gebhart/patrepeval huggingface dataset:
Use of a chemically modified T7 DNA polymerase for manual and automated sequencing of supercoiled DNA. (1988)

Procedures are presented for reliable and accurate nucleotide sequence analysis using as template supercoiled DNA prepared by a modified rapid boiling minipreparation protocol. This method yields DNA templates suitable for sequencing within 1 h of bacterial harvest. We describe optimal reaction conditions for supercoiled miniprep DNA sequencing using a modified T7 DNA polymerase (Sequenase) in dideoxynucleotide chain termination reactions. We demonstrate that under these conditions, the sequencing data obtained with miniprep DNA is indistinguishable from that obtained with CsCl purified supercoiled DNA or from that obtained using single stranded DNA templates. We further show that the supercoiled DNA sequencing reactions can be analyzed on a commercially available automated DNA sequencing system that detects 32P labeled DNA during its electrophoretic separation. Taken together, these developments represent a significant improvement in the process of nucleotide sequence analysis.
Clinical Efficacy of the Microfracture Technique for Articular Cartilage Repair in the Knee (2009)

This systematic analysis shows that microfracture provides effective short-term functional improvement of knee function but insufficient data are available on its long-term results. Shortcomings of the technique include limited hyaline repair tissue, variable repair cartilage volume, and possible functional deterioration. The quality of the currently available data on micro-fracture is still limited by the variability of results and study designs. Further well-designed studies are needed to determine the long-term efficacy of microfracture and to define its specific clinical indications compared to other cartilage repair techniques.
Deep brain stimulation in early-stage Parkinson disease (2020)

This study provides Class II evidence that DBS implanted in early-stage PD decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone.
A Multiproduct Dynamic Pricing Problem and Its Applications to Network Yield Management (1997)

A firm has inventories of a set of components that are used to produce a set of products. There is a finite horizon over which the firm can sell its products. Demand for each product is a stochastic point process with an intensity that is a function of the vector of prices for the products and the time at which these prices are offered. The problem is to price the finished products so as to maximize total expected revenue over the finite sales horizon. An upper bound on the optimal expected revenue is established by analyzing a deterministic version of the problem. The solution to the deterministic problem suggests two heuristics for the stochastic problem that are shown to be asymptotically optimal as the expected sales volume tends to infinity. Several applications of the model to network yield management are given. Numerical examples illustrate both the range of problems that can be modeled under this framework and the effectiveness of the proposed heuristics. The results provide several fundamental insights into the performance of yield management systems.
3-D Spot Modeling for Automatic Segmentation of cDNA Microarray Images (2010)

Spot segmentation--the second essential stage of cDNA microarray image analysis--constitutes a challenging process. At present, several up-to-date spot-segmentation techniques or software programs--proposed in the literature--are often characterized as "automatic." On the contrary, they are in effect not fully automatic since they require human intervention in order to specify mandatory input parameters or to correct their results. Human intervention, however, can inevitably modify the actual results of the cDNA microarray experiment and lead to erroneous biological conclusions. Therefore, the development of an automated spot-segmentation process becomes of exceptional interest. In this paper, an original and fully automatic approach to accurately segmenting the spots in a cDNA microarray image is presented. In order for the segmentation to be accomplished, each real spot of the cDNA microarray image is represented in a three-dimensional (3-D) space by a 3-D spot model. Each 3-D spot model is determined via an optimization problem, which is solved by using a genetic algorithm. The segmentation of real spots is conducted by drawing the contours of their 3-D spot models. The proposed method has been compared with various published and established techniques, using several synthetic and real cDNA microarray images that contain thousands of spots. The outcome has shown that the proposed method outperforms prevalent existing techniques. It is also noise resistant and yields excellent results even under adverse conditions such as the appearance of spots of various sizes and shapes.
Role-Based Access Controls (1992)

Introduction. Access Control Methods. Overview of RBAC. Role Hierarchies. Using RBAC to implement Military Policies. Standard RBAC. RBAC Administration. Integrating RBAC with Existing Infrastructure. Research Prototypes. Commercial RBAC Products. Migrating to RBAC.
Establishment and Characterization of a Simian Virus 40‐Immortalized Osteoblastic Cell Line from Normal Human Bone (1993)

