gebhart/patrepeval huggingface dataset:
Towards direct biochemical analysis with weak inversion ISFETS (2005)

A weak inversion region is shown to exist in ISFET sensors. It is therefore proposed that the ISFET and its ChemFET and EnFET counterparts be used as translinear elements in the synthesis of novel biochemical input stages which perform real-time mathematical manipulation of biochemical signals. A biochemical translinear principle using weakly-inverted ChemFETs is presented. The first order temperature dependence of biochemical translinear circuits is greatly reduced from that of voltage-mode circuits. A low-power current-mode input stage circuit is presented as an application of the principle. This yields a linear relation between drain current and hydrogen ion concentration valid over 4 decades. This paper demonstrates an important and necessary step towards biochemical VLSI.
MEDI-528, an anti-IL-9 humanized antibody for the treatment of asthma. (2010)

In development by MedImmune LLC, under license from Genaera Corp, MEDI-528 is an injectable, humanized mAb against IL-9 for the potential treatment of asthma. In asthma, airway inflammation is usually adequately minimized with standard-of-care treatments, such as inhaled corticosteroids and leukotriene modifiers, but it is sometimes less responsive to such therapies and other anti-inflammatory approaches are required. Several T-helper cell type 2-derived cytokines, such as IL-4, -5, -9 and -13, play a major role in the development of disease pathogenic features in asthma, including airway eosinophilia, increased IgE production, mucus hypersecretion and airway hyperreactivity. As an IL-9 antagonist, MEDI-528 appears to inhibit a range of asthma pathogenic features in antigen-exposed mice. To date, clinical data are modest, although insufficient to judge the efficacy of the drug in humans, and larger and longer-term clinical trials are required. MEDI-528, along with other anticytokine therapies targeting different ILs, remains under investigation in early-phase trials for asthma. Time will tell if this form of therapy can be used as an add-on to less efficacious anti-inflammatory therapy or can replace the existing anti-inflammatory therapies in the treatment of asthma.
<title>Networked sensors: armor for the future force</title> (2001)

The U.S. Army has embarked on an important campaign to field a lighter, more agile force, capable of being deployed in a fraction of the time currently required. The survivability of this force will depend more heavily on the use of integrated command and control capabilities with unsurpassed situational understanding for all levels of command. Arrays of small, low cost sensors will play a key role in detecting, locating, tracking, and identifying targets, particularly in areas where the terrain or other circumstances prevent traditional high performance sensors from providing critical information. Individual sensor types will provide modest performance but with a wide range of sensing modalities. When deployed in large numbers, the data fused from multiple sensing modalities will provide a detailed view of the battlespace over a wide area. A critical element necessary to deploy unattended ground sensor technology is the underlying communications and networking infrastructure. Communication networks will constitute the major challenge to making unattended ground sensors networks practical.
Relative Contribution of LFA-1 and Mac-1 to Neutrophil Adhesion and Migration (1999)

To differentiate the unique and overlapping functions of LFA-1 and Mac-1, LFA-1-deficient mice were developed by targeted homologous recombination in embryonic stem cells, and neutrophil function was compared in vitro and in vivo with Mac-1-deficient, CD18-deficient, and wild-type mice. LFA-1-deficient mice exhibit leukocytosis but do not develop spontaneous infections, in contrast to CD18-deficient mice. After zymosan-activated serum stimulation, LFA-1-deficient neutrophils demonstrated activation, evidenced by up-regulation of surface Mac-1, but did not show increased adhesion to purified ICAM-1 or endothelial cells, similar to CD18-deficient neutrophils. Adhesion of Mac-1-deficient neutrophils significantly increased with stimulation, although adhesion was lower than for wild-type neutrophils. Evaluation of the strength of adhesion through LFA-1, Mac-1, and CD18 indicated a marked reduction in firm attachment, with increasing shear stress in LFA-1-deficient neutrophils, similar to CD18-deficient neutrophils, and only a modest reduction in Mac-1-deficient neutrophils. Leukocyte influx in a subcutaneous air pouch in response to TNF-alpha was reduced by 67% and 59% in LFA-1- and CD18-deficient mice but increased by 198% in Mac-1-deficient mice. Genetic deficiencies demonstrate that both LFA-1 and Mac-1 contribute to adhesion of neutrophils to endothelial cells and ICAM-1, but adhesion through LFA-1 overshadows the contribution from Mac-1. Neutrophil extravasation in response to TNF-alpha in LFA-1-deficient mice dramatically decreased, whereas neutrophil extravasation in Mac-1-deficient mice markedly increased.
Reduction of waste product excretion via nutrient control: Possible strategies for maximizing product and cell yields on serum in cultures of mammalian cells (1986)

