gebhart/patrepeval huggingface dataset:
NUTRIENT-RELATED ANALYSIS OF PATHWAY/GENOME DATABASES (2000)

We present an algorithm that solves two related problems in the analysis of metabolic networks stored within a pathway/genome database. (1) The Forward Propagation Problem: given a set of nutrients that are inputs to the metabolic network, what compounds will be produced by the metabolic network? (2) The Backtracking Problem: given the results of a forward propagation, and given a set of essential compounds that are not produced as a result of the forward propagation, what precursors must be supplied to produce those essential compounds? A program based on this algorithm is applied to the EcoCyc database, which is a pathway/genome database for E. coli that consists of annotated genomes and the metabolic reactions and pathways associated with the known gene products. The inputs to the program are a description of the metabolic network of an organism (EcoCyc), a set of nutrients corresponding to a known minimal growth medium, and a list of essential compounds to be produced. The program "fires" the microorganism's metabolism contained in the database and predicts all synthesized and nonsynthesized essential compounds, along with the missing precursors required to produce the latter. When applied to the EcoCyc database, the program identifies a number of missing precursors that indicate incomplete regions of the database. Thus the program results can be used to evaluate existing pathway databases like EcoCyc.
Biological activity of hemoprotein nitrosyl complexes (2007)

Chemical and biological functions of hemoprotein nitrosyl complexes as well as their photolysis products are discussed in this review. Chemical properties of nitric oxide are discussed, and major chemical reactions such as interaction with thiols, free radicals, and transition metals are considered. Specific attention is paid to the generation of hemoprotein nitrosyl complexes. The mechanisms of nitric oxide reactions with hemoglobin and cytochrome c and physicochemical properties of their nitrosyl complexes are discussed. A review of photochemical reactions of nitrosyl complexes with various ligands is given. Finally, we observe physiological effects of visible radiation on hemoprotein nitrosyl complexes: smooth muscle relaxation and reactivation of mitochondrial respiration.
TGTCACA Motif Is a Novel cis-Regulatory Enhancer Element Involved in Fruit-specific Expression of the cucumisin Gene (2002)

Cucumisin, a subtilisin-like serine protease, is expressed at high levels in the fruit of melon (Cucumis melo L.) and accumulates in the juice. We investigated roles of the promoter regions and DNA-protein interactions in fruit-specific expression of the cucumisin gene. In transient expression analysis, a chimeric gene construct containing a 1.2-kb cucumisin promoter fused to a beta-glucuronidase (GUS) reporter gene was expressed in fruit tissues at high levels, but the promoter activities in leaves and stems were very low. Deletion analysis indicated that a positive regulatory region is located between nucleotides -234 and -214 relative to the transcriptional initiation site. Gain-of-function experiments revealed that this 20-bp sequence conferred fruit specificity and contained a regulatory enhancer. Gel mobility shift experiments demonstrated the presence of fruit nuclear factors that interact with the cucumisin promoter. A typical G-box (GACACGTGTC) present in the 20-bp sequence did not bind fruit protein, but two possible cis-elements, an I-box-like sequence (AGATATGATAAAA) and an odd base palindromic TGTCACA motif, were identified in the promoter region between positions -254 and -215. The I-box-like sequence bound more tightly to fruit nuclear protein than the TGTCACA motif. The I-box-like sequence functions as a negative regulatory element, and the TGTCACA motif is a novel enhancer element necessary for fruit-specific expression of the cucumisin gene. Specific nucleotides responsible for the binding of fruit nuclear protein in these two elements were also determined.
Mutagenic analysis of human immunodeficiency virus type 1 Vpr: role of a predicted N-terminal alpha-helical structure in Vpr nuclear localization and virion incorporation (1995)

