gebhart/patrepeval huggingface dataset:
Transcutaneous immunisation with herpes simplex virus stimulates immunity in mice (2000)

Herpes simplex virus (HSV) is common throughout the world and is a target for vaccine development. Transcutaneous immunisation is a novel technique that uses the application of vaccine antigens in solution on the skin in the presence of cholera toxin (CT) as an adjuvant. This study investigated the potential of transcutaneous immunisation in C3H mice, using CT co-administered with whole inactivated HSV-1 (CT+HSVi) or HSV-1 antigens extracted from infected Vero cells (CT+HSVag) or a control protein (CT+BSA). The application of any of the three vaccines on to bare mouse skin resulted in the migration of Langerhans cells from the epidermis and in the production of serum antibodies to CT. Both HSV preparations generated serum and mucosal (faecal) antibodies to HSV, with the CT+HSVi vaccine being a more potent stimulator of humoral immunity. The CT+HSVag vaccine, however, was the more potent stimulator of cell-mediated immunity, giving rise to a strong delayed type hypersensitivity response and lymphocyte proliferation in vitro. When the mice were challenged by epidermal inoculation of HSV, the CT+HSVag vaccine induced a higher level of protection than the CT+HSVi vaccine, a result which may indicate that the efficacy of HSV vaccines depends on stimulation of cell-mediated rather than humoral responses. The success of topical vaccination suggests that the transcutaneous route may offer a promising potential for novel vaccine delivery which merits further investigation.
A Molecular Iron Catalyst for the Acceptorless Dehydrogenation and Hydrogenation of N-Heterocycles (2014)

A well-defined iron complex (3) supported by a bis(phosphino)amine pincer ligand efficiently catalyzes both acceptorless dehydrogenation and hydrogenation of N-heterocycles. The products from these reactions are isolated in good yields. Complex 3, the active catalytic species in the dehydrogenation reaction, is independently synthesized and characterized, and its structure is confirmed by X-ray crystallography. A trans-dihydride intermediate (4) is proposed to be involved in the hydrogenation reaction, and its existence is verified by NMR and trapping experiments.
FAST-SeqS: A Simple and Efficient Method for the Detection of Aneuploidy by Massively Parallel Sequencing (2012)

Massively parallel sequencing of cell-free, maternal plasma DNA was recently demonstrated to be a safe and effective screening method for fetal chromosomal aneuploidies. Here, we report an improved sequencing method achieving significantly increased throughput and decreased cost by replacing laborious sequencing library preparation steps with PCR employing a single primer pair designed to amplify a discrete subset of repeated regions. Using this approach, samples containing as little as 4% trisomy 21 DNA could be readily distinguished from euploid samples.
Error Correction and Digitalization Concepts in Biochemical Computing (2007)

We offer a theoretical design of new systems that show promise for digital biochemical computing, including realizations of error correction by utilizing redundancy, as well as signal rectification. The approach includes information processing using encoded DNA sequences, DNAzyme biocatalyzed reactions and the use of DNA-functionalized magnetic nanoparticles. Digital XOR and NAND logic gates and copying (fanout) are designed using the same components.
Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist (2000)

The widespread neuropeptide vasoactive intestinal peptide (VIP) has two receptors VPAC(1) and VPAC(2). Solid-phase syntheses of VIP analogs in which each amino acid has been changed to alanine (Ala scan) or glycine was achieved and each analog was tested for: (i) three-dimensional structure by ab initio molecular modeling; (ii) ability to inhibit (125)I-VIP binding (K(i)) and to stimulate adenylyl cyclase activity (EC(50)) in membranes from cell clones stably expressing human recombinant VPAC(1) or VPAC(2) receptor. The data show that substituting residues at 14 positions out of 28 in VIP resulted in a >10-fold increase of K(i) or EC(50) at the VPAC(1) receptor. Modeling of the three-dimensional structure of native VIP (central alpha-helice from Val(5) to Asn(24) with random coiled N and C terminus) and analogs shows that substitutions of His(1), Val(5), Arg(14), Lys(15), Lys(21), Leu(23), and Ile(26) decreased biological activity without altering the predicted structure, supporting that those residues directly interact with VPAC(1) receptor. The interaction of the analogs with human VPAC(2) receptor is similar to that observed with VPAC(1) receptor, with three remarkable exceptions: substitution of Thr(11) and Asn(28) by alanine increased K(i) for binding to VPAC(2) receptor; substitution of Tyr(22) by alanine increased EC(50) for stimulating adenylyl cyclase activity through interaction with the VPAC(2) receptor. By combining 3 mutations at positions 11, 22, and 28, we developed the [Ala(11,22,28)]VIP analog which constitutes the first highly selective (>1,000-fold) human VPAC(1) receptor agonist derived from VIP ever described.
Familial Renal Cell Carcinoma (2012)

