gebhart/patrepeval huggingface dataset:
Metabolic engineering and flux analysis of Corynebacterium glutamicum for L-serine production (2012)

L-Serine plays a critical role as a building block for cell growth, and thus it is difficult to achieve the direct fermentation of L-serine from glucose. In this study, Corynebacterium glutamicum ATCC 13032 was engineered de novo by blocking and attenuating the conversion of L-serine to pyruvate and glycine, releasing the feedback inhibition by L-serine to 3-phosphoglycerate dehydrogenase (PGDH), in combination with the co-expression of 3-phosphoglycerate kinase (PGK) and feedback-resistant PGDH (PGDH(r)). The resulting strain, SER-8, exhibited a lower specific growth rate and significant differences in L-serine levels from Phase I to Phase V as determined for fed-batch fermentation. The intracellular L-serine pool reached (14.22 ± 1.41) μmol g(CDM) (-1), which was higher than glycine pool, contrary to fermentation with the wild-type strain. Furthermore, metabolic flux analysis demonstrated that the over-expression of PGK directed the flux of the pentose phosphate pathway (PPP) towards the glycolysis pathway (EMP), and the expression of PGDH(r) improved the L-serine biosynthesis pathway. In addition, the flux from L-serine to glycine dropped by 24%, indicating that the deletion of the activator GlyR resulted in down-regulation of serine hydroxymethyltransferase (SHMT) expression. Taken together, our findings imply that L-serine pool management is fundamental for sustaining the viability of C. glutamicum, and improvement of C(1) units generation by introducing the glycine cleavage system (GCV) to degrade the excessive glycine is a promising target for L-serine production in C. glutamicum.
p38 Map Kinase Mediates Bax Translocation in Nitric Oxide–Induced Apoptosis in Neurons (2000)

Nitric oxide is a chemical messenger implicated in neuronal damage associated with ischemia, neurodegenerative disease, and excitotoxicity. Excitotoxic injury leads to increased NO formation, as well as stimulation of the p38 mitogen-activated protein (MAP) kinase in neurons. In the present study, we determined if NO-induced cell death in neurons was dependent on p38 MAP kinase activity. Sodium nitroprusside (SNP), an NO donor, elevated caspase activity and induced death in human SH-SY5Y neuroblastoma cells and primary cultures of cortical neurons. Concomitant treatment with SB203580, a p38 MAP kinase inhibitor, diminished caspase induction and protected SH-SY5Y cells and primary cultures of cortical neurons from NO-induced cell death, whereas the caspase inhibitor zVAD-fmk did not provide significant protection. A role for p38 MAP kinase was further substantiated by the observation that SB203580 blocked translocation of the cell death activator, Bax, from the cytosol to the mitochondria after treatment with SNP. Moreover, expressing a constitutively active form of MKK3, a direct activator of p38 MAP kinase promoted Bax translocation and cell death in the absence of SNP. Bax-deficient cortical neurons were resistant to SNP, further demonstrating the necessity of Bax in this mode of cell death. These results demonstrate that p38 MAP kinase activity plays a critical role in NO-mediated cell death in neurons by stimulating Bax translocation to the mitochondria, thereby activating the cell death pathway.
Biological challenges and technological opportunities for respiratory syncytial virus vaccine development (2010)

