gebhart/patrepeval huggingface dataset:
Neurosteroids in Rat Brain:  Extraction, Isolation, and Analysis by Nanoscale Liquid Chromatography−Electrospray Mass Spectrometry (2003)

A method designed for the analysis of sulfated neurosteroids and unconjugated ketonic neurosteroids in rat brain using nanoscale liquid chromatography-electrospray (nano-LC-ES) mass spectrometry is described. Neurosteroids in rat brain tissue were extracted, purified, and separated into two groups, neutral unconjugated steroids and steroid sulfates, by employing solid-phase partition, cation- and anion-exchange chromatography. The steroid sulfate fraction was analyzed by nano-LC-ES mass spectrometry. Contrary to expectations, the sulfates of pregnenolone and dehydroepiandrosterone (DHEA) were not detected. Internal standards, including pregnenolone sulfate, were recovered and the detection limit of the method was 0.3 ng/g of wet brain. Cholesterol sulfate was detected at a level of 1.2 microg/g of wet brain. The neutral unconjugated steroid fraction was derivatized with hydroxylamine hydrochloride to convert oxosteroids into their oximes. The oximes were isolated using cation-exchange chromatography and were analyzed by nano-LC-ES tandem mass spectrometry. The analyses of the neutral unconjugated steroid fraction confirmed the presence in rat brain of pregnenolone, pregnanolone isomers, progesterone, testosterone, and DHEA, which were characterized by their retention times, the mass of the protonated molecules, and characteristic fragment ions. The levels were estimated by addition of [3,4-(13)C(2)]-progesterone as an internal standard and found to be in a range of 0.04-20 ng/g.
Maze router without a grid map (1992)

Maze routers provide powerful and flexible routing algorithms, but require storage of information for every routing grid and layer. With the advance of manufacturing technology, the number of these grids is often so large that routing programs either run out of memory or become very slow due to excessive paging. This paper presents a new data organization which, with certain modifications to the algorithm, reduces and possibly eliminates the entire grid map. The router has been coded with a special data structure library. Categories: 3.2 8.3 5.2 Other routers have beem invented but, in many situations, we would be using maze routers if it was not for this unfortunate memory problem. For example, a maze router can be very useful at the fist stage of gridless routing - see [4]. Many other routers, such as for example [6], also use grid map, and can benefit from the ideas presented in this paper, which will show that by using a smarter algorithm and better data organization, the amount of information that has to be stored for each grid can be reduced and, eventually, the entire grid map can be completely eliminated. Experimental results and areas open to research are discussed at the end of the paper.
Potent HIV-1 protease inhibitors incorporating meso-bicyclic urethanes as P2-ligands: structure-based design, synthesis, biological evaluation and protein–ligand X-ray studies (2008)

Recently, we designed a series of novel HIV-1 protease inhibitors incorporating a stereochemically defined bicyclic fused cyclopentyl (Cp-THF) urethane as the high affinity P2-ligand. Inhibitor with this P2-ligand has shown very impressive potency against multi-drug-resistant clinical isolates. Based upon the -bound HIV-1 protease X-ray structure, we have now designed and synthesized a number of meso-bicyclic ligands which can conceivably interact similarly to the Cp-THF ligand. The design of meso-ligands is quite attractive as they do not contain any stereocenters. Inhibitors incorporating urethanes of bicyclic-1,3-dioxolane and bicyclic-1,4-dioxane have shown potent enzyme inhibitory and antiviral activities. Inhibitor (K(i) = 0.11 nM; IC(50) = 3.8 nM) displayed very potent antiviral activity in this series. While inhibitor showed comparable enzyme inhibitory activity (K(i) = 0.18 nM) its antiviral activity (IC(50) = 170 nM) was significantly weaker than inhibitor . Inhibitor maintained an antiviral potency against a series of multi-drug resistant clinical isolates comparable to amprenavir. A protein-ligand X-ray structure of -bound HIV-1 protease revealed a number of key hydrogen bonding interactions at the S2-subsite. We have created an active model of inhibitor based upon this X-ray structure.
Exploration and virtual camera control in virtual three dimensional environments (1990)

