gebhart/patrepeval huggingface dataset:
Pharmacological regulation of gastric acid secretion in the apical membrane of parietal cells; a new target for antisecretory drugs. (2001)

We examined the local effect of several drugs against secretagogue-stimulated acid secretion in dogs. Test drugs were applied to denervated gastric pouches in conscious dogs either for 5 to 30 min beginning 1 hr after or for 30 min before intravenous infusion of gastric secretagogues (histamine, pentagastrin, or carbachol). The antisecretory effect of test drugs delivered by an intravenous or oral route was also examined. Local application of acid pump inhibitors (omeprazole, leminoprazole) for 30 min beginning 1 hr after histamine infusion significantly inhibited gastric acid secretion. The effect of leminoprazole persisted for more than 8 hr after a 30 min application. A mast cell stabilizer (FPL 52694) applied to pouches for 15 to 30 min also potently inhibited histamine-stimulated gastric acid secretion in a time-dependent manner. The duration of the antisecretory effect of such drugs after a 30 min application was greater than 4 hr. Locally applied leminoprazole and FPL 52694 for 30 min also significantly inhibited pentagastrin- and carbachol-stimulated gastric acid secretion. Although intravenous omeprazole and leminoprazole exerted a potent antisecretory effect on histamine-induced acid secretion FPL 52694 had little or no antisecretory effect following intravenous or oral administration. 16,16-dimethyl prostagladin E2 also locally inhibited histamine-stimulated acid secretion. Acid stable local anesthetics (tetracaine, ethyl-4-aminobenzoate), histamine H2-receptor blockers (cimetidine, ranitidine, and famotidine), and a muscarinic M1-receptor antagonist (pirenzepine) did not exhibit local antisecretory effects. Such results strongly suggest that the apical membrane of parietal cells possesses a pharmcologically sensitive portion similar to the basolateral membrane, which usually mediates gastric acid secretion. The apical membrane represents an intriguing target for new antisecretory drugs, as well as a new medium for further elucidating the functional features of parietal cells.
Antisecretory Effect of Leminoprazole on Histamine-Stimulated Gastric Acid Secretion in Dogs: Potent Local Effect (1995)

Leminoprazole, an acid pump inhibitor, significantly reduces basal and stimulated gastric acid secretion in rats when administered via the systemic or local route. Our aim here was to characterize the antisecretory effect of leminoprazole on gastric acid secretion in conscious dogs. Gastric acid secretion by dogs with a vagally denervated Heidenhain pouch was stimulated by intravenous histamine infusion. Leminoprazole or omeprazole (as a reference drug) was administered either intravenously or locally into the pouch before or after histamine infusion. A bolus intravenous administration of leminoprazole and omeprazole, respectively, significantly and dose-relatedly inhibited the stimulated gastric acid secretion for > 26 hr. Local application of leminoprazole, but not omeprazole, significantly inhibited the acid secretion when applied for 15 to 30 min. The duration of the local antisecretory effect observed after 30 min application was around 8-10 hr. The acid-degraded products of leminoprazole had no effect when applied to the pouch. The blood concentration of leminoprazole was very low at 1 hr after local application. These results indicate that leminoprazole suppresses the secretory function of the parietal cells of dogs, via both the intravenous and local routes. It remains unknown whether or not locally applied leminoprazole produced the acid inhibition by inhibiting the acid pump.
Advances in tenascin-C biology (2011)

Tenascin-C is an extracellular matrix glycoprotein that is specifically and transiently expressed upon tissue injury. Upon tissue damage, tenascin-C plays a multitude of different roles that mediate both inflammatory and fibrotic processes to enable effective tissue repair. In the last decade, emerging evidence has demonstrated a vital role for tenascin-C in cardiac and arterial injury, tumor angiogenesis and metastasis, as well as in modulating stem cell behavior. Here we highlight the molecular mechanisms by which tenascin-C mediates these effects and discuss the implications of mis-regulated tenascin-C expression in driving disease pathology.
Roles of calnexin and Ig-alpha beta interactions with membrane Igs in the surface expression of the B cell antigen receptor of the IgM and IgD classes (1997)

