gebhart/patrepeval huggingface dataset:
Improved Potency of Hyperactive and Actin-resistant Human DNase I Variants for Treatment of Cystic Fibrosis and Systemic Lupus Erythematosus (1998)

The ability of recombinant human DNase I (DNase I) to degrade DNA to lower molecular weight fragments is the basis for its therapeutic use in cystic fibrosis (CF) patients and its potential use as a treatment for systemic lupus erythematosus (SLE). To increase the potency of human DNase I, we have generated and characterized three classes of mutants: (a) hyperactive variants, which have from one to six additional positively charged residues (+1 to +6) and digest DNA much more efficiently relative to wild type, (b) actin-resistant variants, which are no longer inhibited by G-actin, a potent inhibitor of DNase I, and (c) combination variants that are both hyperactive and actin-resistant. For DNA scission in CF sputum where the DNA concentration and length are large, we measured a approximately 20-fold increase in potency relative to wild type for the +3 hyperactive variant Q9R/E13R/N74K or the actin-resistant variant A114F; the hyperactive and actin-resistant combination variant was approximately 100-fold more potent than wild type DNase I. For digesting lower concentrations of DNA complexed to anti-DNA antibodies in human serum, we found a maximal enhancement of approximately 400-fold over wild type for the +2 variant E13R/N74K. The +3 enzymes have approximately 4000-fold enhancement for degrading moderate levels of exogenous DNA spiked into human serum, whereas the +6 enzyme has approximately 30,000-fold increased activity for digesting the extremely low levels of endogenous DNA found in serum. The actin resistance property of the combination mutants further enhances the degree of potency in human serum. Thus, the human DNase I variants we have engineered for improved biochemical and pharmacodynamic properties have greater therapeutic potential for treatment of both CF and SLE.
A self-aligned elevated source/drain MOSFET (1990)

An advanced elevated source/drain CMOS process which features self-aligned lightly-doped drain (LDD) and channel implantation is described. Unlike conventional elevated source/drain structures which employ separate polysilicon deposition steps to define the source/drain and gate electrodes, this new structure provides self-alignment of the LDD regions with the heavily doped channel regions to avoid dopant compensation effects. This process employs a single selective silicon deposition step to define both the epitaxial source/drain and polycrystalline gate regions. A single sidewall spacer is used for both LDD and salicide definition. Unlike conventional elevated source/drain CMOS processes, the final MOSFET structure provides self-alignment of the LDD regions with the heavily doped channel regions. Salicidation is performed after selective silicon deposition to provide low sheet resistances for the source/drain and gate regions. Small-geometry NMOS and PMOS devices have been fabricated which display excellent short channel behavior.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The effect of RU486 on the gene expression profile in an endometrial explant model (2003)

Administration of RU486 in vivo during the receptive phase rapidly renders the endometrium non-receptive to the implanting embryo. In order to identify key pathways responsible for endometrial receptivity we have used cDNA arrays to monitor gene expression changes in short-term endometrial explants in response to RU486. Endometrial biopsies from five normal fertile women at mid-secretory phase were cultured in the presence of estradiol and progesterone with or without RU486 for 12 h. cDNA arrays were produced containing approximately 1000 sequence-verified clones which included genes known to be important in angiogenesis, apoptosis, cell signalling, extracellular matrix remodelling and cell cycle regulation. cDNA probes from the paired endometrial samples were hybridized to the arrays and hybridization signals were quantified. A total of 12 genes displayed significant changes in expression; six were up-regulated and six down-regulated following RU486 treatment. For five of these genes this is the first report suggesting that they are regulated by steroids in the endometrium. JAK1 and JNK1 were two of the genes shown by the arrays to be down-regulated in RU486-treated endometrial explants. This was confirmed by real time RT-PCR. JAK1 immunoreactivity was localized to both glandular epithelium and the stroma of normal endometrium and staining was much stronger in the luteal phase of the cycle. These results show that components of two important signalling pathways in endometrium-the JAK/STAT pathway, and the JNK pathway-are altered by RU486. Genes whose expression is controlled by these pathways are likely to be involved in the mechanism by which steroids render the endometrium receptive to the implanting embryo.
High power cladding light strippers (2008)

