gebhart/patrepeval huggingface dataset:
S2-5: An Anti-HER3 Antibody That Stabilizes the Inactive Conformation Inhibits Both HER2 and Ligand Driven Tumor Growth. (2011)

Abstract Background: HER3 (ErbB3) is a member of the ErbB family of receptor tyrosine kinases (RTK). In normal physiology, ligands (e.g. neuregulin) activate HER3 by promoting dimerization with other RTK's such as HER2 (ErbB2). Inappropriate HER2/HER3 dimerization as a result of HER2 over-expression in cancer results in HER3 mediated activation of the oncogenic PI3K pathway. The HER2− targeted antibody trastuzumab inefficiently inhibits HER2 mediated HER3 activation allowing persistent HER3 signaling that is speculated to limit clinical responses. Consequently, combination of a HER3- targeted agent with trastuzumab may be of clinical benefit. Furthermore, ectopic HER3 activation has recently been implicated in the relief of a feedback loop induced by PI3K inhibitors that may perhaps limit their efficacy in HER2 driven tumors. Since HER3 activation in HER2 driven cancers occurs in a ligand- independent manner, antibodies that primarily inhibit ligand- induced HER3 activation are largely inactive in HER2 driven xenograft models. Results: H3F15, a high affinity (26pM) HER3- targeted fully human IgG1 antibody was selected from the Human Combinatorial Antibody Library (HuCAL) using phage display technology. In a broad range of HER2 amplified breast and gastric cell lines, H3F15 displayed potent inhibition (IC50 &lt;1nM) of HER3/AKT phosphorylation and proliferation. Interestingly, H3F15 also effectively inhibited neuregulin stimulated HER3 phosphorylation and downstream signaling in MCF7 cells indicating that H3F15 inhibits multiple modes of HER3 activation. Determining the H3F15/HER3 crystal structure revealed that H3F15 binds a novel conformational epitope that traps HER3 in the inactive conformation thus preventing its activation by either HER2 or neuregulin. In vivo testing of H3F15 using xenograft tumor models driven by either HER2 (BT474) or HER3 ligands (BxPC3) confirmed that single agent H3F15 (20mg/kg) significantly inhibited tumor growth (83 and 77% inhibition respectively). Furthermore, combinations of H3F15 with either trastuzumab or PI3K- targeted agents were synergistic in a panel of HER2 driven cell lines whilst the in vivo combination of H3F15 (20mg/kg) with trastuzumab (1mg/kg) was sufficient to induce tumor regression. Discussion: H3F15 is a HER3- targeted antagonist IgG1 that stabilizes the inactive form of HER3. This novel mechanism of action enables H3F15 to uniquely inhibit both ligand-induced and HER2−mediated activation of HER3. Thus H3F15 is the first HER3 antibody to display single-agent efficacy in both HER2 and ligand driven xenograft models whilst also inducing tumor regressions in combination with trastuzumab. Based on preclinical data, combining H3F15 with either trastuzumab or PI3K- targeted agents fully inhibits the HER2/HER3 signaling pathway, which may lead to greater and more sustained clinical efficacy in HER2 driven cancers. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S2-5.
CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons (2016)

Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats.
A comparative evaluation of spermicidal activities of iron salts. (1979)

The mechanism of action of the sperm-immobilizing effects of various iron salts has not been established. This study was conducted to determine: 1) the effects of tonicity of the medium containing ferrous and ferric salts on the motility of human sperm and their effect on fructose utilization; and 2) the effect of pH on the medium of sperm motility. Fresh semen samples with 50% or more motility and with a count of more than 70 million per ml were used. A new total spermicidal test which mixes liquified semen with diluted iron salt solutions and observing a drop under a microscope within 40 seconds was used. Aqueous solutions of ferric chloride, ferric ammonium sulfate and ferrous sulfate were prepared in the ranges of their hypotonic, isotonic and hypertonic concentrations. The results show that the interaction of spermatozoa with iron salts accounts for the varying degree of irreversible immobilization. Instantaneous, complete and irreversible sperm immobilization required hypertonic concentrations of ferric chloride, ferric ammonium sulfate and ferrous sulfate. A significant degree of irreversibility was also observed at isotonic concentrations of these salt solutions. Ferric chloride and ferric ammonium sulfate exhibited total spermicidal action at comparatively lower concentrations; both have a higher acidic characteristic compared to ferrous sulfate. Ferric salts are thus more potent sperm-immobilizing agents than ferrous salts. Toxic alteration in enzyme systems, particularly those with sulphydryl groups, is probably the underlying mechanism behind motility inhibition.
Oxidative Stress and the Aging Brain: From Theory to Prevention (2007)