Membrane Igs (mIgs) of all five classes are associated with Ig-alpha beta dimers on the B cell surface. While mIgM requires the presence of these two associated molecules for its surface expression, mIgD does not. To study the structural basis for this differential Ig-alpha beta dependence, we created mutant mIgM and mIgD molecules (chimeras and those with reciprocal point mutations in their transmembrane sequences) and identified two amino acid residues in the transmembrane region of the mIg heavy chains responsible for this transport difference. Without Ig-alpha beta, mIgM and mutant mIgD molecules remained endoglycosidase H sensitive, consistent with endoplasmic reticulum (ER) localization. The molecular chaperone calnexin has previously been implicated in retaining unassembled mIgs in the ER. However, we found that inhibition of the association between calnexin and newly synthesized mIgs by castanospermine treatment did not lead to surface expression of normally retained mIgs. Therefore, calnexin cannot be the only retention molecule. Furthermore, for both wildtype and mutant mIgDs, association with calnexin was rather transient, thereby ruling out calnexin being a major ER retention molecule for mIgDs. Our study with castanospermine also showed that calnexin is required for wildtype mIgD surface expression only if Ig-alpha beta is absent, while the latter alone can function to promote mIg folding, assembly, and transport. Further study using our system will help to identify novel molecules and characterize their involvement in the control of mIg transport.
Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer (2017)

In the setting of a challenge competition, some deep learning algorithms achieved better diagnostic performance than a panel of 11 pathologists participating in a simulation exercise designed to mimic routine pathology workflow; algorithm performance was comparable with an expert pathologist interpreting whole-slide images without time constraints. Whether this approach has clinical utility will require evaluation in a clinical setting.
Paving the Way for Lignin Valorisation: Recent Advances in Bioengineering, Biorefining and Catalysis (2016)

Lignin is an abundant biopolymer with a high carbon content and high aromaticity. Despite its potential as a raw material for the fuel and chemical industries, lignin remains the most poorly utilised of the lignocellulosic biopolymers. Effective valorisation of lignin requires careful fine-tuning of multiple "upstream" (i.e., lignin bioengineering, lignin isolation and "early-stage catalytic conversion of lignin") and "downstream" (i.e., lignin depolymerisation and upgrading) process stages, demanding input and understanding from a broad array of scientific disciplines. This review provides a "beginning-to-end" analysis of the recent advances reported in lignin valorisation. Particular emphasis is placed on the improved understanding of lignin's biosynthesis and structure, differences in structure and chemical bonding between native and technical lignins, emerging catalytic valorisation strategies, and the relationships between lignin structure and catalyst performance.
Mutation to Bax beyond the BH3 Domain Disrupts Interactions with Pro-survival Proteins and Promotes Apoptosis (2011)

Pro-survival members of the Bcl-2 family of proteins restrain the pro-apoptotic activity of Bax, either directly through interactions with Bax or indirectly by sequestration of activator BH3-only proteins, or both. Mutations in Bax that promote apoptosis can provide insight into how Bax is regulated. Here, we describe crystal structures of the pro-survival proteins Mcl-1 and Bcl-x(L) in complex with a 34-mer peptide from Bax that encompasses its BH3 domain. These structures reveal canonical interactions between four signature hydrophobic amino acids from the BaxBH3 domain and the BH3-binding groove of the pro-survival proteins. In both structures, Met-74 from the Bax peptide engages with the BH3-binding groove in a fifth hydrophobic interaction. Various Bax Met-74 mutants disrupt interactions between Bax and all pro-survival proteins, but these Bax mutants retain pro-apoptotic activity. Bax/Bak-deficient mouse embryonic fibroblast cells reconstituted with several Bax Met-74 mutants are more sensitive to the BH3 mimetic compound ABT-737 as compared with cells expressing wild-type Bax. Furthermore, the cells expressing Bax Met-74 mutants are less viable in colony assays even in the absence of an external apoptotic stimulus. These results support a model in which direct restraint of Bax by pro-survival Bcl-2 proteins is a barrier to apoptosis.
Murine pneumotropic virus chimeric Her2/neu virus‐like particles as prophylactic and therapeutic vaccines against Her2/neu expressing tumors (2008)

