gebhart/patrepeval huggingface dataset:
Osteopontin as a Potential Diagnostic Biomarker for Ovarian Cancer (2002)

Our findings provide evidence for an association between levels of a biomarker, osteopontin, and ovarian cancer and suggest that future research assessing its clinical usefulness would be worthwhile.
A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. (2000)

We report the characterization of a novel serine protease of the chymotrypsin family, recently isolated by cDNA-representational difference analysis, as a gene overexpressed in pancreatic cancer. The 2.3-kb mRNA of the gene, named TMPRSS3, is strongly expressed in a subset of pancreatic cancer and various other cancer tissues, and its expression correlates with the metastatic potential of the clonal SUIT-2 pancreatic cancer cell lines. The deduced polypeptide sequence consists of 437 amino acids and exhibits all of the structural features characteristic of serine proteases with trypsin-like activity. TMPRSS3 is membrane bound with a NH2-terminal signal-anchor sequence and a glycosylated extracellular region containing the serine protease domain. Thus, TMPRSS3 is a novel membrane-bound serine protease overexpressed in cancer, which may be of importance for processes involved in metastasis formation and tumor invasion.
Characterization of a Galactokinase-Positive Recombinant Strain of Streptococcus thermophilus (2004)

The lactic acid bacterium Streptococcus thermophilus is widely used by the dairy industry for its ability to transform lactose, the primary sugar found in milk, into lactic acid. Unlike the phylogenetically related species Streptococcus salivarius, S. thermophilus is unable to metabolize and grow on galactose and thus releases substantial amounts of this hexose into the external medium during growth on lactose. This metabolic property may result from the inability of S. thermophilus to synthesize galactokinase, an enzyme of the Leloir pathway that phosphorylates intracellular galactose to generate galactose-1-phosphate. In this work, we report the complementation of Gal(-) strain S. thermophilus SMQ-301 with S. salivarius galK, the gene that codes for galactokinase, and the characterization of recombinant strain SMQ-301K01. The recombinant strain, which was obtained by transformation of strain SMQ-301 with pTRKL2TK, a plasmid bearing S. salivarius galK, grew on galactose with a generation time of 55 min, which was almost double the generation time on lactose. Data confirmed that (i) the ability of SMQ-301K01 to grow on galactose resulted from the expression of S. salivarius galK and (ii) transcription of the plasmid-borne galK gene did not require GalR, a transcriptional regulator of the gal and lac operons, and did not interfere with the transcription of these operons. Unexpectedly, recombinant strain SMQ-301K01 still expelled galactose during growth on lactose, but only when the amount of the disaccharide in the medium exceeded 0.05%. Thus, unlike S. salivarius, the ability to metabolize galactose was not sufficient for S. thermophilus to simultaneously metabolize the glucose and galactose moieties of lactose. Nevertheless, during growth in milk and under time-temperature conditions that simulated those used to produce mozzarella cheese, the recombinant Gal(+) strain grew and produced acid more rapidly than the Gal(-) wild-type strain.
The N4-hydroxycytidine reduction system in toluenized cells of Salmonella typhimurium. (1977)

1. Enzymatic reduction of N4-hydroxycytidine to cytidine in Salmonella typhimurium is highly specific. The reaction occurs only at the nucleoside level. Free base or its 1-methyl analogue is not reduced. 2. The pH optimum shows a broad plateau with a maximum at pH 7.0. The apparent Km value, estimated in the toluene-treated cells, is 4.8 mM and Vmax 1.4 nmoles/min/mg of wet bacterial weight. The reaction is NADH-dependent, although in toluenized bacterial cells it can occure without addition of any exogenous factor.
A Prominent Serine-rich Region in Vmw175, the Major Transcriptional Regulator Protein of Herpes Simplex Virus Type 1, is not Essential for Virus Growth in Tissue Culture (1990)

