gebhart/patrepeval huggingface dataset:
Interlaboratory validation of a CD71-based flow cytometric method (Microflow®) for the scoring of micronucleated reticulocytes in mouse peripheral blood (2004)

An interlaboratory study was performed to validate an anti-CD71/flow cytometry-based technique for enumerating micronucleated reticulocytes (MN-RETs) in mouse peripheral blood. These experiments were designed to address International Workshop on Genotoxicity Test Procedures validation criteria by evaluating the degree of correspondence between MN-RET measurements generated by flow cytometry (FCM) with those obtained using traditional microscopy-based methods. In addition to these cross-methods data, flow cytometric MN-RET measurements for each blood sample were performed at two separate sites in order to evaluate the reproducibility of data between laboratories. In these studies, groups of male CD-1 mice were treated with vehicle (saline or vegetable oil), a negative control (saline or vegetable oil), or four dose levels of five known genotoxicants (clastogens: cyclophosphamide, benzo[a]pyrene, 5-fluorouracil, methotrexate; aneugen: vincristine sulfate). Exposure occurred on 3 consecutive days via intraperitoneal injection, and blood samples were obtained approximately 24 hr after the final treatment. MN-RET frequencies were determined for each sample based on the analysis of 2,000 (microscopy) and 20,000 (FCM) reticulocytes. Regardless of the method utilized, each genotoxic agent was observed to cause statistically significant increases in the frequency of MN-RETs, and each response occurred in a dose-dependent manner. Spearman's correlation coefficient (rs) for FCM versus microscopy-based MN-RET measurements (nine experiments, 252 paired measurements) was 0.740, indicating a high degree of correspondence between methods. The rs value for all flow cytometric MN-RET measurements performed at the two independent sites was 0.857 (n = 248), suggesting that the automated method is highly transferable between laboratories. Additionally, the flow cytometric system offered advantages relative to microscopy-based scoring, including a greater number of cells analyzed, much faster analysis times, and a greater degree of objectivity. Collectively, data presented in this report suggest that the overall performance of mouse peripheral blood micronucleus tests is enhanced by the use of the flow cytometric scoring procedure.
Question-Driven Semantic Filters for Answer Retrieval (2003)

As part of the task of automated question answering from a large collection of text documents, the reduction of the search space to a smaller set of document passages that are actually searched for answers constitutes a difficult but rewarding research issue. We propose a set of precision-enhancing filters for passage retrieval based on semantic constraints detected in the submitted questions. The approach improves the performance of the underlying question answering system in terms of both answer accuracy and time performance.
S-100 Protein and Neuron-Specific Enolase Concentrations in Blood as Indicators of Infarction Volume and Prognosis in Acute Ischemic Stroke (1997)

The results of our study indicate that measuring blood concentrations of S-100 protein periodically in the first 10 days after cerebral infarction helps to predict infarct volume and the long-term neurological outcome more accurately than periodic measurements of blood concentrations of NSE.
Performance of a residential heat pump operating in the cooling mode with single faults imposed (2006)

System behavior of a R410A residential unitary split heat pump system was investigated. The system was operated in cooling mode and used a thermostatic expansion valve (TXV) as the refrigerant expansion device. Seven artificial faults were tested: compressor/reversing valve leakage, improper outdoor air flow, improper indoor air flow, liquid line restriction, refrigerant undercharge, refrigerant overcharge, and presence of non-condensable gas in the refrigerant.
Diagnostic value of mucins (MUC1, MUC2 and MUC5AC) expression profile in endoscopic ultrasound‐guided fine‐needle aspiration specimens of the pancreas (2007)

