gebhart/patrepeval huggingface dataset:
Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors (2010)

Ketones have previously shown beneficial effects in models of neurodegenerative disorders, particularly against associated mitochondrial dysfunction and cognitive impairment. However, evidence of a synaptic protective effect of ketones remains lacking. We tested the effects of ketones on synaptic impairment induced by mitochondrial respiratory complex (MRC) inhibitors using electrophysiological, reactive oxygen species (ROS) imaging and biochemical techniques. MRC inhibitors dose-dependently suppressed both population spike (PS) and field potential amplitudes in the CA1 hippocampus. Pre-treatment with ketones strongly prevented changes in the PS, whereas partial protection was seen in the field potential. Rotenone (Rot; 100 nmol/L), a MRC I inhibitor, suppressed synaptic function without altering ROS levels and PS depression by Rot was unaffected by antioxidants. In contrast, antioxidant-induced PS recovery against the MRC II inhibitor 3-nitropropionic acid (3-NP; 1 mmol/L) was similar to the synaptic protective effects of ketones. Ketones also suppressed ROS generation induced by 3-NP. Finally, ketones reversed the decreases in ATP levels caused by Rot and 3-NP. In summary, our data demonstrate that ketones can preserve synaptic function in CA1 hippocampus induced by MRC dysfunction, likely through an antioxidant action and enhanced ATP generation.
Membrane array technology for drug discovery. (2002)

Lipid membrane arrays are a new technology emerging at the interface of materials science and cell biology. A defining feature of the membrane array architecture is the naturally fluid and functional state of the lipid bilayer membrane, which is maintained in an array of discrete corrals on a solid substrate. Solid-supported membrane arrays are beginning to find important applications in academic research. Recent developments in membrane array manufacturing are positioning this technology to make the transition into industrial drug discovery programs.
Selection of myeloid progenitors lacking BCR/ABL mRNA in chronic myelogenous leukemia patients after in vitro treatment with the tyrosine kinase inhibitor genistein (1996)

Chronic myelogenous leukemia (CML) is a clonal disorder of the hematopoietic stem cell characterized by a chimeric BCR/ABL gene giving rise to a 210-kD fusion protein with dysregulated tyrosine kinase activity. We investigated the effect of genistein, a protein tyrosine kinase inhibitor, on the in vitro growth of CML and normal marrow-derived multi-potent (colony-forming unit-mix [CFU-Mix]), erythroid (burst-forming unit-erythroid [BFU-E]), and granulocyte-macrophage (colony-forming unit-granulocyte-macrophage [CFU-GM]) hematopoietic progenitors. Continuous exposure of CML and normal marrow to genistein induced a statistically significant and dose-dependent suppression of colony formation. Genistein doses causing 50% inhibition of CML and normal progenitors were not significantly different for CFU-Mix (27 mumol/L v 23 mumol/L), BFU-E (31 mumol/L v 29 mumol/L), and CFU-GM (40 mumol/L v 32 mumol/L v 32 mumol/L). Preincubation of CML and normal marrow with genistein (200 mumol/ L for 1 to 18 hours) induced a time-dependent suppression of progenitor cell growth, while sparing a substantial proportion of long-term culture-initiating cells (LTC-IC) from CML (range, 91% +/- 9% to 32% +/- 3%) and normal marrow (range, 85% +/- 8% to 38% +/- 9%). Analysis of individual CML colonies for the presence of the hybrid BCR/ABL mRNA by reverse transcription-polymerase chain reaction (RT-PCR) showed that genistein treatment significantly reduced the mean +/- SD percentage of marrow BCR/ABL+ progenitors both by continuous exposure (76% +/- 18% v 24% +/- 12%, P < or = .004) or preincubation (75% +/- 16% v 21% +/- 10%, P < or = .002) experiments. Preincubation with genistein reduced the percentage of leukemic LTC-IC from 87% +/- 12% to 37% +/- 12% (P < or = .003). Analysis of individual colonies by cytogenetics and RT-PCR confirmed that genistein-induced increase in the percentage of nonleukemic progenitors was not due to suppression of BCR/ABL transcription. Analysis of nuclear DNA fragmentation by DNA gel electrophoresis and terminal deoxynucleotidyl transferase assay showed that preincubation of CML mononuclear and CD34+ cells with genistein induced significant evidence of apoptosis. These observations show that genistein is capable of (1) exerting a strong antiproliferative effect on CFU-Mix, BFU-E, and CFU-GM while sparing the more primitive LTC-IC and (2) selecting benign hematopoietic progenitors from CML marrow, probably through an apoptotic mechanism.
Dielectric behavior of moist swelling clay soils at microwave frequencies (1997)