Aging is characterized by a progressive decline in the efficiency of physiological function and by the increased susceptibility to disease and death. The premise of the mitochondrial free radical theory of aging is that mitochondria are both producers and targets of reactive oxidative species. In the aging brain, as well as in the case of several neurodegenerative diseases, there is a decline in the normal antioxidant defense mechanisms, which increases the vulnerability of the brain to the deleterious effects of oxidative damage. Aging also is accompanied by changes in membrane fatty acid composition, including a decrease in the levels of polyunsaturated fatty acids and an increase in monosaturated fatty acids. The chapter summarizes some of the literature that supports a role for oxidative stress as one aspect of age and disease that contributes to declines in function of the central nervous system. The oxidative stress theory of aging has also come to include a role for inflammation.
Exploration Study of Multifunctional Metallic Nanocomposite Utilizing Single-Walled Carbon Nanotubes for Micro/Nano Devices (2005)

Carbon nanotubes (CNTs) are excellent multifunctional materials in terms of mechanical robustness, thermal, and electrical conductivities. These multifunctional properties, as well as the small size of the structures, make CNTs ideal building blocks in developing nanocomposites. However, the matrix materials and the fabrication processes are critical in achieving the expected multifunctional properties of a CNT-reinforced nanocomposite. This paper has proved that electrochemical co-deposition of a metallic nanocomposite is a good approach for achieving good interfacial bonding between CNTs and a metallic matrix. Good interfacial bonding between a single-walled carbon nanotube (SWCNT) and a copper matrix has been verified by enhanced fracture toughness (increased stickiness) and a shift in the Raman scattering spectra. For the Cu/SWCNT nanocomposite, the radial breath mode (RBM) has disappeared and the tangential or G-band has shifted and widened, which is an indication of better energy transport.
Treatment of intractable autoimmune diseases in MRL/lpr mice using a new strategy for allogeneic bone marrow transplantation (2000)

A new bone marrow transplantation (BMT) method for treating severe autoimmune diseases in chimeric resistant MRL/lpr mice is presented. The method consists of fractionated irradiation (5.5 Gy x 2), followed by portal venous (PV) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV) injection of whole B6 BMCs 5 days after the PV injection (abbreviated as 5.5 Gy x 2 + PV + IV). All recipients survived more than 1 year after this treatment (more than 64 weeks after birth). Abnormal T cells (Thy1.2(+)/B220(+)/CD3(+)/CD4(-)/CD8(-)) present in MRL/lpr mice before the treatment disappear, and hematolymphoid cells are reconstituted with donor-derived cells. The treated mice are free from autoimmune diseases. Levels of autoantibodies (IgG/IgM anti-ssDNA antibodies and IgG/IgM rheumatoid factors) decrease to normal levels. Successful cooperation is achieved among T cells, B cells, and antigen-presenting cells (APCs) of the treated MRL/lpr mice when evaluated by in vitro anti-SRBC responses. Newly developed T cells are tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex (MHC) determinants. These findings clearly indicate that severe autoimmune diseases in MRL/lpr mice are completely ameliorated by the treatment without recourse to immunosuppressants, and that the treated MRL/lpr mice show normal immune functions, strongly suggesting that this strategy would be applicable to humans. (Blood. 2000;95:1862-1868)
Reservation CSMA/CD: a multiple access protocol for LAN's (1989)

