gebhart/patrepeval huggingface dataset:
In Vivo Tracking of Neural Progenitor Cell Migration to Glioblastomas (2003)

The ability to noninvasively track the migration, engraftment, and proliferation of neural progenitor cells (NPCs) has significant clinical and research implications. The purpose of our study was to explore the macroscopic migratory capabilities of NPCs toward brain tumors after implantation into nude mice. We stably transfected C17.2 NPCs with the firefly luciferase gene (F-luc) and implanted cells into (1) the contralateral brain parenchyma (2 x 10(6) cells), (2) the ventricles (2 x 10(6) cells), (3) the vasculature (1 x 10(5) cells), or (4) the intraperitoneal cavity (5 x 10(6) cells) of mice bearing intracranial gliomas (Gli36). Using serial bioluminescence imaging, migration of parenchymally injected cells was observed across the corpus callosum, first detected at 1 week, with maximal density at the tumor site 2-3 weeks after implantation. Similar patterns were also observed with intraventricular injections; however, tumors were populated earlier, presumably because of the shorter distance to travel. Intravenous injections resulted in more modest tumoral NPC populations, whereas virtually no cells could be identified in tumors after intraperitoneal injection. These results confirm the migratory capability of NPCs over considerable distances and their preferential accumulation in brain tumors on CNS rather than peripheral injection.
Differential Effects of Scavenger Receptor BI Deficiency on Lipid Metabolism in Cells of the Arterial Wall and in the Liver (2003)

Scavenger receptor class B, type I (SRBI) is a key regulator of high density lipoprotein (HDL) metabolism. It facilitates the efflux of cholesterol from cells in peripheral tissues to HDL and mediates the selective uptake of cholesteryl esters from HDL in the liver. We investigated the effects of SRBI deficiency in the arterial wall and in the liver using SRBI-deficient mice and wild-type littermates fed a Western-type diet. The SRBI-deficient mice showed massive accumulation of cholesterol-rich HDL in the circulation, reflecting impaired delivery to the liver. Strikingly, SRBI deficiency did not alter hepatic cholesterol (ester) content nor did it affect the expression of key regulators of hepatic cholesterol homeostasis, including HMG-CoA reductase, the low density lipoprotein receptor, and cholesterol 7alpha-hydroxylase. However, a approximately 40% reduction in biliary cholesterol content was observed, and the expression of ABCG8 and ABCG5, ATP half-transporters implicated in the transport of sterols from the liver to the bile, was attenuated by 70 and 35%, respectively. In contrast to the situation in the liver, SRBI deficiency did result in lipid deposition in the aorta and atherosclerosis. Vascular mRNA analysis showed increased expression of inflammatory markers as well as of genes involved in cellular cholesterol homeostasis. Our data show that, although hepatic cholesterol homeostasis is maintained upon feeding a Western-type diet, SRBI deficiency is associated with de-regulation of cholesterol homeostasis in the arterial wall that results in an increased susceptibility to atherosclerosis.
Ca 2+ channel nanodomains boost local Ca 2+ amplitude (2013)

Local Ca(2+) signals through voltage-gated Ca(2+) channels (CaVs) drive synaptic transmission, neural plasticity, and cardiac contraction. Despite the importance of these events, the fundamental relationship between flux through a single CaV channel and the Ca(2+) signaling concentration within nanometers of its pore has resisted empirical determination, owing to limitations in the spatial resolution and specificity of fluorescence-based Ca(2+) measurements. Here, we exploited Ca(2+)-dependent inactivation of CaV channels as a nanometer-range Ca(2+) indicator specific to active channels. We observed an unexpected and dramatic boost in nanodomain Ca(2+) amplitude, ten-fold higher than predicted on theoretical grounds. Our results uncover a striking feature of CaV nanodomains, as diffusion-restricted environments that amplify small Ca(2+) fluxes into enormous local Ca(2+) concentrations. This Ca(2+) tuning by the physical composition of the nanodomain may represent an energy-efficient means of local amplification that maximizes information signaling capacity, while minimizing global Ca(2+) load.
Dissecting the Molecular Mechanism of Chronic Myelogenous Leukemia Using Murine Models (2002)

