gebhart/patrepeval huggingface dataset:
Identification and characterisation of GPR100 as a novel human G‐protein‐coupled bradykinin receptor (2003)

G-protein-coupled receptor 100 (GPR100) was discovered by searching the human genome database for novel G-protein-coupled peptide receptors. Full-length GPR100 was amplified from a cDNA library of the neuroendocrine cell line BON, which is derived from a human pancreas carcinoid. The open-reading frame, present on a single exon, coded for a protein of 374 amino acids with highest sequence identity (43%) to the human orphan somatostatin- and angiotensin-like peptide receptor. The analysis of chromosomal localisation mapped the GPR100 gene to chromosome 1q21.2-q21.3. The stable expression of GPR100 in Chinese hamster ovary cells together with aequorin as calcium sensor and the promiscuous G-protein subunit alpha16 as signal transducer revealed bradykinin and kallidin as effectors to elicit a calcium response. Dose-response curves yielded EC50 values for both ligands in the low nanomolar range, while the respective analogues without arginine at the carboxy-terminus were inactive. Calcium mobilisation was inhibited by the phospholipase C blocker U73122, but not by pertussis toxin, suggesting the involvement of the G-protein subunit alphaq and not alphai or alphao in signal transduction. In line with the main function of kinins as peripheral hormones, we found that GPR100 was expressed predominantly in tissues like pancreas, heart, skeletal muscle, salivary gland, bladder, kidney, liver, placenta, stomach, jejunum, thyroid gland, ovary, and bone marrow, but smaller amounts were also detected in the brain and in cell lines derived from tumours of various origins.
An optical see-through head mounted display with addressable focal planes (2008)

Most existing stereoscopic head mounted displays (HMDs), presenting a pair of stereoscopic images at a fixed focal distance, lack the ability to correctly render the naturally coupled accommodation and convergence cues. Psychophysical studies have shown that such displays may cause many adverse consequences such as visual fatigue, diplopic vision, degraded oculomotor response, and depth perception errors. In this paper, we present a see-through HMD with addressable focal planes utilizing a novel active optical element - a liquid lens. The element, with a varying optical power from -5 to 20 diopters, is able to address the focal distance of the HMD from infinity to the near point of the eye. A monocular prototype was built from off-the-shelf elements and experimental results are presented to validate the proposed designs. We also describe both subjective and objective measurements of the accommodation responses of the viewer to the focal distances presented by the prototype.
Dietary Supplements and Sports Performance: Introduction and Vitamins (2004)

Sports success is dependent primarily on genetic endowment in athletes with morphologic, psychologic, physiologic and metabolic traits specific to performance characteristics vital to their sport. Such genetically-endowed athletes must also receive optimal training to increase physical power, enhance mental strength, and provide a mechanical advantage. However, athletes often attempt to go beyond training and use substances and techniques, often referred to as ergogenics, in attempts to gain a competitive advantage. Pharmacological agents, such as anabolic steroids and amphetamines, have been used in the past, but such practices by athletes have led to the establishment of anti-doping legislation and effective testing protocols to help deter their use. Thus, many athletes have turned to various dietary strategies, including the use of various dietary supplements (sports supplements), which they presume to be effective, safe and legal.
Human Prion Protein cDNA: Molecular Cloning, Chromosomal Mapping, and Biological Implications (1986)

A human complementary DNA whose protein product is considered to be the major component of scrapie-associated fibrils in Creutzfeldt-Jakob disease, kuru, and Gerstmann-Straussler syndrome has been identified and characterized. The extensive homology of this gene sequence to the hamster PrP 27- to 30-kilodalton prion protein complementary DNA clone, and its existence as a single copy in the human genome, leads to the conclusion that this is the human prion gene. This human prion gene has been mapped to human chromosome 20, negating a direct link between the prion protein and Down's syndrome or the amyloid of Alzheimer's disease.
Matrix‐assisted laser desorption of peptides in transmission geometry (1990)

