gebhart/patrepeval huggingface dataset:
Deoxyribonucleic Acid Polymerase: Two Distinct Enzymes in One Polypeptide (1972)

Proteolysis of Escherichia coli DNA polymerase (mol wt 109,000) yields two fragments: a large fragment (mol wt 76,000) which retains polymerase and 3′ → 5′ exonuclease activities, and a small fragment (mol wt 36,000) which retains only the 5′ → 3′ exonuclease activity. The large fragment has been obtained in two ways: by cleavage of the intact enzyme with subtilisin or other proteases, and by isolation from E. coli extracts, presumably after proteolysis had occurred in the extract. The large fragment carries out DNA synthesis on nicked double-stranded DNA without degradation of the strand ahead of the growing point, and catalyzes a 3′ → 5′ exonuclease action on both single- and doublestranded DNA with production of nucleoside monophosphates. The large fragment is inactive in unprimed poly[d(A-T)] synthesis, but catalyzes primed poly[d(A - T)] synthesis at a relatively linear rate generating poly[d(A-T)] molecules up to 10 µm in length. The single cysteine residue and the single disulfide group of the intact enzyme are retained in the large fragment as are the binding sites for a deoxyribonucleoside triphosphate and a 3′-hydroxyl ribonucleotide (primer terminus).
An application of Kalman filtering in nuclear well logging (2005)

The paper describes an application of (adaptive) Kalman filtering to a geophysical subsurface estimation problem. The NGT is a sonde designed to detect the natural gamma rays of various energies emitted from a formation by the thorium (Th), uranium (U) and potassium (K). Using a minicomputer at the surface, the (Th, U, K) concentrations along the borehole have to be estimated on-line from the detection of the gamma rays in five energy windows. The standard technique in the logging industry has been to compute the elemental concentrations at a given depth from the corresponding observed counting rates. The resulting estimates have fairly large statistical errors which have limited the application of the NGT in computer reservoir evaluation. In this paper, it is shown that much better estimates can be obtained from a Kalman filter based on a dynamical model of the (Th, U, K) vertical variations.
Detection of Galactomannan Antigenemia by Enzyme Immunoassay for the Diagnosis of Invasive Aspergillosis: Variables That Affect Performance (2004)

Invasive aspergillosis (IA) is a frequent complication of blood or marrow transplantation. Previous studies have reported that the Aspergillus galactomannan enzyme immunoassay (GM EIA) may be a useful diagnostic tool for IA, but its sensitivity is variable. We examined the performance of the GM EIA in 986 serum samples from 67 patients. Results demonstrated that decreasing the index cutoff for positivity to 0.5 increased its sensitivity, with minimal loss of specificity. The low cutoff increased the duration of test positivity before diagnosis by clinical means. Sensitivity was highest in patients who did not receive preventative mold-active antifungals (87.5%). A rabbit model demonstrated that the level of circulating antigen correlated with the tissue fungus burden. A quantifiable response to antifungal therapy in clinical samples and the rabbit model supports the development of this assay for early diagnosis and therapeutic monitoring. The 0.5 cutoff may allow for better performance as an early diagnostic test.
Microwave Surgical Treatment of the Prostate: Clinical Application of Microwave Surgery as a Tool for Improved Prostatic Electroresection (1987)

Microwave surgery as a tool for improved prostatic electroresection is introduced. Prior to electroresection the prostate was coagulated with 2,450 MHz of microwave which was emitted from the bipolar electrode of a specially designed probe. We conducted a comparative study of 35 patients with bladder neck obstruction. There was a microwave coagulation group treated with subsequent transurethral resection (TUR) and a conventional TUR group. Both groups were analyzed for the amount of blood loss, irrigant absorption and the frequency of complications. Both during and following surgery, the former group had a significant reduction in blood loss and had no complications. We conclude that the combination procedure of microwave coagulation and TUR can minimize the disadvantage of formal TUR and may be of value in the treatment of patients with both prostatic obstruction and of hemorrhagic diathesis as well as in high risk patients.
Prevention and Early Detection of Pressure Ulcers in Patients Undergoing Cardiac Surgery (2006)

