gebhart/patrepeval huggingface dataset:
A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women (2006)

The results of our study suggest that ET alone in hysterectomized postmenopausal women increases the vaginal blood flow and improves some domains of sexual function, but it may not have an impact on diminished sexual desire or activity. Compared with systemic therapy, topical vaginal preparations are found to correlate with better symptom relief despite the lower serum level of estradiol.
In vitro demonstration of neural transmission of avian influenza A virus (2005)

Neural involvement following infections of influenza viruses can be serious. The neural transport of influenza viruses from the periphery to the central nervous system has been indicated by using mouse models. However, no direct evidence for neuronal infection has been obtained in vitro and the mechanisms of neural transmission of influenza viruses have not been reported. In this study, the transneural transmission of a neurotropic influenza A virus was examined using compartmentalized cultures of neurons from mouse dorsal root ganglia, and the results were compared with those obtained using the pseudorabies virus, a virus with well-established neurotransmission. Both viruses reached the cell bodies of the neurons via the axons. This is the first report on axonal transport of influenza A virus in vitro. In addition, the role of the cytoskeleton (microtubules, microfilaments and intermediate filaments) in the neural transmission of influenza virus was investigated by conducting cytoskeletal perturbation experiments. The results indicated that the transport of avian influenza A virus in the neurons was independent of microtubule integrity but was dependent on the integrity of intermediate filaments, whereas pseudorabies virus needed both for neural spread.
Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection (2005)

Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may now be appropriate.
Pathophysiologic role of myocardial apoptosis in post‐infarction left ventricular remodeling (2002)

Left ventricular (LV) remodeling and heart failure (HF) complicate acute myocardial infarction (AMI) even weeks to months after the initial insult. Apoptosis may represent an important pathophysiologic mechanism causing progressive myocardiocyte loss and LV dilatation even late after AMI. This review will discuss the role of apoptosis according to findings in animal experimental data and observational studies in humans in order to assess clinical relevance, determinants, and mechanisms of myocardial apoptosis and potential therapeutic implications. More complete definition of the impact of myocardiocyte loss on prognosis and of the mechanisms involved may lead to improved understanding of cardiac remodeling and possibly improved patients' care. Mitochondrial damage and bcl-2 to bax balance play a central role in ischemia-dependent apoptosis while angiotensin II and beta(1)-adrenergic-stimulation may be major causes of receptor-mediated apoptosis. Benefits due to treatment with ACE-inhibitors and beta-blockers appear to be in part due to reduced myocardial apoptosis. Moreover, infarct-related artery patency late after AMI may be a major determinant of myocardial apoptosis and clinical benefits deriving from an open artery late post AMI (the "open artery hypothesis") may be, at least in part, due to reduced myocardiocyte loss.
A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia (2003)

A tumor-specific, bcr-abl-derived fusion peptide vaccine can be safely administered to patients with chronic myelogenous leukemia (CML) and can elicit a bcr-abl peptide-specific T-cell immune response. In the present phase 2 trial, 14 patients with CML in chronic phase were vaccinated with 6 fusion peptides mixed with Quillaja saponaria (QS-21). No significant toxic effects were observed. In 14 of 14 patients, delayed-type hypersensitivity (DTH) and/or CD4 proliferative responses developed after beginning vaccinations, and 11 of 14 patients showed interferon-gamma (IFN-gamma) release by CD4 enzyme-linked immunospot (ELISPOT) at one or more time points. These responses were CD4(+)CD45RO(+). A peptide-specific CD8(+) interferon-gamma ELISPOT was found in 4 patients. Four patients in hematologic remission had a decrease in Philadelphia chromosome (Ph) percentage (3 concurrently receiving interferon-alpha and 1 on imatinib mesylate), and 3 patients in molecular relapse after allogenic transplantation became transiently polymerase chain reaction (PCR) negative after vaccination; 2 of these patients received concurrent donor lymphocyte infusion (DLI). All 5 patients on IFN-alpha ultimately reached a complete cytogenetic remission. In conclusion, a tumor-specific bcr-abl breakpoint peptide-derived vaccine can be safely administered and can reliably elicit measurable peptide-specific CD4 immune responses, including in patients after bone marrow transplantation, on interferon, or on imatinib mesylate. A relationship between the clinical responses and vaccination cannot be determined from this trial.
Adverse metabolic and cardiovascular consequences of circadian misalignment (2009)

