gebhart/patrepeval huggingface dataset:
Somatic Afferent Stimulation-Plasma Corticosterone, Luteinizing Hormone (LH), and Testosterone Responses in Aged Male Rats under Anesthetization. (1992)

Our previous studies have demonstrated that somatic sensory stimulation can produce increases in secretions of corticosterone, luteinizing hormone (LH), and testosterone in young male Wistar rats of 13-22 weeks old even after emotional factors are eliminated by pentobarbital-anesthetizing of the subjects. In the present study, we examined the effects of somatic sensory stimulation on plasma corticosterone, LH, and testosterone using aged male Wistar rats (24-27 months old) under the same anesthetizing condition as employed in our previous studies. We compared the reflex responses in aged rats with those previously measured in young rats. Nociceptive mechanical stimulation of both hindpaws by pinching for 10 min significantly increased plasma corticosterone levels in aged rats. The magnitude and time-course of this response were equivalent to those in young rats. On the other hand, neither plasma LH nor testosterone levels were changed by nociceptive mechanical stimulation of the hindpaws of aged rats. This is in sharp contrast to the increase in both plasma LH and testosterone caused by the stimulation of young rats. These results indicate a functional dissociation induced by aging between the secretory responses of the anterior pituitary, testes on the one hand and the adrenal cortex on the other hand, to nociceptive somatic sensory stimulation. Aging does not alter corticosterone release from the adrenal cortex to nociceptive somatic sensory stimulation; however, LH secretion from the anterior pituitary and testosterone secretion from the testes to nociceptive somatic sensory stimulation are subject to dysfunction with aging.
Inhibition of angiotensin I–converting enzyme induces radioprotection by preserving murine hematopoietic short-term reconstituting cells (2004)

Angiotensin I-converting enzyme (ACE) inhibitors can affect hematopoiesis by several mechanisms including inhibition of angiotensin II formation and increasing plasma concentrations of AcSDKP (acetyl-N-Ser-Asp-Lys-Pro), an ACE substrate and a negative regulator of hematopoiesis. We tested whether ACE inhibition could decrease the hematopoietic toxicity of lethal or sublethal irradiation protocols. In all cases, short treatment with the ACE inhibitor perindopril protected against irradiation-induced death. ACE inhibition accelerated hematopoietic recovery and led to a significant increase in platelet and red cell counts. Pretreatment with perindopril increased bone marrow cellularity and the number of hematopoietic progenitors (granulocyte macrophage colony-forming unit [CFU-GM], erythroid burst-forming unit [BFU-E], and megakaryocyte colony-forming unit [CFU-MK]) from day 7 to 28 after irradiation. Perindopril also increased the number of hematopoietic stem cells with at least a short-term reconstitutive activity in animals that recovered from irradiation. To determine the mechanism of action involved, we evaluated the effects of increasing AcSDKP plasma concentrations and of an angiotensin II type 1 (AT1) receptor antagonist (telmisartan) on radioprotection. We found that the AT1-receptor antagonism mediated similar radioprotection as the ACE inhibitor. These results suggest that ACE inhibitors and AT1-receptor antagonists could be used to decrease the hematopoietic toxicity of irradiation.
Atom-by-atom nucleation and growth of graphene nanopores (2012)

Graphene is an ideal thin membrane substrate for creating molecule-scale devices. Here we demonstrate a scalable method for creating extremely small structures in graphene with atomic precision. It consists of inducing defect nucleation centers with energetic ions, followed by edge-selective electron recoil sputtering. As a first application, we create graphene nanopores with radii as small as 3 Å, which corresponds to 10 atoms removed. We observe carbon atom removal from the nanopore edge in situ using an aberration-corrected electron microscope, measure the cross-section for the process, and obtain a mean edge atom displacement energy of 14.1 ± 0.1 eV. This approach does not require focused beams and allows scalable production of single nanopores and arrays of monodisperse nanopores for atomic-scale selectively permeable membranes.
Cinnamon: Potential Role in the Prevention of Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes (2010)

