gebhart/patrepeval huggingface dataset:
Anti-Aβ1–11 Antibody Binds to Different β-Amyloid Species, Inhibits Fibril Formation, and Disaggregates Preformed Fibrils but Not the Most Toxic Oligomers (2007)

Different strategies proposed as therapy for Alzheimer disease (AD) have aimed to reduce the level of toxic forms of A beta peptide in the brain. Here, we directly analyze the therapeutic utility of the polyclonal anti-A beta(1-11) antibody induced in 3xTg-AD mice vaccinated with the second generation prototype epitope vaccine. Substoichiometric concentrations of purified anti-A beta(1-11) antibody prevented aggregation of A beta(42) and induced disaggregation of preformed A beta(42) fibrils down to nonfilamentous and nontoxic species. Anti-A beta(1-11) antibody delayed A beta(42) oligomer formation but ultimately appeared to stabilize nonfibrillar conformations, including oligomer-like assemblies. The reduced oligomer-mediated cytotoxicity observed upon preincubation of A beta oligomers with the anti-A beta(1-11) antibody in the absence of oligomer disaggregation suggests a possible oligomer rearrangement in the presence of the antibody. These in vitro observations suggest that preventive vaccination may protect from AD or may delay the onset of the disease, whereas therapeutic vaccination cannot disrupt the toxic oligomers and may only minimally alleviate preexisting AD pathology.
Efficient state updates for key management (2004)

Encryption is widely used to enforce usage rules for digital content. In many scenarios content is encrypted using a group key which is known to a group of users that are allowed to use the content. When users leave or join the group, the group key must be changed. The logical key hierarchy (LKH) algorithm is a very common method of managing these key changes. In this algorithm every user keeps a personal key composed of log n keys (for a group of n users). A key update message consists of O(log n) keys. A major drawback of the LKH algorithm is that users must update their state whenever users join or leave the group. When such an event happens, a key update message is sent to all users. A user who is offline during t key updates, and who needs to learn the keys sent in these updates as well as update its personal key, should receive and process the t key update messages, of total length O(t log n) keys. In this paper, we show how to reduce this overhead to a message of O(log t) keys. We also note that one of the methods that are used in this work to reduce the size of the update message can be used in other scenarios as well. It enables one to generate n pseudorandom keys of length k bits each, such that any successive set of t keys can be represented by a string log(t)/spl middot/k bits, without disclosing any information about the other keys.
An Improved Synthesis of 2-Chlorinated Imidazo[1,2-α]-pyridines and the Application of this Procedure for the Synthesis of Several New Polychlorinated Imidazo[1,2-α]Pyridnes. (1997)

Abstract Polychlorinated imidazo[1,2-α]pyridines were synthesized as analogs of certain chlorinated benzimidazoles. The imidazo[1,2-α]pyridines were obtained by a condensation of ethyl bromoacetate and chlorinated 2-aminopyridines. These condensation products were treated with an ion exchange resin to effect an exchange of hydrobromide salts with hydrochloride salts. These compounds were subsequently treated with POCl3 to convert the imidazo[1,2-α]pyridin-2-ones into 2-chloroimidazo[1,2-a]pyridines.
Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats (2009)

Autonomic and peripheral neuropathies are well-described complications in diabetes. Diabetes mellitus is also associated to central nervous system damage. This little-known complication is characterized by impairment of brain functions and electrophysiological changes associated with neurochemical and structural abnormalities. The purpose of this study was to investigate brain structural and ultrastructural changes in rats with streptozotocin-induced diabetes. Cerebral cortex, hypothalamus, and cerebellum were obtained from controls and 8 weeks diabetic rats. Light and electron microscope studies showed degenerative changes of neurons and glia, perivascular and mitochondrial swelling, disarrangement of myelin sheath, increased area of myelinated axons, presynaptic vesicle dispersion in swollen axonal boutoms, fragmentation of neurofilaments, and oligodendrocyte abnormalities. In addition, depressive mood was observed in diabetic animals. The brain morphological alterations observed in diabetic animals could be related to brain pathologic process leading to abnormal function, cellular death, and depressive behavioral.
Macrocyclic Histone Deacetylase Inhibitors (2010)

