gebhart/patrepeval huggingface dataset:
Intranasal dopamine application increases dopaminergic activity in the neostriatum and nucleus accumbens and enhances motor activity in the open field (2007)

Dopamine (DA) plays an important role in a number of behavioral processes and neurological disorders. The intranasal administration of DA provides improved brain penetrability in comparison to systemic administration. We investigated the effects of intranasal administration of DA on the activity of dopaminergic neurons of the mesostriatal and mesolimbic systems and on motor activity. Rats previously implanted with guide-cannulae in the neostriatum (NS) and nucleus accumbens (NAc) were submitted to microdialysis procedure under urethane anesthesia. Vehicle or DA (0.03, 0.3, or 3.0 mg/kg) was administered bilaterally into the nostrils. In a separate study, animals received an intraperitoneal (i.p.) injection of vehicle or DA (0.03, 0.3, 3.0, or 30.0 mg/kg). Samples were collected every 10 min and analyzed for the content of DA and metabolites using high-performance liquid chromatography. For the open field study, rats were given intranasal vehicle or DA (0.03, 0.3, or 3.0 mg/kg) and placed into the field for 30 min. Motor activity (locomotion and rearing) and grooming were analyzed in blocks of 10 min using Ethovision. Intranasal DA (3.0 mg/kg) significantly increased DA levels in the NS and NAc immediately after administration. A comparable effect was obtained only after i.p. administration of 30 mg/kg DA. In the open field, the 3.0 mg/kg dose significantly decreased grooming behavior in the second 10 min interval and significantly increased locomotor activity in the third 10 min interval. The data indicate that intranasal administration of DA can influence dopaminergic functions and motor activity, and has a potential application in the therapy of diseases affecting the dopaminergic system.
Flow of Blood to the Ovaries of Ewes Throughout the Estrous Cycle1 (1975)

A Doppler ultrasonic blood flow procedure was evaluated to determine if it could be adapted for use on vessels as small (I.D. ≅ 0.5 mm) as the ovarian artery in sheep. When blood was pumped through silastic tubing (I.D. = 0.38 and 0.57 mm) the values calculated for blood flow using the Doppler procedure were highly correlated (P<0.01) with the known flow rates. A second experiment was conducted to compare the Doppler ultrasonic procedure for measuring blood flow to the ovaries of ewes and the uptake of radioactive microspheres. Although it was not possible to measure blood flow directly (ml/min) with the radioactive microsphere method, when the cpm/g of ovarian tissue were compared to the ml/min blood flow calculated using the Doppler procedure, there was a high degree of correlation (r = 0.94, P<0.01). These results suggested that the Doppler ultrasonic procedure was reliable for the quantification of blood flow to the ovaries of ewes. In a final experiment the flow of blood to the ovaries of four ewes was quantified throughout an estrous cycle. Blood samples for hormone analysis and blood flow data were collected at 2–6 h intervals. Significant correlations were noted between serum levels of LH and FSH (P<0.05), LH and prolactin (P<0.05), and FSH and prolactin (P<0.01). Systemic levels of progesterone and blood flow to the ovary bearing the corpus luteum were also correlated (P<0.05). Blood flow to the luteal ovary increased from approximately 0.7 ml/min during the estrual phase of the cycle to 3 to 5 ml/min during the mid-luteal phase. This observation suggests that the amounts of LH and prolactin, as well as other substances, such as oxygen, glucose, cholesterol, etc., which reach the corpus luteum were increased. This mechanism probably plays a very important role in supporting the increased function of the corpus luteum during the mid-luteal phase of the estrous cycle.
Adenovirus-Mediated Delivery of Human Kallistatin Gene Reduces Blood Pressure of Spontaneously Hypertensive Rats (1997)

Human kallistatin, or human tissue kallikrein-binding protein (HKBP), is a serine proteinase inhibitor (serpin). Transgenic mice overexpressing rat kallikrein-binding protein are hypotensive. To elucidate therapeutic potentials of kallistatin in hypertension, the human kallistatin gene in an adenoviral vector was directly introduced into spontaneously hypertensive rats (SHR) through portal vein injection. The kallistatin cDNA construct (RSV-cHKBP) under the promoter control of Rous sarcoma virus 3' long terminal repeat (LTR) was incorporated into adenovirus (Ad.RSV-cHKBP). Recombinant kallistatin in 293 cells transfected with RSV-cHKBP or Ad.RSV-cHKBP was measured by ELISA and by its complex formation with tissue kallikrein. A single intraportal vein injection of Ad.RSV-cHKBP at a dose of 8 x 10(10) pfu results in a significant reduction of blood pressure of SHR for 4 weeks. Human kallistatin mRNA was detected in the liver, spleen, kidney, aorta, and lung of rats receiving gene delivery. Immunoreactive human kallistatin in rat serum was detected at the highest level 1 day post injection and at lesser amounts in rat tissues. This study shows that adenovirus harboring Ad.RSV-cHKBP produces functional kallistatin, and adenovirus-mediated transfer of the human kallistatin gene reduces blood pressures of SHR. The results suggest that kallistatin may function as a vasodilator in vivo and provide important information for a potential gene therapy approach to hypertension.
The use of lectin microarray for assessing glycosylation of therapeutic proteins (2016)

