gebhart/patrepeval huggingface dataset:
Red blood cell membrane phosphatidylethanolamine fatty acid content in various forms of retinitis pigmentosa (1995)

In order to test the hypothesis that retinitis pigmentosa (RP) is associated with fatty acid abnormalities within cell membrane phospholipids, red blood cell membrane (RBC) phosphatidylethanolamine (PE) fatty acid content (% of total fatty acids) was measured using high performance liquid chromatography and capillary column gas chromatography in 155 patients from separate families with different genetic types of RP and 101 normal subjects. After controlling for the effects of age and sex, patients with all genetic forms of RP had significantly (P < 0.001) reduced mean RBC PE 22:6 omega 3 (n-3) (docosahexaenoic acid, DHA) content, and significantly (P < 0.001) elevated mean RBC PE dimethyl acetal (DMA) forms of 16:0, 18:0, and 18:1 omega 9 (n-9) as compared with normal subjects. RBC PE content of 22:5 omega 3 (n-3) (a precursor to DHA) and 18:2 omega 6 (n-6) (the major dietary essential fatty acid) were not significantly different in RP than in controls. Analysis by genetic types of RP showed that the mean RBC PE DHA percentages were significantly reduced by 24%, 14%, 30%, and 17%, respectively, in dominant, recessive, X-linked, and isolate forms of RP. The relative amounts of plasmalogens as indicated by DMA forms of 16:0 and 18:0 were significantly (P < 0.01) increased in dominant (by 33% and 25%), recessive (by 36% and 25%), and isolate cases (by 32% and 26%) of RP as compared with normal subjects. No such differences were seen in X-linked cases versus controls. Our data indicate that RBC PE DHA content is decreased in all genetic types of RP patients as compared to control subjects, and that RBC PE plasmalogens are increased in dominant, recessive, and isolate forms of RP. These data raise the possibility that membrane phospholipid fatty acid abnormalities may contribute to the pathogenesis of RP.
Multiple Regions of Human FcγRII (CD32) Contribute to the Binding of IgG (1995)

The low affinity receptor for IgG, Fc gamma RII (CD32), has a wide distribution on hematopoietic cells where it is responsible for a diverse range of cellular responses crucial for immune regulation and resistance to infection. Fc gamma RII is a member of the immunoglobulin superfamily, containing an extracellular region of two Ig-like domains. The IgG binding site of human Fc gamma RII has been localized to an 8-amino acid segment of the second extracellular domain, Asn154-Ser161. In this study, evidence is presented to suggest that domain 1 and two additional regions of domain 2 also contribute to the binding of IgG by Fc gamma RII. Chimeric receptors generated by exchanging the extracellular domains and segments of domain 2 between Fc gamma RII and the structurally related Fc epsilon RI alpha chain were used to demonstrate that substitution of domain 1 in its entirety or the domain 2 regions encompassing residues Ser109-Val116 and Ser130-Thr135 resulted in a loss of the ability of these receptors to bind hIgG1 in dimeric form. Site-directed mutagenesis performed on individual residues within and flanking the Ser109-Val116 and Ser130-Thr135 domain 2 segments indicated that substitution of Lys113, Pro114, Leu115, Val116, Phe129, and His131 profoundly decreased the binding of hIgG1, whereas substitution of Asp133 and Pro134 increased binding. These findings suggest that not only is domain 1 contributing to the affinity of IgG binding by Fc gamma RII but, importantly, that the domain 2 regions Ser109-Val116 and Phe129-Thr135 also play key roles in the binding of hIgG1. The location of these binding regions on a molecular model of the entire extracellular region of Fc gamma RII indicates that they comprise loops that are juxtaposed in domain 2 at the interface with domain 1, with the putative crucial binding residues forming a hydrophobic pocket surrounded by a wall of predominantly aromatic and basic residues.
Crystallization of membrane proteins (1997)

Five new membrane protein structures have been determined since 1995 using X-ray crystallography: bacterial light-harvesting complex; bacterial and mitochondrial cytochrome c oxidases; mitochondrial bc1 complex; and alpha-hemolysin. These successes are partly based on advances in the crystallization procedures for integral membrane proteins. Variation of the size of the detergent micelle and/or increasing the size of the polar surface of the membrane protein is the most important route to well-ordered membrane protein crystals. The use of bicontinuous lipidic cubic phases also appears to be promising.
Urine Neutrophil Gelatinase-Associated Lipocalin and Interleukin-18 Predict Acute Kidney Injury after Cardiac Surgery (2008)

