gebhart/patrepeval huggingface dataset:
Monoclonal antibodies specific for murine p55 and p75 tumor necrosis factor receptors: identification of a novel in vivo role for p75. (1995)

Monoclonal antibodies (mAbs) specific for the murine p55 and p75 tumor necrosis factor (TNF) receptors were produced after immunization of Armenian hamsters with the purified soluble extracellular domains of each receptor protein. Four p55- (55R) and five p75 (TR75)-reactive mAbs immunoprecipitated the appropriate receptor from the surface of L929 cells. None of the mAbs cross-reacted with the other TNF receptor form. The mAbs were functionally characterized by their ability to inhibit ligand binding and influence TNF-dependent L cell cytolytic activity or proliferation of the murine cytolytic T cell clone CT6. One p55-specific mAb, 55R-593, displayed agonist activity, while two other p55-specific mAbs (55R-170 and -176) were found to be TNF antagonists. The fourth mAb (55R-286) had no functional effects on cells. Several antibodies specific for the p75 TNF receptor partially inhibited recombinant murine TNF-alpha-dependent cytolytic activity (60%). Blocking mAbs specific for p75 but not anti-p55 inhibited TNF-mediated proliferation of CT6 T cells. When used in vivo, p55- but not p75-specific mAbs protected mice from lethal endotoxin shock and blocked development of a protective response against Listeria monocytogenes infection. In contrast, both p55 and p75 mAbs individually blocked development of skin necrosis in mice treated with murine TNF-alpha. These data thus demonstrate the utility of the two families of murine TNF receptor-specific mAbs and identify a novel function of the p75 TNF receptor in vivo.
Nanocolumns composed of GaAs-InAs jointed whiskers and SiO2 covers (1994)

A dense array of nanocolumns composed of GaAs-InAs jointed whiskers and SiO2 covers has been fabricated on InAs substrates. The cylindrical GaAs whisker with a 20 nm diameter and 1.5 μm long is jointed on top of 0.3-μm-long InAs whisker by vapor-liquid-solid epitaxy. The nanocolumns array exhibited photoluminescence at 14 K.
A high efficiency flow cytometer. (1977)

A flow chamber has been developed which collects about 60% of the total cell fluorescence for analysis compared to about 2.5% for conventional flow systems. The chamber, an ellipsoid of revolution, is gold-plated for increased reflectivity. Fluorochrome-stained cells enter the flow cell directly above the primary focus of the ellipsoid at the rate of 1000 cell/sec. A focused argon-ion laser beam enters the flow cell parallel to the semiminor axis and intersects the cell stream at the primary focus. Fluorescent light emanating from this point is reflected toward the secondary focus, where it exits the chamber for analysis. The high efficiency flow cytometer has been used to obtain nucleotide fluorescence distributions from samples of Micrococcus glutamicus bacteria stained with propidium iodide and of spermatozoa stained by the acriflavine-Feulgen procedure.
Familial cerebral amyloid angiopathy related to stroke and dementia. (2001)

The term cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the walls of leptomeningeal and cortical arteries, arterioles and, although less frequently in capillaries and veins. It is commonly associated with Alzheimers disease, Down's syndrome and normal aging, as well as with a variety of familial conditions related to stroke and/or dementia: hereditary cerebral hemorrhage with amyloidosis of Icelandic type (HCHWA-I), various inherited disorders linked to Abeta mutants (including the Dutch variant of HCHWA), and the recently described chromosome 13 familial dementia in British and Danish kindreds. This review focuses on four different types of hereditary CAA, emphasizing the notion that CAA is not only related to stroke but also to neurodegeneration and dementia of the Alzheimer's type.
Modifying Methoxycarbonyl Etomidate Inter-Ester Spacer Optimizes In Vitro Metabolic Stability and In Vivo Hypnotic Potency and Duration of Action (2012)

We created 13 new analogs of methoxycarbonyl etomidate and identified two that have significantly higher potency and potentially address the too-brief duration of action for methoxycarbonyl etomidate. This work may provide a blueprint for optimizing the pharmacological properties of other soft drugs.
Enhanced Insulin-Like Growth Factor Binding Protein–Related Protein 2 (Connective Tissue Growth Factor) Expression in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Sarcoidosis (1999)