We established a human osteoblastic cell line immortalized by simian virus 40 (SV40) in vitro, and designated it SV-HFO. Immunocytochemically, the cells were positive for SV40 large T-antigen, vimentin and osteocalcin, but negative for keratin and epithelial membrane antigen. The cells had characteristic morphologic and ultrastructural features of osteoblasts, produced alkaline phosphatase, and synthesized osteocalcin, the levels of which were elevated by treatment of the cells with 1a,25-dihydroxyvitamin D3. The cells proliferated and showed such osteoblastic properties even under serum-free conditions. The cells grew in soft agar, but did not form tumors when transplanted into athymic nude mice. Karyotypic analysis by the Q-banding technique showed that these cells were of human origin. The SV-HFO cell line is expected to serve as a suitable model for studying metabolism and carcinogenesis in human bone.
The Saccharomyces cerevisiae PLB1 gene encodes a protein required for lysophospholipase and phospholipase B activity. (1994)

Several enzymes with lysophospholipase/phospholipase B activity have been described from the budding yeast Saccharomyces cerevisiae. In vitro, these enzymes are capable of hydrolyzing all phospholipids that can be extracted from yeast cells. Two forms of the enzyme have been isolated from plasma membranes and a third from culture supernatants and the periplasmic space, but their biological roles have not been determined. These highly glycosylated enzymes were reported to have very similar catalytic properties but differed with respect to apparent molecular weight. We isolated a gene from S. cerevisiae, encoding a protein predicted to share 45% amino acid sequence identity with phospholipase B from Penicillium notatum. This yeast gene, designated PLBl, was mapped to the left arm of chromosome VIII. No residual lysophospholipase/phospholipase B activity was detected upon assay of extracts or culture supernatants of aplblA mutant. Thus, either the PLBl gene encodes all of the previously detected isoforms of phospholipase B or its gene product is required for their expression or activation. Deletion of PLBl did not result in any apparent phenotypic defect, suggesting either that we failed to identify the growth conditions that would betray such a defect or that Plblp is functionally redundant with another protein, whose activity has gone undetected. AplblA mutant released wild-type levels of the soluble phosphatidylinositol metabolite glycerophosphoinositol into the growth medium but released greatly reduced levels of the corresponding phosphatidylcholine and phosphatidylethanolamine metabolites. These results indicate that PLBl is principally responsible for the production of the deacylation products of phosphatidylcholine and phosphatidylethanolamine but not phosphatidylinositol.
Assessing Differentiation Status of Human Embryonic Stem Cells Noninvasively Using Raman Microspectroscopy (2010)

Raman microspectroscopy is an attractive approach for chemical imaging of biological specimens, including live cells, without the need for chemi-selective stains. Using a microspectrometer, near-infrared Raman spectra throughout the range 663 cm(-1) to 1220 cm(-1) were obtained from colonies of CA1 human embryonic stem cells (hESCs) and CA1 cells that had been stimulated to differentiate for 3 weeks by 10% fetal bovine serum on gelatin. Distributions and intensities of spectral bands attributed to proteins varied significantly between undifferentiated and differentiated cells. Importantly, compared to proteins and lipids, the band intensities of nucleic acids were dominant in undifferentiated cells with a dominance-reversal in differentiated cells. Thus, we could identify intensity ratios of particular protein-related bands (e.g., 757 cm(-1) tryptophan) to nucleic acid bands (784 cm(-1) DNA/RNA composite) that were effective in discriminating between spectra of undifferentiated and differentiated cells. We observed no discernible negative effects due to the laser exposure in terms of morphology, proliferation, or pluripotency of the stem cells. We conclude that Raman microscopy and complementary data processing procedures provide a rapid, noninvasive approach that can distinguish hESCs from differentiated cells. This is the first report to identify specific Raman markers for the differentiation status of hESCs.
Human Nucleus Pulposis Can Respond to a Pro-inflammatory Stimulus (2003)

