gebhart/patrepeval huggingface dataset:
A Theoretical Insight into the Interaction of Fatty Acids Involved in Royal Jelly with the Human Estrogen Receptor β (2008)

Abstract It has been well-known that fatty acids occurring in the royal jelly of honeybees are effective towards autonomic imbalance, perimenopausal symptoms, osteoporosis, and other conditions. These pharmacological effects of royal jelly similar to those caused by the hormone estrogen are thought to appear due to the interaction of the fatty acids of royal jelly with an estrogen receptor inside the human body. Although the structure of several major fatty acids present in royal jelly has been determined experimentally, no direct evidence of the interaction of these fatty acids with the estrogen receptor have been reported yet. In this study, we therefore give an insight into the interaction of fatty acids with the human estrogen receptor β by quantum mechanical (QM), ONIOM, and molecular dynamics (MD) methods using a model active site.
Induction of Multifunctional Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T Cells Capable of Proliferation in Healthy Subjects by Using a Prime-Boost Regimen of DNA- and Modified Vaccinia Virus Ankara-Vectored Vaccines Expressing HIV-1 Gag Coupled to CD8+T-Cell Epitopes (2006)

A double-blind randomized phase I trial was conducted in human immunodeficiency virus type 1 (HIV-1)-negative subjects receiving vaccines vectored by plasmid DNA and modified vaccinia virus Ankara (MVA) expressing HIV-1 p24/p17 gag linked to a string of CD8(+) T-cell epitopes. The trial had two groups. One group received either two doses of MVA.HIVA (2x MVA.HIVA) (n=8) or two doses of placebo (2x placebo) (n=4). The second group received 2x pTHr.HIVA followed by one dose of MVA.HIVA (n=8) or 3x placebo (n=4). In the pTHr.HIVA-MVA.HIVA group, HIV-1-specific T-cell responses peaked 1 week after MVA.HIVA vaccination in both ex vivo gamma interferon (IFN-gamma) ELISPOT (group mean, 210 spot-forming cells/10(6) cells) and proliferation (group mean stimulation index, 37), with assays detecting positive responses in four out of eight and five out of eight subjects, respectively. No HIV-1-specific T-cell responses were detected in either assay in the 2x MVA.HIVA group or subjects receiving placebo. Using a highly sensitive and reproducible cultured IFN-gamma ELISPOT assay, positive responses mainly mediated by CD4(+) T cells were detected in eight out of eight vaccinees in the pTHr.HIVA-MVA.HIVA group and four out of eight vaccinees in the 2x MVA.HIVA group. Importantly, no false-positive responses were detected in the eight subjects receiving placebo. Of the 12 responders, 11 developed responses to previously identified immunodominant CD4(+) T-cell epitopes, with 6 volunteers having responses to more than one epitope. Five out of 12 responders also developed CD8(+) T-cell responses to the epitope string. Induced T cells produced a variety of anti-viral cytokines, including tumor necrosis factor alpha and macrophage inflammatory protein 1 beta. These data demonstrate that prime-boost vaccination with recombinant DNA and MVA vectors can induce multifunctional HIV-1-specific T cells in the majority of vaccinees.
Review: The chemokine receptor CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 in neuroimmunity - a tale of conflict and conundrum (2010)

The chemokine receptor CXCR3 and its ligands CXCL9, CXCL10 and CXCL11 in neuroimmunity - a tale of conflict and conundrum The chemokines CXCL9, CXCL10 and CXCL11 (also known as monokine induced by interferon-gamma, interferon-inducible protein-10 and interferon-inducible T cell alpha-chemoattractant, respectively) are structurally and functionally related molecules within the non-ELR CXC chemokine subgroup. These chemokines are generally not detectable in most non-lymphoid tissues under physiological conditions but are strongly induced by cytokines, particularly interferon-gamma, during infection, injury or immunoinflammatory responses. CXCL9, CXCL10 and CXCL11 each bind to a common primary receptor, CXCR3, and possibly to additional receptors. They are best known for their role in leucocyte trafficking, principally acting on activated CD4+ Th1 cells, CD8+ T cells and NK cells. An abundance of data demonstrates that CXCL9, CXCL10 and CXCL11 are produced in many diverse pathologic conditions of the central nervous system. More recent attention has focussed on the function of these chemokines in the central nervous system inflammation. The results of these studies have proven to be sometimes surprising and other times contradictory. Here we discuss the likely more subtle and perhaps divergent roles for these chemokines in the pathogenesis of neuroinflammatory diseases.
FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. (1995)