Absence of pressure ulcers is increasingly being used as an indicator of quality nursing care, based on the premise that pressure ulcers are preventable. This retrospective study examined the occurrence, presentation, and timing of pressure ulcer development in 150 patients undergoing cardiac surgery. Pressure ulcer incidents were recorded in groups of patients who underwent surgery with use of a standard foam OR bed mattress; use of a fluid, pressure-reducing OR bed mattress; or use of a fluid, pressuring-reducing mattress after a comprehensive educational program on pressure ulcer prevention was presented to RNs. Tcers decreased when the fluid, pressure-reducing OR bed mattresses were used in conjunction with the comprehensive RN education program.
Efficient generation of human anti-cytomegalovirus IgG monoclonal antibodies from preselected antigen-specific B cells (1993)

Human anti-cytomegalovirus (CMV) specific B cells were enriched to a purity of up to 38% on CMV-coated dishes and subsequently clonally expanded in the presence of human T cell supernatant and irradiated murine thymoma helper cells. The expanded cells were immortalized by a mini-electrofusion with K6H6B5 myeloma cells. Twenty-two anti-CMV positive B cell clones could be obtained from as little as 1.5 ml donor blood. The majority of these clones produced anti-CMV antibodies of the IgG class. Ten anti-CMV positive B cell clones were submitted to separate mini-electrofusions yielding stable, human anti-CMV IgG-producing hybridomas in six out of ten fusions. These antibodies recognized different proteins of the CMV virus, as deduced from the immunofluorescence staining pattern on infected human fibroblasts.
Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: Correlation of genotype to phenotype (2000)

Uridine-diphosphoglucuronate glucuronosyltransferases (UGTs) are a family of enzymes that conjugate various endogenous and exogenous compounds with glucuronic acid and facilitate their excretion in the bile. Bilirubin-UGT(1) (UGT1A1) is the only isoform that significantly contributes to the conjugation of bilirubin. Lesions in the gene encoding bilirubin-UGT(1), lead to complete or partial inactivation of the enzyme causing the rare autosomal recessively inherited conditions, Crigler-Najjar syndrome type-1 (CN-1) and type 2 (CN-2), respectively. Inactivation of the enzyme leads to accumulation of unconjugated bilirubin in the serum. Severe hyperbilirubinemia seen in CN-1 can cause bilirubin encephalopathy (kernicterus). Kernicterus can be fatal or may leave behind permanent neurological sequelae. Here, we have compiled more than 50 genetic lesions of UGT1A1 that cause CN-1 (including 9 novel mutations) or CN-2 (including 3 novel mutations) and have presented a correlation of structure to function of UGT1A1. In contrast to Crigler-Najjar syndromes, Gilbert syndrome is a common inherited condition characterized by mild hyperbilirubinemia. An insertional mutation of the TATAA element upstream to UGT1A1 results in a reduced level of expression of the gene. Homozygosity for the variant promoter is required for Gilbert syndrome, but not sufficient for manifestation of hyperbilirubinemia, which is partly dependent on the rate of bilirubin production. Several structural mutations of UGT1A1, for example, a G71R substitution, have been reported to cause mild reduction of UGT activity toward bilirubin, resulting in mild hyperbilirubinemia, consistent with Gilbert syndrome. When the normal allele of a heterozygote carrier for a Crigler-Najjar type structural mutation contains a Gilbert type promoter, intermediate levels of hyperbilirubinemia, consistent with the diagnosis of CN-2, may be observed.
A Stimulator Output Stage with Capacitor Reduction and Failure-Checking Techniques (2006)

