gebhart/patrepeval huggingface dataset:
Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B (1994)

The therapeutic efficacy of the immunoglobulin G1 (IgG1) monoclonal antibody (MAb) 2H1 to the Cryptococcus neoformans capsular polysaccharide was studied with and without amphotericin B (AmB) in a murine model of intravenous (i.v.) infection. MAb and AmB were administered by intraperitoneal (i.p.) injection after i.v. infection with a C. neoformans serotype D strain. Intraperitoneal administration of MAb 2H1 resulted in rapid distribution to the intravascular compartment, and the half-lives of i.p. and i.v. administered MAb were similar. Administration of MAb 2H1 alone resulted in increased survival, decreased lung fungal burden, and reduced serum glucuronoxylomannan antigen levels when given 2 to 6 h but not 24 h after infection. In vivo, the combination of MAb 2H1 and AmB was more effective at prolonging survival than either agent alone. MAbs of IgM, IgG1, IgG3, and IgA isotypes given 1 day after infection were effective in reducing serum GXM-D levels, with their relative efficacy being IgG1 > IgG3 > IgM > IgA. In vitro, MAb 2H1 was a potent opsonin of C. neoformans and the combination of MAb 2H1 and AmB was more effective than either agent alone in decreasing C. neoformans colony counts in the presence of the murine macrophage cell line J774.16. The results confirm that capsule-binding MAbs can enhance the effect of AmB against C. neoformans and provide support for considering combined therapy in humans.
Nanoparticle-assisted Combination Therapies for Effective Cancer Treatment (2010)

Combination chemotherapy and nanoparticle drug delivery are two areas that have shown significant promise in cancer treatment. Combined therapy of two or more drugs promotes synergism among the different drugs against cancer cells and suppresses drug resistance through distinct mechanisms of action. Nanoparticle drug delivery, on the other hand, enhances therapeutic effectiveness and reduces side effects of the drug payloads by improving their pharmacokinetics. These two active research fields have been recently merged to further improve the efficacy of cancer therapeutics. This review article summarizes the recent efforts in developing nanoparticle platforms to concurrently deliver multiple types of drugs for combination chemotherapy. We also highlight the challenges and design specifications that need to be considered in optimizing nanoparticle-based combination chemotherapy.
Azasteroids as inhibitors of rat prostatic 5.alpha.-reductase (1984)

A series of A-ring heterocyclic steroids has been prepared and tested for inhibition of rat prostatic steroid 5 alpha-reductase in vitro. Strikingly high inhibitory activity was found with a group of 17 beta-substituted 4-methyl-4-aza-5 alpha-androstan-3-ones. These compounds were prepared from 3-keto-delta 4-precursors by oxidative (O3 or NaIO4-KMnO4) A-ring cleavage followed, in turn, by ring closure with an amine and hydrogenation over platinum catalyst. Other A-ring azasteroids were made by Beckmann rearrangement of oximes of 2-oxo-A-nor, 3-oxo- and 4-oxo-5 alpha-androstanes. An A-nor-2-oxo-3-azasteroid was prepared by oxidative decarbonylation of a precursor 2,3-dioxo-4-azasteroid with m-chloroperbenzoic acid. A-ring modifications of the 4-azasteroids included delta 1-unsaturation, 2- and 4-substituents, and 3-carbonyl replacements. Side chains at the 17-position were varied with an emphasis on carboxylate derivatives (salts, esters, and amides).
Capacity scaling in MIMO wireless systems under correlated fading (2002)

Previous studies have shown that single-user systems employing n-element antenna arrays at both the transmitter and the receiver can achieve a capacity proportional to n, assuming independent Rayleigh fading between antenna pairs. We explore the capacity of dual-antenna-array systems under correlated fading via theoretical analysis and ray-tracing simulations. We derive and compare expressions for the asymptotic growth rate of capacity with n antennas for both independent and correlated fading cases; the latter is derived under some assumptions about the scaling of the fading correlation structure. In both cases, the theoretic capacity growth is linear in n but the growth rate is 10-20% smaller in the presence of correlated fading. We analyze our assumption of separable transmit/receive correlations via simulations based on a ray-tracing propagation model. Results show that empirical capacities converge to the limit capacity predicted from our asymptotic theory even at moderate n = 16. We present results for both the cases when the transmitter does and does not know the channel realization.
NKG2D receptor regulates human effector T-cell cytokine production (2011)