Abstract The possibility of performing matrix‐assisted laser desorption experiments in transmission geometry is demonstrated for two neuropeptides (substance P and bombesin), for six analogs of the melanocyte‐stimulating hormone (MSH) core and for coliagenase enzyme substrates. Positive‐ and negative‐ion spectra of several peptides are produced without the presence of a metallic substrate. Cationized quasi‐molecular ions are abundant in the positive spectra. Peak broadening in the high‐mass range can be the consequence of overlapping molecular and adduct ions. The presence of synthesis by‐products can be identified readily from the spectra. Ultimately, picogram detection limits are possible for important bioactive peptides and other large molecules. Because of the clearly demonstrated matrix‐assisted laser ionization in a homogeneous environment, metal substrate participation in the volatilization mechanism seems less likely.
Predicted 3D structure for the human β2 adrenergic receptor and its binding site for agonists and antagonists (2004)

We report the 3D structure of human beta2 adrenergic receptor (AR) predicted by using the MembStruk first principles method. To validate this structure, we use the HierDock first principles method to predict the ligand-binding sites for epinephrine and norepinephrine and for eight other ligands, including agonists and antagonists to beta 2 AR and ligands not observed to bind to beta 2 AR. The binding sites agree well with available mutagenesis data, and the calculated relative binding energies correlate reasonably with measured binding affinities. In addition, we find characteristic differences in the predicted binding sites of known agonists and antagonists that allow us to infer the likely activity of other ligands. The predicted ligand-binding properties validate the methods used to predict the 3D structure and function. This validation is a successful step toward applying these procedures to predict the 3D structures and function of the other eight subtypes of ARs, which should enable the development of subtype-specific antagonists and agonists with reduced side effects.
Significant prolongation of orthotopic corneal-graft survival in FTY720-treated mice. (2003)

FTY720 treatment substantially protects corneal allografts and may provide an immunomodulatory strategy in clinical corneal transplantation.
The Ketogenic Diet Is an Effective Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma (2012)

KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.
Lipoxin B 4 regulates human monocyte/neutrophil adherence and motility: design of stable lipoxin B 4 analogs with increased biologic activity (1998)

Lipoxins are biologically active products of arachidonic acid that are formed via cell-cell interactions, particularly those involving leukocytes. Lipoxin A4 and lipoxin B4 (LXB4), within similar concentration ranges, each inhibit human neutrophil, activate monocyte adherence and motility, and are rapidly converted by initial dehydrogenation to other inactive metabolites by human monocytes. Here, we exposed LXB4 to isolated recombinant 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) and found that it was a good substrate for the enzyme (Km=6.9 microM); we identified the major product as 5-oxo-LXB4 via physical methods including liquid chromatography/tandem mass spectrometry. This is the first evidence of 15-PGDH converting a substrate hydroxyl group at a position other than the omega-6 carbon. Based on these observations, several LXB4 analogs were designed and prepared by total organic synthesis to test as stable mimetics: 5(S)-methyl-LXB4-me, 5(R)-methyl-LXB4-me, and 15-epi-LXB4-me (the aspirin-triggered form of LXB4). Both 5(S)-methyl-LXB4-me and 5(R)-methyl-LXB4-me were resistant to rapid conversion. In addition, actions of the stable analogs were evaluated separately with human mono-cytic cells and neutrophils, and 5(S)-methyl-LXB4-me was more potent (nM range) than LXB4 for both cell types. In contrast, 5(R)-methyl-LXB4-me was potent in inhibiting neutrophil transmigration across endothelial monolayers, but did not stimulate monocyte adherence. These results indicate that LXB4 analogs can be designed to resist rapid transformation and retain bioactivity with both monocytes and neutrophils. Moreover, they suggest that LXB4 stable analogs are useful tools to selectively evaluate the modes of actions of LXB4 with different tissues.
Immortalization of Erythroblasts by c-MYC and BCL-XL Enables Large-Scale Erythrocyte Production from Human Pluripotent Stem Cells (2013)