Herpes simplex virus type 1 (HSV-1) encodes five immediate early (IE) genes of which at least three are involved in the transcriptional regulation of later classes of viral genes. Perhaps the most important of these regulatory proteins is Vmw175, a nuclear phosphoprotein of 1298 predicted amino acid residues. In the absence of functional Vmw175 the virus fails to activate early or late genes or to repress IE gene expression. All viruses of the sub-family alphaherpes-virinae encode polypeptides that are closely related to Vmw175. Mutational studies have shown that regions of homology within this family of gene regulators are generally of functional importance. One of the most striking conserved stretches of amino acid sequence is a run of serine residues followed by a highly acidic region in the amino-terminal fifth of the polypeptide. We have constructed an HSV-1 virus which lacks this serine-rich run within Vmw175. Surprisingly, the virus was viable in tissue culture cells and expressed apparently normal amounts of viral polypeptides. In plaque assays it was very slightly temperature-sensitive and, depending on the state of the host cells, could generate plaques with a syncytial morphology. The mutant protein was able to bind to DNA in a manner indistinguishable from that of the wild-type polypeptide. We conclude that despite its conservation in all of the alphaherpes-virinae so far sequenced, the serine-rich homology is not important for virus growth in tissue culture.
Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers (2018)

The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown to correlate with tumor mutation load (TML), mismatch repair deficiency (dMMR) status, and programmed cell death-ligand 1 (PD-L1) expression. Herein, we quantify TML, dMMR, and PD-L1 expression and determine their interrelationship in gastrointestinal cancers. Here, a total of 4,125 tumors from 14 different gastrointestinal cancer sites were studied using validated assays. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor specimens using the NextSeq platform. TML was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Microsatellite instability (MSI) was assessed using direct analysis of altered known MSI loci in the target regions of the sequenced genes. PD-L1 expression was analyzed by IHC. Interestingly, right-sided colon and small-bowel adenocarcinomas had the highest prevalence of TML-high tumors (14.6% and 10.2%, respectively). Pancreatic neuroendocrine tumors and gastrointestinal stromal tumors had the lowest rates of TML-high (1.3% and 0%, respectively). TML-high was strongly associated with MSI-H (<i>P</i> < 0.0001). However, all TML-high anal cancers (8.3%) were microsatellite stable (MSS). Higher PD-L1 expression was more likely to be seen in MSI compared with MSS tumors (20.6% vs. 7.8%, <i>P</i> < 0.0001).<b>Implications:</b> TML-high rate varied widely among gastrointestinal cancers. Although MSI is conceivably the main driver for TML-high, other factors may be involved. Future clinical trials are needed to evaluate whether the integration of TML, MSI, and PD-L1 could better identify potential responders to immunotherapy. <i>Mol Cancer Res; 16(5); 805-12. ©2018 AACR</i>.
Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS (2007)

The pituitary adenylate cyclase-activating polypeptide (PACAP) receptor is a class II G protein-coupled receptor that contributes to many different cellular functions including neurotransmission, neuronal survival, and synaptic plasticity. The solution structure of the potent antagonist PACAP (residues 6'-38') complexed to the N-terminal extracellular (EC) domain of the human splice variant hPAC1-R-short (hPAC1-R(S)) was determined by NMR. The PACAP peptide adopts a helical conformation when bound to hPAC1-R(S) with a bend at residue A18' and makes extensive hydrophobic and electrostatic interactions along the exposed beta-sheet and interconnecting loops of the N-terminal EC domain. Mutagenesis data on both the peptide and the receptor delineate the critical interactions between the C terminus of the peptide and the C terminus of the EC domain that define the high affinity and specificity of hormone binding to hPAC1-R(S). These results present a structural basis for hPAC1-R(S) selectivity for PACAP versus the vasoactive intestinal peptide and also differentiate PACAP residues involved in binding to the N-terminal extracellular domain versus other parts of the full-length hPAC1-R(S) receptor. The structural, mutational, and binding data are consistent with a model for peptide binding in which the C terminus of the peptide hormone interacts almost exclusively with the N-terminal EC domain, whereas the central region makes contacts to both the N-terminal and other extracellular parts of the receptor, ultimately positioning the N terminus of the peptide to contact the transmembrane region and result in receptor activation.
Synthesis and Histone Deacetylase Inhibitory Activity of New Benzamide Derivatives (1999)

Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC(50) values of the active compounds were in the range of 2-50 microM. Structure-activity relationship on the benzanilide moiety showed that the 2'-substituent, an amino or hydroxy group, was indispensable for inhibitory activity. Although the electronic influence of the substituent in the anilide moiety showed only a small effect on inhibitory activity, the steric factor in the anilide moiety, especially at positions 3'and 4', played an important role in interaction with the enzyme. Among these benzamide derivatives, MS-275 (1), which showed significant antitumor activity in vivo, has been selected for further investigation.
[Triterpenes. XXVI. On the structure of the horse chestnut saponin (aescin) and the aglycones of various glycosides]. (1969)