Abstract Although innate immune signals shape the activation of naive T cells, it is unclear how innate signals influence effector T-cell function. This study determined the effects of stimulating the NKG2D receptor in conjunction with the TCR on human effector CD8+ T cells. Stimulation of CD8+ T cells through CD3 and NKG2D simultaneously or through a chimeric NKG2D receptor, which consists of NKG2D fused to the intracellular region of CD3ζ, activated β-catenin and increased expression of β-catenin–induced genes, whereas T cells stimulated through the TCR or a combination of the TCR and CD28 did not. Activation by TCR and NKG2D prevented expression and production of anti-inflammatory cytokines IL-10, IL-9, IL-13, and VEGF-α in a β-catenin– and PPARγ- dependent manner. NKG2D stimulation also modulated the cytokine secretion of T cells activated simultaneously through CD3 and CD28. These data indicate that activating CD8+ T cells through the NKG2D receptor along with the TCR modulates signal transduction and the production of anti-inflammatory cytokines. Thus, human effector T cells alter their function depending on which innate receptors are engaged in conjunction with the TCR complex.
An accurate LNS arithmetic unit using interleaved memory function interpolator (2002)

A logarithmic number system (LNS) arithmetic unit using a new method for polynomial interpolation in hardware is described. The use of an interleaved memory reduces storage requirements by allowing each stored function value to be used in interpolation across several segments. This strategy always uses fewer words of memory than an optimized polynomial with stored polynomial coefficients. Many accuracy requirements for the LNS arithmetic unit are possible, but a round to nearest cannot be easily achieved. The goal suggested here is to ensure that the worst case LNS relative error is smaller than the worst case FP relative error. Using the interleaved memory interpolator, the detailed design of an LNS arithmetic unit is performed using a second-order polynomial interpolator including approximately 91K bits of ROM.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intrathecal gene transfer by adeno-associated virus for pain. (2005)

Chronic pain is among the most prevalent medical problems, affecting more than half of patients with advanced cancer and many with other common diseases. Current analgesics often fail to provide satisfactory symptom relief and frequently cause severe side effects. Intrathecal (IT) gene transfer is an attractive method for pain research in rodent models, because it allows targeting of a wide variety of secretable peptides and proteins to the spinal cord, an important neural center for the processing of nociceptive signals. The potential of IT gene transfer for improving opioid therapy and for validating new analgesic targets, such as cytokines involved in spinal glial activation, is discussed. The IT space has been notoriously resistant to efficient gene transfer, limiting therapeutic gene expression to less than 2 weeks with most vector systems. Recent progress with adeno-associated virus (AAV) technology allowed efficient long-term gene expression, facilitating studies reflective of the chronic nature of many pain states. AAV is one of the most advanced gene therapy vectors currently undergoing clinical trials for a variety of disorders. In patients, AAV vectors could be administered intrathecally by a lumbar puncture, a safe procedure routinely performed at the bedside. AAV vectors may therefore become an important tool for translational studies to validate newly identified therapeutic targets in clinical pain states.
KRAS Mutations in Non-Small Cell Lung Cancer (2009)

Some non-small cell lung cancers (NSCLCs) harbor a single specific mutated oncogene that is thought to be the primary genetic "driver" leading to cancer. The two most commonly mutated oncogenes in lung cancer encode for the epidermal growth factor receptor (EGFR) and KRAS. EGFR kinase domain mutations were only recently identified, but they have already been established in the clinic as valid predictors of increased sensitivity to EGFR kinase inhibitors (gefitinib and erlotinib). By contrast, even though KRAS mutations were identified in NSCLC tumors more than 20 years ago, we have only just begun to appreciate the clinical value of KRAS tumor status. Recent studies indicate that patients with mutant KRAS tumors fail to benefit from adjuvant chemotherapy, and their disease does not respond to EGFR inhibitors. There is a dire need for therapies specifically for patients with KRAS mutant NSCLC. In this review, we summarize the initial discovery of RAS mutations in NSCLC, describe work exploring associations with clinical factors and outcomes, and provide an overview of current approaches to targeting KRAS mutant NSCLC.
An investigation of InxGa1−xAs/GaAs quantum wells grown by molecular-beam epitaxy (1988)