Mucins are aberrantly expressed in various malignancies. We immunohistochemically tested mucins expression (MUC1, MUC2 and MUC5AC) in EUS-FNA samples from pancreatic occupying lesions for the diagnostic utility. The prevalence of MUC1, MUC2 and MUC5AC expression in pancreatic cancers were 77.5% (31/40), 10.0% (4/40) and 80.0% (32/40), respectively, and in the benign pancreatic diseases 25% (4/16), 31.3% (5/16) and 43.8% (7/16). MUC1 and MUC5AC significantly overexpressed in pancreatic cancer, and MUC1 negatively related with tumor differentiation degree (p < 0.05). The prevalence of MUC1, MUC2 and MUC5AC expression in pancreatic mucinous neoplasms were 66.7% (12/18), 38.9% (7/18) and 88.9% (16/18), respectively, and in the pancreatic non-mucinous neoplasms 60.5% (23/38), 5.3% (2/38) and 57.9% (22/38). MUC2 and MUC5AC significantly overexpressed in pancreatic mucinous neoplasms, especially MUC2 in benign mucinous neoplasms (p < 0.05). Compared with cytology alone, the combination test of MUC1+cytology, and MUC5AC+cytology could achieve higher sensitivity (85 vs. 65%, 100 vs. 65%) and accuracy (89.3% vs. 73.2%, 91.1% vs. 73.2%) for pancreatic cancer diagnosis; the combination test of MUC2 + cytology, and MUC5AC + cytology could achieve higher sensitivity (77.8% vs. 38.9%, 100% vs. 38.9%), and specificity (97.4% vs. 60.5%, 71.1% vs. 60.5%) accuracy (100% vs. 51.8%, 80.4% vs. 51.8%) for mucinous neoplasm diagnosis. The panel MUC1+/MUC2-/MUC5AC+/ was higher specific in pancreatic cancer diagnosis, as well as MUC1-/MUC2+/MUC5AC+/ in pancreatic mucinous neoplasms. Our observations suggest the mucins expression profile in EUS-FNA specimens has higher value for the diagnosis of pancreatic cancer and mucinous neoplasms.
How Staphylococcus aureus biofilms develop their characteristic structure (2012)

Biofilms cause significant problems in the environment and during the treatment of infections. However, the molecular mechanisms underlying biofilm formation are poorly understood. There is a particular lack of knowledge about biofilm maturation processes, such as biofilm structuring and detachment, which are deemed crucial for the maintenance of biofilm viability and the dissemination of cells from a biofilm. Here, we identify the phenol-soluble modulin (PSM) surfactant peptides as key biofilm structuring factors in the premier biofilm-forming pathogen Staphylococcus aureus. We provide evidence that all known PSM classes participate in structuring and detachment processes. Specifically, absence of PSMs in isogenic S. aureus psm deletion mutants led to strongly impaired formation of biofilm channels, abolishment of the characteristic waves of biofilm detachment and regrowth, and loss of control of biofilm expansion. In contrast, induced expression of psm loci in preformed biofilms promoted those processes. Furthermore, PSMs facilitated dissemination from an infected catheter in a mouse model of biofilm-associated infection. Moreover, formation of the biofilm structure was linked to strongly variable, quorum sensing-controlled PSM expression in biofilm microenvironments, whereas overall PSM production remained constant to ascertain biofilm homeostasis. Our study describes a mechanism of biofilm structuring in molecular detail, and the general principle (i.e., quorum-sensing controlled expression of surfactants) seems to be conserved in several bacteria, despite the divergence of the respective biofilm-structuring surfactants. These findings provide a deeper understanding of biofilm development processes, which represents an important basis for strategies to interfere with biofilm formation in the environment and human disease.
Xeroderma Pigmentosum (1974)

Xeroderma pigmentosum is a hereditary disease clinically manifested primarily on sun-exposed skin, which develops abnormal pigmentation and malignant tumors. Mental retardation, areflexia, and other neurological abnormalities are seen in some patients. Only one biochemical defect has been found: cells from various tissues repair ultraviolet-induced deoxyribonucleic acid (DNA) damage slowly, compared with normal cells. Cell fusion studies show that genetic complementation can occur between fibroblasts from certain pairs of patients, thus overcoming the DNA-repair defect in each member of the pair and demonstrating the heterogeneity of the genetic lesion. The patients at NIH who have slow DNA repair comprise four distinct complementation groups, indicating that at least four mutations can cause defective DNA repair.
Albumin gene expression is down-regulated by albumin or macromolecule infusion in the rat. (1992)