The Vpr gene product of human immunodeficiency virus type 1 is a virion-associated protein that is important for efficient viral replication in nondividing cells such as macrophages. At the cellular level, Vpr is primarily localized in the nucleus when expressed in the absence of other viral proteins. Incorporation of Vpr into viral particles requires a determinant within the p6 domain of the Gag precursor polyprotein Pr55gag. In the present study, we have used site-directed mutagenesis to identify a domain(s) of Vpr involved in virion incorporation and nuclear localization. Truncations of the carboxyl (C)-terminal domain, rich in basic residues, resulted in a less stable Vpr protein and in the impairment of both virion incorporation and nuclear localization. However, introduction of individual substitution mutations in this region did not impair Vpr nuclear localization and virion incorporation, suggesting that this region is necessary for the stability and/or optimal protein conformation relevant to these Vpr functions. In contrast, the substitution mutations within the amino (N)-terminal region of Vpr that is predicted to adopt an alpha-helical structure (extending from amino acids 16 to 34) impaired both virion incorporation and nuclear localization, suggesting that this structure may play a pivotal role in modulating both of these biological properties. These results are in agreement with a recent study showing that the introduction of proline residues in this predicted alpha-helical region abolished Vpr virion incorporation, presumably by disrupting this secondary structure (S. Mahalingam, S. A. Khan, R. Murali, M. A. Jabbar, C. E. Monken, R. G. Collman, and A. Srinivasan, Proc. Natl. Acad. Sci. USA 92:3794-3798, 1995). Interestingly, our results show that two Vpr mutants harboring single amino acid substitutions (L to F at position 23 [L23F] and A30F) on the hydrophobic face of the predicted helix coded for relatively stable proteins that retained their ability to translocate to the nucleus but exhibited dramatic reduction in Vpr incorporation, suggesting that this hydrophobic face might mediate protein-protein interactions required for Vpr virion incorporation but not nuclear localization. Furthermore, a single mutation (E25K) located on the hydrophilic face of this predicted alpha-helical structure affected not only virion incorporation but also nuclear localization of Vpr. The differential impairment of Vpr nuclear localization and virion incorporation by mutations in the predicted N-terminal alpha-helical region suggests that this region of Vpr plays a role in both of these biological functions of Vpr.
Syntheses, properties, and molecular and crystal structures of (Me4N)4[E4M10(SPh)16] (E = sulfur or selenium; M = zinc or cadmium): molecular supertetrahedral fragments of the cubic metal chalcogenide lattice (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSyntheses, properties, and molecular and crystal structures of (Me4N)4[E4M10(SPh)16] (E = sulfur or selenium; M = zinc or cadmium): molecular supertetrahedral fragments of the cubic metal chalcogenide latticeIan G. Dance, Anna Choy, and Marcia L. ScudderCite this: J. Am. Chem. Soc. 1984, 106, 21, 6285–6295Publication Date (Print):October 1, 1984Publication History Published online1 May 2002Published inissue 1 October 1984https://pubs.acs.org/doi/10.1021/ja00333a030https://doi.org/10.1021/ja00333a030research-articleACS PublicationsRequest reuse permissionsArticle Views2204Altmetric-Citations319LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Structure and Action of Nemertine Toxins (1985)

Bacq (1936, 1937) discovered two substances by pharmacological experiments using whole body extracts of various nemertine species. “Amphiporine,” found only in hoplonemertines, stimulated nicotinic acetylcholine receptor-mediated events. “Nemertine” evoked spontaneous action potentials in isolated crab nerves. Both substances caused convulsions when injected into crabs. Anabaseine, a pyridine alkaloid isolated from the hoplonemertine Paranemertes peregrina, has chemical and pharmacological properties equivalent to “amphiporine.” Hoplonemertines produce a wide variety of pyridine toxins depending on the species. The heteronemertine Cerebratulus lacteus contains cytolytic (10,000 dalton) and neurotoxic (6,000 dalton) proteins. The neurotoxic polypeptides most closely resemble “nemertine”: they cause repetitive spiking in isolated crustacean axons. Several cytolytic and neurotoxic “isotoxins” occur within Cerebratulus. Both the hoplonemertine and heteronemertine toxins are localized in the integumentary tissues of the body wall and proboscis. So far, the pyridine alkaloid toxins are only found in the Enoplan species, where they probably function as both offensive and defensive toxins. Protein toxins have only been found in Anoplan species; they probably serve as a chemical defense against some predators.
The lipase gene family (2002)

Development of the lipase gene family spans the change in science that witnessed the birth of contemporary techniques of molecular biology. Amino acid sequencing of enzymes gave way to cDNA cloning and gene organization, augmented by in vitro expression systems and crystallization. This review traces the origins and highlights the functional significance of the lipase gene family, overlaid on the background of this technical revolution. The gene family initially consisted of three mammalian lipases [pancreatic lipase (PL), lipoprotein lipase, and hepatic lipase] based on amino acid sequence similarity and gene organization. Family size increased when several proteins were subsequently added based on amino acid homology, including PL-related proteins 1 and 2, phosphatidylserine phospholipase A1, and endothelial lipase. The physiological function of each of the members is discussed as well as the region responsible for lipase properties such as enzymatic activity, substrate binding, heparin binding, and cofactor interaction. Crystallization of several lipase gene family members established that the family belongs to a superfamily of enzymes, which includes esterases and thioesterases. This superfamily is related by tertiary structure, rather than amino acid sequence, and represents one of the most populous families found in nature.
Creation of phosphorylation sites in proteins: construction of a phosphorylatable human interferon alpha. (1989)

