gebhart/patrepeval huggingface dataset:
Recent developments in biological hydrogen production processes (2008)

Biohydrogen production technology can utilize renewable energy sources like biomass for the generation of hydrogen, the cleanest form of energy for the use of mankind. However, major constraints to the commercialization of these processes include lower hydrogen yields and rates of hydrogen production. To overcome these bottlenecks intensive research work has already been carried out on the advancement of these processes such as the development of genetically modified microorganisms, the improvement of the bioreactor design, molecular engineering of the key enzyme hydrogenases, the development of two stage processes, etc. The present paper explores the recent advancements that have been made till date and also presents the state of the art in molecular strategies to improve the hydrogen production.
Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice (2011)

Biochemical studies have suggested conflicting roles for the E3 ubiquitin ligase constitutive photomorphogenesis protein 1 (Cop1; also known as Rfwd2) in tumorigenesis, providing evidence for both the oncoprotein c-Jun and the tumor suppressor p53 as its targets. Here we present what we believe to be the first in vivo investigation of the role of Cop1 in cancer etiology. Using an innovative genetic approach to generate an allelic series of Cop1, we found that Cop1 hypomorphic mice spontaneously developed malignancy at a high frequency in the first year of life and were highly susceptible to radiation-induced lymphomagenesis. Further analysis revealed that c-Jun was a key physiological target for Cop1 and that Cop1 constitutively kept c-Jun at low levels in vivo and thereby modulated c-Jun/AP-1 transcriptional activity. Importantly, Cop1 deficiency stimulated cell proliferation in a c-Jun-dependent manner. Focal deletions of COP1 were observed at significant frequency across several cancer types, and COP1 loss was determined to be one of the mechanisms leading to c-Jun upregulation in human cancer. We therefore conclude that Cop1 is a tumor suppressor that functions, at least in part, by antagonizing c-Jun oncogenic activity. In the absence of evidence for a genetic interaction between Cop1 and p53, our data strongly argue against the use of Cop1-inhibitory drugs for cancer therapy.
A multistep damage recognition mechanism for global genomic nucleotide excision repair (2001)

A mammalian nucleotide excision repair (NER) factor, the XPC-HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed analysis of its binding specificity using various DNA substrates, each containing a single defined lesion. A highly sensitive gel mobility shift assay revealed that XPC-HR23B specifically binds a small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in the bubble. This is evidence that damage recognition for NER is accomplished through at least two steps; XPC-HR23B first binds to a site that has a DNA helix distortion, and then the presence of injured bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs) were hardly recognized by XPC-HR23B, suggesting that additional factors may be required for CPD recognition. Although the presence of mismatched bases opposite a CPD potentiated XPC-HR23B binding, probably due to enhancement of the helix distortion, cell-free excision of such compound lesions was much more efficient than expected from the observed affinity for XPC-HR23B. This also suggests that additional factors and steps are required for the recognition of some types of lesions. A multistep mechanism of this sort may provide a molecular basis for ensuring the high level of damage discrimination that is required for global genomic NER.
The Brezhnev Legacy: Nationalities and Gorbachev (1992)

The vantage point of the early 1990s provides a particularly significant opportunity to examine nationalities' dissent and regime response to it during Leonid Brezhnev's leadership. Despite his 1973 assertion that the nationalities' problem was 'solved', and a similar claim made in the 1986 Soviet Communist Party Programme, any general expectations of assimilationist outcomes for most national minorities in the USSR were clearly premature, at best. This analysis examines empirical data from the period 1965–81 on nationalist actions, and state repression of them. It concludes that the differentiated treatment of various nationalities in 1965–81 was generally successful, in the short term. However, this policy not only failed to promote 'integration', but may actually have aggravated the subsequent political explosion of the late 1980s.
Dynamic spectral-domain optical coherence elastography for tissue characterization (2010)

