gebhart/patrepeval huggingface dataset:
Bound Carbohydrates in Nature (1994)

This 1994 book is based on a series of six lectures delivered at the University of Sienna under the auspices of the Lezioni Lincee. The content of the book reflects and delineates the author's career in biochemical research. The lectures revolve around the special role which bound carbohydrates play in nature. Also discussed are the properties of membrane glycoproteins, involved in the resistance of cells to drugs. The metabolism of sugars and sialic acids, which form a pivotal role in the author's research, are covered in detail. The book chronicles just some of the huge advances which have been made in biochemistry over the past few decades and will prove an invaluable and entertaining first hand account for researchers and graduate students.
Antiproliferative Effect of Somatostatin and Analogs (2001)

Over the past decade, antiproliferative effects of somatostatin and analogs have been reported in many somatostatin receptor-positive normal and tumor cell types. Regarding the molecular mechanisms involved, somatostatin or analogs mediate their action through both indirect and direct effects. Somatostatin acts through five somatostatin receptors (SSTR1-5) which are variably expressed in normal and tumor cells. These receptors regulate a variety of signal transduction pathways including inhibition of adenylate cyclase, regulation of ion channels, regulation of serine/threonine and tyrosine kinases and phosphatases. This review focuses on recent advances in biological mechanisms involved in the antineoplastic activity of somatostatin and analogs.
Heparin chromatography as an in vitro predictor for antibody clearance rate through pinocytosis (2019)

The pharmacokinetic (PK) properties of therapeutic antibodies directly affect efficacy, dose and dose intervals, application route and tissue penetration. In indications where health-care providers and patients can choose between several efficacious and safe therapeutic options, convenience (determined by dosing interval or route of application), which is mainly driven by PK properties, can affect drug selection. Therapeutic antibodies can have greatly different PK even if they have identical Fc domains and show no target-mediated drug disposition. Biophysical properties like surface charge or hydrophobicity, and binding to surrogates for high abundant off-targets (e.g., baculovirus particles, Chinese hamster ovary cell membrane proteins) were proposed to be responsible for these differences. Here, we used heparin chromatography to separate a polyclonal mix of endogenous human IgGs (IVIG) into fractions that differ in their PK properties. Heparin was chosen as a surrogate for highly negatively charged glycocalyx components on endothelial cells, which are among the main contributors to nonspecific clearance. By directly correlating heparin retention time with clearance, we identified heparin chromatography as a tool to assess differences in unspecific cell-surface interaction and the likelihood for increased pinocytotic uptake and degradation. Building on these results, we combined predictors for FcRn-mediated recycling and cell-surface interaction. The combination of heparin and FcRn chromatography allow identification of antibodies with abnormal PK by mimicking the major root causes for fast, non-target-mediated, clearance of therapeutic, Fc-containing proteins.
Determining the mechanical properties of electrospun poly-ε-caprolactone (PCL) nanofibers using AFM and a novel fiber anchoring technique (2015)

Due to its low cost, biocompatibility and slow bioresorption, poly-ε-caprolactone (PCL) continues to be a suitable material for select biomedical engineering applications. We used a combined atomic force microscopy (AFM)/optical microscopy technique to determine key mechanical properties of individual electrospun PCL nanofibers with diameters between 440-1040nm. Compared to protein nanofibers, PCL nanofibers showed much lower adhesion, as they slipped on the substrate when mechanically manipulated. We, therefore, first developed a novel technique to anchor individual PCL nanofibers to micrometer-sized ridges on a substrate, and then mechanically tested anchored nanofibers. When held at constant strain, tensile stress relaxed with fast and slow relaxation times of 1.0±0.3s and 8.8±3.1s, respectively. The total tensile modulus was 62±26MPa, the elastic (non-relaxing) component of the tensile modulus was 53±36MPa. Individual PCL fibers could be stretched elastically (without permanent deformation) to strains of 19-23%. PCL nanofibers are rather extensible; they could be stretched to a strain of at least 98%, and a tensile strength of at least 12MPa, before they slipped off the AFM tip. PCL nanofibers that had aged for over a month at ambient conditions became stiffer and less elastic. Our technique provides accurate nanofiber mechanical data, which are needed to guide construction of scaffolds for cells and other biomedical devices.
Methods in yeast genetics : a Cold Spring Harbor Laboratory course manual (2005)

