gebhart/patrepeval huggingface dataset:
Critical Review: Adhesion in surface micromechanical structures (1997)

We present a review on the state of knowledge of surface phenomena behind adhesion in surface micromechanical structures. After introducing the problem of release-related and in-use adhesion, a theoretical framework for understanding the various surface forces that cause strong adhesion of micromechanical structures is presented. Various approaches are described for reducing the work of adhesion. These include surface roughening and chemical modification of polycrystalline silicon surfaces. The constraints that fabrication processes such as release, drying, assembly, and packaging place on surface treatments are described in general. Finally, we briefly outline some of the important scientific and technological issues in adhesion and friction phenomena in micromechanical structures that remain to be clarified.
Persistent Neutrophil Dysfunction and Suppression of Acute Lung Injury in Mice following Cecal Ligation and Puncture Sepsis (2014)

Sepsis, both in humans and in rodents, is associated with persistent immunosuppression accompanied by defects in innate immunity during the acute phase of sepsis. Mice were rendered septic by cecal ligation and puncture (CLP) followed by the induction of acute lung injury, employing distal airway deposition of IgG immune complexes, in order to quantitatively evaluate innate immune responses following the induction of sepsis. Suppression of innate immune responses in the lung occurred as early as 12 h after CLP and up to 21 days thereafter. The mechanism of innate immune defects included a reduced leak of albumin into the lungs together with reduced levels of tumor necrosis factor in bronchoalveolar lavage fluids and increased levels of interleukin-10 that were persistent. Bone marrow-derived neutrophils (polymorphonuclear neutrophils; PMNs) from CLP mice also had reduced levels of the activation marker CD11b and a depressed respiratory burst following stimulation in vitro. These results were not observed in mice with endotoxemia, where the innate inflammatory response was preserved. However, sustained lymphopenia was present in both models, suggesting differential regulation of innate and adaptive immunity in the two sepsis models. These data indicate that CLP induced a prolonged suppression of inflammatory responses both in the lung and systemically, as defined by bone marrow-derived PMN dysfunction.
Identification of Functional Roles for Both IL-17RB and IL-17RA in Mediating IL-25-Induced Activities (2008)

IL-25 (IL-17E) is a unique IL-17 family ligand that promotes Th2-skewed inflammatory responses. Intranasal administration of IL-25 into naive mice induces pulmonary inflammation similar to that seen in patients with allergic asthma, including increases in bronchoalveolar lavage fluid eosinophils, bronchoalveolar lavage fluid IL-5 and IL-13 concentrations, goblet cell hyperplasia, and increased airway hyperresponsiveness. IL-25 has been reported to bind and signal through IL-17RB (IL-17BR, IL-17Rh1). It has been demonstrated recently that IL-17A signals through a heteromeric receptor composed of IL-17RA and IL-17RC. We sought to determine whether other IL-17 family ligands also utilize heteromeric receptor complexes. The required receptor subunits for IL-25 biological activities were investigated in vitro and in vivo using a combination of knockout (KO) mice and antagonistic Abs. Unlike wild-type mice, cultured splenocytes from either IL-17RB KO or IL-17RA KO mice did not produce IL-5 or IL-13 in response to IL-25 stimulation, and both IL-17RB KO and IL-17RA KO mice did not respond to intranasal administration of IL-25. Furthermore, treatment with antagonistic mAbs to either IL-17RB or IL-17RA completely blocked IL-25-induced pulmonary inflammation and airway hyperresponsiveness in naive BALB/c mice, similar to the effects of an antagonistic Ab to IL-25. Finally, a blocking Ab to human IL-17RA prevented IL-25 activity in a primary human cell-based assay. These data demonstrate for the first time that IL-25-mediated activities require both IL-17RB and IL-17RA and provide another example of an IL-17 family ligand that utilizes a heteromeric receptor complex.
Functional genomics identifies therapeutic targets for MYC-driven cancer (2012)