This paper evaluates three distinct metaphors for exploration and virtual camera control in virtual environments using a six degree of freedom input device. The metaphors are "eyeball in hand", "scene in hand", and "flying vehicle control". These metaphors have been implemented and evaluated using an IRIS workstation and a Polhemus 3Space. The system has the capability to record the motion path followed during an exploration session and this can be recorded and played back to create a movie. Evaluation is through intensive structured interview sessions wherein subjects are required to complete a number of tasks involving three different "toy" environments. None of the metaphors is judged the best in all situations, rather the different metaphors each have advantages and disadvantages depending on the particular task. For example, "scene in hand" is judged to be good for manipulating closed objects, but is not good for moving through an interior; whereas "flying vehicle control" is judged the best for navigating through the interior, but is poor for moving around a closed object.
SETER/PR: a robust 18-gene predictor for sensitivity to endocrine therapy for metastatic breast cancer (2019)

There is a clinical need to predict sensitivity of metastatic hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer to endocrine therapy, and targeted RNA sequencing (RNAseq) offers diagnostic potential to measure both transcriptional activity and functional mutation. We developed the SET<sub>ER/PR</sub> index to measure gene expression microarray probe sets that were correlated with hormone receptors (<i>ESR1</i> and <i>PGR</i>) and robust to preanalytical and analytical influences. We tested SET<sub>ER/PR</sub> index in biopsies of metastastic HR+/HER2- breast cancer against the treatment outcomes in 140 patients. Then we customized the SET<sub>ER/PR</sub> assay to measure 18 informative, 10 reference transcripts, and sequence the ligand-binding domain (LBD) of <i>ESR1</i> using droplet-based targeted RNAseq, and tested that in residual RNA from 53 patients. Higher SET<sub>ER/PR</sub> index in metastatic samples predicted longer PFS and OS when patients received endocrine therapy as next treatment, even after adjustment for clinical-pathologic risk factors (PFS: HR 0.534, 95% CI 0.299 to 0.955, <i>p</i> = 0.035; OS: HR 0.315, 95% CI 0.157 to 0.631, <i>p</i> = 0.001). Mutated <i>ESR1</i> LBD was detected in 8/53 (15%) of metastases, involving 1-98% of <i>ESR1</i> transcripts (all had high SET<sub>ER/PR</sub> index). A signature based on probe sets with good preanalytical and analytical performance facilitated our customization of an accurate targeted RNAseq assay to measure both phenotype and genotype of ER-related transcription. Elevated SET<sub>ER/PR</sub> was associated with prolonged sensitivity to endocrine therapy in patients with metastatic HR+/HER2- breast cancer, especially in the absence of mutated <i>ESR1</i> transcript.
A rapid immunoperoxidase‐based virus neutralization assay for salmonid alphavirus used for a serological survey in Northern Ireland (2003)

A modified virus neutralization (VN) assay was developed to replace an existing assay read on the presence or absence of virus-induced cytopathic effect (CPE). The modified assay used a monoclonal antibody to salmon pancreas disease virus as the first layer of an immunoperoxidase (IPX)-based immunostaining technique to detect viral growth. The IPX-based VN assay required only 3 days to perform, and the adoption of a 96-well microtitre format facilitated a high throughput of samples requiring small volumes of serum, cells and virus. When 352 sera from farmed salmon and 302 sera from farmed trout were tested by both the modified and the original CPE-based assays, overall correlations of 97.72 and 96.03% were, respectively, obtained (96.94% combined). When the modified assay was used to test 188 sera collected from wild salmonids in freshwater river systems in Northern Ireland, no positive results were recorded.
Dorsal root ganglionectomy for failed back surgery syndrome: a 5-year follow-up study (1991)