Virus-like particles (VLPs) have increasingly attracted attention as DNA-free and safe antigen carriers in tumor immunotherapy, requiring only minute amounts of antigens. Previously, we have immunized with murine polyomavirus (MPyV) VLPs carrying human Her2/neu and prevented the outgrowth of a human Her2/neu expressing tumor in a transplantable tumor model as well as outgrowth of spontaneous rat Her2/neu carcinomas in BALB-neuT mice. Here, we examine if prophylactic and therapeutic protection could be obtained with murine pneumotropic virus (MPtV) VLPs, and study the cross-reactivity between human and rat Her2/neu. VLPs from MPyV and MPtV carrying human or rat Her2/neu were tested in two transplantable tumor models against a human Her2/neu positive (D2F2/E2) and a rat Her2/neu positive tumor cell line (TUBO). Rat Her2/neu-VLPs were also tested in BALB-neuT mice. Her2/neu-MPtVLPs were as efficient as prophylactic vaccines against D2F2/E2 and TUBO as those from MPyV. Homologous Her2/neu was better than heterologous, i.e. human Her2/neu-VLPs were better than rat Her2/neu-VLPs against D2F2/E2 and vice versa. Moreover, therapeutic immunization with human Her2/neu-VLPs together with CpG given up to 6 days after challenge protected against D2F2/E2. In BALB-neuT mice, rat Her2/neu-VLPs were less efficient than human Her2/neu-VLPs used in our previous study, implying that protection seen in that study was partly due to the use of human rather than rat Her2/neu. In conclusion, Her2/neu-MPtVLPs are effective both as prophylactic and therapeutic tumor vaccines. Homologous Her2/neu-VLPs are superior to heterologous in transplantable tumor models, while the opposite is true in BALB-neuT mice.
Bombesin receptor in membranes from Swiss 3T3 cells. Binding characteristics, affinity labelling and modulation by guanine nucleotides (1990)

Bombesin-like neuropeptides, including mammalian gastrin-releasing peptide (GRP), are potent mitogens for Swiss 3T3 cells. In this study, we have characterized the bombesin receptor in membrane preparations from these cells. Addition of Mg2+ during cell homogenization was essential to preserve 125I-GRP binding activity in the resulting membrane preparation. The effect of Mg2+ was concentration dependent, with a maximum at 5 mM. Specific binding of 125I-GRP was saturable; Scatchard analysis indicated a single class of high-affinity sites of Kd = (2.1 +/- 0.3) x 10(-10) M at 15 degrees C and Kd = (1.9 +/- 0.4) x 10(-10) M at 37 degrees C, and a maximum binding capacity of 580 +/- 50 fmol/mg of protein (15 degrees C) or 604 +/- 40 fmol/mg of protein (37 degrees C). The kinetically derived dissociation constant was 1.5 x 10(-10) M. 125I-GRP binding was inhibited in a concentration-dependent manner by various peptides containing the highly conserved C-terminal heptapeptide of the bombesin family, including bombesin, GRP, neuromedin B and the 8-14 fragment of bombesin. In contrast, a variety of structurally unrelated mitogens and neuropeptides had no effect. The cross-linking agent ethyleneglycolbis(succinimidylsuccinate) covalently linked 125I-GRP to a single Mr 75 000-85 000 protein in membrane preparations of 3T3 cells. Affinity labelling of this molecule was specific and dependent on the presence of Mg2+ during membrane preparation. Finally, the non-hydrolysable GTP analogue guanosine-5'-[gamma-thio]triphosphate (GTP[S]) caused a concentration-dependent inhibition of 125I-GRP binding and cross-linking to 3T3 cell membranes [concentration giving half-maximal inhibition (IC50) approximately 0.2 microM]. The inhibitory effect was specific (GMP, ATP or ATP[S] had no effect at 10 microM) and was due to an increase in Kd from (1.7 +/- 0.2) x 10(-10) M to (4.3 +/- 0.6) x 10(-10) M in the presence of 10 microM-GTP[S]. This modulation of ligand affinity and cross-linking implies that the bombesin receptors that mediate mitogenesis in Swiss 3T3 cells are coupled to a guanine-nucleotide-binding-protein signal-transduction pathway.
Rapid fluorescence in situ hybridization with repetitive DNA probes: Quantification by digital image analysis (1994)