Chronic myelogenous leukemia (CML) is a complex disease that impinges on stem cell biology, the regulation of blood lineage determination and/or selection, as well as the overall regulation of hematopoietic cell proliferation, survival, adhesion and migration. Establishment of murine models for CML in recent years has enabled experimental analyses of molecular mechanisms in the pathogenesis of CML at the organismal level. This review summarizes the approaches used to develop murine models for CML and the analyses of the roles of functional domains and downstream signaling pathways of BCR-ABL (an oncoprotein generated by the t(9;22)(q34;ql1) translocation found in CML patients) and the roles of related tyrosine kinase oncoproteins, altered cytokine production and oncogene cooperation in the pathogenesis of CML-like disease using murine models. These in vivo studies of leukemogenesis will help to advance therapies for CML, as well as to understand fundamental rules of leukemogenesis and hematopoiesis, which should contribute in turn to the development of therapies for other related diseases.
Biomimetic Synthesis of Lantibiotics (2000)

The lantibiotics are a class of highly posttranslationally modified small peptide antibiotics containing numerous lanthionine and dehydroamino acid residues. We have prepared peptides containing multiple dehydroamino acids and cysteine residues in order to probe the biomimetic synthesis of the lantibiotics from their precursor peptides. A novel synthetic methodology was developed to allow the synthesis of multiple dehydroamino acid containing peptides. Cyclisations were rapid, quantitative and regiospecific. Remarkably the peptide sequences alone appear to contain sufficient information to direct a series of stereo- and regiospecific ring closures. Thus both the two linear peptides for the B and E-rings closed stereoselectively. In the case of the A-ring precursor peptide which contained two dehydroamino acids, cyclisation was again totally regioselective, although not totally stereoselective.
Fabrication of Bioinspired Actuated Nanostructures with Arbitrary Geometry and Stiffness (2008)

Bio-inspired, multifunctional, high-aspect-ratio nanostructured surfaces are fabricated in a variety of materials with controlled geometry and stiffness. A soft-lithography method that allows the one-to-one replication of nanostructures and renders it possible to produce arbitrary nanostructures with cross-sectional shapes, orientations, and 2D lattices that are different from the original master is presented. The actuation of the posts is demonstrated.
Immunoglobulin gene analysis in chronic lymphocytic leukemia in the era of next generation sequencing (2020)

Twenty years after landmark publications, there is a consensus that the somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is an important cornerstone for accurate risk stratification and therapeutic decision-making in patients with chronic lymphocytic leukemia (CLL). The IGHV SHM status has traditionally been determined by conventional Sanger sequencing. However, NGS has heralded a new era in medical diagnostics and immunogenetic analysis is following this trend. There is indeed a growing demand for shifting practice and using NGS for IGHV gene SHM assessment, although it is debatable whether it is always justifiable, at least taking into account financial considerations for laboratories with limited resources. Nevertheless, as this analysis impacts on treatment decisions, standardization of both technical aspects, and data interpretation becomes essential. Also, the need for establishing new recommendations and providing dedicated education and training on NGS-based immunogenetics is greater than ever before. Here we address potential and challenges of NGS-based immunogenetics in CLL. We are convinced that this perspective helps the hematological community to better understand the pros and cons of this new technological development for CLL patient management.
Novel Candidate Genes in Unstable Areas of Human Atherosclerotic Plaques (2006)

The differential expression of 18 genes not previously associated with plaque rupture has been confirmed in stable and unstable regions of the same atherosclerotic plaque. These genes may represent novel targets for the treatment of unstable plaque or useful diagnostic markers of plaque instability.
Clinical implications and utility of field cancerization (2007)

Cancer begins with multiple cumulative epigenetic and genetic alterations that sequencially transform a cell, or a group of cells in a particular organ. The early genetic events might lead to clonal expansion of pre-neoplastic daughter cells in a particular tumor field. Subsequent genomic changes in some of these cells drive them towards the malignant phenotype. These transformed cells are diagnosed histopathologically as cancers owing to changes in cell morphology. Conceivably, a population of daughter cells with early genetic changes (without histopathology) remain in the organ, demonstrating the concept of field cancerization. With present technological advancement, including laser capture microdisection and high-throughput genomic technologies, carefully designed studies using appropriate control tissue will enable identification of important molecular signatures in these genetically transformed but histologically normal cells. Such tumor-specific biomarkers should have excellent clinical utility. This review examines the concept of field cancerization in several cancers and its possible utility in four areas of oncology; risk assessment, early cancer detection, monitoring of tumor progression and definition of tumor margins.
Electrochemical Detection of Natural Antioxidants: Principles and Protocols (2001)