The concentrations of urine NGAL and IL-18 could be useful biomarkers for AKI in patients after cardiac surgery, especially after correction for urine creatinine.
IPACT a dynamic protocol for an Ethernet PON (EPON) (2002)

We investigate design issues for access networks based on passive optical network technology. A PON based on polling, with data encapsulated in Ethernet frames, possesses many desirable qualities, such as dynamic bandwidth distribution, use of a single downstream and a single upstream wavelength, ability to provision a fractional wavelength capacity to each user, and ease of adding a new user. To support dynamic bandwidth distribution, we propose an interleaved polling algorithm called IPACT. We also suggest a scheme for in-band signaling that allows using a single wavelength for both downstream data and control message transmission. To obtain realistic simulation results, we generated synthetic traffic that exhibits the properties of self-similarity and long-range dependence. We then analyzed the network performance under varying offered loads.
Ductal carcinoma in situ of the breast. (1993)

DCIS is an early localized stage of mammary malignancy that has an especially favorable prognosis with appropriate management. It seems to be a direct precursor to invasive carcinoma of the breast and has the same therapeutic options. There are still many outstanding issues to be resolved before the intriguing potential of this disease can be fully realized. Any physician involved in the management of diseases of the breast must be committed to a thorough understanding of all aspects of the biologic factors of this entity, so as to be able to rationally provide appropriate advice and treatment. Ongoing investigations should advance the knowledge and experience with this disease in future years.
Introduction to “This is Watson” (2012)

In 2007, IBM Research took on the grand challenge of building a computer system that could compete with champions at the game of Jeopardy!™. In 2011, the open-domain question-answering (QA) system, dubbed Watson, beat the two highest ranked players in a nationally televised two-game Jeopardy! match. This paper provides a brief history of the events and ideas that positioned our team to take on the Jeopardy! challenge, build Watson, IBM Watson™, and ultimately triumph. It describes both the nature of the QA challenge represented by Jeopardy! and our overarching technical approach. The main body of this paper provides a narrative of the DeepQA processing pipeline to introduce the articles in this special issue and put them in context of the overall system. Finally, this paper summarizes our main results, describing how the system, as a holistic combination of many diverse algorithmic techniques, performed at champion levels, and it briefly discusses the team's future research plans.
Combinatorially Designed Lipid‐like Nanoparticles for Intracellular Delivery of Cytotoxic Protein for Cancer Therapy (2014)

An efficient and safe method to deliver active proteins into the cytosol of targeted cells is highly desirable to advance protein-based therapeutics. A novel protein delivery platform has been created by combinatorial design of cationic lipid-like materials (termed "lipidoids"), coupled with a reversible chemical protein engineering approach. Using ribonuclease A (RNase A) and saporin as two representative cytotoxic proteins, the combinatorial lipidoids efficiently deliver proteins into cancer cells and inhibit cell proliferation. A study of the structure-function relationship reveals that the electrostatic and hydrophobic interactions between the lipidoids and the protein play a vital role in the formation of protein-lipidoid nanocomplexes and intracellular delivery. A representative lipidoid (EC16-1) protein nanoparticle formulation inhibits cell proliferation in vitro and suppresses tumor growth in a murine breast cancer model.
Chromatography Paper Strip Method for Collection, Transportation, and Storage of Rotavirus RNA in Stool Samples (2004)

We developed a novel method that uses sodium dodecyl sulfate-EDTA-treated chromatography paper strips to collect unconcentrated fresh stool samples. After the paper strips were stored for 4 months at room temperature, rotavirus RNA could be successfully amplified by using reverse transcriptase PCR. The use of filter paper strips as a specimen support allows (self-)collection of stool samples by untrained persons. Diarrheal stool samples from remote areas can be stored and transported to a central diagnostic laboratory without the need for freezers or special shipping conditions. This convenient and inexpensive rotavirus sample collection system can be of use in epidemiological surveillance studies and vaccine trials.
Cellular Basis for Bimatoprost Effects on Human Conventional Outflow (2010)

Taken together, results suggest that bimatoprost specifically activates receptors in both cell types of the human conventional outflow pathway to modify intraocular pressure. However, only TM cell monolayers appear to have autocrine, or agonist-independent, receptor signaling that is sensitive to a prostamide receptor antagonist.
A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats (2003)

