gebhart/patrepeval huggingface dataset:
HIV‐1 TAT‐mediated protein transduction and subcellular localization using novel expression vectors1 (2002)

Several novel prokaryotic and eukaryotic expression vectors were constructed for protein transduction and subcellular localization. These vectors employed an N-terminal stretch of 11 basic amino acid residues (47-57) from the human immunodeficiency virus type 1 (HIV-1) TAT protein transduction domain (PTD) for protein translocation and cellular localization. The vectors also contained a six-histidine (His(6)) tag at the N- or C-terminus for convenient purification and detection, and a multiple cloning site for easy insertion of foreign genes. Some heterologous genes including HSV-TK, Bcl-rambo, Smac/DIABLO and GFP were fused in-frame to TAT PTD and successfully overexpressed in Escherichia coli. The purified TAT-GFP fusion protein was able to transduce into the mammalian cells and was found to locate mainly in the cytosol when exogenously added to the cell culture medium. However, using a transfection system, mammalian-expressed TAT-GFP predominantly displayed a nuclear localization and nucleolar accumulation in mammalian cell lines. This discrepancy implies that the exact subcellular localization of transduced protein may depend on cell type, the nature of imported proteins and delivery approach. Taken together, our results demonstrate that a TAT PTD length of 11 amino acids was sufficient to confer protein internalization and its subsequent cellular localization. These novel properties allow these vectors to be useful for studying protein transduction and nuclear import.
ChemInform Abstract: SYNTHESIS OF IRON(II) C2‐CAPPED STRAPPED PORPHYRIN COMPLEXES AND THEIR REACTION WITH DIOXYGEN (1984)

Abstract Die Synthese des "(′3‐überkappten" Porphyrins (IX) ist im Schema aufgezeigt.
Synthesis of "9-deazaguanosine" and other new pyrrolo[3,2-d]pyrimidine C-nucleosides (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of "9-deazaguanosine" and other new pyrrolo[3,2-d]pyrimidine C-nucleosidesMu Ill Lim, Wu Yun Ren, Brian A. Otter, and Robert S. KleinCite this: J. Org. Chem. 1983, 48, 6, 780–788Publication Date (Print):March 1, 1983Publication History Published online1 May 2002Published inissue 1 March 1983https://pubs.acs.org/doi/10.1021/jo00154a005https://doi.org/10.1021/jo00154a005research-articleACS PublicationsRequest reuse permissionsArticle Views323Altmetric-Citations67LEARN 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-Alertsclose Get e-Alerts
Probiotics: overview of microbiological and immunological characteristics (2008)

Over the last few years, probiotics (commercialized as food, dietary supplements of living bacteria or pharmaceuticals) have attracted the interest of scientists as well as consumers. Recent public interest in healthier lifestyles, together with the acceptance by physicians of nonmainstream therapies, has refocused attention on the role of human microbiota in the prevention and therapy of diseases. Modulation of the intestinal microbiota may be achieved by consuming living bacteria or by consuming a combination of probiotics and prebiotics. In addition, we are learning more about the biology of probiotic microorganisms, through sequencing their genomes, and the interactions of probiotics with human cells and with pathogenic bacteria. Results from well-conducted clinical studies help to increase the acceptance of probiotics for the treatment and prevention of selected diseases, both inside and outside the GI tract. Moreover, the use of selected probiotics for particular subject groups may provide more specific health effects. The medical profession is in an ideal position to guide the consumer towards appropriate prophylactic or therapeutic uses of probiotics in health or in specific disease states.
An intense, simple carbon cluster source (1990)

An intense source of positive, negative, and neutral carbon clusters using excimer laser ablation of polyimide is described. The detection probability for large masses using a standard channel plate configuration is shown to increase exponentially with ion velocity. The large clusters are formed via aggregation of atomic carbon or small carbon molecules. The small ‘‘clusters’’ may be molecular fragments from the polymer which rearrange on leaving the surface to form stable structures.
Adolescent idiopathic scoliosis. Is low melatonin a cause? (2000)

Our data suggest that serum melatonin levels may contribute to the pathogenesis of idiopathic scoliosis.
Core valve embolization: Technical challenges and management (2011)

Transcatheter Aortic Valve Implantation with the Core Valve self expanding prosthesis can be complicated by hemodynamic instability in cases of low deployment (implant failure). The management of a low implant may necessitate repositioning the prostheses with the help of a snare catheter. Snaring can however be complicated by embolization of the prosthesis which presents a series of technical challenges that need to be addressed. We have discussed the technical issues and the approach to address them successfully in a systematic manner to ensure optimal procedural and patient outcomes.
Halofuginone: From veterinary use to human therapy (2000)

