gebhart/patrepeval huggingface dataset:
The regulatory network controlling spore formation inClostridium difficile (2014)

Clostridium difficile, a Gram-positive, anaerobic, spore-forming bacterium, is a major cause of nosocomial infections such as antibiotic-associated diarrhea. Spores are the vector of its transmission and persistence in the environment. Despite the importance of spores in the infectious cycle of C. difficile, little was known until recently about the control of spore development in this enteropathogen. In this review, we describe recent advances in our understanding of the regulatory network controlling C. difficile sporulation. The comparison with the model organism Bacillus subtilis highlights major differences in the signaling pathways between the forespore and the mother cell and a weaker connection between morphogenesis and gene expression. Indeed, the activation of the SigE regulon in the mother cell is partially independent of SigF although the forespore protein SpoIIR, itself partially independent of SigF, is essential for pro-SigE processing. Furthermore, SigG activity is not strictly dependent on SigE. Finally, SigG is dispensable for SigK activation in agreement with the absence of a pro-SigK sequence. The excision of the C. difficile skin element is also involved in the regulation of SigK activity. The C. difficile sporulation process might be a simpler, more ancestral version of the program characterized for B. subtilis.
Interleukin-12 delivered by biodegradable microspheres promotes the antitumor activity of human peripheral blood lymphocytes in a human head and neck tumor xenograft/SCID mouse model (2000)

The coengraftment of HNSCC and allogeneic lymphocytes into SCID mice provides a viable model with which to evaluate immunotherapeutic strategies for human cancer. The use of biodegradable microspheres for local sustained delivery of cytokines to augment lymphocyte mediated antitumor immunity within the tumor microenvironment provides a safer and simpler alternative to current cytokine immunotherapy protocols.
Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? (2000)

A series of alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation is considered to be the main cause of cancer. These mutational events include activation of oncogenes and inactivation of tumor suppressor genes. The elucidation of human cancer at the molecular level allows the design of rational, mechanism-based therapeutic agents that antagonize the specific activity of biochemical processes that are essential to the malignant phenotype of cancer cells. Because the frequency of RAS mutations is among the highest for any gene in human cancers, development of inhibitors of the Ras-mitogen-activated protein kinase pathway as potential anticancer agents is a very promising pharmacologic strategy. Inhibitors of Ras signaling have been shown to revert Ras-dependent transformation and cause regression of Ras-dependent tumors in animal models. The most promising new class of these potential cancer therapeutics are the farnesyltransferase inhibitors. The development of these compounds has been driven by the observation that oncogenic Ras function is dependent upon posttranslational modification, which enables membrane binding. In contrast to many conventional chemotherapeutics, farnesyltransferase inhibitors are remarkably specific and have been demonstrated to cause no gross systemic toxicity in animals. Some orally bioavailable inhibitors are presently being evaluated in phase II clinical trials. This review presents an overview on some inhibitors of the Ras signaling pathway, including their specificity and effectiveness in vivo. Because Ras signaling plays a crucial role in the pathogenesis of some hematologic malignancies, the potential therapeutic usefulness of these inhibitors is discussed. (Blood. 2000;96:1655-1669)
Curvelet-based multiple prediction (2010)

Abstract The suppression of multiples is a crucial task when processing seismic reflection data. Using the curvelet transform for surface-related multiple prediction is investigated. From a geophysical point of view, a curvelet can be seen as the representation of a local plane wave and is particularly well suited for seismic data decomposition. For the prediction of multiples in the curvelet domain, first it is proposed to decompose the input data into curvelet coefficients. These coefficients are then convolved together to predict the coefficients associated with multiples, and the final result is obtained by applying the inverse curvelet transform. The curvelet transform offers two advantages. The directional characteristic of curvelets allows for exploitation of Snell's law at the sea surface. Moreover, the possible aliasing in the predicted multiple is better managed by using the curvelet multiscale property to weight the prediction according to the low-frequency part of the data. 2D synthetic and field data examples show that some artifacts and aliasing effects are indeed reduced in the multiple prediction with the use of curvelets, thus allowing for an improved multiple subtraction result.
Quantitative Cytoarchitectural Studies of the Cerebral Cortex of Schizophrenics (1986)

