gebhart/patrepeval huggingface dataset:
Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. (1995)

The murine homeo box gene Nkx2-5 is expressed in precardiac mesoderm and in the myocardium of embryonic and fetal hearts. Targeted interruption of Nkx2-5 resulted in abnormal heart morphogenesis, growth retardation and embryonic lethality at approximately 9-10 days postcoitum (p.c.). Heart tube formation occurred normally in mutant embryos, but looping morphogenesis, a critical determinant of heart form, was not initiated at the linear heart tube stage (8.25-8.5 days p.c.). Commitment to the cardiac muscle lineage, expression of most myofilament genes and myofibrillogenesis were not compromised. However, the myosin light-chain 2V gene (MLC2V) was not expressed in mutant hearts nor in mutant ES cell-derived cardiocytes. MLC2V expression normally occurs only in ventricular cells and is the earliest known molecular marker of ventricular differentiation. The regional expression in mutant hearts of two other ventricular markers, myosin heavy-chain beta and cyclin D2, indicated that not all ventricle-specific gene expression is dependent on Nkx2-5. The data demonstrate that Nkx2-5 is essential for normal heart morphogenesis, myogenesis, and function. Furthermore, this gene is a component of a genetic pathway required for myogenic specialization of the ventricles.
Dihydrotestosterone does not induce prostate adenocarcinoma in L‐W rats (1987)

It has been postulated that dihydrotestosterone (DHT) is the active trophic androgen in initiating pathogenic changes in the prostate gland. Groups of prostate cancer-susceptible male L-W rats (age 3 months) were treated with subcutaneous depots of testosterone or of DHT. After 14 months, prostate adenocarcinomas had developed in 24% of the testosterone-treated rats but not in the DHT-treated rats. In the latter rats, the testes were significantly reduced in weight, there was no evidence of spermatogenesis, and serum testosterone levels were not detectable. It appears that DHT as administered to L-W rats had an antiandrogenic effect.
Signatures of Environmental Exposures Using Peripheral Leukocyte Gene Expression: Tobacco Smoke (2004)

Functional biological markers of environmental exposures are important in epidemiological studies of disease risk. Such markers not only provide a measure of the exposure, they also reflect the degree of physiological and biochemical response to the exposure. In an observational study, using DNA microarrays, we show that it is possible to distinguish between 85 individuals exposed and unexposed to tobacco smoke on the basis of mRNA expression in peripheral leukocytes. Furthermore, we show that active exposure to tobacco smoke is associated with a biologically relevant mRNA expression signature. These findings suggest that expression patterns can be used to identify a complex environmental exposure in humans.
The Expanding Spectrum of G Protein Diseases (1999)

Disease-causing mutations often reveal key pathways of physiologic regulation and their underlying molecular mechanisms. Mutations in the trimeric guanine nucleotide-binding proteins (G proteins), which relay signals initiated by photons, odorants, and a host of hormones and neurotransmitters, cause many diseases. For the most part, the diseases are confined to a set of fascinating but rare endocrine disorders (Table 1).1 A recent study suggests that mutations in G proteins can also lead to essential hypertension.2 If this study is correct, hypertension may be one of several common disorders caused by defects in this ubiquitous family of signaling molecules.This review focuses . . .
Real-Time PCR-Coupled CE-SELEX for DNA Aptamer Selection (2012)

Aptamers are short nucleic acid or peptide sequences capable of binding to a target molecule with high specificity and affinity. Also known as "artificial antibodies," aptamers provide many advantages over antibodies. One of the major hurdles to aptamer isolation is the initial time and effort needed for selection. The systematic evolution of ligands by exponential enrichment (SELEX) is the traditional procedure for generating aptamers, but this process is lengthy and requires a large quantity of target and starting aptamer library. A relatively new procedure for generating aptamers using capillary electrophoresis (CE), known as CE-SELEX, is faster and more efficient than SELEX but requires laser-induced fluorescence (LIF) to detect the aptamer-target complexes. Here, we implemented an alternative system without LIF using real-time- (RT-) PCR to indirectly measure aptamer-target complexes. In three rounds of selection, as opposed to ten or more rounds common in SELEX protocols, a specific aptamer for bovine serum albumin (BSA) was obtained. The specificity of the aptamer to BSA was confirmed by electrophoretic mobility shift assays (EMSAs), an unlabeled competitor assay, and by a supershift assay. The system used here provides a cost effective and a highly efficient means of generating aptamers.
Temperature-sensitive protein–DNA dimerizers (2005)