A novel feedback regulatory mechanism operating on transcription of the albumin gene is described in the rat. In 1946, it was proposed that circulating colloids, including serum albumin, may affect the synthesis and/or secretion of albumin in the liver. The molecular basis for this proposed regulation has now been investigated by adding oncotically active macromolecules to the circulation of normal or genetically albumin-deficient Nagase analbuminemic rats (NAR) and analyzing the hepatic expression of genes, including albumin after 24 h. The transcription rate of the albumin gene was higher in NAR than in normal rats and was dramatically reduced by raising serum albumin to 1.6 g/dl. Intravenous infusion of albumin into normal rats also decreased transcriptional activity of the albumin gene by 50-60%, and this decrease correlated with changes in serum colloid osmotic pressure after albumin infusion. Inhibition of albumin gene transcription was also observed upon intravenous infusion of other protein or nonprotein macromolecules, such as gamma-globulin and dextran. This down-regulation appears to control the steady-state level of albumin mRNA in the liver. Aside from a concomitant decrease in apo E gene transcription after albumin or macromolecule infusion, there was no change in the transcription rate of other genes, including those exhibiting liver-preferred or -specific expression (e.g., tyrosine amino-transferase, cytochrome P-450, alpha 1-antitrypsin, apolipoproteins A-I and B, and transferrin) or general cellular expression (e.g., alpha-tubulin, pro alpha 2 collagen, and beta-actin). Feedback regulation of albumin gene expression by serum colloids may serve as a specific homeostatic mechanism to maintain the steady-state level of total protein in the circulation.
Diversification of the Wnt gene family on the ancestral lineage of vertebrates. (1992)

Diversification of the Wnt genes, a family of powerful developmental regulator molecules, is inferred by molecular evolutionary analyses. Fifty-five recently determined partial sequences from a variety of vertebrates and invertebrates, together with 17 published sequences, mostly from the mouse and Drosophila melanogaster, are analyzed. Wnt-1 through -7 originated before the last common ancestor of arthropods and deuterostomes lived. Another round of gene duplication, involving Wnt-3, -5, -7, and -10, occurred after the echinoderm lineage arose, on the ancestral lineage of jawed vertebrates. Increased constraints were imposed on the Wnt genes when jawed vertebrates originated, as indicated by an overall 4-fold lower rate of amino acid replacements in jawed vertebrates compared with invertebrates and jawless vertebrates. The Wnt genes are thus inferred to have undergone a disproportionately high amount of structural and functional evolution in the relatively short time (approximately 100 million years) between the origin of the echinoderm lineage and the first diversification of jawed vertebrates. A model is presented for the relationship of functional diversification of developmental regulators and their rates of amino acid replacement.
Room temperature oxidation enhancement of porous Si(001) using ultraviolet–ozone exposure (1996)

The interaction of porous silicon (001) with ozone and ultraviolet (uv) was investigated at room temperature and ambient pressure. The O/Si atomic ratio in oxidized samples, as measured by Auger depth profiling, was similar to those measured from thermally oxidized samples. For long exposure times (≳15 min), the O/Si ratio stayed constant throughout the porous layer, indicating full oxidation of the porous structure. Additionally, the carbon concentration decreased significantly in the uv–ozone oxidized layers as compared to the untreated porous layers. Oxide layers up to 400 nm were measured. Fourier transform ir absorption measurements show both an increase in the oxygen concentration and a decrease in hydrogen concentration after oxidation. Photoluminescence data show that this method of oxidation quenches light emission from the porous layer. We believe that uv induced excitation of valence electrons results in higher reactivity and diffusion of oxygen and ozone as well as bond softening. The large volume of voids in the porous structure assist penetration of ozone and atomic oxygen throughout the porous structure while the narrow lateral dimensions of the Si skeleton requires a short diffusion length for full oxidation.
Design of a nonnatural deoxyribonucleoside for recognition of GC base pairs by oligonucleotide-directed triple helix formation (1992)

