gebhart/patrepeval huggingface dataset:
Mini-G proteins: Novel tools for studying GPCRs in their active conformation (2017)

Mini-G proteins are the engineered GTPase domains of Gα subunits. They couple to GPCRs and recapitulate the increase in agonist affinity observed upon coupling of a native heterotrimeric G protein. Given the small size and stability of mini-G proteins, and their ease of expression and purification, they are ideal for biophysical studies of GPCRs in their fully active state. The first mini-G protein developed was mini-Gs. Here we extend the family of mini-G proteins to include mini-Golf, mini-Gi1, mini-Go1 and the chimeras mini-Gs/q and mini-Gs/i. The mini-G proteins were shown to couple to relevant GPCRs and to form stable complexes with purified receptors that could be purified by size exclusion chromatography. Agonist-bound GPCRs coupled to a mini-G protein showed higher thermal stability compared to the agonist-bound receptor alone. Fusion of GFP at the N-terminus of mini-G proteins allowed receptor coupling to be monitored by fluorescence-detection size exclusion chromatography (FSEC) and, in a separate assay, the affinity of mini-G protein binding to detergent-solubilised receptors was determined. This work provides the foundation for the development of any mini-G protein and, ultimately, for the structure determination of GPCRs in a fully active state.
Resistance is futile: the bacteriocin model for addressing the antibiotic resistance challenge (2012)

Pathogenic bacteria resistant to many or all antibiotics already exist. With the decline in microbiological research at pharmaceutical companies, the high rate at which resistance has evolved and spread has demanded a novel approach to addressing this critical human health issue. In the present paper, we propose a new paradigm in antibiotic discovery and development, one that applies ecological and evolutionary theory to design antimicrobial drugs that are more difficult and/or more costly to resist. In essence, we propose to simply adopt the strategies invented and applied by bacteria for hundreds of millions of years. Our research focuses on bacteriocins, powerful biological weapons, and their use as alternative therapeutics in human health.
ISL1 Protein Transduction Promotes Cardiomyocyte Differentiation from Human Embryonic Stem Cells (2013)

This study has presented a new, efficient, and reproducible procedure for cardiomyocytes differentiation. Our results will pave the way for scaled up and controlled differentiation of hESCs to be used for biomedical applications in a bioreactor culture system.
Association between the appendix and the fecalith in adults (2015)

Our data confirm the theory of a statistical association between the presence of a fecalith and acute (nonperforated) appendicitis in adults. There was also a significant association between the healthy appendix and asymptomatic fecaliths. There was no correlation between a gangrenous/perforated appendix and the presence of a fecalith. The fecalith is an incidental finding and not always the primary cause of acute (nonperforated) appendictis or gangrenous (perforated) appendicitis. Further research on the topic is recommended.
Escherichia coli host factor for site-specific DNA inversion: cloning and characterization of the fis gene. (1988)

The Escherichia coli (Es. coli) protein Fis (factor for inversion stimulation) stimulates site-specific DNA inversion of the G segment in phage Mu by binding to a recombinational enhancer. By using synthetic oligonucleotides deduced from the amino-terminal amino acid sequence, we have cloned the gene (termed fis) encoding this specific DNA-binding protein. The DNA sequence shows that the Fis protein is basic and contains 98 amino acids. A helix-turn-helix sequence motif characteristic of many DNA-binding proteins is located at the carboxyl-terminal end of the protein. By marker exchange, we have constructed an insertion mutation of fis. Fis is nonessential for Es. coli growth; however, inversion of the G segment of a Mu prophage was not detected in the fis mutant. The fis gene is located between 71 and 72 min on the Es. coli genetic map.
TheArabidopsis HY5gene encodes a bZIP protein that regulates stimulus-induced development of root and hypocotyl (1997)