A dynamic spectral-domain optical coherence elastography (OCE) imaging technique is reported. In this technique, audio-frequency compressive vibrations are generated by a piezoelectric stack as external excitation, and strain rates in the sample are calculated and mapped quantitatively using phase-sensitive spectral-domain optical coherence tomography. At different driving frequencies, this technique provides contrast between sample regions with different mechanical properties, and thus is used to mechanically characterize tissue. We present images of a three-layer silicone tissue phantom and rat tumor tissue ex vivo, based on quantitative strain rate. Both acquisition speed and processing speed are improved dramatically compared with previous OCE imaging techniques. With high resolution, high acquisition speed, and the ability to characterize the mechanical properties of tissue, this OCE technique has potential use in non-destructive volumetric imaging and clinical applications.
Kras as a key oncogene and therapeutic target in pancreatic cancer (2014)

Pancreatic cancer is one of the deadliest human malignancies and little progress has been achieved in its treatment over the past decades. Advances in our understanding of the biology of this disease provide new potential opportunities for treatment. Pancreatic cancer is preceded by precursor lesions, the most common of which are known as Pancreatic Intraepithelial Neoplasia (PanIN). PanIN lesions, which are the focus of this review, have a high incidence of Kras mutations, and Kras mutations are a hallmark of the late-stage disease. We now know from genetically engineered mouse models that oncogenic Kras is not only driving the formation of pancreatic cancer precursor lesions, but it is also required for their progression, and for the maintenance of invasive and metastatic disease. Thus, an enormous effort is being placed in generating Kras inhibitors for clinical use. Additionally, alternative approaches, including understanding the role of Kras effector pathways at different stages of the disease progression, are being devised to target Kras effector pathways therapeutically. In particular, efforts have focused on the MAPK pathway and the PI3K pathway, for which inhibitors are widely available. Finally, recent studies have highlighted the need for oncogenic Kras to establish feedback mechanisms that maintain its levels of activity; the latter might constitute alternative ways to target Kras in pancreatic cancer. Here, we will review recent basic research and discuss potential therapeutic applications.
Combined cord blood stem cells and gene therapy enhances angiogenesis and improves cardiac performance in mouse after acute myocardial infarction (2005)

Combined therapy with human umbilical cord blood CD34(+) cells and both Ang1 and VEGF genes reduced infarct size, attenuated the progression of cardiac dysfunction and increased capillary density in acute myocardial infarction in mice.
Differential Cytokine and Chemokine Gene Expression by Human NK Cells Following Activation with IL-18 or IL-15 in Combination with IL-12: Implications for the Innate Immune Response (1999)

NK cells constitutively express monocyte-derived cytokine (monokine) receptors and secrete cytokines and chemokines following monokine stimulation, and are therefore a critical component of the innate immune response to infection. Here we compared the effects of three monokines (IL-18, IL-15, and IL-12) on human NK cell cytokine and chemokine production. IL-18, IL-15, or IL-12 alone did not stimulate significant cytokine or chemokine production in resting NK cells. The combination of IL-18 and IL-12 induced extremely high amounts of IFN-gamma protein (225 +/- 52 ng/ml) and a 1393 +/- 643-fold increase in IFN-gamma gene expression over those in resting NK cells. IL-15 and IL-12 induced less IFN-gamma protein (24 +/- 10 ng/ml; p < 0.007) and only a 45 +/- 19-fold increase in IFN-gamma gene expression over those in resting NK cells. The CD56bright NK cell subset produced significantly more IFN-gamma following IL-18 and IL-12 compared with CD56dim NK cells (p < 0.008). However, the combination of IL-15 and IL-12 was significantly more potent than that of IL-18 and IL-12 for NK cell production of IL-10, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and TNF-alpha at the protein and transcript levels. Granulocyte-macrophage CSF was optimally induced by IL-15 and IL-18. Resting CD56+ NK cells expressed IL-18R transcript that was up-regulated by IL-12 or IL-15. Our results show that distinct cytokine and chemokine patterns are induced in NK cells in response to different costimulatory signals from these three monokines. This suggests that NK cell cytokine production may be governed in part by the monokine milieu induced during the early proinflammatory response to infection and by the subset of NK cells present at the site of inflammation.
The preparation of amino-substituted biaryl libraries: The application of solid-supported reagents to streamline solution-phase synthesis (2000)