Metabolic syndrome is associated with insulin resistance, elevated glucose and lipids, inflammation, decreased antioxidant activity, increased weight gain, and increased glycation of proteins. Cinnamon has been shown to improve all of these variables in in vitro, animal, and/or human studies. In addition, cinnamon has been shown to alleviate factors associated with Alzheimer's disease by blocking and reversing tau formation in vitro and in ischemic stroke by blocking cell swelling. In vitro studies also show that components of cinnamon control angiogenesis associated with the proliferation of cancer cells. Human studies involving control subjects and subjects with metabolic syndrome, type 2 diabetes mellitus, and polycystic ovary syndrome all show beneficial effects of whole cinnamon and/or aqueous extracts of cinnamon on glucose, insulin, insulin sensitivity, lipids, antioxidant status, blood pressure, lean body mass, and gastric emptying. However, not all studies have shown positive effects of cinnamon, and type and amount of cinnamon, as well as the type of subjects and drugs subjects are taking, are likely to affect the response to cinnamon. In summary, components of cinnamon may be important in the alleviation and prevention of the signs and symptoms of metabolic syndrome, type 2 diabetes, and cardiovascular and related diseases.
p53 -Dependent and -Independent Nucleolar Stress Responses (2012)

The nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or ribosomal stress. Ribosomal proteins, including RPL11 and RPL5, become increasingly bound to the p53 regulatory protein MDM2 following nucleolar stress. Ribosomal protein binding to MDM2 blocks its E3 ligase function leading to stabilization and activation of p53. In this review we focus on a number of novel regulators of the RPL5/RPL11-MDM2-p53 complex including PICT1 (GLTSCR2), MYBBP1A, PML and NEDD8. p53-independent pathways mediating the nucleolar stress response are also emerging and in particular the negative control that RPL11 exerts on Myc oncoprotein is of importance, given the role of Myc as a master regulator of ribosome biogenesis. We also briefly discuss the potential of chemotherapeutic drugs that specifically target RNA polymerase I to induce nucleolar stress.
Association of polymorphisms within androgen receptor, 5α‐reductase, and PSA genes with prostate volume, clinical parameters, and endocrine status in elderly men (2002)

Abstract BACKGROUND The aim of this study was to assess the impact of polymorphisms of three genes within the androgen pathway on prostate volume, clinical parameters, and endocrine status. METHODS Elderly men with lower urinary tract symptoms underwent clinical and endocrine work‐up. In parallel, polymorphisms within the 5α‐reductase gene (SRD5A2 V89L and A49T), the androgen receptor gene (AR; number of CAG repeats), and the prostate specific antigen (PSA) gene (A → G substitution at position‐158) were determined by polymerase chain reaction and restriction‐length polymorphism analysis by using DNA from peripheral blood. RESULTS A total of 190 men (66.5 ± 9.2 yr) were analyzed. The number of CAG repeats within the AR and the PSA polymorphism revealed no associations to clinical and endocrine parameters. Individuals carrying the mutated SRD5A2 A49T allele (5.3% of the total population) had larger prostates (54.1 vs. 39.3 ml), higher PSA levels (12.2 vs. 4.3 ng/ml), and a 35% reduction in prostatic stroma/epithelial cell ratio. Men with the mutated SRD5A2 V89L gene had lower testosterone levels. CONCLUSIONS In contrast to prostate cancer, polymorphisms within AR and PSA genes do not seem to be of importance for benign prostatic hyperplasia. Polymorphisms within the 5α‐reductase gene are interesting biomarkers for the development of benign prostatic hyperplasia and benign prostatic enlargement. Prostate 52:130–138, 2002. © 2002 Wiley‐Liss, Inc.
Complexity in Influenza Virus Targeted Drug Design: Interaction with Human Sialidases (2010)

With the global spread of the pandemic H1N1 and the ongoing pandemic potential of the H5N1 subtype, the influenza virus represents one of the most alarming viruses spreading worldwide. The influenza virus sialidase is an effective drug target, and a number of inhibitors are clinically effective against the virus (zanamivir, oseltamivir, peramivir). Here we report structural and biochemical studies of the human cytosolic sialidase Neu2 with influenza virus sialidase-targeting drugs and related compounds.
Corneal Edema and Intraocular Pressure (1965)