PR-39, a proline/arginine-rich peptide antibiotic, has been purified from pig intestine and later shown to originate in the bone marrow. Intending to isolate a clone for a human counterpart to PR-39, we synthesized a PCR probe derived from the PR-39 gene. However, when this probe was used to screen a human bone marrow cDNA library, eight clones were obtained with information for another putative human peptide antibiotic, designated FALL-39 after the first four residues. FALL-39 is a 39-residue peptide lacking cysteine and tryptophan. All human peptide antibiotics previously isolated (or predicted) belong to the defensin family and contain three disulfide bridges. The clone for prepro-FALL-39 encodes a cathelin-like precursor protein with 170 amino acid residues. We have postulated a dibasic processing site for the mature FALL-39 and chemically synthesized the putative peptide. In basal medium E, synthetic FALL-39 was highly active against Escherichia coli and Bacillus megaterium. Residues 13-34 in FALL-39 can be predicted to form a perfect amphiphatic helix, and CD spectra showed that medium E induced 30% helix formation in FALL-39. RNA blot analyses disclosed that the gene for FALL-39 is expressed mainly in human bone marrow and testis.
Linear Non-competitive Inhibition of Solubilized Human γ-Secretase by Pepstatin A Methylester, L685458, Sulfonamides, and Benzodiazepines (2002)

Cerebral deposition of amyloid β-protein (Aβ) is believed to play a key role in the pathogenesis of Alzheimer's disease. Because Aβ is produced from the processing of amyloid β-protein precursor (APP) by β- and γ-secretases, these enzymes are considered important therapeutic targets for identification of drugs to treat Alzheimer's disease. Unlike β-secretase, which is a monomeric aspartyl protease, γ-secretase activity resides as part of a membrane-bound, high molecular weight, macromolecular complex. Pepstatin and L685458 are among several structural classes of γ-secretase inhibitors identified so far. These compounds possess a hydroxyethylene dipeptide isostere of aspartyl protease transition state analogs, suggesting γ-secretase may be an aspartyl protease. However, the mechanism of inhibition of γ-secretase by pepstatin and L685458 has not been elucidated. In this study, we report that pepstatin A methylester and L685458 unexpectedly displayed linear non-competitive inhibition of γ-secretase. Sulfonamides and benzodiazepines, which do not resemble transition state analogs of aspartyl proteases, also displayed potent, non-competitive inhibition of γ-secretase. Models to rationalize how transition state analogs inhibit their targets by non-competitive inhibition are discussed.
Tooth-Implant connection: A bibliographic review (2010)

The results obtained were disparate. Studies in the medium or short-term show this as a viable treatment alternative, whereas some studies point to a greater risk of complications, although the use of rigid connection decreases the percentage of intrusion. Other bibliographic reviews have concluded that there is a need for more longitudinal studies on the viability of tooth-implant connection, also concluding that complications are greater when this is the chosen treatment. As a viable alternative with an acceptable success rate, this course of treatment is always associated with rigid connection rather than non-rigid connection. Although intrusion is avoided with rigid connection, this nevertheless remains inadvisable as the primary treatment choice.
Anomalous NIR Luminescence in Mn2+‐Doped Fluoride Perovskite Nanocrystals (2014)

An anomalous near‐infrared (NIR) upconversion (UC) emission band at approximately 770 nm is demonstrated in KZnF 3 :Yb 3+ ,Mn 2+ nanocrystals with heavy Mn 2+ doping. This band would enable advanced biological imaging with improved resolution and enhanced penetration depth. Careful studies based on structure analysis, excitation and emission spectra, and luminescence decay curves indicate that this unusual NIR emission (770 nm) originates from the 6 A 1g (S) 4 T 1g (G)→ 6 A 1g (S) 6 A 1g (S) transitions of the Mn 2+ –Mn 2+ dimers. The influence of Mn 2+ concentration and temperature on the Stokes and UC luminescence properties are also investigated. The proposed mechanism for the observed NIR UC emission involves ground state absorption and excited state absorption processes. The present results not only provide a useful and effective approach to achieving pure NIR UC emission, and also new insights into the development of advanced photonic devices and technologies.
Molecular cloning of the Corynebacterium glutamicum ('Brevibacterium lactofermentum' AJ12036) odhA gene encoding a novel type of 2-oxoglutarate dehydrogenase (1996)