There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h "day." Subjects ate 4 isocaloric meals each 28-h "day." For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling approximately 1,000 assays/subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept approximately 12 h out of phase from their habitual times, systematically decreased leptin (-17%, P < 0.001), increased glucose (+6%, P < 0.001) despite increased insulin (+22%, P = 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (+3%, P = 0.001), and reduced sleep efficiency (-20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work.
Extending the data storage capabilities of a Java-based smartcard (2002)

Present limitations on data memory for Java-based smartcards are a serious restriction for application development. The paper presents a method for enhancing the data memory using virtual memory. Transparency for the off-card application is achieved by the facade design pattern. Security constraints of smartcard applications have implications for the overall architecture and influence the proposed design. The architecture is used in the EU project FASME for storing a larger number of XML-based administrative documents on a JavaCard for electronic government purposes.
Adaptive Silver Films for Detection of Antibody−Antigen Binding (2005)

Antibody-antigen binding events at a monolayer protein concentration have been demonstrated on nanostructured adaptive silver films (ASFs) using surface-enhanced Raman scattering (SERS) and luminescence-based assays. It is shown that proteins stabilize and restructure the ASF to increase the SERS signal while preserving antigen-binding activity. Evidence for antibody-antigen binding on the ASF substrates is the distinct SERS spectral changes of the surface-bound antibody or antigen without special tags. The activity of the surface-bound proteins and their practical application are validated by independent immunochemical assays. Results are presented to demonstrate that these surfaces can be extended to protein arrays with detection applications distinct from current SERS, fluorescence, or luminescence methods.
Resistance to targeted cancer drugs through hepatocyte growth factor signaling (2014)

Cancer therapeutics that target a signaling pathway to which the cancer cells are addicted can deliver dramatic initial responses, but resistance is nearly always inevitable. A variety of mechanisms that cancer cells employ to escape from targeted cancer drugs have been described. We review here the role of Hepatocyte Growth Factor (HGF) and its receptor MET in drug resistance. We present data demonstrating that HGF can confer resistance to a number of kinase inhibitors in a variety of cancer cell lines and discuss our results in relation to the findings of others. Together, these data point at a major role for HGF/MET signaling in resistance to a variety of targeted cancer drugs.
Transient photovoltaic effects in metal–chlorophyll-a–metal sandwich cells (1975)