The dielectric properties of Australian vertisol, a clay soil in which bulk density changes substantially with water content, are investigated by microwave transmission measurements. It is shown that the soil permittivity model of Hallikainen at al. (1985) is not directly applicable to this soil; alternative regression formulae are presented.
Linear-After-The-Exponential Polymerase Chain Reaction and Allied Technologies (2007)

Accurate detection of gene sequences in single cells is the ultimate challenge to polymerase chain reaction (PCR) sensitivity. Unfortunately, commonly used conventional and real-time PCR techniques are often too unreliable at that level to provide the accuracy needed for clinical diagnosis. Here we provide details of linear-after-the-exponential-PCR (LATE-PCR), a method similar to asymmetric PCR in the use of primers at different concentrations, but with novel design criteria to ensure high efficiency and specificity. Compared with conventional PCR, LATE-PCR increases the signal strength and allele discrimination capability of oligonucleotide probes such as molecular beacons and reduces variability among replicate samples. The analysis of real-time kinetics of LATEPCR signals provides a means for improving the accuracy of single cell genetic diagnosis.
Purification and Partial Characterization of &beta;-Glucosidase from Fresh Leaves of Tea Plants (&lt;italic&gt;Camellia sinensis&lt;/italic&gt; (L.) O. Kuntze) (2005)

beta-Glucosidases are important in the formation of floral tea aroma and the development of resistance to pathogens and herbivores in tea plants. A novel beta-glucosidase was purified 117-fold to homogeneity, with a yield of 1.26%, from tea leaves by chilled acetone and ammonium sulfate precipitation, ion exchange chromatography (CM-Sephadex C-50) and fast protein liquid chromatography (FPLC; Superdex 75, Resource S). The enzyme was a monomeric protein with specific activity of 2.57 U/mg. The molecular mass of the enzyme was estimated to be about 41 kDa and 34 kDa by SDS-PAGE and FPLC gel filtration on Superdex 200, respectively. The enzyme showed optimum activity at 50 deg;C and was stable at temperatures lower than 40 degrees C. It was active between pH 4.0 and pH 7.0, with an optimum activity at pH 5.5, and was fairly stable from pH 4.5 to pH 8.0. The enzyme showed maximum activity towards pNPG, low activity towards pNP-Galacto, and no activity towards pNP-Xylo.
Effects of aromatase inhibition on sexual function and well-being in postmenopausal women treated with testosterone: a randomized, placebo-controlled trial (2006)

Increases in total and free T in the physiologic range in postmenopausal women were associated with improved sexual satisfaction, well-being, and mood. In this study, aromatase inhibition did not influence any of these outcomes. Short-term transdermal T therapy did not modify fasting lipids, lipoprotein(a), or C-reactive protein.
Information, marketing, and pricing in the U.S. antiulcer drug market. (1995)

Introduced into the United States in 1977, Tagamet was the pioneer product in the class of antiulcer drugs known as H2antagonists. By promoting ulcer healing through inhibiting acid secretion, Tagamet was able to heal ulcers and treat pre-ulcer conditions pharmacologically on an outpatient basis, thereby substituting for more costly hospital admissions and surgeries. In 1983 another H2-antagonist called Zantac entered, and by early 1987 U.S. Zantac sales surpassed those of the pioneering Tagamet. Today there are four H2-antagonists sold in the United States: Tagamet, Zantac, Pepcid, and Axid. Zantac is now the world's largest selling prescription drug, having estimated worldwide sales in 1994 of about $4 billion. Each of the four H2-antagonists is among the top 100 in world drug sales, although Tagamet lost U.S. patent protection on May 17, 1994. In this paper we examine empirically the role of information in facilitating and explaining growth of the overall antiulcer drug market, as well as in shaping the changing market shares of the four patented products. The dissemination of information is due largely to the use of marketing channels, such as visits by manufacturers' representatives to physicians (called detailing), advertising in medical journals, and most recently, by direct-to-consumer advertising. We examine these and also explore pricing policies, product differentiation, and orderof-entry effects.
Hysteroscopic insemination of mares with low numbers of nonsorted or flow sorted spermatozoa (2002)

