gebhart/patrepeval huggingface dataset:
Microbial synthesis of p‐hydroxybenzoic acid from glucose (2001)

A series of recombinant Escherichia coli strains have been constructed and evaluated for their ability to synthesize p-hydroxybenzoic acid from glucose under fed-batch fermentor conditions. The maximum concentration of p-hydroxybenzoic acid synthesized was 12 g/L and corresponded to a yield of 13% (mol/mol). Synthesis of p-hydroxybenzoic acid began with direction of increased carbon flow into the common pathway of aromatic amino acid biosynthesis. This was accomplished in all constructs with overexpression of a feedback-insensitive isozyme of 3-deoxy-D-arabino-heptulosonic acid 7-phosphate synthase. Expression levels of enzymes in the common pathway of aromatic amino acid biosynthesis were also increased in all constructs to deliver increased carbon flow from the beginning to the end of the common pathway. A previously unreported inhibition of 3-dehydroquinate synthase by L-tyrosine was discovered to be a significant impediment to the flow of carbon through the common pathway. Chorismic acid, the last metabolite of the common pathway, was converted into p-hydroxybenzoic acid by ubiC-encoded chorismate lyase. Constructs differed in the strategy used for overexpression of chorismate lyase and also differed as to whether mutations were present in the host E. coli to inactivate other chorismate-utilizing enzymes. Use of overexpressed chorismate lyase to increase the rate of chorismic acid aromatization was mitigated by attendant decreases in the specific activity of DAHP synthase and feedback inhibition caused by p-hydroxybenzoic acid. The toxicity of p-hydroxybenzoic acid towards E. coli metabolism and growth was also evaluated.
Genome sequencing reveals insights into physiology and longevity of the naked mole rat (2011)

The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
Quantitative Measurement of Intact Alpha-Synuclein Proteoforms from Post-Mortem Control and Parkinson's Disease Brain Tissue by Intact Protein Mass Spectrometry (2014)

A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03).
Rapid prototyping of awareness services using a shared information server (1998)

article Free Access Share on Rapid prototyping of awareness services using a shared information server Author: William F. Walker View Profile Authors Info & Claims ACM SIGCHI BulletinVolume 30Issue 2April 1998pp 95–101https://doi.org/10.1145/279044.279167Published:01 April 1998Publication History 3citation40DownloadsMetricsTotal Citations3Total Downloads40Last 12 Months2Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
The effect of crystallographic orientation on mechanical properties of Ta single crystals grown by electron beam melting methods. (1990)

The Effect of Crystallographic Orientation on Mechanical Properties of Ta
Vehicle location and tracking for IVHS in CDMA microcells (2002)

This paper discusses the use of mobile cellular radio networks for providing vehicle location information to intelligent vehicle/highway system (IVHS) services. We review various automatic vehicle location (AVL) techniques in context to their application in a direct-sequence code-division multiple-access (DS/CDMA) system, in particular, the EIA/TIA/IS-95 standard proposed by Qualcomm Inc. A new matched filter location technique which is suited to the CDMA environment is discussed along with simulated error statistics and recommendations for improvement. We also consider network loading effects in terms of Signaling System 7 (SS7).
Proinsulin Is an Independent Predictor of Coronary Heart Disease (2002)

Increased proinsulin concentrations predict death and morbidity caused by CHD over a period of 27 years, independent of other major cardiovascular risk factors.
Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C. (1995)

Metazoan cyclin C was originally isolated by virtue of its ability to rescue Saccharomyces cerevisiae cells deficient in G1 cyclin function. This suggested that cyclin C might play a role in cell cycle control, but progress toward understanding the function of this cyclin has been hampered by the lack of information on a potential kinase partner. Here we report the identification of a human protein kinase, K35 [cyclin-dependent kinase 8 (CDK8)], that is likely to be a physiological partner of cyclin C. A specific interaction between K35 and cyclin C could be demonstrated after translation of CDKs and cyclins in vitro. Furthermore, cyclin C could be detected in K35 immunoprecipitates prepared from HeLa cells, indicating that the two proteins form a complex also in vivo. The K35-cyclin C complex is structurally related to SRB10-SRB11, a CDK-cyclin pair recently shown to be part of the RNA polymerase II holoenzyme of S. cerevisiae. Hence, we propose that human K35(CDK8)-cyclin C might be functionally associated with the mammalian transcription apparatus, perhaps involved in relaying growth-regulatory signals.
SwarmDock: a server for flexible protein–protein docking (2013)

