gebhart/patrepeval huggingface dataset:
The 9‐hexadecenoic and 11‐octadecenoic acid content of natural fats and oils (1968)

The monoenoic methyl esters from numerous fats and oils which contained appreciablecis-9-hexadecenoic acid (cis-9-16ratio1) were isolated by liquid-solid chromatography on silver nitrate-silica gel. Analysis of the monoenes by packed and capillary column gas-liquid chromatography showed that significant amounts ofcis-11-octadecenoic acid (cis-11-18ratio1) were present in all samples. The amount ofcis-11-18ratio1 found in the monoenoic methyl esters increased proportionally to logarithmic increases in thecis-9-16ratio1 level. Most analyses reported in the literature also show this proportionality. This mathematical relationship suggests that chain elongation ofcis-9-16ratio1 tocis-11-18ratio1 is a biosynthetic pathway operative in a wide variety of species.
Developmental changes in cerebral autoregulatory capacity in the fetal sheep parietal cortex (2002)

We validated laser Doppler flowmetry (LDF) for long-term monitoring and detection of acute changes of local cerebral blood flow (lCBF) in chronically instrumented fetal sheep. Using LDF, we estimated developmental changes of cerebral autoregulation. Single fibre laser probes (0.4 mm in diameter) were implanted in and surface probes were placed on the parietal cerebral cortex at 105 +/- 2 (n = 7) and 120 +/- 2 days gestational age (dGA, n = 7). Basal lCBF was monitored over 5 days followed by a hypercapnic challenge (fetal arterial partial pressure of CO(2), P(a,CO2): 83 +/- 3 mmHg) during which lCBF changes obtained by LDF were compared to those obtained with coloured microspheres (CMSs). Mean arterial blood pressure (MABP) was increased and decreased using phenylephrine and sodium nitroprusside at 110 +/- 2 and 128 +/- 2 dGA. Intracortical and cortical surface laser probes gave stable measurements over 5 days. The lCBF increase during hypercapnia obtained by LDF correlated well with flows obtained using CMS (r = 0.89, P < 0.01). The signals of intracortical and surface laser probes also correlated well (r = 0.91, P < 0.01). Gliosis of 0.35 +/- 0.06 mm around the tip of intracortical probes did not affect the measurements. The range of MABP over which cerebral autoregulation was observed increased from 20-48 mmHg at 110 dGA to 35 to > 95 mmHg at 128 dGA (P < 0.05). Since MABP increased from 33 to 54 mmHg over this period (P < 0.01), the range between the lower limit of cerebral autoregulation and the MABP increased from 13 mmHg at 110 dGA to 19 mmHg at 128 dGA (P < 0.01). LDF is a reliable tool to assess dynamic changes in cerebral perfusion continuously in fetal sheep.
Insulin degludec as an ultralong-acting basal insulin once a day: a systematic review (2012)

Based upon the available evidence, there appear to be no reported differences between IDeg and IGlar, detemir, or BIAsp 30 in the reduction of the primary efficacy end-points of HbA(1c) and mean fasting plasma glucose (FPG) concentrations. Only flexible dosing of IDeg provided a significant reduction in FPG compared to IGlar. IDeg demonstrated a significant reduction in nocturnal hypoglycemia in type 1 diabetes. In type 2 diabetes, IDeg reduced the incidence of hypoglycemia by 18% and 58% compared to IGlar and BIAsp 30, respectively.
Incorporation of Norleucine at Methionine Positions in Recombinant Human Macrophage Colony Stimulating Factor (M-CSF, 4-153) Expressed in Escherichia coli: Structural Analysis (1994)

