gebhart/patrepeval huggingface dataset:
Hepatitis C Virus Structural Proteins Impair Dendritic Cell Maturation and Inhibit In Vivo Induction of Cellular Immune Responses (2003)

Hepatitis C virus (HCV) chronic infection is characterized by low or undetectable cellular immune responses against HCV antigens. Some studies have suggested that HCV proteins manipulate the immune system by suppressing the specific antiviral T-cell immunity. We have previously reported that the expression of HCV core and E1 proteins (CE1) in dendritic cells (DC) impairs their ability to prime T cells in vitro. We show here that immunization of mice with immature DC transduced with an adenovirus encoding HCV core and E1 antigens (AdCE1) induced lower CD4(+)- and CD8(+)-T-cell responses than immunization with DC transduced with an adenovirus encoding NS3 (AdNS3). However, no differences in the strength of the immune response were detected when animals were immunized with mature DC subsequently transduced with AdCE1 or AdNS3. According to these findings, we observed that the expression of CE1 in DC inhibited the maturation caused by tumor necrosis factor alpha or CD40L but not that induced by lipopolysaccharide. Blockade of DC maturation by CE1 was manifested by a lower expression of maturation surface markers and was associated with a reduced ability of AdCE1-transduced DC to activate CD4(+)- and CD8(+)-T-cell responses in vivo. Our results suggest that HCV CE1 proteins modulate T-cell responses by decreasing the stimulatory ability of DC in vivo via inhibition of their physiological maturation pathways. These findings are relevant for the design of therapeutic vaccination strategies in HCV-infected patients.
Toward giga-pixel nanoscopy on a chip: a computational wide-field look at the nano-scale without the use of lenses (2013)

The development of lensfree on-chip microscopy in the past decade has opened up various new possibilities for biomedical imaging across ultra-large fields of view using compact, portable, and cost-effective devices. However, until recently, its ability to resolve fine features and detect ultra-small particles has not rivalled the capabilities of the more expensive and bulky laboratory-grade optical microscopes. In this Frontier Review, we highlight the developments over the last two years that have enabled computational lensfree holographic on-chip microscopy to compete with and, in some cases, surpass conventional bright-field microscopy in its ability to image nano-scale objects across large fields of view, yielding giga-pixel phase and amplitude images. Lensfree microscopy has now achieved a numerical aperture as high as 0.92, with a spatial resolution as small as 225 nm across a large field of view e.g., >20 mm(2). Furthermore, the combination of lensfree microscopy with self-assembled nanolenses, forming nano-catenoid minimal surfaces around individual nanoparticles has boosted the image contrast to levels high enough to permit bright-field imaging of individual particles smaller than 100 nm. These capabilities support a number of new applications, including, for example, the detection and sizing of individual virus particles using field-portable computational on-chip microscopes.
Carboxyl-terminal Modification of a Gastrin Releasing Peptide Derivative Generates Potent Antagonists (1989)

Gastrin releasing peptide (GRP) is a 27-residue peptide hormone which is analogous to the amphibian peptide bombesin. GRP serves a variety of physiological functions and has been implicated as an autocrine factor in the growth regulation of small cell lung cancer cells. We have developed a series of potent GRP antagonists by modification of the COOH terminus of N-acetyl-GRP-20-27. The most potent member of this series, N-acetyl-GRP-20-26-OCH2CH3, exhibits an IC50 of 4 nM in a competitive binding inhibition assay. This compound blocks GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts, inhibits GRP-dependent release of gastrin in vitro, and blocks GRP-induced elevation of [Ca2+]i in H345 small cell lung cancer cells. These results demonstrate that while residues 20-27 of GRP influence binding of the parent peptide to its receptor, the COOH-terminal amino acid is primarily responsible for triggering the subsequent biological response.
Regioselective Aminomethylations of Bicyclic Phenols (2000)

The regioselectivity in the aminomethylations (the Mannich reaction) of bicyclic phenols has been studied.Highly regioselective Mannich reactions enable easy synthetic access to novel bicyclic dialkylaminomethylphenols under very mild reaction conditions.
Hydroxyamidine Inhibitors of Indoleamine-2,3-dioxygenase Potently Suppress Systemic Tryptophan Catabolism and the Growth of IDO-Expressing Tumors (2010)