The use of blocking capacitors in the output stages of implantable stimulators for functional electrical stimulation (FES) applications, is common practice for safety reasons. However, these capacitors tend to dominate the implant volume. This paper describes a stimulator output stage circuit which overcomes this limitation. The circuit features a novel capacitor reduction technique for implant miniaturization, and a simple failure-checking mechanism for enhanced reliability. The approach was verified by simulations in a 0.35 mum CMOS technology
Aromaticity in heterocyclic systems. II. the application of N.M.R. in a study of the synthesis and structure of certain lmidazo[1,2‐c]pyrimidines and related pyrrolo[2,3‐d]pyrimidines (1964)

Abstract Nuclear magnetic resonance spectra have been utilized in several instances to distinguish between ring closure to a derivative of imidazo[1, 2‐c]pyrimidine or pyrrolo[2, 3‐d]pyrimidine. N.m.r. studies have also been employed to select Vc as the most probable structure for 5‐methylthio‐2, 7‐imidazo[1, 2‐c]pyrimidinedione. Ultraviolet absorption spectra and n.m.r. studies in deuterium oxide support the conclusion that there is more aromaticity in the anion V g than in the neutral molecule. The present work describes several new synthetic routes to derivatives of imidazo[1,2‐c]pyrimidine and pyrrolo[2,3‐d]pyrimidine.
Single nucleotide polymorphism hunting in cyberspace (1998)

Large-scale sequencing of human cDNA and genomic DNA libraries has produced a large collection of sequence data in public databases. To date, >900,000 human expressed sequence tag (EST) sequences and >80,000,000 bases of genomic DNA sequence have been deposited in Genbank. This ever-expanding data set is a rich source of gene-associated and anonymous single nucleotide polymorphisms (SNPs). DNA sequence variations can be found by comparing the sequences of redundant ESTs and by comparing sequences from overlapping genomic clones. Initial studies have shown that, with proper computer screening, informative SNP markers can be developed from these DNA databases in an efficient and cost-effective manner. Complete public access to these databases will allow individual investigators to add biological value to the human sequence data generated by large-scale sequencing centers.
Multi-Zone Predictive Modeling of Common Rail Multi-Injection Diesel Engines (2006)

&lt;div class="htmlview paragraph"&gt;The paper deals with the development of a multi-zone phenomenological model for the combustion process in a common rail multi-injection Diesel engine. The model simulates the fuel jet and its interaction with surrounding gases by dividing the jet core into many parcels in order to describe the thermal gradient and the chemical composition within the combustion chamber. This is mandatory for the simulation of the NO pollutant formation, carried out via the Zeldovich mechanism. The air entrainment into the fuel jet is modeled by means of the momentum balance applied to each zone and to the air zone. The stratification of the chemical composition within the cylinder and the details of the spray and its interaction with the air zone are simulated to estimate the spray penetration and speed, the mass of entrained air and the equivalence ratio in each zone. The combustion model is based on the laminar-and-turbulent characteristic-time approach. The three model parameters have been tuned on one engine cycle and the model validation has been accomplished by comparison against a wide set of measurements on a Fiat 1.9 Common-Rail Multi-Jet engine. The simulation results show a very good agreement between measured and predicted engine cycles and NO emissions.&lt;/div&gt;
DNA-mediated gene transfer into adult rat hepatocytes in primary culture. (1990)