Expression of the 17.5-kDa truncated form of human recombinant macrophage colony stimulating factor (rM-CSF, 4-153) in Escherichia coli is complicated by the replacement of methionine residues by norleucine. In order to detect and quantitate this mistranslational event, the intact and the S-carboxyamidomethylated proteins were analyzed by amino acid analysis, automated Edman amino acid sequencing, and electrospray mass spectrometry. In addition, the endoproteinase Glu-C generated peptides were subjected to amino acid sequencing, high-performance liquid chromatography, and electrospray ionization mass spectrometry. The extent of norleucine substitution in different batches of rM-CSF varied between 0% and 20%. The relative instability of methionine residues needs to be considered when calculating the extent of norleucine substitution at methionine positions. The mass spectrometry of the intact rM-CSF allowed for examination of the distribution of multiply substituted methionine to norleucine species, and it enabled detection and quantitation of the norleucine incorporation down to the approximately 3% level. Selective ion chromatograms of molecular ions of interest obtained in reversed-phase high-performance liquid chromatography/electrospray ionization mass spectrometry of proteolytic fragments offered a reliable and fast method of detection and quantitation of norleucine-containing peptides. Norleucine residues were uniformly distributed among all four methionine positions (10, 27, 61, and 65). A substitution of methionine by its structural norleucine analog does not have any effect on the activity of the refolded rM-CSF dimers.
Structure and Expression of Germ Line Immunoglobulin γ2b Transcripts (1988)

We have isolated a cDNA copy of a truncated C gamma 2b transcript produced by Abelson murine leukemia virus transformants that spontaneously switch from mu to gamma 2b. The initiation site of this transcript was 2 kilobases 5' to the gamma 2b switch recombination region, demonstrating its germ line origin. Nucleotide sequence analyses suggest that this transcript does not encode a protein. Expression of germ line gamma 2b transcripts in Abelson murine leukemia virus transformants and in normal spleen cells correlated with endogenous gamma 2b class switch activity.
Intraarticular reaction associated with the use of freeze-dried, ethylene oxide-sterilized bone-patella tendon-bone allografts in the reconstruction of the anterior cruciate ligament (1990)

One hundred nine patients over a 3 year period underwent reconstruction for chronic ACL ruptures using a freeze-dried, ethylene oxide-sterilized bone-patella tendon-bone allograft. Seven patients (6.4%) developed a characteristic persistent intraarticular reaction. This reaction was characterized by persistent synovial effusion with collagenous particulates and cellular inflammatory response. Synovial biopsies in all cases showed a similar chronic inflammatory process, characterized by fibrin, collagen, and phagocytic cells. The intraarticular white cells were predominantly lymphocytes. Removal of the allograft resulted in resolution of the reaction in all of the patients. Three of the seven patients showed HLA conversion. Gas chromatography demonstrated detectable levels of ethylene chlorohydrin, a toxic reaction product of ethylene oxide, within the allograft and synovium 14 months following implantation of one graft. These seven cases presented strongly suggest a nonspecific or immune mediated response that must be further delineated. The use of freeze-dried, ethylene oxide-sterilized allografts using standard techniques cannot be recommended for reconstruction of the ACL.
Mechanism of action of angiostatic steroids: Suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis (1993)

Recently, a novel class of angiostatic steroids which block angiogenesis in several systems has been described. Since the elaboration of proteases is believed to be an important component of angiogenesis, we tested whether these steroids blocked the fibrinolytic response of endothelial cells to the angiogenic protein, basic fibroblast growth factor [bFGF]). Cultured bovine aortic endothelial (BAE) cells were incubated with bFGF and/or medroxyprogesterone acetate (MPA), an angiostatic steroid which has been shown to inhibit vascularization, collagenolysis, and tumor growth. When bFGF (3 ng/ml) was added to confluent monolayers of BAE cells, plasminogen activator (PA) activity in the medium was increased threefold. In contrast, MPA at 10(-6) M, 10(-7) M, 10(-8) M, and 10(-9) M decreased PA levels in the medium by 83%, 83%, 75%, and 39%, respectively. The stimulation of PA levels in BAE cells by bFGF (3 ng/ml) was abrogated by the presence of 10(-6) M MPA. This decrease in PA activity was found to be mediated by a significant increase in plasminogen activator inhibitor type-1 (PAI-1) production. MPA, therefore, negated one of the important enzymatic activities associated with the angiogenic process. In contrast to the decreased levels of secreted PA in cultures exposed simultaneously to MPA and bFGF, cell-associated PA levels remained high, consistent with earlier observations indicating that PAI-1 does not inhibit cell-associated PA. Thus, angiostatic steroids may exert their inhibitory effects on angiogenesis by increasing the synthesis of PAI-1. This, in turn, inhibits PA activity and, therefore, plasmin generation, which is essential for the invasive aspect of angiogenesis.
A Novel Inhibitor of the Mammalian Peptide Transporter PEPT1 (2001)

