gebhart/patrepeval huggingface dataset:
Common and Distinct Elements in Cellular Signaling via EGF and FGF Receptors (2004)

Signaling pathways that are activated by epidermal growth factor (EGF) or fibroblast growth factor (FGF) receptors have been identified and compared (detailed Connections Maps are available at Science's Signal Transduction Knowledge Environment). Both receptors stimulate a similar complement of intracellular signaling pathways. However, whereas activated EGF receptors (EGFRs) function as the main platform for recruitment of signaling proteins, signaling through the FGF receptors (FGFRs) is mediated primarily by assembly of a multidocking protein complex. Moreover, FGFR signaling is subject to additional intracellular and extracellular control mechanisms that do not affect EGFR signaling. The differential circuitry of the intracellular networks that are activated by EGFR and FGFR may affect signal specificity and physiological responses.
Characterization of two cold-sensitive mutants of the beta-galactosidase from Lactobacillus delbruckii subsp. bulgaricus. (1994)

Methoxylamine mutagenesis of the beta-galactosidase gene from Lactobacillus delbrückii subsp. bulgaricus was used to generate cold-sensitive variants. Two variants, P429S and L317F, were characterized kinetically in order to determine the enzymatic consequences of these mutations. The kinetic parameters Km and Vmax on the synthetic substrate o-nitrophenyl-beta-D-galactopyranoside have been determined over a temperature range of 11-45 degrees C. Only the Vmax of the two variants was significantly different than the wild-type enzyme over the temperature range studied. The Vmax of the L317F variant is reduced proportionately at all temperatures compared to the wild-type enzyme while the value of Vmax for the P429S mutant deviates from wild-type only at lower temperatures (in 2 mM Mg2+). This temperature-dependent effect on the Vmax of P429S can be suppressed by increasing the Mg2+ concentration. The results suggest that the binding of this essential metal ion is altered in the P429S variant such that its dissociation is increased by lowering the temperature.
[Botulinic toxin in patients with neurogenic dysfunction of the lower urinary tracts]. (2005)

Botulinic toxin (BT) is a new method of lowering intraurethral pressure in symptoms of obstructive voiding in patients with neurogenic dysfunction of the lower urinary tracts (LUT). Transperineal introduction of 100 units of BT type A (botox, Allergan) was used under electromyographic control into the external urethral sphincter of 9 patients (6 males and 3 females) with LUT neurogenic dysfunction aged 17 to 68 years (mean age 37.2 years). Two patients had subnormal detrusor contractility due to myelodysplasia and diabetic polyneuropathy, two other patients--non-incontinent striated urethral sphincter after hemorrhagic stroke and spinal contusion, five patients suffered from detrusor-sphincteral dyssynergia (DSD) resultant from Schmorl's hernia, multiple sclerosis, Charcot-Marie disease and ischemic stroke of the spinal cord. Three patients had cystostomic drainage. The rest of the patients complained of dysuria, three patients performed self-catheterization, mean volume of the residual urine was 170 ml (180-240 ml). In 10 days residual urine was not found in 2 patients with subnormal detrusor contractility and in 4 patients with DSD. Abdominal pressure fell from 75 to 39 cm, on the average. In DSD patients maximal detrusor pressure fell from 59 to 29 cm, on the average. Mean maximal urinary flow rate rose from 4.3 to 9.6 ml/s. In 20 days, on the average, suprapubic fistula healed in all the patients. In a month, therapeutic effect persisted in all the patients. Complications, side effects were not registered. BT treatment to induce adequate urine evacuation in neurological patients is a promising approach in neurourology. Further studies should find answers to questions about regimen of BT introduction, loss of sensitivity, new indications in urology.
The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines (2020)

The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.
The G Protein β Subunit Is a Determinant in the Coupling of Gs to the β1-Adrenergic and A2a Adenosine Receptors (2001)