A multiple-access protocol for local area networks is described. It is basically a hybrid of carrier-sense multiple access with collision detection (CSMA/CD) and the broadcast recognizing access method (BRAM). CSMA/CD, which is contention-based, works well under light traffic, but message collisions degrade system performance when the channel becomes heavily loaded. BRAM, which is collision-free, has no longer delays at low load, but its efficiency improves as the load increases. Performance models are developed for the hybrid protocol and for the Ethernet protocol, a proven commercial implementation of CSMA/CD-type protocols. It is found that the hybrid protocol gives better performance for a wide range of scenarios.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
ChemInform Abstract: The Chirality Problem in P‐Substituted Oligonucleotides (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Using Functional Tissue Engineering and Bioreactors to Mechanically Stimulate Tissue-Engineered Constructs (2009)

Bioreactors precondition tissue-engineered constructs (TECs) to improve integrity and hopefully repair. In this paper, we use functional tissue engineering to suggest criteria for preconditioning TECs. Bioreactors should (1) control environment during mechanical stimulation; (2) stimulate multiple constructs with identical or individual waveforms; (3) deliver precise displacements, including those that mimic in vivo activities of daily living (ADLs); and (4) adjust displacement patterns based on reaction loads and biological activity. We apply these criteria to three bioreactors. We have placed a pneumatic stimulator in a conventional incubator and stretched four constructs in each of five silicone dishes. We have also programmed displacement-limited stimuli that replicate frequencies and peak in vivo patellar tendon (PT) strains. Cellular activity can be monitored from spent media. However, our design prevents direct TEC force measurement. We have improved TEC stiffness as well as PT repair stiffness and shown correlations between the two. We have also designed an incubator to fit within each of two electromagnetic stimulators. Each incubator provides cell viability like a commercial incubator. Multiple constructs are stimulated with precise displacements that can mimic ADL strain patterns and record individual forces. Future bioreactors could be further improved by controlling and measuring TEC displacements and forces to create more functional tissues for surgeons and their patients.
The Role of MRI in clinical trials of multiple sclerosis: Comparison of image processing techniques (1997)

Magnetic resonance imaging (MRI) has received considerable attention in recent years over its potential for providing indices of multiple sclerosis activity and progression in clinical trials of new pharmaceuticals. The perceived advantages of MRI-derived measurements include greater objectivity, sensitivity, and reproducibility when compared with clinical rating scales. Clinical scales are also somewhat biased toward lesions affecting locomotion. However, the myriad permutations of MRI acquisition parameters, analysis methodologies, and disease indices demand careful consideration when employing MRI. Moreover, the use of MRI in research into the basic mechanisms of a disease may have different requirements than its use in a clinical trial setting. Consequently, a conference was held, sponsored by the US and Canadian multiple sclerosis societies, to review the present status of various MRI processing strategies and their potential role in clinical trials. Thirteen laboratories from North America and Europe as well as regulatory agencies and statistical consultants made formal presentations followed by extended discussion. This report presents the conclusions reached and recommendations for further action that emerged from the meeting.
Liver-Directed Adeno-Associated Viral Gene Therapy for Hemophilia (2013)

Hemophilia A and B are monogenic bleeding disorders resulting from loss of functional coagulation factors VIII or IX, respectively. Prophylactic treatment requires frequent intravenous injections of exogenous factor VIII (F.VIII) or factor IX (F.IX), due to the short half-life of both factors. Hemophilia patients are at risk of developing neutralizing antibodies to F.VIII (~25-30%) or F.IX (~2-4%), which require the use of expensive bypass agents and immune tolerance induction protocols. Viral vector mediated liver gene transfer of F.VIII or F.IX offers an alternative treatment for hemophilia with easily defined clinical endpoints and no need for strict regulation of coagulation factor expression, as both proteins circulate as inactive zymogens. Adeno-associated viral (AAV) vectors are derived from a non-pathogenic human virus that efficiently transduce non-dividing cells, such as hepatocytes, and provide stable transgene expression. <i>In vivo</i> liver gene transfer of AAV-F.VIII and -F.IX vectors has restored hemostasis in murine and canine hemophilia models long-term, and has also been shown to induce immune tolerance. Consequently, two Phase I/II clinical trials have been conducted, based on hepatic AAV-FIX gene transfer to patients with severe hemophilia B. The first trial, utilizing serotype 2, demonstrated transient correction, which was limited by a cellular immune response against the viral capsid. However, sustained therapeutic expression has been achieved in a second trial, using AAV8 for expression of a codon-optimized F.IX transgene. Translation of F.VIII gene transfer studies into the clinic may require additional optimization of gene transfer and vector to effectively express the larger cDNA of F.VIII.
Specific contact resistivity of metal-semiconductor contacts-a new, accurate method linked to spreading resistance (1988)

