gebhart/patrepeval huggingface dataset:
Quantitative Analysis Reveals Expansion of Human Hematopoietic Repopulating Cells After Short-term Ex Vivo Culture (1997)

Ex vivo culture of human hematopoietic cells is a crucial component of many therapeutic applications. Although current culture conditions have been optimized using quantitative in vitro progenitor assays, knowledge of the conditions that permit maintenance of primitive human repopulating cells is lacking. We report that primitive human cells capable of repopulating nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice (SCID-repopulating cells; SRC) can be maintained and/or modestly increased after culture of CD34+CD38− cord blood cells in serum-free conditions. Quantitative analysis demonstrated a 4- and 10-fold increase in the number of CD34+CD38− cells and colony-forming cells, respectively, as well as a 2- to 4-fold increase in SRC after 4 d of culture. However, after 9 d of culture, all SRC were lost, despite further increases in total cells, CFC content, and CD34+ cells. These studies indicate that caution must be exercised in extending the duration of ex vivo cultures used for transplantation, and demonstrate the importance of the SRC assay in the development of culture conditions that support primitive cells.
Enhancement-Mode$hboxSi_3hboxN_4hbox/AlGaN/GaN$MISHFETs (2006)

Enhancement-mode <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$hboxSi_3hboxN_4/hboxAlGaN/GaN$</tex> metal–insulator–semiconductor HFETs (MISHFETs) with a 1- <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$muhboxm$</tex> gate footprint are demonstrated by combining <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$hboxCF_4$</tex> plasma treatment technique and a two-step <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$hboxSi_3hboxN_4$</tex> deposition process. The threshold voltage has been shifted from <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$-$</tex> 4 [for depletion-mode HFET] to 2 V using the techniques. A 15-nm <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$hboxSi_3hboxN_4$</tex> layer is inserted under the metal gate to provide additional isolation between the gate Schottky contact and AlGaN surface, which can lead to reduced gate leakage current and higher gate turn-on voltage. The two-step <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$hboxSi_3hboxN_4$</tex> deposition process is developed to reduce the gate coupling capacitances in the source and drain access region, while assuring the plasma-treated gate region being fully covered by the gate electrode. The forward turn-on gate bias of the MISHFETs is as large as 7 V, at which a maximum current density of 420 mA/mm is obtained. The small-signal RF measurements show that the current gain cutoff frequency <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(f_T)$</tex> and power gain cutoff frequency <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(f_max)$</tex> are 13.3 and 23.3 GHz, respectively.
NMR Investigations of the Role of the Sugar Moiety in Glycosylated Recombinant Human Granulocyte‐Colony‐Stimulating Factor (1997)

Human granulocyte-colony-stimulating factor (G-CSF) is a hematopoietic growth factor that plays a major role in the stimulation of the proliferation and maturation of granulocyte neutrophil cells. With the recent increased understanding of its biological properties in vivo together with available preparations of recombinant human G-CSF, this growth factor has become an essential agent for clinical applications. The presence of an O-linked carbohydrate chain at position 133 greatly improves the physical stability of the protein. To clarify the molecular basis for the stabilisation effect of saccharide moieties on human G-CSF the whole glycoprotein expressed in CHO cells has been investigated by means of two 1H-NMR-spectroscopy and two 1H-detected-heteronuclear 1H-13C experiments at natural abundance, and compared with the non-glycosylated form. The present NMR study reports assignments of 1H and 13C resonances of the bound saccharidic chain NeuNAc(alpha2-3)Gal(beta1-3)[NeuNAc(alpha2-6)]GalNAc, where NeuNAc represents N-acetylneuraminic acid, and demonstrates the alpha-anomeric configuration of the N-acetylgalactosamine-threonine linkage. It also provides results suggesting that the carbohydrate moiety reduces the local mobility around the glycosylation site, which could be responsible for the stabilising effect observed on the glycoprotein.
The ret proto-oncogene is consistently expressed in human pheochromocytomas and thyroid medullary carcinomas. (1990)