Recent advances in molecular genetics have elucidated the biological mechanisms of familial renal cell carcinoma (RCC), which have been responsible for the development and introduction of novel targeted agents that continue to change and refine the management of advanced disease. The genetic pathways have been well characterized and defined for several hereditary kidney cancer syndromes, including von Hippel–Lindau, hereditary papillary RCC, Birt–Hogg–Dubè, and hereditary leiomyomatosis RCC. Each of these hereditary kidney cancer syndromes has distinct clinical manifestations and treatment challenges. In this context, our objective is to provide an overview of the molecular genetics, clinical syndromes, and management strategy of hereditary kidney cancer syndromes.
Biochemistry of prostaglandin endoperoxide H synthase-1 and synthase-2 and their differential susceptibility to nonsteroidal anti-inflammatory drugs. (1995)

The principal pharmacological effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are due to their ability to inhibit prostaglandin synthesis. NSAIDs block the cyclooxygenase activities of the closely related PGH synthase-1 and PGH synthase-2 (PGHS-1 and PGHS-2) isozymes. NSAIDs are therapeutically useful due to their analgesic, anti-pyretic, anti-inflammatory, and anti-thrombogenic properties. Major side-effects of NSAIDs include their ulcerogenic and nephrotoxic activities. All clinically approved NSAIDs in general use today inhibit both PGHS-1 and PGHS-2. Recently, inhibitors have been identified that are selective toward PGHS-2 and that have potent analgesic and anti-inflammatory activities with minimal ulcerogenic activity. If the new PGHS-2 selective NSAIDs can effectively inhibit inflammatory prostaglandin synthesis by PGHS-2, without inhibiting PGHS-1 prostaglandin synthesis required to regulate sodium and water resorption, and renal blood flow, it is likely that these new drugs will also have significantly less renal toxicity than present-day NSAIDs. In this article, the mechanisms of actions of NSAIDs primarily at the biochemical level, including the reactions catalyzed by PGHSs, will be discussed. In addition, the biochemical properties of these isozymes, and the differential regulation of the PGHS-1 and PGHS-2 genes, will be examined.
A novel family 9 endoglucanase gene (celD), whose product cleaves substrates mainly to glucose, and its adjacent upstream homolog (celE) from Fibrobacter succinogenes S85 (1996)

Two adjacent, highly homologous endoglucanase genes, celD and celE from Fibrobacter succinogenes S85, which were separated by an AT-rich 223-nucleotide intergenic region were characterized. The celD gene codes for endoglucanase D (EGD), a protein of 668 residues with a molecular mass of 71.7 kDa, while the celE gene encodes endoglucanase E, a protein of 467 amino acids with a molecular mass of 50.7 kDa. Both gene products belong to family 9 of glycosyl hydrolases. EGD displays an array of serine-rich periodic sequences (SRPS) near its C terminus which separate the catalytic domain from a basic terminal domain (BTD) rich in positively charged amino acids. Endoglucanase E has a BTD which is homologous to that of EGD, but it lacks the SRPS and 151 residues present at the N terminus of EGD. The SRPS structures may function as flexible linkers which facilitate interactions between the BTDs and acidic membrane proteins from F. succinogenes S85. The recombinant EGD showed pH and temperature optima of 5.5 and 35 degrees C, respectively. The enzyme cleaved barley-beta-glucan, carboxymethyl cellulose, and acid-swollen cellulose with specific activities of 19.1, 11.5 and 1.7 micromol x min-1 x mg of protein-1, respectively. There was a rapid drop in viscosity during hydrolyses of carboxymethyl cellulose, which is characteristic of an endoglucanase. Glucose was the main hydrolysis product of acid-swollen cellulose. Monospecific polyclonal antibodies against EGD detected the expression of a 68-kDa cellulose-inducible protein corresponding in size to the recombinant EGD in the culture fluid of F. succinogenes S85 and several larger proteins. The celE gene appeared to have little activity when expressed from the beta-galactosidase promoter in pBluescript in Escherichia coli; however, reverse transcriptase PCR analysis with internal primers for the gene revealed that a cellulose-inducible message was made in F. succinogenes, thereby documenting expression of the gene.
The Effect of the Low Blink Rate in Rabbits on Topical Drug Penetration (1995)