An overview is provided of the use of cyclic voltammetry and electrochemical detectors for HPLC to characterize antioxidants that are active as reducing agents at inert electrodes. Results are presented for cyclic voltammetry at a glassy carbon electrode in 50% methanol, 50% 0.1 M HClO4, a solution typically used in HPLC separations of natural antioxidants. The relative reducing strength of each antioxidant is estimated by the formal potential, and information is also obtained regarding the reversibility of the oxidation of the antioxidants, and the extent to which the carbon electrode is contaminated by the products of oxidation. Cyclic voltammetry of complex mixtures such as blood serum and wine produces a measure of the total antioxidant status due to antioxidants with a low oxidation potential. The results of cyclic voltammetry studies are relevant to interpreting the performance of carbon electrodes in electrochemical detectors for HPLC.
Recombinant amyloid beta-peptide production by coexpression with an affibody ligand (2008)

The coexpression of an engineered aggregation-inhibiting binding protein offers a novel route to the recombinant production of amyloidogenic Abeta peptides that can be advantageously employed to study the molecular basis of AD. The presented expression system is the first for which expression and purification of the aggregation-prone Arctic variant (E22G) of Abeta(1-42) is reported.
Computer simulated visual and tactile feedback as an aid to manipulator and vehicle control (1981)

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1981.
Expression of Ly49E and CD94/NKG2 on Fetal and Adult NK Cells (2001)

Murine NK cells express inhibitory receptors belonging to the Ly49 and CD94/NKG2 family. Ly49E and CD94 are the only NK cell receptor transcripts detectable in fetal NK cells. Still unproved is the surface expression of Ly49E on NK cells. Here we generated two novel mAbs, a mAb recognizing Ly49E with cross-reactivity to Ly49C, and a mAb against NKG2A/C/E. Ly49E was immunoprecipitated as a disulfide-linked homodimer with 46-kDa subunits. Removal of N-linked carbohydrates revealed a 31-kDa protein backbone. NKG2A was immunoprecipitated as a 38-kDa protein. Although the frequency of fetal NK cells expressing Ly49E was higher than 25%, it decreased drastically from 2 wk after birth. Phenotypic analysis showed that approximately 90% of fetal NK cells and approximately 50% of adult NK cells express high levels of CD94/NKG2. The remaining 50% of adult NK cells expressed low surface levels of CD94/NKG2. Expression of Ly49E and CD94/NKG2 was not restricted to NK cells, but was also observed on NK T and memory T cells. Functional analysis showed that sorted Ly49E(+) and CD94/NKG2(+) fetal NK cells could discriminate between MHC class I-positive and MHC class I-negative tumor cells. We also demonstrated that Ly49E becomes phosphorylated following pervanadate stimulation of fetal NK cells. The expression levels of Ly49E and CD94/NKG2 were similar in wild-type compared with beta(2)-microglobulin(-/-) mice. In conclusion, generation of mAbs against Ly49E and NKG2 extended the phenotypic and functional characterization of NK cells.
Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: A comparison of AFP, DCP, and AFP-L31 (2007)

Current surveillance strategies for hepatocellular carcinoma (HCC) are applied uniformly in patients with cirrhosis, regardless of their cancer risk. The aim of this study was to compare the performance characteristics of the biomarkers alpha-fetoprotein (AFP), des-gamma carboxyprothrombin (DCP), and lectin-bound AFP (AFP-L3) in the diagnosis of HCC, and to determine the effect of risk factors for HCC on test performance. Eighty-four patients with HCC and 169 patients with cirrhosis were enrolled and their serum analyzed for total AFP, AFP-L3 and DCP. Receiver-operating characteristic (ROC) curves were constructed to determine the performance characteristics. DCP was significantly better than total AFP or AFP-L3 in differentiating HCC from cirrhosis, with a sensitivity of 86% and specificity of 93%. When subjects were divided into two groups by their risk for HCC, all 3 markers had a lower sensitivity and area under the ROC curve in the high-risk group compared to the low-risk group. In conclusion, DCP has the best performance characteristics of all 3 serum markers for the diagnosis of HCC. Serum biomarkers may be less sensitive and specific in the highest risk patients.
Changes in sarcoma 180 cells associated with drug-induced resistance to adenosine analogs. (1972)