Histone deacetylase inhibitors (HDACi) are an emerging class of novel anti-cancer drugs that cause growth arrest, differentiation, and apoptosis of tumor cells. In addition, they have shown promise as anti-parasitic, anti-neurodegenerative, anti-rheumatologic and immunosuppressant agents. To date, several structurally distinct small molecule HDACi have been reported including aryl hydroxamates, benzamides, short-chain fatty acids, electrophilic ketones, and macrocyclic peptides. Macrocyclic HDACi possess the most complex cap-groups which interact with HDAC enzyme's outer rim and have demonstrated excellent HDAC inhibition potency and isoform selectivity. This review focuses on the recent progress and current state of macrocyclic HDACi.
CNP: An FPGA-based processor for Convolutional Networks (2009)

Convolutional networks (ConvNets) are biologically inspired hierarchical architectures that can be trained to perform a variety of detection, recognition and segmentation tasks. ConvNets have a feed-forward architecture consisting of multiple linear convolution filters interspersed with pointwise non-linear squashing functions. This paper presents an efficient implementation of ConvNets on a low-end DSP-oriented field programmable gate array (FPGA). The implementation exploits the inherent parallelism of ConvNets and takes full advantage of multiple hardware multiply accumulate units on the FPGA. The entire system uses a single FPGA with an external memory module, and no extra parts. A network compiler software was implemented, which takes a description of a trained ConvNet and compiles it into a sequence of instructions for the ConvNet Processor (CNP). A ConvNet face detection system was implemented and tested. Face detection on a 512 times 384 frame takes 100 ms (10 frames per second), which corresponds to an average performance of 3.4 times 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">9</sup> connections per second for this 340 million connection network. The design can be used for low-power, lightweight embedded vision systems for micro-UAVs and other small robots.
Inter-alpha-trypsin inhibitor-related immunoreactivity in human tissues and body fluids. (1992)

The distribution of inter-alpha-trypsin inhibitor (ITI) and related inhibitors was investigated in normal human tissues and body fluids by using an enzyme-linked immunosorbent assay (ELISA) and a streptavidin-biotin-peroxidase immunohistochemical technique. ITI-related immunoreactivity was localized in different cell types of various organs, such as liver, kidney, testis, gross intestine, cutis and brain. Specific immunoreactivity was also detected in serum, urine and bronchial mucus. This widespread, but not ubiquitous pattern of localization suggests that, in addition to the well known plasmatic role, ITI and/or ITI-related inhibitors may play a number of different physiological roles in various human tissues.
New corrosion resistant materials based on neodym-iron-boron (1997)

The properties of neodymium-iron-boron sintered magnets are optimised to attain high temperature stability and excellent corrosion resistance without coating or surface treatment. By the addition of elements to form intermetallic phases the intergranular region of this new material consists mainly of intermetallic phases and the corrosible Nd-rich phase is avoided as far as possible. Same additives which guarantee excellent corrosion properties comparable to SmCo permanent magnets are used to get better temperature coefficients of the remanence and the coercivity. A reduction of the temperature influence by 20 to 30% is achieved. Magnetic properties can be adjusted for the operation temperatures. By variation of the chemical composition high temperature applications up to 250/spl deg/C can be accommodated.
Synthesis, in Vitro Anti-Human Immunodeficiency Virus Structure—Activity Relationships and Biological Stability of 5′-O-Myristoyl Analogue Derivatives of 3′-Azido-2′,3′-Dideoxythymidine (AZT) as Potential Prodrugs (1998)

5'-O-Myristoyl analogue derivatives of 3'-azido-2',3'-dideoxythymidine (AZT), designed as potential double-barrelled prodrugs to AZT and the myristic acid analogues, were synthesized. Their ability to protect CEM cells against human immunodeficiency virus (HIV)-induced cytopathogenicity was determined and structure-activity paradigms were developed. 3'-Azido-2',3'-dideoxy-5'-O-(4-oxatetradecanoyl)thymidine (EC50 = 1.4 nM) and 3'-azido-2',3'-deoxy-5'-O-(12-bromododecanoyl)thymidine (EC50 = 3.2 nM) were the most effective anti-HIV-1 agents, relative to AZT (EC50 = 10 nM). These myristoyl analogue derivatives were more lipophilic (calculated log P = 4.5-8.1 range) than the parent compound AZT (log P = 0.06), and a linear correlation between their log P and HPLC log retention times was observed. The ester cleavage half-lives (t1/2) for esters upon in vitro incubation with porcine liver esterase, rat plasma or rat brain homogenate was dependent on the steric bulk, and electronegative inductive effect of the alpha-substituent (H, Br, F), of the 5'-O-myristoyl analogue moiety. 3'-Azido-2',3'-dideoxy-5'-O-(11-(4-iodophenoxy) undecanoyl)-thymidine exhibited t1/2 values of 80.4, 3.7 and 150.0 min upon incubation with porcine liver esterase, rat plasma and rat brain homogenate, respectively.
Discovery and characterization of a new transposable element, Tn4811, in Streptomyces lividans 66 (1992)