"Methods in Yeast Genetics" is a course that has been offered annually at Cold Spring Harbor for the last 30 years. This provides a set of teaching experiments along with the protocols and recipes for the standard techniques and reagents used in the study of yeast biology.
Microwave imaging for tissue assessment: initial evaluation in multitarget tissue-equivalent phantoms (1996)

A prototype microwave imaging system is evaluated for its ability to recover two-dimensional (2-D) electrical property distributions under transverse magnetic (TM) illumination using multitarget tissue equivalent phantoms. Experiments conducted in a surrounding lossy saline tank demonstrate that simultaneous recovery of both the real and imaginary components of the electrical property distribution is possible using absolute imaging procedures over a frequency range of 300-700 MHz. Further, image reconstructions of embedded tissue-equivalent targets are found to be quantitative not only with respect to geometrical factors such as object size and location but also electrical composition. Quantitative assessments based on full-width half-height criteria reveal that errors in diameter estimates of reconstructed targets are less than 10 mm in all cases, whereas, positioning errors are less than 1 mm in single object experiments but degrade to 4-10 mm when multiple targets are present. Recovery of actual electrical properties is found to be frequency dependent for the real and imaginary components with background values being typically within 10-20% of their correct size and embedded object having similar accuracies as a percentage of the electrical contrast, although errors as high as 50% can occur. The quantitative evaluation of imaging performance has revealed potential advantages in a two-tiered receiver antenna configuration whose measured field values are more sensitive to target region changes than the typical tomographic type of approach which uses reception sites around the full target region perimeter. This measurement strategy has important implications for both the image reconstruction algorithm where there is a premium on minimizing problem size without sacrificing image quality and the hardware system design which seeks to economize on the amount of measured data required for quantitative image reconstruction while maximizing its sensitivity to target perturbations.
A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD (2006)

Among patients with frontotemporal lobar degeneration (FTLD), the respective frequencies of dominant 17q21-linked tau-negative FTLD (with unidentified molecular defect) and 17q21-linked tau-positive FTLD (due to MAPT mutations) remain unknown. Here, in a series of 98 genealogically unrelated Belgian FTLD patients, we identified an ancestral 8 cM MAPT containing haplotype in two patients belonging to multiplex families DR2 and DR8, without demonstrable MAPT mutations, in which FTLD was conclusively linked to 17q21 [maximum summed log of the odds (LOD) score of 5.28 at D17S931]. Interestingly, the same DR2-DR8 ancestral haplotype was observed in five additional familial FTLD patients, indicative of a founder effect. In the FTLD series, the DR2-DR8 ancestral haplotype explained 7% (7 out of 98) of FTLD and 17% (7 out of 42) of familial FTLD and was seven times more frequent than MAPT mutations (1 out of 98 or 1%). Clinically, DR2-DR8 haplotype carriers presented with FTLD often characterized by language impairment, and in one carrier the neuropathological diagnosis was FTLD with rare tau-negative ubiquitin-positive inclusions. Together, these results strongly suggest that the DR2-DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations.
Dysfunctional Voltage-Gated K + Channels in Pulmonary Artery Smooth Muscle Cells of Patients With Primary Pulmonary Hypertension (1998)

These results indicate that KV channel function in PPH-PASMCs is inhibited compared with SPH-PASMCs. The resulting membrane depolarization and increase in [Ca2+]cyt lead to pulmonary vasoconstriction and PASMC proliferation. Our data suggest that defects in PASMC KV channels in PPH patients may be a unique mechanism involved in initiating and maintaining pulmonary vasoconstriction and appear to play a role in the pathogenesis of PPH.
Using guides to explore multimedia databases (1989)