Malignant tumors arise, in part, because the immune system does not adequately recognize and destroy them. Expression of indoleamine-2,3-dioxygenase (IDO; IDO1), a rate-limiting enzyme in the catabolism of tryptophan into kynurenine, contributes to this immune evasion. Here we describe the effects of systemic IDO inhibition using orally active hydroxyamidine small molecule inhibitors. A single dose of INCB023843 or INCB024360 results in efficient and durable suppression of Ido1 activity in the plasma of treated mice and dogs, the former to levels seen in Ido1-deficient mice. Hydroxyamidines potently suppress tryptophan metabolism in vitro in CT26 colon carcinoma and PAN02 pancreatic carcinoma cells and in vivo in tumors and their draining lymph nodes. Repeated administration of these IDO1 inhibitors impedes tumor growth in a dose- and lymphocyte-dependent fashion and is well tolerated in efficacy and preclinical toxicology studies. Substantiating the fundamental role of tumor cell-derived IDO expression, hydroxyamidines control the growth of IDO-expressing tumors in Ido1-deficient mice. These activities can be attributed, at least partially, to the increased immunoreactivity of lymphocytes found in tumors and their draining lymph nodes and to the reduction in tumor-associated regulatory T cells. INCB024360, a potent IDO1 inhibitor with desirable pharmaceutical properties, is poised to start clinical trials in cancer patients.
Liquid-liquid emulsification by static mixers for use in microencapsulation (1996)

4e report a feasibility study on liquid-liquid emulsification by static mixers for use in microencapsulation. This study was concerned with developing a quantitative correlation between the size of the microspheres and process parameters. The process parameters considered included operational variables and physical properties associated with both the dispersion and dispersed phases. The effect of mixing element design on mixing efficiency and particle-size distribution was evaluated using three different static mixers. The performance of static mixers and conventional continuously stirred-tank reactors was assessed in several different aspects. Dimensional analysis was used to establish a correlation based on protein-free poly(lactic acid-co-glycolid acid) and poly(methyl methacrylate) microspheres in an oil-in-water emulsion using 1/4", 1/2" and 1" static mixers. This correlation accurately described the preparation of protein-loaded microspheres and provided large-scale microsphere production with a empirical basis.
Hydrodynamic studies on micellar solutions of styrene–butadiene block copolymers in selective solvents (1985)

Hydrodynamic radius of micelles of several block copolymers in different selective solvents (for both types of blocks) was determined from photon correlation spectroscopy. The boundaries of micellar solutions in heptane (good solvent for polybutadiene block) and dimethylformamide (good solvent for polystyrene block) were established for polymers in terms of their molecular mass and block composition. The photon correlation spectroscopy data in combination with intrinsic viscosities of block copolymers in selective solvents were used to determine micellar molecular mass and aggregation number. The influence of temperature on the micelle size was examined. The block copolymer micelles could solubilize a certain amount of insoluble homopolymer within their insoluble core. 1 H nmr spectra were examined to study the influence of temperature on micellar systems.
Diversity of the vif gene of human immunodeficiency virus type 1 in Uganda. (1997)

Little sequence information is available for human immunodeficiency virus type 1 (HIV-1) vif genes of African origin. Here we describe 37 new complete vif genes of 18 AIDS patients from Uganda and show that vif has a high in vivo genetic variability. vif proviral DNA sequences of peripheral blood cells were determined by direct sequencing of PCR products. Only 52% of the deduced Vif amino acids were absolutely conserved; when Vif sequences previously analysed were considered, only 32% of the Vif consensus sequence comprised conserved and as such possibly functionally important motifs. The high inter-individual vif variability was in contrast to a very low intra-individual variability. One patient carried a vif gene with a stable C-terminal deletion, but N-terminal truncations were not found in patients' predominant vif sequences. The vif genes analysed comprised subtypes A, D and an A/D mosaic. Phylogenetic analyses additionally showed that HIV- 1 in Uganda has spread across the boundaries of ethnic groups.
Acinetobacter baumannii outer membrane protein A targets the nucleus and induces cytotoxicity (2007)