The ability to strip cladding light from double clad fiber (DCF) fibers is required for many different reasons, one example is to strip unwanted cladding light in fiber lasers and amplifiers. When removing residual pump light for example, this light is characterized by a large numerical aperture distribution and can reach power levels into the hundreds of watts. By locally changing the numerical aperture (N.A.) of the light to be stripped, it is possible to achieve significant attenuation even for the low N.A. rays such as escaped core modes in the same device. In order to test the power-handling capability of this device, one hundred watts of pump and signal light is launched from a tapered fusedbundle (TFB) 6+1x1 combiner into a high power-cladding stripper. In this case, the fiber used in the cladding stripper and the output fiber of the TFB was a 20/400 0.06/0.46 N.A. double clad fiber. Attenuation of over 20dB in the cladding was measured without signal loss. By spreading out the heat load generated by the unwanted light that is stripped, the package remained safely below the maximum operating temperature internally and externally. This is achieved by uniformly stripping the energy along the length of the fiber within the stripper. Different adhesive and heat sinking techniques are used to achieve this uniform removal of the light. This suggests that these cladding strippers can be used to strip hundreds of watts of light in high power fiber lasers and amplifiers.
Multi-rate nonlinear state and parameter estimation in a bioreactor (1998)

This paper concerns real-time, multirate, nonlinear, state and parameter estimation in a pilot-scale, mouse-mouse hybridoma cell, biochemical reactor. A multirate estimator was designed and implemented to estimate specific growth rate and concentrations of viable cells, total cells, glucose, glutamine, and monoclonal antibodies (MAb) in the reactor. These were estimated from frequent measurement (inferred values) of oxygen uptake rate (OUR) and infrequent and delayed measurements of the concentrations of viable cells, total cells, glucose, glutamine, and MAb. The infrequent measurements were available every 2 to 17 hours with time delays of 0.08 to 2.00 hours, and OUR was inferred from dissolved oxygen concentration measurements that were available every 0.17 hour.
Improved efficacy and enlarged spectrum of activity of a novel anthracycline disaccharide analogue of doxorubicin against human tumor xenografts. (1998)

On the basis of a structure-activity study of a new series of anthracycline disaccharides, we recently identified a doxorubicin analogue (MEN 10755) with a promising antitumor activity. In the present study, to better support the pharmacological interest of MEN 10755, we extended the preclinical evaluation of antitumor efficacy to a large panel of 16 human tumor xenografts, which originated from different clinicopathological types. Tumors with typical multidrug-resistant phenotype were excluded because MEN 10755 was found unable to overcome resistance mediated by transport systems. In the doxorubicin-responsive series, MEN 10755 exhibited a higher activity in three of five tumors, as documented by a more marked tumor growth inhibition and an increased value of log-cell kill. In the series of doxorubicin-resistant tumors, MEN 10755 was found effective in 6 of 11 tumors (1 breast, 3 lung, and 2 prostate carcinomas). The overall response rates were 31% and 69% for doxorubicin and MEN 10755, respectively. The improvement in drug efficacy was also supported by a substantial increase in the long-term survivor rate of animals implanted with responsive tumors. Most of the tumors refractory to doxorubicin and responsive to MEN 10755 were characterized by overexpression of the antiapoptotic protein Bcl-2. In one of these tumors (MX-1 breast carcinoma), we examined the ability of MEN 10755 to induce phosphorylation of Bcl-2 after a single treatment with therapeutic doses. The results indicated that, unlike doxorubicin, MEN 10755 induced protein phosphorylation. A similar modification was produced by Taxol, which is known to be very effective against the tumor. The correlation between drug efficacy and Bcl-2 phosphorylation may underly a peculiar feature related to improvement of efficacy of the disaccharide analogue. In conclusion, the present study supports some favorable features of the novel doxorubicin analogue in terms of both efficacy and tolerability with comparison to doxorubicin, although the improvement is somewhat tumor- and schedule-dependent.
Improvements to the Synthesis of Polyimide Aerogels (2011)