MYC oncogene family members are broadly implicated in human cancers, yet are considered "undruggable" as they encode transcription factors. MYC also carries out essential functions in proliferative tissues, suggesting that its inhibition could cause severe side effects. We elected to identify synthetic lethal interactions with c-MYC overexpression (MYC-SL) in a collection of ~3,300 druggable genes, using high-throughput siRNA screening. Of 49 genes selected for follow-up, 48 were confirmed by independent retesting and approximately one-third selectively induced accumulation of DNA damage, consistent with enrichment in DNA-repair genes by functional annotation. In addition, genes involved in histone acetylation and transcriptional elongation, such as TRRAP and BRD4, were identified, indicating that the screen revealed known MYC-associated pathways. For in vivo validation we selected CSNK1e, a kinase whose expression correlated with MYCN amplification in neuroblastoma (an established MYC-driven cancer). Using RNAi and available small-molecule inhibitors, we confirmed that inhibition of CSNK1e halted growth of MYCN-amplified neuroblastoma xenografts. CSNK1e had previously been implicated in the regulation of developmental pathways and circadian rhythms, whereas our data provide a previously unknown link with oncogenic MYC. Furthermore, expression of CSNK1e correlated with c-MYC and its transcriptional signature in other human cancers, indicating potential broad therapeutic implications of targeting CSNK1e function. In summary, through a functional genomics approach, pathways essential in the context of oncogenic MYC but not to normal cells were identified, thus revealing a rich therapeutic space linked to a previously "undruggable" oncogene.
Phenotypic and genetic analysis of Clock, a new circadian rhythm mutant in Drosophila melanogaster. (1990)

Clock is a semidominant X-linked mutation that results in shortening the period of Drosophila melanogaster's free-running locomotor activity rhythm from ca. 24.0 to ca. 22.5 hr. This mutation similarly shortened the phase response curve, determined by resetting activity rhythms with light pulses. Eclosion peaks for Clk cultures were separated by only 22.5 hr instead of the normal 24 hr. Clk was mapped close to, but separable from, another rhythm mutation--period01--by recombination. The estimated distance between these two mutations was short enough to suggest that Clk could be a per allele. If this is the case, the new mutant is unique in that it, unlike other per variants, is associated with essentially normal 1-min courtship song rhythms when Clk is expressed in males. Also, the new rhythm variant could not, in contrast to a short-period per mutation, have its effects on free-running activity rhythms uncovered by deletions. This result, and the lack of coverage of Clk's effects by duplications, suggest that it is not a simple hypomorphic or amorphic mutation.
MUC1-specific targeting immunotherapy with bispecific antibodies: inhibition of xenografted human bile duct carcinoma growth. (1996)

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we synthesized two bispecific antibodies (BsAbs), MUC1 x CD3 BsAb constructed with MUSE11 (anti-MUC1 tumor antigen) and OKT-3 (anti-CD3), and MUC1 x CD28 BsAb constructed with MUSE11 and 15E8 (anti-CD28) antibodies. These two BsAbs reacted well with both MUC1-positive target tumor cells and effector lymphokine-activated killer (LAK) cells. Investigation of in vitro cytotoxicity [3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide assay] revealed that the MUC1 x CD3 BsAb could antigen-specifically enhance the cytotoxicity of LAK cells. Addition of the two BsAbs (MUC1 x CD3 BsAb plus MUC1 x CD28 BsAb) in vitro resulted in a 60% cytotoxicity, similar to that obtained with BsAb (MUC1 x CD3) alone. Interleukin 12-induced LAK cells demonstrated far greater cytotoxicity (50%) than their interleukin 2-induced counterparts (LAK cells), and this was also enhanced by the BsAbs. When 2 x 10(7) LAK cells sensitized with both kinds of BsAbs were administered four times i.v. to BDC-grafted severe combined immunodeficient mice (tumor size 5 mm in diameter), inhibition of tumor growth was observed. Thus, BsAb-LAK therapy for control of BDC warrants clinical trials.
Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus (2003)