Acinetobacter baumannii is an emerging opportunistic pathogen responsible for healthcare-associated infections. The outer membrane protein A of A. baumannii (AbOmpA) is the most abundant surface protein that has been associated with the apoptosis of epithelial cells through mitochondrial targeting. The nuclear translocation of AbOmpA and the subsequent pathology on host cells were further investigated. AbOmpA directly binds to eukaryotic cells. AbOmpA translocates to the nucleus by a novel monopartite nuclear localization signal (NLS). The introduction of rAbOmpA into the cells or a transient expression of AbOmpA-EGFP causes the nuclear localization of these proteins, while the fusion proteins of AbOmpADeltaNLS-EGFP and AbOmpA with substitutions in residues lysine to alanine in the NLS sequences represent an exclusively cytoplasmic distribution. The nuclear translocation of AbOmpA induces cell death in vitro. Furthermore, the microinjection of rAbOmpA into the nucleus of Xenopus laevis embryos fails to develop normal embryogenesis, thus leading to embryonic death. We propose a novel pathogenic mechanism of A. baumannii regarding the nuclear targeting of the bacterial structural protein AbOmpA.
Self-Adjuvanting Lipopeptide Vaccines (2008)

Despite the important role of adjuvants for vaccine development, relatively few adjuvants have been successfully incorporated into vaccines intended for human administration. This is in part due to the high toxicity associated with many experimental adjuvants. This lack of choice effectively hinders the ability to produce vaccines against many diseases, or to improve current vaccine formulations. The conjugation of immunostimulatory lipids to peptide antigens, to produce self-adjuvanting lipopeptide vaccines, has been tested in human clinical trials. These systems appear to have a number of advantages over more traditional adjuvants (e.g. alum salts) including the capacity for these vaccines to be administered via mucosal routes (e.g. orally or nasally) instead of by injection, elicitation of antigen-specific cytotoxic T-lymphocytes and mucosal immunity, as well as little-to-no observed toxicity. Several lipopeptide vaccine systems have been described in the literature, ranging from the conjugation of single fatty acid chains, to the conjugation of more complex lipids and glycolipids onto peptide antigens. The following review provides an overview of the most studied lipopeptide vaccine systems grouped into the following categories: 1) bacterial lipopeptides, including tri-palmitoyl-S-glyceryl cysteine (Pam3Cys) and di-palmitoyl-S--glyceryl cysteine (Pam2Cys); 2) the lipid-core peptide (LCP) and multiple antigen lipophilic adjuvant carrier (MALAC) systems; 3) single-chain palmitoylated peptides; and 4) glycolipids (e.g. monophosphoryl lipid A). The review also discusses the potential mechanisms of action for lipopeptide and glycolipopeptide vaccines, as well as structure activity relationships, and provides examples of studies utilising each system.
Bioinformatics Methods and Protocols (1999)

Computer-assisted analysis of DNA sequences used to be a task for the &amp;ldquo;local expert.&amp;rdquo; However, various genome sequencing projects as well as the availability of sequencing services are providing a constantly increasing number of scientists with DNA sequence data. These data need to be interpreted to include the information into experimental schemes.
A New Look at T Cells (1998)

Recent technological advances have shed unexpected light on the CD8+ T cell responses to pathogens and have raised concerns that a familiar quantitative assay is wrong. The most exciting of the new advances is the MHC tetramer. Ever since T cells were first identified, there have been attempts to
Cardiac-derived stem cells. (2000)

Current scientific dogma holds that cardiomyocyte stem cells do not exist in the adult mammalian heart, and furthermore, that there is little, if any, potential for the regeneration of damaged myocardium. In order to approach this topic, I have begun with a brief overview of advances in stem cell research in other organ systems, such as the bone marrow and the brain. Very recent progress in cardiac stem cell research is then discussed, which indicates that a cardiomyocyte progenitor cell contributes to cardiomyocyte replacement throughout life. This progenitor cell may reside in the heart itself, or derive from a circulating marrow stem cell.
Low temperature direct bonding of non-hydrophilicsurfaces (1994)

The authors have found that extremely strong bonds can be formed between wafer surfaces of LPCVD silicon dioxide after a dry plasma pretreatment. The bonded wafers were examined for bond yield, interfacial quality, and mechanical strength. Preliminary results indicate that successful low-temperature bonds can be formed to non-hydrophilic surfaces.
Podophyllotoxin as a probe for the colchicine binding site of tubulin. (1977)