The deoxyribonucleoside 1-(2-deoxy-beta-D-ribofuranosyl)-3-methyl-5-amino-1H-pyrazolo4,3-d]py rimidin-7-one (P1) was designed such that two specific hydrogen bonds would form with guanine (G) of a Watson-Crick guanine-cytosine (GC) base pair in the major groove of double-helical DNA. One edge of the P1 heterocycle mimics N3-protonated cytosine, which would circumvent the pH dependence observed for the formation of triple helices containing C + GC base triplets. P1 was synthesized in five steps and incorporated by automated methods in pyrimidine oligodeoxyribonucleotides. From affinity cleaving analyses, the stabilities of base triplets decrease in the order P1.GC &gt;&gt; P1.CG &gt;&gt; P1.AT approximately P1.TA (pH 7.4, 35-degrees-C). P1 binds GC base pairs within a pyrimidinte triple-helix motif as selectively and strongly as C but over an extended pH range. Oligodeoxyribonucleotides containing P1 residues were shown to bind within plasmid DNA a single 15 base pair site containing five GC base pairs at pH 7.8 and a single 16 base pair site containing six contiguous GC base pairs at pH 7.4.
Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer (2017)

Compared to <i>ALK</i> rearrangements, <i>ROS1</i> rearrangements are associated with lower rates of extrathoracic metastases, including fewer brain metastases, at initial metastatic diagnosis. <i>ROS1</i> resistance mutations, particularly G2032R, appear to be the predominant mechanism of resistance to crizotinib, underscoring the need to develop novel ROS1 inhibitors with activity against these resistant mutants.
Double-scattering/reflection in a Single Nanoparticle for Intensified Ultrasound Imaging (2015)

Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled).
Tautomycetin and tautomycin suppress the growth of medullary thyroid cancer cells via inhibition of glycogen synthase kinase-3β (2009)

Medullary thyroid cancer (MTC) is a relatively uncommon neuroendocrine tumor that arises from the calcitonin-secreting parafollicular cells of the thyroid gland. Unfortunately, MTC frequently metastasizes, precluding curative surgical resection and causing significant morbidity. Thus, there is an urgent need for new treatment modalities. Tautomycin and tautomycetin are antifungal antibiotics isolated from Streptomyces spiroverticillatus and Streptomyces griseochromogens, respectively. Glycogen synthase kinase-3beta is a serine/threonine protein kinase that regulates multiple cellular processes and is important in various cancers, including MTC. Treatment with tautomycin and tautomycetin decreased neuroendocrine markers, suppressed hormonal secretion, and inhibited growth through apoptosis in MTC cells. Importantly, we describe a novel action of these compounds: inhibition of glycogen synthase kinase-3beta.
Inactivation of the Carbamoyltransferase Gene Refines Post-Polyketide Synthase Modification Steps in the Biosynthesis of the Antitumor Agent Geldanamycin (2004)

The post-polyketide synthase modification of geldanamycin (1) biosynthesis is of interest as a means of introducing structural diversity into the compound. From the inactivation of a gene encoding carbamoyltransferase, we demonstrated that the C-17 hydroxylation and the C-21 oxidation precede O-carbamoylation and that the hypothetical progeldanamycin does not possess a double bond at C-4 and C-5. More importantly, our result revealed new intermediates 4,5-dihydro-7-O-descarbamoyl-7-hydroxygeldanamycin (3) and 4,5-dihydrogeldanamycin (5), indicating that O-carbamoylation occurs prior to the C-4,5 cis double bond formation in geldanamycin biosynthesis.
The structure of a thirty-six kilobase region of the human chromosome including the fibroblast interferon gene IFN-β (1981)

