gebhart/patrepeval huggingface dataset:
A novel DNA replication origin identified in the human heat shock protein 70 gene promoter. (1994)

A general and sensitive method for the mapping of initiation sites of DNA replication in vivo, developed by Vassilev and Johnson, has revealed replication origins in the region of simian virus 40 ori, in the regions upstream from the human c-myc gene and downstream from the Chinese hamster dihydrofolate reductase gene, and in the enhancer region of the mouse immunoglobulin heavy-chain gene. Here we report that the region containing the promoter of the human heat shock protein 70 (hsp70) gene was identified as a DNA replication origin in HeLa cells by this method. Several segments of the region were cloned into pUC19 and examined for autonomously replicating sequence (ARS) activity. The plasmids carrying the segments replicated episomally and semiconservatively when transfected into HeLa cells. The segments of ARS activity contained the sequences previously identified as binding sequences for a c-myc protein complex (T. Taira, Y. Negishi, F. Kihara, S. M. M. Iguchi-Ariga, and H. Ariga, Biochem. Biophys. Acta 1130:166-174, 1992). Mutations introduced within the c-myc protein complex binding sequences abolished the ARS activity. Moreover, the ARS plasmids stably replicated at episomal state for a long time in established cell lines. The results suggest that the promoter region of the human hsp70 gene plays a role in DNA replication as well as in transcription.
Factor IX Chongqing: a New Mutation in the Calcium-Binding Domain of Factor IX Resulting in Severe Hemophilia B (1990)

A Chinese patient with sporadic, severe hemophilia B was found to have a low level of total factor IX antigen (3.5 U/dl), but less apparent antigen in an assay using a calcium-dependent antibody fraction (1.1 U/dl). This suggested a defect in the factor IX Gla domain coded mainly by exon 2 of the factor IX gene. Exon 2 was therefore amplified and sequenced. An A to T substitution was found at nucleotide 6455 of the patient's factor IX gene. This transversion changes the codon for Glu 27 in normal factor IX to a codon for Val. Since Glu 27 becomes an essential Gla residue, the defect should result in altered calcium-binding or calcium-dependent conformation of the patient's factor IX. The introduction of a hydrophobic side chain also appears to affect the hemophilic protein's stability. In leukocyte DNA from the patient's mother, the nucleotide sequence of exon 2 was entirely normal. Thus, barring somatic mosaicism within her germ cells, the new mutation occurred in oogenesis of her ovary.
Phosphorene: An Unexplored 2D Semiconductor with a High Hole Mobility (2014)

We introduce the 2D counterpart of layered black phosphorus, which we call phosphorene, as an unexplored p-type semiconducting material. Same as graphene and MoS2, single-layer phosphorene is flexible and can be mechanically exfoliated. We find phosphorene to be stable and, unlike graphene, to have an inherent, direct, and appreciable band gap. Our ab initio calculations indicate that the band gap is direct, depends on the number of layers and the in-layer strain, and is significantly larger than the bulk value of 0.31-0.36 eV. The observed photoluminescence peak of single-layer phosphorene in the visible optical range confirms that the band gap is larger than that of the bulk system. Our transport studies indicate a hole mobility that reflects the structural anisotropy of phosphorene and complements n-type MoS2. At room temperature, our few-layer phosphorene field-effect transistors with 1.0 μm channel length display a high on-current of 194 mA/mm, a high hole field-effect mobility of 286 cm(2)/V·s, and an on/off ratio of up to 10(4). We demonstrate the possibility of phosphorene integration by constructing a 2D CMOS inverter consisting of phosphorene PMOS and MoS2 NMOS transistors.
Straw Production and Grain Yield Relationships in Winter Wheat (2001)