Summary A subline of mouse Sarcoma 180 (S-180) cells, resistant to adenosine analogs, was selected in cell culture by serial passage in the presence of increasing concentrations of N 6 -furfuryladenosine. These cells (S-180/KR) were cross-resistant to a number of other adenosine analogs, including N 6 -(Δ 2 -isopentenyl)adenosine (IPAR). The resistance was unaltered after 5 months maintenance in absence of the drug. S-180/KR cells showed increased sensitivity to certain purine and pyrimidine nucleoside analogs such as 6-thiopurine ribonucleoside and 5-fluorodeoxyuridine. The activity of purine nucleoside phosphorylase (purine nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) an enzyme that in crude cell extracts but not in whole cells cleaved IPAR-8- 14 C to the noncytotoxic free base at 10% the rate for inosine, was equal in sensitive and resistant cells. In contrast, the activity of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4), an enzyme that provides an alternate metabolic pathway for utilization of adenosine (K m 29 µm) was increased 45% in extracts of resistant cells. No cleavage of IPAR by this enzyme to inosine in cells or cell extracts was observed, but IPAR was a competitive inhibitor of adenosine deamination with a K i of 1.3 mm. The change that appears to be solely responsible for resistance to adenosine analogs was the 20,000-fold reduction in the activity of adenosine kinase (adenosine 5′-triphosphate:adenosine 5′-phosphotransferase, EC 2.7.1.20). This enzyme converts adenosine and its analogs to their 5′-monophosphates. The elution pattern of adenosine kinase of both cells on diethylaminoethyl cellulose and K m for adenosine (0.5 µm) were identical. In resistant cells, deficient in adenosine kinase but containing increased adenosine deaminase, the rate of uptake of adenosine was slightly reduced; V max 18.2 and 5.1 nmoles/hr/mg cells in S-180 (K t 47 µm) and S-180/KR (K t 20 µm), respectively. These changes were reflected in altered growth response to adenosine when de novo synthesis of purine nucleotides was blocked by amethopterin. In sensitive, but not in resistant cells, IPAR accumulated in trichloroacetic acid-soluble pool in the form of 5′-monophosphate, which comprised 75% of cellular IPAR metabolites. In resistant cells deficient in adenosine kinase and unable to otherwise metabolize IPAR, the rate of uptake of IPAR was greatly reduced; V max 3.3 and 0.08 nmoles/hr/mg cells in S-180 (K t 24 µm) and S-180/KR (K t 14 µm), respectively.
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome (2009)

Bowtie is an ultrafast, memory-efficient alignment program for aligning short DNA sequence reads to large genomes. For the human genome, Burrows-Wheeler indexing allows Bowtie to align more than 25 million reads per CPU hour with a memory footprint of approximately 1.3 gigabytes. Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches. Multiple processor cores can be used simultaneously to achieve even greater alignment speeds. Bowtie is open source (http://bowtie.cbcb.umd.edu).
Enhanced solubility of heterologous proteins by fusion expression using stress-inducedEscherichia coliprotein, Tsf (2007)

Through two-dimensional electrophoresis, Escherichia coli proteome response to a protein denaturant, guanidine hydrochloride, was analyzed and elongation factor Ts (Tsf) detected as a stress-induced protein. Many host proteins aggregated, or their synthesis levels decreased significantly under conditions of protein denaturation as 34 out of 699 soluble proteins knocked out and 63 proteins decreased by over 2.5-fold. Interestingly, the expression level of Tsf increased 1.61-fold compared with a nonstress condition. Contrary to direct expression, various heterologous proteins were solubly expressed in E. coli when subjected to N-terminus fusions of Tsf. Owing most likely to an intrinsic high folding efficiency, Tsf seemed to play critical roles in sequestering interactive surfaces of heterologous proteins from nonspecific protein-protein interactions leading to formation of inclusion bodies. It has been also demonstrated that Tsf is effective in aiding the production of a biologically active bacterial cutinase, which could be of interest to biotechnology and commercial applications.
High-speed high-security signatures (2012)