Zusammenfassung Das kristalline Hauptsaponin “Aescin” aus den Samen von Aesculus hippocastanum L. stellt ein komplexes Gemisch dar, dessen Einzelverbindungen ein gemeinsames Bauschema haben. Es enthalt ein hochhydroxyliertes Triterpenderivat (Protoaescigenin und Barringtogenol C), das esterartig am C-21 Angelica-bzw. Tiglinsaure und an C-22 vorwiegend Essigsaure enthalt. Uber die OH-Gruppe an C-3 ist eine d -Glucuronsaure glykosidisch gebunden, die in Stellung 2 und 4 zwei Molekule d -Glucose tragt, dabei kann eine d -Glucose teilweise durch d -Xylose oder d -Galaktose ersetzt sein. Die Untersuchung des Aglykonanteils wurde an dem durch enzymatische Spaltung aus Aescin gewonnenen Protoaescigenin-diester XII durchgefuhrt, dessen Struktur durch Rontgenstrukturanalyse geklart worden ist. Durch NMR-Spektroskopie wurde nachgewiesen, dass die Stellung der Sauren auch in den genuinen Saponinen der Pflanze vorliegt. Ferner wurde durch vergleichende NMR-Spektroskopie mit Protoaescigenin die 21β,22α-Diol-Gruppierung von Theasapogenol A und E, Camelliagenin D und Barrigenol R 1 , sowie die 22α-Hydroxy-gruppe in Dihydro-priverogenin A, Camelliagenin B und C und Barrigenol A 1 gesichert.
Untersuchungen zur Substanzpolymerisation spirocyclischer Orthoester mit Et3O+SbCl (1982)

Abstract Die Iösungsmittelfreie kationische Ringöffnungspolymerisation der spirocyclischen Orthoester 1b und 1c ist mit Et 3 O + SbCl initiierbar und führt zu farblosen transparenten Polyesterethern 2b bzw. 2c, , deren Glasübergangstemperatur −14°C bzw. −41°C beträgt. Der gaschromatographisch ermittelte Umsatz‐Zeit‐Verlauf der Polymerisation wird dargestellt und diskutiert. Der als Schlüsselsubstanz für die Synthese von vernetzten Copolymeren aus 1b und 1c benötigte Bis(spiroorthoester) 3 ist aus formelreinem DGEBA und γ‐Butyrolacton als farblose kristalline Verbindung synthetisierbar. Bei der Copolymerisation des Bis(spiroorthoesters) 3 mit 1b im Masseverhältnis 1:9 tritt eine Volumenexpansion von 5,5% auf.
The Pareto archived evolution strategy: a new baseline algorithm for Pareto multiobjective optimisation (2003)

Most popular evolutionary algorithms for multiobjective optimisation maintain a population of solutions from which individuals are selected for reproduction. In this paper, we introduce a simpler evolution scheme for multiobjective problems, called the Pareto archived evolution strategy (PAES). We argue that PAES may represent the simplest possible non-trivial algorithm capable of generating diverse solutions in the Pareto optimal set. The algorithm is identified as being a (1+1) evolution strategy, using local search from a population of one but using a reference archive of previously found solutions in order to identify the approximate dominance ranking of the current and candidate solution vectors. PAES is intended as a good baseline approach, against which more involved methods may be compared, and may also serve well in some real-world applications when local search seems superior to or competitive with population-based methods. The performance of the new algorithm is compared with that of a MOEA based on the niched Pareto GA on a real world application from the telecommunications field. In addition, we include results from experiments carried out on a suite of four test functions, to demonstrate the algorithm's general capability.
Simple Network Paging Protocol - Version 1(b) (1994)

This RFC suggests a simple way for delivering both alphanumeric and numeric pages (one-way) to radio paging terminals. Gateways supporting this protocol, as well as SMTP, have been in use for several months for nationwide paging and messaging. In addition, email filters and SNPP client software for Unix and Windows are available at no cost. Please contact the author for more information.
Eruption-Triggered Avalanche, Flood, and Lahar at Mount St. Helens—Effects of Winter Snowpack (1983)