Cross-linked polyimide aerogels are viable approach to higher temperature, flexible insulation for inflatable decelerators. Results indicate that the all-polyimide aerogels are as strong or stronger than polymer reinforced silica aerogels at the same density. Currently, examining use of carbon nanofiber and clay nanoparticles to improve performance. Flexible, polyimide aerogels have potential utility in other applications such as space suits, habitats, shelter applications, etc. where low dusting is desired
Mucosa-associated bacterial flora of the human colon (1997)

Biopsy samples of mucosa were taken during colonoscopy from the proximal colon and rectum of 12 patients, six with ulcerative colitis (UC) and six with non-inflammatory conditions. After anaerobic transport to the laboratory, biopsy specimens were examined by quantitative bacteriological culture on selective and non-selective media for total aerobic count, total anaerobic count, Bacteroides spp., lactobacilli, bifidobacteria and asaccharolytic, lactic acid producers. Isolates of the genus Bacteroides were identified to species level. Counts from proximal colonic and rectal biopsy samples in the same patient were not significantly different. Viable aerobic counts (aerobes and facultative organisms) ranged from 2.4 x 10(3) to 1.3 x 10(6) cfu/sample biopsy (5.6 mg) and total anaerobic counts were 10-10(2) times higher at (1.4 x 10(5))-(3 x 10(7)) cfu/sample. Bacteroides spp. predominated at both sites (range 8.6 X 10(4) to 1.4 x 10(7) cfu/sample), comprising 66% of total counts from proximal colon (range in individual patients 31-80%) and 68.5% from rectum (range 38-91%). Lactobacilli were isolated from eight biopsy samples from five patients, counts ranging from 3.6 X 10(2) to 1 X 10(5) cfu/sample; bifidobacteria were isolated from both sites from 10 of the 12 patients, counts ranging from 50 to 1.8 x 10(6) cfu/sample. From the 24 biopsy samples, 235 isolates representing 11 species of Bacteroides were identified. For any individual patient, only a few species (2-7; mean 4.4) of Bacteroides were found, with just one or two species predominating. B. vulgatus was cultured from both samples of seven patients (where it was the major isolate in four) and from single samples of two others; B. fragilis was cultured from both sites in six patients, being the major isolate in one patient and second commonest in three, but was not detected in the other six; the majority of other isolates were B. merdae/distasonis, B. ovatus, B. thetaiotaomicron and B. uniformis. B. thetaiotaomicron was isolated from both biopsy samples in all three UC patients with active inflammation (16 of the 60 isolates from these patients) but from only four of the other 18 samples from non-inflamed colonic mucosa (nine of 175 isolates).
Oil Base Foam Fracturing Applied to the Niobrara Shale Formation (1980)

ABSTRACT The Niobrara Shale wells in the Overland Dome field of Wyoming have undergone a variety of well completion procedures. Stimulation treatments have utilized gelled oil, gelled water, water base foams, and co-mingled CO2 and oil. These systems have not been completely successful. In the authors’ opinion, these systems have not satisfied the fluid loss and fluid compatibility requirements necessary to successfully fracture the Niobrara Shale formation. The oil foam system described in this paper has excellent fluid loss properties, is an efficient proppant carrier, and is compatible with the formation. The use of this fluid appears to offer the most promising technique thus far used to stimulate the Niobrara Shale. The process appears economical. The largest treatment performed to date has been 100,000 pounds of sand with 100,000 gallons of foamed oil, utilizing less than 400 hydraulic horsepower. Use of the oil base foam fracturing procedure has successfully led to the reactivation of the field. It has also been applied to the shaley, silty Frontier Formation in this same field. The most successful previous treatment had a sustained maximum production of 8-10 BOPD. Utilization of improved completion procedures and the oil foam fracturing process has resulted in stabilized increased production from old, existing wells. On new wells the production has ranged to BOPD. For better application of the fracturing fluid to the most potential zones, natural fractures were identified and these zones were perforated on a limited entry basis. The previously commercially unproductive Frontier Formation in this field has been treated with the same technique and has resulted in economical wells. This paper will describe the geology, completion techniques, and the fluid and procedures used to stimulate the Niobrara Shale formation.
Target-Sequence Recognition by Separate-type Cys2/His2 Zinc Finger Proteins in Plants (1996)