The lack of knowledge about the mechanism of erythrocyte biogenesis through self-replication makes the in vitro generation of large quantities of cells difficult. We show that transduction of c-MYC and BCL-XL into multipotent hematopoietic progenitor cells derived from pluripotent stem cells and gene overexpression enable sustained exponential self-replication of glycophorin A(+) erythroblasts, which we term immortalized erythrocyte progenitor cells (imERYPCs). In an inducible expression system, turning off the overexpression of c-MYC and BCL-XL enabled imERYPCs to mature with chromatin condensation and reduced cell size, hemoglobin synthesis, downregulation of GCN5, upregulation of GATA1, and endogenous BCL-XL and RAF1, all of which appeared to recapitulate normal erythropoiesis. imERYPCs mostly displayed fetal-type hemoglobin and normal oxygen dissociation in vitro and circulation in immunodeficient mice following transfusion. Using critical factors to induce imERYPCs provides a model of erythrocyte biogenesis that could potentially contribute to a stable supply of erythrocytes for donor-independent transfusion.
Hereditary lymphedema: evidence for linkage and genetic heterogeneity (1998)

Hereditary or primary lymphedema is a developmental disorder of the lymphatic system which leads to a disabling and disfiguring swelling of the extremities. Hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression and variable age at onset. Three multigeneration families demonstrating the phenotype of hereditary lymphedema segregating as an autosomal dominant trait with incomplete penetrance were genotyped for 366 autosomal markers. Linkage analysis yielded a two-point LOD score of 6.1 at straight theta = 0. 0 for marker D5S1354 and a maximum multipoint LOD score of 8.8 at marker D5S1354 located at chromosome 5q34-q35. Linkage analysis in two additional families using markers from the linked region showed one family consistent for linkage to distal chromosome 5. In the second family, linkage to 5q was excluded for all markers in the region with LOD scores Z < -2.0. The vascular endothelial growth factor C receptor ( FLT4 ) was mapped to the linked region, and partial sequence analysis identified a G-->A transition at nucleotide position 3360 of the FLT4 cDNA, predicting a leucine for proline substitution at residue 1126 of the mature receptor in one nuclear family. This study localizes a gene for primary lymphedema to distal chromosome 5q, identifies a plausible candidate gene in the linked region, and provides evidence for a second, unlinked locus for primary lymphedema.
A 16-channel CMOS neural stimulating array (1992)

A probe designed for the highly selective long-term stimulation of neuronal assemblies in the central nervous system is described. The micromachined multishank probe incorporates CMOS circuitry to control the output current on 16 iridium oxide (IrO) electrode sites. Serial site addresses and current amplitude data are loaded into the probe at 4 MHz and converted to analog stimulus currents. The probe circuitry dissipates only 80 mu W from +or-5-V supplies when not delivering stimulus currents and uses five external leads. It permits the IrO sites to be activated by voltammetry from off-chip, provides per-channel pulse time-outs to prevent accidental overstimulation of the tissue, and signals the external world, using a status bit, in the event of certain trouble conditions. The stimulating site impedances and the stimulus currents can be measured from off chip on demand. The circuitry is implemented in a single-metal, single-poly, CMOS process with 3- mu m minimum features using 7100 transistors in an area of 11 mm/sup 2/.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Primary Structure and Characteristics of a Lectin from Skin Mucus of the Japanese Eel Anguilla japonica (2002)

Two types of lactose-binding lectins, AJL-1 and AJL-2, were purified from the skin mucus extract of the Japanese eel Anguilla japonica by lactose affinity chromatography and subsequent gel filtration. The molecular masses of AJL-1 and AJL-2 were 16,091 and 31,743 Da, respectively. Intact AJL-1 was comprised of two identical 16-kDa subunits having blocked N termini and no disulfide bonds. AJL-2 was a homodimer with disulfide bonds. Based on the N-terminal amino acid sequence of the AJL-2 monomer, the nucleotide sequence of cDNA encoding this lectin was determined by 3'- and 5'-rapid amplification of cDNA ends. The deduced amino acid sequence showed approximately 30% homology with C-type lectins, which bind to carbohydrates in a Ca(2+)-dependent manner. In addition, AJL-2 exhibited highly conserved consensus amino acid residues of the C-type carbohydrate recognition domain, although this lectin showed Ca(2+)-independent activity. Gene expression of AJL-2 was detected only in the skin by Northern blot analysis, and this lectin localization was demonstrated in the club cells by immunohistochemistry. These results indicate that AJL-2 is secreted on the body surface and function as a component of skin mucus. AJL-2 agglutinated Escherichia coli and suppressed its growth, suggesting that this lectin is involved in host defense.
FormPlus: a form authoring toolkit (2002)