The candidate tumor-suppressor gene hyaluronidase 2 (HYAL2) encodes a glycosylphosphatidylinositol-anchored cell-surface protein that serves as an entry receptor for jaagsiekte sheep retrovirus, a virus that causes contagious lung cancer in sheep that is morphologically similar to human bronchioloalveolar carcinoma. The viral envelope (Env) protein alone can transform cultured cells, and we hypothesized that Env could bind and sequester the HYAL2 receptor and thus liberate a potential oncogenic factor bound and negatively controlled by HYAL2. Here we show that the HYAL2 receptor protein is associated with the RON receptor tyrosine kinase (also called MST1R or Stk in the mouse), rendering it functionally silent. In human cells expressing a jaagsiekte sheep retrovirus Env transgene, the Env protein physically associates with HYAL2. RON liberated from the association with HYAL2 becomes functionally active and consequently activates the Akt and mitogen-activated protein kinase pathways leading to oncogenic transformation of immortalized human bronchial epithelial cells. We find activated RON in a subset of human bronchioloalveolar carcinoma tumors, suggesting RON involvement in this type of human lung cancer.
Phosphorylation-induced structural changes in smooth muscle myosin regulatory light chain (2010)

We have performed complementary time-resolved fluorescence resonance energy transfer (TR-FRET) experiments and molecular dynamics (MD) simulations to elucidate structural changes in the phosphorylation domain (PD) of smooth muscle regulatory light chain (RLC) bound to myosin. PD is absent in crystal structures, leaving uncertainty about the mechanism of regulation. Donor-acceptor pairs of probes were attached to three site-directed di-Cys mutants of RLC, each having one Cys at position 129 in the C-terminal lobe and the other at position 2, 3, or 7 in the N-terminal PD. Labeled RLC was reconstituted onto myosin subfragment 1 (S1). TR-FRET resolved two simultaneously populated structural states of RLC, closed and open, in both unphosphorylated and phosphorylated biochemical states. All three FRET pairs show that phosphorylation shifts the equilibrium toward the open state, increasing its mol fraction by approximately 20%. MD simulations agree with experiments in remarkable detail, confirming the coexistence of two structural states, with phosphorylation shifting the system toward the more dynamic open structural state. This agreement between experiment and simulation validates the additional structural details provided by MD simulations: In the closed state, PD is bent onto the surface of the C-terminal lobe, stabilized by interdomain salt bridges. In the open state, PD is more helical and straight, resides farther from the C-terminal lobe, and is stabilized by an intradomain salt bridge. The result is a vivid atomic-resolution visualization of the first step in the molecular mechanism by which phosphorylation activates smooth muscle.
MetAMOS: a modular and open source metagenomic assembly and analysis pipeline (2013)

We describe MetAMOS, an open source and modular metagenomic assembly and analysis pipeline. MetAMOS represents an important step towards fully automated metagenomic analysis, starting with next-generation sequencing reads and producing genomic scaffolds, open-reading frames and taxonomic or functional annotations. MetAMOS can aid in reducing assembly errors, commonly encountered when assembling metagenomic samples, and improves taxonomic assignment accuracy while also reducing computational cost. MetAMOS can be downloaded from: https://github.com/treangen/MetAMOS.
T-cell non-Hodgkin lymphoma (2005)

T-cell non-Hodgkin lymphomas (NHLs) are uncommon malignancies. The current WHO/EORTC classification recognizes 9 distinct clinicopathologic peripheral T-cell NHLs. These disorders have unique characteristics and require individualized diagnostic and therapeutic strategies. Tremendous progress has been made in recent years in the understanding of the pathogenesis of these disorders. Specific chromosomal translocations and viral infections are now known to be associated with certain lymphomas. In this review, we describe their clinical and pathologic features. We also discuss the use of molecular studies in the diagnostic work-up of T-cell lymphomas. Because of the rarity of these disorders and the lack of well-designed clinical trials, the treatment of peripheral T-cell NHLs is often challenging. Additional studies are required to learn more about the biology of these diseases, which may lead to more optimal and possibly targeted therapies.
Analysis of Residential Demand Response and double-auction markets (2011)

