gebhart/patrepeval huggingface dataset:
Hyperacute rejection of vascularized heart transplants in BALB/c Gal knockout mice (2000)

Pig-to-primate vascularized xenografts undergo hyperacute rejection (HAR). This results from pre-formed xenoreactive antibodies directed against galactose-alpha1,3-galactose (alphaGal) in the donor organ and activation of the complement cascade. We describe an in vivo murine model of HAR using a BALB/c mice system devoid of histocompatibility or complement differences between donor and recipient to investigate in isolation, the effects of alphaGal epitope and anti-alphaGal antibody interactions in causing rejection of vascularized heart transplants. Gal KO mice were immunized with rabbit red blood cell membranes to induce high anti-alphaGal antibody titers that were predominantly IgM by ELISA (enzyme-linked immunosorbent assay). When alphaGal-expressing mice hearts were transplanted heterotopically into these recipients (n= 12), 67% of grafts rejected within 24 h, the majority within 16 h with histological features of HAR. In contrast, none of the grafts in the non-immunized Gal KO recipient control group (n=11) underwent HAR. Interestingly, approximately 50% of the remaining grafts in both the immunized and non-immunized Gal KO recipient group were rejected between 7 and 27 days by a rejection process characterized by a dense infiltrate of macrophage/monocytes, perivascular cuffing and tissue destruction similar to recent descriptions of delayed xenograft rejection (DXR). In addition, some grafts (21.5%) continued to survive in the immunized Gal KO recipients despite the presence of anti-alphaGal antibody and normal complement activity and these showed well-preserved myocardium when harvested whilst still functioning well at days 30 or 90. No rejection was seen when Gal KO donors were used in this system (n=4), nor when alphaGal-expressing BALB/c hearts were transplanted into alphaGal-expressing BALB/c recipients (n=5). This in vivo small animal model offers the opportunity to test a variety of strategies to overcome HAR prior to more resource intensive pig-to-primate studies, and may provide insights into the processes similar to DXR and accommodation.
Adaptive interference rejection for wide-band systems (2003)

The authors describe the RAC (reflective array compressor) exciser, an adaptive band-reject or notch filter based on the multiply-convole chirp-Z transform algorithm. This system uses RAC, which are surface-acoustic-wave dispersive delay lines, in a preprocessor for rejection of overpowering interferers in wideband signal-processing systems. The exciser has been successful in adaptively removing unpredictable interference (e.g. push to talk), as well as tailoring stop/passband functions. The performance of this filtering process of Taylor-weighted input signals attenuates unwanted signals by greater than 40 dB (residual sidelobes) and allows for automatic excision of over 150 narrowband signals from a 30-MHz instantaneous bandwidth. For this filter design, similar downchirp RACs are used for chip generation, signal compression, and signal expansion, reducing time-frequency errors associated with designs using dissimilar devices. Temperature effects are reduced by placing these devices in a stabilized temperature environment.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Appropriate prescribing of medications: an eight-step approach. (2007)

A systematic approach advocated by the World Health Organization can help minimize poor-quality and erroneous prescribing. This six-step approach to prescribing suggests that the physician should (1) evaluate and dearly define the patient's problem; (2) specify the therapeutic objective; (3) select the appropriate drug therapy; (4) initiate therapy with appropriate details and consider nonpharmacologic therapies; (5) give information, instructions, and warnings; and (6) evaluate therapy regularly (e.g., monitor treatment results, consider discontinuation of the drug). The authors add two additional steps: (7) consider drug cost when prescribing; and (8) use computers and other tools to reduce prescribing errors. These eight steps, along with ongoing self-directed learning, compose a systematic approach to prescribing that is efficient and practical for the family physician. Using prescribing software and having access to electronic drug references on a desktop or handheld computer can also improve the legibility and accuracy of prescriptions and help physicians avoid errors.
Characterisation of the faecal microbiota in Japanese patients with paediatric-onset primary sclerosing cholangitis (2016)

Dear Sir,

Primary sclerosing cholangitis (PSC) is a liver disease often associated with IBD.1 Dysbiosis of the gut microbiota is implicated in PSC aetiology in adults,2–4 but less is known about paediatric-onset PSC.