Respiratory syncytial virus (RSV) is an important cause of respiratory disease causing high rates of hospitalizations in infants, significant morbidity in children and adults, and excess mortality in the elderly. Major barriers to vaccine development include early age of RSV infection, capacity of RSV to evade innate immunity, failure of RSV-induced adaptive immunity to prevent reinfection, history of RSV vaccine-enhanced disease, and lack of an animal model fully permissive to human RSV infection. These biological challenges, safety concerns, and practical issues have significantly prolonged the RSV vaccine development process. One great advantage compared to other difficult viral vaccine targets is that passively administered neutralizing monoclonal antibody is known to protect infants from severe RSV disease. Therefore, the immunological goals for vaccine development are to induce effective neutralizing antibody to prevent infection and to avoid inducing T-cell response patterns associated with enhanced disease. Live-attenuated RSV and replication-competent chimeric viruses are in advanced clinical trials. Gene-based strategies, which can control the specificity and phenotypic properties of RSV-specific T-cell responses utilizing replication-defective vectors and which may improve on immunity from natural infection, are progressing through preclinical testing. Atomic level structural information on RSV envelope glycoproteins in complex with neutralizing antibodies is guiding design of new vaccine antigens that may be able to elicit RSV-specific antibody responses without induction of RSV-specific T-cell responses. These new technologies may allow development of vaccines that can protect against RSV-mediated disease in infants and establish a new immunological paradigm in the host to achieve more durable protection against reinfection.
Intrauterine Infection and Preterm Delivery (2000)

Preterm delivery is the chief problem in obstetrics today, accounting for 70 percent of perinatal mortality and nearly half of long-term neurologic morbidity.1,2 Approximately 10 percent of all births are preterm, but most of the serious illness and death is concentrated in the 1 to 2 percent of infants who are born at less than 32 weeks of gestation and who weigh less than 1500 g. Approximately 20 percent of preterm births are the result of a physician's decision to bring about delivery for maternal or fetal indications, and the remainder follow the spontaneous onset of labor or rupture . . .
Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells (2007)

Appropriate hematopoietic stem cell (HSC) self-renewal reflects the tight regulation of cell cycle entry and lineage commitment. Here, we show that Id1, a dominant-negative regulator of E protein transcription factors, maintains HSC self-renewal by preserving the undifferentiated state. Id1-deficient HSCs show increased cell cycling, by BrdU incorporation in vivo, but fail to efficiently self-renew, leading to low steady-state HSC numbers and premature exhaustion in serial bone marrow transplant assays. The increased cycling reflects the perturbed differentiation process, because Id1 null HSCs more readily commit to myeloid differentiation, with inappropriate expression of myeloerythroid-specific genes. Thus, Id1 appears to regulate the fate of HSCs by acting as a true inhibitor of differentiation.
How to Build a Beowulf: A Guide to the Implementation and Application of PC Clusters (1999)

This how-to guide provides step-by-step instructions for building aBeowulf-type computer, including the physical elements that make up aclustered PC computing system, the software required (most of which isfreely available), and insights on how to organize the code to exploitparallelism.Supercomputing research-the goal of which is to make computers that are ever faster and more powerful-has been at the cutting edge of computer technology since the early 1960s. Until recently, research cost in the millions of dollars, and many of the companies that originally made supercomputers are now out of business.The early supercomputers used distributed computing and parallel processing to link processors together in a single machine, often called a mainframe. Exploiting the same technology, researchers are now using off-the-shelf PCs to produce computers with supercomputer performance. It is now possible to make a supercomputer for less than $40,000. Given this new affordability, a number of universities and research laboratories are experimenting with installing such Beowulf-type systems in their facilities.This how-to guide provides step-by-step instructions for building a Beowulf-type computer, including the physical elements that make up a clustered PC computing system, the software required (most of which is freely available), and insights on how to organize the code to exploit parallelism. The book also includes a list of potential pitfalls.
Molecular characteristics of some commercial high‐molecular‐weight hyaluronans (2002)

Commercially available hyaluronan (HA) samples were investigated by the method of size exclusion chromatography (SEC). The fractions eluted from the SEC column were on-line molecularly characterized by using a multi-angle laser light scattering (MALLS) photometer. Along with the SEC-MALLS technique, the high-molecular-weight HA biopolymers were (off-line) analyzed by capillary viscometry.
Hydrolysis of RNA by transition metal complexes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrolysis of RNA by transition metal complexesMichael K. Stern, James K. Bashkin, and Erik D. SallCite this: J. Am. Chem. Soc. 1990, 112, 13, 5357–5359Publication Date (Print):June 1, 1990Publication History Published online1 May 2002Published inissue 1 June 1990https://pubs.acs.org/doi/10.1021/ja00169a057https://doi.org/10.1021/ja00169a057research-articleACS PublicationsRequest reuse permissionsArticle Views544Altmetric-Citations85LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
From wood to fuels: Integrating biofuels and pulp production (2006)

