gebhart/patrepeval huggingface dataset:
A recombinantEscherichia coliheat-stable enterotoxin b (STb) fusion protein eliciting neutralizing antibodies (1996)

STb is a heat-stable enterotoxin elaborated by enterotoxigenic Escherichia coli strains associated with weaning piglets and is responsible for diarrhoea in those animals. The maltose binding protein (MBP) of E. coli was used as a carrier for STb, a poorly immunogenic molecule. Constructions were produced where the gene coding for mature STb toxin (MBP-STb) and a fragment of the gene spanning the major epitopic region of STb (AA8-AA30) (MBP-STb2) were fused to malE gene coding for MBP. The fusion proteins accumulated in the periplasm and were detected with a polyclonal antibody raised against the purified toxin. MBP-STb induced secretion in the biological model whereas MBP-STb2 was non-toxic. Immunization of rabbits evoked an antibody response to STb for these two fusion proteins. However, only MBP-STb elicited antibodies that effectively neutralized the toxicity of pure STb toxin as determined in the rat loop assay.
Traficet-EN, an Oral CCR9-Specific Antagonist, Induces High Levels of Remission in the Open-Label Phase of PROTECT-1 in Crohnʼs Disease (2008)

Purpose: The chemokine receptor CCR9 and its sole ligand TECK (CCL25) regulate trafficking of T lymphocytes to the intestinal mucosa. It plays a central role in the pathophysiology of Crohn's disease (CD). Traficet-EN (CCX282-B), an orally administered CCR9-specific antagonist, is in advanced clinical development for treatment of IBD. Approximately 500 subjects have received at least 1 dose of Traficet-EN in eight human clinical trials. PROTECT-1 (Prospective, Randomized, Oral-Therapy Evaluation in Crohn's disease Trial) evaluates safety and efficacy of CCX282-B in patients with moderate to severe CD. Methods: The study has 3 phases: Following a randomized, double-blind, placebo-controlled 12-week induction period (A) involving 430 subjects, all subjects receive 250 mg CCX282-B b.i.d. open label for 4 weeks (B), and responders (CDAI drop of at least 70 points), then continue in a 36-week placebo-controlled maintenance period (C). Study enrollment has been completed. Final results from the 4-week active treatment period are presented here. Results: 211 subjects completed the 4-week treatment with CCX282-B 250 mg b.i.d. Baseline mean (SD) age was 37 (12) yrs, 53% of subjects were women, and the mean duration of CD was 7 (6) yrs. The study population represented individuals with high CD activity, as reflected by a mean baseline CDAI of 332 (57) and CRP level of 29 (28) mg/L. After 4-week open label CCX282-B treatment, 82% of subjects had a CDAI drop of ≥70 points, 75% had ≥100-point drop, and, remarkably, nearly half (45%) of subjects were in clinical remission (CDAI≤150) compared to their baseline status. The mean decrease in CDAI was 192 points. Remitters tended to have lower baseline CDAI levels (322 vs. 340 in non-remitters), but CRP levels were similar (30 vs. 28 mg/L). Study drug was well tolerated. Conclusion: A 4-week active treatment with Traficet-EN in the PROTECT-1 trial led to a high percentage of patients achieving clinical remission. These results are highly encouraging and compare favorably with the response rates reported with high-dose glucocorticoids and biologic therapies for Crohn's disease.
Exploiting Structure and Managing Wires to Increase Density and Performance (2005)

SummaryDesigners have implementation choices to realize their specific VLSI systems. Both the increasing complexity of designs and the increasing constraints on quality imposed by wires will motivate ASIC designers to adopt a growing number of custom techniques. Unlike traditional ASIC design flows, custom methodologies exploit the physical structure inherent in designs and explicitly manage routing. However, while custom designs can achieve up to a factor-of-3 greater performance and density, they can also require an order of magnitude more design effort. We have presented a sequence of successive custom remedies to improve the quality of ASIC designs: floorplanning, tiling, crafted-cells and, finally, custom crafted-macros. In example applications, these approaches taken together close the gap between ASICs and custom design to within a factor-of-1.1 for performance and to within a factor-of-1.6 for density with only modest additional effort. The underlying theme of our approach is to identify critical components of a design and judiciously employ custom techniques only on these few pieces to maximize quality while minimizing effort.
The Prevalence and Risk Factors of Ocular Trauma: The Singapore Indian Eye Study (2011)