The Corynebacterium glutamicum ('Brevibacterium lactofermentum' AJ12036) odhA gene, encoding 2-oxoglutarate dehydrogenase (E1o subunit of the 2-oxoglutarate dehydrogenase complex), has been isolated and identified as an homologous counterpart of the Escherichia coll sucA and Bacillus subtilis odhA genes. The nucleotide sequence of a 4394 bp chromosomal fragment containing the C. glutamicum odhA gene was determined. The odhA gene comprised 3771 bp (1257 codons, including the initiation codon) and a molecular mass of 138656 Da was predicted for the OdhA polypeptide. Northern blot analysis revealed a 3.9 kb transcript. The size of the transcript, together with the presence of a rho-independent terminator-like structure, suggests that C. glutamicum odhA is monocistronic. Cells harbouring plasmids carrying C. glutamicum odhA showed a threefold increase in specific 2-oxoglutarate dehydrogenase complex activity and expression of a protein with an apparent molecular mass of 136 kDa, in good agreement with the predicted size of the OdhA polypeptide. The C-terminal region of the C. glutamicum OdhA protein shows strong sequence similarity to E1os from other organisms. C. glutamicum OdhA has an N-terminal extension not found in previously reported E1os. The amino acid sequence of this extension shows similarity to that of the C-terminal region of dihydrolipoamide S-succinyltransferase (E2o) subunits of 2-oxoglutarate dehydrogenase complexes and dihydrolipoamide S-acetyltransferase (E2p) subunits of pyruvate dehydrogenase complexes. It suggests that the C. glutamicum odhA gene might encode a novel bifunctional protein with E1o and E2o activities.
Antitumor activity of N,N'-bis(ethyl)spermine homologues against human MALME-3 melanoma xenografts. (1992)

The spermine analogues, N1,N12-bis(ethyl)spermine (BESPM), N1,N11-bis(ethyl)norspermine (BENSPM), and N1,N14-bis(ethyl)-homospermine (BEHSPM) behave similarly in down-regulating the key polyamine biosynthetic enzymes, ornithine and S-adenosylmethionine decarboxylase, but differ distinctly in their abilities to induce the polyamine catabolic enzyme, spermidine/spermine-N1-acetyltransferase; BENSPM is 6-fold more effective than BESPM in increasing spermidine/spermine-N1-acetyltransferase activity and BEHSPM is 10-fold less effective. Since MALME-3 human melanoma cells are extremely responsive to spermidine/spermine-N1-acetyltransferase induction (i.e., increases greater than 200-fold) and since this induction correlates with growth inhibition among melanoma cell lines, the ability of these homologues to inhibit the growth of MALME-3 xenografts was examined. Analogues were administered i.p. three times per day (i.e., every 8 h) for 6 days at the following doses per injection: BEHSPM, 1.5, 3, or 6 mg/kg; BESPM, 10, 20, or 40 mg/kg; BENSPM, 20, 40, or 80 mg/kg. At the highest tolerated doses, all of the analogues fully suppressed growth of established (100-200 mm3) MALME-3 tumor during treatment and sustained tumor growth inhibition following treatment as follows: BEHSPM, 14 days; BESPM, 27 days, and BENSPM, 37 days. The tumor delay (to reach 1000 mm3 relative to control) at the highest tolerated doses was as follows: BEHSPM, 20 days; BESPM, 34 days, and BENSPM, 63 days. The rank order of analogue host toxicity as indicated by weight loss was opposite that for antitumor activity, BEHSPM was most toxic, BESPM, intermediate, and BENSPM, least toxic. Thus, the most effective of the three homologues, BENSPM, was best tolerated, and produced an initial tumor regression, full suppression of tumor regrowth during treatment, and sustained inhibition of tumor regrowth for 37 days after treatment stopped. Owing to its potent antitumor activity, mild host toxicity, and novel apparent mechanism of action, BENSPM is being considered for further development toward clinical trial.
Bacteriophage Receptors, Mechanisms of Phage Adsorption and Penetration into Host Cell (2010)

Bacteriophages are an attractive tool for application in the therapy of bacterial infections, for biological control of bacterial contamination of foodstuffs in the alimentary industry, in plant protection, for control of water-borne pathogens, and control of environmental microflora. This review is mainly focused on structures governing phage recognition of host cell and mechanisms of phage adsorption and penetration into microbial cell.
A Novel Antimicrobial Peptidoglycan Recognition Protein in the Cornea (2009)

PGLYRP1 is a novel antimicrobial protein of the corneal epithelium and protects the ocular surface from bacterial infections.
Carbon‐14 labeling of Saxagliptin (BMS‐477118) (2007)