At present, halofuginone is the only known inhibitor of collagen synthesis that is type specific. Halofuginone was found to inhibit collagen α1(I) gene expression and collagen synthesis in vitro in cell cultures and in various animal models in vivo characterized by excessive deposition of collagen, which results in fibrosis. Toxicity studies both in animals and in normal volunteers revealed no major side effects. Halofuginone was successfully used topically in a patient with chronic graft-versus-host disease and at present is being tested in a clinical trial of patients with scleroderma. Collagen is an important component of the stroma and is involved in endothelial cell migration and assembly to form and recruit new blood vessels—angiogenesis. Both stromal support and angiogenesis are critical for tumor growth. Based on this rationale, using various tumor models such as bladder carcinoma, prostate cancer, and glioma, we demonstrated that inhibition of collagen α1(I) gene expression by halofuginone caused inhibition of angiogenesis, which resulted in arrest of tumor growth. Thus, inhibition of collagen type I synthesis provides an attractive new target for cancer therapy. Many of the possible targets for halofuginone therapy pose enormous clinical problems, most of them without solutions. The ability of extremely low concentrations of halofuginone, given orally, locally or injected intraperitoneally, to inhibit collagen α1(I) synthesis specifically and transiently at the transcriptional level suggests that this compound fulfills the criteria for a successful and effective antifibrotic and anticancer therapy. Drug Dev. Res. 50:371–378, 2000. © 2000 Wiley-Liss, Inc.
Automotive electrical systems: architecture and components (2003)

Automotive electrical power systems that address the demands of increased electrical power, improved fuel economy and reduced emissions are discussed. Considerations related to high-efficiency automotive electrical power systems such as the selection of the types of electrical machines and power converters, selection of system voltages, battery voltage equalization, load management, energy management, regenerative braking, centralized and distributed power system architectures, DC and AC power distribution systems, and multiplexing are also discussed.
Botox-induced prostatic involution (1998)

Botulinum toxin type A injection into the prostate gland induces selective denervation and subsequent atrophy of the prostate. Apoptosis was seen diffusely throughout the gland. It may be possible that in the future, this long-acting neurotoxin could be used for the treatment of common pathologies of the human prostate.
Aloisines, a New Family of CDK/GSK-3 Inhibitors. SAR Study, Crystal Structure in Complex with CDK2, Enzyme Selectivity, and Cellular Effects (2002)

Cyclin-dependent kinases (CDKs) regulate the cell cycle, apoptosis, neuronal functions, transcription, and exocytosis. The observation of CDK deregulations in various pathological situations suggests that CDK inhibitors may have a therapeutic value. In this article, we report on the identification of 6-phenyl[5H]pyrrolo[2,3-b]pyrazines (aloisines) as a novel potent CDK inhibitory scaffold. A selectivity study performed on 26 kinases shows that aloisine A is highly selective for CDK1/cyclin B, CDK2/cyclin A-E, CDK5/p25, and GSK-3 alpha/beta; the two latter enzymes have been implicated in Alzheimer's disease. Kinetic studies, as well as the resolution of a CDK2-aloisine cocrystal structure, demonstrate that aloisines act by competitive inhibition of ATP binding to the catalytic subunit of the kinase. As observed with all inhibitors reported so far, aloisine interacts with the ATP-binding pocket through two hydrogen bonds with backbone nitrogen and oxygen atoms of Leu 83. Aloisine inhibits cell proliferation by arresting cells in both G1 and G2.
Kinetics of Thermal Dehydroxylation and Carbonation of Magnesium Hydroxide (1996)

The kinetics of simultaneous dehydroxylation and carbonation of precipitated Mg(OH) 2 were studied using isothermal and nonisothermal thermogravimetric analyses. Specimens were analyzed using X‐ray diffraction, transmission electron microscopy, and through measurements of the volume of carbon dioxide evolved in a subsequent reaction with hydrochloric acid. From 275° to 475°C, the kinetics of isothermal dehydroxylation in helium were best fit to a contracting‐sphere model, yielding an activation energy of 146 kJ/mol, which was greater than values reported in the literature for isothermal dehydroxylation under vacuum (53–126 kJ/mol). The carbonation kinetics were complicated by the fact that dehydroxylation occurred simultaneously. The overall kinetics also could be fit to a contracting‐sphere model, yielding a net activation energy of 304 kJ/mol. The most rapid carbonation kinetics occurred near 375°C. At this temperature, Mg(OH) 2 underwent rapid dehydroxylation and subsequent phase transformation, whereas thermodynamics favored the formation of carbonate. During carbonation, MgCO 3 precipitated on the surface of disrupted Mg(OH) 2 crystals acting as a kinetic barrier to both the outward diffusion of H 2 O and the inward diffusion of CO 2 .
Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: implications for vaccine development (1997)

