gebhart/patrepeval huggingface dataset:
Development of Potent Glucagon-like Peptide-1 Agonists with High Enzyme Stability via Introduction of Multiple Lactam Bridges (2010)

Glucagon-like peptide-1 (GLP-1) has the ability to lower the blood glucose level, and its regulatory functions make it an attractive therapeutic agent for the treatment of type 2 diabetes. However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely compromises its effective clinical use. Whereas specific DPP-IV inhibitors have been developed, NEP 24.11 targets multiple sites in the GLP-1 sequence, which makes it difficult to block. To address this drawback, we have designed and synthesized conformationally constrained GLP-1 analogues by introducing multiple lactam bridges that stabilized both alpha-helices in the N- and C-terminal regions simultaneously. In addition to improving the receptor activation capability (up to 5-fold) by fixing the alpha-helical conformations required for optimal receptor interaction, the introduced lactam bridges provided outstanding shielding over NEP 24.11 (half-life of >96 h). These highly constrained peptides are the first examples of NEP 24.11-resistant GLP-1 analogues.
Acute Gastroduodenal Disease after Thermal Injury (1974)

To determine the incidence and the natural history of acute gastroduodenal disease after thermal injury, early and serial gastroduodenoscopies were performed in 32 adult patients with burns. Gastric erosions were present in 25 of 29 (86 per cent) with large burns. Seventeen of 23 (74 per cent) had lesions within 72 hours after the burn. In seven patients (22 per cent) a gastric ulcer developed. Ulcerations occurred only in diffusely abnormal areas and were not discovered before 72 hours after the burn. Nine patients (28 per cent) had a duodenal ulceration; all but one had concomitant gastric disease. In two cases, an ulcer was observed to evolve from an erosive "duodenitis." The early development, morphology and histology of the lesions suggested ischemic damage of the mucosa. Nine of 15 patients studied serially had progression of mucosal disease; sepsis, hypotension and hypoxia complicated the clinical course. Life-threatening hemorrhage or perforation occurred mainly in patients with ulcers (eight of nine cases). (N Engl J Med 291:925–929, 1974)
Human embryonic stem cell lines are contaminated: what should we do? (2005)

Human embryonic stem (hES) cells have the potential to differentiate into any desired cells and to be used in cell replacement therapies for some diseases. However, existing hES cell lines would not be suitable for the therapies as they are contaminated with other biological products. In order to produce the safest hES cell lines for therapeutic purposes, all steps for the establishment of hES cell lines must avoid the use of animal serum and/or animal feeder cell lines. Safe and fast approaches to producing hES cell lines based on recent research advances in both humans and animals have been suggested.
The Molecular Phylogeny and Systematics of the Actinomycetes (1994)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Elevated levels of members of the STAT family of transcription factors in breast carcinoma nuclear extracts (1995)

The transcription factor, milk protein binding factor (MPBF/Stat5), is a member of the STAT family of signalling molecules which mediates prolactin signal transduction in lactating mammary gland by binding to GAS (gamma-interferon activation site) DNA elements. We have determined the levels of STAT factors in nuclear extracts from a variety of human breast tissues including carcinoma and normal 'resting' breast by electrophoretic mobility-shift assay. The results show that the level of STAT binding activity is low in normal 'resting' breast and benign lesions while carcinoma samples have significantly higher (P < 0.01) amounts of STAT binding activity. Supershift analysis suggests that Stat1 and possibly other members of the STAT family of signalling factors, including Stat3, are activated in breast cancer tissues.
A peptide isolated by phage display binds to ICAM-1 and inhibits binding to LFA-1 (1996)

