are transparently encrypted and decrypted with the specified key without further user intervention; cleartext is never stored on a disk or sent to a remote file server. CFS can use any available file system for its underlying storage without modification, including remote file servers such as NFS. System management functions, such as file backup, work in a normal manner and without knowledge of the key.
Gaussian Process Models of Dynamic PET for Functional Volume Definition in Radiation Oncology (2012)

In routine oncologic positron emission tomography (PET), dynamic information is discarded by time-averaging the signal to produce static images of the “standardised uptake value” (SUV). Defining functional volumes of interest (VOIs) in terms of SUV is flawed, as values are affected by confounding factors and the chosen time window, and SUV images are not sensitive to functional heterogeneity of pathological tissues. Also, SUV iso-contours are highly affected by the choice of threshold and no threshold, or other SUV-based segmentation method, is universally accepted for a given VOI type. Gaussian Process (GP) time series models describe macro-scale dynamic behavior arising from countless interacting micro-scale processes, as is the case for PET signals from heterogeneous tissue. We use GPs to model time-activity curves (TACs) from dynamic PET and to define functional volumes for PET oncology. Probabilistic methods of tissue discrimination are presented along with novel contouring methods for functional VOI segmentation. We demonstrate the value of GP models for voxel classification and VOI contouring of diseased and metastatic tissues with functional heterogeneity in prostate PET. Classification experiments reveal superior sensitivity and specificity over SUV calculation and a TAC-based method proposed in recent literature. Contouring experiments reveal differences in shape between gold-standard and GP VOIs and correlation with kinetic models shows that the novel VOIs contain extra clinically relevant information compared to SUVs alone. We conclude that the proposed models offer a principled data analysis technique that improves on SUVs for oncologic VOI definition. Continuing research will generalize GP models for different oncology tracers and imaging protocols with the ultimate goal of clinical use including treatment planning.
Arthroplasty of the Knee in Rheumatoid Arthritis and Osteoarthritis (1972)

The literature related to arthroplasty of the knee is reviewed and the surgical technique and postoperative management for knee arthroplasty using the McKeever and MacIntosh prostheses are described. The results after follow-ups ranging from one to nine years in eighty-two patients with rheumatoid arthritis and seventeen patients with osteoarthritis are presented using a method of evaluation based on demerits assigned for pain, limitation of motion, deformity, instability, quadriceps weakness, and need for support. Using the described method of evaluation, fifty-six of the ninety-nine rheumatoid knees and seventeen of the nineteen osteoarthritic knees which could be evaluated, had good or excellent results. From these findings it is concluded that knee arthroplasty of the type described when performed in properly selected patients is an effective method to relieve pain and restore function.
Relating oxygen partial pressure, saturation and content: the haemoglobin–oxygen dissociation curve (2015)

The delivery of oxygen by arterial blood to the tissues of the body has a number of critical determinants including blood oxygen concentration (content), saturation (S O2 ) and partial pressure, haemoglobin concentration and cardiac output, including its distribution. The haemoglobin-oxygen dissociation curve, a graphical representation of the relationship between oxygen satur-ation and oxygen partial pressure helps us to understand some of the principles underpinning this process. Historically this curve was derived from very limited data based on blood samples from small numbers of healthy subjects which were manipulated in vitro and ultimately determined by equations such as those described by Severinghaus in 1979. In a study of 3524 clinical specimens, we found that this equation estimated the S O2 in blood from patients with normal pH and S O2 >70% with remarkable accuracy and, to our knowledge, this is the first large-scale validation of this equation using clinical samples. Oxygen saturation by pulse oximetry (S pO2 ) is nowadays the standard clinical method for assessing arterial oxygen saturation, providing a convenient, pain-free means of continuously assessing oxygenation, provided the interpreting clinician is aware of important limitations. The use of pulse oximetry reduces the need for arterial blood gas analysis (S aO2 ) as many patients who are not at risk of hypercapnic respiratory failure or metabolic acidosis and have acceptable S pO2 do not necessarily require blood gas analysis. While arterial sampling remains the gold-standard method of assessing ventilation and oxygenation, in those patients in whom blood gas analysis is indicated, arterialised capillary samples also have a valuable role in patient care. The clinical role of venous blood gases however remains less well defined.
Low-loss and stable fiber-to-waveguide connection utilizing UV curable adhesive (1992)

A low-loss and stable fiber-to-waveguide connection was realized utilizing a newly developed UV curable epoxy resin which has improved humidity durability. The average connection loss was as low as 0.09 dB/point with a return loss of 46 dB. The loss increase was not observed after a heat-cycle test between -40 and 85 degrees C, a high-temperature test at 85 degrees C, or a low-temperature test at -40 degrees C. In a high-humidity test at 70 degrees C and 90% relative humidity, the loss increase was less than 0.2 dB after 400 h.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Design of metal‐binding sites onto self‐assembled peptide fibrils (2009)