Dorsal root ganglionectomy has been suggested as a method for the treatment of chronic intractable radicular pain, with theoretical advantages over dorsal rhizotomy, which does not interrupt ventral root afferents. The indications for these procedures in patients with persistent pain following lumbosacral spine surgery are not well established. Long-term results have been reported infrequently, and no published series has a mean follow-up period of more than 30 months. The authors have reviewed their experience with a series of 13 patients with failed back surgery syndrome, in whom dorsal root ganglionectomy was performed. Patients were selected on the basis of clinical presentation and diagnostic root blocks suggesting a monoradicular pain syndrome. Follow-up data were obtained at a mean of 5.5 years following dorsal root ganglionectomy. Follow-up interviews to assess outcome were conducted by a disinterested third party. Treatment "success" (at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in two patients at 2 years after surgery and in none at 5.5 years. Equivocal success (at least 50% relief, without clearcut patient satisfaction) was recorded in one patient at 2 and at 5.5 years postoperatively. Improvements in activities of daily living were recorded in a minority of patients. Loss of sensory and motor function was reported frequently by patients. A minority of patients had reduced or eliminated analgesic intake. These results suggest that dorsal root ganglionectomy has a limited role in the management of failed back surgery syndrome, and that methods to select patients to receive this procedure should be refined or alternative approaches should be considered.
A molecular marker confirms that the rate of adult maturation is largely independent of the rate of pre-adult development inDrosophila melanogaster (1996)

The separation of adult from pre-adult life seen with animals such as Drosophila melanogaster, which are holometabolous and undergo complete metamorphosis, provides the opportunity to examine the contribution of pre-adult rate of development on the rate of maturation and aging of the adult. Recent work has shown that when ambient temperature is used to alter the rate of development there is little effect on adult life span. From this work it has been concluded that the rate of aging is largely independent of the rate of pre-adult development. However, the techniques used to examine life span did not allow for the examination of the earliest events of adult life. Our experimental design used a molecular marker linked to life span as a sensitive measure of determining physiological age. In this way, we were able to evaluate the effect of pre-adult rate of development on the earliest events of adult life. Using ambient temperature to alter both the rate of development in the pre-adult and the rate of aging in the adult independently, we were able to show that it is the ambient temperature at which the adults are living that is the principle determinant of the rate of maturation and aging of the adult. Little effect was seen on the rate of adult maturation in response to an acceleration or a slowing down of the rate of pre-adult development as measured by our molecular marker. These data support the conclusions drawn by others who examined the effect of the rate of development on adult life expectancy. The timing mechanisms at work during pre-adult and adult life appear to be largely regulated separately. If there is such a thing as a physiological clock, it appears to be reset upon eclosion.
Tri-Gate Transistor Architecture with High-k Gate Dielectrics, Metal Gates and Strain Engineering (2006)

We have combined the benefits of the fully depleted tri-gate transistor architecture with high-k gate dielectrics, metal gate electrodes and strain engineering. High performance NMOS and PMOS trigate transistors are demonstrated with I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DSAT</sub> =1.4 mA/μm and 1.1 mA/μm respectively (I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OFF</sub> =100nA/μm, V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">CC </sub> =1.1V and L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">G</sub> =40nm) with excellent short channel effects (SCE)-DIBL and subthreshold swing, DeltaS. The contributions of strain, the lang100rang vs. lang110rang substrate orientations, high-k gate dielectrics, and low channel doping are investigated for a variety of channel dimensions and FIN profiles. We observe no evidence of early parasitic corner transistor turn-on in the current devices which can potentially degrade I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ON</sub> -I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OFF</sub> and DeltaS
Electrical parameters of human blood (2002)

Blood samples taken from healthy donors are diluted with 0.9% saline, to obtain samples with hematocrit values ranging from 31 to 50. Bio-impedance spectroscopy is then performed on these samples. Complex impedance measurements in the frequency range from 100 kHz to 1 MHz were fitted into Cole-Cole diagrams, using a LMS algorithm. Data were interpreted in terms of an equivalent resistor-capacitor circuit. In this hematocrit range, all four Cole-Cole parameters R/sub c/, R/sub i/, F/sub c/, and /spl alpha/, are shown to be a linear function of hematocrit. With increasing concentration of red blood cells, the intracellular conductivity is also increased while extracellular conductivity is reduced and, Cole-Cole plots are shifted upwards to the right, in the complex plane, indicating a higher /spl alpha/ and a lower F/sub c/. We suggest that, parameters R/sub c/, R/sub i/, F/sub c/, and /spl alpha/, are a potential index for clinically evaluating blood samples.
Internalization and catabolism of radiolabelled antibodies to the MHC class-II invariant chain by B-cell lymphomas (1996)