The animal did not blink for 20-30 min. after the instillation. With either fluorophore, the tear film fluorescence remained constant after the first few minutes and fell precipitously at the first blink. Comparison with the loss kinetics in the human eye, an exponential decline with an average rate constant of 0.16 min-1, indicates that the AUC will be 3 times greater in the rabbit, and the penetration of a drug can be overestimated to the same degree from the low blink rate alone. There was a rise in the corneal fluorescence, attributable to penetration of the fluorophore, after the eye was washed at the end of the experiment. This was used to estimate the epithelial permeability which averaged 1.5 x 10(-4) cm hr for fluorescein and 1.9 x 10(-5) cm hr-1 for FITC Dextran. For most drugs, however, the epithelial permeability is sufficiently high that all the material present in the tear film will partition into the cornea in a few minutes. Considerations of contact time become irrelevant under these circumstances.
HCN2 Overexpression in Newborn and Adult Ventricular Myocytes (2001)

Ventricular pacemaker current (I(f)) shows distinct voltage dependence as a function of age, activating outside the physiological range in normal adult ventricle, but less negatively in neonatal ventricle. However, heterologously expressed HCN2 and HCN4, the putative molecular correlates of ventricular I(f), exhibit only a modest difference in activation voltage. We therefore prepared an adenoviral construct (AdHCN2) of HCN2, the dominant ventricular isoform at either age, and used it to infect neonatal and adult rat ventricular myocytes to investigate the role of maturation on current gating. The expressed current exhibited an 18-mV difference in activation (V(1/2) -95.9+/-1.9 in adult; -77.6+/-1.6 mV in neonate), comparable to the 22-mV difference between native I(f) in adult and neonatal cultures (V(1/2) -98.7 versus -77.0 mV). This did not result from developmental differences in basal cAMP, because saturating cAMP in the pipette caused an equivalent positive shift in both preparations. In the neonate, AdHCN2 caused a significant increase in spontaneous rate compared with control (88+/-5 versus 48+/-4 bpm). In adult, where HCN2 activates more negatively, the effect was evident only during anodal excitation, requiring significantly less stimulus energy than control (2149+/-266 versus 3140+/-279 mV. ms). Thus, ventricular maturational state influences the voltage dependence of expressed HCN2, resulting in distinct physiological impact of expressed channels in neonate and adult myocytes. The full text of this article is available at http://www.circresaha.org.
Platinum/iridium tips with controlled geometry for scanning tunneling microscopy (1990)

An electrochemical etching procedure using a saturated CaCl2/H2O/concentrated HCl (60%/36%/4% by volume) solution has been developed to fabricate platinum/iridium tips with controlled geometry for scanning tunneling microscopy (STM). These tips, which have a high aspect ratio (5°–10° cone half angle) and a small radius of curvature (∼500 Å), are particularly useful for the imaging and metrology of precision-engineered surfaces. Initial attempts to use the tips showed them to be unreliable for STM imaging. Auger electron spectroscopy indicated the presence of a carbon contamination layer. By eliminating CO2 from the etching environment, the contamination was reduced and the reliability of the resulting tips improved dramatically. The imaging versatility of these tips is demonstrated for sputter-deposited gold on silicon, for a gold-coated polymethylmethacrylate lithographic test pattern, and for highly oriented pyrolytic graphite.
Estimating Family Long-Term Care Decisions in the Presence of Endogenous Child Characteristics (1995)