Quantitative morphometric determinations of neuronal and glial density, neuron-glia ratios, and neuronal size were performed in the prefrontal, anterior cingulate, and primary motor cortex of ten controls and ten schizophrenics diagnosed by Feighner criteria under blind conditions to assess whether neuronal degeneration had occurred. Stepwise multiple regression and multiple classification analyses were used to evaluate the effect of potential confounding variables such as age, postmortem interval, fixation, hypoxia, and neuroleptic exposure on the measures studied. The neuronal density was significantly lower in layer VI of the prefrontal, layer V of the cingulate, and layer III of motor cortex. There was also a trend toward fewer neurons in most layers of both prefrontal and motor cortex, although by discriminant analysis this generalized pattern was significant only for the prefrontal area. The glial density also tended to be lower throughout most layers of all three cortical regions. There were no differences in the neuron-glia ratios or neuronal size between the two groups. The data do not support the presence of neuronal degeneration in schizophrenic cortex as it is conventionally described by neuropathologists, but do suggest the possibility that cytoarchitectural variations in cortical structure might exist in this group of schizophrenics.
Design of the Phase Sequences for Selected Mapping OFDM System (2004)

Peak to average power ratio (PAPR) distribution of the periodic orthogonal frequency division multiplexing (OFDM) symbol sequences is evaluated and it is shown that the OFDM symbol sequence with short period is expected to have high PAPR. PAPR bound of two sequences with Hamming distance D is derived. Using these results, we identify two conditions for the optimal phase sequences of selected mapping (SLM) and propose rows of a cyclic Hadamard matrix constructed by m-sequence as near optimal phase sequences for SLM, which has the best performance to reduce the PAPR of OFDM signals with small redundancy and no signal distortion.
Selective binding of RGMc/hemojuvelin, a key protein in systemic iron metabolism, to BMP-2 and neogenin (2008)

Juvenile hemochromatosis is a severe and rapidly progressing hereditary disorder of iron overload, and it is caused primarily by defects in the gene encoding repulsive guidance molecule c/hemojuvelin (RGMc/HJV), a recently identified protein that undergoes a complicated biosynthetic pathway in muscle and liver, leading to cell membrane-linked single-chain and heterodimeric species, and two secreted single-chain isoforms. RGMc modulates expression of the hepatic iron regulatory factor, hepcidin, potentially through effects on signaling by the bone morphogenetic protein (BMP) family of soluble growth factors. To date, little is known about specific pathogenic defects in disease-causing RGMc/HJV proteins. Here we identify functional abnormalities in three juvenile hemochromatosis-linked mutants. Using a combination of approaches, we first show that BMP-2 could interact in biochemical assays with single-chain RGMc species, and also could bind to cell-associated RGMc. Two mouse RGMc amino acid substitution mutants, D165E and G313V (corresponding to human D172E and G320V), also could bind BMP-2, but less effectively than wild-type RGMc, while G92V (human G99V) could not. In contrast, the membrane-spanning protein, neogenin, a receptor for the related molecule, RGMa, preferentially bound membrane-associated heterodimeric RGMc and was able to interact on cells only with wild-type RGMc and G92V. Our results show that different isoforms of RGMc/HJV may play unique physiological roles through defined interactions with distinct signaling proteins and demonstrate that, in some disease-linked RGMc mutants, these interactions are defective.
Molecular cloning and sequence analysis of the Chlamydomonas gene coding for radial spoke protein 3: flagellar mutation pf-14 is an ochre allele. (1989)