Connective tissue growth factor is a recently described chemoattractant and fibroblast mitogen which, because of sequence homology and weak binding to insulin-like growth factor (IGF)-1, has been proposed as the eighth member of the IGF binding protein (IGFBP) superfamily, named IGFBP-related protein 2 (IGFBP-rP2). Previous studies have implicated IGFBP-rP2 in a number of heterogeneous fibrotic pathologies, including renal fibrosis, dermal scleroderma, and bleomycin-induced pulmonary fibrosis in mice. Because profibrogenic cytokines may be produced by inflammatory cells, we developed a multiplex competitive reverse transcription/polymerase chain reaction to quantify IGFBP-rP2 transcripts in bronchoalveolar lavage cells from healthy subjects and patients with idiopathic pulmonary fibrosis (IPF) and pulmonary sarcoidosis. IGFBP-rP2 messenger RNA expression was enhanced > 10-fold (P < 0.003) in patients with IPF; > 40-fold (P < 0.006) in stage I/II sarcoidosis patients, and > 90-fold (P < 0.005) in stage III/IV sarcoidosis patients by comparison with healthy nonsmoking control subjects. We suggest these increases are predominantly associated with lymphocyte- and neutrophil-driven IGFBP-rP2 production. These findings, together with previous reports implicating other IGFBPs in the pathogenesis of pulmonary fibrosis, suggest that the complex network of IGFBPs within the human lung is an important determinant of the outcome of the fibroproliferative response to injury.
CopY Is a Copper-inducible Repressor of the Enterococcus hirae Copper ATPases (1997)

The cop operon of Enterococcus hirae effects copper homeostasis in this organism. It encodes a repressor, CopY, an activator, CopZ, and two P-type copper ATPases, CopA and CopB. Expression of all four genes is regulated by the ambient copper. In this regulation, CopY apparently acts as a copper-inducible repressor. By DNase I footprinting, it was shown that purified CopY protected two discrete sites in the region encompassing nucleotides -71 to -11 relative to the translational start site and containing hyphenated inverted repeats. Transcription is initiated between these repeats at nucleotide -42, in a domain that remained accessible to DNase I in the DNA-repressor complex. Chemical cross-linking revealed that CopY exists as a dimer in solution. In DNA band-shift assays, it was apparent that the CopY-DNA interaction occurred in two discrete steps. Half-maximal binding of repressor to the two operator sites was observed at 2 x 10(-9) M and 5 x 10(-9) M CopY, respectively. Copper ions released CopY from the promoter/operator with an apparent half-binding constant for Cu(I) of 20 microM. The site-directed mutations A-61T and A-30T essentially abolished the binding of CopY to the respective binding sites, and the double mutation A-61T/A-30T inactivated both binding sites. Thus, CopY is a copper-inducible repressor of the cop operon of E. hirae, exhibiting highly specific DNA-protein interactions with two sites on the cop promoter/operator and playing a key role in copper homeostasis in E. hirae.
Direct measurement of effects of shallow-trench isolation on carrier profiles in sub-50 nm n-MOSFETs (2005)

The effects of shallow-trench isolation (STI) on the carrier profile of the extension region in sub-50-nm n-MOSFET were directly measured for the first time. The extension overlap length drastically decreased by 3 run within a distance from STI (Y) of 50 nm. In contrast, the channel concentration gradually increased within Y of 100 nm. The STI effect was also measured for transistors with a gate width of less than 130 nm in 6T-SRAM cell. Reduction of the STI effect by nitrogen co-implant suppressed sub-threshold leakage current by up to an order of magnitude and decreased fluctuation in the threshold voltage by 8 %.
Synthesis of (.+-.)-PF1092A, B, and C; New Nonsteroidal Progesterone Receptor Ligands. (1997)

Wepreviously isolated three eremophilane-type sesquiterpenoids PF1092A (1), PF1092B (2), and PF1092C
Multimodality in Vivo Molecular-Genetic Imaging (2004)