The literature pertaining to the relationship between intraocular pressure and edema of the cornea was reviewed in an earlier communication (Ytteborg and Dohlman).1Results of animal experiments were reported in the same paper. The immediate effect of varying the intraocular pressure on epithelial and stromal hydration, as well as on transparency, was observed. Raising or lowering of the intraocular pressure for a few hours had little effect onstromalhydration.Epithelialedema seemed to appear sooner and progress more rapidly as (a) the level of intraocular pressure was increased, and/or (b) stromal swelling increased after endothelial damage. The experiments were short so that the cornea, in most cases, did not have time to reach a new steady state of hydration. In the present paper, the long term effects were studied in human subjects having low, normal, or raised intraocular pressure, assumed to have remained steady for some time. Observations
Large Margin Gaussian Mixture Models with Differential Privacy (2012)

As increasing amounts of sensitive personal information is aggregated into data repositories, it has become important to develop mechanisms for processing the data without revealing information about individual data instances. The differential privacy model provides a framework for the development and theoretical analysis of such mechanisms. In this paper, we propose an algorithm for learning a discriminatively trained multiclass Gaussian mixture model-based classifier that preserves differential privacy using a large margin loss function with a perturbed regularization term. We present a theoretical upper bound on the excess risk of the classifier introduced by the perturbation.
Engineerable femtosecond pulse shaping by second-harmonic generation with Fourier synthetic quasi-phase-matching gratings (1998)

We describe a pulse-shaping technique that uses second-harmonic generation with Fourier synthetic quasi-phase-matching gratings. We demonstrate both amplitude and phase tailoring by generating a picosecond squarelike pulse as well as trains of femtosecond pulses with a terahertz-range repetition rate from either a compressed or a chirped pump pulse.
Receptor-Binding Protein of Lactococcus lactis Phages: Identification and Characterization of the Saccharide Receptor-Binding Site (2006)

Phage p2, a member of the lactococcal 936 phage species, infects Lactococcus lactis strains by binding initially to specific carbohydrate receptors using its receptor-binding protein (RBP). The structures of p2 RBP, a homotrimeric protein composed of three domains, and of its complex with a neutralizing llama VH domain (VHH5) have been determined (S. Spinelli, A. Desmyter, C. T. Verrips, H. J. de Haard, S. Moineau, and C. Cambillau, Nat. Struct. Mol. Biol. 13:85-89, 2006). Here, we show that VHH5 was able to neutralize 12 of 50 lactococcal phages belonging to the 936 species. Moreover, escape phage mutants no longer neutralized by VHH5 were isolated from 11 of these phages. All of the mutations (but one) cluster in the RBP/VHH5 interaction surface that delineates the receptor-binding area. A glycerol molecule, observed in the 1.7-A resolution structure of RBP, was found to bind tightly (Kd= 0.26 microM) in a crevice located in this area. Other saccharides bind RBP with comparable high affinity. These data prove the saccharidic nature of the bacterial receptor recognized by phage p2 and identify the position of its binding site in the RBP head domain.
Pharmacological Effects of a Combination of Fenoterol Hydrobromide and Ipratropium Bromide (1986)

The bronchospasmolytic and cardiovascular effects of fenoterol hydrobromide and ipratropium bromide alone and in combination were investigated using metered aerosols in guinea pigs and dogs and intravenous injection in dogs. The additive effect of the combination on bronchospasmolysis could be demonstrated. The slight cardiovascular side-effects of fenoterol hydrobromide alone were reduced to an insignificant level with the combination administered as a metered aerosol, but were still present when the combination was administered parenterally. Ipratropium bromide in both forms of administration had no effect on the cardiovascular system.
Isochorismate Synthase (PchA), the First and Rate-limiting Enzyme in Salicylate Biosynthesis of Pseudomonas aeruginosa (2003)

In Pseudomonas aeruginosa the extracellular metabolite and siderophore pyochelin is synthesized from two major precursors, chorismate and l-cysteine via salicylate as an intermediate. The regulatory role of isochorismate synthase, the first enzyme in the pyochelin biosynthetic pathway, was studied. This enzyme is encoded by pchA, the last gene in the pchDCBA operon. The PchA protein was purified to apparent electrophoretic homogeneity from a PchA-overexpressing P. aeruginosa strain. The native enzyme was a 52-kDa monomer in solution, and its activity strictly depended on Mg(2+). At pH 7.0, the optimum, a K(m) = 4.5 microm and a k(cat) = 43.1 min(-1) were determined for chorismate. No feedback inhibitors or other allosteric effectors were found. The intracellular PchA concentration critically determined the rate of salicylate formation both in vitro and in vivo. In cultures grown in iron-limiting media to high cell densities, overexpression of the pchA gene resulted in overproduction of salicylate as well as in enhanced pyochelin formation. From this work and earlier studies, it is proposed that one important factor influencing the flux through the pyochelin biosynthetic pathway is the PchA concentration, which is determined at a transcriptional level, with pyochelin acting as a positive signal and iron as a negative signal.
Development of an oral formulation of omeprazole (1985)