Plant developmental processes are controlled by both endogenous programs and environmental stimuli. As a photomorphogenetic mutant, hy5 of Arabidopsis has been isolated and characterized. Our detailed characterization has revealed that the mutant is deficient in a variety of stimulus responses, including gravitropic response and waving growth of roots, as well as light-dependent hypocotyl elongation. In the roots and hypocotyl, the hy5 mutation also affects greening and specific cell proliferation such as lateral root formation and secondary thickening. Those phenotypes indicate that the HY5 gene is responsible for the regulation of fundamental developmental processes of the plant cell: cell elongation, cell proliferation, and chloroplast development. Molecular cloning of the HY5 gene using a T-DNA-tagged mutant has revealed that the gene encodes a protein with a bZIP motif, one of the motifs found in transcriptional regulators. Nuclear localization of the HY5 protein strongly suggests that the HY5 gene modulates the signal transduction pathways under the HY5-related development by controlling expression of genes downstream of these pathways.
In vitro site-specific integration of bacteriophage DNA catalyzed by a recombinase of the resolvase/invertase family (1998)

The genome of the broad host range Streptomyces temperate phage, phiC31, is known to integrate into the host chromosome via an enzyme that is a member of the resolvase/invertase family of site-specific recombinases. The recombination properties of this novel integrase on the phage and Streptomyces ambofaciens attachment sites, attP and attB, respectively, were investigated in the heterologous host, Escherichia coli, and in an in vitro assay by using purified integrase. The products of attP/B recombination, i.e., attL and attR, were identical to those obtained after integration of the prophage in S. ambofaciens. In the in vitro assay only buffer, purified integrase, and DNAs encoding attP and attB were required. Recombination occurred irrespective of whether the substrates were supercoiled or linear. A mutant integrase containing an S12F mutation was completely defective in recombination both in E. coli and in vitro. No recombination was observed between attB/attB, attP/attP, attL/R, or any combination of attB or attP with attL or attR, suggesting that excision of the prophage (attL/R recombination) requires an additional phage- or Streptomyces-encoded factor. Recombination could occur intramolecularly to cause deletion between appropriately orientated attP and attB sites. The results show that directionality in phiC31 integrase is strictly controlled by nonidentical recombination sites with no requirement to form the topologically defined structures that are more typical of the resolvases/invertases.
Rituximab in B-cell disorders other than non-Hodgkinʼs Iymphoma (2002)

Rituximab is a human/mouse chimeric monoclonal antibody that binds to the CD20 antigen and is expressed at all stages of B-cell development. Rituximab has demonstrated efficacy as monotherapy and in combination with chemotherapy in the treatment of both indolent and aggressive non-Hodgkin's lymphoma (NHL). Rituximab treatment results in rapid depletion of B-cells and this has led to the consideration of other B-cell disorders as candidates for rituximab therapy. Recent studies have demonstrated the efficacy of rituximab in a variety of such disorders, including chronic lymphocytic leukemia (CLL), post-transplant lymphoproliferative disorder (PTLD), Waldenström's macroglobulinemia (WM), multiple myeloma (MM), idiopathic thrombocytopenic purpura (ITP), hairy-cell leukemia (HCL) and cold agglutinin disease (CAD). In patients with CLL, increasing the dose and/or frequency of rituximab treatment has given improved response rates compared with the standard dose schedule used in NHL, and combination immunochemotherapy has yielded an overall response rate of 92% (with a 60% complete response rate). Clinical trials have also demonstrated evidence of efficacy for rituximab in PTLD, WM and relapsed or refractory ITP. Efficacy of rituximab in CAD and relapsed or refractory HCL has also been demonstrated in small studies and case reports. Available data thus indicate that rituximab can be an effective therapy in a wide range of CD20+ lymphoid disorders.
Identification and partial characterization of Mycobacterium avium and Mycobacterium intracellulare by using DNA probes (1989)