Multimodality imaging is increasingly being used in molecular-genetic studies in small animals. The coupling of nuclear and optical reporter genes represents the beginning of a far wider application of this technology. Optical imaging and optical reporter systems are cost-effective and time-efficient, they require less resources and space than PET or MRI, and they are particularly well suited for small animal imaging and for in vitro assays to validate different reporter systems. However, optical imaging techniques are limited by depth of light penetration and scatter and do not yet provide optimal quantitative or tomographic information. These issues are not limiting for PET- or MRI-based reporter systems, and PET- and MRI-based animal studies are more easily generalized to human applications. Many of the shortcomings of each modality alone can be overcome by the use of dual- or triple-modality reporter constructs that incorporate the opportunity for PET, fluorescence and bioluminescence imaging. We optimistically expect that some form of tomographic, small animal optical imaging capability will be developed soon, and that this will provide the opportunity for the colocalization of optical signals to anatomical structures provided by tomographic CT and MR imaging.
Future Trends in Miniaturization for Wireless Applications (2004)

he future of miniaturization of wireless networks is described from the viewpoint of today’s trends in miniaturization, such as microelectromechanical systems and nanotechnology, along with the move away from computer processing–centric systems to distributed networks. The complexity, convergence of technologies, and connectivity of the remote wireless sensor known as the “mote” are discussed in relation to distributed networks. The growth of this technology is compared with growth predicted by Moore’s law, which charts a linear progression of technology such as size of a resistor, as well as by the technology S-curve, which charts a logarithmic growth such as that seen by the Internet. We show that growth in the number of applications for motes is likely to more closely follow the predictions of the S-curve. The capabilities of this technology, in terms of functionality, have the potential for the log-linear growth experienced in the modern microcircuit world.
Strategies and challenges in eliciting immunity to melanoma (2008)

The ability of CD8+ T cells to recognize melanoma tumors has led to the development of immunotherapeutic approaches that use the antigens CD8+ T cells recognize. However, clinical response rates have been disappointing. Here we summarize our work to understand the mechanisms of self-tolerance that limit responses to currently utilized antigens and our approach to identify new antigens directly tied to malignancy. We also explore several aspects of the anti-tumor immune response induced by peptide-pulsed dendritic cells (DCs). DCs differentially augment the avidity of recall T cells specific for self-antigens and overcome a process of aberrant CD8+ T-cell differentiation that occurs in tumor-draining lymph nodes. DC migration is constrained by injection route, resulting in immune responses in localized lymphoid tissue, and differential control of tumors depending on their location in the body. We demonstrate that CD8+ T-cell differentiation in different lymphoid compartments alters the expression of homing receptor molecules and leads to the presence of systemic central memory cells. Our studies highlight several issues that must be addressed to improve the efficacy of tumor immunotherapy.
Radioactive Tracers: Review of Principle Factors in Design and Application (1996)

Abstract Radioactive tracers have been successfully utilized to interpret the placement of stimulation treatments. Completion effectiveness can be verified best when stimulation operations are traced. The advances in tracer technology require a thorough understanding of all the factors that affect the design and use of tracers, including the commercial manufacture of nuclides, the economic benefits of their use, the regulatory and licensing requirements, the choice of materials and systems, exposure doses and exposure risk, procedures for well reversal (flow-back) and the technology behind multi-isotope logging (gamma spectrum analysis).
Molecular anatomy of the antibody binding site. (1983)

The binding region of immunoglobulins, which includes the portion of the molecule having the most variability in its amino acid sequence, is shown to have a surprisingly constant structure that can be characterized in terms of a simple, well-defined model. The binding region is composed of the antigen combining site plus its immediate vicinity and arises by noncovalent association of the light and heavy chain variable domains (VL and VH, respectively). The antigen combining site itself consists of six polypeptide chain segments ("hypervariable loops") which comprise some 80 amino acid residues and are attached to a framework of VL and VH beta-sheet bilayers. Having analyzed refined x-ray crystallographic coordinates for three antigen-binding fragments (Fab KOL (Marquart, M., Deisenhofer, J., and Huber, R. (1980) J. Mol. Biol. 141, 369-391), MCPC 603 (Segal, D., Padlan, E. A., Cohen, G. H., Rudikoff, S., Potter, M., and Davies, D. R. (1974) Proc. Natl. Acad. Sci. U. S. A. 71, 4298-4302), and NEW (Saul, F. A., Amzel, L. M., and Poljak, R. J. (1978) J. Biol. Chem. 253, 585-597] we use the results to introduce a general model for the VL-VH interface forming the binding region. The region consists of two closely packed beta-sheets, and its geometry corresponds to a 9-stranded, cylindrical barrel of average radius 0.84 nm with an average angle of -53 degrees between its two constituent beta-sheets. The barrel forms the bottom and sides of the antigen combining site. The model demonstrates that the structural variability of the binding region is considerably less than was thought previously. Amino acid residues which are part of the domain-domain interface and appear not to be accessible to solvent or antigen contribute to antibody specificity.
Antimalarial drugs in the treatment of rheumatological diseases. (1997)