Mammalian cells grown in culture excrete lactic acid and ammonium ions in quantities that may limit growth and reduce product synthesis. Frequent replenishment of the culture medium is often necessary to prevent waste product accumulation which could inhibit cell growth. Since increased medium replenishment results in increased usage of animal serum, the most expensive raw material, excessive production of waste products lowers the cell and product yield on serum, and hence increases production costs. Strategies for reducing the production of lactic acid and ammonium bymammalian cells via controlled addition of glucose and glutamine will be demonstrated. Mathematical relations coupling ammonium and glutamine kinetics will be described. Additionally, a method for automatic on-line estimation of the cell concentration was developed. This method involves calculating the ATP production rate from the oxygen uptake rate and the lactic acid production rate. Automatic online estimation of the cell concentration is critical if nutrient levels in large-scale mammaliancell cultures are to be accurately maintained via process control.
DNA chain length markers and the influence of base composition on electrophoretic mobility of oligodeoxyribonucleotides in plyacrylamide-gels (1979)

The specific influence of the four nucleobases on electrophoretic mobility of oligodeoxyribonucleotides in polyacrylamide-gels under denaturing and nondenaturing conditions has been investigated using homooligomers from the four deoxyribonucleotides as chain length standards. Homooligomers of same chain lengths exhibit remarkable differences in mobility. Specific retardation of any other oligonucleotide investigated was found to be mainly dependent on base composition but not on sequence. A simple procedure is presented for calculating mobilities relative to the standards on denaturing gels. This allows a reliable identification of oligonucleotides on acrylamide-gels by exact chain length determination with respect to base composition and furthermore a detailed interpretation of complex reaction mixtures. The homooligomers also show the same differences in mobility on nondenaturing gels. The significance of this effect for strand separation is discussed.
IL-10+CTLA-4+ Th2 Inhibitory Cells Form in a Foxp3-Independent, IL-2–Dependent Manner from Th2 Effectors during Chronic Inflammation (2012)

Activated Th cells influence other T cells via positive feedback circuits that expand and polarize particular types of response, but little is known about how they may also initiate negative feedback against immunopathological reactions. In this study, we demonstrate the emergence, during chronic inflammation, of GATA-3(+) Th2 inhibitory (Th2i) cells that express high levels of inhibitory proteins including IL-10, CTLA-4, and granzyme B, but do so independently of Foxp3. Whereas other Th2 effectors promote proliferation and IL-4 production by naive T cells, Th2i cells suppress proliferation and IL-4 production. We show that Th2i cells develop directly from Th2 effectors, in a manner that can be promoted by effector cytokines including IL-2, IL-10, and IL-21 ex vivo and that requires T cell activation through CD28, Card11, and IL-2 in vivo. Formation of Th2i cells may act as an inbuilt activation-induced feedback inhibition mechanism against excessive or chronic Th2 responses.
RasOncogene Mutations in Benign and Malignant Thyroid Neoplasms (1991)

Current models for tumorigenesis propose that a series of genetic alterations occur during the progression from the normal cell to the malignant phenotype. Mutations in each of the three ras genes (K-ras, H-ras, and N-ras) have been identified in many human neoplasms, including thyroid cancer. In this study we examined genomic DNA from benign and malignant thyroid neoplasms for mutations that are known to activate the ras oncogenes (codons 12, 13, and 61). DNA from frozen surgically excised tissue (n = 8) and from formalin-fixed paraffin-embedded tissue (n = 30) was amplified by the polymerase chain reaction and screened for mutations using oligonucleotide-specific hybridization. No mutations were identified in follicular adenomas (n = 9). In follicular carcinomas, 2 of 14 tumors contained mutations (N-ras 61, Gln to Arg), and both of these patients had bone metastases. One of 15 papillary carcinomas had a ras mutation (H-ras 12, Gly to Ser). In contrast to other studies, we found that ras mutations are relatively uncommon in both benign and malignant thyroid neoplasms. Studies of larger numbers of tumors and comparisons of different patient populations will be required to assess a possible association of mutations in N-ras 61 with clinically aggressive follicular cancer.
Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study (2018)

Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T-score ≤-2.0 and ≥-3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open-label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker β-CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and β-CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
Seeding Bimetallic Nanostructures as a New Class of Plasmonic Colloids (2013)

Colloidal plasmonics is a rapidly developing field, with applications of metal nanoparticles that range from biosensing to photocatalysis. Historically, Au- or Ag-only nanoparticles have been investigated for these uses. However, there is emerging interest in multifunctional plasmonic colloids as well as a desire to expand the light scattering and absorption properties of Au or Ag nanoparticles. Both of these goals can be achieved by incorporating a second metal. In this Perspective, recent advances in the synthesis and application of Au–Ag and Au–Pd nanostructures are discussed. The highlighted nanostructures were synthesized through the seed-mediated method, an approach that provides for structurally complex nanoarchitectures while maintaining sample homogeneity. Overall, these architecturally controlled bimetallic nanostructures are representative of a new class of plasmonic colloids in which composition and structure can be manipulated to achieve unique optical properties and functionality.
Monoclonal antibodies (F36/22 and M7/105) to human breast carcinoma. (1983)

