gebhart/patrepeval huggingface dataset:
Mitochondria as Therapeutic Targets of Estrogen Action in the Central Nervous System (2004)

Neuron viability and defense against neurodegenerative disease can be achieved by targeting mitochondrial function to reduce oxidative stress, increase mitochondrial defense mechanisms, or promote energetic metabolism and Ca2+ homeostasis. Exposure to estrogen prior to contact with toxic agents can protect neurons against a wide range of degenerative insults. The proactive defense state induced by estrogen is mediated by complex mechanisms ranging from chemical to biochemical to genomic but which converge upon regulation of mitochondria function. Estrogen preserves ATP levels via increased/enhanced oxidative phosphorylation and reduced ATPase activity thereby increasing mitochondrial respiration efficiency, resulting in a lower oxidative load. In addition, estrogen increases antiapoptotic proteins, Bcl-2 and Bcl-xL, which prevents activation of the permeability transition pore protecting against estrogen-induced increase in mitochondrial Ca2+ sequestration. These effects are likely to be enhanced by antioxidant effects of estrogen, preventing the initiation of the deleterious "mitochondrial spiral". The extent to which each of these mechanisms contribute to the overall proactive defense state induced by estrogen remains to be determined. However, each aspect of the cascade appears to make a significant if not obligatory impact on the neuroprotective effects of estrogens. Moreover each component of the cascade is required for estrogen regulation of mitochondrial function. Mechanisms of estrogen action and results of the clinical efficacy of estrogen therapy for prevention or treatment of Alzheimer's disease are considered in the context of clinical use of estrogen therapy and the design of brain selective estrogens or NeuroSERMs.
C‐myc oncogene expression: A marker for females at risk of breast carcinoma (1993)

In an attempt to identify patients at risk of breast cancer, 9E 10 c-myc monoclonal antibody was used to detect the oncogene products in 64 breast tissue biopsies. There were 44 specimens of benign breast disorders: 21 from patients who developed subsequent breast cancer, and 23 from patients who did not. The remainder were malignant tumor biopsies from those who developed breast cancer. C-myc over-expression was identified in 12 (60%) of the breast carcinomas; it was also noted in 13 (62%) of the benign biopsies from patients who developed subsequent breast carcinoma. Expression was observed in only 3 (13%) controls--patients who did not develop cancer. A prospective study is now warranted to determine the clinical usefulness of our findings.
GaAs lasers utilizing light propagation along curved junctions (1970)

A junction laser in which the light propagation within the device is along curved-junction paths is reported here. Path curvatures with radii ranging from 0.25 to 1.00 mm were obtained by the intentional introduction of curved diffused junctions. It was found that for radii of curvature smaller than a critical value of about 0.4 mm, the threshold-current density increases very rapidly. This value is in good agreement with the theoretical value, which is obtained by assuming that the gradient of the refractive index across the GaAs junction determines the minimum bending radius for low-loss propagation. The design of these curved-junction devices is critically dependent on the suppression of lasing along undesired junction paths perpendicular to the desired direction by bending these paths through a smaller than critical radius.
Further purification of a CFU-S inhibitor: in vivo effects after cytosine arabinoside treatment. (1983)

This paper describes a large scale extraction procedure which allows the preparation of a stable CFU-S inhibitor from fetal calf bone marrow. The use of BioGel P-2 gels results in an increase of the specific activity of the inhibitor as well as in the yield of the preparation. When injected into mice, the inhibitory fraction (Ve/Vo 1.17-1.8) prevent CFU-S entry into cycle after cytosine arabinoside at a dose of 4 micrograms per mouse. When administered during lethal protocols of Ara-C treatment, it significantly increases the percentage of surviving animals. Thus, this low molecular weight factor (below 2,000 D), devoid of species-specificity, enhances the tolerance of animals to high doses of chemotherapy and might be of interest in cancer treatment.
Shuffled belief propagation decoding (2003)

In this paper, we propose a shuffled version of the belief propagation (BP) algorithm for the decoding of low-density parity-check (LDPC) codes. We show that when the Tanner graph of the code is acyclic and connected, the proposed scheme is optimal in the sense of MAP decoding and converges faster (or at least no slower) than the standard BP algorithm. Interestingly, this new version keeps the computational advantages of the forward-backward implementations of BP decoding. Both serial and parallel implementations are considered. We show by simulation that the new schedule offers better performance/complexity trade-offs.
The high-power constricted plasma discharge column II. Experimental investigation (1971)