A have been used to treat rheumatic diseases for more than a century [1]. In evaluating these medications over the last four decades, three clinical characteristics have become better understood: effectiveness, safety and an expanding number of conditions for which these drugs may be used. Although much work has been expended to elucidate mechanisms of action, those relevant to antimalarial effect on rheumatic diseases have not yet been confirmed. Three antimalarials are now employed to treat connective tissue diseases: chloroquine, hydroxychloroquine and quinacrine. The latter drug is used at present only for patients with lupus skin lesions who fail to respond to one of the other drugs or who cannot take them. Quinacrine is not used more often for long-term therapy because it imparts a yellowish discolouration to the skin.
A passive planar micromixer with obstructions for mixing at low Reynolds numbers (2007)

Passive mixers rely on the channel geometry to mix fluids. However, many previously reported designs either work efficiently only at moderate to high Reynolds numbers (Re), or require a complex 3D channel geometry that is often difficult to fabricate. In this paper, we report design, simulation, fabrication and characterization of a planar passive microfluidic mixer capable of mixing at low Reynolds numbers. The design incorporates diamond-shaped obstructions within the microchannel to break-up and recombine the flow. Simulation and experimental results of the developed micromixer show excellent mixing performance over a wide range of flow conditions (numerically: 0.01 < Re < 100, experimentally: 0.02 < Re < 10). The micromixer is also characterized by low pressure drop, an important characteristic for integration into complex, cascading microfluidic systems. Due to the simple planar structure of the micromixer, it can be easily realized and integrated with on-chip microfluidic systems, such as micro total analysis systems (μTAS) or lab on a chip (LOC).
Golimumab (2009)

Golimumab, a human anti-TNFalpha IgG1kappa monoclonal antibody, was approved in the US and Canada in April 2009 as a treatment for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and is undergoing regulatory review in the EU for these indications. The product was developed by Centocor and Janssen Pharmaceutical KK (Johnson & Johnson subsidiaries), in collaboration with Schering-Plough and Mitsubishi Tanabe Pharma. Golimumab faces numerous protein therapeutic competitors on the market, but, as the first patient-administered, once-monthly dosed anti-TNFalpha drug, it will likely be an attractive option for patients.
Coexpression of the collagen-binding stress protein HSP47 gene and the alpha 1(I) and alpha 1(III) collagen genes in carbon tetrachloride-induced rat liver fibrosis. (1994)

HSP47 is a collagen-binding stress protein and is assumed to act as a collagen-specific molecular chaperone during the biosynthesis and secretion of procollagen in the living cell. The synthesis of HSP47 has been reported to correlate with that of collagen in several cell lines. We examined the expression of HSP47 mRNA during the progression of carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Northern blot analysis revealed that the expression of HSP47 mRNA was markedly induced during the progression of fibrosis in parallel with alpha 1(I) and alpha 1(III) collagen mRNAs. By in situ hybridization, the distribution of HSP47 transcripts was similar to that of alpha 1(I) collagen and was observed only in cells lining collagen fibrils. These collagen-positive cells were confirmed to be Ito cells by immunohistochemistry for desmin. The absence of high levels of HSP47 mRNA in the liver of rats treated with only a single administration of CCl4 indicated that the induction of HSP47 mRNA was not due to the direct effect of CCl4 as a stressor, but was due to the progression of liver fibrosis. The function of HSP47 in liver fibrosis will also be discussed.
A Dose-Response Study of Prophylactic Intravenous Ephedrine for the Prevention of Hypotension During Spinal Anesthesia for Cesarean Delivery (2000)