Cancer cachexia induces host protein wastage but the mechanisms are poorly understood. Branched-chain amino acids play a regulatory role in the modulation of both protein synthesis and degradation in host tissues. Leucine, an important amino acid in skeletal muscle, is higher oxidized in tumor-bearing animals. A leucine-supplemented diet was used to analyze the effects of Walker 256 tumor growth on body composition in young weanling Wistar rats divided into two main dietary groups: normal diet (N, 18% protein) and leucine-rich diet (L, 15% protein plus 3% leucine), which were further subdivided into control (N or L) or tumor-bearing (W or LW) subgroups. After 12 days, the animals were sacrificed and their carcass analyzed. The tumor-bearing groups showed a decrease in body weight and fat content. Lean carcass mass was lower in the W and LW groups (W = 19.9 0.6, LW = 23.1 1.0 g vs N = 29.4 1.3, L = 28.1 1.9 g, P < 0.05). Tumor weight was similar in both tumor-bearing groups fed either diet. Western blot analysis showed that myosin protein content in gastrocnemius muscle was reduced in tumor-bearing animals (W = 0.234 0.033 vs LW = 0.598 0.036, N = 0.623 0.062, L = 0.697 0.065 arbitrary intensity, P < 0.05). Despite accelerated tumor growth, LW animals exhibited a smaller reduction in lean carcass mass and muscle myosin maintenance, suggesting that excess leucine in the diet could counteract, at least in part, the high host protein wasting in weanling tumor-bearing rats.
Cloning and Expression of a Viral Phosphoprotein: Structure Suggests Vesicular Stomatitis Virus NS May Function by Mimicking an RNA Template (1986)

The phosphoprotein (NS) gene from the Indiana serotype of vesicular stomatitis virus (VSV; Mudd-Summers strain) was cloned and sequenced. The NS gene encodes a protein of 265 amino acids which was expressed from a simian virus 40 vector in COS cells. The post-translational modification characteristic of viral NS, the extensive phosphorylation of a cluster of serine and threonine residues, was also evident in recombinant NS protein. The NS gene displays a property common to the phosphoprotein genes of negative-strand RNA viruses: the phosphoprotein mRNA has a second open reading frame (ORF) which could encode a small (7500 mol. wt.) protein. Both measles virus and Sendai virus employ the second ORF of their phosphoprotein gene, and the resultant proteins have an amino acid composition similar to that predicted for the VSV ORF. Comparison of phosphoproteins from different VSV strains revealed two conserved domains that we propose are critical for the function of NS in transcription and replication.
Intensely Cytotoxic Anthracycline Prodrugs:  Glucuronides (1997)

We previously reported the synthesis of a series of doxorubicin analogue prodrugs that give rise to intensely cytotoxic metabolites in the presence of carboxylate esterases. We now report studies on structurally related beta-glucuronide prodrugs that are converted to similar potent metabolites in the presence of beta-glucuronidases. These prodrugs were prepared by reductive condensation of daunomycin or doxorubicin with methyl 1-O-[(1'RS)-1'-ethoxy-4'-oxobutyl]-2,3,4-tri-O-acetyl-beta-D- glucopyranosyluronate in the presence of sodium cyanoborohydride followed by base-mediated cleavage of the glucuronate protective groups. The doxorubicin derivatives were isolated in very low yield, most likely because of the inherent base lability of the parent aglycone. By contrast, fairly good yields of the more base-stable daunomycin analogues were obtained. The target daunomycin glucuronide, N-[(4"RS)-4"-ethoxy-4"-(sodium 1"'-O-beta-D-glucopyranuronate)butyl]daunorubicin (6a), had a half-life of 30 h when incubated at a concentration of 12 microM in aqueous 0.05 M phosphate buffer, pH 7.4, at 37 degrees C. Under identical conditions in the presence of 197 units/mumol of Escherichia coli beta-glucuronidase, 6a was hydrolyzed with a half-life of 1.7 h. The single metabolite observed was chromatographically identical with that formed from the hydrolysis of N-(4,4-diacetoxybut-1-yl)daunomycin by carboxylate esterases. 6a was approximately 10,000-fold more toxic to human A375 melanoma cells in the presence of E. coli beta-glucuronidase than in the absence of the enzyme. These findings indicate the therapeutic potential of anthracycline glucuronide prodrugs as independent entities or four use in conjunction with enzyme tissue-targeting strategies such as antibody-directed enzyme prodrug therapy (ADEPT) or gene-directed enzyme prodrug therapy (GDEPT).
Superoxide dismutase in CSF from amyotrophic lateral sclerosis patients with and without CuZn-superoxide dismutase mutations (2001)