Photovoltaic effects in (Cr‖Chl-a‖Hg) and (Cr‖Chl-a‖Hg/In) sandwich cells under cw and microsecond pulsed excitation have been studied. The (Cr‖Chl-a‖Hg) cell exhibits strong rectification in the dark, whereas the effect in the (Cr‖Chl-a‖Hg/In) cell is weak and in the opposite direction. Upon cw excitation, the photovoltaic current in (Cr‖Chl-a‖Hg) quickly reaches a steady state with no obvious transients. The current flow is in the direction from Cr to Hg though the Chl-a film. The action spectrum of the cw as well as the pulsed photovoltaic currents matches closely the absorption spectrum of the Chl-a film. In contrast, the (Cr‖Chl-a‖Hg/In) cell behaves very differently. Transient photovoltaic currents preceding the steady state currents are seen under cw excitation in spectral regions where the Chl-a film absorbs strongly. The transient current flow is in the direction from Cr to Hg/In, but it quickly reverses direction to reach a steady state current of opposite sign. At wavelengths absorbed only slightly by Chl-a, the transients are not apparent, and only the steady state current is seen (Hg/In to Cr). The action spectrum of the steady state current shows an ’’inverse’’ type behavior revealing a minimum in response where Chl-a absorbs most. Under pulsed excitation, both the sign and the shape of the photovoltaic current pulse is seen to depend on the excitation wavelength. The action spectrum of the pulsed photovoltaic current in the (Cr‖Chl-a‖Hg/In) cell actually shows a ’’reversal’’ effect where the sign of the signal changes with wavelength. External bias voltage can be applied and it influences both the direction of the photocurrent as well as the shape of the action spectrum. The rectifying and the photovoltaic properties of both cells are directly related to the existence of potential barriers at the contact between the p-type Chl-a and the electrodes. These barriers appear to resemble the Schottky barriers used to describe the contacts between metals and inorganic semicondutors. The remarkable difference in the two cells can be explained as being due to the presence of a single barrier at the Cr‖Chl-a contact, in the (Cr‖Chl-a‖Hg) cell, and two opposing barriers in the (Cr‖Chl-a‖Hg/In) cell, one at the Cr‖Chl-a contact, as before, and a stronger barrier at the Chl-a‖Hg/In contact. The action spectra clearly reflect the relative strength of the front and the back barriers and the penetration depth of the excitation light. The appearance of the transient photocurrent spike is apparently due to the electrical polarization of the Chl-a microcrystals by light under the influence of the built-in field at the rectifying contacts. The switching effect in the photovoltaic current in the (Cr‖Chl-a‖Hg/In) cell is seen as a result of such polarization and the consequent mutual biasing of the two opposing contact barriers. The power conversion efficiency of the (Cr‖Chl-a/Hg) cell is better than 10−2% based on monochromatic illumination, a value among the best yet reported for organic cells.
Quantitative examination of the thermoelectric power of n-type Si in the phonon drag regime (1990)

A quantitative comparison between theory and experiment is presented for the thermoelectric power of n-type Si at low temperatures, where crystal boundary scattering of phonons is predominant. The expression for the Seebeck coefficient is obtained by simultaneously solving the coupled Boltzmann equations for electrons and phonons. The thermoelectric power is measured from samples of two different donor concentrations (ND=8×1014 cm−3 and 7×1015 cm−3) at temperatures ranging from 25 to 200 K, where the thickness is varied by etching the samples (370–73 μm). The phonon mean free path for crystal boundary scattering, determined from experimental thermopower, agrees well with that gained from the theory of thermal conductivity corrected for the phonon velocities of interest. An additional measurement of the thermal conductivity yields the mean free path for phonon–phonon scattering, which is about two orders of magnitude less than that obtained from thermopower. This difference confirms the influence of the different parts of the phonon spectrum involved in the calculation of the appropriate transport parameters.
A novel enzyme "N.ALPHA.-benzyloxycarbonyl amino acid urethane hydrolase II" from Lactobacillus fermenti 36 ATCC 9338. (1985)

A novel enzyme, "Nα-benzyloxycarbonyl amino acid urethane hydrolase II", was isolated from the cell-free extract of Lactobacillus fermenti 36 ATCC 9338. The enzyme showed hydrolytic activity toward Nα-benzyloxycarbonyl arginine. The purified enzyme was homogeneous as indicated by disc gel electrophoresis. The molecular weight of the native enzyme is about 200, 000 as estimated by gel filtration method. The isoelectric point was 5.0. The enzyme activity was inhibited by p-chloromercuri-benzoic acid and ethylenediaminetetraacetic acid. The presence of divalent cations (i.e., Co2+ or Zn2+) is essential for its activity.
Modulation of Gene Expression by Cancer Chemopreventive Dithiolethiones through the Keap1-Nrf2 Pathway (2003)