Omeprazole has a low water solubility and is chemically labile in an acid environment. In the formulation of an oral dosage form of omeprazole the possibilities of dissolution rate limited absorption and preabsorption degradation must be kept in mind. A water suspension of omeprazole was tested in a pilot bioavailability study. The suspension was given to six healthy, fasting volunteers on two occasions--together with sodium bicarbonate solution and together with the same volume of water. When the suspension was given with water the bioavailability was reduced by about 50% owing to preabsorption degradation. In another bioavailability study the slowest of three granule formulations with differing in vitro dissolution rates showed a reduced extent of absorption. A controlled-release pellet formulation (enteric-coated) was formulated and tested in a series of bioavailability studies. A single dose given with food resulted in a delayed absorption and possibly lower bioavailability than under fasting conditions. When the granules were given on an empty stomach before the morning meal the length of time between dosage and meal was of no importance. Concomitant administration of a liquid antacid had no influence on the bioavailability of omeprazole.
Photo‐ and Thermoresponsive Polymersomes for Triggered Release (2012)

Microfluidics: Thermo- and photoresponsive polymersomes are assembled using capillary microfluidic devices. Encapsulants can be selectively released from the thermoresponsive polymersomes if they are incubated at and above temperatures of 40 °C, whereas the photoresponsive polymersomes selectively release encapsulants if illuminated with laser light (see picture; NP = nanoparticle).
Enabling Effective Yield Learning through Actual DFM-Closure at the SoC Level (2007)

The aim of this paper is to extend the intensive yield learning and manufacturability process further into the process life cycle. This necessarily means employing chips of high circuit complexity, up to the final products complexity. In this way, the actual effects that the design flow will have in combining low-levels of IP can be understood more accurately. The paper will also describe how analysis recipes can be used to isolate different behavior effects and associate them to failure cause. We will also demonstrate techniques which can be adopted in the early ramp-up phase to improve the DFM rules maturity level by progressively fine tuning them with respect to the measured data.
Structure of a Major Antigenic Site on the Respiratory Syncytial Virus Fusion Glycoprotein in Complex with Neutralizing Antibody 101F (2010)

Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in infants and elderly people. Currently there is no effective vaccine against RSV, but passive prophylaxis with neutralizing antibodies reduces hospitalizations. To investigate the mechanism of antibody-mediated RSV neutralization, we undertook structure-function studies of monoclonal antibody 101F, which binds a linear epitope in the RSV fusion glycoprotein. Crystal structures of the 101F antigen-binding fragment in complex with peptides from the fusion glycoprotein defined both the extent of the linear epitope and the interactions of residues that are mutated in antibody escape variants. The structure allowed for modeling of 101F in complex with trimers of the fusion glycoprotein, and the resulting models suggested that 101F may contact additional surfaces located outside the linear epitope. This hypothesis was supported by surface plasmon resonance experiments that demonstrated 101F bound the peptide epitope ∼16,000-fold more weakly than the fusion glycoprotein. The modeling also showed no substantial clashes between 101F and the fusion glycoprotein in either the pre- or postfusion state, and cell-based assays indicated that 101F neutralization was not associated with blocking virus attachment. Collectively, these results provide a structural basis for RSV neutralization by antibodies that target a major antigenic site on the fusion glycoprotein.
DNA-binding sequence of the human prostate-specific homeodomain protein NKX3.1 (2000)