Programmable DNA-binding polyamides coupled to short peptides have led to the creation of synthetic artificial transcription factors. A hairpin polyamide-YPWM tetrapeptide conjugate facilitates the binding of a natural transcription factor Exd to an adjacent DNA site. Such small molecules function as protein-DNA dimerizers that stabilize complexes at composite DNA binding sites. Here we investigate the role of the linker that connects the polyamide to the peptide. We find that a substantial degree of variability in the linker length is tolerated at lower temperatures. At physiological temperatures, the longest linker tested confers a "switch"-like property on the protein-DNA dimerizer, in that it abolishes the ability of the YPWM moiety to recruit the natural transcription factor to DNA. These observations provide design principles for future artificial transcription factors that can be externally regulated and can function in concert with the cellular regulatory circuitry.
Dynamic effects of pair correlation functions on spin relaxation by translational diffusion in liquids (1975)

It is shown how the equilibrium pair correlation function between spin-bearing molecules in liquids may be incorporated as an effective force in the relative diffusion expressions, and how one may solve for the resulting time correlation functions and spectral densities needed for studies of spin relaxation by translational diffusion. The use of finite difference methods permits the solution no matter how complex the form of the pair correlation function (pcf) utilized. In particular, a Percus–Yevick pcf as well as one corrected from computer dynamics, both for hard spheres, are utilized. Good agreement with the experiments of Harmon and Muller on dipolar relaxation in liquid ethane is obtained from this analysis. Effects of ionic interactions in electrolyte solutions upon dipolar relaxation are also obtained in terms of Debye–Hückel theory for the pcf. Analytic solutions are given which are appropriate for the proper boundary-value problem for the relative diffusion of molecules (i.e., a distance of minimum approach) that has usually been neglected in the spin relaxation theories. Other molecular dynamics aspects of spin relaxation by translational diffusion in liquids are briefly discussed.
Intrinsic fluctuations in Vertical NAND flash memories (2012)

Vertical NAND (VNAND) technology relies on polysilicon for channel material. Two intrinsic variation sources of the cell threshold voltage induced by polysilicon traps have been identified and simulated: Random Trap Fluctuation (RTF) and Random Telegraph Noise (RTN). We demonstrate that RTN is enhanced by the polysilicon material and an original model explains the asymmetric RTN distribution observed after endurance. This work enables the prediction of V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> distribution for VNAND devices in MLC operation.
Molecular cloning and analysis of the rat kallikrein-binding protein gene (1991)

The gene encoding rat kallikrein-binding protein (RKBP), a serine protease inhibitor, has been isolated and analyzed with the aid of the polymerase chain reaction. The gene is approximately 10 kilobases in length with four introns of approximately 2.2, 1.8, 0.9, and 0.84 kilobases. This gene is composed of five exons and encodes a polypeptide of 416 amino acid residues. The reactive center region of RKBP is encoded by the fifth exon with the putative P1-P1' residues being Lys-Ser. The organization of the RKBP gene is homologous to those of human alpha 1-antitrypsin and alpha 1-antichymotrypsin in size and arrangement of exons and introns, suggesting that they belong to the same subgroup of serpins. In the 5'-flanking region of the RKBP gene, a variant TATA box sequence, ATAAATA, is found 20 base pairs upstream from the transcription initiation site. The 5'-flanking region of the RKBP gene was able to direct transcription of the reporter gene chloramphenicol acetyltransferase when transfected into a rat hepatoma cell line. An internal promoter-like region was found in the first intron of the RKBP gene, downstream from the transcription initiation site and upstream from the translation initiation codon, however, it was unable to direct expression of the chloramphenicol acetyltransferase reporter gene in our experiments. The expression of RKBP in rat liver was induced by sex hormone treatment as indicated by dot-blot analysis. A genomic Southern blot using an RKBP cDNA probe revealed multiple bands suggesting that the RKBP gene belongs to a family of highly conserved genes.
Selective complexation of disaccharides by a novel D 2-symmetrical receptor in protic solvent mixtures (1996)