One in twenty Indian adults in this urban Southeast Asian population had a history of ocular trauma, similar to the prevalence reported in Malays living in Singapore. Men and cigarette smokers were more likely to have incurred ocular trauma.
Silicon nitride for integrated photonic applications (2016)

Due to its flexible optical properties silicon nitride is an attractive material for integrated photonic circuits. In this paper, we review the results we have obtained on near-infrared photonic devices including low loss waveguides based on SiN layers deposited with low temperature PECVD using an ammonia-free chemistry. In particular, we discuss the fabrication of subwavelength suspended structures to extend the use of SiN to mid-infrared photonic devices.
Milder routes to chelated ruthenium complexes for Z-selective metathesis (2013)

A novel method to effect the salt metathesis and C-H activation of ruthenium-based, Z-selective metathesis catalysts contg. a&#13;\nchelated N-heterocyclic carbene (NHC) ligand using sodium carboxylates is reported. This method allows for the successful&#13;\nformation of stable chelated species contg. a variety of alterations to the NHC ligand that had decompd. under the previous&#13;\napproach. As such, several new, chelated metathesis-active ruthenium complexes are described, including a catalyst system&#13;\nexhibiting &gt;95% Z-selectivity and record TONs (up to 8100) in homodimerization reactions of terminal olefins. Moreover, a&#13;\ncatalyst has been synthesized that gives highly cis, highly tactic polymers via ring opening metathesis polymn. of strained, cyclic&#13;\nolefins, marking the first time tactic polymers have been made using a ruthenium-based metathesis catalysts.
Morphology and function of lacrimal gland acinar cells in primary culture. (1989)

The objectives of the current investigation were fourfold: (1) to establish an effective procedure for the isolation of acinar cells from the rat lacrimal gland; (2) to evaluate the functional capacity of freshly isolated cells; (3) to determine defined culture conditions which permit maintenance of viable, differentiated cells, as well as secretory component (SC) production, during long-term culture; and (4) to characterize the morphological features of cultured cells. Acinar cells were isolated by serial incubation of gland fragments in chelating and enzymatic solutions, followed by centrifugation through a Ficoll gradient. The yield of viable cells/gland appeared to be age-dependent: cell recovery was inversely proportional to the age of the animals. Immunofluorescence analysis of freshly isolated cells showed the presence of SC, the IgA antibody receptor, within isolated cells. In addition, experiments with a labeled analog (Nle4-D-Phe7-alpha MSH) of alpha-melanocyte-stimulating hormone (alpha-MSH) demonstrated specific binding sites on freshly isolated cells; alpha-MSH is a known modulator of acinar protein secretion. Maximum binding of the alpha-MSH analog occurred within 30 min, was dependent upon cell density and was reduced by coincubation with unlabeled alpha-MSH. To determine the culture requirements of acinar cells, cells were cultured on a variety of substrates (plastic or modified plastic [Primaria], coated with or without extracellular matrix [Matrigel]) in the presence or absence of various supplements and/or fetal calf serum (FCS) for 0.7 to 3.5 weeks. Cell attachment, function and long-term viability required an extracellular matrix. Moreover, in long term cultures (25 days), acinar cell attachment was enhanced by the inclusion of supplements to media containing 10% FCS. Replacement of serum with fibroblast growth factor, high-density lipoprotein and an increased concentration of epidermal growth factor resulted in a distinct "cobblestone" morphology characteristic of epithelial cell cultures. Electron microscopic analysis of cells cultured in supplemented serum-free media demonstrated extensive rough endoplasmic reticulum and Golgi, intermediate filaments and numerous secretory granules, as well as tight junctions and desmosomes. In addition to cell maintenance and attachment, acinar cell synthesis and/or secretion of SC was positively influenced by inclusion of supplements in the media. In summary, we have isolated lacrimal gland acinar cells, which express receptors for IgA antibodies and alpha-MSH. In addition, we have defined culture conditions which permit the long-term maintenance of SC-secreting acinar cells.
Photothermal Optical Coherence Tomography for Molecular Contrast Imaging (2008)

Photothermal optical coherence tomography with laser-heated gold nanorods as the photothermal source is proposed as a novel molecular imaging technique. A description of the technique and validation experiments are reported.
Multilayer Neural Networks and Function Reconstruction By Using a Priori Knowledge (1999)