An explosive eruption of Mount St. Helens on 19 March 1982 had substantial impact beyond the vent because hot eruption products interacted with a thick snowpack. A blast of hot pumice, dome rocks, and gas dislodged crater-wall snow that avalanched through the crater and down the north flank. Snow in the crater swiftly melted to form a transient lake, from which a destructive flood and lahar swept down the north flank and the North Fork Toutle River.
New considerations in the design of microstrip antennas (1998)

Printed microstrip antennas and arrays are known to have limitations in terms of bandwidth and efficiency, all imposed by the very presence of the dielectric substrate. Microstrip arrays printed on a very thin film and separated from the ground-plane by foam were successfully designed; however, the fabrication difficulties associated with the use of foam considerably increases the fabrication cost. In this paper, a new concept is presented. Rather than using a superstrata geometry, the "printed circuit" is etched out of metal and supported at "strategic points" by (metallic or nonmetallic) posts. The main motivation for this work was to obtain large microstrip arrays, which exhibit a higher efficiency than conventional ones, and can be fabricated using inexpensive large quantity production techniques. However, this technology was also used to develop many new types of microstrip antennas. Microstrip elements and arrays based on this technology were designed and fabricated for the L, S, and C bands.
Cytokine regulation of constitutive production of interleukin-8 and -6 by human pancreatic cancer cell lines and serum cytokine concentrations in patients with pancreatic cancer (2002)

Patients with pancreatic cancer frequently demonstrate symptoms such as weight-loss and muscle wasting and have clinical evidence of a systemic inflammatory response. Such effects may be mediated by pro-inflammatory cytokines derived from tumor cells. The production of interleukin-6 and -8 by pancreatic cancer cell lines and the influence of other cytokines on this production was studied. IL-8 was produced by all cell lines and production was increased following exposure to IL-1 and TNF. Cytokine-stimulated, but not basal IL-8 production was reduced by co-incubation with IL-4 in the MIA PaCa-2 and PANC-1 cell lines. The CFPAC cell line produced IL-6, but this production was not altered by IL-1, TNF or IL-4. In the PANC-1 cell line IL-8 and IL-8 receptors were only detected by PCR in cells which had been stimulated with TNF or IL-1. Serum concentrations of IL-6 and IL-8 were elevated in patients with pancreatic cancer compared with controls. In conclusion, human pancreatic cancer cell lines elaborate pro-inflammatory cytokines which have the potential to mediate elements of the systemic inflammatory response.
SmgGDS Regulates Cell Proliferation, Migration, and NF-κB Transcriptional Activity in Non-small Cell Lung Carcinoma (2007)

Non-small cell lung carcinoma (NSCLC) is promoted by the increased activities of several small GTPases, including K-Ras4B, Rap1A, Rap1B, RhoC, and Rac1. SmgGDS is an unusual guanine nucleotide exchange factor that activates many of these small GTPases, and thus may promote NSCLC development or progression. We report here that SmgGDS protein levels are elevated in NSCLC tumors, compared with normal lung tissue from the same patients or from individuals without cancer. To characterize SmgGDS functions in NSCLC, we tested the effects of silencing SmgGDS expression by transfecting cultured NSCLC cells with SmgGDS small interfering RNA (siRNA). Cells with silenced SmgGDS expression form fewer colonies in soft agar, do not proliferate in culture due to an arrest in G(1) phase, and exhibit disrupted myosin organization and reduced cell migration. The transcriptional activity of NF-kappaB in NSCLC cells is diminished by transfecting the cells with SmgGDS siRNA, and enhanced by transfecting the cells with a cDNA encoding SmgGDS. Because RhoA is a major substrate for SmgGDS, we investigated whether diminished RhoA expression mimics the effects of diminished SmgGDS expression. Silencing RhoA expression with RhoA siRNA disrupts myosin organization, but only moderately decreases cell proliferation and does not inhibit migration. Our finding that the aggressive NSCLC phenotype is more effectively suppressed by silencing SmgGDS than by silencing RhoA is consistent with the ability of SmgGDS to regulate multiple small GTPases in addition to RhoA. These results demonstrate that SmgGDS promotes the malignant NSCLC phenotype and is an intriguing therapeutic target in NSCLC.
An integrated process for post-packaging release and vacuum sealing of electroplated nickel packages (2004)