Mutations in CuZn-superoxide dismutase (CuZn-SOD) have been linked to familial amyotrophic lateral sclerosis (ALS), and motor neurone death is caused by the gain of a toxic property of the mutant protein. Here we determined amounts, activity and molecular forms of CuZn-SOD in CSF from ALS patients carrying the D90A and other CuZn-SOD mutations and patients without such mutations. There were no differences in amount of protein and enzymic activities of CuZn-SOD between 37 neurological controls, 54 sporadic and 12 familial ALS cases, and 10 cases homozygous for the D90A mutation. Three cases heterozygous for the A89V, S105L and G114A CuZn-SOD mutations showed low amounts of CuZn-SOD. There was no evidence for accumulation of inactive protein in any of the groups. Immunoblots showed no evidence for the presence of any precipitates or other molecular forms of CuZn-SOD with higher molecular weight in the groups. About 25% of the CuZn-SOD subunits in CSF from controls shows an N-terminal truncation. This truncated portion does not differ between controls and ALS groups not carrying CuZn-SOD mutations, but is 70% larger in samples from D90A homozygous ALS patients. The findings suggest an essentially normal amount and activity of D90A mutant CuZn-SOD in CNS tissues of ALS cases. The increased occurrence of N-terminally truncated mutant subunits may indicate a difference in degradation routes compared with the wild-type enzyme, resistance against subsequent proteolytic steps and/or a compromised downstream proteolytic machinery. Molecular fragments accumulated to a greater extent from the D90A mutant enzyme might contribute to the motor neurone degeneration. We also determined the other SOD isoenzymes: in the controls, CuZn-SOD contributed 75%, extracellular SOD 25% and Mn-SOD <5% of the total SOD activity. There was no difference in the amount of extracellular SOD between any of the groups.
Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction. (1989)

The pivotal role that protein-tyrosine kinases (PTKs) play in the growth regulation of eukaryotic cells is manifest in the frequent appearance of members of the PTK family as growth factor receptors or as the transforming agents of acutely transforming retroviruses. A feature common to all members of the PTK family is a highly conserved catalytic domain which is characteristic of the group as a whole and whose activity appears to be tightly regulated within the cell by other domains of the PTK. Degenerate oligonucleotide probes corresponding to two invariant amino acid sequence motifs within the catalytic domains of all PTK family members were synthesized and employed in the polymerase chain reaction (PCR) to amplify cDNA sequences between them. An M13 PCR library was produced in this way from cDNA prepared against mRNA from the murine hemopoietic cell line FDC-P1. The PCR library was then screened by DNA sequencing for PTK-related sequences. Two sequences were identified that, on the basis of sequence comparison with known PTKs, may encode representatives of a new class of PTK.
Bandgap features and thermoelectric properties of Ti-based half-Heusler alloys (2003)

Electronic transport properties of narrow-gap TiNiSn and presumed wider-gap TiCoSb half-Heusler alloys are investigated by systematically doping the three sublattice sites. The two alloys are found to exhibit different doping trends. While all three sites in TiCoSb can be doped to enhance semimetallic behavior, only the Ti and Ni sites in TiNiSn can be efficiently doped. Meanwhile, several 3d dopants are found to lead to more localized electronic properties. These findings, together with results on Hall effect and thermopower measurements, have shed light on the bandgap structure of these metal-based semiconductors. Power factor and dimensionless figure of merit ZT reaching /spl sim/5.7/spl times/10/sup -3/ W/m-K/sup 2/ and /spl sim/0.5 at 680 K, respectively, are obtained in the Sb-doped (TiHf)NiSn system. The quite favorable thermoelectric parameters obtained in these low-mobility alloys are attributed to the existence of a moderately heavy electron band mass.
Machine-learning rule-based fuzzy logic control for depth of anaesthesia (1994)

A machine-learning rule-based fuzzy logic controller for depth of anaesthesia which is similar to the way an anaesthetist works is presented in this paper. The results of discussions with anaesthetists to obtain a rule base and the application of fuzzy logic to predict the primary depth of anaesthesia (PDOA) and to control drug administration are very promising. By using simple rules from machine learning trials, similar results for the prediction of PDOA were obtained and can be used to design a drug infusion controller. The robustness of the self-organising fuzzy logic control (SOFLC) algorithm is good and can supplement the anaesthetist&apos;s experience for administering drug to patients when the system is dynamic and time-varying. Using these results, the design of a hierarchical architecture for the determination of the level of depth of anaesthesia is being investigated, which will include the use of clinical signs and refinements in the control of drug administered to patients.
AZITHROMYCIN THERAPY FOR PATIENTS WITH BRONCHIOLITIS OBLITERANS SYNDROME AFTER LUNG TRANSPLANTATION (2004)