A mixed phage library containing random peptides from four to eight residues in length flanked by cysteine residues was screened using a recombinant soluble, form of human ICAM-1, which included residues 1-453, (ICAM-1(1-453)). Phage bound to immobilized ICAM-1(1-453) were eluted by three methods: (1) soluble ICAM-1(1-453), (2) neutralizing murine monoclonal antibody, (anti-ICAM-1, M174F5B7), (3) acidic conditions. After three rounds of binding and elution, a single, unique ICAM-1 binding phage bearing the peptide EWCEYLGGYLRCYA was isolated; the identical phage was selected with each method of elution. Attempts to isolate phage from non-constrained (i.e., not containing cysteines) libraries did not yield a phage that bound to ICAM-1. Phage displaying EWCEYLGGYLRCYA bound to immobilized ICAM-1(1-453) and to ICAM-1(1-185), a recombinant ICAM-1, which contains only the two amino-terminal immunoglobulin domains residing within residues 1-185. This is the region of the ICAM-1 that is bound by LFA-1. The phage did not bind to proteins other than ICAM-1. The phage bound to two ICAM-1 mutants, which contained amino acid substitutions that dramatically decreased or eliminated the binding to LFA-1. Studies were also performed with the corresponding synthetic peptide. The linear form of the synthetic EWCEYLGGYLRCYA peptide was found to inhibit LFA-1 binding to immobilized ICAM-1(1-453) in a protein-protein binding assay. By contrast, the disulfide, cyclized, form of the peptide was inactive. The EWCEYL portion of the sequence is homologous to the EWPEYL sequence found within rhinovirus coat protein 14, a nonintegrin protein that binds to ICAM-1. Taken together, the results suggests that the EWCEYLGGYLRCYA sequence is capable to binding to immobilized ICAM-1. Phage display appears to represent a new approach for the identification of peptides that interfere with ICAM-1 binding to beta 2 integrins.
Learning modular neural network policies for multi-task and multi-robot transfer (2017)

Reinforcement learning (RL) can automate a wide variety of robotic skills, but learning each new skill requires considerable real-world data collection and manual representation engineering to design policy classes or features. Using deep reinforcement learning to train general purpose neural network policies alleviates some of the burden of manual representation engineering by using expressive policy classes, but exacerbates the challenge of data collection, since such methods tend to be less efficient than RL with low-dimensional, hand-designed representations. Transfer learning can mitigate this problem by enabling us to transfer information from one skill to another and even from one robot to another. We show that neural network policies can be decomposed into “task-specific” and “robot-specific” modules, where the task-specific modules are shared across robots, and the robot-specific modules are shared across all tasks on that robot. This allows for sharing task information, such as perception, between robots and sharing robot information, such as dynamics and kinematics, between tasks. We exploit this decomposition to train mix-and-match modules that can solve new robot-task combinations that were not seen during training. Using a novel approach to train modular neural networks, we demonstrate the effectiveness of our transfer method for enabling zero-shot generalization with a variety of robots and tasks in simulation for both visual and non-visual tasks.
Preferential incorporation of nucleoside analogs after template switching during human immunodeficiency virus reverse transcription (1994)

We assessed the effects of 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI), and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) on reverse transcription in CD4-positive cells by isolating truncated human immunodeficiency virus (HIV) DNA fragments. Jurkat cells were treated with AZT (2 microM), ddI (200 microM), or 3TC (50 microM) prior to infection with HIV. Low-molecular-weight DNA was isolated and amplified by PCR with primer pairs which identify different segments of HIV proviral DNA. We found that the HIV DNA fragments generated from drug-treated, HIV-exposed Jurkat cells were truncated at a ratio of 15:1 [i.e., (-) strong-stop DNA to HIV DNA generated after the first template switch]. Full-length DNA was observed in the case of untreated, HIV-infected cultures. Following nucleoside analog treatment of HIV-exposed Jurkat cells, reverse transcription was terminated only after the synthesis of (-) strong-stop DNA. The nucleoside analogs tested, i.e., AZT, ddI, and 3TC, preferentially chain terminated viral DNA synthesis immediately following the first template switch. The (-) strong-stop HIV DNA was present in AZT-treated and untreated cultures for at least 6 days. We also carried out cell-free reverse transcription/template-switching reactions involving tRNA(Lys3) or a deoxyoligonucleotide as a primer, as a means of studying the selective incorporation of AZT triphosphate into proviral DNA. When reactions were primed with tRNA(Lys3), we found that AZT triphosphate was preferentially incorporated after template switching.
Neurotoxicity associated with dual actions of homocysteine at the N -methyl- d -aspartate receptor (1997)