Winter wheat ( Triticum aestivum L.) –fallow is the predominant cropping system in low‐precipitation regions (&lt;250 mm annually) of the inland Pacific Northwest (PNW) in the USA. Wind erosion is a recurrent problem during and after fallow periods when inadequate crop residue amounts are retained on the soil surface. Management options that optimize both grain yield and straw production are needed. A 3‐yr field study was conducted to determine sowing rate and sowing date effects on straw and grain yield, and grain yield components of winter wheat cultivars with semidwarf, standard height, or tall growth habit. Four winter wheat cultivars were evaluated at three sowing rates (65, 130, and 195 seeds m −2 ) and three sowing dates in August, September, and October. A split plot design was used, with sowing dates as main plots and sowing rate × cultivar combinations as subplots. The greatest effect of sowing date was on straw production. Straw biomass from mid‐August sowing averaged 6.70 Mg ha −1 compared with 4.65 and 2.78 Mg ha −1 from mid‐September and mid‐October sowing, respectively. Grain yield was highest for mid‐August sowing during two years and lowest for mid‐October sowing all years. Averaged across years, the semidwarf cultivar produced the highest grain yield on all sowing dates and was equal to the standard height and tall cultivars for straw production. Path coefficient analysis showed that variation in grain yield was due primarily to differences in spikes per unit area (SPU) and kernels per spike (KPS). Late sowing resulted in a large reduction in SPU and, therefore, grain yield. For cropland susceptible to wind erosion in east‐central Washington, early sowing results in increased wheat straw production and generally higher grain yield compared with mid‐to‐late sowing dates.
The enemy within: intronic miR-26b represses its host gene,ctdsp2, to regulate neurogenesis (2012)

Differentiation of multipotent stem cells occurs through the highly coordinated control of gene expression. Repressor element 1 (RE1) silencing transcription factor (REST), a master transcriptional regulator in neuronal stem cells, restricts neuronal gene expression. REST activity is context-dependent and is modified by its cofactors, such as Ctdsp2. In this issue of Genes & Development, Dill and colleagues (pp. 25-30) report on the microRNA-mediated regulation of neural differentiation. Interestingly, this microRNA is post-transcriptionally regulated and modulates expression of its host gene, ctdsp2.
A simple tool for detecting undiagnosed diabetes and pre-diabetes (2008)

undiagnosed diabetes are 88%, 75%, 14%, 99.3%, and 0.85, respectively. For pre-diabetes or undiagnosed diabetes, the results are 75%, 65%, 49%, 85%, and 0.75, respectively. We validated the tool using v-fold cross-validation and performed an independent validation against NHANES 1999 –2004 data. CONCLUSIONS — The Diabetes Risk Calculator is the only currently available noninvasive screening tool designed and validated to detect both pre-diabetes and undiagnosed diabetes in the U.S. population. Diabetes Care 31:1040–1045, 2008
Nucleobase pairing and photodimerization in a biologically derived metal-organic framework nanoreactor (2019)

Biologically derived metal-organic frameworks (bio-MOFs) are of great importance as they can be used as models for bio-mimicking and in catalysis, allowing us to gain insights into how large biological molecules function. Through rational design, here we report the synthesis of a novel bio-MOF featuring unobstructed Watson-Crick faces of adenine (Ade) pointing towards the MOF cavities. We show, through a combined experimental and computational approach, that thymine (Thy) molecules diffuse through the pores of the MOF and become base-paired with Ade. The Ade-Thy pair binding at 40-45% loading reveals that Thy molecules are packed within the channels in a way that fulfill both the Woodward-Hoffmann and Schmidt rules, and upon UV irradiation, Thy molecules dimerize into Thy<>Thy. This study highlights the utility of accessible functional groups within the pores of MOFs, and their ability to 'lock' molecules in specific positions that can be subsequently dimerized upon light irradiation, extending the use of MOFs as nanoreactors for the synthesis of molecules that are otherwise challenging to isolate.
Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin (1989)

The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.
Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study (2011)

MicroRNAs may serve as useful biomarkers in OSCC and PSCC. The influence of HPV on miRNA may provide a mechanism for the distinct clinical behaviour of HPV-infected tumours.
Functional analysis of female‐biased odorant binding protein 6 for volatile and nonvolatile host compounds in Adelphocoris lineolatus (Goeze) (2017)