The objectives of this study were 1) to compare pregnancy rates resulting from 2 methods of insemination using low sperm numbers and 2) to compare pregnancy rates resulting from hysteroscopic insemination of 5 x 106 nonsorted and 5 x 106 spermatozoa sorted for X- and Y-chromosome-bearing populations (flow sorted). Semen was collected with an artificial vagina from 2 stallions of known acceptable fertility. Oestrus was synchronised (June to July) in 40 mares, age 3-10 years, by administering 10 ml altrenogest orally for 10 consecutive days, followed by 250 microg cloprostenol i.m. on Day 11. All mares were given 3000 iu hCG i.v. at the time of insemination to induce ovulation. Mares were assigned randomly to 1 of 3 treatment groups: mares in Treatment 1 (n = 10) were inseminated with 5 x 10(6) spermatozoa deposited deep into the uterine horn with the aid of ultrasonography. Mares in Treatment 2 (n = 10) were inseminated with 5 x 10(6) spermatozoa deposited onto the uterotubal junction papilla via hysteroscopic insemination. Mares in Treatment 3 (n = 20) were inseminated using the hysteroscopic technique with 5 x 10(6) flow sorted spermatozoa. Spermatozoa were stained with Hoechst 33342 and sorted into X- and Y-chromosome-bearing populations based on DNA content using an SX MoFlo sperm sorter. Pregnancy was determined ultrasonographically at 16 days postovulation. Hysteroscopic insemination resulted in more pregnancies (5/10 = 50%) than did the ultrasound-guided technique (0/10 = 0%; P<0.05) when nonsorted sperm were inseminated. Pregnancy rates were not significantly lower (P>0.05) when hysteroscopic insemination was used for sorted (5/20 = 25%) and nonsorted spermatozoa (5/10 = 50%). Therefore, hysteroscopic insemination of low numbers of flow sorted stallion spermatozoa resulted in reasonable pregnancy rates.
TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients (2014)

Only a minority of myelodysplastic syndrome (MDS) patients respond to hypomethylating agents (HMAs), but strong predictors of response are unknown. We sequenced 40 recurrently mutated myeloid malignancy genes in tumor DNA from 213 MDS patients collected before treatment with azacitidine (AZA) or decitabine (DEC). Mutations were examined for association with response and overall survival. The overall response rate of 47% was not different between agents. Clonal TET2 mutations predicted response (odds ratio [OR] 1.99, P = .036) when subclones unlikely to be detected by Sanger sequencing (allele fraction <10%) were treated as wild-type (WT). Response rates were highest in the subset of TET2 mutant patients without clonal ASXL1 mutations (OR 3.65, P = .009). Mutations of TP53 (hazard ratio [HR] 2.01, P = .002) and PTPN11 (HR 3.26, P = .006) were associated with shorter overall survival but not drug response. Murine-competitive bone marrow transplantation followed by treatment with AZA demonstrated that Tet2-null cells have an engraftment advantage over Tet2-WT cells. AZA significantly decreased this advantage for Tet2-null cells (P = .002) but not Tet2-WT cells (P = .212). Overall, Tet2 loss appears to sensitize cells to treatment with AZA in vivo, and TET2 mutations can identify patients more likely to respond to HMAs.
Thermoelectric power in porous silicon (1998)

Thermoelectric power measurements have been made on macroporous (pore width &amp;gt;500 Å°) porous silicon samples prepared by an anodic dissolution technique. The sign of thermopower is found to be negative indicating that conduction takes place due to electrons in the conduction band. The conduction mechanism is found to be due to variable range hopping near the Fermi level for temperatures below 150 K. At higher temperatures the conduction is due to the tunneling of carriers in the localized states in the band edges. It was concluded that these localized states are formed because the nanocrystallites in porous silicon are randomly distributed in size and orientation leading to fluctuations in band gap. This results in the constitution of a disordered system on a macroscopic scale.
Microvalves with bistable buckled polymer diaphragms (1996)