The binding of [3H]podophyllotoxin to tubulin, measured by a DEAE-cellulose filter paper method, occurs with an affinity constant of 1.8 X 10(6) M-1 (37 degrees at pH 6.7). Like colchicine, approximately 0.8 mol of podophyllotixin are bound per mol of tubulin dimer, and the reaction is entropy-driven (43 cal deg-1 mol-1). At 37 degrees the association rate constant for podophyllotoxin binding is 3.8 X 10(6) M-1 h-1, approximtaely 10 times higher than for colchicine; this is reflected in the activation energies for binding which are 14.7 kcal/mol for podophyllotoxin and 20.3 kcal/mol for colchicine. The dissociation rate constant for the tubulin-podophyllotoxin complex is 1.9 h-1, and the affinity constant calculated from the ratio of the rates is close to that obtained by equilibrium measurements. Podophyllotxin and colchicine are mutually competitive inhibitors. This can be ascribed to the fact that both compounds have a trimethoxyphenyl ring and analogues of either compound with bulky substituents in their trimethoxyphenyl moiety are unable to inhibit the the binding of either of the two ligands. Tropolone, which inhibits colchicine binding competitively, has no effect on the podophyllotoxin/tubulin reaction. Conversely, podophyllotoxin does not influence tropolone binding. Moreover, the tropolone binding site of tubulin does not show the temperature and pH lability of the colchicine and podophyllotoxin domains, hence this lability can be ascribed to the trimethoxyphenyl binding region of tubulin. Since podophyllotoxin analogues with a modified B ring do not bind, it is concluded that both podophyllotoxin and colchicine each have at least two points of attachment to tubulin and that they share one of them, the binding region of the trimethoxyphenyl moiety.
Differences in the Metabolism and Disposition of Ursodeoxycholic Acid and of Its Taurine–Conjugated Species in Patients With Primary Biliary Cirrhosis (1999)

The clinical effectiveness of ursodeoxycholate in the treatment of liver disease may be limited by its poor absorption and extensive biotransformation. Because in vitro and in vivo studies suggest that the more hydrophilic bile acid tauroursodeoxycholate has greater beneficial effects than ursodeoxycholate, we have compared for the first time the absorption, metabolism, and clinical responses to these bile acids in patients with primary biliary cirrhosis (PBC). Twelve female patients with PBC were sequentially administered tauroursodeoxycholate and ursodeoxycholate (750 mg/d for 2 months) in a randomized, cross-over study. Bile acids were measured in serum, duodenal bile, urine, and feces by gas chromatography-mass spectrometry (GC-MS). Biliary ursodeoxycholate enrichment was higher during tauroursodeoxycholate administration (32.6% vs. 29.2% during ursodeoxycholate; P <.05). Lithocholic acid concentration was consistently higher in all biological fluids during ursodeoxycholate administration. Fecal bile acid excretion was the major route of elimination of both bile acids; ursodeoxycholate accounted for 8% and 23% of the total fecal bile acids during tauroursodeoxycholate and ursodeoxycholate administration, respectively (P <.05). Tauroursodeoxycholate was better absorbed than ursodeoxycholate, and, although it was partially deconjugated and reconjugated with glycine, it underwent reduced biotransformation to more hydrophobic metabolites. This comparative study suggests that tauroursodeoxycholate has significant advantages over ursodeoxycholate that may be of benefit for long-term therapy in PBC.
Mechanisms of Chromium Action: Low-Molecular-Weight Chromium-Binding Substance (1999)

Chromium has long been known to be essential for proper lipid and carbohydrate metabolism in mammals, with chromium deficiency leading to symptoms associated with adult-onset diabetes and cardiovascular disease. Elucidating the structure, function, and mode of action of the biologically active form of chromium has proved enigmatic. However, a naturally-occurring oligopeptide, low-molecular-weight chromium-binding substance (LMWCr), has been found in our laboratory to activate insulin receptor kinase activity up to 7-fold with a dissociation constant of 250 picomolar in the presence of 100 nanomolar insulin, and it has been partially characterized in terms of structural and spectroscopic properties. LMWCr may function in a manner similar to that of the calcium-binding signal protein calmodulin. In other words, LMWCr is maintained in its active apo-oligopeptide form; in response to a chromium flux, LMWCr binds 4 chromic ions. The holoprotein is then capable of binding to insulin receptor (and perhaps other enzymes) activating the enzyme. Establishing a link between the nutrient chromium, LMWCr's activation of insulin receptor kinase activity, and adult-onset diabetes and related conditions could result in a new treatment for these conditions.
Measurements of helium metastable density in an atmospheric pressure glow discharge (2004)