We analysed the faecal microbiota of 27 Japanese patients with paediatric-onset PSC as well as 16 age-matched patients with UC and 23 healthy controls (HCs) (see online supplementary table S1) with pyrosequencing data of 16S rRNA gene V1-V2 region (accession #DRA004773). We assessed the influence of medications on the gut microbiota and found that salazosulfapyridine (SASP) treatment affected the microbiota structure with significant changes in the abundance of six major genera between the treated and untreated patients with PSC, perhaps due to its bactericidal property (see online supplementary figure S1). We thus report the analysis of 13 patients with PSC and 15 patients with UC and 23 HCs, all SASP untreated (see online supplementary table S2).

### Supplementary tables

[gutjnl-2016-312533supp_tables.pdf] 

### Supplementary figure

[gutjnl-2016-312533supp_figure.pdf] 

Clustering analysis of the 16S reads revealed that the microbiota in the PSC and HC groups had significantly high species richness compared with the UC group, and the species richness of PSC samples was lower than that of HCs. The PSC group also exhibited an intermediate trend in the Shannon's index between the UC and HC groups (figure 1A). The unweighted UniFrac metric revealed a significant difference in the overall microbiota structure among the three groups, in which the PSC samples tended to aggregate between the HC and UC samples (figure 1B, C). Collectively, the data suggested that the patients with …
<i>Bin3</i> Deletion Causes Cataracts and Increased Susceptibility to Lymphoma during Aging (2008)

Bin3 encodes an evolutionarily conserved and ubiquitously expressed member of the BAR superfamily of curved membrane and GTPase-binding proteins, which includes the BAR, PCH/F-BAR, and I-BAR adapter proteins implicated in signal transduction and vesicular trafficking. In humans, Bin3 maps to chromosome 8p21.3, a region widely implicated in cancer suppression that is often deleted in non-Hodgkin's lymphomas and various epithelial tumors. Yeast studies have suggested roles for this gene in filamentous actin (F-actin) organization and cell division but its physiologic functions in mammals have not been investigated. Here we report that homozygous inactivation of Bin3 in the mouse causes cataracts and an increased susceptibility to lymphomas during aging. The cataract phenotype was marked by multiple morphologic defects in lens fibers, including the development of vacuoles in cortical fibers and a near total loss of F-actin in lens fiber cells but not epithelial cells. Through 1 year of age, no other phenotypes were apparent; however, by 18 months of age, Bin3(-/-) mice exhibited a significantly increased incidence of lymphoma. Bin3 loss did not affect normal cell proliferation, F-actin organization, or susceptibility to oncogenic transformation. In contrast, it increased the proliferation and invasive motility of cells transformed by SV40 large T antigen plus activated ras. Our findings establish functions for Bin3 in lens development and cancer suppression during aging. Further, they define Bin3 as a candidate for an unidentified tumor suppressor that exists at the human chromosome 8p21.3 locus.
Effect of light and gamma-irradiation on pyridinolines and telopeptides of type I collagen in urine (1995)

Journal Article Effect of light and gamma-irradiation on pyridinolines and telopeptides of type I collagen in urine Get access A Blumsohn, A Blumsohn Dept. of Human Metab. and Clin. Biochem., Univ. of Sheffield, UK Search for other works by this author on: Oxford Academic Google Scholar A Colwell, A Colwell Dept. of Human Metab. and Clin. Biochem., Univ. of Sheffield, UK Search for other works by this author on: Oxford Academic Google Scholar K Naylor, K Naylor Dept. of Human Metab. and Clin. Biochem., Univ. of Sheffield, UK Search for other works by this author on: Oxford Academic Google Scholar R Eastell R Eastell Dept. of Human Metab. and Clin. Biochem., Univ. of Sheffield, UK Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 41, Issue 8, 1 August 1995, Pages 1195–1197, https://doi.org/10.1093/clinchem/41.8.1195 Published: 01 August 1995
17‐Beta Hydroxysteroid Dehydrogenase 13 Is a Hepatic Retinol Dehydrogenase Associated With Histological Features of Nonalcoholic Fatty Liver Disease (2018)