Chlamydomonas reinhardtii flagellar motility mutant pf-14 fails to assemble radial spokes because of a deficiency for assembly-competent radial spoke protein 3 (Huang, B., G. Piperno, Z. Ramanis, and D. J. L. Luck. 1981. J. Cell Biol. 88:80-88). Here, we raise an antiserum to protein 3 and use it to isolate the corresponding structural gene from an expression library. Southern blot analysis indicates that the gene is single copy and has not undergone major rearrangement in mutant pf-14 cells. Northern blot analysis suggests that wild-type amounts of an apparently normal 2.3-kb transcript accumulate in mutant cells during flagellar regeneration. When this mutant RNA is hybrid selected and translated in vitro, however, it produces a slightly truncated polypeptide 3 with an altered charge. The mutant protein 3 fails to assemble into pf-14 flagella and is maintained within a cytoplasmic pool of unassembled radial spoke polypeptides, as indicated by immunoblot analysis of proteins from whole cells and isolated axonemes using antisera to several radial spoke polypeptides. Interestingly, amounts of the mutant protein are greatly diminished relative to other spoke components. Complete genomic and cDNA nucleotide sequences were determined, and the pf-14 mutation was identified. It is a C-to-T transition near the 5' end of the protein coding region, which changes codon 21 to the ochre termination signal UAA. The size and charge of the mutant protein, and its reduced levels in cells, suggest that it is produced by relatively inefficient translational initiation as codon 42. The unphosphorylated isoform of radial spoke protein 3 is identified, and the sequence similarities between intervening sequences of the radial spoke protein 3 gene and a conserved intervening sequence of the two Chlamydomonas beta-tubulin genes (Youngblom, J., J. A. Schloss, and C. D. Silflow. 1984. Mol. Cell. Biol. 4:2686-2696) are reported.
Motor Bearing Fault Diagnosis Using Trace Ratio Linear Discriminant Analysis (2013)

Bearings are critical components in induction motors and brushless direct current motors. Bearing failure is the most common failure mode in these motors. By implementing health monitoring and fault diagnosis of bearings, unscheduled maintenance and economic losses caused by bearing failures can be avoided. This paper introduces trace ratio linear discriminant analysis (TR-LDA) to deal with high-dimensional non-Gaussian fault data for dimension reduction and fault classification. Motor bearing data with single-point faults and generalized-roughness faults are used to validate the effectiveness of the proposed method for fault diagnosis. Comparisons with other conventional methods, such as principal component analysis, local preserving projection, canonical correction analysis, maximum margin criterion, LDA, and marginal Fisher analysis, show the superiority of TR-LDA in fault diagnosis.
Cutting Edge: Ig Heavy Chain 3′ HS1–4 Directs Correct Spatial Position-Independent Expression of a Linked Transgene to B Lineage Cells (1999)

The Ig H chain locus is regulated by a set of cis-acting elements. Hypersensitive sites (HS) located 3' of the IgH, HS1-4, has been suggested to act as a locus control region (LCR) in cell lines. To assess the proposed role of HS1-4 acting as an LCR, we generated transgenic mice harboring a VH promoter-beta-globin reporter gene linked to the Ig H chain HS1-4 3'regulatory sequences. Transgene expression is strictly confined to B lymphocytes, with no detectable expression outside the B cell lineage in all transgenic founder lines. Furthermore, reporter gene activity is integration independent but not copy number dependent. Thus, additional sequences are required to allow the HS1-4 regulatory region to act as a classical LCR in mice. Our data are discussed in the context of tissue-specific gene expression in B lineage cells.
Exploiting uncalibrated stereo on a UAV platform (2010)

Uncalibrated stereo imagery experimental and analytical results are presented for path planning and navigation. An
Army Research and Development Engineering Command micro-size UAV was outfitted with two commercial cameras
and flown over varied landscapes. Polaris Sensor Technologies processed the data post flight with an image
correspondence algorithm of their own design. Stereo disparity (depth) was computed despite a quick assembly, image
blur, intensity saturation, noise and barrel distortion. No camera calibration occurred. Disparity maps were computed at
a processing rate of approximately 5 seconds per frame to improve perception. Disparity edges (treeline to ground, voids
and plateaus) were successfully observed and confirmed to be properly identified. Despite the success of localizing this
disparity edges sensitivity to saturated pixels, lens distortion and defocus were strong enough to overwhelm more subtle
features such as the contours of the trees, which should be possible to extract using this algorithm. These factors are
being addressed. The stereo data is displayed on a flat panel 3D display well suited for a human machine interface in
field applications. Future work will entail extraction of intelligence from acquired data and the overlay of such data on
the 3D image as displayed.
InBase: the Intein Database (2002)

Inteins are self-catalytic protein splicing elements. InBase (http://www.neb.com/neb/inteins.html), the Intein Database and Registry, is a curated compilation of published and unpublished information about protein splicing. It presents general information as well as detailed data for each intein, including tabulated comparisons and a comprehensive bibliography. An intein-specific BLAST server is now available to assist in identifying new inteins.
Metallation of N-Substituted β-Lactams. A Method for the Introduction of 3-Substituents into β-Lactams (1972)