The EPF family is a group of transcription factors containing canonical Cys2/His2-type zinc finger motifs that were first discovered in plants. These zinc finger proteins are characterized by two zinc fingers that are separated by spacers of various lengths, which are much longer than typical spacers (HC-link) in cluster-type zinc finger proteins. We describe here direct evidence that the two zinc fingers make contact with two tandemly repeated AGT core sequences that are separated by about 13 base pairs, by contrast to the cluster-type zinc finger proteins that bind to contiguous triplet sequences. DNA binding affinities were sensitive to the spaces between the core sequences, and the sensitivity to the spacing was greatly affected by the DNA sequence between the core sequences, with GC-rich sequences endowing much higher specificity than AT-rich sequences. Among the members of the EPF family, EPF1 was less sensitive to the spacing than EPF2-5. These results suggest that EPFs recognize their cognate target DNAs not only by the sequence of the core sites but also by the spacing between the core sites and, moreover, that different members in the EPF family distinguish their specific target genes by reference to these two parameters. This represents a unique type of target-sequence recognition among Cys2/His2-type zinc finger transcription factors. In addition, site-directed mutagenesis studies demonstrated that the two zinc fingers contribute synergistically to the binding to DNA, indicating that both fingers are necessary for the high affinity DNA binding.
Highly Attenuated HIV Type 2 Recombinant Poxviruses, but Not HIV-2 Recombinant Salmonella Vaccines, Induce Long-Lasting Protection in Rhesus Macaques (1995)

Immunization schemes employing priming with vector-based vaccine candidates followed by subunit booster administrations have been explored and shown to have merit in the human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus systems. In this study, we have assessed the priming capacity of highly attenuated poxvirus vector (NYVAC and ALVAC)-based HIV-2 recombinants, as well as Salmonella typhimurium HIV-2 recombinants in rhesus macaques. ALVAC- and NYVAC-based vaccine candidates expressing the HIV-2 gag, pol, and env genes or NYVAC-based recombinants expressing either gp160 or gp120 were used to immunize rhesus macaques in combination protocols with alum-adjuvanted HIV-2 rgp160. Following intravenous challenge exposure with 100 infectious doses of the HIV-2SBL6669 parental virus genotype mixture, seven of eight animals were protected from infection. The seven protected animals were rechallenged 6 months postprimary challenge, without additional booster inoculations, with the same dose of the HIV-2SBL6669 parental virus. Five of the seven animals remained protected against HIV-2 infection at 6 months following the second challenge. In contrast, oral immunization with recombinant Salmonella expressing the HIV-2 gag and the gp120 portion of the envelope either alone or in combination with alum-adjuvanted rgp160 failed to confer protection. These results suggest that the NYVAC- and ALVAC-based recombinants may confer long-lasting protection and that these two highly attenuated poxvirus vaccine vectors may represent promising candidates for developing an acquired immunodeficiency syndrome vaccine.
Brain-computer interfaces based on the steady-state visual-evoked response (2000)

The Air Force Research Laboratory has implemented and evaluated two brain-computer interfaces (BCI's) that translate the steady-state visual evoked response into a control signal for operating a physical device or computer program. In one approach, operators self-regulate the brain response; the other approach uses multiple evoked responses.
Robot Path Planning with Obstacles, Actuator, Gripper, and Payload Constraints (1989)