This paper estimates the effects of various parent and child characteristics on the choice of care arrangement of the parent taking into account the potential endogeneity of some of the child characteristics. This potential endogeneity is controlled for by using an instrumental variables approach with panel data. The procedure conditions on the parent receiving no significant care in the first year of the panel causing first year variables to be valid instruments for the second year variables. The estimation procedure shows that, after controlling for endogeneity, potentially endogenous child variables have smaller effects. The estimates predict moderate effects of parent sex, age, race, andrhealth and child sex and marital status, and large effects of parent marital status and child distance.
Selective epitaxial growth Si resonant-cavity photodetector (1998)

An novel resonant-cavity Si photodiode was fabricated using a selective epitaxial growth process. The photodiode shows a bandwidth over 5 GHz, and a quantum efficiency over 65% at 700 nm. Compared to the previously reported Si resonant-cavity Si photodetectors, this photodiode process is more compatible with Si integrated circuit technology.
Phytate (IP6) is a powerful agent for preventing calcifications in biological fluids: usefulness in renal lithiasis treatment. (2000)

The extraordinary capacity of phytate (myo-inositol hexaphosphate), a substance present in blood, urine, interstitial and intracellular fluids, to inhibit crystallization of calcium salts (oxalate and phosphate) is discussed. Its role in preventing calcium renal stone formation is specifically presented and discussed. "In vitro" and "in vivo" experiments, as well as clinical studies clearly demonstrated that phytate plays an important role as a crystallization inhibitor of calcium salts in biological fluids and becomes a clear alternative in the treatment of calcium oxalate renal lithiasis.
Antitumor Effect of Paclitaxel Is Mediated by Inhibition of Myeloid-Derived Suppressor Cells and Chronic Inflammation in the Spontaneous Melanoma Model (2013)

The antitumor effects of paclitaxel are generally attributed to the suppression of microtubule dynamics resulting in defects in cell division. New data demonstrated that in ultralow noncytotoxic concentrations, paclitaxel modulated in immune cells in vitro the activity of small Rho GTPases, the key regulators of intracellular actin dynamics. However, the immunomodulatory properties of paclitaxel in vivo have not been evaluated. In this study, using the ret transgenic murine melanoma model, which mimics human cutaneous melanoma, we tested effects of ultralow noncytotoxic dose paclitaxel on functions of myeloid-derived suppressor cells (MDSCs), chronic inflammatory mediators, and T cell activities in the tumor microenvironment in vivo. Administration of paclitaxel significantly decreased accumulation and immunosuppressive activities of tumor-infiltrating MDSCs without alterations of the bone marrow hematopoiesis. This was associated with the inhibition of p38 MAPK activity, TNF-α and production, and S100A9 expression in MDSCs. The production of mediators of chronic inflammation in the tumor milieu also was diminished. Importantly, reduced tumor burden and increased animal survival upon paclitaxel application was mediated by the restoration of CD8 T cell effector functions. We suggest that the ability of paclitaxel in a noncytotoxic dose to block the immunosuppressive potential of MDSCs in vivo represents a new therapeutic strategy to downregulate immunosuppression and chronic inflammation in the tumor microenvironment for enhancing the efficacy of concomitant anticancer therapies.
The cyclin-dependent kinase inhibitor, p21 WAF1 , promotes angiogenesis by repressing gene transcription of thioredoxin-binding protein 2 in cancer cells (2009)