This paper proposes a new methodology to approximate functions by incorporating a priori information. The relationship between the proposed scheme and multilayer neural networks is explored theoretically and numerically. This approach is particularly interesting for the very relevant class of limited spectrum functions. The number of free parameters is smaller if compared to Back-Propagation Algorithm opening the way for better generalization results.
In situreal-time investigation of kinetics of nucleation and growth of sol-gel-derived functional oxide thin films (2008)

Early-stage nucleation and growth kinetics of sol-gel-derived multiferroic ${\text{BiFeO}}_{3}$ thin films were investigated in situ and in real time by combining transmission electron microscopy and grazing-incidence small-angle x-ray scattering (GISAXS). While the initial phase of the nuclei was identified to be ${\text{Bi}}_{2}{\text{O}}_{2}{\text{CO}}_{3}$, the quantitative GISAXS analysis unambiguously revealed that the early-stage kinetic nucleation growth in the thin films was dominated by an oriented-attachment mechanism as opposed to the conventional Ostwald ripening in metallic and ceramic systems.
Transacylation rates of aminoacyladenosine moiety at the 3'-terminus of aminoacyl-transfer ribonucleic acid (1983)

The rates of migration of the aminoacyl group (transacylation) between 2'-O-(aminoacyl)-tRNA and 3'-O-(aminoacyl)-tRNA were studied by the nuclear magnetic resonance (NMR) analyses of 3'-terminal fragment models, with regard to the significance of transacylation in the process of protein biosynthesis. 2'(3')-O-L-Alanyladenosine, -valyladenosine, -isoleucyladenosine, -phenylalanyladenosine, and -methionyladenosine, and 2'(3')-O-L-phenylalanyladenosine 5'-phosphate and methionyladenosine 5'-phosphate were chemically synthesized, and the rates of transacylation in deuterated buffer were directly measured by the NMR saturation transfer method. The dependences of transacylation rates on p2H and temperature were analyzed. The results indicate that the transacylation rates are significantly affected by the ionization states of the alpha-amino group of the amino acid moiety but not by the presence of the 5'-phosphate group of the adenylate moiety. The second-order rate constants for the base-catalyzed transacylation reactions were also determined for the ionized form (with alpha-N2H3+ group) of (aminoacyl)adenosines. The transacylation rates of (aminoacyl)adenosines in 1H2O solution at p1H 7.3 and 37 degrees C (intracellular environment) were evaluated as 3-11 s-1 for the 2' leads to 3' transacylation and 1-4 s-1 for the 3' leads to 2' transacylation, indicating that the transacylation rate of free aminoacyl-tRNA is slower than the overall rate of polypeptide chain elongation per ribosome. This suggests the presence of some enzymatic factor for enhancing the transacylation rates of aminoacyl-tRNAs in the polypeptide chain elongation process in vivo.
A strategy for generating cancer-specific monoclonal antibodies to aberrantO-glycoproteins: identification of a novel dysadherin-Tn antibody (2019)

Successful application of potent antibody-based T-cell engaging immunotherapeutic strategies is currently limited mainly to hematological cancers. One major reason is the lack of well-characterized antigens on solid tumors with sufficient cancer specific expression. Aberrantly O-glycosylated proteins contain promising cancer-specific O-glycopeptide epitopes suitable for immunotherapeutic applications, but currently only few examples of such antibody epitopes have been identified. We previously showed that chimeric antigen receptor T-cells directed towards aberrantly O-glycosylated MUC1 can control malignant growth in a mouse model. Here, we present a discovery platform for the generation of cancer-specific monoclonal antibodies targeting aberrant O-glycoproteins. The strategy is based on cancer cell lines engineered to homogeneously express the truncated Tn O-glycoform, the so-called SimpleCells. We used SimpleCells of different cancer origin to elicit monoclonal antibodies with selectivity for aberrant O-glycoproteins. For validation we selected and characterized one monoclonal antibody (6C5) directed to a Tn-glycopeptide in dysadherin (FXYD5), known to be upregulated in cancer and promote metastasis. While dysadherin is widely expressed also in normal cells, we demonstrated that the 6C5 epitope is specifically expressed in cancer.
Contribution of T-Cell Receptor Repertoire Breadth to the Dominance of Epitope-Specific CD8+T-Lymphocyte Responses (2006)