We have recently reported the identification of a new oncogene, named PTC, frequently activated in human thyroid papillary carcinomas. This gene is a novel rearranged form of the ret proto-oncogene and we have shown that this rearrangement occurred in vivo as a tumor-specific somatic event. In an effort to further examine the role of this oncogene in human malignancies, we have investigated the expression of the ret oncogene in a number of human tumors. We consistently detected expression of normal-sized transcripts of the ret proto-oncogene in human pheochromocytomas and in human medullary thyroid carcinomas (MTC), both of familial and sporadic type. Moreover, we showed that ret mRNA levels were increased following (Bu)2cAMP-induced differentiation of a human MTC cell line (TT). Since the ret gene has been mapped on chromosome 10, close to the gene which predisposes patients to the MEN2A syndrome, we suggest that this region of chromosome 10 might be involved in the proliferative and differentiative patterns of these neuroectodermal tissues.
Virus-Based Toolkit for the Directed Synthesis of Magnetic and Semiconducting Nanowires (2004)

We report a virus-based scaffold for the synthesis of single-crystal ZnS, CdS, and freestanding chemically ordered CoPt and FePt nanowires, with the means of modifying substrate specificity through standard biological methods. Peptides (selected through an evolutionary screening process) that exhibit control of composition, size, and phase during nanoparticle nucleation have been expressed on the highly ordered filamentous capsid of the M13 bacteriophage. The incorporation of specific, nucleating peptides into the generic scaffold of the M13 coat structure provides a viable template for the directed synthesis of semiconducting and magnetic materials. Removal of the viral template by means of annealing promoted oriented aggregation-based crystal growth, forming individual crystalline nanowires. The unique ability to interchange substrate-specific peptides into the linear self-assembled filamentous construct of the M13 virus introduces a material tunability that has not been seen in previous synthetic routes. Therefore, this system provides a genetic toolkit for growing and organizing nanowires from semiconducting and magnetic materials.
Novel Vaccination Protocol with Two Live Mucosal Vectors Elicits Strong Cell-Mediated Immunity in the Vagina and Protects against Vaginal Virus Challenge (2008)

Most HIV infections result from heterosexual transmission to women. Because cellular immunity plays a key role in the control of the infection, we sought to strengthen cellular immune responses in vaginal tissue. We explored a novel prime-boost protocol that used two live mucosal agents that trigger different pathways of innate immunity and induce strong cellular immunity. Adenovirus serotype 5 (Ad5) has frequently been used as a boost for DNA vaccines. In this study we used attenuated, recombinant L. monocytogenes-gag (rLm-gag) to prime mice by various mucosal routes-oral, intrarectal, and intravaginally (ivag)-followed by a systemic or mucosal boost with replication-defective rAd5-gag. Mice primed with a single administration of rLm-gag by any route and then boosted with rAd5-gag intramuscularly exhibited abundant Gag-specific CD8 T cells in spleen and vaginal lamina propria. Conversely, when boosted with rAd5-gag ivag, the immune response was reoriented toward the vagina with strikingly higher CD8 T cell responses in that tissue, particularly after ivag immunization by both vectors (ivag/ivag). Five weeks to 5 mo later, ivag/ivag-immunized mice continued to show high levels of effector memory CD8 T cells in vagina, while the pool of memory T cells in spleen assumed a progressively more central memory T cell phenotype. The memory mice showed high in vivo CTL activity in vagina, a strong recall response, and robust protection after ivag vaccinia-gag challenge, suggesting that this prime-boost strategy can induce strong cellular immunity, especially in vaginal tissues, and might be able to block the heterosexual transmission of HIV-1 at the vaginal mucosa.
Development of liquid 1-methylcyclopropene delivery formulations for modifying ethylene response of fresh produce (2015)