Transposition of a new 5.4-kb transposon, Tn4811, of Streptomyces lividans to the melC operon of Streptomyces antibioticus on plasmid pIJ702 was discovered. The nucleotide sequence of this copy of Tn4811, which contained an imperfect (9 of 11 bp) terminal inverted repeat, five putative Streptomyces coding sequences for an oxidoreductase and its transcription regulator, and three transposition-related proteins, was determined. SLP- strains of S. lividans contained one copy (A) of Tn4811, while SLP2+ strains contained an additional copy (B) on the SLP2 plasmid. The nucleotide sequences at three insertion junctions of Tn4811 were determined. Copy B lacked 41 bp from the left end. At the other five junctions the duplication of a putative 3-bp target sequence (TGA) was observed. A sequence of less than 3 kb homologous to Tn4811 was present in S. antibioticus. DNA homologous to Tn4811 was not detected in 14 other Streptomyces species.
Effect of Stored-Blood Transfusion on Oxygen Delivery in Patients With Sepsis (1993)

We failed to demonstrate a beneficial effect of red blood cell transfusion on measured systemic oxygen uptake in patients with sepsis. Patients receiving old transfused red blood cells developed evidence of splanchnic ischemia. We postulate that the poorly deformable transfused red blood cells cause micro-circulatory occlusion in some organs, which may lead to tissue ischemia in some organs.
RNAi and microRNAs: From animal models to disease therapy (2006)

The discovery of the phenomenon of RNA interference (RNAi) and its existence in mammals quickly suggested a great potential for use in disease therapy. Rapid advances have been made in the development of RNAi-based technologies and promising results have been obtained from studies on mammalian cell culture systems and animal in vivo models. However, the progress in our understanding of the RNAi pathway and the related function of microRNAs (miRNAs) have also raised concerns regarding various types of side effects that may restrict the use of this technology in human therapy. At the same time, our new knowledge about the functional roles of miRNAs as regulators of many cellular processes, including proliferation, differentiation, development, and neuronal function, is revolutionizing cell biology and will have a major impact on medical research. In this review, we focus on the discoveries that have been made in animal models and how this insight can be translated to human medicine and disease therapy. In this connection, we will particularly discuss the challenges associated with the efforts to develop RNAi-based therapeutics.
Laparoscopic Liver Resection for Malignant Liver Tumors (2002)

In patients with small malignant tumors, located in the left lateral segments or in the anterior segments of the right liver, laparoscopic resection is feasible and safe. The complication rate is low, except in patients with HCC on cirrhotic liver. By using laparoscopic ultrasound, a 1-cm free surgical margin should be routinely obtained. The late outcome needs to be evaluated in expert centers.
The effect of insertion depth on the theoretical SAR patterns of 915 MHz dipole antenna arrays for hyperthermia (1989)

Interstitial microwave antenna array hyperthermia (IMAAH) is presently used clinically in the treatment of cancer. This paper presents the theoretical specific absorption rate (SAR) patterns of 915 MHz microwave antenna arrays for varying insertion depths. The antennas were oriented in a 2 x 2 cm square array. Insertion depth, defined as distance from skin to antenna tip, ranged from 5.9 to 17.6 cm. Two different antenna configurations were considered. In the first the antenna had a distal section a quarter-wavelength long (resonant case), while the second had a distal section approximately 13% longer than a quarter-wavelength (non-resonant case). SAR patterns were calculated from theoretical expressions, and displayed as lines of constant SAR normalized to the maximum SAR value in the array. The results show that regions of concentrated power deposition or 'hotspots' occurred in the centre of the array and moved in a complex but predictable fashion as insertion depth was varied. For insertion depths shorter than a resonant half-wavelength, there occurred one hotspot distal to the antenna junctions. As insertion depth was increased beyond a resonant half-wavelength, the hotspot moved proximal to the antenna junctions and eventually split in two. For depths very much longer than a resonant half-wavelength a hotspot centred about the antenna junction dominated the SAR pattern. For the resonant case the maximum SAR was often along the central axis of the array, while for the non-resonant case the maximum SAR was at the antennas with a local maximum on the central axis.
Substrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. Analysis of fatty acid analogs containing carbonyl groups, nitrogen heteroatoms, and nitrogen heterocycles in an in vitro enzyme assay and subsequent identification of inhibitors of human immunodeficiency virus I replication. (1992)