The cyclin-dependent kinase inhibitor, p21(WAF1), induces cell-cycle arrest and can act as a tumor suppressor. However, increasing evidence indicates that p21(WAF1) can also increase resistance to some anticancer therapies and thus promote tumor growth. The mechanisms explaining this paradox have not been explained. We found that conditioned media from MCF-7 breast cancer cells transfected with a p21(WAF1)-specific small interfering RNA (siRNA) significantly reduced endothelial cell migration, invasion and vascular sprouting. Liquid chromatography/mass spectrometry analysis of the conditioned media revealed that p21(WAF1) knockdown significantly reduced secretion of thioredoxin (Trx), a redox protein known to promote tumor angiogenesis. p21(WAF1) knockdown decreased Trx enzymatic activity in cancer cells, by effects on the expression levels of intracellular thioredoxin-binding protein 2 (TBP2), known to bind and inactivate Trx. Consistent with these findings, media from cancer cells transfected with TBP2 siRNA promoted endothelial cell invasion and blocked the anti-angiogenic effect of p21(WAF1) siRNA. Addition of Trx siRNA blocked the pro-angiogenic effects of TBP2 siRNA. Chromatin immunoprecipitation assays showed p21(WAF1) bound TBP2 gene promoter. Taken together, our data suggests that p21(WAF1) can induce Trx secretion and angiogenesis in cancer cells, by direct transcriptional repression of the TBP2 promoter.
CD40 expression by human peripheral blood eosinophils. (1996)

In this study, we have investigated CD40 expression in human peripheral blood eosinophils and in human chronically inflamed nasal tissues, i.e., nasal polyps. We show by both reverse transcriptase-PCR and Northern blot analysis that eosinophils from allergic subjects express human CD40 mRNA. We also show that constitutive CD40 mRNA expression in eosinophils could be upregulated by exposure to IgA immune complexes and downregulated by IL-10 and the synthetic steroid budesonide. In addition, we demonstrate that eosinophils express CD40 protein by flow cytometry. Such expression is biologically functional as cross-linking CD40 with CD40 mAbs enhances eosinophil survival in a dose-dependent fashion; in addition, CD40 ligation stimulates eosinophils to release GM-CSF. CD40-mediated eosinophil survival was largely inhibited by an anti-GM-CSF neutralizing antibody suggesting GM-CSF involvement in the survival enhancing mechanism. CD40 mRNA was also detected in total RNA extracted from nasal polyp tissues but not in RNA isolated from normal nasal mucosa (inferior turbinate); by immunohistochemistry, we were able to detect immunoreactive CD40 protein in a variety of cell types in the polyp stroma, but primarily in eosinophils. These observations suggest previously unforeseen interactions between eosinophils and cells expressing the CD40 ligand and, thus, novel pathways by which eosinophils may contribute to the regulation of airway inflammation.
Mismatch repair in heteroduplex DNA. (1975)

DNA with base pair mismatches was prepared by annealing mixtures of genetically marked DNA from bacteriophage lambda. This heteroduplex DNA was used to transfect bacteria under conditions minimizing recombination. Genetic analysis of the progeny phages indicates that: (i) Mismatch repair occurs, usually giving rise to a DNA molecule with one chain with the genotype arising from repair and one parental chain. (ii) The frequency of repair of a given mismatch to wild type depends on the marker, ranging from 3 to 20%. (iii) Excision tracts may extend several hundred nucleotides but are usually shorter than about 2000 nucleotides. (iv) In Rec-mediated bacteriophage crosses, recombination of markers closer than about 10-3 nucleotide pairs frequently occurs by mismatch repair within heteroduplex DNA. (V) The average amount of heteroduplex DNA formed in a Rec-mediated recombination event is a few thousand nucleotide pairs.
MULTIPLE INTERACTING PROGRAMS: A REPRESENTATION FOR EVOLVING COMPLEX BEHAVIOR (1998)

Abstract This paper defines a representation for expressing complex behaviors called multiple interacting programs MIPs and describes an evolutionary method for evolving solutions to difficult problems expressed as MIPs structures. The MIPs representation is a generalization of neural network architectures that can model any type of dynamic system. The evolutionary training method described is based on an evolutionary program originally used to evolve the architecture and weights of recurrent neural networks. Example experiments demonstrate the training method's ability to evolve appropriate MIPs solutions for difficult problems. An analysis of the evolved solutions shows their dynamics to be interesting and nontrivial.
Effectiveness of Sensor-Augmented Insulin-Pump Therapy in Type 1 Diabetes (2010)

In both adults and children with inadequately controlled type 1 diabetes, sensor-augmented pump therapy resulted in significant improvement in glycated hemoglobin levels, as compared with injection therapy. A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level. (Funded by Medtronic and others; ClinicalTrials.gov number, NCT00417989.)