The objective of this dissertation is to develop 1-methylcycopropene (1-MCP) liquid formulations for fresh produce, to manage the undesirable effects of ethylene. The formulation can be used as a sprayable formulation for pre-harvest application, or made into a capsule for post-harvest application. The formulation consists of (1) a cyclodextrin based material (α or modified β-cyclodextrin) as the encapsulant for 1-MCP, (2) a moisture blocking formulation (e.g. polyol/hydrocolloid formulation) to further enclose 1-MCP, and (3) a water based solution to facilitate the release of the formulation. To develop this formulation, five sub-objectives were achieved. 1. Synthesis and characterization of modified β-cyclodextrin 2. Encapsulation of 1-MCP into modified β-cyclodextrin and quantification of 1-MCP inclusion ratio 3. Stabilization of the complex as liquid formulation using materials such as polyol/hydrocolloid blend and mineral oil 4. Evaluation of the sprayability of the liquid formulation and release of 1-MCP 5. Evaluation of biological efficacy of the 1-MCP released from the liquid formulation The key conclusions of this dissertation are as follows. • Modification of β-cyclodextrin was optimized to yield 90-95% powder. The powder has better modified pore size and particle size, which are more favorable for 1-MCP encapsulation than β-cyclodextrin. • 1-MCP can be encapsulated under 0.1 atm headspace concentration both using solid-gas method (inclusion level 0.5%) and in solution-gas method (inclusion level 0.3%). • A stable formulation was developed consisting of mineral oil, HPC and polysorbate for both α and modified β-cyclodextrins. After 30 days of storage at room temperature, more than 90% of 1-MCP can be retained in the formulation. After 14 days of storage at 55°C (equivalent to 1 year storage at room temperature), more than 80% of 1-MCP can be retained in the formulation. • After hydration using different concentrations of xanthan gum, liquid formulation can be sprayed and complete release can be obtained in 6 hours. • 1-MCP released from the formulation is biologically effective that no dimer or isomer formation at treatment level (1 ppm). It was able to extend the shelf life of bananas (color stage 2-2.5) from 2 days to 5 days at room temperature.
A method for respiration monitoring by the use of a bioacoustic signal (2000)

The sound that generates during the act of respiration can be picked up by a bioacoustic sensor, a specially designed microphone. The aim of the work was to describe a method for monitoring of respiration and where the start and stop of the respiration phases can be timed accurately. A method is presented where the time position of the different respiration phases can be determined by a time resolution of 51 ms. A microphone applied over the trachea and the features of the respiration sounds frequency content was used for the development of the method.
TRIM65 regulates microRNA activity by ubiquitination of TNRC6 (2014)

MicroRNAs (miRNAs) are small evolutionarily conserved regulatory RNAs that modulate mRNA stability and translation in a wide range of cell types. MiRNAs are involved in a broad array of biological processes, including cellular proliferation, differentiation, and apoptosis. To identify previously unidentified regulators of miRNA, we initiated a systematic discovery-type proteomic analysis of the miRNA pathway interactome in human cells. Six of 66 genes identified in our proteomic screen were capable of regulating lethal-7a (let-7a) miRNA reporter activity. Tripartite motif 65 (TRIM65) was identified as a repressor of miRNA activity. Detailed analysis indicates that TRIM65 interacts and colocalizes with trinucleotide repeat containing six (TNRC6) proteins in processing body-like structures. Ubiquitination assays demonstrate that TRIM65 is an ubiquitin E3 ligase for TNRC6 proteins. The combination of overexpression and knockdown studies establishes that TRIM65 relieves miRNA-driven suppression of mRNA expression through ubiquitination and subsequent degradation of TNRC6.
Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases (2013)

Significance This study defines a unique mechanism controlling the activation of Hippo signaling and consequent inhibition of cell growth. Specifically, serum starvation is found to induce the large tumor suppressor (LATS)1/2 kinases to phosphorylate and thus stabilize the 130 kDa isoform of the membrane-associated polarity protein angiomotin (Amot130). As a consequence, Amot130 recruits the E3 protein-ubiquitin ligase atrophin-1 interacting protein 4. This multiprotein complex then signals the degradation of Yes-associated protein (YAP) and the inhibition of cell growth. These findings significantly modify our current view that YAP phosphorylation by LATS1/2 is sufficient for its inhibition in mammals and thus for growth arrest.
Designing Combinatorial Library Mixtures Using a Genetic Algorithm (1997)