The authors present the design and implementation of FormPlus, a form authoring toolkit for on-screen form design and filing. It is implemented on an IBM OS/2 Presentation Manager platform. FormPlus provides major front-end functions for form processing such as converting paper forms into electronic forms, designing forms, and filling in forms. No knowledge about programming is necessary. FormPlus also provides an object-oriented API (application programming interface) for programmers to develop their own applications with minimum effort. FormPlus is designed to be easily extendable to incorporate new objects and to allow data import and export.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Germination of Spores of Clostridium bifermentans by Certain Amino Acids, Lactate and Pyruvate in the Presence of Sodium or Potassium Ions (1971)

Spores of Clostridium bifermentans germinated in the presence of l-alanine and sodium ions. The rate of germination was not altered by the addition of d-alanine but was increased by l-α-amino-n-butyrate, l-lactate, l- or d-arginine, l-histidine, dl-ornithine, l-lysine, pyruvate, l- or d-serine, l-phenylalanine or l-proline and decreased by d-phenylalanine, l-isoleucine, glycine or l-threonine. Combinations of some organic acids such as l-phenylalanine, l-arginine, l-lactate, l-serine and glycine induced germination in the absence of l-alanine. No germination occurred in the presence of l-alanine if sodium ions were absent and replacement of sodium by potassium ions reduced the germination rate in different mixtures of organic acids. Use of different cations also altered the germination rate, although the change depended on the organic germinants present.
Abstract 4329: Novel HER2 targeting antibody-drug conjugates based on DNA-interacting duocarmycin and an unique linker technology with great potential in breast cancer and NSCLC. (2013)

Abstract We have generated cleavable linker-duocarmycin payloads that previously have been shown to be highly stable in human plasma and to cause excellent in vitro and in vivo efficacy when conjugated to antibodies directed against multiple targets in different models. In our HER2 program, we have used these linker-duocarmycin payloads to generate HER2-targeting antibody-drug conjugates (ADCS) and prepare these for FIM studies. HER2 is a validated target in breast (BC) and gastric cancer (GC) that is currently used to target trastuzumab towards HER2-positive BC and GC tumors. We have generated a set of cysteine-coupled ADCs using newly developed duocarmycins conjugated to a therapeutic HER2/neu antibody. In vitro studies with the anti-Her2 ADCs showed that compared to the naked Ab, the ADCs tested have gained a more than 100-fold potency and more than two-fold efficacy in cell killing capacity. Studies in HER2 positive and negative cell lines indicated that cytotoxicity was HER2- mediated. HER2 binding and ADCC activity was not affected by conjugation. Single dose and multiple dose xenograft studies in mice using a human HER2-positive breast cancer cell line showed dose-dependent anti-tumor activity of the ADCs in vivo. Patient-derived xenografts (PDx) using primary tumors from HER2-positive breast cancer and NSCLC patients demonstrated the ability of the ADC to induce complete remission of tumors that remained unresponsive to the naked Ab trastuzumab. Also taken into account toxicology studies in rodents and cynomolgous monkeys, we conclude that we have generated a new class of HER2-based ADCs that have great potential to become effective treatment for HER2-positive tumors, including breast cancer and NSCLC. From a series of compounds, a preclinical candidate was selected that is currently being prepared for Phase I clinical trials that will start in 2014. Citation Format: Wim Dokter, Patrick Beusker, Gijs Verheijden, Ruud Ubink, Miranda van der Lee, Diels van den Dobbelsteen, Peter Goedings, Jacques Lemmens, Vincent de Groot, Marco Timmers. Novel HER2 targeting antibody-drug conjugates based on DNA-interacting duocarmycin and an unique linker technology with great potential in breast cancer and NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4329. doi:10.1158/1538-7445.AM2013-4329
Sequence and transcriptional analysis of the vaccinia virus HindIII I fragment (1988)