The synthesis of an optically active, 1,1′-binaphtyl-derived cyclophane receptor with a preorganized central cavity lined with four anionic phosphodiester groups for ionic hydrogen bonding is described. In competitive protic solvent mixtures, this receptor forms stable 1:1 complexes with disaccharides whereas the smaller monosaccharides are not significantly bound.
Tongxinluo reduces myocardial no-reflow and ischemia-reperfusion injury by stimulating the phosphorylation of eNOS via the PKA pathway (2010)

The objective of the present study was to investigate whether pretreatment with single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of 1.0 μg·kg(-1)·min(-1) 30 min before ischemia), and TXL + N(ω)-nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10 mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P < 0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from 78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS, and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635), and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635) without an apparent influence on PKA activity. In conclusion, pretreatment with a single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.
Novel human antibody therapeutics: The age of the Umabs (2008)

Monoclonal antibodies represent a major and increasingly important category of biotechnology products for the treatment of human diseases. The state-of-the-art of antibody technology has evolved to the point where therapeutic monoclonal antibodies, that are practically indistinguishable from antibodies induced in humans, are routinely generated. We depict how our science-based approach can be used to further improve the efficacy of antibody therapeutics, illustrated by the development of three monoclonal antibodies for various cancer indications: zanolimumab (directed against CD4), ofatumumab (directed against CD20) and zalutumumab (directed against epidermal growth factor receptor).
Emergence of TNIK inhibitors in cancer therapeutics (2017)

The outcome of patients with metastatic colorectal cancer remains unsatisfactory. To improve patient prognosis, it will be necessary to identify new drug targets based on molecules that are essential for colorectal carcinogenesis, and to develop therapeutics that target such molecules. The great majority of colorectal cancers (>90%) have mutations in at least one Wnt signaling pathway gene. Aberrant activation of Wnt signaling is a major force driving colorectal carcinogenesis. Several therapeutics targeting Wnt pathway molecules, including porcupine, frizzled receptors and tankyrases, have been developed, but none of them have yet been incorporated into clinical practice. Wnt signaling is most frequently activated by loss of function of the adenomatous polyposis coli (APC) tumor suppressor gene. Restoration of APC gene function does not seem to be a realistic therapeutic approach, and, therefore, only Wnt signaling molecules downstream of the APC gene product can be considered as targets for pharmacological intervention. Traf2 and Nck-interacting protein kinase (TNIK) was identified as a regulatory component of the β-catenin and T-cell factor-4 (TCF-4) transcriptional complex. Several small-molecule compounds targeting this protein kinase have been shown to have anti-tumor effects against various cancers. An anthelmintic agent, mebendazole, was recently identified as a selective inhibitor of TNIK and is under clinical evaluation. TNIK regulates Wnt signaling in the most downstream part of the pathway, and its pharmacological inhibition seems to be a promising therapeutic approach. We demonstrated the feasibility of this approach by developing a small-molecule TNIK inhibitor, NCB-0846.
Inhibition of Porphyromonas gingivalis Biofilm by Oxantel (2009)

Porphyromonas gingivalis is a major pathogen of chronic periodontitis and exists in a biofilm on the surface of the tooth root. Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by P. gingivalis and disrupted established biofilms at concentrations below its MIC against planktonic cells. Oxantel was more effective against P. gingivalis in biofilm than metronidazole, a commonly used antibiotic for periodontitis.
Interspecific protoplast fusion and genetic recombination betweenStreptomyces griseusandStreptomyces griseolus (1992)