Bioethanol currently contributes ∼2% to the total US transportation fuels mix, and another ∼0.01% is based on biodiesel. To make a substantial contribution to the United States' energy portfolio, biofuels production needs to grow substantially over the next decade by a factor of 10 or more. Although the contribution of agro-energy crops and agriculture waste for biofuels production is being intensively developed, the potential of the forest products industry to contribute to this effort has been generally underestimated. The forest products industry is one of a few nationally based industries that have the necessary skill set and infrastructure available to process sufficient biomass for the rapid short-term development and commercialization of biofuel and biochemical technologies. On an annual basis, the US pulp and paper industry collects and processes approximately 108 million tons of wood for the production of pulp and paper in a sustainable manner. Wood extractives from pulping provide approximately 700 million liters of turpentine and tall oil annually that could be employed for biodiesel applications. Wood chip preextraction technologies could make available to the biofuels industry about 14 million tons of hemicelluloses annually while at the same time enhancing the production of kraft pulps. This review highlights the chemical resources available from wood and summarizes which biomaterials are needed for pulp production and which could be utilized for biofuels, with a special emphasis on select hemicelluloses that are currently degraded during kraft pulping that could be utilized for bioethanol production. The review further describes the operational considerations by which the biofuels and pulp manufacturing industries could synergistically operate together.
Is β-homo-proline a pseudo-γ-turn forming element of β-peptides? An IR and VCD spectroscopic study on Ac-β-HPro-NHMe in cryogenic matrices and solutions (2010)

In order to test the pseudo-γ-turn forming capability of β-homo-proline (β(3)-HPro) 2-[(2S)-1-acetylpyrrolidin-2-yl]-N-methylacetamide (Ac-β(3)-HPro-NHMe) was synthesized and its potential energy landscape was investigated by infrared (IR) and vibrational circular dichroism (VCD) spectroscopy combined with density functional calculations. Based upon a comparison between experimental and computed spectra three different pseudo-γ-turn-like trans conformers and a cis conformer were identified in low-temperature Ar and Kr matrices. The computations in agreement with the observations reveal that, in contrast to its α-Pro analogue, the room-temperature abundance of the cis conformer is significant, falling above 10% in the isolated phase. Furthermore, solution-phase vibrational spectra and computations show that the cis conformer is predominant in polar solvents. This result indicates that β(3)-HPro is significantly less apt to form pseudo-γ-turns when compared to the γ-turn forming tendency of α-proline. The present study also shows that the interpretation of solution-phase VCD spectra of flexible molecules should be done with extra caution.
N-acetyltranferase NAT1 and NAT2 genotypes and lung cancer risk (1998)