The ability to develop a rational basis for the binding of inorganic materials to specific binding sites within self-assembling biological scaffolds has important applications in nanobiotechnology. Amyloid-forming peptides are a class of such scaffolds and show enormous potential as templates for the fabrication of low resistance, conducting nanowires. Here we report the use of a self-assembling peptide building block as scaffold for the systematic introduction of metal-binding residues at specific locations within the structure. The octapeptide NSGAITIG (Asparagine-Serine-Glycine-Alanine-Isoleucine-Threonine-Isoleucine-Glycine) from the fiber protein of adenovirus has been identified in previous structural studies as an elementary fibril-forming building block. Using this building block as a scaffold, we have designed three new cysteine-containing octa-peptides to study their eventual fibril-forming ability and potential templating of metal nanoparticles. We find that the cysteine substitutions do not alter the fibril-forming potential of the peptides, and that the fibrils formed bind efficiently to silver, gold, and platinum nanoparticles; furthermore, we report unexpected behavior of serine in nucleating gold and platinum nanoparticles. We find that combination of cysteine and serine residues projecting from adjacent sites on a peptide scaffold represents a potentially useful strategy in nucleating inorganic materials. The ability to reliably produce metal-coated fibrils is a vital first step towards the exploitation of these fibrils as conducting nanowires with applications in nano-circuitry. Short, biologically inspired self-assembling peptide scaffolds derived from natural fibrous proteins with known three-dimensional structure may provide a viable approach towards the rational design of inorganic nanowires.
Two-Component Systems of <i>Helicobacter pylori</i> Contribute to Virulence in a Mouse Infection Model (2003)

Helicobacter pylori encodes three histidine kinases and five response regulators belonging to the family of two-component regulatory systems which are involved in transcriptional control. Here we demonstrate that isogenic mutants of H. pylori P76 with deletions of the response regulator open reading frame (ORF) HP1365 and ORFs HP244, HP165, and HP1364 encoding histidine kinases are unable to colonize the stomachs of BALB/c mice, suggesting an essential role of these systems in the regulation of important virulence properties of H. pylori. Furthermore, we demonstrate that the genes under the control of the P(HP1408) and P(HP119) promoters which are regulated by the two-component system HP166-HP165 are not essential for single mutant colonization of mice but are required under competitive colonization conditions.
Understanding thin-client/server computing (1997)

• What Is Thin-Client/Server Computing? • How Does Thin-Client/Server Computing Work? • What Do You Need to Do, and Where Do You Need to Do It? o Mobile Task-Based User o Office Task-Based User o Knowledge Workers o Power Users with Creative and Analytic Task Needs • Addressing the Issues: Management and Scalability, Access, Performance, Security, and Total Cost of Ownership o Management and Scalability o Access o Performance o Security o Total Cost of Ownership • In Conclusion
Room‐temperature preparation and characterization of poly (ethylene glycol)‐coated silica nanoparticles for biomedical applications (2003)

Monodisperse, spherical, polyethylene glycol (PEG)-coated silica nanoparticles have been prepared at room temperature and characterized for the purpose of biomedical applications. The particles were synthesized by the hydrolysis of tetramethyl orthosilicate (TMOS) in alcohol media under catalysis by ammonia, and their size can range from about 50-350 nm in diameter. We studied the particle size and size distribution using a scanning electron microscope (SEM) and an asymmetric field-flow fractionation (AFFF) multiangle static light-scattering instrument. The chemical and/or physical binding of PEG to the silica nanoparticles was studied by infrared spectroscopy, and the weight percentage of PEG attached to the particles was quantified. The PEG-coated silica nanoparticles showed enhanced colloidal stability when redispersed into aqueous solutions from the dried state as a result of the steric stabilization function of the PEG polymer grafted on the surface of particles. A nonspecific protein-binding test was also carried out to show that the PEG coating can help reduce the protein adsorption onto the surface of the particles, relating to the biocompatibility of these PEG-coated particles. Also, the inclusion of magnetic nanoparticles into the silica particles was shown as an example of the possible applications of PEG-coated silica particles. These silica nanoparticles, as a matrix for encapsulation of certain reagents, have potential for applications to in vivo diagnosis, analysis, and measurements inside intact biologic systems.
Extracellular regulators of axonal growth in the adult central nervous system (2006)

Robust axonal growth is required during development to establish neuronal connectivity. However, stable fibre patterns are necessary to maintain adult mammalian central nervous system (CNS) function. After adult CNS injury, factors that maintain axonal stability limit the recovery of function. Extracellular molecules play an important role in preserving the stability of the adult CNS axons and in restricting recovery from pathological damage. Adult axonal growth inhibitors include a group of proteins on the oligodendrocyte, Nogo-A, myelin-associated glycoprotein, oligodendrocyte-myelin glycoprotein and ephrin-B3, which interact with axonal receptors, such as NgR1 and EphA4. Extracellular proteoglycans containing chondroitin sulphates also inhibit axonal sprouting in the adult CNS, particularly at the sites of astroglial scar formation. Therapeutic perturbations of these extracellular axonal growth inhibitors and their receptors or signalling mechanisms provide a degree of axonal sprouting and regeneration in the adult CNS. After CNS injury, such interventions support a partial return of neurological function.
High-voltage bulk photovoltaic effect and the photorefractive process in LiNbO3 (1974)