AZI is a promising drug for some patients with BOS after lung transplantation. The exact mechanism of action is unknown at the present time.
Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase‐4 inhibitor linagliptin * (2011)

Renal impairment has only a minor effect on linagliptin pharmacokinetics. Consequently, there will be no need for adjusting the linagliptin dose in renally impaired patients with T2DM.
Quantification and duration of viraemia during hepatitis A infection as determined by real‐time RT‐PCR (2002)

Human transmission studies and molecular techniques have provided evidence that transient viraemia occurs during infection with hepatitis A virus (HAV). However, the duration of its presence and levels during the phases of clinical disease and convalescence has not yet been well studied in human patients. Real‐time RT‐PCR techniques are increasingly used to quantify RNA viruses for diagnosis and/or research purposes. We have optimized a one‐step RT‐PCR that contains a dual‐labelled fluorogenic probe to quantify the 5′ noncoding region (5′NCR) of HAV. This method has a dynamic range (5–5 × 10 6 copies). The coefficient of regression of the standard curve was, on average 0.978. Intra‐assay CVs% varied from 6.1% to 0.98%, and interassay CVs% from 6.46% to 2.1%. In the currently reported study 41 HAV IgM positive serum samples and 200 serum samples from healthy blood donors were tested by the quantitative RT‐PCR method. The mean values on the first day of diagnosis found was 6.38 × 10 5 copies/mL. In a longitudinal study, viraemia persisted for an average of 60 days after clinical onset. These results show that viraemia in HAV infection lasts for many weeks.
Synthesis of 2,2′‐bipyridyl‐type compounds via the suzuki‐miyaura cross‐coupling reaction (2007)

Abstract magnified image 2,2′‐Bipyridyl‐type compounds may be prepared by Suzuki‐Miyaura coupling of a 2‐pyridylboronic ester with 2‐haloazines and ‐azoles. Ten examples are presented with yields of 47 to 84%. Both arylbromides and arylchlorides undergo the coupling, but the reaction is sensitive to ring substitution adjacent to the halogen.
Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency (2007)

CD1d-restricted natural killer T (NKT) cells, expressing the invariant T cell antigen receptor (TCR) chain encoded by Valpha14-Jalpha18 gene segments in mice and Valpha24-Jalpha18 in humans [invariant NKT (iNKT) cells], contribute to immunoregulatory processes, such as tolerance, host defense, and tumor surveillance. iNKT cells are positively selected in the thymus by CD1d molecules expressed by CD4(+)/CD8(+) cortical thymocytes. However, the identity of the endogenous lipid(s) responsible for positive selection of iNKT cells remains unclear. One candidate lipid proposed to play a role in positive selection is isoglobotrihexosylceramide (iGb3). However, no direct evidence for its physiological role has been provided. Therefore, to directly investigate the role of iGb3 in iNKT cell selection, we have generated mice deficient in iGb3 synthase [iGb3S, also known as alpha1-3galactosyltransferase 2 (A3galt2)]. These mice developed, grew, and reproduced normally and exhibited no overt behavioral abnormalities. Consistent with the notion that iGb3 is synthesized only by iGb3S, lack of iGb3 in the dorsal root ganglia of iGb3S-deficient mice (iGb3S(-/-)), as compared with iGb3S(+/-) mice, was confirmed. iGb3S(-/-) mice showed normal numbers of iNKT cells in the thymus, spleen, and liver with selected TCR Vbeta chains identical to controls. Upon administration of alpha-galactosylceramide, activation of iNKT and dendritic cells was similar in iGb3S(-/-) and iGb3S(+/-) mice, as measured by up-regulation of CD69 as well as intracellular IL-4 and IFN-gamma in iNKT cells, up-regulation of CD86 on dendritic cells, and rise in serum concentrations of IL-4, IL-6, IL-10, IL-12p70, IFN-gamma, TNF-alpha, and Ccl2/MCP-1. Our results strongly suggest that iGb3 is unlikely to be an endogenous CD1d lipid ligand determining thymic iNKT selection.