A small library of isomeric benzylamino biaryls was generated in a semi-automated fashion using a solution-phase strategy employing a solid-supported, readily filterable base to facilitate electrophilic substitution followed in sequence by a metal-catalyzed cross-coupling reaction.
Determination of Number of Clusters in K-Means Clustering and Application in Colour Image Segmentation (2000)

The main disadvantage of the k-means algorithm is that the number of clusters, K, must be supplied as a parameter. In this paper we present a simple validity measure based on the intra-cluster and inter-cluster distance measures which allows the number of clusters to be determined automatically. The basic procedure involves producing all the segmented images for 2 clusters up to Kmax clusters, where Kmax represents an upper limit on the number of clusters. Then our validity measure is calculated to determine which is the best clustering by finding the minimum value for our measure. The validity measure is tested for synthetic images for which the number of clusters in known, and is also implemented for natural images.
Acetylcholine Receptor Channel Structure Probed in Cysteine-Substitution Mutants (1992)

In order to understand the structural bases of ion conduction, ion selectivity, and gating in the nicotinic acetylcholine receptor, mutagenesis and covalent modification were combined to identify the amino acid residues that line the channel. The side chains of alternate residues--Ser248, Leu250, Ser252, and Thr254--in M2, a membrane-spanning segment of the alpha subunit, are exposed in the closed channel. Thus alpha 248-254 probably forms a beta strand, and the gate is closer to the cytoplasmic end of the channel than any of these residues. On channel opening, Leu251 is also exposed. These results lead to a revised view of the closed and open channel structures.
Biosynthetic Characterization and Chemoenzymatic Assembly of the Cryptophycins. Potent Anticancer Agents from Nostoc Cyanobionts (2006)

The lichen cyanobacterial symbiont Nostoc sp. ATCC 53789 and its close relative Nostoc sp. GSV 224 are prolific producers of natural products, generating >25 derivatives of the cryptophycin class of secondary metabolites. Cryptophycin 1, the prototypic member of the class, is a potent tubulin-depolymerizing agent, and several semisynthetic derivatives are being developed as anticancer therapeutics. Here we provide a detailed characterization of the cryptophycin metabolic pathway by stable-isotope labeling experiments and through cloning, sequencing, and annotating the cryptophycin biosynthetic gene cluster. A comparative secondary metabolomic analysis based on polyketide (PK)/non-ribosomal peptide gene clusters from the phylogenetically related, non-cryptophycin producing cycad symbiont, Nostoc punctiforme ATCC 29133, was used to identify the cryptophycin biosynthetic genes that encompass approximately 40 kb within the lichen symbiont Nostoc sp. ATCC 53789 genome. The pathway encodes a collinear set of enzymes, including three modular PK synthases, two non-ribosomal peptide synthetase modules, and an integrated adenylation/ketoreductase didomain for elaboration of the leucic acid subunit. In addition, genes encoding key tailoring steps, including a FAD-dependent halogenase and CYP450 epoxidase, were identified. The inherent flexibility of the cryptophycin biosynthetic enzymes was harnessed to generate a suite of new analogues by altering the pool of PK starter units and selected amino acid extender groups. Characterization of the cryptophycin CYP450 enabled development of the first stereospecific synthesis of cryptophycin 2, through a tandem chemoenzymatic synthesis from the natural seco-cryptophycin 4 chain elongation intermediate.
Point-to-point motion commands that eliminate residual vibration (2005)

Several point-to-point motion commands are presented that eliminate residual vibration for a single degree-of-freedom mechanical system. It is shown how any vibrationless motion command of fixed duration can be converted into one of arbitrary duration. Comparisons are made based on force, energy and power.
The Primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress-response pathway (2008)