Despite recent advances in antiviral therapy for human immunodeficiency virus (HIV) infection, successful global intervention will require an effective vaccine. Expanding evidence suggests that cytotoxic T-lymphocyte (CTL) responses will be an important component of such a vaccine. The varying geographic distribution of HIV type 1 (HIV-1) clades, with the relative absence of clade B HIV-1 outside the developed world, is considered a major obstacle to the development of a single efficacious vaccine. An understanding of cross-reactive CTL responses between different HIV-1 clades is crucial in the design of a vaccine which will be broadly immunogenic. In this study, we examined the ability of HIV-1 Gag-, reverse transcriptase-, and Env-specific CTL clones isolated from individuals infected in the United States to recognize non-B clade viral sequences and found that all were cross-reactive with the majority of non-B clade viral sequences tested. We next studied HIV-1-specific CTL responses in African individuals infected with clade A, C, or G virus and evaluated cross-recognition of clade B virus. Of 14 persons evaluated, all demonstrated cross-reactivity with the U.S. clade B viral constructs. We conclude that significant CTL cross-reactivity exists between clade B and non-B epitopes, suggesting that CTL cross-recognition among HIV-1 clades is more widespread than anticipated and that a vaccine based on a single clade may be broadly applicable.
Engineering microbial chemical factories to produce renewable “biomonomers” (2012)

By applying metabolic engineering tools and strategies to engineer synthetic enzyme pathways, the number and diversity of commodity and specialty chemicals that can be derived directly from renewable feedstocks is rapidly and continually expanding. This of course includes a number of monomer building-block chemicals that can be used to produce replacements to many conventional plastic materials. This review aims to highlight numerous recent and important advancements in the microbial production of these so-called "biomonomers." Relative to naturally-occurring renewable bioplastics, biomonomers offer several important advantages, including improved control over the final polymer structure and purity, the ability to synthesize non-natural copolymers, and allowing products to be excreted from cells which ultimately streamlines downstream recovery and purification. To highlight these features, a handful of biomonomers have been selected as illustrative examples of recent works, including polyamide monomers, styrenic vinyls, hydroxyacids, and diols. Where appropriate, examples of their industrial penetration to date and end-product uses are also highlighted. Novel biomonomers such as these are ultimately paving the way toward new classes of renewable bioplastics that possess a broader diversity of properties than ever before possible.
Crosslinking of Rabbit Fibrin in Vivo (1974)

Summary Crosslinking found in clots produced in vivo by inducing thrombosis in the rabbit jugular vein was compared with that in platelet-poor rabbit plasma clots formed in vitro. Polyacrylamide gel electrophoresis of the dissolved washed clots showed that the sequence of events in vivo was the same as has previously been observed in vitro and that γ dimerization was followed by α polymerization, with extensive crosslinking being evident in even the earliest clots.
Design, Synthesis, Protein−Ligand X-ray Structure, and Biological Evaluation of a Series of Novel Macrocyclic Human Immunodeficiency Virus-1 Protease Inhibitors to Combat Drug Resistance (2009)

The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic macrocyclic HIV protease inhibitors are described. The inhibitors are designed to effectively fill in the hydrophobic pocket in the S1'-S2' subsites and retain all major hydrogen bonding interactions with the protein backbone similar to darunavir (1) or inhibitor 2. The ring size, the effect of methyl substitution, and unsaturation within the macrocyclic ring structure were assessed. In general, cyclic inhibitors were significantly more potent than their acyclic homologues, saturated rings were less active than their unsaturated analogues and a preference for 10- and 13-membered macrocylic rings was revealed. The addition of methyl substituents resulted in a reduction of potency. Both inhibitors 14b and 14c exhibited marked enzyme inhibitory and antiviral activity, and they exerted potent activity against multidrug-resistant HIV-1 variants. Protein-ligand X-ray structures of inhibitors 2 and 14c provided critical molecular insights into the ligand-binding site interactions.
The taming of IL-12: suppressing the production of proinflammatory cytokines (1999)

Interleukin (IL)-12 is a cytokine that possesses both proinflammatory and immunoregulatory activity. IL-12, and the interferon-gamma (IFN-gamma) that is induced by IL-12, play central roles in the development of the Th1-type immune responses that are required for immunity to intracellular pathogens. Recently a number of these pathogens, including Leishmania, measles virus, and human immunodeficiency virus (HIV), have been shown to subvert the development of cell-mediated immunity by actively inhibiting the production of IL-12. Similarly, the ligation of phagocytic receptors on macrophages has also been shown to suppress IL-12 production. The suppression of IL-12 production by receptor ligation occurs by at least two distinct mechanisms: one involves a direct inhibition of gene transcription and the other depends on the production of inhibitory cytokines. We review studies in which IL-12 has been experimentally manipulated, and we compare the mechanisms by which this regulation can occur. Because the IL-12 that is produced during acute inflammation and chronic autoimmune disorders can lead to exacerbated disease, the development of pharmacological means to suppress IL-12 production is currently under investigation. This review focuses on the production of IL-12 by antigen-presenting cells and the methods by which the down-regulation of IL-12 production can be exploited either by pathogens or for therapeutic ends.
Role of p16/MTS1, cyclin D1 and RB in primary oral cancer and oral cancer cell lines (1999)