Glycans or carbohydrates attached to therapeutic glycoproteins can directly affect product quality, safety and efficacy, and therefore must be adequately analyzed and controlled throughout product life cycles. However, the complexity of protein glycosylation poses a daunting analytical challenge. In this study, we evaluated the utility of a lectin microarray for assessing protein glycans. Using commercial lectin chips, which contain 45 lectins toward distinct glycan structures, we were able to determine the lectin binding patterns of a panel of 15 therapeutic proteins, including 8 monoclonal antibodies. Lectin binding signals were analyzed to generate glycan profiles that were generally consistent with the known glycan patterns for these glycoproteins. In particular, the lectin-based microarray was found to be highly sensitive to variations in the terminal carbohydrate structures such as galactose versus sialic acid epitopes. These data suggest that lectin microarray could be used for screening glycan patterns of therapeutic glycoproteins.
ChemInform Abstract: BIS(2‐OXO‐3‐OXAZOLIDINYL)PHOSPHINIC CHLORIDE (1) AS A COUPLING REAGENT FOR N‐ALKYL AMINO ACIDS (1985)

Abstract Die Titelverbindung (I) ist ein vorteilhaftes Kupplungsreagens für die Verknüpfung von N‐Methylaminosäuren, wie z.B. (II) und (III).
Spread Spectrum Modulation for Acoustic Communication in Shallow Water Channel (2007)

A wireless underwater acoustic communication system based on the combination of chirp modulation and direct-sequence spread-spectrum signaling is presented. The use of chirp signals takes advantage of the low Doppler sensitivity in the matched filter operation whereas the choice of pseudo noise (PN) sequences allows one to reduce narrowband interference arising from other users and self-interference due to multipath propagation. The system here described is made of a transmitter encoding the bits with linear chirps multiplied by PN sequences, and a rake receiver that allows one to positively exploit the energy present in the most significant propagation paths. Moreover a tracking procedure that allows an adaptation to the instantaneous Doppler shift has been devised and tested. Results, obtained on real data over a long-range shallow-water channel with a moving transmitting platform, are presented and discussed.
Polyamines in plant physiology. (1990)

The diamine putrescine, the triamine spermidine, and the tetramine spermine are ubiquitous in plant cells, while other polyamines are of more limited occurrence. Their chemistry and pathways of biosynthesis and metabolism are well characterized. They occur in the free form as cations, but are often conjugated to small molecules like phenolic acids and also to various macromolecules. Their titer varies from approximately micromolar to more than millimolar, and depends greatly on environmental conditions, especially stress. In cereals, the activity of one of the major polyamine biosynthetic enzymes, arginine decarboxylase, is rapidly and dramatically increased by almost every studied external stress, leading to 50-fold or greater increases in putrescine titer within a few hours. The physiological significance of this increase is not yet clear, although most recent work suggests an adaptive, protective role. Polyamines produced through the action of ornithine decarboxylase, by contrast, seem essential for DNA replication and cell division. The application of exogenous polyamines produces effects on patterns of senescence and morphogenesis, suggesting but not proving a regulatory role for polyamines in these processes. The evidence for such a regulatory role is growing.
Downregulation of DNA repair proteins and increased DNA damage in hypoxic colon cancer cells is a therapeutically exploitable vulnerability (2017)

Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures. Tumors with high expression of HIF signatures and low expression of repair proteins showed the worst survival. In human tumors, expression of the repair proteins RAD51, KU70 and RIF1 was strongly suppressed in hypoxic peri-necrotic tumor areas. Experimentally induced hypoxia in patient derived colonospheres <i>in vitro</i> or <i>in vivo</i> (through vascular clamping) was sufficient to downregulate repair protein expression and caused DNA damage. Hypoxia-induced DNA damage was prevented by expressing the hydroperoxide-scavenging enzyme glutathione peroxidase-2 (GPx2), indicating that reactive oxygen species mediate hypoxia-induced DNA damage. Finally, the hypoxia-activated prodrug Tirapazamine greatly augmented DNA damage and reduced the fraction of stem-like (Aldefluor<sup>bright</sup>) tumor cells <i>in vitro</i>, and <i>in vivo</i> following vascular clamping. We conclude that decreased expression of DNA repair proteins and increased DNA damage in hypoxic tumor areas may be therapeutically exploited with hypoxia-activated prodrugs, and that such drugs reduce the fraction of Aldefluor<sup>bright</sup> (stem-like) tumor cells.
The role of transforming growth factor beta in the generation of suppression: an interaction between CD8+ T and NK cells. (1994)