Dominant epitope-specific CD8(+) T-lymphocyte responses play a central role in controlling viral spread. We explored the basis for the development of this focused immune response in simian immunodeficiency virus (SIV)- and simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys through the use of two dominant (p11C and p199RY) and two subdominant (p68A and p56A) epitopes. Using real-time PCR to quantitate T-cell receptor (TCR) variable region beta (Vbeta) family usage, we show that CD8(+) T-lymphocyte populations specific for dominant epitopes are characterized by a diverse Vbeta repertoire, whereas those specific for subdominant epitopes employ a dramatically more focused Vbeta repertoire. We also demonstrate that dominant epitope-specific CD8(+) T lymphocytes employ TCRs with multiple CDR3 lengths, whereas subdominant epitope-specific cells employ TCRs with a more restricted CDR3 length. Thus, the relative dominance of an epitope-specific CD8(+) T-lymphocyte response reflects the clonal diversity of that response. These findings suggest that the limited clonal repertoire of subdominant epitope-specific CD8(+) T-lymphocyte populations may limit the ability of these epitope-specific T-lymphocyte populations to expand and therefore limit the ability of these cell populations to contribute to the control of viral replication.
Mechanism of Electrochemical Hydrogenation of Epitaxial Graphene (2015)

Mechanism of electrochemical hydrogen adsorption on epitaxial graphene (EG) was observed to be dependent on defects in EG as observed by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and Raman spectroscopy. To determine the material dependence on electrochemical hydrogenation, a set of different EG samples (Si-face EG [∼2 ML], C-face EG [∼10 ML], M-plane EG [∼25 ML], defective Si-face EG [>50 ML]) and a graphite disk [>500 ML] were characterized using a home built electrochemical cell developed in previous work, dilute perchloric acid (HClO4) solution, silver/silver chloride (Ag/AgCl) reference electrode in saturated KCl (0.198 V vs. NHE) and potentiostat. The Nyquist plots obtained from EIS of epitaxial graphene with low defect density showed only one semicircle covering the entire frequency range attributed to adsorption of hydrogen at the relatively chemically inert basal plane surface and further supported by lack of hydrogen peaks in the CV. Samples with high defect density showed an additional semicircle at the intermediate to high frequency ranges linked to adsorption and charge transfer of hydrogen to graphene. The increased presence of point defects in epitaxial graphene augments the surface area of the material resulting in increased diffusion of hydrogen ions though the graphene lattice allowing for hydrogen to adsorb to additional sites within the lattice.
ChemInform Abstract: MARASMIC ACID. I. TOTAL SYNTHESIS OF (.+‐.)‐ISOMARASMIC ACID (1981)

Abstract Reaktion des ausgehend vom Aldehyd (I) über die Stufen (IIa)‐(IIc) erhältlichen Diesters (IV) mit Diazomethan gibt ein Gemisch der Pyrazoline (Va) + (Vb), das durch Photolyse in das Tricyclodecen (Vc) übergeht.
The Genomics of Heart Failure: Design and Rationale of the HERMES Consortium (2021)

HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
Postoperative Testing to Predict Recurrent Cushing Disease in Children (2009)

In pediatric patients with CD, low UFCs after TSS are not good predictors of sustained remission; morning ACTH and cortisol values and/or an oCRH test after TSS predicted patients that recurred.
Identification of Two APOBEC3F Splice Variants Displaying HIV-1 Antiviral Activity and Contrasting Sensitivity to Vif* (2010)