Abstract An efficient synthesis of carbon‐14‐labeled Saxagliptin (BMS‐477118) is described. Initial synthesis of the key radiolabeled intermediate ( S )‐ N ‐Boc‐2‐(3′‐hydroxyadamantyl)glycine 2a utilized adamantanemethanol in a 10‐step sequence. To shorten the sequence, 1‐adamantylzinc bromide was reacted with ethyl [1, 2‐ 14 C]oxalyl chloride catalyzed by [1,1′‐bis(diphenylphosphino)ferrocene]dichloropalladium (II). In five steps, 2b was synthesized in an overall yield of 20% based on ethyl [1, 2‐ 14 C]oxalyl chloride. Compound 2b was subsequently converted to [ 14 C] BMS‐477118 in a short sequence. Copyright © 2007 John Wiley &amp; Sons, Ltd.
A new semiconductor photocell (1957)

A new differential photocell utilizing lateral photocell effect at a semiconductor junction is described. It can detect the position of a light spot to less than 100 A. Through an associated lens, one can measure an angular motion smaller than 0.1 second of arc. The output voltage of the cell is a linear function of the position of the light spot, with zero output for the light spot in the center, reversing in sign when the light spot changes from one side to the other of the center position. The linearity is better than 1.5 per cent over a distance of 0.030 inches. The equivalent noise resistance of the cell is equal to its output resistance, approximately 100 ohms. The sensitivity of the cell is approximately 200 micro-amperes per lumen and its frequency response is about the same as that of junction transistors. The response curve can be shifted electronically, constituting an electronic equivalent to a mechanical movement of the cell. Also, a square wave applied to the junction gives an electronic equivalent to a light chopper. Some applications are suggested.
Recombinant Modified Vaccinia Virus Ankara–Based Vaccine Induces Protective Immunity in Mice against Infection with Influenza Virus H5N1 (2007)

Since 2003, the number of human cases of infections with highly pathogenic avian influenza viruses of the H5N1 subtype is still increasing, and, therefore, the development of safe and effective vaccines is considered a priority. However, the global production capacity of conventional vaccines is limited and insufficient for a worldwide vaccination campaign. In the present study, an alternative H5N1 vaccine candidate based on the replication-deficient modified vaccinia virus Ankara (MVA) was evaluated. C57BL/6J mice were immunized twice with MVA expressing the hemagglutinin (HA) gene from influenza virus A/Hongkong/156/97 (MVA-HA-HK/97) or A/Vietnam/1194/04 (MVA-HA-VN/04). Subsequently, recombinant MVA-induced protective immunity was assessed after challenge infection with 3 antigenically distinct strains of H5N1 influenza viruses: A/Hongkong/156/97, A/Vietnam/1194/04, and A/Indonesia/5/05. Our data suggest that recombinant MVA expressing the HA of influenza virus A/Vietnam/1194/04 is a promising alternative vaccine candidate that could be used for the induction of protective immunity against various H5N1 influenza strains.
Washout of Cr(III)-Acetate-HPAM Gels from Fractures (2003)

Abstract This paper investigates washout of mature Cr(III)-acetate-HPAM gels from fractures. After gel placement, the pressure gradient for gel washout during brine or oil flow was similar to the pressure gradient observed during gel placement. The mechanism of gel failure involved the displacement of relatively mobile gel from wormholes. Generally, only a small fraction of the gel (&amp;lt;5%) was displaced during the washout process. Resistance to washout can be increased by injecting a more concentrated gel. However, this approach exhibits significantly higher pressure gradients during gel placement. The presence of a constriction in a fracture inhibited gel washout during the first pulse of brine flow after gel placement. However, during subsequent brine flow, gel erosion occurred upstream of the constriction to the same extent as downstream. The extrusion, leakoff, and washout behavior in fractures in strongly oil-wet polyethylene cores were similar to those in strongly water-wet Berea sandstone. Gel washout can be reduced by controlling gel placement rate. A Cr(III)-acetate-HPAM gel placed in a 0.04-in. wide fracture at 826 ft/d was about five times more resistant to washout than a gel placed at 4,130 ft/d. Gel washout can also be reduced using secondary crosslinking reactions. Post-placement reaction with Cr(III) acetate increased resistance to washout for a resorcinol-formaldehyde-HPAM gel by a factor from two to three. During steady state flow after first breaching the gel, a Cr(III)-acetate-HPAM gel reduced permeability to water (within the fracture) moderately more (2.5 to 4.7 times) than that to oil. Disproportionate permeability reduction in fractures was most evident at low flow rates.
The Effects of Soluble Growth Factors on Embryonic Stem Cell Differentiation Inside of Fibrin Scaffolds (2007)