CD8+ T cells have suppressor effector functions, but the mechanisms involved in the generation of this activity are poorly understood. We report that natural killer (NK) cells have an important role in the acquisition of this function. CD8+ cells induce NK cells to produce transforming growth factor-beta (TGF-beta) which, in turn, stimulates CD8+ T cells to become suppressors of antibody production. Using a monocyte-dependent and -independent method to induce antibody production, we first observed that the addition of NK cells to CD8+ cells was required for optimal suppression. Next, we determined that the interaction of CD8+ T cells with NK cells resulted in a striking increase NK cell TGF-beta mRNA and its production. This cytokine appeared to be involved in the induction of T suppressor cell activity since: (a) anti-TGF-beta 1 completely abrogated the suppression of immunoglobulin G synthesis; (b) TGF-beta 1 could substitute for NK cells in inducing CD8+ T cells to develop suppressor activity; and (c) a short exposure of T cells to TGF-beta 1 in the absence of B cells was sufficient for the generation of suppressor activity by CD8+ T cells. Interferon gamma did not have this property. These studies provide strong evidence that in addition to its suppressive properties, TGF-beta is involved in the generation of CD8+ T suppressor effector cells. Because NK cell function is decreased in many autoimmune diseases, these cells may fail to interact properly with these individuals' CD8+ cells in generating suppressors of aggressive anti-self responses.
Is there a 'magic bullet' to improve response rates in surveys of medical practitioners? (1999)

The authors conducted a meta-analysis of randomised controlled trials evaluating the effectiveness of an advance telephone prompt from a medical peer to improve survey response rates among Australian medical practitioners. (non-author abstract)
A nationwide population-based study to determine whether coeliac disease is associated with infertility (2010)

Swedish population-based cohort study. Duodenal/jejunal biopsy data on CD (Marsh III; villous atrophy (VA); n=18,005 unique women) were collected from all (n=28) pathology departments in Sweden. From this dataset, 11,495 women with CD, aged 18-45 years, were identified at some point before the end of follow-up. Multinomial logistic regression and Cox regression were used to estimate fertility in these women compared with that in 51,109 age-matched reference women. Fertility was defined as the number of children according to the Swedish Multi-Generation Register. Results During follow-up, 16,309 births occurred in women with CD and 69,245 in the reference women. The cumulative number of children slightly increased in women with CD compared with the reference group. Adjusting for age, calendar period and parity and stratifying by education, the overall fertility hazard ratio (HR) in CD was 1.03 (95% CI 1.01 to 1.05). Specifically, the fertility HR was 1.05 (95% CI 0.96 to 1.14) for CD diagnosed in women before 18 years, 1.04 (95% CI 1.01 to 1.07) for CD diagnosed in women between 18 and 45 years and 1.02 (95% CI 0.99 to 1.04) for CD diagnosed in women > 45 years of age. Taking date of CD diagnosis into account, fertility was decreased 0-2 years before time of diagnosis (HR=0.63; 95% CI 0.57 to 0.70), was identical to that of controls 0-5 years subsequent to diagnosis and increased to 1.12 (95% CI 1.03 to 1.21) thereafter. Conclusion Overall, women with CD had a normal fertility, but their fertility was decreased in the last 2 years preceding CD diagnosis.
Simultaneous spatial and frequency-domain filtering at the antenna inputs achieving up to +10dBm out-of-band/beam P1dB (2013)

Multi-antenna transceivers with beam-forming are recently gaining interest for low GHz frequencies (<;6GHz) [1-4]. In the antenna beam, (phase-shifted) signals from multiple antennas add constructively, improving SNR, while out-of-beam signals add destructively (i.e. spatial filtering). Usually the summation point is behind some gain blocks, which then need to be capable of handling strong signals. To improve the input-referred compression point P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1dB</sub> , a fully passive switched-capacitor approach was presented in [4], providing P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1dB</sub> =+2dBm, but at a high noise penalty: NF=18dB. Here we propose to sum immediately at the baseband capacitors of passive mixer-first switched-RC downconverters. We show that this can render a direction-dependent RF impedance (spatial filtering) together with RF bandpass frequency filtering at lower noise and higher P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1dB</sub> .
Equine Herpesviruses: a Brief Review (2014)

Nine equine herpesviruses (EHV) have been known to infect equines. Equine herpesvirus type-1 (EHV1) is an important and ubiquitous viral pathogen of the horse and produces syndromes of respiratory disease, epidemic abortion and sporadic encephalomyelitis. This review article is focused on some aspects of EHV1 biology, its life cycle and pathogenicity in the natural host. Vaccination is one of the best options to fight EHV1 infection. Various strategies of vaccination that have been investigated and developed over the past decades will be presented in this review. Diagnosis is important to start specific treatment. The latest diagnostic techniques which were developed recently together with conventional will also be discussed.
Stimulation of rat ovarian cell steroidogenesis by high density lipoproteins modified with tetranitromethane. (1985)