We attempted to identify the Mycobacterium avium complex (MAC) isolated in Japan by using DNA probes specific for M. avium or Mycobacterium intracellulare (Gen-Probe Rapid Diagnostic System for MAC; Gen-Probe, Inc., San Diego, Calif.). The source and drug susceptibility distributions were examined. This assay system proved to be rapid, sensitive, specific, and reliable for identification of MAC and of the species as either M. avium or M. intracellulare. The DNA probe test showed that of the generally accepted MAC serovars, serovars 1 to 6, 8 to 11, and 21 belonged to M. avium and 7 and 12 to 20 belonged to M. intracellulare. Moreover, with the DNA probe test we found that the distribution patterns of M. avium and M. intracellulare isolates in Japan differed depending on the district in which MAC was isolated. The ratio of M. avium was much higher in eastern Japan. In Tokai and Shimane districts, the ratio of M. avium and M. intracellulare isolates significant in human disease was related to that of isolates from soil and house dust (natural sources). In M. avium, human disease-associated isolates were more resistant to rifampin, streptomycin, and kanamycin than were isolates from natural sources. However, this source dependence was not evident for M. intracellulare. In human disease-associated MAC, M. avium isolates were more resistant to most agents, except for quinolones, than were M. intracellulare isolates.
Development of Arthritis, Periarthritis and Periostitis in Rats Given Adjuvants. (1956)

Summary and ConclusionsA reproducible generalized or focal arthritis, synovitis, periostitis and tendonitis has been induced in rats by intracutaneous injections of a Freund-type adjuvant which was most potent when macerated striated muscle tissue was added to the inoculum. The pathogenetic mechanisms underlying the production of these changes is at present unclear.
Identification of residues involved in the binding of methionine byEscherichia coli methionyl&#x2010;tRNA synthetase (1991)

Comparison of the amino-acid sequences of several methionyl-tRNA synthetases indicates the occurrence of a few conserved motifs, having a possible functional significance. The role of one of these motifs, centered at position 300 in the E. coli enzyme sequence, was assayed by the use of site-directed mutagenesis. Substitution of the His301 or Trp305 residues by Ala resulted in a large decrease in methionine affinity, whereas the change of Val298 into Ala had only a moderate effect. The catalytic rate of the enzyme was unimpaired by these substitutions. It is concluded that the above conserved amino-acid region is located at or close to the amino-acid binding pocket of methionyl-tRNA synthetase.
Dynamic Multidimensional Wavelet Neural Network and Its Application (2000)

We propose an efficient neural network called a dynamic multidimensional wavelet neural network (DMWNN). Since the resulting network based on wavelet theory can provide the efficient representation of a nonlinear function and has the capability to keep some previous information for later use, it can perform effective dynamic mapping with lower input signal dimensions. These features of the DMWNN show one way to compensate for the weakness of the diagonal recurrent neural network (DRNN) and feed-forward wavelet neural network (FWNN). Effectiveness in application of the proposed neural network is also demonstrated through simulation results.
Mitochondrial Medicine: Pharmacological targeting of mitochondria in disease (2007)

Mitochondria play a central role in cell life and death and are known to be important in a wide range of diseases including the cancer, diabetes, cardiovascular disease, and the age-related neurodegenerative diseases. The unique structural and functional characteristics of mitochondria enable the selective targeting of drugs designed to modulate the function of this organelle for therapeutic gain. This review discusses mitochondrial drug targeting strategies and a variety of novel mitochondrial drug targets including the electron transport chain, mitochondrial permeability transition, Bcl-2 family proteins and mitochondrial DNA. Mitochondrial drug-targeting strategies will open up avenues for manipulating mitochondrial functions and allow for selective protection or eradication of cells for therapeutic gain in a variety of diseases.
A bromocoumarin-based linker for synthesis of photocleavable peptidoconjugates with high photosensitivity (2008)

A new bromocoumarin-based bi-functional linker was developed for preparing photocleavable peptides and proteins with high photolytic efficiency, which have many potential applications in the study and engineering of biological systems.
X‐ray crystallographic analysis of the structural basis for the interactions of pokeweed antiviral protein with its active site inhibitor and ribosomal RNA substrate analogs (1999)