The design and implementation of a multimedia database is surveyed and an interface technique called guides is presented, which simplifies database access by alleviating the need to construct search queries. The user is given a selection of images of people who embody easily understood points of view. A user can choose a guide as a companion while browsing the database. At each database node the user is provided with the guides next choice and thus can follow the interest path of a certain type of individual. The graphical tools and interface provided to the text, graphics and sound database are presented. The design and functionality of alphabetical and topical indexes, multimedia tours, timelines and animated maps are detailed. Future directions for development are indicated. The concept of guides can be easily generalized and applied to other databases.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Two-Dimensional Separations:  Capillary Electrophoresis Coupled to Channel Gel Electrophoresis (1996)

Two-dimensional separations provide extremely high peak capacities. Coupling capillary zone electrophoresis with ultrathin channel gel electrophoresis offers a convenient and efficient way to perform such two-dimensional microseparations. By means of in situ polymerization, high-concentration (up to 50%T) polyacrylamide gels are prepared in 75 mm long, 25 mm wide, and 40 microns thick rectangular channels. By moving the outlet end of the capillary electrophoresis capillary across the entrance of the channel, both separations are completely preserved. Mixtures of peptides labeled by fluorescein isothiocyanate (FITC) are well resolved in less than 15 min, with theoretical plate numbers in the range of 20,000-50,000 for each independent separation. Significant enhancement in separation efficiency and peak capacity over one-dimensional separations are demonstrated by this combination. The two-dimensional separations of a model mixture of peptides, a tryptic digest of trypsinogen, and < 0.05% of an individual B2 neuron from the marine mollusk Aplysia californica are presented.
Small molecules from the human microbiota (2015)

Developments in the use of genomics to guide natural product discovery and a recent emphasis on understanding the molecular mechanisms of microbiota-host interactions have converged on the discovery of small molecules from the human microbiome. Here, we review what is known about small molecules produced by the human microbiota. Numerous molecules representing each of the major metabolite classes have been found that have a variety of biological activities, including immune modulation and antibiosis. We discuss technologies that will affect how microbiota-derived molecules are discovered in the future and consider the challenges inherent in finding specific molecules that are critical for driving microbe-host and microbe-microbe interactions and understanding their biological relevance.
Discovery of (R)-1-(3-(4-Amino-3-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (CHMFL-EGFR-202) as a Novel Irreversible EGFR Mutant Kinase Inhibitor with a Distinct Binding Mode (2017)

On the basis of Ibrutinib's core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered novel epidermal growth factor receptor (EGFR) inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M. Compound 19 displayed a good selectivity profile among 468 kinases/mutants tested in the KINOMEscan assay (S score (1) = 0.02). In particular, it did not exhibit apparent activities against INSR and IGF1R kinases. The X-ray crystal structure revealed that this class of inhibitors formed a covalent bond with Cys797 in a distinct "DFG-in-C-helix-out" inactive EGFR conformation. Compound 19 displayed strong antiproliferative effects against EGFR mutant-driven nonsmall cell lung cancer (NSCLC) cell lines such as H1975, PC9, HCC827, and H3255 but not the wild-type EGFR expressing cells. In the H1975 and PC9 cell-inoculated xenograft mouse models, compound 19 exhibited dose-dependent tumor growth suppression efficacy without obvious toxicity. Compound 19 might be a potential drug candidate for EGFR mutant-driven NSCLC.
Microsoft Office Excel 2003オフィシャルマニュアル (2004)

第１部 Ｅｘｃｅｌの基本 第２部 ワークシートの作成 第３部 ワークシートの書式設定と編集 第４部 グラフィックと印刷 第５部 数式とデータ分析 第６部 共同作業とインターネット 第７部 Ｅｘｃｅｌとアプリケーションの統合 第８部 グラフ 第９部 データベースとリストの管理 第１０部 Ｖｉｓｕａｌ Ｂａｓｉｃとマクロ 付録
Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection. (1998)