Proliferation-competent and differentiation-competent adult rat hepatocytes in primary culture were investigated for their ability to express reporter genes (firefly luciferase, bacterial chloramphenicol acetyltransferase, and bacterial beta-galactosidase) driven by tumor virus or eucaryotic promoters that vary in transcriptional efficiency and tissue specificity. Supercoiled plasmid DNA molecules were introduced into the cells by the calcium phosphate coprecipitation protocol of C. Chen and H. Okayama (Mol. Cell. Biol. 7:2745-2752, 1987). Reporter gene expression was virtually restricted to hepatocytes and was efficient (2 to 20% of the cells). The patterns and absolute levels of reporter gene expression depended on assay conditions employed (plasmid concentration [optimal at 2.4 micrograms of DNA per ml] and duration of exposure [optimal between 5 and 10 h]), culture growth cycle stages (lag, log, or stationary phase), properties and tissue specificity of the promoter(s) tested, and composition (and timing of fluid change) of the culture medium with or without the hepatocyte mitogen human transforming growth factor-alpha. Initial observations suggest that during hepatocellular growth transitions, human transforming growth factor-alpha differentially regulates exogenously introduced promoters associated with hepatocyte-specific function and proliferation. These findings provide a simple, fast, and powerful approach to analyzing the molecular and cellular biology of hepatocyte growth control.
Mediaworm: a qos capable router architecture for clusters (2002)

With the increasing use of clusters in real-time applications, it has become essential to design high-performance networks with quality-of-service (QoS) guarantees. We explore the feasibility of providing QoS in wormhole switched routers, which are widely used in designing scalable, high-performance cluster interconnects. In particular, we are interested in supporting multimedia video streams with CBR and VBR traffic, in addition to the conventional best-effort traffic. The proposed MediaWorm router uses a rate-based bandwidth allocation mechanism, called Fine-Grained VirtualClock (FGVC), to schedule network resources for different traffic classes. Our simulation results on an 8-port router indicate that it is possible to provide jitter-free delivery to VBR/CBR traffic up to an input load of 70-80 percent of link bandwidth and the presence of best-effort traffic has no adverse effect on real-time traffic. Although the MediaWorm router shows a slightly lower performance than a pipelined circuit switched (PCS) router, commercial success of wormhole switching, coupled with simpler and cheaper design, makes it an attractive alternative. Simulation of a (2/spl times/2) fat-mesh using this router shows performance comparable to that of a single switch and suggests that clusters designed with appropriate bandwidth balance between links can provide required performance for different types of traffic.
Single residue substitutions that change the gating properties of a mechanosensitive channel in Escherichia coli. (1996)

MscL is a channel that opens a large pore in the Escherichia coli cytoplasmic membrane in response to mechanical stress. Previously, we highly enriched the MscL protein by using patch clamp as a functional assay and cloned the corresponding gene. The predicted protein contains a largely hydrophobic core spanning two-thirds of the molecule and a more hydrophilic carboxyl terminal tail. Because MscL had no homology to characterized proteins, it was impossible to predict functional regions of the protein by simple inspection. Here, by mutagenesis, we have searched for functionally important regions of this molecule. We show that a short deletion from the amino terminus (3 amino acids), and a larger deletion of 27 amino acids from the carboxyl terminus of this protein, had little if any effect in channel properties. We have thus narrowed the search of the core mechanosensitive mechanism to 106 residues of this 136-amino acid protein. In contrast, single residue substitutions of a lysine in the putative first transmembrane domain or a glutamine in the periplasmic loop caused pronounced shifts in the mechano-sensitivity curves and/or large changes in the kinetics of channel gating, suggesting that the conformational structure in these regions is critical for normal mechanosensitive channel gating.
Cancer-associated molecular signature in the tissue samples of patients with cirrhosis† (2004)

Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P <.001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P <.001). Many genes were previously known to be related to HCC. The 273-gene signature was validated as cancer-associated genes by matching this set to additional independent tumor tissue samples from 163 patients with HCC, 56 patients with lung carcinoma, and 38 patients with breast carcinoma. From this signature, 30 genes were altered most significantly in tissue samples from high-risk individuals with cirrhosis and from patients with HCC. Among them, 12 genes encoded secretory proteins found in sera. In conclusion, we identified a unique gene signature in the tissue samples of patients with cirrhosis, which may be used as candidate markers for diagnosing the early onset of HCC in high-risk populations and may guide new strategies for chemoprevention. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Reflections on the DNS, RFC 1591, and Categories of Domains (2001)