Progeny from a 4-factor interspecific protoplast-fusion cross between Streptomyces griseus and Streptomyces griseolus were analysed. All 9 of the 14 possible progeny phenotypes detected by the selection procedure were identified and repeated progeny testing confirmed that the majority were genetically stable. 0.15% of the cross progeny were prototrophic. Selected recombinant progeny, when backcrossed to the parent species and to each other, also produced recombinants confirming that they arose by chromosomal recombination rather than by complementing heterozygotes formation.
In situ IR spectroscopic studies of Ni surface segregation induced by CO adsorption on Cu–Ni/SiO2 bimetallic catalysts (2014)

It is of great importance to study the catalytic structures under real reaction conditions especially for the bimetallic catalysts, where facile surface restructure or surface segregation can be driven by adsorbate adsorption. Here, we report CO interaction with Cu-Ni/SiO2 bimetallic model catalysts studied by CO temperature programmed desorption (TPD) and in situ CO polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) under CO pressures varying from ultrahigh vacuum (UHV) to near ambient pressure. Under UHV conditions, Cu is enriched on the surface of Cu-Ni/SiO2 bimetallic catalysts. CO spillover from Cu to Ni on Cu-Ni/SiO2 bimetallic catalysts has been observed at about 200 K under UHV conditions. In situ CO PM-IRRAS shows surface segregation of Ni on the Cu-Ni/SiO2 bimetallic catalysts induced by CO adsorption at ambient pressure CO. The behavior of CO induced surface segregation can lead to severe errors in Ni active site measurements by the selective CO chemisorption on Cu-Ni/SiO2 bimetallic catalysts.
Vaccination of Cotton Rats with a Chimeric FG Glycoprotein of Human Respiratory Syncytial Virus Induces Minimal Pulmonary Pathology on Challenge (1991)

The cotton rat model of human respiratory syncytial virus (RSV) infection was used to study the safety and efficacy of a chimeric FG glycoprotein that was expressed in insect cells using a baculovirus vector. Histologic and virologic examination of vaccinated rat lungs was done after challenge with RSV. When rats were challenged 1 month after vaccination, severe pulmonary inflammation characterized by both a mononuclear and polymorphonuclear cell infiltrate and 30%-40% involvement of lung tissue was observed with a formalin-inactivated RSV vaccine. The FG glycoprotein induced minimal lung inflammation (involving 2%-5% of the lung), while negative controls had 1%-3% lung involvement. Two doses with as little as 20 ng of FG glycoprotein formulated in an aluminum hydroxide adjuvant completely protected the cotton rats from RSV challenge. Thus the chimeric FG glycoprotein is highly immunogenic and induces minimal pulmonary inflammation in the cotton rat model.
Identification of the three-dimensional thioredoxin motif: related structure in the ORF3 protein of the Staphylococcus aureus mer operon (1992)

We have developed a computerized search pattern for recognition of the three-dimensional redox site of thioredoxins based on primary and predicted secondary structure. This pattern, developed in the ARIADNE protein expert system, is used to search for thioredoxin-like tertiary structural motif among proteins for which the only structural information is the primary sequence. The pattern was trained on 102 protein sequences (25 functionals and 77 controls); it matches all 25 members of the functional set under cutoff conditions that include only 2 members of the control set, for a sensitivity of 1.0 and a specificity of 0.97. The pattern matches only one of the two thioredoxin-like domains in protein disulfide isomerases (PDIs) and their analogues, suggesting that the C-terminal domain is more structurally similar to thioredoxin than the N-terminal domain. The Escherichia coli DsbA protein, a possible PDI analogue, appears to be more structurally similar to the N-terminal thioredoxin-like domain of PDIs. Thioredoxin-like redox functionality has been proposed for lutropin and follitropin, in part on the basis of their having -Cys-X-Pro-Cys- sequences. None match our pattern; all lack a predicted alpha-helix pattern element immediately after the active site. Hypothetical proteins in the National Biomedical Research Foundation Protein Identification Resource database were searched for matches to the pattern. The most interesting match was a hypothetical protein (161 residues) from the third open reading frame in the Staphylococcus aureus mer operon, which is involved in mercury detoxification. The match to our pattern and the hydrophobicity distribution in aligned elements of secondary structure not in our pattern strongly suggest that it has thioredoxin-like structure.
Block precoding for MUI/ISI-resilient generalized multicarrier CDMA with multirate capabilities (2001)