Local production of cytokines plays a critical role in the regulation of pathophysiologic processes leading to rejection of transplanted organs. In the present study, the possible role of interleukin-17 (IL-17), a recently identified cytokine with unique properties, was investigated. IL-17 is specifically produced by activated T cells, whereas biological activities are restricted to the activation of nonhematopoietic cells. In vitro, IL-17 induced primary human proximal tubular epithelial cells, a type of cell regulating local interstitial inflammatory responses, to secrete higher levels of IL-6, IL-8, and monocyte chemoattractant protein-1, but not of the chemokine RANTES. The effect was specific for IL-17, because it was completely abrogated by a neutralizing anti-IL-17 antibody and was demonstrated to be dose- and time-dependent. In addition, IL-17 increased the production of complement component C3 by human proximal tubular epithelial cells, but not of other complement components. Immunofluorescence showed expression of IL-17 in kidney biopsies from patients suffering from graft rejection (8 of 8 positive), whereas pretransplant biopsies and normal kidneys were negative (0 of 6). Analysis of whole kidney isolates confirmed the presence of IL-17 mRNA by reverse transcription-PCR. IL-17 expression could also be found in in vitro cultured and activated graft-infiltrating T cells. These results represent the first demonstration of IL-17 protein expression in pathologic conditions and suggest that IL-17 might be important in the regulation of local inflammatory responses.
Realizing S-Reliability for services via recovery-driven intrusion tolerance mechanism (2010)

Service-Oriented Architecture (SOA) paradigm facilitates the design of large systems as a set of loosely coupled services interacting with each other. These services, in turn, can be combined to form a more complex service. But, for services to be useful, they must satisfy non-functional requirements, especially security-related quality of service. Unfortunately, software vulnerabilities expose these services to malicious actors, and make them susceptible to attacks. Therefore, security quality of service is critical in order to ensure confidentiality, integrity, and availability for system data and services. Due to the distributed and decentralized nature of services, publishing and guaranteeing security quality of service are crucial so that potential applications and clients can make use of the provided services. In this paper, we will first discuss how Intrusion Tolerance Quality of Service (IT-QoS) can be modeled and specified. Then, we will show how a recovery-driven intrusion tolerance architecture is able to ensure differentiated levels of S-Reliability, an important IT-QoS for a Service.
High incidence of acute sub-clinical circumflex artery ‘injury’ following mitral isthmus ablation (2011)

Acute sub-clinical circumflex 'injury' following MI ablation is not uncommon. Ablation within the CS, proximity of the circumflex and the CS, and a small distal circumflex were risk factors for 'injury'.
Klotho Ameliorates Medullary Fibrosis and Pressure Natriuresis in Hypertensive Rat Kidneys (2018)

Renal expression of klotho is reduced in hypertension. Experiments were performed to examine whether exogenous klotho protein supplementation ameliorates pressure natriuresis in early phase of hypertension, using stroke-prone spontaneously hypertensive rats (sp-SHR). The interactions between klotho protein and renal renin-Ang (angiotensin) system were examined with immunoprecipitation and cell culture methods. Uninephrectomy was performed in sp-SHRs to induce nephrosclerosis, and they were treated with exogenous klotho protein or vehicle. Exogenous klotho protein supplementation to sp-SHR decreased blood pressure, renal Ang II levels, AGT (angiotensinogen) expression, HIF (hypoxia-inducible factor)-1α abundance, and medullary fibronectin levels, with increased renal klotho expression and serum and urine klotho levels. Klotho supplementation also reduced kidney weight, renal phosphorylated Akt, and mTOR (mammalian target of rapamycin) abundance. Furthermore, klotho supplementation restored renal autoregulation of glomerular filtration rate and enhanced pressure-induced natriuresis in sp-SHR. Klotho protein bound to AT1R (Ang II type-1 receptor) and decreased the presence of AT1R on HK-2 (human proximal tubular) cells, attenuating inositol triphosphate generation. Klotho protein suppressed Ang II-induced increments of AGT expression in HK-2 cells. Collectively, the present data demonstrate that klotho binds with the AT1R to suppress Ang signal transduction, participating in inactivating renal renin-Ang system. Our results also suggest that exogenous klotho supplementation represses Akt-mTOR signaling to reduce renal hypertrophy and restore the autoregulatory ability of glomerular filtration rate in uninephrectomized sp-SHRs. Finally, the present findings implicate that klotho supplementation inhibits HIF-1α pathway and medullary fibrosis, contributing to enhancements of pressure natriuresis and reduction in blood pressure.
A 24-base-pair DNA sequence from the MAT locus stimulates intergenic recombination in yeast. (1986)