The signaling specificity of five purified G protein betagamma dimers, beta(1)gamma(2), beta(2)gamma(2), beta(3)gamma(2), beta(4)gamma(2), and beta(5)gamma(2), was explored by reconstituting them with G(s) alpha and receptors or effectors in the adenylyl cyclase cascade. The ability of the five betagamma dimers to support receptor-alpha-betagamma interactions was examined using membranes expressing the beta(1)-adrenergic or A2a adenosine receptors. These receptors discriminated among the defined heterotrimers based solely on the beta isoform. The beta(4)gamma(2) dimer demonstrated the highest coupling efficiency to either receptor. The beta(5)gamma(2) dimer coupled poorly to each receptor, with EC(50) values 40-200-fold higher than those observed with beta(4)gamma(2). Strikingly, whereas the EC(50) of the beta(1)gamma(2) dimer at the beta(1)-adrenergic receptor was similar to beta(4)gamma(2), its EC(50) was 20-fold higher at the A2a adenosine receptor. Inhibition of adenylyl cyclase type I (AC1) and stimulation of type II (AC2) by the betagamma dimers were measured. betagamma dimers containing Gbeta(1-4) were able to stimulate AC2 similarly, and beta(5)gamma(2) was much less potent. beta(1)gamma(2), beta(2)gamma(2), and beta(4)gamma(2) inhibited AC1 equally; beta(3)gamma(2) was 10-fold less effective, and beta(5)gamma(2) had no effect. These data argue that the beta isoform in the betagamma dimer can determine the specificity of signaling at both receptors and effectors.
Immunoreactivity and function of oligosaccharides in cobra venom factor. (1994)

Cobra venom factor (CVF) is the nontoxic C-activating glycoprotein in cobra venom. It is a structural and functional analogue of complement component C3. Previous work has established that the major oligosaccharide chain of CVF is a symmetric fucosylated biantennary complex-type N-linked chain containing an alpha-galactosylated Le(x) antigenic epitope, Gal alpha 1-3Gal beta 1-4 (Fuc alpha 1-3) GlcNAc beta 1, a novel carbohydrate structure. We show that naturally occurring anti-alpha-Gal Ab present in normal human serum binds to CVF. In view of a possible human application of CVF, we studied the effect of this anti-alpha-Gal Ab on CVF function as well as the effect of oligosaccharide modification or removal on CVF activity and immunoreactivity with the anti-alpha-Gal Ab. The immunoreactivity of CVF with the anti-alpha-Gal Ab is abolished upon de-alpha-galactosylation or complete deglycosylation. De-alpha-galactosylated CVF and deglycosylated CVF were found to be equally active in forming a stable C3/C5 convertase with human factor B and in decomplementing human serum indicating that the oligosaccharide chains of CVF are not required for its C-activating function. Consistent with the unaltered functional activity, deglycosylation of the molecule caused only minor changes in secondary structure as judged by far UV circular dichroism analysis. However, the oligosaccharide chains appear to contribute to the thermal stability of CVF, because deglycosylation caused the molecule to be more sensitive to temperature. Inasmuch as rCVF produced in mammalian cells can be expected to contain sialylated oligosaccharide chains, we also prepared sialylated CVF by enzymatic sialylation of de-alpha-galactosylated and de-alpha-fucosylated CVF with 2,6-sialyltransferase. It was found that the secondary structure and the activity of sialylated CVF were unchanged compared to native CVF.
Telomerase activity exclusively in cervical carcinomas and a subset of cervical intraepithelial neoplasia grade III lesions: strong association with elevated messenger RNA levels of its catalytic subunit and high-risk human papillomavirus DNA. (1998)

In this study, we investigated telomerase activity and human telomerase reverse transcriptase (hTERT) mRNA expression in relation to high-risk human papillomavirus (HPV) DNA presence in the spectrum of cervical premalignant lesions. Reconstruction experiments revealed that telomerase activity determined by the telomeric repeat amplification protocol assay and hTERT mRNA by reverse transcriptase-PCR could be detected in down to 100 and 1 SiHa cervical cancer cells, respectively. Telomeric repeat amplification protocol analysis on cervical tissue specimens revealed that none of the histomorphologically normal cervical samples (n = 8) and cervical intraepithelial neoplasia (CIN) grade I (n = 10) and grade II (n = 8) lesions had detectable telomerase activity. However, telomerase activity was shown in 40% of CIN grade III lesions (n = 15) and 96% of squamous cell carcinomas (n = 24). Despite the fact that hTERT mRNA was found at much higher frequencies, semiquantitative reverse transcriptase-PCR revealed that elevated hTERT mRNA levels were strongly correlated with detectable telomerase activity. Furthermore, telomerase activity and elevated hTERT mRNA levels were only detected in cases that contained high-risk HPV DNA. In contrast, low or undetectable hTERT mRNA levels were demonstrated in both high-risk HPV positive and negative cases. These data indicate that telomerase activity detectable with the assay used and concomitant elevated levels of hTERT mRNA reflect a rather late step in the CIN to squamous cell carcinoma sequence, which follows infection with high-risk HPV.
Frequency spectrum analysis of finger photoplethysmographic waveform variability during haemodialysis (2010)