This paper presents a packaging technology that employs a thick nickel film to vacuum seal a MEMS structure at the wafer level. The package is fabricated in a 3-mask process by electroplating a 40-micron thick nickel film over an 8-micron sacrificial photoresist that is removed prior to package sealing. The large fluidic access port enables an 800/spl times/800 /spl mu/m package to be released in less than three hours. Implementation of electrical feedthroughs in this process requires no planarization. Device release is performed after the formation of the first level package. Several mechanisms, based upon localized melting and Pb/Sn solder bumping, for sealing low fluidic resistance feedthroughs have been investigated. This package has been fabricated with an integrated Pirani gauge to further characterize the different sealing technologies. These gauges have been used to establish the hermeticity of the different sealing technologies and have measured a sealing pressure of /spl sim/1.5Torr.
Cadherin-6 gene expression in conventional renal cell carcinoma: a useful marker to detect circulating tumor cells. (2005)

Our data indicate that cadherin-6 gene is frequently expressed in conventional RCCs. Cadherin-6 is a useful molecular marker to detect the circulating cancer cells disseminated from conventional RCC.
Lyase to live by: Sphingosine phosphate lyase as a therapeutic target (2009)

This review provides evidence that SPL is a potential target for pharmacological manipulation for the treatment of malignant, autoimmune, inflammatory and other diseases.
Electric-field-directed growth of aligned single-walled carbon nanotubes (2001)

Electric-field-directed growth of single-walled carbon nanotubes by chemical-vapor deposition is demonstrated. The field-alignment effect originates from the high polarizability of single-walled nanotubes. Large induced dipole moments lead to large aligning torques and forces on the nanotube, and prevent randomization of nanotube orientation by thermal fluctuations and gas flows. The results shall open up possibilities in directed growth of ordered molecular-wire architectures and networks on surfaces.
Detecting protein-DNA interactions in vivo: distribution of RNA polymerase on specific bacterial genes. (1984)

We present an approach for determining the in vivo distribution of a protein on specific segments of chromosomal DNA. First, proteins are joined covalently to DNA by irradiating intact cells with UV light. Second, these cells are disrupted in detergent, and a specific protein is immunoprecipitated from the lysate. Third, the DNA that is covalently attached to the protein in the precipitate is purified and assayed by hybridization. To test this approach, we examine the cross-linking in Escherichia coli of RNA polymerase to a constitutively expressed, lambda cI gene, and to the uninduced and isopropyl beta-D-thiogalactoside (IPTG)-induced lac operon. As expected, the recovery of the constitutively expressed gene in the immunoprecipitate is dependent on the irradiation of cells and on the addition of RNA polymerase antiserum. The recovery of the lac operon DNA also requires transcriptional activation with IPTG prior to the cross-linking step. After these initial tests, we examine the distribution of RNA polymerase on the leucine operon of Salmonella in wild-type, attenuator mutant, and promoter mutant strains. Our in vivo data are in complete agreement with the predictions of the attenuation model of regulation. From these and other experiments, we discuss the resolution, sensitivity, and generality of these methods.
RNAi Extends Its Reach (2003)

Genes are silenced when tiny regulatory RNAs bind to target messenger RNAs. But it is becoming clear that RNA interference goes beyond these interactions. In their perspective, [Matzke and Matzke][1] discuss recent work ([Schramke and Allshire][2]) that shows that the silencing pathway can induce heterochromatin formation in DNA that is normally euchromatic. The heterochromatin can spread laterally to silence nearby genes.

 [1]: http://www.sciencemag.org/cgi/content/full/301/5636/1060
 [2]: http://www.sciencemag.org/cgi/content/short/301/5636/1069
Fast Object Hypotheses Generation Using 3D Position and 3D Motion (2006)

This contribution proposes a method to generate object hypotheses from stereo obstacle detection and image motion. Our algorithm is a general approach since it does not require any a priori information about the shape of the observed objects but relies on the basic assumption that the objects are rigid. The algorithm has two processing stages: First, obstacles are detected using stereo vision. Second, each obstacle is segmented into clusters of consistent motion in 3D space. The clustering process explicitly accounts for measurement uncertainties of stereo disparity and 2d motion. Our system may serve as a general feature for higher-level object detection and classification.