Primary open-angle glaucoma (POAG) is a genetically complex neuropathy that affects retinal ganglion cells and is a leading cause of blindness worldwide. WDR36, a gene of unknown function, was recently identified as causative for POAG at locus GLC1G. Subsequent studies found disease-associated variants in control populations, leaving the role of WDR36 in this disease unclear. To address this issue, we determined the function of WDR36. We studied Wdr36 in zebrafish and found it is the functional homolog of yeast Utp21. Utp21 is cell essential and functions in the nucleolar processing of 18S rRNA, which is required for ribosome biogenesis. Evidence for functional homology comes from sequence alignment, ubiquitous expression, sub-cellular localization to the nucleolus and loss-of-function phenotypes that include defects in 18S rRNA processing and abnormal nucleolar morphology. Additionally, we show that loss of Wdr36 function leads to an activation of the p53 stress-response pathway, suggesting that co-inheritance of defects in p53 pathway genes may influence the impact of WDR36 variants on POAG. Although these results overall do not provide evidence for or against a role of WDR36 in POAG, they do provide important baseline information for future studies.
Hypoglycemic and Hypotensive Activity of a Root Extract of Smilax aristolochiifolia, Standardized on N-trans-Feruloyl-Tyramine (2014)

The metabolic syndrome (MS) is a condition consisting of various metabolic abnormalities that are risk factors for developing kidney failure, cardiovascular, vascular and cerebrovascular diseases, among others. The prevalence of this syndrome shows a marked increase. The aim of this study was to investigate the pharmacological effect of Smilax aristolochiifolia root on some components of MS and obtain some of the active principle using chromatographic techniques. The compound isolated was N-trans-feruloyl tyramine NTF (1), and its structure was determined by spectroscopic and spectrometric analyses. The whole extract and the standardized fractions were able to control the weight gain around 30%; the fraction rich in NTF was able to decrease the hypertriglyceridemia by 60%. The insulin resistance decreased by approximately 40%; the same happened with blood pressure, since the values of systolic and diastolic pressure fell on average 31% and 37% respectively, to levels comparable to normal value. The treatment also had an immunomodulatory effect on the low-grade inflammation associated with obesity, since it significantly decreased the relative production of pro-inflammatory cytokines regarding anti-inflammatory cytokines, both kidney and adipose tissue. Therefore it can be concluded that the extract and fractions of Smilax aristolochiifolia root with NTF are useful to counteract some symptoms of MS in animal models.
Heparin oligosaccharides bind L- and P-selectin and inhibit acute inflammation (1993)

Initial attachment of leukocytes to the vessel wall at sites of inflammation is supported by a family of carbohydrate-binding adhesion molecules called the selectins. Selectin ligands include sialyl-Lewis x (sLex, Neu5Ac alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc--) and related structures. We report here that defined heparin oligosaccharides interact with the selectins. Heparin chains containing four or more monosaccharide residues inhibited the function of L- and P-selectin, but not E-selectin, in vitro. In a competition enzyme-linked immunosorbent assay measuring inhibition of solution-phase selectin-Ig fusion proteins (selectin-Ig) binding to immobilized bovine serum albumin-sLex neoglycoprotein, a heparin-derived tetrasaccharide mixture inhibited 50% of L- and P-selectin-Ig binding (IC50) at 200 +/- 40 mumol/L and 850 +/- 110 mumol/L, respectively. A single hexasulfated tetrasaccharide (delta UA2S alpha 1-4GlcNS6S alpha 1-4IdoA2S alpha 1-4GlcNS6S) was particularly active against L- and P-selectin-Ig (IC50 = 46 +/- 5 mumol/L and 341 +/- 24 mumol/L). By comparison, the tetrasaccharide sLex was not inhibitory at concentrations up to 1 mmol/L. In cell adhesion assays, heparin tetrasaccharides reduced binding of neutrophils to COS cells expressing P-selectin but not to COS cells expressing E-selectin. They also blocked colon cancer cell adhesion to L- and P-selectin but not E-selectin. In a model of acute inflammation, intravenously administered heparin tetrasaccharides diminished influx of neutrophils into the peritoneal cavities of thioglycollate-treated mice. We conclude that heparin oligosaccharides, including non-anticoagulant tetrasaccharides, are effective L- and P-selectin inhibitors in vitro and have anti-inflammatory activity in vivo.
A rapid single step staining technique for DNA analysis by flow microfluorimetry. (1980)