We conclude that both scoliotic and degenerate human nucleus pulposus can respond to an exogenous pro-inflammatory stimulus by secreting increased amounts of IL-6, IL-8, and PGE2 but not TNF-alpha and that degenerate disc tissue is more sensitive to a pro-inflammatory stimulus than its scoliotic counterpart.
HMGB1 Levels Are Increased in Patients with Juvenile Idiopathic Arthritis, Correlate with Early Onset of Disease, and Are Independent of Disease Duration (2013)

Levels of extracellular HMGB1 are increased in the inflamed joints of patients with JIA. This warrants further studies of HMGB1 as a mediator of JIA pathogenesis as well as a biomarker for inflammatory activity and as a target for therapy. The variation in levels of HMGB1 and S100 proteins in relation to disease onset indicates a difference in inflammatory phenotype during disease progression.
Modeling, Force Sensing, and Control of Flexible Cannulas for Microstent Delivery (2012)

This paper presents a kinetostatic modeling framework for flexible cannulas (concentric tubing robots) subject to tip loads. Unlike existing methods that allow fast computation of the beam tip position, this modeling framework provides fast computation of both the tip position and the entire shape of the deflected robot. A method for online force sensing based on inverse kinetostatic solution is also proposed and assistive telemanipulation control methods for microstent delivery are presented. The modeling framework uses polynomial approximation and linear interpolation based on elliptic integral solutions to the deflection of lightweight beams. To date, there are no systems capable of stent delivery in retinal vasculature. The modeling and control frameworks of this paper are validated experimentally on pilot studies for microstent delivery. We believe that the methods presented in this paper open the way for robot-assisted retinal microvascular stenting that may potentially revolutionize the treatment of blinding retinal vasculature diseases.
Tunneling hot spots and heating in magnetic tunnel junctions (2004)

In this work the thermal heating of tunnel junctions is investigated doing one-dimensional numerical simulations by solving the heat equation. The temperature increase is proportional to the power density jV, which is confirmed by transport measurements on patterned μm size junctions. The observed temperature increase was 2.3 K/(mW μm−2) compared to a simulation result of 0.9 K/(mW μm−2). Tunneling AFM measurements on 4, 5.4, and 6.7 Å barrier half-junctions, show hot spots with current densities up to 13 times the average density value. The current concentration could explain the higher heating observed experimentally compared to the simulated value. The hot spot density is 600–900/μm2 occupying roughly 5% of the barrier surface.
Cadmium-Free CuInS2/ZnS Quantum Dots for Sentinel Lymph Node Imaging with Reduced Toxicity (2010)

Semiconductor quantum dots (QDs) could significantly impact the performance of biomedical near-infrared (NIR) imaging by providing fluorescent probes that are brighter and more photostable than conventional organic dyes. However, the toxicity of the components of NIR emitting II-VI and IV-VI QDs that have been made so far (Cd, Hg, Te, Pb, etc.) has remained a major obstacle to the clinical use of QDs. Here, we present the synthesis of CuInS(2)/ZnS core/shell QDs emitting in the NIR ( approximately 800 nm) with good quantum yield and stability even after transfer into water. We demonstrate the potential of these QDs by imaging two regional lymph nodes (LNs) in vivo in mice. We then compare the inflammatory response of the axillary LN induced by different doses of CuInS(2)/ZnS and CdTeSe/CdZnS QDs and show a clear difference in acute local toxicity, the onset of inflammation only occurring at a 10 times more concentrated dose for CuInS(2)/ZnS QDs than for their Cd-containing counterparts.
Structural specializations of immunoglobulin superfamily members for adhesion to integrins and viruses (1998)