A phosphorylation site was introduced into human interferon alpha A (IFN-alpha A) by site-specific mutation of the coding sequence. Three slightly different phosphorylation sites were created by using the predicted amino acid consensus sequences for phosphorylation by the cAMP-dependent protein kinase. The resultant modified interferons (IFN-alpha A-P) were expressed in Escherichia coli and purified. The purified proteins exhibit antiviral activity on bovine and human cells similar to that of the unmodified IFN-alpha A. The IFN-alpha A-P proteins can be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase with [gamma-32P]ATP to high specific activity (2000-5000 Ci/mmol; 1 Ci = 37 GBq) with retention of biological activity. The 32P-labeled IFN-alpha A-P proteins bind to cells and can be covalently bound to the IFN-alpha/beta receptor with a bifunctional reagent as can human IFN-alpha A. The introduction of phosphorylation sites into proteins provides a procedure to prepare a large variety of radioactive proteins for research and clinical use.
Age related macular degeneration (2003)

Age related macular degeneration is an increasing problem worldwide. Current treatment options can delay progression, and research continues into ways of reversing retinal damage An epidemic of "ageing" is impending in the Western world. According to the latest predictions released by the United Nations, the number of people aged over 60 will triple from 606 million worldwide in 2000 to nearly 2 billion by 2050. The increase in the population aged over 80 is expected to be more than fivefold, from 69 million in 2000 to 379 million by 2050. People aged over 60 constitute about 20% of the population in more developed regions of the world; by 2050 they will probably account for 33%. 1 The United Kingdom is predicted to have about 16 million people over the age of 60 by 2040. 2 One major implication of this demographic change is the emergence of conditions that are directly related to ageing. Age related macular degeneration is already the leading cause of blindness in the Western world. Between 20 and 25 million people are affected worldwide, a figure that will triple with the increase in the ageing population in the next 30-40 years. 2 According to the World Health Organization, 8 million people have severe blindness due to age related macular degeneration, excluding the countries where data are scare. 3 In a recent systematic review Fletcher et al estimate that somewhere between 182 000 and 300 000 people in the United Kingdom are blind or partially sighted as a result of age related macular degeneration. 4
The subtilisin E gene of Bacillus subtilis is transcribed from a sigma 37 promoter in vivo. (1984)

A cloned Bacillus subtilis gene (sprE) expressed only during the stationary growth phase is shown to encode the subtilisin E protease, an enzyme associated with sporulation. We have determined the DNA sequence of the sprE promoter region and the promoter-proximal half of the structural gene. The sprE gene codes for a putative 29-residue signal peptide and a 77-residue leader peptide preceding the mature subtilisin sequence. By plasmid integration and phage PBS1 transduction, we have mapped the sprE locus between glyB and metD on the B. subtilis chromosome, a region also containing the hyperprotease-producing hpr gene. In vitro the sprE gene is transcribed by the minor form of RNA polymerase containing a 37,000-dalton sigma factor (sigma 37). We show by S1 nuclease mapping that sprE transcription initiates at dual start sites both in vitro and in vivo and that the promoter for the downstream site has a characteristic sigma 37 recognition sequence. We propose that the physiological role of the sigma 37 RNA polymerase is to transcribe a class of genes that are catabolite repressed, that encode extracellular enzymes, or that are expressed only during the stationary phase of growth.
Heteropoly Salts Containing Cobalt and Hexavalent Tungsten in the Anion1 (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHeteropoly Salts Containing Cobalt and Hexavalent Tungsten in the Anion1Louis C. W. Baker and Thomas P. McCutcheonCite this: J. Am. Chem. Soc. 1956, 78, 18, 4503–4510Publication Date (Print):September 1, 1956Publication History Published online1 May 2002Published inissue 1 September 1956https://doi.org/10.1021/ja01599a001RIGHTS & PERMISSIONSArticle Views1817Altmetric-Citations157LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts
Eradication of multidrug-resistant A. baumannii in burn wounds by antiseptic pulsed electric field (2014)

Emerging bacterial resistance to multiple drugs is an increasing problem in burn wound management. New non-pharmacologic interventions are needed for burn wound disinfection. Here we report on a novel physical method for disinfection: antiseptic pulsed electric field (PEF) applied externally to the infected burns. In a mice model, we show that PEF can reduce the load of multidrug resistant <i>Acinetobacter baumannii</i> present in a full thickness burn wound by more than four orders of magnitude, as detected by bioluminescence imaging. Furthermore, using a finite element numerical model, we demonstrate that PEF provides non-thermal, homogeneous, full thickness treatment for the burn wound, thus, overcoming the limitation of treatment depth for many topical antimicrobials. These modeling tools and our <i>in vivo</i> results will be extremely useful for further translation of the PEF technology to the clinical setting, as they provide the essential elements for planning of electrode design and treatment protocol.
‘Planned Growth of Incomes’ or ‘Emergency Gimmick’? The Labour Party, The Social Partners and Incomes Policy, 1964-70 (2004)