Demand response and dynamic pricing programs are expected to play increasing roles in the modern smart grid environment. While direct load control of end-use loads has existed for decades, price driven response programs are only beginning to be explored at the distribution level. These programs utilize a price signal as a means to control demand. Active markets allow customers to respond to fluctuations in wholesale electrical costs, but may not allow the utility to control demand. Transactive markets, utilizing distributed controllers and a centralized auction, can be used to create an interactive system which can limit demand at key times on a distribution system, decreasing congestion. With the current proliferation of computing and communication resources, the ability now exists to create transactive demand response programs at the residential level. With the combination of automated bidding and response strategies, coupled with education programs and customer response, emerging demand response programs have the ability to reduce utility demand and congestion in a more controlled manner. This paper will explore the effects of a residential double-auction market, utilizing transactive controllers, on the operation of an electric power distribution system.
Liver Sinusoidal Endothelial Cells Are a Site of Murine Cytomegalovirus Latency and Reactivation (2009)

Latent cytomegalovirus (CMV) is frequently transmitted by organ transplantation, and its reactivation under conditions of immunosuppressive prophylaxis against graft rejection by host-versus-graft disease bears a risk of graft failure due to viral pathogenesis. CMV is the most common cause of infection following liver transplantation. Although hematopoietic cells of the myeloid lineage are a recognized source of latent CMV, the cellular sites of latency in the liver are not comprehensively typed. Here we have used the BALB/c mouse model of murine CMV infection to identify latently infected hepatic cell types. We performed sex-mismatched bone marrow transplantation with male donors and female recipients to generate latently infected sex chromosome chimeras, allowing us to distinguish between Y-chromosome (gene sry or tdy)-positive donor-derived hematopoietic descendants and Y-chromosome-negative cells of recipients' tissues. The viral genome was found to localize primarily to sry-negative CD11b(-) CD11c(-) CD31(+) CD146(+) cells lacking major histocompatibility complex class II antigen (MHC-II) but expressing murine L-SIGN. This cell surface phenotype is typical of liver sinusoidal endothelial cells (LSECs). Notably, sry-positive CD146(+) cells were distinguished by the expression of MHC-II and did not harbor latent viral DNA. In this model, the frequency of latently infected cells was found to be 1 to 2 per 10(4) LSECs, with an average copy number of 9 (range, 4 to 17) viral genomes. Ex vivo-isolated, latently infected LSECs expressed the viral genes m123/ie1 and M122/ie3 but not M112-M113/e1, M55/gB, or M86/MCP. Importantly, in an LSEC transfer model, infectious virus reactivated from recipients' tissue explants with an incidence of one reactivation per 1,000 viral-genome-carrying LSECs. These findings identified LSECs as the main cellular site of murine CMV latency and reactivation in the liver.
Optical Processes in Semiconductors (1972)

Optical processes in semiconductors , Optical processes in semiconductors , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Non-A, Non-B Hepatitis Transmission in Chimpanzees: A Project of the Transfusion-Transmitted Viruses Study Group (1978)

Experimental transmission of non-A, non-B hepatitis was apparently accomplished in 5 chimpanzees following inoculation with presumably infectious human sera. Administration of sera from implicated donors with normal alanine aminotransferase (ALT) values, as well as from those with abnormal ALT levels, resulted in the development of ALT abnormalities in the inoculated chimpanzees. Transmission from donors with normal ALT values implies that healthy carriers of non-A, non-B virus exist. Evidence is presented which indicates that a period of viremia precedes the clinical illness by at least 12 days.
Encapsulation of Biologicals within Silicate, Siloxane, and Hybrid Sol−Gel Polymers:  An Efficient and Generic Approach (1998)