The fate of antibody (Ab) LL1, which reacts with the invariant chain (Ii) subunit of the immature MHC class-II antigen (CD74) after binding to the surface of B-cell lymphomas was investigated. This Ab was internalized and catabolized very rapidly, much faster than other Abs that are considered to be rapidly internalized, such as CD19, CD22 and anti-(transferrin receptor). Such internalization did not depend on Ab cross-linking. The capacity of this uptake process was determined in long-term experiments by increasing the Ab concentration: in 1 day, approx. 8 x 10(5) Ab molecules per cell were catabolized. This analysis was facilitated by the use of radiolabels that are trapped within cells after catabolism of the Abs to which they were conjugated. If the Ab is a reliable marker for the Ii antigen, which is likely, we can conclude that Ii directed to the cell surface appears to be sufficient, indeed more than sufficient, to account for the cell content of mature class-II molecules.
Steroidogenic Acute Regulatory Protein in Bovine Corpora Lutea1 (1996)

Steroidogenic acute regulatory protein (StAR) transfers cholesterol from the outer to the inner mitochondrial membrane to initiate steroidogenesis. Our purpose was to determine the tissue distribution of StAR mRNA and the occurrence of StAR gene products in the bovine corpus luteum (CL). Tissues were taken from the slaughterhouse or by ovariectomy of cattle at specific times after estrus or ovulation. StAR mRNA was identified by Northern analysis employing a 1.6-kb cDNA mouse StAR probe, and polyclonal antiserum against mouse StAR was used in Western analysis of StAR protein in bovine luteal tissue. The mRNA for cytochrome P450 side-chain cleavage enzyme (P450scc) was also evaluated by means of a homologous cDNA probe. Two isoforms of StAR mRNA, approximately 2.9 and 1.8 kb, were present in bovine CL, adrenal, theca, and granulosa cells and caruncles and cotyledons. One, or sometimes two, protein bands were recognized by the mouse StAR antiserum. P450scc mRNA colocalized in all sites where StAR mRNA was found, and in bovine liver. StAR mRNA was low in developing CL, increased 9- to 15-fold during the mid- to late-luteal phase, and disappeared in CL that had regressed. StAR protein concentrations were highly correlated with StAR mRNA throughout the estrous cycle (r = 0.93, p < 0.05). P450scc mRNA abundance did not vary through the luteal phase except for its disappearance in regressed CL. Corpora lutea from intact animals treated with prostaglandin F2 alpha displayed a 50% decline in StAR mRNA over 12 h while P450scc mRNA remained unchanged. At 24 h StAr mRNA was undetectable, while P450scc mRNA had declined to 50% of pretreatment values. We conclude that StAR mRNA and protein are tightly coupled in the bovine CL, being present at low levels during CL development and in elevated concentrations during the midluteal phase, and disappearing in regressed CL within 24 h of prostaglandin-induced luteolysis. We have further shown, for the first time, that StAR mRNA is present in the mammalian placenta.
Development and clinical evaluation of a polymerase chain reaction test for detection of Chlamydia trachomatis (1992)

A polymerase chain reaction (PCR) for the detection of Chlamydia trachomatis was developed and evaluated. Two primer-probe sets were designed; one detected a specific sequence of the plasmid, and the other detected the gene encoding the major outer membrane protein. Both sets reacted species specifically and amplified sequences from all human serovars. A simple protocol was used for sample pretreatment. The PCR was optimized by addition of tetramethylammonium chloride and bovine serum albumin. The results of the PCR with the plasmid primer-probe set were compared with those of culture and the Chlamydiazyme and Gen-Probe PACE 2 tests for urogenital specimens from 220 patients. The rates of prevalence of infection with C. trachomatis were 22.7, 16.4, 15.0, and 14.5%, respectively. The sensitivities of the Chlamydiazyme and Gen-Probe PACE 2 assays compared with culture were 66.7 and 61.1%, respectively, and their sensitivities compared with PCR were 60.0 and 60.0%, respectively. The sensitivity of culture compared with PCR was 70.0%. Forty-eight of the 50 specimens positive by PCR with the plasmid primer-probe set could be confirmed by PCR with the major outer membrane protein primer-probe set or culture. It is concluded that the PCR is the most sensitive technique for laboratory detection of C. trachomatis.
Nucleotide Sequence Variation at Two Genes of the Phenylpropanoid Pathway, the FAH1 and F3H Genes, in Arabidopsis thaliana (2001)