The pokeweed antiviral protein (PAP) belongs to a family of ribosome-inactivating proteins (RIP), which depurinate ribosomal RNA through their site-specific N-glycosidase activity. We report low temperature, three-dimensional structures of PAP co-crystallized with adenyl-guanosine (ApG) and adenyl-cytosine-cytosine (ApCpC). Crystal structures of 2.0-2.1 A resolution revealed that both ApG or ApCpC nucleotides are cleaved by PAP, leaving only the adenine base clearly visible in the active site pocket of PAP. ApCpC does not resemble any known natural substrate for any ribosome-inactivating proteins and its cleavage by PAP provides unprecedented evidence for a broad spectrum N-glycosidase activity of PAP toward adenine-containing single stranded RNA. We also report the analysis of a 2.1 A crystal structure of PAP complexed with the RIP inhibitor pteoric acid. The pterin ring is strongly bound in the active site, forming four hydrogen bonds with active site residues and one hydrogen bond with the coordinated water molecule. The second 180 degrees rotation conformation of pterin ring can form only three hydrogen bonds in the active site and is less energetically favorable. The benzoate moiety is parallel to the protein surface of PAP and forms only one hydrogen bond with the guanido group of Arg135.
Mechanism of IgM Polymerization (1974)

The stoichiometry of J chain in pentamer IgM has been determined by measuring the radiolabeled thiols in the constituent chains after complete reduction and alkylation of the polymer. One mole of J was found to be disulfide bonded to 1 mol of pentamer. The linkage of J chain in IgM has been determined by correlating the J disulfides cleaved with the subunits released after limited reduction and alkylation of the polymer. The analyses showed that: ( a ) Significant amounts of monomers, as well as small quantities of dimers, trimers, and tetramers, were generated by the reducing conditions employed. ( b ) The number of J disulfide bonds broken did not correspond to the extent of depolymerization. ( c ) No J disulfides were cleaved in the J-containing dimer products of the limited reduction. These data demonstrated that the J chain is located as a disulfide clasp between two of the IgM monomer subunits. From the observed linkage, the assembly of IgM is postulated to proceed by a series of sequential disulfide exchanges beginning with the formation of the J-containing dimer.
Preventing Pneumocystis carinii Pneumonia in Persons Infected with Human Immunodeficiency Virus (1995)

Although the incidence of Pneumocystis carinii pneumonia (PCP) among adults infected with human immunodeficiency virus (HIV) has declined, no decline in PCP incidence has been observed among HIV-infected children, and PCP remains the most common serious opportunistic infection among both adults and children in the United States. Some evidence of airborne transmission of P. carinii exists, and some clusters of cases of PCP have been reported; however, data are insufficient to recommend that persons with PCP be separated from immunosuppressed persons as a standard practice. The incidence of PCP can be reduced substantially if persons at risk for PCP are identified and receive adequate chemoprophylaxis. Several drugs and drug combinations are highly effective in preventing PCP. For both adults and children, oral trimethoprim-sulfamethoxazole (TMP-SMZ) is the preferred form of prophylaxis. Adverse effects are commonly associated with the use of TMP-SMZ and in some cases may necessitate withdrawal of the drug until the effects resolve. However, reintroduction at the same dose or at a lower and gradually increasing dose will often permit the continued use of TMP-SMZ. For persons intolerant of TMP-SMZ, dapsone alone and dapsone plus pyrimethamine are effective alternatives. A third alternative is aerosolized pentamidine. Additional drugs of unproven efficacy but of potential use in exceptional cases are available.
Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling (2009)