Photoluminescence (PL) and transmission electron microscopy have been used to study strained InxGa1−xAs/GaAs (x=0.24–0.28) quantum wells (QWs) grown by molecular-beam epitaxy. The three QWs grown without growth interruptions produce high intensity PL peaks of narrow full width at half-maximum (2.9 meV). On the other hand, the PL peaks in the QWs grown with 30-s interruptions are relatively broad, less symmetric, and show lower PL intensities, compared with the noninterrupted QWs. Our results show that high-quality strained InxGa1−xAs/GaAs QWs can be grown without growth interruptions.
In Vivo Efficacy of Anti-Glycoprotein 41, But Not Anti-Glycoprotein 120, Immunotoxins in a Mouse Model of HIV Infection (2003)

Immunotoxins (ITs) targeting the HIV envelope protein are among the most efficacious antiviral therapies when tested in vitro. Yet a first-generation IT targeted to gp120, CD4-PE40 (chimeric immunotoxin using CD4 and the translocation and enzymatic domains of Pseudomonas exotoxin A), showed limited promise in initial clinical testing, highlighting the need for improved ITs. We have used a new mouse model of HIV infection to test the comparative efficacy of anti-HIV ITs targeted to gp120 or to gp41. Irradiated SCID/nonobese diabetic mice are injected with a tumor of human CD4(+) cells susceptible to infection and at a separate site persistently HIV-infected cells. The spread of infection from infected to susceptible tumor is monitored by plasma p24 and the presence of HIV-infected cells in the spleen. Anti-gp41 ITs in combination with tetrameric CD4-human Ig fusion protein have pronounced anti-HIV effects. Little if any anti-HIV efficacy was found with either CD4-PE40 or an Ab-targeted anti-gp120 IT. These data support continued exploration of the utility of ITs for HIV infection, particularly the use of anti-gp41 ITs in combination with soluble CD4 derivatives.
"Let There Be Light": Examining Interfaces for Homes of the Future. (2001)

As smart devices proliferate in the home and become universally networked, users will experience an increase in both the number of the devices they can control and the available interaction modalities for controlling them. Researchers have explored the possibilities of speechand gesturebased interfaces in desktop scenarios, but it is also necessary to explore these technologies in the context of an intelligent environment, one in which the user’s focus moves off of the desktop and into a physically disparate set of networked smart devices. We report results from a lab study where six families tried various traditional and nontraditional interfaces for controlling lights in the home. Results indicate that speech is the preferred interface for controlling lights. More importantly, the study indicates location awareness and gaze tracking are vital when building a usable intelligent environment system for the home, even though users did not perceive added value from these technologies.
Properties of orderly recruited motor units with tripolar cuff electrode (1988)

Summary form only given, as follows. Motor units of the soleus and m. gastrocnemius muscles were recruited in order according to size with stimuli delivered by a tripolar nerve cuff electrode. One stimulus controlled the firing rate, while the second recruited the motor units, with the electrode's center pole serving both stimuli. A series of test procedures verified that motor units were indeed recruited according to their size, that firing rate increase and motor unit recruitment were independent of each other, that a wide range of firing rate and recruitment control strategies could be implemented, and that the force fatigue profile showed resistance at low recruitment levels and progressive susceptibility as larger motor units were recruited.
Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins (2015)

Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive mutagenesis of expression plasmids and RNAi screening, we reveal that circularization of the Drosophila laccase2 gene is regulated by both intronic repeats and trans-acting splicing factors. Analogous to what has been observed in humans and mice, base-pairing between highly complementary transposable elements facilitates backsplicing. Long flanking repeats (∼ 400 nucleotides [nt]) promote circularization cotranscriptionally, whereas pre-mRNAs containing minimal repeats (<40 nt) generate circular RNAs predominately after 3' end processing. Unlike the previously characterized Muscleblind (Mbl) circular RNA, which requires the Mbl protein for its biogenesis, we found that Laccase2 circular RNA levels are not controlled by Mbl or the Laccase2 gene product but rather by multiple hnRNP (heterogeneous nuclear ribonucleoprotein) and SR (serine-arginine) proteins acting in a combinatorial manner. hnRNP and SR proteins also regulate the expression of other Drosophila circular RNAs, including Plexin A (PlexA), suggesting a common strategy for regulating backsplicing. Furthermore, the laccase2 flanking introns support efficient circularization of diverse exons in Drosophila and human cells, providing a new tool for exploring the functional consequences of circular RNA expression across eukaryotes.
Dislocation density in GaN determined by photoelectrochemical and hot-wet etching (2000)

Defects in GaN layers grown by hydride vapor-phase epitaxy have been investigated by photoelectrochemical (PEC) etching, and by wet etching in hot H3PO4 acid and molten potassium hydroxide (KOH). Threading vertical wires (i.e., whiskers) and hexagonal-shaped etch pits are formed on the etched sample surfaces by PEC and wet etching, respectively. Using atomic-force microscopy, we find the density of “whisker-like” features to be 2×109 cm−2, the same value found for the etch-pit density on samples etched with both H3PO4 and molten KOH. This value is comparable to the dislocation density obtained in similar samples with tunneling electron microscopy, and is also consistent with the results of Youtsey and co-workers [Appl. Phys. Lett. 73, 797 (1998); 74, 3537 (1999)].
Purification to homogeneity and enzymatic characterization of an alpha-N-acetylgalactosaminide alpha 2 leads to 6 sialyltransferase from porcine submaxillary glands. (1979)

By means of affinity chromatography on CDP-hexanolamine-agarose, a CMP-N-acetylneuraminate: alpha-N-acetylgalactosaminide alpha 2 leads to 6 sialyltransferase (EC 2.4.99.1) has been purified 117,000-fold to homogeneity from Triton X-100 extracts of porcine submaxillary glands. The enzyme consists of several electrophoretic forms that can be partially resolved by chromatography on Sephadex G-200, the largest of which has a molecular weight of approximately 160,000 as estimated by sodium dodecyl sulfate-gel electrophoresis. Periodate oxidation studies show that the linkage formed by this enzyme with ovine submaxillary asialo-mucin as the acceptor substrate is NeuAc alpha 2 leads to 6GalNAc alpha 1 leads to O-Thr/Ser. On the basis of initial rate studies and the patterns of inhibition observed with alternate acceptor substrates, the transferase is proposed to have either a random equilibrium kinetic mechanism or an ordered steady state mechanism with the acceptor substrate binding first. Among a wide variety of oligosaccharides, glycoproteins, and simple glycosides (including p-nitrophenyl-alpha-N-acetylgalactosaminide), the only acceptor substrates for this enzyme are those glycoproteins containing the structure, R leads to 3GalNAc alpha 1 leads to O-Thr/Ser, where R may be H or a beta-galactoside.
Fate of the DNA in plasmid-containing Escherichia coli minicells ingested by human neutrophils (1987)

Escherichia coli minicells containing the plasmid pSC101 (approximately 10 kb) or pBR322 (approximately 4 kb) were opsonized and incubated with human neutrophils. The neutrophils responded to the minicells as they would to native E coli: they ingested the minicells, discharged their granule contents into the minicell-containing phagosomes, and expressed a respiratory burst. After one hour of incubation, the fate of the ingested plasmid DNA was examined. No DNA degradation was detected by trichloroacetic acid precipitation or agarose gel electrophoresis. Moreover, when pBR322 recovered from ingested minicells was transformed into E coli, no mutations in either of the antibiotic resistance genes carried by the plasmid were detected out of many thousand transformants screened. These findings confirm the surprisingly limited effect of neutrophils on ingested DNA.
The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases (2007)