Protein-protein interactions are central to almost all biological functions, and the atomic details of such interactions can yield insights into the mechanisms that underlie these functions. We present a web server that wraps and extends the SwarmDock flexible protein-protein docking algorithm. After uploading PDB files of the binding partners, the server generates low energy conformations and returns a ranked list of clustered docking poses and their corresponding structures. The user can perform full global docking, or focus on particular residues that are implicated in binding. The server is validated in the CAPRI blind docking experiment, against the most current docking benchmark, and against the ClusPro docking server, the highest performing server currently available.
Thiopurine methyltransferase activity in a French population: h.p.l.c. assay conditions and effects of drugs and inhibitors. (1994)

1. Thiopurine methyltransferase (TPMT) is a cytosolic enzyme involved in the catabolism of thiopurine drugs, which are used to treat cancer patients and organ transplant recipients. Because TPMT activity is polymorphic and under genetic control, large interindividual variations in the immunosuppressive activity and toxicity of these drugs may, at least in part, be inherited. 2. We have developed a specific h.p.l.c. method for measuring 6-methyl mercaptopurine formed from 6-mercaptopurine (6-MP) in red blood cell lysates during the TPMT assay procedure. In blinded assays of 55 samples from adult blood donors, the results of the h.p.l.c. method correlated with those of the radiochemical reference method (r = 0.83, P < 0.001). 3. Using this h.p.l.c. assay, we tested the effect of known inhibitors of TPMT activity (syringic acid, p-anisic acid and tropolone) in vitro and showed that they were highly inhibitory. We also found that drugs often administered concomitantly with 6-MP (prednisone, prednisolone, 6-methylprednisolone, cyclophosphamide, methotrexate, and trimethoprim-sulphamethoxazole) had little or no effect on TPMT activity in vitro. 4. In a group of 300 French individuals, TMPT activity was highly variable, ranging from 4.7 to 35.3 nmol h-1 ml-1 of packed red blood cells (nmol h-1 ml-1 PRBC) with a mean value of 19.3 +/- 4.9. TMPT activity was not influenced by sex. 5. This sensitive and reproducible h.p.l.c. assay for TPMT activity in red blood cells may prove useful for prospective clinical studies designed to optimise dosage regimens of thiopurine drugs (detection limit for 6-methyl mercaptopurine is 5 ng ml-1, intra- and inter-assay variations are 6.8 and 8.2%, respectively).
Network-Aware Operator Placement for Stream-Processing Systems (2006)

To use their pool of resources efficiently, distributed stream-processing systems push query operators to nodes within the network. Currently, these operators, ranging from simple filters to custom business logic, are placed manually at intermediate nodes along the transmission path to meet application-specific performance goals. Determining placement locations is challenging because network and node conditions change over time and because streams may interact with each other, opening venues for reuse and repositioning of operators. This paper describes a stream-based overlay network (SBON), a layer between a stream-processing system and the physical network that manages operator placement for stream-processing systems. Our design is based on a cost space, an abstract representation of the network and on-going streams, which permits decentralized, large-scale multi-query optimization decisions. We present an evaluation of the SBON approach through simulation, experiments on PlanetLab, and an integration with Borealis, an existing stream-processing engine. Our results show that an SBON consistently improves network utilization, provides low stream latency, and enables dynamic optimization at low engineering cost.
Inhibition of interleukin-1 by an interleukin-1 receptor antagonist prevents graft-versus-host disease (1991)

Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT). Dysregulation of inflammatory monokines such as tumor necrosis factor alpha (TNF alpha) has been noted in both clinical and experimental GVHD. We present evidence that interleukin-1 (IL-1), another inflammatory monokine, is an important mediator of GVHD. Expression of the gene for IL-1 alpha as well as the gene for TNF alpha is increased in the skin of mice with GVHD. Inhibition of IL-1 function by the in vivo administration of IL-1 receptor antagonist (IL-1ra) reduces the immunosuppression and mortality of GVHD without impairing the engraftment of hematopoietic stem cells. GVHD thus appears to be a systemic inflammatory process in which monokines, especially IL-1, appear to be important mediators. Inhibition of IL-1 by IL-1ra represents a novel approach to the understanding and control of GVHD.
Reduced Mobility of Fibroblast Growth Factor (FGF)-Deficient Myoblasts Might Contribute to Dystrophic Changes in the Musculature of FGF2/FGF6/mdx Triple-Mutant Mice (2003)

Development and regeneration of muscle tissue is a highly organized, multistep process that requires cell proliferation, migration, differentiation, and maturation. Previous data implicate fibroblast growth factors (FGFs) as critical regulators of these processes, although their precise role in vivo is still not clear. We have explored the consequences of the loss of multiple FGFs (FGF2 and FGF6 in particular) for muscle regeneration in mdx mice, which serve as a model for chronic muscle damage. We show that the combined loss of FGF2 and FGF6 leads to severe dystrophic changes in the musculature. We found that FGF6 mutant myoblasts had decreased migration ability in vivo, whereas wild-type myoblasts migrated normally in a FGF6 mutant environment after transplantation of genetically labeled myoblasts from FGF6 mutants in wild-type mice and vice versa. In addition, retrovirus-mediated expression of dominant-negative versions of Ras and Ral led to a reduced migration of transplanted myoblasts in vivo. We propose that FGFs are critical components of the muscle regeneration machinery that enhance skeletal muscle regeneration, probably by stimulation of muscle stem cell migration.
Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010 (2012)

This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions and have added a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules, 131, or 74.8%, are other than "S" (synthetic), with 85, or 48.6%, actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the anti-infective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 30-year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly.
1 LEARNING TO SEE: RESEARCH IN TRAINING A ROBOT VISION SYSTEM (2016)

Engineered or hard-coded autonomous behaviors tend to be “brittle, ” working for a narrow range of conditions but failing outside that range. Trainable robots capable of learning and adapting to new environments and conditions have the potential for greater robustness and reusability. Trainable robots would not be restricted to learning from their own experience, but could potentially integrate models or lessons learned by other similar robots operating in different conditions, thus achieving a “learning force multiplier”. In this research we began an investigation of issues and methods in robot learning, from definition of the learning objective, training methods, learning algorithms, and integration of models or lessons from multiple training sessions. Our objective in this initial research was not to develop new robot learning technologies, but to explore issues and approaches across all aspects of robot learning. In this stage of the project, we focused on learning to see, specifically learning to discriminate between “Go ” and “NoGo ” terrain.
Fabrication and Characterization of Carbon Nanotube/Poly(vinyl alcohol) Composites (1999)

Are nanotubes ideally suited to a straightforward reinforcing role? Results reported here indicate that that may not be the case, but they could find application as a polymer modifier. A successful route is described for the fabrication of large composite films containing carbon nanotubes based on the formation of a stable colloidal intermediate, a route that should be broadly applicable to a range of nanotube materials and polymers. The resulting thermo-mechanical and electrical properties are discussed. While the stiffness of the composites at room temperature is rather low they show promise at high temperatures.
Importance of Membrane Fusion Mediated by Human Immunodeficiency Virus Envelope Glycoproteins for Lysis of Primary CD4-Positive T Cells (2000)