Fluorescence in situ hybridization (FISH) has become an important tool not only in cytogenetic research but also in routine clinical chromosome diagnostics. Here, results of a quantification of fluorescence signals after in situ hybridization with repetitive DNA probes are reported using a non-enzymatic hybridization technique working with a buffer system not containing any formamide or equivalent chemical denaturing agents. Following simultaneous denaturation of both cells and DNA probes, the renaturation time was reduced to less than 30 min. For one of the DNA probes reasonable FISH-signals were even achieved after about 30 s renaturation time. In addition, the number of washing steps was reduced drastically. As a model system, two repetitive DNA probes (pUC 1.77, D15Z1) were hybridized to human metaphase spreads and interphase nuclei obtained from peripheral blood lymphocytes. The probes were labelled with digoxigenin and detected by FITC-anti-digoxigenin. The hybridization time was reduced step by step and the resulting fluorescence signals were examined systematically. For comparison the pUC 1.77 probe was also hybridized according to a FISH protocol containing 50% formamide. By renaturation for 2 h and overnight two FISH signals per nucleus were obtained. Using shorter renaturation times, no detectable FISH signals were observed. Quantification of the FISH signals was performed using a fluorescence microscope equipped with a cooled colour charge coupled device (CCD) camera. Image analysis was made interactively using a commercially available software package running on a PC (80486). For the pUC 1.77 probe the major binding sites (presumptive chromosomes 1) were clearly distinguished from the minor binding sites by means of the integrated fluorescence intensity. For the two (pUC 1.77) or four (D15Z1) brightest spots on the metaphase spreads and in the interphase nuclei hybridized without formamide, integrated fluorescence intensity distributions were measured for different renaturation times (0.5, 15, 30 min). The intra-nuclear variation in the intensity of the two brightest in situ hybridization spots appeared to be slightly higher (CV between 16 and 32%) than the corresponding variation in the metaphase spreads (CV between 10 and 19%). For the D15Z1 probe FISH signals were detected after hybridization without formamide and 15 min and 30 min renaturation. Always four bright spots were visible and tentatively assigned on the metaphase spreads (presumptive chromosome 15 and 9). The intensity variation of each pair of homologues in a metaphase spread showed a CV of 14 or 15%, respectively, for the presumptive chromosome 15, and 8 or 9%, respectively, for the presumptive chromosome 9.
Design and synthesis of array structured telecommunication processing applications (1997)

This paper describes an automated design andsynthesis methodology for telecommunications ASIC's.Array frames, an array structured visualization of theprocessing problem, are used in the specification anddebugging of the design. This allows design much closer to thespecification level. The array frame concept is integratedinto the Dali structured control logic design environment. AnSDH (Synchronous Digital Hierarchy) style exampledemon-strates the use of array frames. The array frame approachwas successfully applied in industrial applications.
Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells (2010)

Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. To evaluate anti-CD19-CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. One infusion of anti-CD19-CAR-transduced T cells completely eliminated normal B cells from mice for at least 143 days. Anti-CD19-CAR-transduced T cells eradicated intraperitoneally injected lymphoma cells and large subcutaneous lymphoma masses. The antilymphoma efficacy of anti-CD19-CAR-transduced T cells was critically dependent on irradiation of mice before anti-CD19-CAR-transduced T-cell infusion. Anti-CD19-CAR-transduced T cells had superior antilymphoma efficacy compared with the anti-CD19 monoclonal antibody from which the anti-CD19 CAR was derived. Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19-CAR-transduced T cells in a clinically relevant murine model.
Plasticized Starch/Tunicin Whiskers Nanocomposite Materials. 2. Mechanical Behavior (2001)

In a previous work [Macromolecules 2000, 33, 8344], nanocomposite materials were obtained using glycerol plasticized starch as the matrix and a colloidal suspension of tunicinan animal cellulosewhiskers as the reinforcing phase. The mechanical behavior of resulting films was characterized in both the linear and the nonlinear range. The effects of the filler and water contents were evaluated, and the results were discussed on the basis of the knowledge of the structural morphology reported in the first part of the paper. The reinforcing effect of tunicin whiskers strongly depended on the ability of cellulose filler to form a rigid network, resulting from strong interactions between whiskers such as hydrogen bonds, and therefore on the moisture content. It was shown that increasing water content induced the crystallization of amylopectin chains and the accumulation of plasticizer in the cellulose/amylopectin interfacial zone. Both phenomena strongly interfere with hydrogen-bonding forces likely to hold the percolating tunicin whiskers network together.
Harmonically mode-locked fiber ring laser with an internal Fabry–Perot stabilizer for soliton transmission (1993)