N-Alkyl and N-aryl β-lactams yield lithio carbanions upon reaction with lithium diisopropylamide in tetrahydrofuran at −78°. These lithio salts react with a variety of electrophiles (e.g. ketones, esters, reactive alkyl halides) to give the 3-substituted derivatives in fair to good yield. The procedure is useful for the preparation of rather complex 3-substituted β-lactams from readily available simple derivatives.
Xylitol for preventing acute otitis media in children up to 12 years of age (2011)

There is fair evidence that the prophylactic administration of xylitol among healthy children attending day care centres reduces the occurrence of AOM by 25%. This meta-analysis is limited since the data arise from a small number of studies, mainly from the same research group.
Purification and Characterization from Tobacco (Nicotiana tabacum) Leaves of Six Small, Wound-Inducible, Proteinase Isoinhibitors of the Potato Inhibitor II Family (1993)

Six small molecular mass, wound-inducible trypsin and chymotrypsin inhibitor proteins from tobacco (Nicotiana tabacum) leaves were isolated to homogeneity. The isoinhibitors, cumulatively called tobacco trypsin inhibitor (TTI), have molecular masses of approximately 5500 to 5800 D, calculated from gel filtration analysis and amino acid content. The amino acid sequence of the entire 53 residues of one isoinhibitor, TTI-1, and the sequence of 36 amino acid residues from the N terminus of a second isoinhibitor, TTI-5, were determined. The two isoinhibitors differ only at residue 11, which is threonine in TTI-1 and lysine in TTI-5. The isoinhibitors are members of the potato inhibitor II family and show considerable identity with the small molecular mass members of this family, which include the eggplant inhibitor, two small molecular mass trypsin and chymotrypsin inhibitors from potatoes, and an inhibitor from pistils of the ornamental plant Nicotiana alata. Antibodies produced against the isoinhibitors in rabbits were used in radial immunoassays to quantify both the systemic wound inducibility of TTI in tobacco leaves and its constitutive levels in flowers.
High-resolution analysis of the human HLA-DR polymorphism by hybridization with sequence-specific oligonucleotide probes. (1986)

The human major histocompatibility complex class II antigens of the HLA-D are highly polymorphic, surface proteins essential in the cellular interactions necessary for an immune response. The analysis of this polymorphism is crucial for (i) histocompatibility matching for transplantation and (ii) understanding the association between HLA-D and certain important diseases. The polymorphism of certain HLA-D haplotypes may escape detection by current methodologies. Analysis at the genomic level of the polymorphism of one of the HLA-D subregions HLA-DR, using oligonucleotide probes specific for the polymorphic regions, is capable of distinguishing single nucleotide differences. The DRw6 haplotype was analyzed in view of the lack of DRw6 specific sera. On the basis of nucleotide sequence analysis, the DRw6 haplotype consists of at least two subtypes. When analyzed with oligonucleotide probes, this split identifies new polymorphic groups that differ from the DRw6 serological subgroups.
MicroRNA 18 and 124a Down-Regulate the Glucocorticoid Receptor: Implications for Glucocorticoid Responsiveness in the Brain (2009)

Glucocorticoids (GCs) exert profound effects on a variety of physiological processes, including adaptation to stress, metabolism, immunity, and neuronal development. Cellular responsiveness to GCs depends on numerous factors, including the amount of the glucocorticoid receptor (GR) protein. We tested the hypothesis that micro-RNAs (miRs), a recently discovered group of noncoding RNAs involved in mRNA translation, might control GR activity by reducing GR protein levels in neuronal tissues. We tested a panel of five miRs consisting of 124aa, 328, 524, 22, and 18. We found that miRs 18 and 124a reduced GR-mediated events in addition to decreasing GR protein levels. miR reporter assays revealed binding of miR-124a to the 3' untranslated region of GR. In correspondence, the activation of the GR-responsive gene glucocorticoid-induced leucine zipper was strongly impaired by miR-124a and -18 overexpression. Although miR-18 is expressed widely throughout the body, expression of miR-124a is restricted to the brain. Endogenous miR-124a up-regulation during neuronal differentiation of P19 cells was associated with a decreasing amount of GR protein levels and reduced activity of luciferase reporter constructs bearing GR 3' untranslated regions. Furthermore, we show that miR-124a expression varies over time during the stress hyporesponsive period, a neonatal period when GC signaling is modulated. Our findings demonstrate a potential role for miRs in the regulation of cell type-specific responsiveness to GCs, as may occur during critical periods of neuronal development. Ultimately, our results may provide a better understanding of the etiology of stress-related diseases as well as the efficacy of GC therapy.
The Synthesis of 4-Substituted Isoquinoline Derivatives from Diethyl(4-isoquinolyl)borane (1987)