A microvalve with a bistable buckled diaphragm has been developed which can be employed for microfluidic systems. The bistable diaphragm is used to open or close the inlet of the microvalve. There is no power consumption either in the closed or in the open state, and the valve is closed tight against an inlet gas pressure of up to 470 hPa. The case of the valve is made by molding in PMMA and joined to a polyimide diaphragm thick by adhesive bonding. The temperature treatment and mechanical loading during bonding, and the different thermal expansions of PMMA and polyimide, result in a compressive stress and in buckling of the diaphragm. The microvalve has an outer diameter of 5 mm and is 1 mm thick.
World Health Organization classification of tumors (2000)

The World Health Organization announces a new series entitled World Health Organization Classification of Tumors. This continuation of the International Histological Classification of Tumors project will include information on molecular genetics and will cover all tumor sites within the next 5 years.
Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy. (2000)

The Na+/I- symporter (NIS) present in the membranes of thyroid cells is responsible for the capacity of the thyroid to concentrate iodide. This allows treatment of thyroid cancers with 131I. We propose to enlarge this therapeutic strategy to nonthyroid tumors by using an adenoviral vector to deliver the NIS gene into the tumor cells. We constructed a recombinant adenovirus encoding the rat NIS gene under the control of the cytomegalovirus promoter (AdNIS). Infection of SiHa cells (human cervix tumor cells) with AdNIS resulted in perchlorate-sensitive 125I uptake by these cells to a level 125-225 times higher than that in noninfected cells. Similar results were obtained for other human tumor cell lines, including MCF7 and T-47D (mammary gland), DU 145 and PC-3 (prostate), A549 (lung), and HT-29 (colon), demonstrating that the AdNIS vector can function in tumor cells of various origins. In addition, AdNIS-infected tumor cells were selectively killed by exposure to 131I, as revealed by clonogenic assays. To assess the efficiency of this cancer gene therapy strategy in vivo, we injected the AdNIS vector in human tumors (SiHa or MCF7 cells) established s.c. in nude mice. Immunohistological analysis confirmed the expression of the NIS protein in the tumor. Three days after intratumoral injection, AdNIS-treated tumors could specifically accumulate 125I or 123I, as revealed by kinetics and imaging experiments. A quantitative analysis demonstrated that the uptake in AdNIS-injected tumors was 4-25 times higher than that in nontreated tumors. On average, 11% of the total amount of injected 125I could be recovered per gram of AdNIS-treated tumor tissue. Altogether, these data indicate that AdNIS is very efficient in triggering significant iodide uptake by a tumor, outlining the potential of this novel cancer gene therapy approach for a targeted radiotherapy.
Configuration and dynamic reconfiguration of component-based applications with microsoft .NET (2004)

Dynamic reconfiguration provides of powerful mechanism to adapt component-based distributed applications to changing environmental conditions. We have designed and implemented a framework for dynamic component reconfiguration on the basis of the Microsoft .NET environment. Within this paper we present an experimental evaluation of our infrastructure for dynamic reconfiguration of component-based applications. Our framework supports the description of application configurations and profiles and allows for selection of a particular configuration and object/component instantiation based on measured environmental conditions. In response to changes in the environment, our framework will dynamically load new configurations, thus implementing dynamic reconfiguration of an application. Configuration code for components and applications has to interact with many functional modules and therefore is often scattered around the whole application. We use aspect-oriented programming techniques to handle configuration aspects separately from functional code. The timing behavior of dynamic reconfiguration depends heavily on properties of the underlying programming environment and the operating system. We have studied to which extend and with which performance impact the Microsoft .NET Platform/sup 1/ supports dynamic reconfiguration. The paper thoroughly discusses our experimental results.
Geometry-enhanced magnetoresistance of narrow Au∕InAs hybrid structures incorporating a two-dimensional electron system (2006)

We have investigated the magnetoresistance of metal-semiconductor hybrid structures at 4.2 K. The devices consisted of polycrystalline Au and an InAs-based heterostructure that hosted a high-mobility two-dimensional electron system. We have varied the electrical parameters and, in particular, the width-to-length ratio W∕L of the linear hybrid structures. The recently discovered extraordinary magnetoresistance effect is most pronounced for narrow devices with W∕L⩽0.05, consistent with our theoretical prediction. Relative resistance changes with a factor of 1000 are observed at 1 T. To achieve this an interface resistance of only 10−8Ωcm2 is a prerequisite. This can be prepared routinely by in situ cleaved edge overgrowth.
Population differences in haplotype structure within a human olfactory receptor gene cluster (2002)