Human high density lipoprotein (devoid of apo-E) was modified by nitration of tyrosine residues with tetranitromethane. As a result of extensive cross-linking, monomeric apo-A-I was markedly depleted, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the modified HDL did not effectively bind to high-affinity sites present on dispersed rat ovarian cells and isolated rat ovarian membranes. Nonetheless, the modified HDL retained the ability to stimulate steroidogenesis by both dispersed rat ovarian cells and cultured rat granulosa cells to a degree at least equal to that of native HDL. Modified HDL stimulated luteal steroidogenesis under basal conditions and when cells were stimulated with luteinizing hormone or 8-bromo-cAMP. Although modified HDL did not effectively bind to high-affinity sites, it exhibited substantial "nonspecific" or "low-affinity" binding which was not displaceable by native HDL. These data suggest that high-affinity binding is not an essential event in the "HDL pathway" and that HDL can deliver its sterols through low-affinity cellular associations.
Turing Machines with Atoms (2013)

We study Turing machines over sets with atoms, also known as nominal sets. Our main result is that deterministic machines are weaker than nondeterministic ones; in particular, P≠NP in sets with atoms. Our main construction is closely related to the Cai-Furer-Immerman graphs used in descriptive complexity theory.
Atomic Emission Method for Total Boron in Blood during Neutron-Capture Therapy (2001)

The present method is feasible, accurate, and one of the fastest for boron determination during BNCT. Our results indicate that it is preferable to determine boron in plasma and in whole blood. Indirect erythrocyte-boron determination thus becomes possible and avoids the impact of preanalytical confounding factors, such as the influence of the hematocrit of the patient. Such an approach enables a more reliable estimation of the irradiation dose.
Optimizing copy number variation analysis using genome-wide short sequence oligonucleotide arrays (2010)

The detection of copy number variants (CNV) by array-based platforms provides valuable insight into understanding human diversity. However, suboptimal study design and data processing negatively affect CNV assessment. We quantitatively evaluate their impact when short-sequence oligonucleotide arrays are applied (Affymetrix Genome-Wide Human SNP Array 6.0) by evaluating 42 HapMap samples for CNV detection. Several processing and segmentation strategies are implemented, and results are compared to CNV assessment obtained using an oligonucleotide array CGH platform designed to query CNVs at high resolution (Agilent). We quantitatively demonstrate that different reference models (e.g. single versus pooled sample reference) used to detect CNVs are a major source of inter-platform discrepancy (up to 30%) and that CNVs residing within segmental duplication regions (higher reference copy number) are significantly harder to detect (P < 0.0001). After adjusting Affymetrix data to mimic the Agilent experimental design (reference sample effect), we applied several common segmentation approaches and evaluated differential sensitivity and specificity for CNV detection, ranging 39-77% and 86-100% for non-segmental duplication regions, respectively, and 18-55% and 39-77% for segmental duplications. Our results are relevant to any array-based CNV study and provide guidelines to optimize performance based on study-specific objectives.
Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis (2013)

Introduction To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) risk, we surveyed studies on the association of the TNFSF4 rs2205960, rs1234315, rs844644, and rs844648 polymorphisms with SLE. Methods A literature-based search was conducted to identify all relevant studies. A total of eight independent studies were identified and subsequently reviewed in the meta-analysis. Results The meta-analysis showed an association between the TNFSF4 rs2205960 polymorphism and SLE in all subjects [ odds ratio (OR) 1.327, 95 % confidence interval (CI) 1.227–1.436, P < 0.001]. In a subgroup analysis by ethnicity, a significantly increased risk for SLE was associated with TNFSF4 rs2205960 T allele among patients of European (OR 1.254, 95 % CI 1.185–1.328, P < 0.001) and Asian ethnicity (OR 1.425, 95 % CI 1.352–1.501, P < 0.001). The meta-analysis of the rs1234315 polymorphism revealed no association between SLE and the rs1234315 T allele in all subjects (OR 1.167, 95 % CI 0.874–1.558, P = 0.296), but the results of the subgroup analysis revealed significant association in subjects of Asian ethnicity (OR 1.386, 95 % CI 1.318–1.458, P < 0.001). No association was found between the rs844644 and rs844648 polymorphisms and SLE. Conclusion The results of our meta-analysis suggest that the TNFSF4 rs2205960 polymorphism may confer susceptibility to SLE in different populations and that the TNFSF4 rs1234315 polymorphism is associated with susceptibility to SLE in Asians.
How I treat mycosis fungoides and Sézary syndrome (2009)

The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a "stage-based" approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-alpha, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.