The circulation and migration of leukocytes are critical for immune surveillance and immune response to infection or injury. The key step of leukocyte recruitment involves the adhesion between immunoglobulin superfamily (IgSF) proteins on endothelium and integrin molecules on leukocyte surfaces. Some of the IgSF members are subverted as virus receptors. Four crystal structures of N-terminal two-domain fragments of these IgSF proteins have been determined: intercellular adhesion molecule-1 (ICAM-1), ICAM-2, vascular adhesion molecule-1 (VCAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). An acidic residue near the bottom of domain 1 plays a key role in integrin binding. For ICAM-1 and ICAM-2, this glutamic acid residue is located on a flat surface, complementary to the flat surface of the I domain of the integrin to which they bind, lymphocyte function-associated antigen-1 (LFA-1). For VCAM-1 and MAdCAM-1, the acidic residue is aspartic acid, and it resides on a protruded CD loop which may be complementary to a more pocket-like structure in the alpha 4 integrins to which they bind, which lack I domains. A number of unique structural features of this subclass of IgSF have been identified which are proposed to consolidate the domain structure to resist force during adhesion to integrins. Different mechanisms are proposed for the different CAMs to present the integrin-binding surface toward the opposing cell for adhesion, and prevent cis interaction with integrins on the same cell. Finally, CD4 and ICAM-1 are compared in the context of ligand binding and virus binding, which shows how human immunodeficiency virus and rhinovirus fit well with the distinct structural feature of their cognate receptors.
Labeling TiO2 Nanoparticles with Dyes for Optical Fluorescence Microscopy and Determination of TiO2–DNA Nanoconjugate Stability (2009)

Visualization of nanoparticles without intrinsic optical fluorescence properties is a significant problem when performing intracellular studies. Such is the case with titanium dioxide (TiO2) nanoparticles. These nanoparticles, when electronically linked to single-stranded DNA oligonucleotides, have been proposed to be used both as gene knockout devices and as possible tumor imaging agents. By interacting with complementary target sequences in living cells, these photoinducible TiO2-DNA nanoconjugates have the potential to cleave intracellular genomic DNA in a sequence specific and inducible manner. The nanoconjugates also become detectable by magnetic resonance imaging with the addition of gadolinium Gd(III) contrast agents. Herein two approaches for labeling TiO2 nanoparticles and TiO2-DNA nanoconjugates with optically fluorescent agents are described. This permits direct quantification of fluorescently labeled TiO2 nanoparticle uptake in a large population of living cells (>10(4) cells). X-ray fluorescence microscopy (XFM) is combined with fluorescent microscopy to determine the relative intracellular stability of the nanoconjugates and used to quantify intracellular nanoparticles. Imaging the DNA component of the TiO2-DNA nanoconjugate by fluorescent confocal microscopy within the same cell shows an overlap with the titanium signal as mapped by XFM. This strongly implies the intracellular integrity of the TiO2-DNA nanoconjugates in malignant cells.
Long-Term Oral l-Arginine Administration Improves Peripheral and Hepatic Insulin Sensitivity in Type 2 Diabetic Patients (2001)

L-Arginine treatment significantly improves but does not completely normalizc peripheral and hepatic insulin sensitivity in type 2 diabetic patients.
Francisella tularensisregulates the expression of the amino acid transporter SLC1A5 in infected THP-1 human monocytes (2012)

Francisella tularensis, a Gram-negative bacterium that causes the disease tularemia in a large number of animal species, is thought to reside preferentially within macrophages in vivo. F. tularensis has developed mechanisms to rapidly escape from the phagosome into the cytoplasm of infected cells, a habitat with a rich supply of nutrients, ideal for multiplication. SLC1A5 is a neutral amino acid transporter expressed by human cells, which serves, along with SLC7A5 to equilibrate cytoplasmic amino acid pools. We herein analysed whether SLC1A5 was involved in F. tularensis intracellular multiplication. We demonstrate that expression of SLC1A5 is specifically upregulated by F. tularensis in infected THP-1 human monocytes. Furthermore, we show that SLC1A5 downregulation decreases intracellular bacterial multiplication, supporting the involvement of SLC1A5 in F. tularensis infection. Notably, after entry of F. tularensis into cells and during the whole infection, the highly glycosylated form of SLC1A5 was deglycosylated only by bacteria capable of cytosolic multiplication. These data suggest that intracellular replication of F. tularensis depends on the function of host cell SLC1A5. Our results are the first, which show that Francisella intracellular multiplication in human monocyte cytoplasm is associated with a post-translational modification of a eukaryotic amino acid transporter.
Laser Crosslink Configurations for RF Satellite Communications Systems (1985)