A method is presented to obtain the time-optimal motions for robotic manipulators. It considers the full nonlinear dy namics of the manipulator, its actuator saturation limits, and gripper and payload constraints. It also accounts for both the presence of obstacles in the work space and restrictions on the motion of the manipulator's joints. The method is com putationally practical and has been implemented for the optimal trajectory planning of general six degree-of-freedom manipulators. Examples are presented that demonstrate the substantial improvement in manipulator performance that can be achieved using this method.
p21 as a Common Signaling Target of Reactive Free Radicals and Cellular Redox Stress (1995)

Reactive free radicals have been implicated in mediating signal transduction by a variety of stimuli. We have investigated the role of p21ras in mediating free radical signaling. Our studies revealed that signaling by oxidative agents which modulate cellular redox status, such as H2O2, hemin, Hg2+, and nitric oxide was prevented in cells in which p21ras activity was blocked either through expression of a dominant negative mutant or by treating with a farnesyltransferase inhibitor, as assessed by NF-kappa B binding activity. Furthermore, the NF-kappa B response to these oxidative stress stimuli was found to be enhanced when cells from the human T cell line, Jurkat, were pretreated with L-buthionine-(S,R)-sulfoximine, an inhibitor of glutathione synthesis. We directly assayed p21ras and mitogen-activated protein kinase activities in Jurkat cells and found both of these signaling molecules to be activated in cells treated with the redox modulating agents. Blocking glutathione synthesis made cells 10- to 100-fold more sensitive to these agents. Finally, using recombinant p21ras in vitro, we found that redox modulators directly promoted guanine nucleotide exchange on p21ras. This study suggests that direct activation of p21ras may be a central mechanism by which a variety of redox stress stimuli transmit their signal to the nucleus.
Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism (2016)

Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans.
Advances in factor analysis and structural equation models (1979)

The articles in this book develop the basic ideas of causal modeling and illustrate them for a wide range of applications in the social sciences. Causal modeling requires researchers to think through all the conceptual implications associated with a given specification. A causal model is said to be misspecified (and inadequate) if the assumptions are incorrect and do not allow the desired causal interpretation of the parameters. A common source of misspecification derives from the omission of a major causative factor that is correlated with at least 1 predictor variable included in the model. Causal modeling in the social sciences is especially challenging and complex because the causes of a given outcome are typically unknown or not susceptible to direct observation. Moreover the observed patterns among the variables may be consistent with a variety of causal explantations. Thus it is often desirable to formulate and test a variety of models. Some models may be ruled out on comon sense grounds. For example although educational aspirations may differ by race aspirations cannot cause race. Other models might be rejected only if they yield inferences inconsistent (within statistical limits) with the pattern of relationships actually observed. Causal modeling can be used to state theory more exactly to test theory more precisely and to yield a more thorough understanding of data. The methods in this book do not provide final answers to the question of model specification. What they offer the researcher is the flexibility to formulate and test a variety of causal models and to guide the analysis toward more adequate explanations of the relationships embedded in data.
Ischemic Colitis and Complications of Constipation Associated With the Use of Alosetron Under a Risk Management Plan: Clinical Characteristics, Outcomes, and Incidences (2010)

Serious outcomes associated with IC and CoC appear to be mitigated since introduction of alosetron under the RMP.
Isolation of Genetic Suppressor Elements (GSEs) from Random Fragment cDNA Libraries in Retroviral Vectors (2003)

Cellular phenotypes resulting from decreased function of a specific gene are manifested as recessive, since they are suppressed in the presence of a normal allele of the corresponding gene. The powerful gene-transfer techniques, which have played a key role in the studies of dominant phenotypes, are not readily applicable to recessive traits, since expression of a recessive allele does not generally affect the cellular phenotype. In haploid organisms, random gene disruption can be used as a general method of cloning recessive genes, but this approach is limited to genes that are not essential for cell growth and is not, at least presently, applicable to diploid cells. This explains why studies of recessive genes of higher eukaryotes (e.g., tumor suppressor genes) are in many cases lagging far behind the analysis of dominant genes (e.g., oncogenes).