In established T-cell lines, the membrane-fusing capacity of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins mediates cytopathic effects, both syncytium formation and single-cell lysis. Furthermore, changes in the HIV-1 envelope glycoproteins are responsible for the increased CD4(+) T-cell-depleting ability observed in infected monkeys upon in vivo passage of simian-human immunodeficiency virus (SHIV) chimeras. In this study, a panel of SHIV envelope glycoproteins and their mutant counterparts defective in membrane-fusing capacity were expressed in primary human CD4(+) T cells. Compared with controls, all of the functional HIV-1 envelope glycoproteins induced cell death in primary CD4(+) T-cell cultures, whereas the membrane fusion-defective mutants did not. Death occurred almost exclusively in envelope glycoprotein-expressing cells and not in bystander cells. Under standard culture conditions, most dying cells underwent lysis as single cells. When the cells were cultured at high density to promote syncytium formation, the envelope glycoproteins of the passaged, pathogenic SHIVs induced more syncytia than those of the respective parental SHIV. These results demonstrate that the HIV-1 envelope glycoproteins induce the death of primary CD4(+) T lymphocytes by membrane fusion-dependent processes.
Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder (2008)

All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexamfetamine was generally well tolerated by these patients.
EFFECT OF ORGANIC SUBSTANCE ON THE GROWTH OF PORPHYRIDIUM CRUENTUM (2001)

The growth of P. cruentum when added organic carbon source. organic nitrogen source and group B vitamin into medium were investigated in the present work. Results showed that glucose promoted growth rate observably. When added 2% (W/V) glucose into the medium, the growth rate was doubled and biomass increased 92.6% to that of control after incubated 10 days. organic nitrogen source restrained the growth or harmed to P. cruentum. Vitamin B_(2) and B_(12) also promoted the growth rate.
A new flow-cytometry-based opsonophagocytosis assay for the rapid measurement of functional antibody levels against Group B Streptococcus (2012)

Opsonophagocytosis is the primary mechanism for the clearance of Group B Streptococcus (GBS) by the host, and levels of opsonic antibodies may correlate with protection in preclinical models. A killing-based opsonophagocytosis assay (OPA), can be used to determine the functional activity of vaccine-induced GBS-specific antibodies. The assay, which measures the number of bacterial colonies surviving phagocytic killing in the presence of specific antibodies and complement, is rather expensive, time-consuming and poorly standardized. Here we describe a rapid, sensitive and reproducible fluorescent OPA assay (fOPA) based on flow cytometry analysis (FACS), which allows internalized bacteria to be distinguished from those associated to the plasma membrane of phagocytic cells. Fixed GBS were labeled with pHrodo™, a fluorescent dye which dramatically increases the emitted fluorescence at the acidic conditions present in the phagocytic endosomal compartment. Labeled bacteria were incubated with HL-60 cells differentiated to phagocytes, antibodies and complement, and then analyzed by FACS. A further improvement to our method, allowing to reduce assay variability, consisted on a step of selection of effector cells among the HL-60 population. Analysis of sera from mice immunized with different GBS vaccines revealed comparable sensitivity and specificity with the traditional killing OPA assay (kOPA), and a good correlation between the fluorescent signal of bacteria internalized by HL-60 phagocytes and killing. Remarkably, the pHrodo-based approach reduced the variability observed with other fOPA assays. The obtained data indicate the proposed fOPA as a reliable and useful tool for functional antibody assessment.
20세기 초기 종결어미의 분포와 용법 -표기체와 사용역을 중심으로- (2014)

This paper attempts to examine the use of Korean final endings in the 1900s according to type of text. Most previous studies on early twentieth century final endings have focused on the honorific system; however, the use of final endings in that period is also closely related to writing style shifts. I intend to explore the influence of extralinguistic changes including the advent of modern media and the acceptance of modern knowledge into writing styles by analyzing the use of final endings. I use a corpus consisting of newspaper articles and novels written in pure Korean script, along with editorials and textbooks written in the mixed script of Korean and Classical Chinese. Results showed that the final endings that came into use around the turn of the century were mostly used in pure Korean texts, while endings that were typically used in the fifteenth century eonhaemun were mostly used in mixed script texts. I also found distributional differences according to the text registers (novels, news reports, editorials, and textbooks), and that they reflect the degree of conservativeness of the text. Moreover, the same final endings could be used in different ways depending on the register.