We describe a modulator-driven, erbium-fiber ring laser that produces chirp-free pulses with width adjustable over the range of 5 to 100 ps. A high-finesse Fabry-Perot étalon with a free spectral range equal to the 2.5-GHz laser repetition rate eliminates unwanted laser ring modes and stabilizes the pulse amplitude. Using this laser, we have extended the error-free distance of a series of soliton transmission experiments by 2000-3000 km over previous results with a mode-locked semiconductor laser.
A Convolutional Neural Network with Dynamic Correlation Pooling (2017)

A dynamic correlation pooling method is proposed based on Mahalanobis distance to improve the accuracy of image recognition. The proposed correlation technique employs the correlation information between adjacent pixels of the image and is applied to Lenet-5 convolution neural network model, the performance of which is tested on data sets of MMIST, USPS and CIFAR-10, respectively. The empirical studies show that the proposed pooling method can improve the convergence rate and recognition accuracy in comparison with the max pooling, average pooling, stochastic pooling and mixed pooling.
A neural network model of spatio-temporal pattern recognition, recall, and timing (2003)

The author describes the design of a self-organizing, hierarchical network model of unsupervised serial learning. The model learns to recognize, store, and recall sequences of unitized patterns, using either short-term memory (STM) or both STM and long-term memory (LTM) mechanisms. Timing information is learned and recall both from STM and from LTM is performed with a learned rhythmical structure. The network, bearing similarities to ART, learns to map temporal sequences to unitized patterns, which makes it suitable for hierarchical operations. It is therefore capable of self-organizing codes for sequences of sequences. The capacity is only limited by the number of nodes provided. Selected simulation results are reported to illustrate system properties.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Induction of Cytolytic T Lymphocytes with Syngeneic Trinitrophenyl-Coupled Membranes (1979)

Evidence is presented that trinitrophenyl-coupled tumor membranes are able to induce cytolytic T lymphocytes (CTL) when co-cultured with syngeneic spleen cells. These haptenated membranes stimulate spleen cells from naive and immune mice. The specificity of these CTL is determined by the H-2 antigens of the membranes used for stimulation.
Chain-length dependence of the protein and cell resistance of oligo(ethylene glycol)-terminated self-assembled monolayers on gold (2001)

Oligo(ethylene glycol) (O-EG(n))-terminated alkanethiol surface-assembled monolayers (SAMs) have been reported to demonstrate protein-resistant properties similar to those of poly(ethylene glycol) (PEG). In this study, we compared the relative protein resistance of short and long ethylene oxide chains, SAMs of PEG 5000, PEG 2000, O-EG(3) (molecular weight = 120), and O-EG(6) (molecular weight = 240), on gold surfaces. Surface plasmon resonance showed that these monolayers were all protein-resistant within the uncertainty of the measurement. However, they exhibited different adhesive properties toward 3T3 mouse fibroblast adhesion in supplemented Dulbecco's modified Eagles medium. The results show that the cell adhesion was sensitive to the concentration of proteins supplemented in the culture medium and to the length of PEG chains.
Engineered threshold voltage in AlGaN/GaN HEMTs for normally-off operation (2015)

This work proposed the normally-off gate-recessed AlGaN/GaN high electron mobility transistors (HEMTs) with more suitable threshold voltages by adjusting the Al mole fraction in the various AlGaN layer thickness under the gate region. It is found that the slope of threshold voltage versus Al mole fraction curves is decreased with decreasing the thickness of AlGaN layer due to the decrease of piezoelectric effect on 2DEG concentration.
Anomalous origin of the right vertebral artery: review of the literature and case report of right vertebral artery origin distal to the left subclavian artery. (1999)

We present the case of a 57-year-old patient who was admitted to the hospital for preoperative cerebral angiography because of an intraspinal mass at the level of C1 and C2. Angiographic examination revealed an abnormal origin of the right vertebral artery, which normally originates from the right subclavian artery. Thus, the right vertebral artery was the last branch of the supraaortic vessels. We also review herein the incidence of the various anomalous origins of the right vertebral artery in the literature and discuss their potential embryologic development and clinical significance.