We investigated different doses of IV ephedrine as prophylaxis for hypotension during spinal anesthesia for cesarean delivery and found that the smallest effective dose was 30 mg. However, this dose did not completely eliminate hypotension, caused reactive hypertension in some patients, and did not improve neonatal outcome.
Early Adaptation and Acquired Resistance to CDK4/6 Inhibition in Estrogen Receptor–Positive Breast Cancer (2016)

Small-molecule inhibitors of the CDK4/6 cell-cycle kinases have shown clinical efficacy in estrogen receptor (ER)-positive metastatic breast cancer, although their cytostatic effects are limited by primary and acquired resistance. Here we report that ER-positive breast cancer cells can adapt quickly to CDK4/6 inhibition and evade cytostasis, in part, via noncanonical cyclin D1-CDK2-mediated S-phase entry. This adaptation was prevented by cotreatment with hormone therapies or PI3K inhibitors, which reduced the levels of cyclin D1 (CCND1) and other G1-S cyclins, abolished pRb phosphorylation, and inhibited activation of S-phase transcriptional programs. Combined targeting of both CDK4/6 and PI3K triggered cancer cell apoptosis in vitro and in patient-derived tumor xenograft (PDX) models, resulting in tumor regression and improved disease control. Furthermore, a triple combination of endocrine therapy, CDK4/6, and PI3K inhibition was more effective than paired combinations, provoking rapid tumor regressions in a PDX model. Mechanistic investigations showed that acquired resistance to CDK4/6 inhibition resulted from bypass of cyclin D1-CDK4/6 dependency through selection of CCNE1 amplification or RB1 loss. Notably, although PI3K inhibitors could prevent resistance to CDK4/6 inhibitors, they failed to resensitize cells once resistance had been acquired. However, we found that cells acquiring resistance to CDK4/6 inhibitors due to CCNE1 amplification could be resensitized by targeting CDK2. Overall, our results illustrate convergent mechanisms of early adaptation and acquired resistance to CDK4/6 inhibitors that enable alternate means of S-phase entry, highlighting strategies to prevent the acquisition of therapeutic resistance to these agents. Cancer Res; 76(8); 2301-13. ©2016 AACR.
An efficient semaphore implementation scheme for small-memory embedded systems (2002)

In object-oriented programming, updates to the state variables of objects (by the methods of the object) have to be protected through semaphores to ensure mutual exclusion. Semaphore operations are invoked each time an object is accessed, and this represents significant run-time overhead. This is of special concern in cost-conscious, small-size embedded systems-such as those used in automotive applications-where costs must be kept to an absolute minimum. Object-oriented programming can be feasible in such applications only if the OS provides efficient, low-overhead semaphores. The authors present a new semaphore implementation scheme which saves one context switch per semaphore lock operation in most circumstances and gives performance improvements of 18-25% over traditional semaphore implementation schemes.
Plasma metalloproteinase activity is enhanced in the euglobulin fraction of breast and lung cancer patients (2000)

Matrix metalloproteinases (MMP) have been implicated in tumor invasion and metastasis. We verified, by gelatin zymography, MMP activity in the euglobulin plasma fraction of 82 healthy controls, 66 patients with benign diseases and 149 patients with breast, lung, colon or brain cancer. The euglobulin fractions assayed showed 4 gelatinolytic bands of 62, 92, 120 and 200 kDa. The median (Md) value for 92 kDa-MMP activity was significantly increased in breast (Md 1.34 arbitrary units [AU]/ml plasma, range 0.0-7.2) and lung cancer patients (Md 1.43 AU/ml, range 0.0-3.6) compared with the controls (Md 0.48 AU/ml, range 0.0-1.8). Patients with colon cancer or gliomas presented values of MMP-9 similar to those of the healthy population. Multivariate analysis indicated that plasma MMP-9 activity was not predicted by the known clinicopathological parameters such as age, stage, tumor size, number of positive lymph nodes, histologic grade, histologic type, nuclear grade or mitotic index. Lung cancer patients also presented high values of MMP-9 (Md 1.43, range 0.0-3.6 [n = 26]), without association with tumor stage or histologic type. The levels of 92 kDa-MMP activity in the plasma euglobulin fraction could be a potentially useful tumor marker in breast and lung cancer.