A method to determine the specific contact resistivity of metal-semiconductor contacts has been developed. It allows the separation of the total series resistance between two contacts into the contributing component resistances. The principle of the method is the subtraction of the semiconductor spreading resistance from the total two-contact resistance. This requires geometrically well-defined small contacts that are fabricated precisely by lithographic methods. Using this method, accurate values were obtained for the specific contract resistivity of an aluminium-1.5% silicon alloy to p-type silicon wafers having dopant densities from 5*10/sup 14/ to 2*10/sup 20/ cm/sup -3/. The specific contact resistivity values are lower than previously published values obtained using earlier methods in which parasitic and nonideal effects could not be quantified or eliminated. The lower values indicate that contact resistance has a less-limiting effect on the performance of integrated circuits than presently believed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Serodiagnosis of <i>Bartonella bacilliformis</i> Infection by Indirect Fluorescence Antibody Assay: Test Development and Application to a Population in an Area of Bartonellosis Endemicity (2000)

Bartonella bacilliformis causes bartonellosis, a potentially life-threatening emerging infectious disease seen in the Andes Mountains of South America. There are no generally accepted serologic tests to confirm the disease. We developed an indirect fluorescence antibody (IFA) test for the detection of antibodies to B. bacilliformis and then tested its performance as an aid in the diagnosis of acute bartonellosis. The IFA is 82% sensitive in detecting B. bacilliformis antibodies in acute-phase blood samples of laboratory-confirmed bartonellosis patients. When used to examine convalescent-phase sera, the IFA is positive in 93% of bartonellosis cases. The positive predictive value of the test is 89% in an area of Peru where B. bacilliformis is endemic and where the point prevalence of infection is 45%.
Genetic analysis of hydroxymethylglutaryl‐coenzyme A reductase regulated degradation (1998)

Hydroxymethylglutaryl-coenzyme A reductase degradation occurs in the endoplasmic reticulum, and is regulated by the mevalonate pathway. In order to discover the molecules that mediate the degradation process and its control, we conducted a genetic analysis of the degradation of the yeast Hmg2p isozyme of hydroxymethylglutaryl-coenzyme A reductase. Hmg2p degradation occurs by the action of HRD genes that direct Hmg2p to the ubiquitin-proteasome pathway. Regulation of HRD-dependent Hmg2p degradation appears to occur by the action of a separate set of CRD genes.
Facile preparation of silicon hollow spheres and their use in electrochemical capacitive energy storage (2012)

Nanostructured silicon hollow spheres with a thin shell have been synthesized by magnesium reduction of silica spheres, which possess a high BET surface area and are electrochemically active in capacitive energy storage with a maximum specific capacitance of 193 F g(-1) in the neutral Na(2)SO(4) aqueous solution.
Enhanced and Enduring Protection against Tuberculosis by Recombinant BCG-Ag85C and Its Association with Modulation of Cytokine Profile in Lung (2008)

These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all likelihood would show enhanced survival of guinea pigs.
Inhibition of Restriction in Streptomyces clavuligerus by Heat Treatment (1986)