The design of combinatorial mixture libraries should take account of a number of factors. This paper describes the application of a genetic algorithm to optimizing the diversity of libraries while minimizing the effort that will be needed to deconvolute the biological hits by mass-spectroscopic techniques. It differs from previous applications of genetic algorithms to combinatorial library design in that each chromosome encodes an entire library with the result that properties of the library are optimized. Our method is such that it is easily extensible to optimizing the distributions of any number of physical or other properties of the library. The method allows for the combinatorial constraint inherent in mixtures that every substituent at each diversity site must occur in combination with every substituent at every other site. We present results showing that the genetic algorithm can produce good library designs in timely manner.
A 60 Gb/s MDM-WDM Si photonic link with < 07 dB power penalty per channel (2014)

Mode-division-multiplexing (MDM) and wavelength-division-multiplexing (WDM) are employed simultaneously in a multimode silicon waveguide to realize on-chip MDM and MDM-WDM transmission. Asymmetric Y-junction MDM multiplexers and demultiplexers are utilized for low coherently suppressed demultiplexed crosstalk at the receiver. We demonstrate aggregate bandwidths of 20 Gb/s and 60 Gb/s for MDM and MDM-WDM on-chip links, respectively, with measured 10(-9) BER power penalties between 0.1 dB and 0.7 dB per channel.
Distribution of Core Oligosaccharide Types in Lipopolysaccharides from Escherichia coli (2000)

In the lipopolysaccharides of Escherichia coli there are five distinct core oligosaccharide (core OS) structures, designated K-12 and R1 to R4. The objective of this work was to determine the prevalences of these core OS types within the species. Unique sequences in the waa (core OS biosynthesis) gene operon were used to develop a PCR-based system that facilitated unequivocal determination of the core OS types in isolates of E. coli. This system was applied to the 72 isolates in the E. coli ECOR collection, a compilation of isolates that is considered to be broadly representative of the genetic diversity of the species. Fifty (69. 4%) of the ECOR isolates contained the R1 core OS, 8 (11.1%) were representatives of R2, 8 (11.1%) were R3, 2 (2.8%) were R4, and only 4 (5.6%) were K-12. R1 is the only core OS type found in all four major phylogenetic groups (A, B1, B2, and D) in the ECOR collection. Virulent extraintestinal pathogenic E. coli isolates tend to be closely related to group B2 and, to a lesser extent, group D isolates. All of the ECOR representatives from the B2 and D groups had the R1 core OS. In contrast, commensal E. coli isolates are more closely related to group A, which contains isolates representing each of the five core OS structures. R3 was the only core OS type found in 38 verotoxigenic E. coli (VTEC) isolates from humans and cattle belonging to the common enterohemorrhagic E. coli serogroups O157, O111, and O26. Although isolates from other VTEC serogroups showed more core OS diversity, the R3 type (83.1% of all VTEC isolates) was still predominant. When non-VTEC commensal isolates from cattle were analyzed, it was found that most possessed the R1 core OS type.
Slot-coupled small triangular microstrip antenna (1997)

The design of slot-coupled, reduced-size triangular microstrip antennas with a shorting-pin or chip-resistor loading is described. The fundamental mode of TM10 is studied. Impedance matching can be achieved simply by adjusting the coupling-slot size, with the slot center fixed at the null-field point of the TM10 mode, and the required slot size increasing with increasing loading resistance. The case with a chip-resistor loading also shows a lower resonant frequency and a significantly enhanced operating bandwidth, as compared with the shorting-pin loading case. Details of the experimental results are presented and discussed. © 1997 John Wiley & Sons, Inc. Microwave Opt Technol Lett 16: 371–374, 1997.
Tissue Factor in the Pathogenesis of Atherosclerosis (1997)