NKX3.1 is a member of the NK class of homeodomain proteins and is most closely related to Drosophila NK-3. NKX3.1 has predominantly prostate-specific expression in the adult human. Previous studies suggested that NKX3.1 exerts a growth-suppressive effect on prostatic epithelial cells and controls differentiated glandular functions. Using a binding site selection assay with recombinant NKX3.1 protein we identified a TAAGTA consensus binding sequence that has not been reported for any other NK class homeoprotein. By electromobility shift assay we demonstrated that NKX3.1 preferentially binds the TAAGTA sequence rather than the binding site for Nkx2.1 (CAAGTG) or Msx1 (TAATTG). Using mutated binding sites in competitive gel shift assays, we analyzed the nucleotides in the TAAGTA consensus sequence that are important for NKX3.1 binding. The consensus binding site of a naturally occurring polymorphic NKX3.1 protein with arginine replaced by cysteine at position 52 was identical to the wild-type binding sequence. The binding affinities of wild-type and polymorphic NKX3.1 for the TAAGTA consensus site were very similar, with values of 20 and 22 nM, respectively. Wild-type and polymorphic NKX3.1 specifically repressed transcription of luciferase from a reporter vector with three copies of the NKX3.1-binding site upstream from a thymidine kinase promoter. The data show that among NK family proteins NKX3.1 binds a novel DNA sequence and can behave as an in vitro transcriptional repressor.
Conformationally Defined Retinoic Acid Analogues. 5. Large-Scale Synthesis and Mammary Cancer Chemopreventive Activity for (2E,4E,6Z,8E)-8- (3‘,4‘-Dihydro-1‘(2‘H)-naphthalen-1‘-ylidene)-3,7-dimethyl-2,4,6-octatrienoic Acid (9cUAB30) (2003)

Retinoids that activate the nuclear retinoid X receptors (RXRs) display potential for chemoprevention of breast cancer. We previously reported that 9cUAB30 (1) is an RXR-selective retinoid. To explore its in vivo chemopreventive activity, multigram quantities of 1 were needed. Here, we describe a modified synthesis that yields up to 100 g of 1. We further demonstrate that 1 is very effective in the prevention of N-methyl-N-nitrosourea induced mammary cancers in rats without signs of toxicity.
Neuronal organization of fetal striatal grafts in kainate- and sham- lesioned rat caudate nucleus: light- and electron-microscopic observations (1988)

Behavioral and biochemical studies have suggested that fetal striatal grafts in the adult rat neostriatum can reverse deficits induced by excitotoxic lesions of the host caudate tissue. In this study, fetal day 17-18 striatal grafts were examined at 2, 5-6, 12, and 44-48 weeks following their implantation into saline- or kainic acid-treated host caudate nucleus in order to compare the neuronal organization of the grafts and the host caudate nucleus and to determine whether the differentiation of graft tissue was influenced by the period of implantation or prior lesion of the host caudate nucleus with kainic acid. Compared to host neostriatum, the grafts at the light-microscopic level lacked bundles of myelinated axons and had neurons that were tightly packed in clusters and rich in Nissl substance. Neurons in the grafts were mostly of medium size, had significantly larger cross-sectional areas, and more frequently exhibited indented nuclei than host caudate neurons. At the electron-microscopic level, grafts 2 weeks following implantation contained many features seen in the normally developing neostriatum, such as growth cones, immature synapses, and degenerating profiles. Grafts appeared mature by 5-6 weeks and contained at least 6 types of neurons and 8 types of axon terminals, which formed synapses with cell bodies, dendrites, spines, and axon initial segments. Both symmetric and asymmetric synapses were found within the grafts. The density of synapses was significantly lower in all the transplants than in host tissue, with the exception of the 5-6 week grafts, where values were statistically comparable to host caudate. A significantly higher proportion of axodendritic synapses was present in the graft neuropil than in the caudate nucleus. The lengths of the synaptic junctions in the grafts were the same as those in the neostriatum. There was little qualitative or quantitative difference in synaptic organization between transplants in kainic acid and sham-lesioned host, with grafts in both host treatment conditions exhibiting the same synaptic density and proportion of axodendritic/axospinous synapses. The development of a high differentiated ultrastructure within striatal grafts is consistent with recent anatomical evidence showing interconnections between striatal grafts and host-lesioned caudate nucleus. Although graft neuropil shows striking similarities in neuronal organization to the caudate nucleus, it also exhibits some distinct differences that may have implications for understanding the functional properties of fetal striatal grafts in animal models of Huntington's disease.