Approximately half of all human genes undergo alternative mRNA splicing. This process often yields homologous gene products exhibiting diverse functions. Alternative splicing of APOBEC3G (A3G) and APOBEC3F (A3F), the major host resistance factors targeted by the HIV-1 protein Vif, has not been explored. We investigated the effects of alternative splicing on A3G/A3F gene expression and antiviral activity. Three alternatively spliced A3G mRNAs and two alternatively spliced A3F mRNAs were detected in peripheral blood mononuclear cells in each of 10 uninfected, healthy donors. Expression of these splice variants was altered in different cell subsets and in response to cellular stimulation. Alternatively spliced A3G variants were insensitive to degradation by Vif but displayed no antiviral activity against HIV-1. Conversely, alternative splicing of A3F produced a 37-kDa variant lacking exon 2 (A3FΔ2) that was prominently expressed in macrophages and monocytes and was resistant to Vif-mediated degradation. Alternative splicing also produced a 24-kDa variant of A3F lacking exons 2-4 (A3FΔ2-4) that was highly sensitive to Vif. Both A3FΔ2 and A3FΔ2-4 displayed reduced cytidine deaminase activity and moderate antiviral activity. These alternatively spliced A3F gene products, particularly A3FΔ2, were incorporated into HIV virions, albeit at levels less than wild-type A3F. Thus, alternative splicing of A3F mRNA generates truncated antiviral proteins that differ sharply in their sensitivity to Vif.
Correction: Human Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration (2013)

The nuclear pore complex (NPC) mediates nucleo-cytoplasmic transport of macromolecules and is an obligatory point of passage and functional bottleneck in the replication of some viruses. The Human Immunodeficiency Virus (HIV) has evolved the required mechanisms for active nuclear import of its genome through the NPC. However the mechanisms by which the NPC allows or even assists HIV translocation are still unknown. We investigated the involvement of four key nucleoporins in HIV-1 docking, translocation, and integration: Nup358/RanBP2, Nup214/CAN, Nup98 and Nup153. Although all induce defects in infectivity when depleted, only Nup153 actually showed any evidence of participating in HIV-1 translocation through the nuclear pore. We show that Nup358/RanBP2 mediates docking of HIV-1 cores on NPC cytoplasmic filaments by interacting with the cores and that the C-terminus of Nup358/RanBP2 comprising a cyclophilin-homology domain contributes to binding. We also show that Nup214/CAN and Nup98 play no role in HIV-1 nuclear import per se: Nup214/CAN plays an indirect role in infectivity read-outs through its effect on mRNA export, while the reduction of expression of Nup98 shows a slight reduction in proviral integration. Our work shows the involvement of nucleoporins in diverse and functionally separable steps of HIV infection and nuclear import.
3-4′-Bipiperidines via Sequential [4 + 4]−[3,3]−Retro-Mannich Reactions (2009)

An approach to assembling unsymmetrically coupled piperidines is described, involving initial [4 + 4] photocycloaddition of 2-pyridones, followed by Cope rearrangement and retro-Mannich reaction. In these reactions, four stereogenic centers set during cycloaddition are relayed or erased during the subsequent steps. Two methods for retro-Mannich reaction are demonstrated.
Identification of coupling direction: Application to cardiorespiratory interaction (2002)

We consider the problem of experimental detection of directionality of weak coupling between two self-sustained oscillators from bivariate data. We further develop the method introduced by Rosenblum and Pikovsky [Phys. Rev. E 64, 045202 (2001)], suggesting an alternative approach. Next, we consider another framework for identification of directionality, based on the idea of mutual predictability. Our algorithms provide directionality index that shows whether the coupling between the oscillators is unidirectional or bidirectional, and quantifies the asymmetry of bidirectional coupling. We demonstrate the efficiency of three different algorithms in determination of directionality index from short and noisy data. These techniques are then applied to analysis of cardiorespiratory interaction in healthy infants. The results reveal that the direction of coupling between cardiovascular and respiratory systems varies with the age within the first 6 months of life. We find a tendency to change from nearly symmetric bidirectional interaction to nearly unidirectional one (from respiration to the cardiovascular system).
NONINVASIVE MEASUREMENT OF VENOUS PH IN SEPTIC PATIENTS: PRELIMINARY RESULTS. (2006)

Soller, Babs R; Yang, Ye; Landry, Michelle R; Walz, J Matthias; Soyemi, Olusola O; Scott, Peter; Heard, Stephen O; Mullen, Marie Author Information
Improving the efficiency of UNIX buffer caches (1989)

This paper reports on the effects of using hardware virtual memory assists in managing file buffer caches in UNIX. A controlled experimental environment was constructed from two systems whose only difference was that one of them (XMF) used the virtual memory hardware to assist file buffer cache search and retrieval. An extensive series of performance characterizations was used to study the effects of varying the buffer cache size (from 3 Megabytes to 70 MB); I\O transfer sizes (from 4 bytes to 64 KB); cache-resident and non-cache-resident data; READs and WRITEs; and a range of application programs.