This study investigates the peripheral circulatory and autonomic response to volume withdrawal in haemodialysis based on spectral analysis of photoplethysmographic waveform variability (PPGV). Frequency spectrum analysis was performed on the baseline and pulse amplitude variabilities of the finger infrared photoplethysmographic (PPG) waveform and on heart rate variability extracted from the ECG signal collected from 18 kidney failure patients undergoing haemodialysis. Spectral powers were calculated from the low frequency (LF, 0.04-0.145 Hz) and high frequency (HF, 0.145-0.45 Hz) bands. In eight stable fluid overloaded patients (fluid removal of >2 L) not on alpha blockers, progressive reduction in relative blood volume during haemodialysis resulted in significant increase in LF and HF powers of PPG baseline and amplitude variability (P < 0.01), when expressed in mean-scaled units. The augmentation of LF powers in PPGV during haemodialysis may indicate the recovery and possibly further enhancement of peripheral sympathetic vascular modulation subsequent to volume unloading, whilst the increase in respiratory HF power in PPGV is most likely a sign of preload reduction. Spectral analysis of finger PPGV may provide valuable information on the autonomic vascular response to blood volume reduction in haemodialysis, and can be potentially utilized as a non-invasive tool for assessing peripheral circulatory control during routine dialysis procedure.
Trastuzumab Emtansine: A Unique Antibody-Drug Conjugate in Development for Human Epidermal Growth Factor Receptor 2–Positive Cancer (2011)

Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor (HER2)-targeted antibody-drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine), in phase III development for HER2-positive cancer. Extensive analysis of T-DM1 in preclinical studies has shown that T-DM1 combines the distinct mechanisms of action of both DM1 and trastuzumab, and has antitumor activity in trastuzumab- and lapatinib-refractory experimental models. Clinically, T-DM1 has a consistent pharmacokinetics profile and minimal systemic exposure to free DM1, with no evidence of DM1 accumulation following repeated T-DM1 doses. Although a few covariates were shown to affect interindividual variability in T-DM1 exposure and clearance in population-pharmacokinetics analyses, the magnitude of their effect on T-DM1 exposure was not clinically relevant. Phase I and phase II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are recruiting patients: EMILIA (NCT00829166) is evaluating T-DM1 compared with lapatinib plus capecitabine, and MARIANNE (NCT01120184) is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Additional combinations of T-DM1 (for example, with GDC-0941) and additional disease settings (early-stage HER2-positive breast cancer) are also under investigation. Data from the phase III trials and other studies of T-DM1-containing agents are eagerly awaited.
A reliable multicast framework for light-weight sessions and application level framing (1995)

This paper describes SRM (Scalable Reliable Multicast), a reliable multicast framework for application level framing and light-weight sessions. The algorithms of this framework are efficient, robust, and scale well to both very large networks and very large sessions. The framework has been prototyped in wb, a distributed whiteboard application, and has been extensively tested on a global scale with sessions ranging from a few to more than 1000 participants. The paper describes the principles that have guided our design, including the IP multicast group delivery model, an end-to-end, receiver-based model of reliability, and the application level framing protocol model. As with unicast communications, the performance of a reliable multicast delivery algorithm depends on the underlying topology and operational environment. We investigate that dependence via analysis and simulation, and demonstrate an adaptive algorithm that uses the results of previous loss recovery events to adapt the control parameters used for future loss recovery. With the adaptive algorithm, our reliable multicast delivery algorithm provides good performance over a wide range of underlying topologies.
Overexpression of Platelet-Derived Growth Factor Receptor α in Endothelial Cells of Hepatocellular Carcinoma Associated with High Metastatic Potential (2005)