Covalent attachment of myristic acid (C14:0) to the amino-terminal glycine residue of a variety of eukaryotic cellular and viral proteins can have a profound influence on their biological properties. The enzyme that catalyzes this modification, myristoyl-CoA-protein N-myristoyltransferase (NMT), has been identified as a potential target for antiviral and antifungal therapy. Its reaction mechanism is ordered Bi Bi with myristoyl-CoA binding occurring before binding of peptide and CoA release preceding release of myristoylpeptide. Perturbations in the binding of its acyl-CoA substrate would therefore be expected to have an important influence on catalysis. We have synthesized 56 analogs of myristic acid (C14:0) to further characterize the acyl-CoA binding site of Saccharomyces cerevisiae NMT. The activity of fatty acid analogs was assessed using a coupled in vitro assay system that employed the reportedly nonspecific Pseudomonas acyl-CoA synthetase, purified S. cerevisiae NMT, and octapeptide substrates derived from residues 2-9 of the catalytic subunit of cyclic AMP-dependent protein kinase and the Pr55gag polyprotein precursor of human immunodeficiency virus I (HIV-I). Analysis of ketocarbonyl-, ester-, and amide-containing myristic acid analogs (the latter in two isomeric arrangements, the acylamino acid (-CO-NH-) and the amide (-NH-CO)) indicated that the enzyme's binding site is able to accommodate a dipolar protrusion from C4 through C13. This includes the region of the acyl chain occurring near C5-C6 (numbered from carboxyl) that appears to be bound in a bent conformation of 140-150 degrees. The activities of NMT's acyl-CoA substrates decrease with increasing polarity. This relationship was particularly apparent from an analysis of a series of analogs in which the hydrocarbon chain was terminated by (i) an azido group or (ii) one of three nitrogen heterocycles (imidazole, triazole, and tetrazole) alkylated at either nitrogen or carbon. This inverse relationship between polarity and activity was confirmed after comparison of the activities of the closely related ester- or amide-containing tetradecanoyl-CoA derivatives. Members from all of the analog series were surveyed to determine whether they could inhibit replication of human immunodeficiency virus I (HIV-I), a retrovirus that depends upon N-myristoylation of its Pr55gag for propagation. 12-Azidododecanoic acid was the most active analog tested, producing a 60-90% inhibition of viral production in both acutely and chronically infected T-lymphocyte cell lines at a concentration of 10-50 microM without associated cellular toxicity.
Flexible Wireless Temperature Sensors Based on Ni Microparticle‐Filled Binary Polymer Composites (2012)

Ni microparticle-filled binary polymer composites are developed as temperature sensors which possess greater improved reproducibility compared to single polymer composite sensors.
An NMR approach to structural proteomics (2002)

The influx of genomic sequence information has led to the concept of structural proteomics, the determination of protein structures on a genome-wide scale. Here we describe an approach to structural proteomics of small proteins using NMR spectroscopy. Over 500 small proteins from several organisms were cloned, expressed, purified, and evaluated by NMR. Although there was variability among proteomes, overall 20% of these proteins were found to be readily amenable to NMR structure determination. NMR sample preparation was centralized in one facility, and a distributive approach was used for NMR data collection and analysis. Twelve structures are reported here as part of this approach, which allowed us to infer putative functions for several conserved hypothetical proteins.
Selective Expansion of Chimeric Antigen Receptor-targeted T-cells with Potent Effector Function using Interleukin-4 (2010)