The polyphagous mirid bug Adelphocoris lineolatus relies heavily on olfactory cues to track suitable host plants. Thus, a better understanding of the molecular basis of its olfactory detection could contribute to the development of effective pest management strategies. In the present study, we report the expression profile of the odorant binding protein gene A. lineolatus odorant binding protein 6 (AlinOBP6). Quantitative real-time PCR experiments suggest that AlinOBP6 is female adult antennae-biased. Cellular immunolocalization analyses show that AlinOBP6 is highly expressed in the lymph of both multiporous sensilla basiconica and uniporous sensilla chaetica. A ligand binding analysis showed that recombinant AlinOBP6 not only bound tightly to host plant volatile compounds but also to nonvolatile compounds. Homology modelling and molecular docking analyses confirmed these unusual ligand binding profiles and revealed that the amino acid residues involved in the recognition of volatile and nonvolatile compounds are distinct. The results of our study are the first to suggest that an antenna- and female-biased OBP in an hemipteran insect is expressed in both olfactory and gustatory sensilla as a mechanism to respond to volatile and nonvolatile host compounds. These findings warrant further research into the molecular mechanisms of chemosensation for mirid bugs in responsive to host plant location.
Glyceraldehyde 3‐phosphate dehydrogenase modulates nonoxidative pentose phosphate pathway to provide anabolic precursors in hypoxic tumor cells (2018)

Cancer cells exhibit enhanced lactate production to satisfy biosynthetic adenosine triphosphate requirements and also supply ribose 5‐phosphate (R5P) and nicotinamide adenine dinucleotide phosphate via the pentose phosphate pathway (PPP). Yet, little is known about the mechanism by which glycolytic flux is diverted to PPP to fulfill the increased demand for anabolic precursors and reducing equivalents. Here we show, using a 13 C‐labeling methodology quantifying glycolysis and the PPP metabolism, that hypoxic cancer cells not only increase net glycolytic flux but also activate the exchange fluxes catalyzed by aldolase and transaldolase. The increased carbon exchange in the upward direction promotes the supplementation of R5P through the nonoxidative PPP and essentially controls the anaplerosis of upper glycolytic metabolites consumed for biosynthesis. This cascade of events is regulated by glyceraldehyde 3‐phosphate dehydrogenase which plays a critical role in diverting metabolites for the synthesis of nucleotide precursors and thus acts as a limiting enzyme under hypoxia. © 2018 American Institute of Chemical Engineers AIChE J , 64: 4289–4296, 2018
First Synthesis of Fully Modified 4′-SelenoRNA and 2′-OMe-4′-selenoRNA Based on the Mechanistic Considerations of an Unexpected Strand Break (2014)

This study investigated oligonucleotide (ON) synthesis containing 4'-selenoribonucleoside(s) under standard phosphoramidite conditions. Careful operation using a manual ON synthetic system revealed that an unexpected strand break occurred to afford a C2-symmetric homodimer as a byproduct. In addition, this side reaction occurred during I2 oxidation. On the basis of these findings, the first synthesis of fully modified 4'-selenoRNA and 2'-OMe-4'-selenoRNA was achieved using tert-butyl hydroperoxide (TBHP) as the alternative oxidant.
Response by J. Mars and J. W. Rector III to the reply by the author (1995)

We thank B. Zhou and S.A. Greenhalgh for their response. We would first like to correct Zhou and Greenhalgh. Our comments in the preceding discussion apply only to the invertibility of the τ‐p transform.
Measurement of Malondialdehyde in Plasma by High Performance Liquid Chromatography with Fluorimetric Detection (1991)

The thiobarbituric acid test for malondialdehyde is widely used as an indicator of lipid peroxidation and free radical activity. We describe a simple and sensitive high performance liquid chromatographic (HPLC) method for measuring the malondialdehyde-thiobarbituric acid adduct using fluorimetric detection. Extraction into organic solvent or other complex sample preparation is not required and the assay is sensitive to less than 0.05 mumol/L. This method could easily be applied to any setting where a measure of lipid peroxidation is required.
Cell damage in near-infrared multimode optical traps as a result of multiphoton absorption. (1996)