We investigated the population differences in patterns of single nucleotide polymorphisms (SNPs) for a 400 kb olfactory receptor (OR) gene cluster on human chromosome 17p13.3. Samples were drawn from 35 individuals, of four different ethnogeographical origins: Pygmies, Bedouins, Yemenite Jews and Ashkenazi Jews. Of the 74 SNPs identified, two segregated between pseudogenized and intact ORs, while a third involved a change in a highly conserved motif proposed to mediate ligand-induced signal transduction. Linkage disequilibrium (LD) was computed based on phase inference across the cluster using Clark's haplotype subtraction algorithm. We also calculated LD directly from the genotypes using the expectation-maximization (EM) algorithm. Both methods yielded very similar results. Our analyses revealed substantial differences in nucleotide diversity, haplotype distribution and LD patterns among the different human populations. In particular, the two Jewish populations had low haplotype diversity and negligible decay of LD across the entire genomic region. Intriguingly, the three functional SNPs segregated at different frequencies in the different ethnogeographical groups, with the Pygmies having higher frequencies of the intact OR genes. Our data suggests that OR genes may have evolved to create different functional repertoires in distinct human populations.
Efficient Intracellular siRNA Delivery by Ethyleneimine‐Modified Amphiphilic Macromolecules (2011)

New materials that can bind and deliver oligonucleotides such as short interfering RNA (siRNA) without toxicity are greatly needed to fulfill the promise of therapeutic gene silencing. Amphiphilic macromolecules (AMs) were functionalized with linear ethyleneimines to create cationic AMs capable of complexing with siRNA. Structurally, the parent AM is formed from a mucic acid backbone whose tetra-hydroxy groups are alkylated with 12-carbon aliphatic chains to form the hydrophobic component of the macromolecule. This alkylated mucic acid is then mono-functionalized with poly(ethylene glycol) (PEG) as a hydrophilic component. The resulting AM contains a free carboxylic acid within the hydrophobic domain. In this work, linear ethyleneimines were conjugated to the free carboxylic acid to produce an AM with one primary amine (1N) or one primary amine and four secondary amines (5N). Further, an AM with amine substitution both to the free carboxylic acid in the hydrophobic domain and also to the adjacent PEG was synthesized to produce a polymer with one primary amine and eight secondary amines (9N), four located on each side of the AM hydrophobic domain. All amine-functionalized AMs formed nanoscale micelles but only the 5N and 9N AMs had cationic zeta potentials, which increased with increasing number of amines. All AMs exhibited less inherent cytotoxicity than linear polyethyleneimine (L-PEI) at concentrations of 10 µM and above. By increasing the length of the cationic ethyleneimine chain and the total number of amines, successful siRNA complexation and cellular siRNA delivery was achieved in a malignant glioma cell line. In addition, siRNA-induced silencing of firefly luciferase was observed using complexes of siRNA with the 9N AM and comparable to L-PEI, yet showed better cell viability at higher concentrations (above 10 µM). This work highlights the promise of cationic AMs as safe and efficient synthetic vectors for siRNA delivery. Specifically, a novel polymer (9N) was identified for efficient siRNA delivery to cancer cells and will be further evaluated.
Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with 18F-Labeled Affibody Molecule ZHER2:2395 in a Mouse Model for Ovarian Cancer (2011)

This study showed that (18)F-NOTA-Z(HER2)(:2395) is a promising new imaging agent for HER2 expression in tumors. Affibody molecules were successfully labeled with (18)F within 30 min, based on the complexation of Al(18)F by NOTA. Further research is needed to determine whether this technique can be used for patient selection for HER2-targeted therapy.
Anti-Flt1 Peptide, a Vascular Endothelial Growth Factor Receptor 1–Specific Hexapeptide, Inhibits Tumor Growth and Metastasis (2005)

We show that a peptide (anti-Flt1) specific for VEGFR1 inhibits growth and metastasis of tumor that secretes VEGF. The effects on endothelial cell functions, in vitro, indicate that the anticancer activity of anti-Flt1 peptide with reduced blood vessel density could also be due to the blocking of VEGFR1-mediated endothelial cell migration and tube formation. Although the effects of anti-Flt1 peptide still remain to be further characterized, the receptor 1-specific peptide antagonist, anti-Flt1, has potential as a therapeutic agent for various angiogenesis-related diseases, especially cancer.