The isolation of a human genomic cosmid hybrid containing the interferon beta gene has recently been reported (Gross et al., 1981). This hybrid was mapped using single and double digests and cross-hybridisation with the sub-cloned EcoRI and BgIII fragments. Purified fragments and subclones were used as hybridisation probes against chromosomal "Southern" blots to show that at least half of the region has been cloned without alteration. This cannot at present be confirmed for the rest of the region due to the presence of highly repetitive DNA on these cloned fragments. Sequencing data on the 5'-end of the fibroblast IFN-beta gene shows a high density of direct and inverted repeats. The IFN-beta mRNA coding region contains no intron, although the possibility of other transcription starts is not ruled out. The cloned region shows no similarities to known genomic clones containing IFN-alpha genes.
Detection of Norwalk virus in stool by polymerase chain reaction (1992)

A method of reverse transcription (RT) and polymerase chain reaction (PCR) for the detection of Norwalk virus in human stools was developed. A cationic detergent, cetyltrimethylammonium bromide, was found to effectively remove from stool extracts factors that inhibit the RT-PCR assay. The specificities of the tests were shown by hybridization of the amplified DNA with Norwalk virus-specific cDNA probes and a consistent correlation between virus detection in stools and infection of volunteers. RT-PCR detected virus in stool samples diluted 10(-4) and was about 100 times more sensitive than dot blot hybridization. In serial stool samples collected before and at different times after inoculation of 10 volunteers with Norwalk virus, 37 of 55 were positive by RT-PCR, but only 27 were positive by dot blot hybridization (chi 2 = 22.96; P less than 0.001). Further application of this method should allow detection of Norwalk virus in food or environmental samples such as shellfish and shellfish waters.
Gateway-Assisted Vector Construction to Facilitate Expression of Foreign Proteins in the Chloroplast of Single Celled Algae (2014)

With a rising world population, demand will increase for food, energy and high value products. Renewable production systems, including photosynthetic microalgal biotechnologies, can produce biomass for foods, fuels and chemical feedstocks and in parallel allow the production of high value protein products, including recombinant proteins. Such high value recombinant proteins offer important economic benefits during startup of industrial scale algal biomass and biofuel production systems, but the limited markets for individual recombinant proteins will require a high throughput pipeline for cloning and expression in microalgae, which is currently lacking, since genetic engineering of microalgae is currently complex and laborious. We have introduced the recombination based Gateway® system into the construction process of chloroplast transformation vectors for microalgae. This simplifies the vector construction and allows easy, fast and flexible vector design for the high efficiency protein production in microalgae, a key step in developing such expression pipelines.
Trends in mortality in children hospitalized with meningococcal infections, 1957 to 1987 (1989)

We reviewed charts of 261 children seen at Children's Hospital of Wisconsin from 1957 to 1987 with culture-proven meningococcemia or meningococcal meningitis, and we analyzed trends in mortality and disease severity for that interval. Overall case fatality was 10%, ranging from 9% in the period 1957 to 1963, to 16% in the period 1980 to 1987 (P = 0.15). The percent of patients admitted with severe disease increased from 14% to 38% (P = 0.001). When stratified by disease severity, case-fatality rates did not change with time. We conclude that technologic advances of the past 30 years had no measurable impact on mortality from meningococcal infection in our hospital and that crude case-fatality rates can be misleading if disease severity is not considered.
Prenatal diagnosis of cystic fibrosis by methylumbelliferylguanidinobenzoate protease titration in amniotic fluid (1983)

Amniotic fluids were obtained from 19 mothers who had previously given birth to a child with cystic fibrosis. Measurement of methylumbelliferylguanidinobenzoate (MUGB) reactive proteases suggested that all 19 would have unaffected babies. Amongst the first 10 cases to come to term there were 5 infants with cystic fibrosis. It is concluded that MUGB protease titration is not suitable for the early prenatal diagnosis of cystic fibrosis.