Severely elevated levels of total homocysteine (approximately millimolar) in the blood typify the childhood disease homocystinuria, whereas modest levels (tens of micromolar) are commonly found in adults who are at increased risk for vascular disease and stroke. Activation of the coagulation system and adverse effects of homocysteine on the endothelium and vessel wall are believed to underlie disease pathogenesis. Here we show that homocysteine acts as an agonist at the glutamate binding site of the N-methyl-D-aspartate receptor, but also as a partial antagonist of the glycine coagonist site. With physiological levels of glycine, neurotoxic concentrations of homocysteine are on the order of millimolar. However, under pathological conditions in which glycine levels in the nervous system are elevated, such as stroke and head trauma, homocysteine's neurotoxic (agonist) attributes at 10-100 microM levels outweigh its neuroprotective (antagonist) activity. Under these conditions neuronal damage derives from excessive Ca2+ influx and reactive oxygen generation. Accordingly, homocysteine neurotoxicity through overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both homocystinuria and modest hyperhomocysteinemia.
Performing Mathematical Operations with Metamaterials (2014)

We introduce the concept of metamaterial analog computing, based on suitably designed metamaterial blocks that can perform mathematical operations (such as spatial differentiation, integration, or convolution) on the profile of an impinging wave as it propagates through these blocks. Two approaches are presented to achieve such functionality: (i) subwavelength structured metascreens combined with graded-index waveguides and (ii) multilayered slabs designed to achieve a desired spatial Green's function. Both techniques offer the possibility of miniaturized, potentially integrable, wave-based computing systems that are thinner than conventional lens-based optical signal and data processors by several orders of magnitude.
The twin-pass dual access catheter for assessment of the no-reflow phenomenon. (2010)

Distal vessel contrast injection using the Twin-Pass catheter in the presence of no-reflow is a simple and rapid technique that allows for the definition of four distinct clinical scenarios. This allows for rapid treatment of the underlying pathological process, reducing the period of end-organ ischemia, limiting occasional unnecessary stent deployment and further improving procedural results.
Cloning and Characterization of Long‐Chain Fatty Alcohol Oxidase LjFAO1 in Lotus japonicus (2008)

The Lotus japonicus EST database was searched against Arabidopsis thaliana AtFAO3, a full-length cDNA that encodes a membrane-bound, flavin-containing, hydrogen peroxide generating, long-chain fatty alcohol oxidase. One EST fragment was detected, and the corresponding full-length cDNA was obtained by screening a cDNA library of L. japonicus. The LjFAO1 genomic DNA was amplified by PCR, to give a product 3.6 kb in length. Comparison between the LjFAO1 cDNA and genomic DNA revealed that the LjFAO1 contains 3 exons and 2 introns. RT-PCR analysis showed that the LjFAO1 was expressed in the whole plant, with the highest expression level in the apex and the lowest expression level in the siliques. The LjFAO1 gene was down-regulated by cold stress in both the apex and the cotelydon of the 8-day old seedlings, the first time that a long-chain alcohol oxidase has been shown to respond directly to stress. The full length cDNA and a C-terminal truncated version were overexpressed in Escherichia coli. The full length version of LjFAO1 exhibited long-chain fatty alcohol oxidase activity and was subsequently purified by Ni-NTA chromatography. The active LjFAO1 protein showed substrate specificities toward 1-dodecanol, 1-hexadecanol, and 1,16-hexadecanediol with Km values 59.6 +/- 14.8 (microM), 40.9 +/- 8.2 (microM) and 19.4 +/- 1.5 (microM), respectively, suggesting apparent differences in substrate preferences with AtFAO3.
Diagnostic Criteria for the Neuropathologic Assessment of Alzheimer’s Disease (1997)