The goal of this research was to determine the effects of different growth factors on the survival and differentiation of murine embryonic stem cell-derived neural progenitor cells (ESNPCs) seeded inside of fibrin scaffolds. Embryoid bodies were cultured for 8 days in suspension, retinoic acid was applied for the final 4 days to induce ESNPC formation, and then the EBs were seeded inside of three-dimensional fibrin scaffolds. Scaffolds were cultured in the presence of media containing different doses of the following growth factors: neurotrophin-3 (NT-3), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-AA, ciliary neurotrophic factor, and sonic hedgehog (Shh). The cell phenotypes were characterized using fluorescence-activated cell sorting and immunohistochemistry after 14 days of culture. Cell viability was also assessed at this time point. Shh (10 ng/ml) and NT-3 (25 ng/ml) produced the largest fractions of neurons and oligodendrocytes, whereas PDGF (2 and 10 ng/ml) and bFGF (10 ng/ml) produced an increase in cell viability after 14 days of culture. Combinations of growth factors were tested based on the results of the individual growth factor studies to determine their effect on cell differentiation. The incorporation of ESNPCs and growth factors into fibrin scaffolds may serve as potential treatment for spinal cord injury.
Synthesis and Biological Activity of Novel Retinamide and Retinoate Derivatives (2004)

Retinoic acid and its amide derivative, N-(4-hydroxyphenyl)retinamide (4-HPR), have been proposed as chemopreventative and chemotherapeutic agents. However, their low cytotoxic activity and water solubility limit their clinical use. In this study, we synthesized novel retinoid derivatives with improved cytotoxicity against cancer cells and increased hygroscopicity. Our syntheses were preceded by selective O-acylation and N-acylation, which led to the production of retinoate and retinamide derivatives, respectively, in one pot directly from aminophenol derivatives and retinoic acid without protection. Transcription assays in COS-1 cells indicated that the N-acylated derivatives (2A-5A) and 4-HPR (1A) were much weaker ligands for all three subtypes of retinoic acid receptor (RAR) than all-trans retinoic acid (ATRA), although they showed some selectivity for RARbeta and RARgamma. In contrast, the O-acylated retinoate derivatives (1B-5B) activated all three RAR isotypes without specificity to an extent similar to ATRA. The cytotoxicity was determined using an MTT assay with HCT116 colon cancer cells, and the IC(50) of N-acylated retinamide derivative 4A and O-acylated retinoate derivative 5B was 1.67 microM and 0.65 microM, respectively, which are about five and 13-fold better than that of 4-HPR (8.21 microM), a prototype N-acylated derivative. When retinoate derivative 5B was coupled to organic acid salts, the resulting salt derivatives 5C and 5D had RAR activation and cytotoxicity similar to those of 5B. These data may delineate the relationship between the structure and function of retinoate and retinamide derivatives.
Cancer chemoprevention. (1994)

Chemoprevention has matured greatly in recent years with the significant reversal or suppression of premalignancy by chemopreventive agents in several sites. The future of chemoprevention will be determined largely by several ongoing phase III trials, including trials of retinoids, beta-carotene, and alpha-tocopherol in the aerodigestive tract, of tamoxifen and fenretinide in the breast, and of finasteride in the prostate.
Urinary dopamine response to angiotensin II is not abnormal in type 1 (insulin-dependent) diabetes mellitus (1993)

To examine the interaction between angiotensin II (ANGII) and dopamine in type 1 diabetes mellitus, urinary dopamine excretion was examined during ANGII infusion in 15 diabetic patients and 10 control subjects after pretreatment with lithium 750 mg and placebo. The antinatriuretic response and the urinary dopamine response to ANGII did not differ within or between the two groups on each study day. No correlation was observed between the decrements in urinary sodium excretion and urinary dopamine output during ANGII infusion in either group. The effect of insulin on urinary dopamine excretion was studied separately in seven non-diabetic subjects; sodium and potassium retention occurred during a hyperinsulinaemic euglycaemic clamp, but urinary dopamine did not change. The data suggest that the relationship between urinary sodium excretion and tubular dopamine synthesis remains normal in early type 1 diabetes mellitus both at baseline and during the antinatriuresis induced by angiotensin II. The cause of the reduction in urinary dopamine during ANGII infusion is unclear, but is probably not mediated directly by changes in proximal tubular sodium transport.