Cloned hybridoma cell lines were obtained from fusions of murine myeloma cells with lymphocytes of mice immunized against human breast cancer cells. Hybridomas F36/22 and M7/105 produced antibodies whose binding to breast cancer cells could not be inhibited by prior absorptions with fibroblasts, lymphoblastoid cells, or erythrocytes. Results from cell surface binding assays using a panel of tumor cell lines indicated that antibodies F36/22 and M7/105 recognized determinants expressed maximally on breast cancer cells. Antibody F36/22 reacted with normal mammary epithelial membranes and milk fat globule membranes, whereas antibody M7/105 produced no detectable binding to these specimens. Antigens carrying these epitopes each showed reactivity with concanavalin A lectin. The determinant corresponding to antibody F36/22 was detectable in histological sections of a subset of breast tumors obtained at surgery.
ZnO Nanowire Transistors (2004)

ZnO nanowire field-effect transistors (FETs) were fabricated and studied in vacuum and a variety of ambient gases from 5 to 300 K. In air, these n-type nanowire transistors have among the highest mobilities yet reported for ZnO FETs (mu(e) = 13 +/- 5 cm(2) V(-1) s(-1)), with carrier concentrations averaging 5.2 +/- 2.5 x 10(17) cm(-3) and on-off current ratios ranging from 10(5) to 10(7). Four probe measurements show that the resistivity of the Ti/Au-ZnO contacts is 0.002-0.02 Omega.cm. The performance characteristics of the nanowire transistors are intimately tied to the presence and nature of adsorbed surface species. In addition, we describe a dynamic gate effect that seems to involve mobile surface charges and causes hysteresis in the transconductance, among other effects.
Klotho controls the brain–immune system interface in the choroid plexus (2018)

Located within the brain's ventricles, the choroid plexus produces cerebrospinal fluid and forms an important barrier between the central nervous system and the blood. For unknown reasons, the choroid plexus produces high levels of the protein klotho. Here, we show that these levels naturally decline with aging. Depleting klotho selectively from the choroid plexus via targeted viral vector-induced knockout in <i>Klotho</i><sup>flox/flox</sup> mice increased the expression of multiple proinflammatory factors and triggered macrophage infiltration of this structure in young mice, simulating changes in unmanipulated old mice. Wild-type mice infected with the same Cre recombinase-expressing virus did not show such alterations. Experimental depletion of klotho from the choroid plexus enhanced microglial activation in the hippocampus after peripheral injection of mice with lipopolysaccharide. In primary cultures, klotho suppressed thioredoxin-interacting protein-dependent activation of the NLRP3 inflammasome in macrophages by enhancing fibroblast growth factor 23 signaling. We conclude that klotho functions as a gatekeeper at the interface between the brain and immune system in the choroid plexus. Klotho depletion in aging or disease may weaken this barrier and promote immune-mediated neuropathogenesis.
TMPRSS13, a type II transmembrane serine protease, is inhibited by hepatocyte growth factor activator inhibitor type 1 and activates pro‐hepatocyte growth factor (2010)

Type II transmembrane serine proteases (TTSPs) are structurally defined by the presence of a transmembrane domain located near the N-terminus and a C-terminal extracellular serine protease domain. The human TTSP family consists of 17 members. Some members of the family have pivotal functions in development and homeostasis, and are involved in tumorigenesis and viral infections. The activities of TTSPs are regulated by endogenous protease inhibitors. However, protease inhibitors of most TTSPs have not yet been identified. In this study, we investigated the inhibitory effect of hepatocyte growth factor activator inhibitor type 1 (HAI-1), a Kunitz-type serine protease inhibitor, on several members of the TTSP family. We found that the protease activity of a member, TMPRSS13, was inhibited by HAI-1. A detailed analysis revealed that a soluble form of HAI-1 with one Kunitz domain (NK1) more strongly inhibited TMPRSS13 than another soluble form of HAI-1 with two Kunitz domains (NK1LK2). In addition, an in vitro protein binding assay showed that NK1 formed complexes with TMPRSS13, but NK1LK2 did not. TMPRSS13 converted single-chain pro-hepatocyte growth factor (pro-HGF) to a two-chain form in vitro, and the pro-HGF converting activity of TMPRSS13 was inhibited by NK1. The two-chain form of HGF exhibited biological activity, assessed by phosphorylation of the HGF receptor (c-Met) and extracellular signal-regulated kinase, and scattered morphology in human hepatocellular carcinoma cell line HepG2. These results suggest that TMPRSS13 functions as an HGF-converting protease, the activity of which may be regulated by HAI-1.
Exploitation of S-Layer Anisotropy: pH-Dependent Nanolayer Orientation for Cellular Micropatterning (2013)