Photocurrents in doped LiNbO3 crystals are shown to be due to a bulk photovoltaic effect with saturation voltages in excess of 1000 V (∼105 V/cm). This effect accounts for the light-induced index changes in LiNbO3. An explanation of the photovoltaic effect, based on the asymmetry of the lattice, is proposed.
Safety of Antioxidant Vitamins (1996)

As a result of the many scientific and popular press reports of the benefits of antioxidant vitamins (vitamin A, beta-carotene, vitamin E, and ascorbic acid), it is estimated that 40% of the US population is consuming vitamin supplements. The efficacy of these supplements is not yet proved, and some have questioned their safety. Approximately 10 to 15 cases of vitamin A toxic reactions are reported per year in the United States, usually at doses greater than 100,000 IU/d. No adverse effects have been reported for beta-carotene. The frequency of vitamin E toxic reactions is not well delineated, but case reports are few at dosages less than 3200 mg/d. Ascorbic acid toxic reactions are rare at dosages less than 4 g/d. Despite a lack of clinical trial data, it seems that antioxidant vitamins are safe, although prudence might dictate their avoidance by women of childbearing potential, persons with liver disease or renal dysfunction, and those taking certain medications or undergoing specific laboratory tests.
Small Materialized Aggregates: A Light Weight Index Structure for Data Warehousing (1998)

Small Materialized Aggregates (SMAs for short) are considered a highly flexible and versatile alternative for materialized data cubes. The basic idea is to compute many aggregate values for small to medium-sized buckets of tuples. These aggregates are then used to speed up query processing. We present the general idea and present an application of SMAs to the TPC-D benchmark. We show that application of SMAs to TPC-D Query 1 results in a speed up of two orders of magnitude. Then, we elaborate on the problem of query processing in the presence of SMAs. Last, we briefly discuss some further tuning possibilities for SMAs.
A lossless image compression algorithm using variable block size segmentation (1995)

The redundancy in digital image representation can be classified into two categories: local and global. In this paper, we present an analysis of two image characteristics that give rise to local and global redundancy in image representation. Based on this study, we propose a lossless image compression scheme that exploits redundancy both at local and global levels in order to obtain maximum compression efficiency. The proposed algorithm segments the image into variable size blocks and encodes them depending on the characteristics exhibited by the pixels within the block. The proposed algorithm is implemented in software and its performance is better than other lossless compression schemes such as the Huffman, the arithmetic, the Lempel-Ziv and the JPEG.
A Novel two Step Procedure for Immobilizing Living Cells in Microcapsules for Improving Xenograft Survival (1991)

Histologically identified surface irregularities caused by the physical entrapment of encapsulated cells in the microcapsular membrane matrix of standard alginate-polylysine microcapsules potentiated graft rejection in mice. We have therefore devised a novel two step procedure to prevent the entrapment of cells in the capsular membrane matrix. With the new method the capsular membrane appeared uniform and without the physical entrapment of cells in the capsular membrane matrix. Furthermore, after 7 days of intraperitoneal implantation of encapsulated rat hepatocytes in mice, microcapsular membrane perforations and leukocyte infiltrations were not observed. Also a greater percentage of the modified capsules, free from fibrous encapsulation, were recovered after 7 and 11 days of intraperitoneal implantation compared to the standard microcapsule preparations.
Virus or TLR Agonists Induce TRAIL-Mediated Cytotoxic Activity of Plasmacytoid Dendritic Cells (2006)

Among dendritic cells, plasmacytoid dendritic cells (PDC) represent a functionally distinct lineage. Regarding innate immunity, PDC secrete large amounts of type I IFN upon viral exposure or stimulation by microbial products such as unmethylated CpG-motif containing oligo-DNA due to their selective expression of TLR7 and TLR9. We asked whether they could acquire cytotoxic functions during the early phases of infection or after activation with TLR7 or TLR9 agonists. In the present study, we describe a human PDC cell line called GEN2.2, derived from leukemic PDC, that shares most of the phenotypic and functional features of normal PDC. We show that after contact with the influenza virus, GEN2.2, as well as normal PDC, acquires TRAIL and killer activity against TRAIL-sensitive target cells. Moreover, we show that activation of GEN2.2 cells by CpG-motif containing oligo-DNA or R848 also induces TRAIL and endows them with the ability to kill melanoma cells. Therefore, PDC may represent a major component of innate immunity that could participate to the clearance of infected cells and tumor cells. This phenomenon could be relevant for the efficacy of TLR7 or TLR9 agonists in the therapy of infectious disease and cancer.