This study was initiated to develop inhibitors of the intestinal H(+)/peptide symporter. We provide evidence that the dipeptide derivative Lys[Z(NO(2))]-Pro is an effective competitive inhibitor of mammalian PEPT1 with an apparent binding affinity of 5-10 microM. Characterization of the interaction of Lys[Z(NO(2))]-Pro with the substrate binding domain of PEPT1 has been performed in (a) monolayer cultures of human Caco-2 cells expressing PEPT1, (b) transgenic Pichia pastoris cells expressing PEPT1, and (c) Xenopus laevis oocytes expressing PEPT1. By competitive uptake studies with radiolabeled dipeptides, HPLC analysis of Lys[Z(NO(2))]-Pro in cells, and electrophysiological techniques, we unequivocally show that Lys[Z(NO(2))]-Pro binds with high affinity to PEPT1, competes competitively with various dipeptides for uptake into cells, but is not transported itself. Lack of transport was substantiated by the absence of Lys[Z(NO(2))]-Pro in Caco-2 cell extracts as determined by HPLC analysis, and by the absence of any positive inward currents in oocytes when exposed to the inhibitor. The fact that Lys[Z(NO(2))]-Pro can bind to PEPT1 from the extracellular as well as the intracellular site was shown in the oocyte expression system by a strong inhibition of dipeptide-induced currents under voltage clamp conditions. Our findings serve as a starting point for the identification of the substrate binding domain in the PEPT1 protein as well as for studies on the physiological and pharmacological role of PEPT1.
Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells (2016)

Dimethyl fumarate (DMF) is an electrophilic drug that is used to treat autoimmune conditions, including multiple sclerosis and psoriasis. The mechanism of action of DMF is unclear but may involve the covalent modification of proteins or DMF serving as a prodrug that is converted to monomethyl fumarate (MMF). We found that DMF, but not MMF, blocked the activation of primary human and mouse T cells. Using a quantitative, site-specific chemical proteomic platform, we determined the DMF sensitivity of >2400 cysteine residues in human T cells. Cysteines sensitive to DMF, but not MMF, were identified in several proteins with established biochemical or genetic links to T cell function, including protein kinase Cθ (PKCθ). DMF blocked the association of PKCθ with the costimulatory receptor CD28 by perturbing a CXXC motif in the C2 domain of this kinase. Mutation of these DMF-sensitive cysteines also impaired PKCθ-CD28 interactions and T cell activation, designating the C2 domain of PKCθ as a key functional, electrophile-sensing module important for T cell biology.
Precise Breakpoint Localization of Large Genomic Deletions using PacBio and Illumina Next-Generation Sequencers (2013)

Herein we present the applicability of single-molecule (PacBio RS) and second-generation sequencing technology (Illumina) to the characterization of large genomic deletions. By testing samples previously characterized using a Sanger approach, our methods determined that both next-generation sequencing platforms were able to identify the position of deletion breakpoints. Our results point out various advantages of next-generation sequencing platforms when characterizing genomic deletions; however, special attention must be dedicated to identical sequences flanking the breakpoints, such as poly(N) motifs.
Autonet: a high-speed, self-configuring local area network using point-to-point links (1991)

Autonet is a self-configuring local area network composed of switches interconnected by 100 Mb/s, full-duplex, point-to-point links. The switches contain 12 ports that are internally connected by a full crossbar. Switches use cut-through to achieve a packet forwarding latency as low as 2 ms/switch. Any switch port can be cabled to any other switch port or to a host network controller. A processor in each switch monitors the network's physical configuration. A distributed algorithm running on the switch processor computes the routes packets are to follow and fills in the packet forwarding table in each switch. With Autonet, distinct paths through the set of network links can carry packets in parallel, allowing many pairs of hosts to communicate simultaneously at full link bandwidth. A 30-switch network with more than 100 hosts has been the service network for Digital's Systems Research Center since February 1990.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Gap plasmon-based metasurfaces for total control of reflected light (2013)