Previous attempts to explain Britain's failure to develop an effective incomes policy have tended to focus on general causes. These have included the small scale of industry, the weakness of ‘peak associations’ of employers and trade unionists, or fragmentation and lack of expertise in government. While this article does not attempt to challenge the importance of these factors, it will attempt to tell a more detailed and specific story about Labour's attempt to construct a ‘social bargain’ in the late 1960s. Using recently released documents from the archives of central government, unions and employers, this piece will attempt to show that Labour's confusion as to the aims of incomes policy was another important reason for the policy's failure. Ideological divisions at elite policy-making levels made the whole project less than realistic from the start. While the Government was uncertain as to the aims of policy, trade unions and employers were initially sceptical towards, and later totally opposed to, in...
Chain: a delay-insensitive chip area interconnect (2002)

The increasing complexity of system-on-a-chip designs exposes the limits imposed by the standard synchronous bus. The authors propose a mixed system as a solution.
Enhancing axon regeneration in peripheral nerves also increases functionally inappropriate reinnervation of targets (2005)

The specificity of reinnervation of peripheral targets by regenerating motor axons was studied in mice by using retrograde fluorescent tracers applied to the cut ends of the tibial and common fibular nerves after transection and surgical repair of the sciatic nerve. When the nerve ends were aligned and secured with fibrin glue, more motoneurons labeled after application of tracer to the common fibular nerve were found in regions of the spinal cord that normally contain only tibial motoneurons. The magnitude of such inappropriate reinnervation did not change at different times after repair. Intentional misalignment of the cut nerve stumps at the time of repair resulted in more extensive inappropriate reinnervation of the different peripheral targets. If the proximal stump of the cut nerve was electrically stimulated at the time of repair, if the distal stump was treated with chondroitinase ABC, or if both protocols were applied, the number of motoneurons labeled was increased. This increase was accompanied by more extensive reinnervation of inappropriate targets than found after untreated nerve repair. Although alterations in the caudorostral distributions of labeled motoneurons observed were not as great as observed after purposeful misalignment of the cut nerve ends, the topographic relationship between the spinal locations of motoneuron somata and the peripheral targets of their axons is disrupted. Enhancement of motor axon regeneration by induction of growth-promoting signaling pathways, reduction in growth inhibition in the environment of regenerating axons, or both, is accompanied by an increase in the amount of functionally inappropriate reinnervation of peripheral targets.
Paclitaxel in head and neck and other cancers: future prospects. (1997)

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a member of the taxanes, has been shown to have antitumor activity in a wide variety of cancers, such as breast cancer and ovarian cancer. Paclitaxel also has antitumor activity in certain previously relatively unresponsive tumors, such as lung, head and neck, esophageal, and bladder cancers. The optimal dose for each tumor has not been well defined. While 3-hour infusion appears to be the most convenient, studies of both longer and shorter infusions are in progress. Any incremental benefit of higher dose or longer schedule will need to be evaluated on the basis of the higher costs and toxicities. The results of many initial studies using combination chemotherapy with paclitaxel have generated considerable enthusiasm, but careful comparison studies and evaluation of toxicities are needed. Additional roles of paclitaxel include its ability to act synergistically with radiotherapy, and thus possibly help improve the local control of tumors, such as head and neck, esophageal, bladder, and lung cancers. Studies testing the role of the taxanes in neoadjuvant therapy before radiotherapy or surgery are just beginning. Paclitaxel is thus one of the very important new agents in the treatment of cancer, and further work is needed to define its optimal use.
A Decline in Mupirocin Resistance in Methicillin-ResistantStaphylococcus aureusAccompanied Administrative Control of Prescriptions (2004)

Susceptibility to mupirocin was assessed in methicillin-resistant Staphylococcus aureus isolates selected from eras corresponding to differences in usage rate and prescription policies at a Veterans Affairs medical center. The eras studied encompassed from the time of introduction of the drug to its widespread use, through recommended judicious use, and finally to subsequent stringent administrative control. Prescriptions declined from 3.0 to 0.1 per 1,000 patient days. Precipitous declines first in the numbers of isolates with high-level resistance (from 31% to 4%) and then in those with low-level resistance (from 26% to 10%) accompanied prescription control.
Distinct Cytokine Patterns Identified from Multiplex Profiles of Murine DSS and TNBS-Induced Colitis (2008)

Our studies provide insight into disease immunopathogenesis and illustrate the significant potential of utilizing multiplex cytokine profiles and bioinformatics as diagnostic tools in IBD.