The provisional criteria proposed in 1985 by Khachaturian et al. emphasized numbers of plaques and neglected tangles, as did CERAD (Consortium to Establish a Registry for Alzheimer's Disease). The decision to set an arbitrary number of plaques as "pathologic" assumed that some neuritic plaques are a normal phenomenon in the aging brain. Neuritic plaques and neurofibrillary tangles are age-related lesions, but they are pathologic (i.e., lesions) no matter how many there are. In a clinically demented patient without vascular or other neurodegenerative lesions, a clinico-pathologic diagnosis of AD (a clinico-pathologic entity) can be made with a high level of confidence by demonstrating, and without counting, plaques and tangles. The vast majority of AD cases are straightforward, and diagnostic lesions can be appreciated with a simple silver stain. If patients' histories are unknown or uncertain, the clinical significance of the observed plaques and tangles must remain debatable. This is the essence of the consensus statement with which I wholeheartedly agree. In such cases without a dementia history, one can offer a neuropathologic diagnosis of Senile or Pre-senile Cerebral Disease (not "dementia") of the Alzheimer type. Precise clinico-pathologic correlations and some quantitative measures are needed for elucidating the pathogenesis of AD and for establishing a primary dementing diagnosis when AD is mixed with other dementing diseases. These correlations must be based on periodic and fairly extensive neuropsychological testing followed shortly thereafter by a detailed postmortem neuropathologic evaluation.
Optimizing MIMO antenna systems with channel covariance feedback (2003)

We consider a narrowband point-to-point communication system with n/sub T/ transmitters and n/sub R/ receivers. We assume the receiver has perfect knowledge of the channel, while the transmitter has no channel knowledge. We consider the case where the receiving antenna array has uncorrelated elements, while the elements of the transmitting array are arbitrarily correlated. Focusing on the case where n/sub T/=2, we derive simple analytic expressions for the ergodic average and the cumulative distribution function of the mutual information for arbitrary input (transmission) signal covariance. We then determine the ergodic and outage capacities and the associated optimal input signal covariances. We thus show how a transmitter with covariance knowledge should correlate its transmissions to maximize throughput. These results allow us to derive an exact condition (both necessary and sufficient) that determines when beamforming is optimal for systems with arbitrary number of transmitters and receivers.
A variational model for filling-in gray level and color images (2002)

A variational approach for filling-in regions of missing data in gray-level and color images is introduced in this paper. The approach is based on joint interpolation of the image gray-levels and gradient/isophores directions, smoothly extending in an automatic fashion the isophote lines into the holes of missing data. This interpolation is computed solving the variational problem via its gradient descent flow, which lends to a set of coupled second order partial differential equations, one for the gray-levels and one for the gradient orientations. The process underlying this approach can be considered as an interpretation of the Gestaltist's principle of good continuation. No limitations are imposed on the topology of the holes, and all regions of missing data can be simultaneously processed, even if they are surrounded by completely different structures. Applications of this technique include the restoration of old photographs and removal of superimposed text like dates, subtitles, or publicity. Examples of these applications are given.
Catheter Complications Associated With Implantable Systems for Peritoneal Insulin Delivery: An analysis of frequency, predisposing factors, and obstructing materials (1995)

Catheter obstruction is a frequent adverse technical event occurring with implanted insulin pumps. Progress is expected in the biocompatibility of catheter material and more specifically in the stability of insulin preparations to prevent immuno-inflammatory reactions and insulin amyloid deposits that appear to be involved in catheter failures.
Alginate Hydrogels as Biomaterials (2006)