In the quest to miniaturise photonics, it is of paramount importance to control light at the nanoscale. We reveal the main physical mechanism responsible for operation of gap plasmon-based gradient metasurfaces, comprising a periodic arrangement of metal nanobricks, and suggest that two degrees of freedom in the nanobrick geometry allow one to independently control the reflection phases of orthogonal light polarisations. We demonstrate, both theoretically and experimentally, how orthogonal linear polarisations of light at wavelengths close to 800 nm can be manipulated independently, efficiently and in a broad wavelength range by realising polarisation beam splitters and polarisation-independent beam steering, showing at the same time the robustness of metasurface designs towards fabrication tolerances. The presented approach establishes a new class of compact optical components, viz., plasmonic metasurfaces with controlled gradient birefringence, with no dielectric counterparts. It can straightforwardly be adapted to realise new optical components with hitherto inaccessible functionalities.
Attenuation of Recombinant Yellow Fever 17D Viruses Expressing Foreign Protein Epitopes at the Surface (2005)

The yellow fever (YF) 17D vaccine is a live attenuated virus. Three-dimensional (3D) homology modeling of the E protein structure from YF 17D virus and its comparison with that from tick-borne encephalitis virus revealed that it is possible to accommodate inserts of different sizes and amino acid compositions in the flavivirus E protein fg loop. This is consistent with the 3D structures of both the dimeric and trimeric forms in which the fg loop lies exposed to solvents. We demonstrate here that YF 17D viruses bearing foreign humoral (17D/8) and T-cell (17D/13) epitopes, which vary in sequence and length, displayed growth restriction. It is hypothesized that interference with the dimer-trimer transition and with the formation of a ring of such trimers in order to allow fusion compromises the capability of the E protein to induce fusion of viral and endosomal membranes, and a slower rate of fusion may delay the extent of virus production. This would account for the lower levels of replication in cultured cells and of viremia in monkeys, as well as for the more attenuated phenotype of the recombinant viruses in monkeys. Testing of both recombinant viruses (17D/8 and 17D/13) for monkey neurovirulence also suggests that insertion at the 17D E protein fg loop does not compromise the attenuated phenotype of YF 17D virus, further confirming the potential use of this site for the development of new live attenuated 17D virus-based vaccines.
ErbB3 (HER3) interaction with the p85 regulatory subunit of phosphoinositide 3-kinase (1998)

ErbB3 (HER3), a unique member of the ErbB receptor family, lacks intrinsic protein tyrosine kinase activity and contains six Tyr-Xaa-Xaa-Met (YXXM) consensus binding sites for the SH2 domains of the p85 regulatory subunit of phosphoinositide 3-kinase. ErbB3 also has a proline-rich sequence that forms a consensus binding site for the SH3 domain of p85. Here we have investigated the interacting domains of ErbB3 and p85 by a unique application of the yeast two-hybrid system. A chimaeric ErbB3 molecule containing the epidermal growth factor receptor protein tyrosine kinase domain was developed so that the C-terminal domain of ErbB3 could become phosphorylated in the yeast system. We also generated several ErbB3 deletion and Tyr-->Phe site-specific mutants, and observed that a single ErbB3 YXXM motif was necessary and sufficient for the association of ErbB3 with p85. The incorporation of multiple YXXM motifs into the ErbB3 C-terminus enabled a stronger ErbB3/p85 interaction. The proline-rich region of ErbB3 was not necessary for interaction with p85. However, either deletion or mutation of the p85 SH3 domain decreased the observed ErbB3/p85 association. Additionally an ErbB3/p85 SH3 domain interaction was detected by an assay in vitro. These results were consistent with a model in which pairs of phosphorylated ErbB3 YXXM motifs co-operate in binding to the tandem SH2 domains of p85. Although a contributing role for the p85 SH3 domain was suggested, the N- and C-terminal SH2 domains seemed to be primarily responsible for the high-affinity association of p85 and ErbB3.
Expression of hepatocyte growth factor and its receptor c- met proto-oncogene in hepatocellular carcinoma (1997)