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. A single-nucleotide polymorphism (SNP), rs6834314, was associated with serum liver enzymes in the general population, presumably reflecting liver fat or injury. We studied rs6834314 and its nearest gene, 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13), to identify associations with histological features of NAFLD and to characterize the functional role of HSD17B13 in NAFLD pathogenesis. The minor allele of rs6834314 was significantly associated with increased steatosis but decreased inflammation, ballooning, Mallory-Denk bodies, and liver enzyme levels in 768 adult Caucasians with biopsy-proven NAFLD and with cirrhosis in the general population. We found two plausible causative variants in the HSD17B13 gene. rs72613567, a splice-site SNP in high linkage with rs6834314 (r<sup>2</sup> = 0.94) generates splice variants and shows a similar pattern of association with NAFLD histology. Its minor allele generates simultaneous expression of exon 6-skipping and G-nucleotide insertion variants. Another SNP, rs62305723 (encoding a P260S mutation), is significantly associated with decreased ballooning and inflammation. Hepatic expression of HSD17B13 is 5.9-fold higher (P = 0.003) in patients with NAFLD. HSD17B13 is targeted to lipid droplets, requiring the conserved amino acid 22-28 sequence and amino acid 71-106 region. The protein has retinol dehydrogenase (RDH) activity, with enzymatic activity dependent on lipid droplet targeting and cofactor binding site. The exon 6 deletion, G insertion, and naturally occurring P260S mutation all confer loss of enzymatic activity. Conclusion: We demonstrate the association of variants in HSD17B13 with specific features of NAFLD histology and identify the enzyme as a lipid droplet-associated RDH; our data suggest that HSD17B13 plays a role in NAFLD through its enzymatic activity.
Incorporating multi-chip module packaging constraints into system design (1996)

Computer system design addresses the optimization of metrics such as cost, performance, power, and reliability in the presence of physical constraints. The advent of large area, low cost Multi-Chip Modules (MCM) will lead to a new class of optimal system designs. This paper explores the early analysis of the impact of packaging technology on this design process. Our goal is to develop a suite of tools to evaluate computing system architectures under the constraints of various technologies. The design of the memory hierarchy in high speed microprocessors is used to explore the nature and type of trade-offs that can be made during the conceptual design of computing systems.
Increasing the Affinity Between Carbon-Coated LiFePO<sub>4</sub>/C Electrodes and Conventional Organic Electrolyte by Spontaneous Grafting of a Benzene-Trifluoromethylsulfonimide Moiety (2015)

The grafting of benzene-trifluoromethylsulfonimide groups on LiFePO4/C was achieved by spontaneous reduction of in situ generated diazonium ions of the corresponding 4-amino-benzene-trifluoromethylsulfonimide. The diazotization of 4-amino-benzene-trifluoromethylsulfonimide was a slow process that required a high concentration of precursors to promote the spontaneous grafting reaction. Contact angle measurements showed a hydrophilic surface was produced after the reaction that is consistent with grafting of benzene-trifluoromethylsulfonimide groups. Elemental analysis data revealed a 2.1 wt % loading of grafted molecules on the LiFePO4/C powder. Chemical oxidation of the cathode material during the grafting reaction was detected by X-ray diffraction and quantified by inductively coupled plasma atomic emission spectrometry. Surface modification improves the wettability of the cathode material, and better discharge capacities were obtained for modified electrodes at high C-rate. In addition, electrochemical impedance spectroscopy showed the resistance of the modified cathode was lower than that of the bare LiFePO4/C film electrode. Moreover, the modified cathode displayed superior capacity retention after 200 cycles of charge/discharge at 1 C.
Purine Nucleoside Phosphorylase: A New Marker for Free Oxygen Radical Injury to the Endothelial Cell (1990)