Acetyltransferases, encoded by the NAT1 and NAT2 genes, are involved in the activation/inactivation reactions of numerous xenobiotics, including tobacco-derived aromatic amine carcinogens. Several allelic variants of NAT1 and NAT2, which cause variations in acetylation capacity, have been detected. The NAT2 slow acetylator phenotype/genotype has been inconsistently associated with lung cancer and, to date, the role of NAT1 polymorphism in lung cancer has not been reported. The effect of NAT1 and NAT2 genetic polymorphisms on individual lung cancer risk was evaluated among 150 lung cancer patients and 172 control individuals, all French Caucasian smokers. The NAT1 alleles (*3, *4, *10, *11, *14, and *15) and the NAT2 alleles (*4, *5, *6, *7) were differentiated by polymerase chain reaction-based restriction fragment length polymorphism methods using DNA extracted from peripheral white blood cells. Genotypes were classified according to current knowledge of the functional activity of the variant alleles. The NAT1*10 and NAT1*11 alleles were considered as rapid alleles, the NAT1*4 and the NAT1*3 as normal alleles and NAT1*14 and NAT1*15 as slow-acetylation alleles. Logistic regression analyses were performed taking into account the age, sex, smoking and occupational exposures. A significant association was observed between lung cancer and NAT1 genotypes (P(homogeneity) < 0.02) with a gene dose effect (P(trend) < 0.01); compared with homozygous rapid acetylators, the lung cancer risk was 4.0 (95% confidence interval 0.8-19.6) for heterozygous rapid acetylators, 6.4 (95% confidence interval 1.4-30.5) for homozygous normal acetylators and 11.7 (95% confidence interval 1.3-106.5) for heterozygous slow acetylators. None of the individuals were homozygous slow acetylators. Similar results were obtained whatever the adjustment considered. No significant association was found between NAT2 genotype and lung cancer. The NAT1 polymorphism may thus be an important modifier of individual susceptibility to smoking-induced lung cancer.
Photon-counting double-random-phase encoding for secure image verification and retrieval (2012)

Preprint
An implantable CMOS circuit interface for multiplexed microelectrode recording arrays (1992)

A second-generation multichannel probe designed for measuring single-unit activity in neural structures is described. The probe includes CMOS circuitry for electronically positioning the recording sites with respect to the active neurons and for amplifying and multiplexing the recorded signals. The probe selects eight active recording sites from among 32 on the probe shank using a static input channel selector. The neural signals on the selected channels are then amplified and multiplexed to the outside world. The probe offers a typical AC gain of 300 (15 Hz to 7 kHz), a DC gain of 0.3, and an equivalent input noise of 15 mu V rms. Operating from a single 5-V supply, the probe dissipates 2.5 mW of power and implements channel selection, self-testing, data output, and initialization using three external leads. The probe is realized using 12 masks in a high-yield single-sided dissolved wafer process with a 3- mu m feature size for the circuitry and a 3- mu m pitch on the electrode shanks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
N,N-dimethylglycyl-amido derivative of minocycline and 6-demethyl-6-desoxytetracycline, two new glycylcyclines highly effective against tetracycline-resistant gram-positive cocci (1994)

The in vitro activities of the N,N-dimethylglycyl-amino derivative of minocycline (DMG-MINO) and 6-dimethyl-6-dexoxytetracycline (DMG-DMDOT), members of a new generation of tetracyclines, were evaluated by an agar dilution method and were compared with those of tetracycline and minocycline against 224 tetracycline-resistant and 73 tetracycline-susceptible recent clinical isolates of gram-positive cocci, including multiple-antibiotic-resistant methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The MICs of DMG-MINO and DMG-DMDOT were up to 500- to 2,000-fold lower than those of tetracycline against methicillin-resistant S. aureus and Streptococcus pneumoniae (MIC for 50% of strains tested [MIC50], < 0.06 microgram/ml). Against Streptococcus groups A, B, C, and G and Enterococcus faecalis, the MIC50 was 0.5 microgram/ml. MIC50s were greater only for coagulase-negative staphylococci (2 micrograms/ml). These data indicate that DMG-MINO and DMG-DMDOT are very potent drugs, and further in vitro and in vivo studies are warranted.
Antigen Presentation by Major Histocompatibility Complex Class I-B Molecules (1994)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Resistance to Activated Protein C in Nine Thrombophilic Families: Interference in a Protein S Functional Assay (1993)