RFC 1591, Name System Structure and Delegation, laid out the basic administrative design and principles for the allocation and administration of domains, from the top level down. It was written before the introduction of the world wide web (WWW) and rapid growth of the Internet put significant market, social, and political pressure on domain name allocations. In recent years, 1591 has been cited by all sides in various debates, and attempts have been made by various bodies to update it or adjust its provisions, sometimes under pressures that have arguably produced policies that are less well thought out than the original. Some of those efforts have begun from misconceptions about the provisions of 1591 or the motivation for those provisions. The current directions of the Internet Corporation for Assigned Names and Numbers (ICANN) and other groups who now determine the Domain Name System (DNS) policy directions appear to be drifting away from the policies and philosophy of 1591. This document is being published primarily for historical context and comparative purposes, essentially to document some thoughts about how 1591 might have been interpreted and adjusted by the Internet Assigned Numbers Authority (IANA) and ICANN to better reflect today's world while retaining characteristics and policies that have proven to be effective in supporting Internet growth and stability. An earlier variation of this memo was submitted to ICANN as a comment on its evolving Top-level Domain (TLD) policies.
Characterization of Dominant-Negative Forms of Anthrax Protective Antigen (2003)

Certain mutations within the protective antigen (PA) moiety of anthrax toxin endow the protein with a dominant-negative (DN) phenotype, converting it into a potent antitoxin. Proteolytically activated PA oligomerizes to form ring-shaped heptameric complexes that insert into the membrane of an acidic intracellular compartment and promote translocation of bound edema factor and/or lethal factor to the cytosol. DN forms of PA co-oligomerize with the wild-type protein and block the translocation process. We prepared and characterized 4 DN forms: a single, a double, a triple, and a quadruple mutant. The mutants were made by site-directed mutation of the cloned form of PA in Escherichia coli and tested by various assays conducted on CHO cells or in solution. All 4 mutant PAs were competent for heptamerization and ligand binding but were defective in the pH-dependent functions: pore formation, ability to convert to the SDS-resistant heptamer, and ability to translocate bound ligand. The single mutant (F427K) showed less attenuation than the others in the pH-dependent functions and lower DN activity in a CHO cell assay. The quadruple (K397D + D425K + F427A + 2beta2-2beta3) deletion showed the most potent DN activity at low concentrations but also gave indications of low stability in a urea-mediated unfolding assay. The double mutant (K397D + D425K) and the triple (K397D + D425K + F427A) showed strong DN activity and slight reduction in stability relative to the wild-type protein. The properties of the double and the triple mutants make these forms worthy of testing in vivo as a new type of antitoxic agent for treatment of anthrax.
Impact of linker length on the activity of PROTACs (2010)

Conventional genetic approaches have provided a powerful tool in the study of proteins. However, these techniques often preclude selective manipulation of temporal and spatial protein functions, which is crucial for the investigation of dynamic cellular processes. To overcome these limitations, a small molecule-based novel technology termed "PROteolysis TArgeting ChimeraS (PROTACs)" has been developed, targeting proteins for degradation at the post-translational level. Despite the promising potential of PROTACs to serve as molecular probes of complex signaling pathways, their design has not been generalized for broad application. Here, we present the first generalized approach for PROTAC design by fine-tuning the distance between the two participating partner proteins, the E3 ubiquitin ligase and the target protein. As such, we took a chemical approach to create estrogen receptor (ER)-α targeting PROTACs with varying linker lengths and the loss of the ER in cultured cells was monitored via western blot and fluorometric analyses. We found a significant effect of chain length on PROTAC efficacy, and, in this case, the optimum distance between the E3 recognition motif and the ligand was a 16 atom chain length. The information gathered from this experiment may offer a generalizable PROTAC design strategy to further the expansion of the PROTAC toolbox, opening new possibilities for the broad application of the PROTAC strategy in the study of multiple signaling pathways.