The effect of ischemia and reperfusion on purine nucleoside phosphorylase was studied in an isolated perfused rat liver model. This enzyme is localized primarily in the cytoplasm of the endothelial and Kupffer cells; some activity is associated with the parenchymal cells. Levels of this enzyme accurately predicted the extent of ischemia and reperfusion damage to the microvascular endothelial cell of the liver. Livers from Lewis rats were subjected to 30, 45 and 60 min of warm (37 degrees C) no flow ischemia that was followed by a standard reperfusion period lasting 45 min. Purine nucleoside phosphorylase was measured at the end of the no flow ischemia and reperfusion periods as was superoxide generation (O2-). Bile production was monitored throughout the no flow ischemia and reperfusion periods. Control perfusions were carried out for 120 min. A significant rise in purine nucleoside phosphorylase levels as compared with controls was observed at the end of ischemia in all the three groups. The highest level, 203.5 +/- 29.2 mU/ml, was observed after 60 min of ischemia. After the reperfusion period, levels of purine nucleoside phosphorylase decreased in the 30- and 45-min groups 58.17 +/- 9.66 mU/ml and 67.5 +/- 17.1 mU/ml, respectively. These levels were equal to control perfusions. In contrast, after 60 min of ischemia, levels of purine nucleoside phosphorylase decreased early in the reperfusion period and then rose to 127.8 +/- 14.8 mU/ml by the end of reperfusion (p less than 0.0001). Superoxide generation at the beginning of reperfusion was higher than in controls with similar values observed at the end of 30, 45 and 60 min of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of extracellular matrices on porcine umbilical cord matrix stem cells (2008)

The three transcription factors, Nanog, Oct-4 and Sox-2, are central regulators of pluripotency in embryonic stem cells.Porcine umbilical cord (PUC) matrix stem cells also express these transcription factors.Wharton's jelly is composed of an extracellular matrix high in hyaluronic acid and various collagens and serves as a reservoir for several growth factors and cytokines.We expect that Wharton's jelly includes a stem cell niche that provides a microenvironment that maintains and supports the stem-cell characteristics of PUCs.The mechanisms by which the PUCs remain primitive within the Wharton's jelly are unknown.We developed methods for producing an extracellular matrix product extracted from porcine Wharton's jelly that we named Pormatrix (PMX).When PMX is incubated at 37 o C, it becomes a matrical gel that provides a matrix allowing PUC attachment and growth.Concentrating the protein in PMX by filtration provides a low molecular weight by-product which we refer to as flow through (FT).In Experiment 1, PUCs were seeded on Pormatrix, Matrigel or plastic substrates in the presence or absence of FT.PUCs cultured on Matrigel, Matrigel+FT, Plastic+FT and PMX had higher expression of Nanog compared to PUCs cultured on PMX+FT (P-value <0.05).In Experiment 2, the PMX and Matrigel were diluted to low protein concentrations (1.2-1.5 mg/ml protein) so that gelling did not occur.Adding FT to PMX, Matrigel and plastic increased gene expression of Nanog 2.78 fold compared to treatments without FT (P =0.10).Sox-2 expression was increased by adding FT to Matrigel but adding FT to the other matrix proteins had no effect resulting in a tendency for a matrix*FT interaction(P=0.10).The transcription factor Oct-4 remained unchanged regardless of treatment.To evaluate the effects of in vitro maintenance on Nanog, Oct-4 and Sox-2 we measured the relative gene expression in PUCs over the first six passages in vitro.Nanog, Oct-4 and Sox-2 did not differ over these passages.This may indicate that during the first six passages in vitro, PUCs remain relatively primitive.In summary, we prepared an extract from Wharton's jelly from porcine umbilical cords.The extract supported PUC attachment and growth and appeared to regulate gene expression.Perhaps with further investigation the interactions of PUCs with their in vivo environment can be elucidated.
Estimation of the Sound Field at Arbitrary Positions in Distributed Microphone Networks Based on Distributed Ray Space Transform (2018)

In this paper we propose a parametric sound field reconstruction approach. In particular, the technique is based on the estimation of three parameters for each acoustic source (source position, radiation pattern and source signal) given the signals acquired by few arbitrarily placed microphone arrays. This allows us to synthesize the signal of a virtual microphone placed in any point of the acoustic scene.
In vitro affinity maturation of a natural human antibody overcomes a barrier to in vivo affinity maturation (2014)