Nine thrombophilic patients who had had previous diagnoses of functional protein S deficiency were reinvestigated. The functional protein S assays gave dose-response curves that were not parallel to those of the reference plasma. The same pattern was true for approximately half of the first-degree relatives of the propositi. When protein S was extracted from the plasma of the patients by immunoabsorption, it had a normal ratio of functional activity to immunologic concentration. Restriction fragment length polymorphism analysis, informative in one family, showed no linkage between the protein S gene marker and the abnormal behavior of the protein S functional assay. All the propositi and 23/36 first-degree relatives were resistant to the prolongation of activated partial thromboplastin time induced by activated protein C. Furthermore, there was striking concordance in all patients and relatives between the abnormal pattern of the protein S functional assay and resistance to activated protein C. We conclude that a plasma-based functional protein S assay is sensitive to activated protein C resistance and this may lead to spuriously low results in the assay. In agreement with the results of others, this study indicates that resistance to activated protein C is a frequent hemostatic defect in selected thrombophilic populations.
Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) (2011)

A 5-level version of the EQ-5D has been developed by the EuroQol Group. Further testing is required to determine whether the new version improves sensitivity and reduces ceiling effects.
The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin-resistant Enterococcus faecium (1999)

A progressive increase in the incidence of vancomycin resistance in strains of Enterococcus faecium (VREF) has severely constrained treatment options for patients with infection caused by this emerging pathogen. Quinupristin/dalfopristin (Synercid), the first injectable streptogramin antibiotic, is active in vitro against VREF, with an MIC90 of 1.0 mg/L. We studied the clinical efficacy and safety of quinupristin/dalfopristin in the treatment of VREF infection. Two prospective studies were conducted simultaneously. The first enrolled only patients with VREF infection; the second included patients with infection caused by other gram-positive bacterial pathogens in addition to VREF. Patients were enrolled if they had signs and symptoms of active infection and no appropriate alternative antibiotic therapy. The recommended treatment regimen of quinupristin/dalfopristin was 7.5 mg/kg i.v. every 8 h for a duration judged appropriate by the investigator. A total of 396 patients with VREF infection were enrolled. The most frequent indications for treatment included intra-abdominal infection, bacteraemia of unknown origin, urinary tract infection, catheter-related bacteraemia, and skin and skin structure infection. This patient population had a high prevalence of severe underlying illness, including a history of diabetes mellitus, transplantation, mechanical ventilation, dialysis, chronic liver disease with cirrhosis and oncological disorders. The mean (+/- S.D.) duration of treatment was 14.5 +/- 10.7 days (range: 1-108). The majority of patients (82.1%) were treated every 8 h, as assessed on day 2 of treatment, while 15.9% were treated every 12 h. The clinical success rate was 73.6% [142/193 clinically evaluable patients; 95% confidence interval (CI): 67.4%, 79.8%], the bacteriological success rate 70.5% (110/156 bacteriologically evaluable patients; 95% CI: 63.4%, 77.7%) and the overall success (both clinical and bacteriological success) rate 65.8% (102/156 bacteriologically evaluable patients; 95% CI: 57.9%, 72.9%). VREF bacteraemia at entry, mechanical ventilation and laparotomy were associated with a worse outcome. Quinupristin/dalfopristin was generally well tolerated. The most common systemic adverse events related to treatment were arthralgias (9.1%) and myalgias (6.6%). Related laboratory abnormalities were infrequent. In these severely ill patients with VREF infection and no other clinically appropriate therapeutic alternatives, quinupristin/dalfopristin demonstrated substantial efficacy and a good nervous system, cardiovascular, gastrointestinal, renal and hepatic tolerability.
Si/SiGe modulation doped field-effect transistor with two electron channels (1991)

Si/SiGe modulation doped field-effect transistors with a two-dimensional electron gas in a cap and in a regular channel, 10 nm and 40 nm underneath the gate, were realised. The bias dependent population of the channels is explained by means of the bandstructure. High extrinsic transconductances of 155 mS/mm for the upper channel and 80 mS/mm for the deeper channel were obtained. Significant device improvements due to source/drain contact implantation are demonstrated by comparison with simultaneously processed devices with alloyed contacts.