One of the most important components of G1 checkpoint is the retinoblastoma protein (pRB110). The activity of pRB is regulated by its phosphorylation, which is mediated by genes such as cyclin D1 and p16/MTS1. All three genes have been shown to be commonly altered in human malignancies. We have screened a panel of 26 oral squamous cell carcinomas (OSCC), nine premalignant and three normal oral tissue samples as well as eight established OSCC cell lines for mutations in the p16/MTS1 gene. The expression of p16/MTS1, cyclin D1 and pRB110 was also studied in the same panel. We have found p16/MTS1 gene alterations in 5/26 (19%) primary tumours and 6/8 (75%) cell lines. Two primary tumours and five OSCC cell lines had p16/MTS1 point mutations and another three primary and one OSCC cell line contained partial gene deletions. Six of seven p16/MTS1 point mutations resulted in termination codons and the remaining mutation caused a frameshift. Western blot analysis showed absence of p16/MTS1 expression in 18/26 (69%) OSCC, 7/9 (78%) premalignant lesions and 8/8 cell lines. One cell line, H314, contained a frameshift mutation possibly resulting in a truncated p16/MTS1 protein. pRB was detected in 14/25 (56%) of OSCC but only 11/14 (78%) of these contained all or some hypophosphorylated (active) pRB. In premalignant samples, 6/8 (75%) displayed pRB, and all three normal samples and eight cell lines analysed contained RB protein. p16/MTS1 protein was undetectable in 10/11 (91%) OSCCs with positive pRB. Overexpression of cyclin D1 was observed in 9/22 (41%) OSCC, 3/9 (33%) premalignant and 8/8 (100%) of OSCC cell lines. Our data suggest p16/MTS1 mutations and loss of expression to be very common in oral cancer cell lines and less frequent in primary OSCC tumours. A different pattern of p16/MTS1 mutations was observed in OSCC compared to other cancers with all the detected p16/MTS1 mutations resulting in premature termination codons or a frameshift. The RB protein was expressed in about half (44%) of OSCCs and its expression inversely correlated with p16/MTS1 expression. In conclusion, we show that abnormalities of the RB pathway are a common mechanism of oral carcinogenesis.
Energy metabolism in developing brain cells (1992)

During development different energy substrates are available to cells in brain in plentiful supply. The metabolic environment, which is dictated by the milk diet rich in fat, ensures that substrates in addition to glucose are available as fuels. Some substrates serve readily as primary fuels for respiration, whereas other substrates can serve other functions in addition to serving as primary fuels. Primary fuels for respiration serve to supply acetyl CoA directly and as a result always have first priority. With this criteria in mind, a consideration of substrate priority for respiration by developing brain is presented. Many studies in the decade, 1970-1980, in human infants and in the rat pup model show that both glucose and the ketone bodies, acetoacetate and D-(-)-3-hydroxybutyrate, are taken up by brain and used for energy production and as carbon sources for lipogenesis. Products of fat metabolism, free fatty acids, ketone bodies, and glycerol dominate metabolic pools in early development as a consequence of the milk diet. This recognition of a distinctive metabolic environment from the well-fed adult was taken into consideration within the last decade when methods became available to obtain and study each of the major cell populations, neurons, astrocytes, and oligodendrocytes in near homogeneous state in primary cultures. Studies on these cells made it possible to examine the distinctive metabolic properties and capabilities of each cell population to oxidize the metabolites that are available in development. Studies by many investigators on these cell populations show that all three can use glucose and the ketone bodies in respiration and for lipogenesis. Only one cell type, the astrocytes, can beta-oxidize fatty acids such as octanoate. By comparing the production of labeled carbon dioxide from glucose labeled on carbon-1 compared with carbon-6, it is clear that all three cell populations are capable of active hexose monophosphate shunt activity. Neurons and oligodendrocytes are capable of making good use of acetoacetate and D-(-)-3-hydroxybutyrate, whereas the best substrate for astrocytes is fatty acid. Under comparable conditions of incubation with astrocytes, fatty acids serve better than ketones, which in turn serve better than glucose in respiration. Some of the major factors that can explain the differing observations by different investigators on the capacity for substrate oxidation are presented. Over the last decade, astrocytes have captured the attention of neurobiologists because they have special attributes as metabolic support cells for the management of intermediary metabolism in brain.(ABSTRACT TRUNCATED AT 400 WORDS)