Antibodies isolated from human donors are increasingly being developed for anti-infective therapeutics. These antibodies undergo affinity maturation in vivo, minimizing the need for engineering of therapeutic leads for affinity. However, the affinities required for some therapeutic applications may be higher than the affinities of the leads obtained, requiring further affinity maturation in vitro. To improve the neutralization potency of natural human antibody MSL-109 targeting human cytomegalovirus (CMV), we affinity matured the antibody against the gH/gL glycoprotein complex. A phage display library where most of the six complementary-determining regions (CDRs) were allowed to vary in only one amino acid residue at a time was used to scan for mutations that improve binding affinity. A T55R mutation and multiple mutations in position 53 of the heavy chain were identified that, when present individually or in combination, resulted in higher apparent affinities to gH/gL and improved CMV neutralization potency of Fab fragments expressed in bacterial cells. Three of these mutations in position 53 introduced glycosylation sites in heavy chain CDR 2 (CDR H2) that impaired binding of antibodies expressed in mammalian cells. One high affinity (KD<10 pM) variant was identified that combined the D53N and T55R mutations while avoiding glycosylation of CDR H2. However, all the amino acid substitutions identified by phage display that improved binding affinity without introducing glycosylation sites required between two and four simultaneous nucleotide mutations to avoid glycosylation. These results indicate that the natural human antibody MSL-109 is close to a local affinity optimum. We show that affinity maturation by phage display can be used to identify and bypass barriers to in vivo affinity maturation of antibodies imposed by glycosylation and codon usage. These constraints may be relatively prevalent in human antibodies due to the codon usage and the amino acid sequence encoded by the natural human repertoire.
Crystal structures of leukotriene A <sub>4</sub> hydrolase in complex with captopril and two competitive tight‐binding inhibitors (2002)

Leukotriene (LT) A4 hydrolase/aminopeptidase is a bifunctional zinc enzyme that catalyzes the final step in the biosynthesis of LTB4, a potent chemoattractant and immune modulating lipid mediator. Here, we report a high-resolution crystal structure of LTA4 hydrolase in complex with captopril, a classical inhibitor of the zinc peptidase angiotensin-converting enzyme. Captopril makes few interactions with the protein, but its free thiol group is bound to the zinc, apparently accounting for most of its inhibitory action on LTA4 hydrolase. In addition, we have determined the structures of LTA4 hydrolase in complex with two selective tight-binding inhibitors, a thioamine and a hydroxamic acid. Their common benzyloxyphenyl tail, designed to mimic the carbon backbone of LTA4, binds into a narrow hydrophobic cavity in the protein. The free hydroxyl group of the hydroxamic acid makes a suboptimal, monodentate complex with the zinc, and strategies for improved inhibitor design can be deduced from the structure. Taken together, the three crystal structures provide the molecular basis for the divergent pharmacological profiles of LTA4 hydrolase inhibitors. Moreover, they help define the binding pocket for the fatty acid-derived epoxide LTA4 as well as the subsites for a tripeptide substrate, which in turn have important implications for the molecular mechanisms of enzyme catalyses.
A new design approach to large input/output number multimode interference couplers and its application to low-crosstalk WDM routers (1998)

A new design approach for N/spl times/N multimode interference (MMI) couplers with large N is described which yields a device design with extremely low imbalance and insertion loss. Analytical expressions for the phase errors in MMI devices are derived from basic principles; these expressions enable significant phase-error reduction to be obtained by optimizing the index-contrast. This optimization in conjunction with the proper placement of the access waveguides allows significant improvement in the device performance. An application of the design approach is illustrated through the design of an 8/spl times/8 MMI-based, phased-array demultiplexer with low crosstalk.
A High Dynamic-Range Neural Recording Chopper Amplifier for Simultaneous Neural Recording and Stimulation (2017)

Closed-loop neuromodulation is essential for the advance of neuroscience and for administering therapy in patients suffering from drug-resistant neurological conditions. Neural stimulation generates large artifacts at the recording sites, which easily saturate traditional recording front ends. This paper presents a neural recording chopper amplifier capable of handling in-band artifacts up to 40 mVpp while preserving the accompanying small neural signals. New techniques have been proposed that solve the issues of low input impedance and electrode-offset rejection, which enable a DC input impedance of 300 MΩ and a dynamic range of 69 dB (200 Hz-5 kHz) and 78 dB (1-200 Hz). Implemented in a 40-nm CMOS process, the prototype occupies an area of 0.071 mm2/channel, and consumes 2 μW from a 1.2 V supply. The input-referred noise is 7 μV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rms</sub> (200 Hz-20 kHz) and 2 μV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">rms</sub> (1-200 Hz). The total harmonic distortion for a 20-mV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</sub> input at 1 kHz is -74 dB. This paper improves the linearity by 14-26 dB, dynamic range by 11-28 dB, and input-impedance for chopped front ends by a factor of 11 as compared with the current state of the art, while achieving similar power and noise performance.