The complete sequence of the vaccinia virus HindIII I fragment, which is composed of 6,498 base pairs, encodes six complete and two incomplete open reading frames (ORFs). Computer analysis revealed an amino acid sequence homology between ORF I 4 and the large subunit of the ribonucleotide reductase complex. The two small polypeptides derived from ORFs I 2 and I 5, with molecular weights of 8,500 and 8,700, respectively, have a very high hydrophobic amino acid sequence composition. S1 analysis revealed that ORF I 4 is expressed at early stages of infection, ORFs I 1, I 2, I 5, and I 7 are expressed in the late phase of infection, and ORF I 3 is constitutively expressed. Screening a vaccinia virus genomic library revealed a large vaccinia virus insert overlapping the HindIII I and O fragments which contains a previously undetected HindIII P fragment of approximately 300 base pairs. S1 analysis revealed an early (O1) and a late (O2) start site of transcription initiation located within the HindIII O fragment.
Real‐time polymerase chain reaction quantification of specific butyrate‐producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer (2008)

Butyrate producers were decreased and E. faecalis increased in the feces of colon cancer patients. These shifts in the colonic bacterial population could potentially lead to epithelial cell damage and increased turnover and may be a factor leading to colon cancer.
Remission of Chronic Lymphocytic Leukemia After Smallpox Vaccination (1979)

<h3>To the Editor.—</h3> I would like to record a case to confirm the observations of Hansen and Libnoch in theArchives(138:1137-1138, 1978) that smallpox vaccination may be followed by remission of chronic lymphocytic leukemia (CLL). In the patient described herein, the vaccination did not result in any unusual immediate local or generalized vaccinia reaction. The remission was not as complete as in the patient described by Hansen and Libnoch, and relapse is now occurring. <h3>Report of a Case.—</h3> A 56-year-old woman was diagnosed as having CLL in July 1970, at which time her CBC count showed the following: hemoglobin, 12.0 g/dL; WBC count, 16,200/cu mm. Differential cell count showed 27% segmented neutrophils and 72% lymphocytes. Bone marrow examination results showed infiltration with mature lymphocytes to about 25% to 50% of all formed elements. Sections of bone marrow particles contained several large abnormal lymphoid follicles. Physical examination results were normal
Isoleucine synthesis in Corynebacterium glutamicum: molecular analysis of the ilvB-ilvN-ilvC operon (1993)

Acetohydroxy acid synthase (AHAS) and isomeroreductase (IR) catalyze subsequent reactions in the flux of metabolites towards isoleucine, valine, leucine, and pantothenate. A 4,705-bp DNA fragment from Corynebacterium glutamicum known to code for AHAS and IR was sequenced and analyzed by Northern (RNA blot) analysis. As in other bacteria, the AHAS of this gram-positive organism is encoded by two genes, ilvB and ilvN. Gene disruption verified that these genes encode the single AHAS activity in C. glutamicum. The start of ilvB was determined by amino-terminal sequencing of a fusion peptide. By Northern analysis of the ilvBNC cluster, three in vivo transcripts of 3.9, 2.3, and 1.1 kb were identified, corresponding to ilvBNC, ilvNC, and ilvC messages, respectively. The ilvC transcript (encoding IR) was by far the most abundant one. With a clone from which the ilvB upstream regions had been deleted, only the ilvNC and ilvC transcripts were synthesized, and with a clone from which the ilvN upstream regions had been deleted, only the smallest ilvC transcript was formed. It is therefore concluded that in the ilv operon of C. glutamicum, three promoters are active. The amounts of the ilvBNC and ilvNC transcripts increased in response to the addition of alpha-ketobutyrate to the growth medium. This was correlated to an increase in specific AHAS activity, whereas IR activity was not increased because of the relatively large amount of the ilvC transcript present under all conditions assayed. Therefore, the steady-state level of the ilvBNC and ilvNC messages contributes significantly to the total activity of the single AHAS. The ilvC transcript of this operon, however, is regulated independently and present in a large excess, which is in accord with the constant IR activities determined.