This paper shows that a $390 mass-market quad-core 2.4GHz Intel Westmere (Xeon E5620) CPU can create 109000 signatures per second and verify 71000 signatures per second on an elliptic curve at a 2128 security level. Public keys are 32 bytes, and signatures are 64 bytes. These performance figures include strong defenses against software side-channel attacks: there is no data flow from secret keys to array indices, and there is no data flow from secret keys to branch conditions.
Regulation of T Lymphocyte Metabolism (2004)

Upon stimulation, lymphocytes develop from small resting cells into highly proliferative and secretory cells. Although a great deal of study has focused on the genetic program induced by Ag receptor signals, lymphocytes must also regulate their metabolic function to meet the energetic demands of activation. In this review, we discuss the changes in cellular metabolism that accompany lymphocyte activation, with a particular emphasis on glucose metabolism, a major source of both energy and biosynthetic building blocks. We will also cover the signaling pathways that positively and negatively regulate these changes to maintain metabolic homeostasis in cells that are rapidly growing, dividing, and differentiating.
3-Bromotyrosine and 3,5-Dibromotyrosine Are Major Products of Protein Oxidation by Eosinophil Peroxidase:  Potential Markers for Eosinophil-Dependent Tissue Injury in Vivo (1999)

Detection of specific reaction products is a powerful approach for dissecting out pathways that mediate oxidative damage in vivo. Eosinophil peroxidase (EPO), an abundant protein secreted from activated eosinophils, has been implicated in promoting oxidative tissue injury in conditions such as asthma, allergic inflammatory disorders, cancer, and helminthic infections. This unique heme protein amplifies the oxidizing potential of H2O2 by utilizing plasma levels of Br- as a cosubstrate to form potent brominating agents. Brominated products might thus serve as powerful tools for identifying sites of eosinophil-mediated tissue injury in vivo; however, structural identification and characterization of specific brominated products formed during EPO-catalyzed oxidation have not yet been reported. Here we explore the role of EPO and myeloperoxidase (MPO), a related leukocyte protein, in promoting protein oxidative damage through bromination and demonstrate that protein tyrosine residues serve as endogenous traps of reactive brominating species forming stable ring-brominated adducts. Exposure of the amino acid L-tyrosine to EPO, H2O2, and physiological concentrations of halides (100 mM Cl-, </=100 microM Br-) produced two new major products with distinct retention times on reverse phase HPLC. The products were identified as 3-bromotyrosine and 3, 5-dibromotyrosine by electrospray ionization mass spectrometry and multinuclear (1H and 15N) NMR spectroscopy. Formation of the ring-brominated forms of the amino acid occurred readily at neutral pH with the enzymatic system and a variety of reactive brominating species, including HOBr/OBr-, N-bromoamines, and N,N-dibromoamines. Addition of primary amines (e.g., Nalpha-acetyllysine and taurine) to L-tyrosine exposed to either HOBr/OBr- or the EPO-H2O2-Br- system enhanced phenolic ring bromination, suggesting N-bromoamines are preferred brominating intermediates in these reactions. Reduction of N-bromoamines (e.g., Nalpha-acetyl,Nepsilon-bromolysine) by L-tyrosine was shown to result in the loss of reactive halogen with a near stoichiometric increase in the level of tyrosine ring bromination (i.e., carbon-bromine bonds). Although both EPO and MPO could use Br- to halogenate protein tyrosine residues in vitro, only EPO effectively brominated the aromatic amino acid at physiological levels of halides and H2O2. Collectively, these results suggest that 3-bromotyrosine and 3,5-dibromotyrosine are attractive candidates for serving as molecular markers for oxidative damage of proteins by reactive brominating species in vivo. They also suggest that in biological mixtures where amine groups are abundant, the trapping of EPO-generated HOBr/OBr- as N-bromoamines will serve to effectively "funnel" reactive brominating equivalents to stable ring-brominated forms of tyrosine.
Daylight Quantum Key Distribution over 1.6 km (2000)

Quantum key distribution (QKD) has been demonstrated over a point-to-point 1.6-km atmospheric optical path in full daylight. This record transmission distance brings QKD a step closer to surface-to-satellite and other long-distance applications.