HO nuclease is a site-specific double-strand endonuclease present in haploid Saccharomyces cerevisiae undergoing mating type interconversion. HO nuclease initiates mating type interconversion by making a double-strand break within the MAT locus. To define the recognition site for the enzyme in vitro, we have constructed a number of point mutations and deletions within or adjacent to the HO recognition site. Digestion of these substrates with HO in vitro reveals that the minimal recognition site is 18 base pairs long, although several shorter substrates and substrates containing point mutations are cleaved at low levels in vitro. A 24-base-pair HO recognition site stimulates homologous recombination when present in a region unrelated to MAT. Recombinants arise from both gene conversion and crossover events. The identification of the HO recognition site provides a way of introducing a defined initiation site for recombination.
Light-frames: A pragmatic framework for optical packet transport (2004)

We propose an architecture and an algorithm for the realization of a pragmatic framework for optical packet transport. The architecture enables the transport of IP packets over optical frames in a network. While doing so, it relaxes the need for address recognition as well as for high speed switching, the two key hindering factors that have prevented contemporary optical packet transport solutions from being deployed. We propose the light-frames architecture for sub-lambda level provisioning of optical paths. The idea is to create a logical topology that allows N/sup 2/ connectivity using optical paths that are by themselves sublambda provisionable yielding in packet transport. We show that by using substantially fewer resources, we can provide N/sup 2/ connectivity in arbitrary graphs to support optical packet transport.
The electronic conduction mechanism of hydrogenated nanocrystalline silicon films (2002)

The hydrogenated nano-crystalline silicon films (nc-Si:H) were prepared by using the ultra-high vaccum PECVD system. The nc-Si:H films consist of a mass of nano-grains and a great deal of interfaces between grains. It was found that the room temperature conductivity of nc-Si:H is in the range of 10/sup -3//spl sim/10/sup 0/ (Q/spl middot/cm)/sup -1/, which is higher than that of intrinsic crystalline silicon. In this paper, the two-phase random composite model was used to calculate the conductivities of crystalline grains and interface of nc-Si:H films. The results show that the high conductivity of nc-Si:H arises from the contribution of the crystalline grains. Based on the experimental and calculating results the conduction model of nc-Si:H films is proposed.
Neural Architectures for Named Entity Recognition (2016)

Guillaume Lample, Miguel Ballesteros, Sandeep Subramanian, Kazuya Kawakami, Chris Dyer. Proceedings of the 2016 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies. 2016.
Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. (1984)

The association between T3 and the T cell antigen receptor was examined using the T3 bearing T cell leukemic line Jurkat. A monoclonal antibody, C305, was produced, which reacted with idiotypic-like determinants expressed on Jurkat. The molecule with which this antibody reacted was a disulfide-linked heterodimer of 90 kD, composed of polypeptides of 42 and 54 kD. Thus, C305 reacted with a molecule with characteristics of the putative T cell antigen receptor described by others. A series of mutants of Jurkat, induced with ethyl methane sulfonate or radiation, was selected for T3 or antigen receptor negativity. In every instance, there was a concomitant loss of both T3 and the antigen receptor as assessed by quantitative absorption, indirect immunofluorescence, and antibody plus complement-mediated cytotoxicity. The absence of antigen receptor molecules was confirmed on diagonal gels, excluding the possibility that conformational changes of the antigen receptor on such T3-negative mutants were responsible for the failure of such mutants to react with C305. Moreover, in a mutant that expressed a marked decrease in the level of T3 expression, there was a comparable decrease in the expression of antigen receptor determinants. These results suggest that there is an obligate requirement for the coexpression of T3 and the T cell antigen receptor. Furthermore, attempts to activate such mutants with the lectin phytohemagglutinin suggested that the expression of T3 and/or the antigen receptor was required for activation of these cells.