[Image: see text] Alginate hydrogels are proving to have a wide applicability as biomaterials. They have been used as scaffolds for tissue engineering, as delivery vehicles for drugs, and as model extracellular matrices for basic biological studies. These applications require tight control of a number of material properties including mechanical stiffness, swelling, degradation, cell attachment, and binding or release of bioactive molecules. Control over these properties can be achieved by chemical or physical modifications of the polysaccharide itself or the gels formed from alginate. The utility of these modified alginate gels as biomaterials has been demonstrated in a number of in vitro and in vivo studies.Micro-CT images of bone-like constructs that result from transplantation of osteoblasts on gels that degrade over a time frame of several months leading to improved bone formation.
Antineutrophil cytoplasmic autoantibodies in Wegener’s granulomatosis recognize conformational epitope(s) on proteinase 3 (1992)

Although proteinase 3 (PR3) has been identified as a major autoantigen in Wegener's granulomatosis, the precise antibody specificity(ies) and requirements for epitope recognition have not been characterized. We analyzed 11 sera containing antineutrophil cytoplasmic antibodies (cANCA) for binding to azurophilic granule proteins extracted from neutrophils under various conditions and for binding to native or rPR3. Ten of 11 (91%) of the cANCA sera bound to PR3 extracted by nonionic detergents when tested by immunoprecipitation or by IEF followed by capillary immunoblotting. Antibody binding to PR3 was retained when IEF was performed under dissociating conditions (8 M urea) indicating that PR3 is the major autoantigen in azurophilic granules and that association with other proteins is not required for antigenicity. In contrast, antigenicity was totally destroyed by exposure of PR3 to reducing agents or to low pH (less than 3.0) and was either lost or considerably diminished after boiling in SDS. cANCA sera also showed little or no binding to rPR3 expressed as a fusion protein in Escherichia coli or synthesized by wheat germ ribosomes in vitro. Inasmuch as PR3 enzymatic activity was partially retained after acid extraction, these findings indicate that cANCA bind to a limited number of conformational epitopes on PR3. In addition, IEF followed by capillary immunoblotting appears to be a sensitive and specific method to detect anti-PR3 antibodies in Wegener's granulomatosis.
Adsorption Characteristics of PHPA on Formation Solids (1990)

ABSTRACT One of the most important uses for polymers in drilling fluids is shale stabilization. The shale stabilizing mechanism is not very well understood, but many think it results from hydrated polymer molecules interacting with water and shale surfaces by a process of adsorption. Adsorption is a complex surface phenomenon. Measurement of solution viscosity may not be adequate to quantify the adsorption characteristics of polymers. This study focuses on the static adsorption of a partially hydrolyzed polyacrylamide polymer (PHPA) on formation solids. The study also investigates various factors affecting adsorption of polymers. The adsorption was quantified by adsorption density, which is the amount of polymer adsorbed per unit surface area of solid particles. Application of laboratory findings to field situations is also discussed.
Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1 (1997)

Several in vitro and in vivo studies indicate that application of high doses of dominant T cell epitopes can induce a state of antigen-specific non-responsiveness (anergy). In the present study, we developed a murine model of an allergic immune response to Bet v 1, the major birch pollen allergen. Mice were sensitized by injection of rBet v 1 and the allergic state was proven by the presence of allergen-specific IgE and positive immediate-type skin tests to Bet v 1. In epitope mapping experiments, an immunodominant T cell epitope of Bet v 1 in BALB/c mice was identified by the use of overlapping peptides. This peptide (BV 139) was subsequently employed for treatment. Two tolerization protocols were used: in one approach, the peptide was administered to naive mice before immunization (group BV139-S), in the second, already sensitized mice were treated (S-BV139). The results demonstrated that administering high doses of the dominant T cell epitope of Bet v 1 profoundly diminished T cell proliferation to the peptide in the BV139-S group, and to the peptide as well as to the whole protein in the S-BV139 group. Skin test reactivity to Bet v 1 was reduced in the BV139-S group. However, no differences in terms of specific antibody production between treated and untreated mice could be observed. This study provides evidence that administration of dominant T cell epitopes can down-regulate the allergen-specific T cell response. Proceeding on the assumption that the T lymphocyte response to allergens is crucial for the induction and maintenance of the allergic disease, a modulation of the immune response to allergens by treatment with T cell epitope peptides could represent a promising concept for immunotherapy in the future.