We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.
Crystallization and preliminary X-ray crystallographic analysis of shikimate kinase fromErwinia chrysanthemi (1997)

Shikimate kinase from Erwinia chrysanthemi, overexpressed in Escherichia coli has been crystallized by the vapour-diffusion method using sodium chloride as a precipitant. Mass spectrometry was used to confirm the purity of the shikimate kinase and dynamic light scattering was used to assess conditions for the monodispersity of the enzyme. The crystals are tetragonal, space group P4(1)2(1)2 or enantiomorph with cell dimensions a = b = 108.5 and c = 92.8 A (at 100 K). Native crystals diffract to better than 2.6 A on a synchrotron X-ray source. The asymmetric unit is likely to contain two molecules, corresponding to a packing density of 3.6 A(3) Da(-1).
Synthesis of alkyl-.BETA.-D-thioglucopyranosides, a series of new nonionic detergents. (1985)

As a part of our search for new types of detergent useful for biological applications, a series of alkyl-β-D-thioglucopyranosides was synthesized in several steps from glucose. The overall yield was about 80%. Critical micelle concentrations of n-hexyl-, n-heptyl-, n-octyl-, and n-nonyl-β-D-thioglucopyranoside were determined. Because of their electroneutrality, high solubility in water and high critical micelle concentration, n-heptyl-and n-octyl-β-D-thioglucopyranoside seem to be potentially useful detergents for applications in biological systems.
Printed thin-film transistors and complementary logic gates that use polymer-coated single-walled carbon nanotube networks (2005)

This paper reports on the electrical properties of thin-film transistors (TFTs) that use polymer-coated networks of single-walled carbon nanotubes (SWNTs) as the semiconductor with source and drain electrodes formed by high-resolution printing techniques. P-channel, n-channel, and ambipolar TFTs are demonstrated with bare SWNT networks, networks coated with polyethylene imine and with polyethylene oxide, respectively. Studies of the scaling of properties with channel length and tube density reveal important information about the operation of these devices. Complementary inverters made with n- and p-channel devices show gain larger than one and illustrate the potential use of these types of TFTs for complex logic circuits.
Expression of the stem cell factor receptor C-KIT (CD117) in acute leukemias. (1998)

Membrane expression of CD117 can be found on leukemic blasts from approximately 60% of adult and childhood AML patients, often associated with an immature immunophenotype (CD34). Moreover, AML with t(8;21) are frequently CD117 positive. Despite earlier reports, most recent studies have not been able to demonstrate any significant prognostic impact of CD117 expression in either childhood or adult AML. A small proportion of T-lineage ALL (9%), mainly consisting of immature pro-T/pre-T-ALL, is CD117 positive. CD117 expression is rare in B-cell-precursor-ALL and occurs in less than 3% of cases. CD117 in combination with other antigens might facilitate the immunologic characterization of acute leukemias, especially those of myeloid and early T-cell origin.
Endothelial cell response to lactate: Implication of PAR modification of VEGF (2006)

Angiogenesis, the process of formation of new blood vessels from pre-existing one, occurs in many physiological and pathological conditions, most of which are underlined by hypoxia and resultant accumulation of lactate. Although lactate is known to induce angiogenesis, the mechanism of its action on endothelial cells (ECs) is not known. The present study was designed to examine the response of ECs to lactate. Morphological analysis revealed that human umbilical vein endothelial cells (HUVECs) in culture respond to lactate by switching over to angiogenic phenotype concomitant with upregulation of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2) as determined by reverse transcription-PCR (RT-PCR). Apart from increase in the levels of VEGF protein as determined by ELISA, chorio allantoic membrane (CAM) assay using the cell extracts revealed that lactate also increased the angiogenic potency of VEGF. Isolated VEGF, when blotted and subsequently probed with anti-PAR antibody, revealed considerable reduction in poly-adenosyl ribosylation of VEGF associated with a significant decrease in the levels of NAD(+), in presence of lactate. Thus it appears that ECs respond to lactate by increasing the production of VEGF and modulating its angiogenic potency through poly-ADP ribosylation (PAR)-dependent mechanism and thereby switch over to angiogenic phenotype.