Enzyme inducers such as 3H-1,2-dithiole-3-thione (D3T) enhance the detoxication of environmental carcinogens and protect against neoplasia. The putative molecular sensor for inducers is Keap1, a sulfhydryl-rich protein that sequesters the transcription factor Nrf2 in the cytoplasm. Expression of these detoxication enzymes is blunted in nrf2-deficient mice; moreover, these mice are more sensitive to carcinogenesis, and the protective actions of dithiolethiones are lost with nrf2 disruption. Hepatic gene expression profiles were examined by oligonucleotide microarray analysis in vehicle- or D3T-treated wild-type mice as well as in nrf2 single and keap1-nrf2 double knockout mice to identify those genes regulated by the Keap1-Nrf2 pathway. Transcript levels of 292 genes were elevated in wild-type mice 24 h after treatment with D3T; 79% of these genes were induced in wild-type, but not nrf2-deficient mice. These nrf2-dependent, D3T-inducible genes included known detoxication and antioxidative enzymes. Unexpected clusters included genes for chaperones, protein trafficking, ubiquitin/26 S proteasome subunits, and signaling molecules. Gene expression patterns in keap1-nrf2 double knockout mice were similar to those in nrf2-single knockout mice. D3T also led to nrf2-dependent repression of 31 genes at 24 h; principally genes related to cholesterol/lipid biosynthesis. Collectively, D3T increases the expression of genes through the Keap1-Nrf2 signaling pathway that directly detoxify toxins and generate essential cofactors such as glutathione and reducing equivalents. Induction of nrf2-dependent genes involved in the recognition and repair/removal of damaged proteins expands the role of this pathway beyond primary control of electrophilic and oxidative stresses into secondary protective actions that enhance cell survival.
Heterodyne swept-source optical coherence tomography for complete complex conjugate ambiguity removal (2005)

Fourier domain (FD) techniques have increasingly gained attention in optical coherence tomography (OCT). This is primarily due to their demonstrated sensitivity of two to three orders of magnitude over conventional time-domain techniques. FDOCT images are subject to two primary sources of artifacts. First, a complex conjugate ambiguity arises because the Fourier transform of the real-valued spectral interferometric signal is Hermitian symmetric. This ambiguity leads to artifactual superposition of reflectors at positive and negative pathlength differences between the sample and reference reflectors. Second, noninterferometric and sample autocorrelation terms appear at dc, obscuring reflectors at zero pathlength difference. We show that heterodyne detection in swept-source OCT (SSOCT) enables the resolution of complex conjugate ambiguity and the removal of noninterferometric and autocorrelation artifacts. We also show that complex conjugate ambiguity resolution via frequency shifting circumvents fall-off induced by finite source linewidth in SSOCT when samples are shifted to large pathlength differences. We describe an efficient heterodyne SSOCT design that enables compensation of power losses from frequency-shifting elements. Last, we demonstrate this technique, coupled with wavenumber triggering and electronic demodulation, for in vivo imaging of the human anterior eye segment.
Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV) (1999)

In view of presumed non-pathogenicity, tumor suppressive properties, and site-specific integration of the viral genome the human parvovirus, adeno-associated virus (AAV) has gained great interest as a gene transduction vector. Data on the seroprevalence of antibodies to AAV vary between reports, probably due to the different serological methods used. In order to understand better the immune response to AAV during natural infection, sera from different age groups and various geographical regions were compared for AAV antibodies using an ELISA. The data show that the prevalence of antibodies to AAV is similar in Europe (Germany, France, and Switzerland), Brazil, and Japan, indicating worldwide infection. It was confirmed that infection takes place during childhood. However, declining seropositivity thereafter and a second increase of seropositivity after 30 years of age suggests reinfection or reactivation of latent virus in particular as the prevalence of IgM antibodies in adults is relatively high. Furthermore, pregnant women were found to be significantly more frequently seropositive than non-pregnant controls, hinting at a reactivation of persistent AAV (up to 80% of women carry AAV in genital tissue) in specific hormonal conditions, e.g., pregnancy. Cross-reaction of serum antibodies with the different AAV types (defined by complement fixation) was observed by ELISA and neutralization tests confirming earlier results. The results suggest an unstable AAV antibody response allowing lifelong reinfection or reactivation of persisting virus possibly due to partial immunotolerance after an infection in utero, at delivery or during early infancy.
Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager (2017)