We have developed a tunable, facile, and reliable cell patterning method using a self-assembled crystalline protein monolayer that, depending on its orientation, can exhibit either cell adhesive (cytophilic) or cell repulsive (cytophobic) surface properties. Our technique exploits, for the first time, the inherent biological anisotropy of the bacterial cell wall protein SbpA capable of interacting with its cytophilic inner side with components of the cell wall, while its outer cytophobic side interacts with the environment. By simply altering the recrystallization protocol from a basic to an acidic condition, the SbpA-protein layer orientation and function can be switched from preventing unspecific protein adsorption and cell adhesion to effectively promote cell attachment, spreading, and proliferation. As a result, the same protein solution can be used to form cell adhesive and repulsive regions over large areas on a single substrate using a simple pH-dependent self-assembly procedure. The reliable establishment of cytophobic and cytophilic SbpA layers allows the generation of well-defined surface patterns that exhibit uniform height (9-10 nm), p4 lattice symmetry with center-to-center spacing of the morphological units of 12 nm, as well as similar surface potential and charge distributions under cell culture conditions. The pH-dependent "orientation switch" of the SbpA protein nanolayer was integrated with micromolding in capillaries (MIMIC) technology to demonstrate its application for cell patterning using a variety of cell lines including epithelial, fibroblast and endothelial cells.
Combination treatment for massive cavernous hemangioma of the face: YAG laser photocoagulation plus direct steroid injection followed by YAG laser resection with sapphire scalpel tips, aided by superselective embolization (1990)

A massive cavernous hemangioma of the face in an 11 month old child has been successfully resected utilizing a combination of laser and non-laser techniques. The hemangioma was initially treated twice with YAG laser photocoagulation plus direct injection of steroids. This treatment promptly stopped the rapid growth and induced blanching as well as a 25% shrinkage with each treatment. Arteriogram with superselective embolization produced a further shrinkage of the hemangioma. Finally, the contact YAG laser with sapphire scalpel tips was utilized for complete and cosmetically satisfactory hemangioma resection. The treatment of a massive cavernous hemangioma by a combination of modalities is discussed.
Expression and Analysis of Recombinant Salmon Parvalbumin, the Major Allergen in Atlantic Salmon (Salmo salar) (1999)

The parvalbumin from white muscle of Atlantic salmon was previously found to be a major allergen, and designated Sal s1. Two distinct cDNAs, 14.1 and 24.1, which comprise the entire parvalbumin-encoding regions, were cloned, revealing transcripts from two different parvalbumin genes. In the present study, the protein-coding regions of these cDNAs were subcloned into an Escherichia coli expression vector (pET-19b). Both proteins were expressed and the generated target proteins were localized in both soluble and insoluble fractions of the expression host. The recombinant products in the soluble fraction were purified using the His tag-purification system and analysed on Western blots with anti-salmon parvalbumin polyclonal rabbit sera and sera from patients allergic to fish. Both recombinant products (His10-14.1 and His10-24.1) reacted positively with salmon parvalbumin-specific immunoglobulin G (IgG) from rabbits, and with specific immunoglobulin E (IgE) from the sera of six fish-allergic patients. The allergenicity of His10-14.1 was confirmed using enzyme-linked immunosorbent assay (ELISA). The 14.1 cDNA of salmon parvalbumin was shown to be the dominant type represented in a muscle cDNA library.
A synthetic peptide inhibitor of human immunodeficiency virus replication: correlation between solution structure and viral inhibition. (1992)

A peptide designated DP-107 was synthesized containing amino acid residues 558-595 of the envelope glycoprotein gp160 of human immunodeficiency virus type 1 strain LAI (HIV-1LAI). Algorithms for secondary structure have predicted that this region of the envelope transmembrane protein should form an extended alpha-helix. Consistent with this prediction, analysis by circular dichroism (CD) indicated that, under physiological conditions, DP-107 is approximately 85% helical. The high degree of stable secondary structure in a synthetic peptide of this size suggests self-association typical of a coiled coil or leucine zipper. In biological assays, the peptide efficiently blocked virus-mediated cell-cell fusion processes as well as infection of peripheral blood mononuclear cells by both prototypic and primary isolates of HIV-1. A single amino acid substitution in the peptide greatly destabilized its solution structure as measured by CD and abrogated its antiviral activity. An analogue containing a terminal cysteine was oxidized to form a dimer, and this modification lowered the dose required for antiviral effect from 5 to about 1 microgram/ml. These results suggest that both oligomerization and ordered structure are necessary for biological activity. They provide insights also into the role of this region in HIV infection and the potential for development of a new class of antiviral agents.