Radiation-induced damage of normal tissues restricts the therapeutic doses of ionizing radiation that can be delivered to tumors and thereby limits the effectiveness of radiotherapy. Thrombospondin-1 signaling through its cell surface receptor CD47 limits recovery from several types of stress, and mice lacking either gene are profoundly resistant to radiation injury. We describe strategies to protect normal tissues from radiation damage using CD47 or thrombospondin-1 antibodies, a CD47-binding peptide, or antisense suppression of CD47. A morpholino oligonucleotide targeting CD47 confers radioresistance to human endothelial cells in vitro and protects soft tissue, bone marrow, and tumor-associated leukocytes in irradiated mice. In contrast, CD47 suppression in mice bearing melanoma or squamous lung tumors prior to irradiation result in 89% and 71% smaller tumors, respectively. Thus, inhibiting CD47 signaling maintains the viability of normal tissues following irradiation while increasing the radiosensitivity of tumors.
Evaluation of Efficient Archival Storage Techniques. (2004)

The ever-increasing volume of archival data that need to be retained for long periods of time has motivated the design of low-cost, high-efficiency storage systems. Inter-file compression has been proposed as a technique to improve storage efficiency by exploiting the high degree of similarity among archival data. We evaluate the two main inter-file compression techniques, data chunking and delta encoding, and compare them with traditional intra-file compression. We report on experimental results from a range of representative archival data sets.
Boron neutron capture therapy of intracerebral rat gliosarcomas. (1990)

The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively. On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days. The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived greater than 15 months. In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation.
Kinetics of perrhenate uptake and comparative biodistribution of perrhenate, pertechnetate, and iodide by NaI symporter-expressing tissues in vivo. (2004)

Perrhenate is avidly taken up by NIS in a manner similar to iodide and pertechnetate in vivo, with the exception of organification of iodide by the thyroid. By more fully appreciating the behavior of perrhenate, especially in relation to iodide and pertechnetate, we can better realize its potential role in the diagnosis and therapy of NIS-bearing tissues.
Experience with inhaled nitric oxide therapy in hypoxic respiratory failure of the newborn. (2005)

Inhaled nitric oxide appears to be an effective rescue therapy for the management of PPHN associated with hypoxic respiratory failure. It is safe and well tolerated with no evidence of clinical or biochemical side effects.
Image formation in NMR by a selective irradiative process (1974)

A new method of image formation by NMR is described. It is based on selective RF irradiation of the sample in switched magnetic field gradients. Selective irradiation may be achieved by tailored (or simple) excitation or tailored (or simple) saturation. Preliminary experiments illustrating various aspects of the method are described, and a two dimensional picture or image of a simple object is presented.
Microindel detection in short-read sequence data (2010)

Supplementary data are available at Bioinformatics online.
Circuit hot electron effect simulation (1987)

Hot electron effects resulting from high electric fields in submicron devices can severely degrade device characteristics. As a result, severe performance degradation can occur at the circuit level. No simulator exists to predict this effect. The purpose of this paper is to present circuit hot electron effect simulation using our recently developed simulator. As a result, a circuit performance degradation due to hot electron can be simulated and the MOSFETs which results in this degradation can be identified.
INTERBRANCH SEQUENCES IN THE WHEAT ARABINO-XYLAN: SELECTIVE ENZYMOLYSIS STUDIES (1963)

A Streptomyces xylanase degrades the soluble arabino-xylan of wheat with formation of polymeric fragments and several oligosaccharides. The overall data, together with information about the spatial requirements of the xylanase, show that (a) the arabino-xylan molecules are constituted predominantly of highly branched regions in which isolated and paired L-arabinosyl branches are separated by single D-xylosyl units; (b) at unequal intervals (averaging 20−25 main-chain units) this type of sequence is interrupted by "open regions" of at least two to five unbranched D-xylosyl units; and (c) infrequently, an L-arabinosyl branch is removed from other branches at either side by at least two D-xylosyl units.A new tetrasaccharide isolated from the enzymic digest is shown to be O-α-L-arabino-furanosyl-(1 → 3)-O-[β-D-xylopyranosyl-(1 → 4)]-O-β-D-xylopyranosyl-(1 → 4)-D-xylose.