We report on cell damage of single cells confined in continuous-wave (cw), near-infrared (NIR) multimode optical traps as a result of multiphoton absorption phenomena. Trapping beams at NIR wavelengths less than 800 nm are capable of damaging cells through a two-photon absorption process. Cell damage is more pronounced in multimode cw traps compared with single-frequency true cw NIR traps because of transient power enhancement by longitudinal mode beating. Partial mode locking in tunable cw Ti:sapphire lasers used as trapping beam sources can produce unstable subnanosecond pulses at certain wavelengths that amplify multiphoton absorption effects significantly. We recommend the use of single-frequency long-wavelength NIR trapping beams for optical micromanipulation of vital cells.
Drift-Step-Recovery Diode Characterization by a Bipolar Pulsed Power Circuit (2012)

A stack of drift- step-recovery diodes (DSRDs) can produce high-voltage pulses with a rise rate of the order of 1 kV/ns. Their building blocks, i.e., the DSRD dies, are designed and manufactured at Soreq Nuclear Research Center based on silicon epitaxial layers. A characterization circuit for DSRDs is presented. The circuit features a power MOSFET, which serves to pump the DSRD in the forward direction and then to pulse it in the reverse direction, and a bias voltage source to balance the forward pumping current with respect to the reverse discharge. Placing the DSRD in series between the MOSFET and the load results in temporal and polarity separation of the MOSFET and DSRD pulses at the load, thus allowing viewing of the net DSRD signal. High-voltage probes are employed to measure the MOSFET and load voltages. Based on this measurement, we formulate the voltage and current extraction of the circuit signals. A 1-ns 190-V epi-Si DSRD die was characterized by this circuit. We show that the DSRD pulses when its reverse discharge is equal to the forward charge, as expected. The DSRD switching loss was measured. An accurate 98% energy balance, which includes the input and output energies with respect to the MOSFET and DSRD switching losses, was obtained. The relationship between the bias voltage, the pumping current, and the main supply voltage is provided. The experimental results are supported by a numerical simulation of the DSRD in the circuit using the Synopsys technological computer-aided design incorporated with a SPICE solver.
Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5'-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)- related toxicity compared with controls. (2001)

Deficiency of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-fluorouracil (5-FU) catabolism, has been linked to toxic side effects of 5-FU. The most prominent mutation of the DPD gene resulting in severe DPD deficiency is a G to A mutation in the GT 5'-splice recognition site of intron 14 (exon 14-skipping mutation). The corresponding mRNA lacks exon 14, and the enzymatic activity of the translated DPD protein is virtually absent. We developed a reverse transcription-PCR-based assay suitable for routine identification of the exon 14-skipping mutation and screened a control cohort of 851 Caucasian individuals as well as a cohort of 25 cancer patients reported by their physicians to have suffered from WHO grades 3-4 toxicity upon 5-FU chemotherapy. Within the control cohort, in total, eight heterozygotes were detected (0.94%): one heterozygote in 51 healthy donors, (1.96%); five heterozygotes in 572 hospital patients (0.87%); and two heterozygotes in 228 colorectal tumor patients (0.88%). Among the 25 patients with severe 5-FU-related toxicity, 5 (20%) were heterozygous and 1 (4%) was homozygous for the exon 14-skipping mutation. All six patients had experienced WHO grade 4 myelosuppression. Lethal outcome was seen in the homozygous and two of the heterozygous cases. We conclude that carriers of the DPD exon 14-skipping mutation are at significantly increased risk to experience life-threatening myelosuppression upon 5-FU treatment, even when the allelic status is heterozygous. These data lead us to suggest routine testing for the exon 14-skipping mutation before 5-FU treatment.
ADME‐Enabling Technologies in Drug Design and Development. Edited by Donglu Zhang and Sekhar Surapaneni (2013)

Wiley, Hoboken 2012. 622 pp., hardcover, $175.00.—ISBN 978-0-470-54278-1
The effect of elotuzumab on natural killer (NK) cell function against multiple myeloma (MM). (2011)