The gene expression of hepatocellular carcinoma vascular endothelium is different between tumors with different metastatic potential. Platelet-derived growth factor receptor alpha, which is overexpressed in endothelium of highly metastatic hepatocellular carcinoma, may serve as a biomarker for predicting metastasis and a therapeutic target for highly metastatic hepatocellular carcinoma.
Metabotropic glutamate receptors and neuroadaptation to antidepressants: imipramine‐induced down‐regulation of β‐adrenergic receptors in mice treated with metabotropic glutamate 2/3 receptor ligands (2005)

Antidepressant drugs have a clinical latency that correlates with the development of neuroadaptive changes, including down-regulation of beta-adrenergic receptors in different brain regions. The identification of drugs that shorten this latency will have a great impact on the treatment of major depressive disorders. We report that the time required for the antidepressant imipramine to reduce the expression of beta-adrenergic receptors in the hippocampus is reduced by a co-administration with centrally active ligands of type 2/3 metabotropic glutamate (mGlu2/3) receptors. Daily treatment of mice with imipramine alone (10 mg/kg, i.p.) reduced the expression of beta-adrenergic receptors in the hippocampus after 21 days, but not at shorter times, as assessed by western blot analysis of beta1-adrenergic receptors and by the amount of specifically bound [3H]CGP-12177, a selective beta-adrenergic receptor ligand. Down-regulation of beta-adrenergic receptors occurred at shorter times (i.e. after 14 days) when imipramine was combined with low doses (0.5 mg/kg, i.p.) of the selective mGlu2/3 receptor agonist LY379268, or with the preferential mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.). Higher doses of LY379268 (2 mg/kg, i.p.) were inactive. This intriguing finding suggests that neuroadaptation to imipramine--at least as assessed by changes in the expression of beta1-adrenergic receptors--is influenced by drugs that interact with mGlu2/3 receptors and stimulates further research aimed at establishing whether any of these drugs can shorten the clinical latency of classical antidepressants.
Intraruminal administration ofMegasphaera elsdeniimodulated rumen fermentation profile in mid-lactation dairy cows (2011)

This study evaluated the effects of intraruminal administration of Megasphaera elsdenii on ruminal fermentation patterns, the profile of plasma metabolites, and milk yield and composition of mid-lactation dairy cows. Eight primiparous, ruminally cannulated Holstein cows were arranged in a paired 2×2 crossover design. Cows were randomly assigned to one of two treatments: 1) intraruminal inoculation of 35 ml suspension per day of M. elsdenii ATCC 25940 (MEGA), containing 10 8 cfu/ml of bacteria, dissolved in 35 ml of saline (0·15 m ), or 2) carrier alone (35 ml saline; CTR). Both postprandial and preprandial rumen volatile fatty acids (VFA) and plasma metabolite measurements were analysed. Postprandial VFA patterns were affected the most, with butyrate ( P &lt;0·01) and valerate ( P &lt;0·01) proportions increasing, and acetate ( P &lt;0·01), isobutyrate ( P =0·05) and isovalerate ( P &lt;0·01) decreasing in MEGA cows. Preprandial data measured at various days showed that MEGA dosage tended to increase the molar proportion of propionate ( P =0·09) and lower the acetate to propionate ratio ( P =0·07) in the rumen fluid. There was no effect of treatment on rumen pH and on the concentration of lactate in the rumen as well as on selected preprandial plasma metabolites. Postprandial plasma concentrations of cholesterol tended to increase ( P =0·07) in MEGA cows compared with CTR. Concentrations of non-esterified fatty acids (NEFA) in the plasma were lower in MEGA cows after the morning feeding ( P &lt;0·01). Sampling hour also affected plasma NEFA in this study. Plasma β-hydroxybutyrate (BHBA) were not affected by the treatment ( P &gt;0·05); however, after the morning feeding BHBA concentration was increased in both groups of cows. Dry matter intake and milk yield and composition were not affected by treatment. In conclusion, results indicate that M. elsdenii has the potential to modulate the rumen fermentation profile in mid-lactation Holstein cows, but these effects were only slightly reflected in changes in plasma metabolites and milk composition.
RESEARCH ON THE ACCESS NETWORK AND MAC TECHNIQUE FOR BEYOND 3G SYSTEMS (2007)