A new procedure is reported for the staining of DNA, for flow microfluorimetry. It allows the production of stained cell nuclei in a single step by incorporating the DNA stain with a solution of the nonionic detergent Triton-X-100. This method has been found to be applicable to all DNA fluorochromes tested (ethidium bromide, propidium iodide, mithramycin, DAPI, Hoechst 33342). DNA histograms obtained in this way are comparable to those using conventional staining techniques, e.g., ethanol fixation followed by staining. Using this procedure the DNA content distribution of solid tissue or cells from suspension or monolayer cultures can be generated in less than 5 min.
Altered nitric oxide production mediates matrix-specific PAK2 and NF-κB activation by flow (2012)

Shear stress generated by distinct blood flow patterns modulates endothelial cell phenotype to spatially restrict atherosclerotic plaque development. Signaling through p21-activated kinase (PAK) mediates several of the deleterious effects of shear stress, including enhanced NF-κB activation and proinflammatory gene expression. Whereas shear stress activates PAK in endothelial cells on a fibronectin matrix, basement membrane proteins limit shear-induced PAK activation and inflammation through a protein kinase A-dependent pathway; however, the mechanisms underlying this regulation were unknown. We show that basement membrane proteins limit membrane recruitment of PAK2, the dominant isoform in endothelial cells, by blocking its interaction with the adaptor protein Nck. This uncoupling response requires protein kinase A-dependent nitric oxide production and subsequent PAK2 phosphorylation on Ser-20 in the Nck-binding domain. Of importance, shear stress does not stimulate nitric oxide production in endothelial cells on fibronectin, resulting in enhanced PAK activation, NF-κB phosphorylation, ICAM-1 expression, and monocyte adhesion. These data demonstrate that differential flow-induced nitric oxide production regulates matrix-specific PAK signaling and describe a novel mechanism of nitric oxide-dependent NF-κB inhibition.
Bacteria in Midguts of Field-Collected <I>Anopheles albimanus</I> Block <I>Plasmodium vivax</I> Sporogonic Development (2003)

Bacterial infections were investigated in midguts of insectary and field-collected Anopheles albimanus Weidemann from southern Mexico. Serratia marcescens, Enterobacter cloacae and Enterobacter amnigenus 2, Enterobacter sp., and Serratia sp. were isolated in field samples obtained in 1998, but only Enterobacter sp. was recovered in field samples of 1997 and no bacteria were isolated from insectary specimens. These bacteria were offered along with Plasmodium vivax infected blood to aseptic insectary An. albimanus, and the number of infected mosquitoes as well as the oocyst densities assessed after 7d. Plasmodium vivax infections in mosquitoes co-infected with En. amnigenus 2, En. cloacae, and S. marcensces were 53, 17, and 210 times, respectively, lower than in control mosquitoes, and the mean oocyst density in mosquitoes co-infected with En. cloacae was 2.5 times lower than in controls. Mortality was 13 times higher in S. marcensces-infected mosquitoes compared with controls. The overall midgut bacterial infection in mosquito field populations may influence P. vivax transmission, and could contribute to explain the annual variations in malaria incidence observed in the area.
Harmonic shells (2009)

We propose a procedural method for synthesizing realistic sounds due to nonlinear thin-shell vibrations. We use linear modal analysis to generate a small-deformation displacement basis, then couple the modes together using nonlinear thin-shell forces. To enable audio-rate time-stepping of mode amplitudes with mesh-independent cost, we propose a reduced-order dynamics model based on a thin-shell cubature scheme. Limitations such as mode locking and pitch glide are addressed. To support fast evaluation of mid-frequency mode-based sound radiation for detailed meshes, we propose far-field acoustic transfer maps (FFAT maps) which can be precomputed using state-of-the-art fast Helmholtz multipole methods. Familiar examples are presented including rumbling trash cans and plastic bottles, crashing cymbals, and noisy sheet metal objects, each with increased richness over linear modal sound models.
Molecular genetics of familial cutaneous melanoma. (1998)

The gene p16/CDKN2A is an important determinant of melanoma risk. A commercial test is presently available to assess the status of this locus. However, because of uncertainties regarding the interpretation of the results of p16/CDKN2A genetic testing, we do not recommend routine clinical use of this test at this time.