The sol−gel encapsulation of labile biological materials with catalytic and recognition functions within robust polymer matrices remains a challenging task, despite the considerable research that has been focused on this field. Herein, we describe a new class of precursors, based around polyol silicates and polyol siloxanes, especially those derived from glycerol, that addresses problems faced with traditional bioencapsulation protocols. Poly(glyceryl silicate) (PGS) was prepared and employed for sol−gel bioentrapment, in an approach distinguished by a high biocompatibility and mild encapsulation conditions, and which enables the reproducible and efficient confinement of proteins and cells inside silica. The methodology was extended to metallosilicate, alkylsiloxane, functionalized siloxane, and composite sol−gels, thereby allowing the fabrication of a physicochemically diverse range of bio-doped polymers. The hybrid materials display activities approaching those of the free biologicals, together with the high stabilities and robustness that characterize sol−gel bioceramics. Indeed, the bioencapsulates performed better than those fabricated from tetramethoxysilane, poly(methyl silicate) or alcohol-free poly(silicic acid), even when the latter were doped with glycerol. The activity enhancements appear to derive at least in part from the unusual microstructure of PGS sol−gels, in particular their high porosity, although the underlying mechanisms are unclear. Differences in precursor hydrolysis/condensation, development of gel structure, biological-matrix interactions, precursor toxicity, and pore collapse probably all contribute to the observed efficiency of the PGS materials. The performances of the encapsulates are compared with conventional sol−biogels and other immobilizates, in representative biocatalyst, biosensor, and biodiagnostic applications.
The role of phage display in therapeutic antibody discovery (2014)

Phage display involves the expression of selected proteins on the surface of filamentous phage through fusion with phage coat protein, with the genetic sequence packaged within, linking phenotype to genotype selection. When combined with antibody libraries, phage display allows for rapid in vitro selection of antigen-specific antibodies and recovery of their corresponding coding sequence. Large non-immune and synthetic human libraries have been constructed as well as smaller immune libraries based on capturing a single individual's immune repertoire. This completely in vitro process allows for isolation of antibodies against poorly immunogenic targets as well as those that cannot be obtained by animal immunization, thus further expanding the utility of the approach. Phage antibody display represents the first developed methodology for high throughput screening for human therapeutic antibody candidates. Recently, other methods have been developed for generation of fully human therapeutic antibodies, such as single B-cell screening, next-generation genome sequencing and transgenic mice with human germline B-cell genes. While each of these have their particular advantages, phage display has remained a key methodology for human antibody discovery due its in vitro process. Here, we review the continuing role of this technique alongside other developing technologies for therapeutic antibody discovery.
Glucagon‐like peptide‐1 (GLP‐1): a trial of treatment in non‐insulin‐dependent diabetes mellitus (1997)

Glucagon-like peptide-1 (7-36) amide (GLP-1) is released from the gut into the circulation after meals and is the most potent physiological insulinotropic hormone in man. In contrast to presently available therapeutic agents for non-insulin-dependent diabetes mellitus (NIDDM), GLP-1 has the advantages of both suppressing glucagon secretion and delaying gastric emptying. We report the first chronic study of subcutaneous (s/c) GLP-1 treatment in NIDDM. Five patients with poorly controlled NIDDM were entered into a six-week, double-blind crossover trial. Each received three weeks treatment with s/c GLP-1 40 nmol or saline, given three times a day immediately before meals. A standardized test meal was given at the beginning and end of each treatment period. GLP-1 reduced plasma glucose area under the curve (AUC) following the standard test meal by 25% (AUC, 0-180 mins, GLP-1 start of treatment 482.2 +/- 38.2 vs. saline start of treatment 635.7 +/- 45.4 mmol min L-1, F = 16.4, P < 0.02). The beneficial effect of GLP-1 on plasma glucose concentration was fully maintained for the three-week treatment period. Plasma glucagon levels were significantly lower for 60 min postprandially after GLP-1 treatment. In this group of patients there was no significant increase in postprandial insulin levels with GLP-1. We have demonstrated a significant improvement in postprandial glycaemic control with s/c GLP-1 treatment that was fully maintained over a three-week treatment period. GLP-1 improves glycaemic control even in the absence of an insulinotropic effect and is a potential treatment for NIDDM.