Based on the requirements of beyond 3G mobile communication systems, the access network architecture and media access control technique for B3G systems are studied. The proposed novel access network architecture, which can reduce network complexity and improve system performance, is introduced. Centralized mini-slot packet reservation multiple access (CMPRMA), based on OFDMA, is proposed, which not only can inherit the advantages of MPRMA and support real-time traffic well, but can also supply the resource reservation scheme for data traffic and support transmission for data traffic efficiently
Zhongyuan Offers Drilling Service for Microbes (2001)

No. 1 Drilling Company of Zhongyuan Petroleum Exploration Bureau and US-based Microbes Inc.signed a drilling engineering contract for six wells in Jilin Oil Field worth more than 11 million yuan in mid-October 2001.
Variability of hepatitis C virus (1995)

The discovery and characterization of the main causative agent of non-A, non-B hepatitis (NANBH) represent a major success in the application of cloning techniques in the identification of new infectious agents.'The technique that led to the characterization and the development of antibody tests for hepatitis C virus (HCV12 has since been applied successfully to determine the etiological agent of other diseases, such as hepatitis E virus, responsible for enterically transmitted NANBH.3HCV contains a positive sense RNA genome approximately 10,000 bases in length.In overall genome organization and presumed method of replication, it is most similar to members of the flauiviridae family particularly in the coding for a single polyprotein that is then cleaved into a series of structural proteins (nucleocapsid protein, two membrane glycoproteins) and nonstructural proteins, with presumed enzymatic roles in virus replication.Without a cell culture system to investigate differences in neutralization and cytopathic properties of HCV, nucleotide sequence comparisons and typing assays developed from sequence data have become the principal techniques for characterizing different variants of HCV.This type of analysis is relatively easy to perform, especially because viral sequences can be amplified by the polymerase chain reaction (PCR) directly from clinical specimens.Sequence comparisons of HCV have provided information about the virus a t several levels.It is possible to identify and classify HCV into a series of distinct "genotypes," which differ substantially in nucleotide sequence from one another and show varied geographical and epidemiological distributions.In particular, the inferred amino acid sequences of the envelope glycoproteins differ considerably, and it is likely that antibody elicited by infection with one genotype would fail to neutralize others.The extent of variation observed within HCV is comparable with that between serotypes of other RNA viruses, and may pose problems in the development of vaccines for HCV.
Thrombosis in Myeloproliferative Disorders: Prevalence, Prognostic Factors, and the Role of Leukocytes and JAK2V617F (2007)

An underlying myeloproliferative disorder (MPD), especially polycythemia vera (PV) or essential thrombocythemia (ET), is a risk factor for thrombosis. Considering large selected studies, prevalence rates for major thrombosis, at time of diagnosis, range from approximately 34 to 39% for PV and 10 to 29% for ET; the corresponding figures for thrombosis at follow-up are approximately 8 to 19% for PV and 8 to 31% for ET. In all instances, arterial events were more frequent than venous events. In both PV and ET, advanced age and history of thrombosis are independent predictors of recurrent thrombosis. In addition, leukocytosis, but not thrombocytosis, has been identified as a potential risk factor for thrombosis in both diseases. The particular observation is consistent with the laboratory demonstration, in these disorders, of increased number of activated granulocytes and granulocyte-platelet aggregates, upregulation of platelet P-selectin and tissue factor expression by granulocytes, and the antithrombotic value of hydroxyurea therapy. Most recently, a JAK2 gain-of-function mutation ( JAK2V617F) was described in virtually all patients with PV and approximately 50% of those with ET. Whether the presence of this specific mutation or its allele burden modifies the risk of thrombosis in patients with MPDs currently is under investigation.
Recombinant Vaccinia Virus Expressing the Herpes Simplex Virus Type 1 Glycoprotein C Protects Mice against Herpes Simplex Virus Challenge (1989)

The gene encoding the herpes simplex virus type 1 (HSV-1) glycoprotein C (gC) was isolated and cloned into a vaccinia virus insertion vector, and the resulting vaccinia-gC vector was used to construct a recombinant vaccinia virus that expressed gC (VVgC5). Infection of cells with VVgC5 resulted in cell surface expression of authentic HSV-1 gC. HSV-1 gC-specific neutralizing antibodies were produced in VVgC5-immunized mice, and lymphocytes exhibited an HSV-1-specific proliferation response in vitro following infection. More importantly, VVgC5-immunized mice were resistant to subsequent lethal HSV-1 challenge.