Syntheses of 4-substituted isoquinolines by the palladiumcatalyzed cross-coupling reactions of diethyl(4-isoquinoly1)borane with organic halides are described.Few general.methodsfor the synthesis of the 4-substituted isoquinoline system, a common structural unit of several isoquinoline alkaloids, have been devised. 1In connection with our previous workP2 it was envisioned that the cross-coupling reaction of diethyl(4-isoquinoly1)borane with organic halides in the presence of palladium catalyst would provide a versatile method for the direct introduction of a substituent into the 4-position of isoquinoline.We wish to report here simple and regioselective preparation of various 4-substituted isoquinoline derivatives (1)The reaction of (1 mol eq.) with aryl bromides (&) (1.5 mol eq.) was conducted in the presence of powdered KOH (3 mol eq. 1 , Bu4NBr (0.5 mol eq.) and Pd(Pn3P)4 (0.1 mol eq.) in THF at reflux under nitrogen to give 4-arylisoquinolines (3)in moderate to good yields as summarized in Table 1.The formation of other 4-substituted isoquinoline derivatives (g) was also successful under the same conditions as shown in Table 2.The present procedure for the preparation of 4-aryl-1,2,3,4-tetrahydroisoquinolines is straightforward and simple as compared with the known methods. 4
Intramolecular Carbozincation of Unactivated Alkenes Occurs through a Zinc Radical Transfer Mechanism (2007)

The cyclizations of a number of terminally unsaturated alkenyl zinc iodides to cyclopentylmethylzinc iodides, formerly believed to be nonradical in nature, have been revealed as radical chain cyclizations initiated by adventitious oxygen. Five cases are presented in which the published carbozincation cis/trans selectivities are essentially the same as those found for the cyclizations of the unsaturated alkyl iodide precursors of the alkylzinc iodides by the iodine atom transfer method at approximately the same temperatures. In addition, it has been found that one of the organozinc cyclizations does not occur in a system in which oxygen has been rigorously excluded. The combined findings strongly suggest that these organozinc cyclizations occur by a zinc radical transfer mechanism rather than by a conventional carbometallation that is thought to occur with the analogous organolithium and organomagnesium cyclizations.
Genetic Control of DH Reading Frame and Its Effect on B-Cell Development and Antigen-Specifc Antibody Production (2010)

The power of the adaptive immune system to identify novel antigens depends on the ability of lymphocytes to create antigen receptors with diverse antigen-binding sites. For immunoglobulins, CDR (complementarity-determining region)-H3 lies at the center of the antigen-binding site, where it often plays a key role in antigen binding. It is created de novo by VDJ rearrangement and is thus the focus for rearrangement-dependent diversity. CDR-H3 is biased for the inclusion of tyrosine. In seeking to identify the mechanisms controlling CDR-H3 amino acid content, we observed that the coding sequence of DH gene segments demonstrate conservation of reading frame (RF)-specific sequence motifs, with RF1 enriched for tyrosine and depleted of hydrophobic and charged amino acids. Use of DH RF1 in functional VDJ transcripts is preferred from the earliest stages of B-cell development, "pushing" CDR-H3 to include specific categories of tyrosine-enriched antigen-binding sites. With development and maturation, the composition of the CDR-H3 repertoire appears to be pulled into a more refined specific range. Forcing the use of alternative DH RFs by means of gene targeting alters the expressed repertoire, enriching alternative sequence categories. This change in the repertoire variably affects antibody production and the development of specific B-cell subsets.