Predictions of future satellite communications traffic indicate an increased capacity for satellite communications systems is required. Crosslinks between satellites provide improvements in communications throughput for these systems. Crosslinks also increase system flexibility and remove the dependence of world-wide information flow on relay ground stations located outside the continental United States. Laser crosslinks provide the additional advantage of eliminating susceptibility to space-based or ground-based jammers. Laser terminals are also smaller and require smaller antennas than a radio frequency (RF) terminal. This paper describes the advantages of adding laser crosslinks to RF satellite communications systems. Characteristics of the required RF/optical interfaces on-board the satellites are addressed. Terminal configurations that provide reliable, accurate laser communications at high data rates are described.
Detection of protein biomarkers using high-throughput immunoblotting following focal ischemic or penetrating ballistic-like brain injuries in rats (2008)

These results suggest distinct post-injury protein profiles between brain injury types (traumatic vs. ischemic) that will facilitate strategies aimed at the differential diagnosis and prognosis of acute brain injury.
The cardiovascular safety of incretin-based therapies: a review of the evidence (2013)

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in people with diabetes and therefore managing cardiovascular (CV) risk is a critical component of diabetes care. As incretin-based therapies are effective recent additions to the glucose-lowering treatment armamentarium for type 2 diabetes mellitus (T2D), understanding their CV safety profiles is of great importance. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with beneficial effects on CV risk factors, including weight, blood pressure and lipid profiles. Encouragingly, mechanistic studies in preclinical models and in patients with acute coronary syndrome suggest a potential cardioprotective effect of native GLP-1 or GLP-1 receptor agonists following ischaemia. Moreover, meta-analyses of phase 3 development programme data indicate no increased risk of major adverse cardiovascular events (MACE) with incretin-based therapies. Large randomized controlled trials designed to evaluate long-term CV outcomes with incretin-based therapies in individuals with T2D are now in progress, with the first two reporting as this article went to press.
Identification and characterization of a human cytomegalovirus gene coding for a membrane protein that is conserved among human herpesviruses (1989)

A rabbit antiserum was raised against envelope material from purified human cytomegalovirus strain AD169. The serum recognized polypeptides 200, 170, 160, 75, 58, and 45 kilodaltons in size. It was used to screen a cDNA library constructed from poly(A)+ RNA from human cytomegalovirus-infected cells in the expression vector lambda gt11. A recombinant bacteriophage expressing cytomegalovirus-specific sequences was identified, and the corresponding gene was mapped to the HindIII R fragment. The gene is transcribed into a late 1.5-kilobase RNA. The nucleotide sequence of the coding region was determined. Computer analysis of the gene product revealed a polypeptide containing multiple potential membrane-spanning domains, representing a type of protein not identified in the envelope of herpesviruses before. The protein shows homology on the amino acid level to hypothetical proteins from reading frames BBRF3 of Epstein-Barr virus, UL10 of herpes simplex virus type 1, and ORF50 of varicella-zoster virus. By using an antiserum raised against procaryote-expressed parts of the cytomegalovirus membrane protein, a 45-kilodalton structural component of the virus was identified as the gene product.
Identification of potential ibrutinib combinations in hematological malignancies using a combination high-throughput screen (2017)

Matrix high-throughput screening (HTS) methods are increasingly employed to rapidly define potential therapeutic drug combinations. We used combination HTS to identify compounds showing synergistic anti-proliferative activity with ibrutinib, an irreversible, small-molecule inhibitor of Bruton's tyrosine kinase. The goal was to identify ibrutinib combinations with maximum synergistic effects in heme malignancy lines, particularly in non-Hodgkin lymphoma including diffuse large B-cell lymphoma (DLBCL). Growth inhibition (GI) was used to measure cell viability; synergy scores characterized strength of synergistic interaction. Single-agent ibrutinib demonstrated varying degrees of activity across 30 cell lines evaluated. In DLBCL lines, TMD8 was the most sensitive to ibrutinib (GI<sub>50</sub> = 0.001); combinations with BCL-2 inhibitor ABT-199, and PI3K inhibitors IPI-145 and GDC-0941 showed the strongest synergistic activity. Anti-proliferative synergies were also observed with BET bromodomain inhibitor (+)-JQ1, XPO1 inhibitor selinexor, and IRAK4 inhibitor, and confirmed using apoptosis assay. These findings are intended to inform and advance treatment of B-cell malignancies.