Inefficient transformation of Streptomyces clavuligerus protoplasts by DNA from the plasmid pIJ702, isolated from S. lividans, was attributed to restriction in view of the observation that efficient transformation was observed using modified pIJ702 (isolated from S. clavuligerus). The restriction system could be partially inhibited by treating protoplasts at 45 degrees C prior to transformation. This treatment increased the transformation frequencies of pIJ702 DNA by 100-fold and was used to introduce other plasmids into S. clavuligerus.
YBaCuO and TlBaCaCuO Superconductor Thin Films via an Electrodeposition Process (1992)

Thin‐film superconductors of (YBCO) and (TBCCO) were fabricated via an electrodeposition process. The YBCO superconductor precursor thin films were deposited at potentials ranging from −2.5 to −4 V vs. an reference electrode. The YBCO films were deposited under both constant and pulsed‐potential conditions. The post‐annealed YBCO films showed zero resistance of approximately 74 K on Ni, 78 K on , and 91 K on substrates. The best critical current densities obtained for the YBCO films at 4 K and zero magnetic field and their respective substrates are as follows: 4000 A/cm2 on , 3960 A/cm2 on (constant potential), 5160 A/cm2 on (pulsed potential), 500 A/cm2 on a Ni strip, 325 A/cm2 on a Ni wire, and 500 A/cm2 on a Ag wire. The precursors of the superconducting TBCCO films were codeposited at a constant potential of −4 V and also under pulsed‐potential conditions. The post‐annealed TBCCO films showed zero resistance at about 102 K on substrate. The critical current density at 76 K of a TBCCO film deposited at constant potential on a silver‐coated substrate was 20,000 A/cm2 in zero magnetic field and 5,000 A/cm2 in a 10 kOe field parallel to the film plane. The critical current density of pulsed‐potential deposited TBCCO film on was 56,000 A/cm2 at 76 K in zero field.
Comparison of Viral Env Proteins from Acute and Chronic Infections with Subtype C Human Immunodeficiency Virus Type 1 Identifies Differences in Glycosylation and CCR5 Utilization and Suggests a New Strategy for Immunogen Design (2013)

Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and subjects with chronic infections in the context of subtype C heterosexual transmission. We found that the transmitted viruses all used CCR5 and required high levels of CD4 to infect target cells, suggesting selection for replication in T cells and not macrophages after transmission. In addition, the transmitted viruses were more likely to use a maraviroc-sensitive conformation of CCR5, perhaps identifying a feature of the target T cell. We confirmed an earlier observation that the transmitted viruses were, on average, modestly underglycosylated relative to the viruses from chronically infected subjects. This difference was most pronounced in comparing the viruses in acutely infected men to those in chronically infected women. These features of the transmitted virus point to selective pressures during the transmission event. We did not observe a consistent difference either in heterologous neutralization sensitivity or in sensitivity to soluble CD4 between the two groups, suggesting similar conformations between viruses from acute and chronic infection. However, the presence or absence of glycosylation sites had differential effects on neutralization sensitivity for different antibodies. We suggest that the occasional absence of glycosylation sites encoded in the conserved regions of env, further reduced in transmitted viruses, could expose specific surface structures on the protein as antibody targets.
Thermo- and photo-oxidative stability and improved processability of polyamide stabilized with a new functional additive (2005)

During processing polyamides can undergo thermo-mechanical degradation due to the mechanical stress and to the high temperature applied to the melt. Degradation can occur also during the polyamides lifetime due to many driving forces, like temperature, ultraviolet radiations, etc. The mechanisms of degradation are not well understood and the stabilization with usual stabilizers, like phenol antioxidants, is not so efficient as for other classes of polymers. The aim of this work is the study of the effects of the addition of a new multifunctional additive on the processing and on the thermo- and photo-stabilization of polyamide-6. This additive is able to prevent the thermo-mechanical degradation and also to enlarge the molecular weight distribution improving the processability of this polymer in operations where the elongational flow is involved. Moreover, the presence of this additive extends significantly the lifetime of the polyamide when subjected to thermo- and photo-oxidative stress. Copyright © 2005 John Wiley & Sons, Ltd.