Potential increase in capacity along with the need to provide multimedia services and cope with multiuser interference (MUI) and intersymbol interference (ISI) arising due to wireless multipath propagation, motivate well multirate wideband code-division multiple-access (CDMA) systems. Unlike most existing continuous-time symbol-periodic and multipath-free studies, the present paper develops an all-digital block-precoded filter-bank framework capable of encompassing single- or multirate transceivers for asynchronous or quasi-synchronous CDMA transmissions through multipath channels. Thanks to symbol blocking and through appropriate design of user codes, the resulting generalized multicarrier (GMC) CDMA system not only subsumes known multicarrier CDMA variants, but also equips them with flexible multirate capabilities. It is computationally simple, and guarantees symbol recovery regardless of the (possibly unknown) FIR multipath channels in both downlink and uplink setups. Simulations corroborate that the novel GMC-CDMA system outperforms existing multirate alternatives in the presence of asynchronism and multipath, and illustrate the feasibility of recovering blindly multirate transmissions received through unknown frequency-selective channels in the uplink. The performance of GMC-CDMA system in UMTS channels is also simulated and compared with existing multirate schemes.
Pretreatment with Protease Is a Useful Experimental Strategy for Enhancing Adenovirus-Mediated Cancer Gene Therapy (2000)

A key impediment to the development of effective virus-mediated gene therapy for cancer is the low level of gene transfer that occurs after the administration of recombinant viral vectors. Improving in vivo infection and transduction efficiency is an important goal for gene therapy. The limited distribution of gene delivery is particularly problematic when large vectors such as recombinant adenoviruses and retroviruses are used to mediate transgene delivery to solid tumors. To facilitate the spread of virus, we have investigated the potential of administering proteases prior to the intratumoral inoculation of recombinant replication deficient adenovirus. For these studies, we chose proteases that are active against collagen and the other extracellular matrix proteins found in primary brain tumor tissue, but are not widely expressed in normal brain. Various concentrations of a mixture of collagenase/dispase or trypsin were inoculated into xenografts of human glioblastoma multiforme-derived brain tumor cell lines U87, U251, and SF767. Subsequently, recombinant adenovirus encoding the beta-galactosidase gene was administered and tumor tissue was examined for evidence of virus infection. Both collagenase/dispase and trypsin enhanced virus infection, indicating that protease pretreatment may be a useful strategy for enhancing virus-mediated gene transduction for many in vivo applications.
Mycobacteria : molecular biology and virulence (1999)

List of ContributorsPreface1 Recombination2 Mobile Genetic Elements/Plasmids3 Mycobacteriophages4 Gene Expression And Regulation5 Genomics of Mycobacterium Tuberculosis and Mycobacterium Leprae6 Molecular Epidemiology: Human7 Molecular Epidemiology: Mycobacterium8 Molecular Epidemiology: Other Mycobacteria9 Molecular Diagnostics10 Immunodiagnosis of Mycobacterial Infection11 Mycobacterial Growth and Dormancy12 Cell Wall: Physical Structure and Permeability13 The Cell-Wall Core of Mycobacterium: Structure, Biogenesis and Genetics14 Iron Metabolism15 Antibiotic and Antibiotic Resistance in Mycobacteria16. Immunotherapy for Mycobacterial Disease17 Vaccines18 Mycobacterial Antigens19 Mycobacterium and the Seduction of the Macrophage20 Cytokines in Immunity to TuberculosisIndex