2572 Background: Elotuzumab (Elo), an anti-CS1 monoclonal antibody (mAb) in development for MM, exerts anti-MM effects via NK cell-mediated ADCC. CS1 is also expressed on NK cells. We provide data to suggest that Elo may enhance NK cell cytotoxicity via mechanisms beyond ADCC. Methods: Primary cells were procured under IRB-approved protocols. Interferon-gamma (IFN-g) and granzyme B (GrB) production were measured by ELISPOT, NK92 cytotoxicity was determined by chromium release. Flow cytometry characterized NK cell subsets and effects of Elo on NK cell activation. Elo, Elo-G2M3 (non-CD16 binding), and isotype mAbs were from Abbott Biotherapeutics Results: Pts with advanced MM have proportionally fewer cytotoxic CD56dim NK cells in peripheral blood (22%+/-2) vs. pts with early MM (69%+/-10, n=8, p=0.005). While Elo increased CD69 expression on healthy donor NK cells (22.8%+/-7) vs. isotype (4.8% +/- 3, n=5, p = 0.01), no increase in NK cell cytotoxicity against autologous NK cells was observed. Across a range of effector:target (E:T) ratios, Elo (and G2M3 at higher E:Ts) enhanced NK cell IFN-g production (e.g., E:T 25:1, control = 86+/-6, G2M3= 109+/-4, Elo = 275+/-12, p = 0.0001, all pair-wise comparisons significant) and GrB production (e.g., E:T 50:1, control = 113+/-11, G2M3 = 179+/-6, Elo = 331+/-25, p=0.0001, all pair-wise comparisons significant). Elo increased CD107a expression (9.3%+/-2.2) on NK cells in MM bone marrow aspirates vs. isotype control (5.8%+/-0.5, n=3, p = 0.04). Elo also enhanced the killing of CS1+ targets by CD16- NK92 cells. Conclusions: Elo activates NK cells and promotes cytotoxicity via IFN-g and GrB degranulation specifically directed against MM targets, observations confirmed by increased CD107a expression on NK cells in bone marrow of pts with MM. Elo facilitates NK cell function against MM by mechanisms in addition to ADCC based on 1) G2M3 enhancement of IFN-g and GrB production against MM cells, 2) Elo induced CD69 expression independent of presence of MM targets and 3) Elo-enhanced killing of CS1 expressing target cells by a CD16 negative NK cell line. Elo does not induce cytotoxicity against NK cells.
ChemInform Abstract: Creatones A and B. Revision of the Structure for the Product of Oxidation of Creatinine and Creatine. (1990)

Abstract Earlier reports on the oxidation of creatinine (I) assumed the structure (VI) for the oxidation product.
Synchronous synthesis of alpha- and beta-chemokines by cells of diverse lineage in the central nervous system of mice with relapses of chronic experimental autoimmune encephalomyelitis. (1997)

Chemokines are secreted peptides that exhibit selective chemoattractant properties for target leukocytes. Two subfamilies, alpha- and beta-chemokines, have been described, based on structural, genetic, and functional considerations. In acute experimental autoimmune encephalomyelitis (EAE), chemokines are up-regulated systemically and in central nervous system (CNS) tissues at disease onset. Functional significance of this expression was supported by other studies; intervention with an antichemokine antibody abrogated passive transfer of EAE, and chemokines expressed in brains of transgenic mice recruited appropriate leukocyte populations into the CNS compartment. Chemokine expression in the more relevant circumstance of chronic EAE has not been addressed. We monitored the time course and cellular sources of chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha, interferon-gamma-inducible protein of 10 kd, KC, and regulated on activation, normal T-cell expressed and secreted cytokine) in CNS and peripheral tissues during spontaneous relapses of chronic EAE. We found coordinate chemokine up-regulation in brain and spinal cord during clinical relapse, with expression confined to CNS tissues. Monocyte chemoattractant protein-1, interferon-gamma-inducible protein of 10 kd, and KC were synthesized by astrocytic cells, whereas macrophage inflammatory protein-1 alpha and regulated on activation, normal T-cell expressed and secreted cytokine were elaborated by infiltrating leukocytes. The results demonstrate stringent regulation of multiple chemokines in vivo during a complex organ-specific autoimmune disease. We propose that chemokine expression links T-cell antigen recognition and activation to subsequent CNS inflammatory pathology in chronic relapsing EAE.