The c-met proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC). In this study, we examined HGF concentration and expression of the c-met-proto-oncogene product (c-met) in 62 patients with HCC to determine the relationship between the level of expression and clinicopathological features, and patient outcome following hepatectomy. Western blotting was used to examine the c-met expression, and HGF concentration in tumors was measured using an enzyme-linked immunosorbent assay. c-met was found to be overexpressed in HCC compared with nontumorous liver tissue (P < .01), and correlated with an increased incidence of intrahepatic metastases (P = .039). Patients were divided into two groups, low c-met HCC and high c-met HCC. Patients with high c-met HCC had a significantly shorter 5-year survival than patients with low c-met HCC (33.5% vs. 80.3%, respectively; P < .05). However, there was no correlation between HGF concentration in the tumor tissue and clinicopathological factors and patient survival. These results indicate that expression of c-met played an important role in tumor growth and metastases in patients who underwent hepatectomy for HCC.
CHOLESTERIC LIQUID CRYSTALS FOR OPTICAL APPLICATIONS (1971)

The optical and thermal properties of mixtures of MBBA and COC are reported on as an example of cholesteric liquid crystals incorporating molecules which are not cholesterol derivatives. These materials exhibit relatively broad optical bandwidths, efficient polarizing characteristics, extremely weak temperature dependences, and high structural order properties which should be useful in optical devices.
Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T‐cell subset (2004)

Summary CD4+ CD25+ T regulatory cells (TReg), suppress antigen-specific immune responses and are important for allograft tolerance. During pregnancy the mother tolerates an allograft expressing paternal antigens (the fetus) requiring substantial changes in immune regulation over a programmed period of time. We analysed whether immune-suppressive TReg cells were altered during pregnancy and therefore might play a part in this tolerant state. The presence of TReg cells was assessed in the blood of 25 non-pregnant, 63 pregnant and seven postnatal healthy women by flow cytometry. We observed an increase in circulating TReg cells during early pregnancy, peaking during the second trimester and then a decline postpartum. Isolated CD25+ CD4+ cells expressed FoxP3 messenger RNA, a marker of TReg cells, and suppressed proliferative responses of autologous CD4+ CD25- T cells to allogeneic dendritic cells. These data support the concept that normal pregnancy is associated with an elevation in the number of TReg cells which may be important in maintaining materno-fetal tolerance.
Nanoparticles:  Scaffolds and Building Blocks (2003)

Nanoparticles provide key tools for bridging the gap between "bottom-up" synthetic methods and "top-down" fabrication. In this Account we describe some of the unique structural aspects of nanoparticles and the use of these attributes to the creation of devices with tunable specificity and environmental response. We also explore the use of nanoparticles as "building blocks" for the creation of nanocomposite materials that feature structural control from the molecular to the micron scale.
Osmoregulation in Enterobacteriaceae: role of proline betaine transport systems (1988)

In a wide variety of organisms, L-proIine and glycine betaine are amongst the compounds accumulated intracellularly as compatible solutes to counteract the effects of turgor reduction during growth in water-stressed environments. Two osmoregulatory transport systems, ProP and ProU, have been identified and characterized in the enterobacteria, each of which participates in the active concentration of both L-proline and glycine betaine from the culture medium in response to osmotic stress. The expression of genes encoding the components of the ProU porter is induced 400-fold upon growth in high-osmolarity medium; elucidation of the molecular mechanisms underlying such regulation would possibly enable understanding of the large class of processes that involve transduction of mechanical signals to chemical ones within biological systems. A complete understanding of the molecular basis by which ProP and ProU function in osmoregulation would also provide insight into the mechanisms of similar adaptation at the cellular level in the economically important genera of microbes and higher plants.
Holographically Observed Torsion in a Cylindrical Shaft (1970)

Using holographic interferometry, the rotation of a rigid cylinder and the torsion of a flexible shaft (RTV silastic rubber) have been observed. The experimentally generated fringe patterns are compared with computed ones and good agreement is obtained.