Polyclonal T-cells can be directed against cancer using transmembrane fusion molecules known as chimeric antigen receptors (CARs). Although preclinical studies have provided encouragement, pioneering clinical trials using CAR-based immunotherapy have been disappointing. Key obstacles are the need for robust expansion ex vivo followed by sustained survival of infused T-cells in patients. To address this, we have developed a system to achieve selective proliferation of CAR(+) T-cells using IL-4, a cytokine with several pathophysiologic and therapeutic links to cancer. A chimeric cytokine receptor (4alphabeta) was engineered by fusion of the IL-4 receptor alpha (IL-4Ralpha) ectodomain to the beta(c) subunit, used by IL-2 and IL-15. Addition of IL-4 to T-cells that express 4alphabeta resulted in STAT3/STAT5/ERK phosphorylation and exponential proliferation, mimicking the actions of IL-2. Using receptor-selective IL-4 muteins, partnering of 4alphabeta with gamma(c) was implicated in signal delivery. Next, human T-cells were engineered to co-express 4alphabeta with a CAR specific for tumor-associated MUC1. These T-cells exhibited an unprecedented capacity to elicit repeated destruction of MUC1-expressing tumor cultures and expanded through several logs in vitro. Despite prolonged culture in IL-4, T-cells retained specificity for target antigen, type 1 polarity, and cytokine dependence. Similar findings were observed using CARs directed against two additional tumor-associated targets, demonstrating generality of application. Furthermore, this system allows rapid ex vivo expansion and enrichment of engineered T-cells from small blood volumes, under GMP-compliant conditions. Together, these findings provide proof of principle for the development of IL-4-enhanced T-cell immunotherapy of cancer.
Isothermal Viscosity-Molecular Weight Dependence for Long Polymer Chains (1955)

Evidence is given showing that the equation, logη=3.4 logZ+K, represents an empirical law of flow which holds generally for sufficiently long flexible chain molecules in bulk or in solution. Here η is the viscosity, Z is the number of atoms in the chain, and K is a constant which is dependent on the polymer type and on the temperature. All of the available data which cover wide molecular weight ranges for linear (and branched) molecules in bulk or in solution, including results on polyesters, polyamides, polystyrene, polyisobutylene, polydimethyl siloxane, and polymethyl methacrylate, support this conclusion. For chains having fewer than a critical number, Zc, of chain atoms (Zc being characteristic of the polymer species) the dependence of η on Z is less severe but more complex. These results are in semiquantitative agreement with the recent theory of F. Bueche. On the basis of this theory, values for the concentration of chain entanglements in various polymers are obtained from the observed values of Zc.
Isolation of a Chinese Hamster Ovary (CHO) cDNA Encoding Phosphatidylglycerophosphate (PGP) Synthase, Expression of Which Corrects the Mitochondrial Abnormalities of a PGP Synthase-defective Mutant of CHO-K1 Cells (1999)

Phosphatidylglycerophosphate (PGP) synthase catalyzes the first step in the cardiolipin (CL) branch of phospholipid biosynthesis in mammalian cells. In this study, we isolated a Chinese hamster ovary (CHO) cDNA encoding a putative protein similar in sequence to the yeast PGS1 gene product, PGP synthase. The gene for the isolated CHO cDNA was named PGS1. Expression of the CHO PGS1 cDNA in CHO-K1 cells and production of a recombinant CHO PGS1 protein with a N-terminal extension in Escherichia coli resulted in 15-fold and 90-fold increases of PGP synthase specific activity, respectively, establishing that CHO PGS1 encodes PGP synthase. A PGP synthase-defective CHO mutant, PGS-S, isolated previously (Ohtsuka, T., Nishijima, M., and Akamatsu, Y. (1993) J. Biol. Chem. 268, 22908-22913) exhibits striking reductions in biosynthetic rate and cellular content of phosphatidylglycerol (PG) and CL and shows mitochondrial morphological and functional abnormalities. The CHO PGS-S mutant transfected with the CHO PGS1 cDNA exhibited 620-fold and 7-fold higher PGP synthase activity than mutant PGS-S and wild type CHO-K1 cells, respectively, and had a normal cellular content and rate of biosynthesis of PG and CL. In contrast to mutant PGS-S, the transfectant had morphologically normal mitochondria. When the transfectant and mutant PGS-S cells were cultivated in a glucose-depleted medium, in which cellular energy production mainly depends on mitochondrial function, the transformant but not mutant PGS-S was capable of growth. These results demonstrated that the morphological and functional defects displayed by the PGS-S mutant are due directly to the reduced ability to make normal levels of PG and/or CL.