There are limited strategies for the treatment of hepatocellular carcinoma (HCC). In this study, we prepared a Bispecific T cell engager (BiTE) targeting Glypican 3 (GPC3) and CD3. The GPC3/CD3 BiTE was prepared by fusing the single-chain variable fragment (scFv) of the humanized anti-GPC3 antibody (9F2) with the scFv of the anti-CD3 antibody (OKT3). The <i>in vitro</i> and <i>in vivo</i> cytotoxic activities of the GPC3/CD3 BiTE were evaluated against various HCC cell lines. The GPC3/CD3 BiTE could efficiently mediate the T cell killing of GPC3-positive HCC <i>in vitro</i>, which was dependent on GPC3 expression on the surface of HCC cells. Moreover, our study indicates that, in the presence of the GPC3/CD3 BiTE, T cells could efficiently destroy GPC3-positive human HCC cells <i>in vitro</i> and <i>in vivo</i>. Additionally, our study further proved that GPC3 is not expressed in normal tissues. Thus, GPC3 may be a cancer-specific antigen. Collectively, these findings suggest that this anti-GPC3 BiTE might be a promising anti-tumor reagent for patients with GPC3-positive HCC.
A systematic approach to the validation of process control parameters for monoclonal antibody production in fed-batch culture of a murine myeloma (2000)

A systematic approach to the validation of control ranges of control parameters for a cell culture process producing a monoclonal antibody is described. Specifically, the structure and functional activity of a monoclonal IgG1 antibody produced at the outer limits of numerical ranges of fed-batch culture control parameters such as pH and temperature were examined, with the aim of providing assurance that antibody produced under varying culture conditions was of consistent quality based on a carefully defined set of specifications. An experimental design was created using a half-fractional factorial design for fed-batch culture incorporating half of the thirty two possible combinations of five selected control parameters at high and low levels. Statistical analysis of all data gathered from the study allowed an assessment of the effects of the process control parameters at either high or low outer limits on fed-batch culture response variables such as growth rate and specific antibody productivity. Measured values for the responses of growth rate and specific antibody productivity throughout this study ranged from 0.22-0.44 d(-1) and 6.4-32 microg monoclonal antibody/10(6) cells/d respectively. Analytical characterisation of monoclonal antibody purified from each fed-batch culture considered the purity, structure and biological activity of the glycoprotein. All antibody preparations were identical to each other and to the current antibody reference standard or control. Glycosylation analysis of certain samples from the study demonstrated that the distribution of glycoforms of the antibody was not affected by the varying process control conditions of the fed-batch cultures.
5-Phosphoribosyl 1-pyrophosphate synthetase converts the acyclic nucleoside phosphonates 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and 9-(2-phosphonylmethoxyethyl)adenine directly to their antivirally active diphosphate derivatives (1991)

The acyclic nucleoside phosphonates 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) are potent inhibitors of DNA viruses and retroviruses, respectively. Unlike nucleoside triphosphates, the metabolically active (diphosphorylated) forms of HPMPA and PMEA (designated HPMPApp and PMEApp) are synthesized in a reversible reaction in which the pyrophosphate group of 5-phosphoribosyl 1-pyrophosphate (PRPP) is directly transferred to HPMPA and PMEA by purified PRPP synthetase. In this respect, PRPP synthetase does not act stereospecifically in that it recognizes both the S-enantiomer and the R-enantiomer of HPMPA as substrate. PRPP synthetase also recognizes other acyclic adenine and 2,6-diaminopurine riboside phosphonates as a substrate. It is now imperative to evaluate the potential role of PRPP synthetase, as activating enzyme, in the antiviral action of this type of molecules in intact cells.