The density of metastable helium atoms in a dielectric barrier discharge operating in helium with some impurities present has been measured using laser-collisional-induced fluorescence and absorption techniques. Time-resolved measurements indicate that helium metastables contribute to the production of impurity ions, in this case N2+, in the postdischarge current phase of a glow discharge. In our particular discharge environment, the helium metastable density is (1.5±1.4)×1010cm−3, a result consistent with failure to observe absorption by metastables in a multipass absorption measurement.
Design concept for optical fibers with enhanced SBS threshold (2005)

We propose a criterion to predict the relative value of the stimulated Brillouin scattering (SBS) threshold in single-mode optical fibers with different refractive index profiles. We confirm our results by several representative measurements. We show that with the proper profile design one can achieve more than 3 dB increase in the SBS threshold compared to the standard single-mode optical fiber.
An assessment study of absorption effect: LED vs tungsten halogen lamp for noninvasive glucose detection (2014)

Noninvasive glucose monitoring development is critical for diabetic patient continuous monitoring. However, almost all the available devices are invasive and painful. Noninvasive methods such as using spectroscopy have shown some good results. Unfortunately, the drawback was that the tungsten halogen lamps usage that is impractical if applied on human skin. This paper compared the light emitting diode (LED) to traditional tungsten halogen lamps as light source for glucose detection where the type of light source plays an important role in achieving a good spectrum quality. Glucose concentration measurement has been developed as part of noninvasive technique using optical spectroscopy. Small change and overlapping in tungsten halogen results need to replace it with a more convenient light source such as LED. Based on the result obtained, the performance of LED for absorbance spectrum gives a significantly different and is directly proportional to the glucose concentration. The result shows a linear trend and successfully detects lowest at 60 to 160 mg/dL glucose concentration.
Pathogenesis and Treatment of Sickle Cell Disease (1997)

In 1949, the discovery that sickle hemoglobin (α2 βS2) has an abnormal electrophoretic mobility prompted Linus Pauling and his colleagues to christen sickle cell anemia “a molecular disease.”1 The ensuing five decades have produced a wealth of information on the mechanisms by which a single base substitution in the gene encoding the human β-globin subunit, with the resulting replacement of β6 glutamic acid by valine, leads to the protean and devastating clinical manifestations of sickle cell disease. Until recently there was a disappointing lag in the application of this knowledge to the design of safe and effective . . .
Both Familial Parkinson's Disease Mutations Accelerate α-Synuclein Aggregation (1999)

Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major component of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD, but their pathogenic mechanism is not understood. Here we show that both wild type and mutant alpha-synuclein form insoluble fibrillar aggregates with antiparallel beta-sheet structure upon incubation at physiological temperature in vitro. Importantly, aggregate formation is accelerated by both PD-linked mutations. Under the experimental conditions, the lag time for the formation of precipitable aggregates is about 280 h for the wild type protein, 180 h for the A30P mutant, and only 100 h for the A53T mutant protein. These data suggest that the formation of alpha-synuclein aggregates could be a critical step in PD pathogenesis, which is accelerated by the PD-linked mutations.
Molecular pathogenesis of oral squamous carcinoma (2000)

Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of oncogenes and tumour suppressor genes. This can result in increased production of growth factors or numbers of cell surface receptors, enhanced intracellular messenger signalling, and/or increased production of transcription factors. In combination with the loss of tumour suppressor activity, this leads to a cell phenotype capable of increased cell proliferation, with loss of cell cohesion, and the ability to infiltrate local tissue and spread to distant sites. Recent advances in the understanding of the molecular control of these various pathways will allow more accurate diagnosis and assessment of prognosis, and might lead the way for more novel approaches to treatment and prevention.