The FAH1 and F3H genes encode ferulate-5-hydroxylase and flavanone-3-hydroxylase, which are enzymes in the pathways leading to the synthesis of sinapic acid esters and flavonoids, respectively. Nucleotide variation at these genes was surveyed by sequencing a sample of 20 worldwide Arabidopsis thaliana ecotypes and one Arabidopsis lyrata spp. petraea stock. In contrast with most previously studied genes, the percentage of singletons was rather low in both the FAH1 and the F3H gene regions. There was, therefore, no footprint of a recent species expansion in the pattern of nucleotide variation in these regions. In both FAH1 and F3H, nucleotide variation was structured into two major highly differentiated haplotypes. In both genes, there was a peak of silent polymorphism in the 5' part of the coding region without a parallel increase in silent divergence. In FAH1, the peak was centered at the beginning of the second exon. In F3H, nucleotide diversity was highest at the beginning of the gene. The observed pattern of variation in both FAH1 and F3H, although suggestive of balancing selection, was compatible with a neutral model with no recombination.
The human thymus microenvironment: heterogeneity detected by monoclonal anti-epithelial cell antibodies. (1985)

Monoclonal antibodies were raised against human thymus stromal cells and their specificity for the epithelial component of thymus stroma assessed by double immunofluorescence using anti-keratin antibodies to identify epithelium. Our monoclonal antibodies identify six distinct patterns of epithelial cell antigen expression within the thymus: pan epithelial (antibody IP1); cortex (MR3 and MR6); cortical/medullary junction (IP2); subcapsule and subpopulation of medulla (MR10/MR14); Hassall's corpuscles and adjacent subpopulation of medulla (IP3); Hassall's corpuscles only (MR13/IP4). This heterogeneity of antigen expression suggests that many different epithelial microenvironments exist within the human thymus.
Alterations in peptidoglycan of Neisseria gonorrhoeae induced by sub-MICs of beta-lactam antibiotics (1987)

Exposure of Neisseria gonorrhoeae to sub-MICs of selected beta-lactam antibiotics caused distortion of normal cell morphology. Analysis of the peptidoglycan indicated that the cells were accumulating increased quantities of disaccharide pentapeptide in their cell walls. The O-acetylated form of the disaccharide pentapeptide was not detected among the major peaks. The correlation of antibiotic binding to gonococcal penicillin-binding protein 2 and accumulation of non-O-acetylated disaccharide pentapeptide suggested an explanation for the previously observed relationship of penicillin-binding protein 2 and O-acetylation of peptidoglycan.
A Comprehensive Structure–Function Analysis ofArabidopsisSNI1 Defines Essential Regions and Transcriptional Repressor Activity (2006)

The expression of systemic acquired resistance (SAR) in plants involves the upregulation of many Pathogenesis-Related (PR) genes, which work in concert to confer resistance to a broad spectrum of pathogens. Because SAR is a costly process, SAR-associated transcription must be tightly regulated. Arabidopsis thaliana SNI1 (for Suppressor of NPR1, Inducible) is a negative regulator of SAR required to dampen the basal expression of PR genes. Whole genome transcriptional profiling showed that in the sni1 mutant, Nonexpresser of PR genes (NPR1)-dependent benzothiadiazole S-methylester-responsive genes were specifically derepressed. Interestingly, SNI1 also repressed transcription when expressed in yeast, suggesting that it functions as an active transcriptional repressor through a highly conserved mechanism. Chromatin immunoprecipitation indicated that histone modification may be involved in SNI1-mediated repression. Sequence comparison with orthologs in other plant species and a saturating NAAIRS-scanning mutagenesis of SNI1 identified regions in SNI1 that are required for its activity. The structural similarity of SNI1 to Armadillo repeat proteins implies that SNI1 may form a scaffold for interaction with proteins that modulate transcription.
Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing (2015)

While a number of factors trend with fetal fraction across the cohort as a whole, they are not the sole determinants of fetal fraction. In this study, the variability for any one patient does not appear large enough to justify postponing testing to a later gestational age.