TF antigen and activity are found in abundance in human atherosclerotic plaques, particularly in the lipid-rich core. TF is also readily induced in the arterial wall by balloon injury and accumulates in the resulting neointima. In chronic atherosclerosis, the macrophage is likely to be the major source of TF within the plaque. TF accumulates as an early event associated with the migration of monocytes to the vessel wall in response to chemoattractants, such as MCP-1, and their differentiation into macrophages. As SMC become activated in the developing plaque, they provide a second source of TF. Macrophages and SMC accumulate lipid and become foam cells, ultimately degenerating into a necrotic core rich in TF. Spontaneous plaque rupture or acute interventions expose active TF in the core to circulating blood, triggering thrombosis. In acute arterial injury, SMC appear to be the chief source of TF. In normal vessels, the induction of TF in the medial SMC is not sufficient to generate fibrin, presumably because the TF is not readily accessible on the luminal surface. In contrast, endothelial denudation of previously injured arteries may expose intimal TF to circulating blood, resulting in rapid fibrin deposition. In advanced human atherosclerosis, it is likely that even in areas that do not contain "unstable" or "stable" plaques, the vessel wall is not normal and more closely resembles that of a previously injured artery possessing an active intima. Interventions, such as balloon angioplasty, coronary atherectomy, or stent placement may expose intimal TF, leading to fibrin deposition. As the initiator of coagulation, TF is a potential target for inhibiting the thrombotic complications of atherosclerosis. TFPI (reviewed in 52) is currently under clinical investigation as an anticoagulant and its effects on intimal hyperplasia in animal models are being studied. Direct factor Xa inhibitors, such as tick anticoagulant peptide (TAP) and leech anticoagulant peptide (ATS), are also under investigation (53-54). Finally, the recent crystallization of TF (55) and the TF:VIIa (56) should provide important new insights into the design of molecules for directly inhibiting TF.
An OX40/OX40L interaction directs successful immunity to hepatitis B virus (2018)

Depending on age of acquisition, hepatitis B virus (HBV) can induce a cell-mediated immune response that results in either cure or progressive liver injury. In adult-acquired infection, HBV antigens are usually cleared, whereas in infancy-acquired infection, they persist. Individuals infected during infancy therefore represent the majority of patients chronically infected with HBV (CHB). A therapy that can promote viral antigen clearance in most CHB patients has not been developed and would represent a major health care advance and cost mitigator. Using an age-dependent mouse model of HBV clearance and persistence in conjunction with human blood and liver tissue, we studied mechanisms of viral clearance to identify new therapeutic targets. We demonstrate that age-dependent expression of the costimulatory molecule OX40 ligand (OX40L) by hepatic innate immune cells is pivotal in determining HBV immunity, and that treatment with OX40 agonists leads to improved HBV antigen clearance in young mice, as well as increased strength of T cell responses in young mice and adult mice that were exposed to HBV when they were young and developed a CHB serological profile. Similarly, in humans, we show that hepatic OX40L transcript expression is age-dependent and that increased OX40 expression on peripheral CD4<sup>+</sup> T cells in adults is associated with HBV clearance. These findings provide new mechanistic understanding of the immune pathways and cells necessary for HBV immunity and identify potential therapeutic targets for resolving CHB.
Pyrazolopyrimidine nucleosides. 12. Synthesis and biological activity of certain pyrazolo[3,4-d]pyrimidine nucleosides related to adenosine (1981)

The chemical synthesis of certain 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides is described. Using 1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (1) as the starting material, the reactive intermediate 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine (2) was prepared in excellent yield. Compound 2 served as a versatile precursor for the synthesis of a number of 4-substituted pyrazolo[3,4-d]pyrimidine nucleosides. In antitumor studies of these nucleosides, in vitro and in vivo, it was found that any alteration of the 4-amino substituent of 4-amino-1-beta-D-ribofuranosylpyrazolo[3,4-d]pyrimidine (3) was accompanied by a significant decrease or loss of antitumor activity. On the other hand, introduction of certain substituents at the 3 position of 3 (synthesis reported previously) led to a dramatic increase in antitumor activity in comparison to the parent compound.