Measurements are made of the electrical parameters of high current discharges in capillaries and the results compared with a recent theory put forward by Wheeler in 1970. There is excellent agreement between the experimental electrical characteristic and the theoretical prediction which has the form EαI2/5. The capillary voltage drop is found to depend on the nature of the initial gas filling. This is unexpected and leads to a thorough investigation of the process and consequence of wall evaporation. It is shown that the discharge plasma is almost exclusively composed of ionized wall material with an average ionic charge of the order of 3. However, it is suggested that the initial phase of the discharge, which is controlled by the gas filling, influences the subsequent rate of evaporation of wall material.
Plasma cardiac natriuretic peptide determination as a screening test for the detection of patients with mild left ventricular impairment. (1996)

Plasma brain natriuretic peptide seemed to be a better indicator of left ventricular function than plasma atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However, the overall diagnostic accuracy of circulating atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide as indicators of normal and impaired ventricular function in an unselected group of patients with coronary heart disease and a high frequency of previous myocardial infarction was relatively modest.
La communication animale (1977)

Animal communication Animals ranging from insects to mammals communicate by means of chemicals, movements and sounds. Man also uses these modes of communication, but he adds his own unique kind of language
PATHOGENESIS OF TYPE 1 DENGUE VIRUS INFECTION IN SUCKLING, WEANLING AND ADULT MICE (1969)

Interrelationships between age of host and degree of adaptation of virus were studied by measuring lethality, virus production, antibody formation and interferon production. Low, medium, and high mouse-passaged lines (MP-3, MP-33, and MP-125) of type 1 dengue virus were inoculated intracerebrally into suckling, weanling, and adult mice. Each line multiplied to the highest titer in suckling mice and caused a rapidly fatal infection before the development of detectable circulating antibodies. Peak virus titers were lower in older mice, and marked dissimilarities appeared in the neurologic manifestation of disease as well as in mortality patterns. Weanling mice remained uniformly susceptible to the MP-125 and MP-33 lines but approximately 60 per cent survived infection with MP-3 virus. More pronounced differences occurred in adults. While MP-125 virus was still uniformly lethal, 95 and 10 per cent survived infections with MP-3 and MP-33 lines, respectively. In such cases irregular symptomatology and abortive CNS disease were not infrequent and recovery could be correlated with the development of an immune response and the elimination of virus from the brain. Exogenous interferon, passively administered to suckling animals prior to the inoculation of a lethal dose of any of the three virus lines, was capable of preventing mortality in a significant number. However, under the conditions of experimental infection with all nine virus-host combinations, detectable levels of actively induced interferon appeared in the brain only after virus titers reached approximately 105 per gram of brain and thereafter were directly related to virus titer. Such a relationship indicated that 1) interferon had little or no effect on the outcome of infection, 2) the differences in virulence between virus lines were not determined by their relative abilities to induce or respond to interferon and 3) the amount of interferon produced was not influenced by age.
PRL Tyrosine Phosphatases Regulate Rho Family GTPases to Promote Invasion and Motility (2006)

Phosphatase found in regenerating liver (PRL)-1, PRL-2, and PRL-3 [also known as PTP4A1, PTP4A2, and PTP4A3, respectively] constitute a unique family of putative protein tyrosine phosphatases (PTPs) modified by farnesylation. PRL-3 is amplified and its message is up-regulated in colorectal carcinoma metastases. Its ectopic expression promotes invasive and metastatic properties, supporting a causal link between PRL-3 and late-stage cancer development. However, neither PRL phosphatase substrates nor their signaling pathways have been defined. To address possible mechanisms for the biological activity of PRL-3, we sought to identify its downstream targets, reasoning that regulators of motility and invasion, such as the Rho family of small GTPases, might be logical candidates. We found that levels of active RhoA and RhoC were increased 4- to 7-fold in SW480 colorectal carcinoma cells expressing exogenous PRL-1 and PRL-3, and that PRL-mediated motility and Matrigel invasion were blocked by pharmacologic inhibition of Rho kinase (ROCK), a key Rho effector. In contrast, the activity of Rac was reduced by PRL PTPs, whereas Cdc42 activity was unaffected. PRL-3 stimulated transcription driven by the serum response element in a Rho-dependent manner. We also confirmed that the ability of PRL PTPs to induce invasion and motility is dependent on farnesylation. Catalytic PRL-3 mutants (C104A or D72A) were impaired in PRL-3-induced invasion and Rho activation, indicating that these properties require phosphatase activity. We conclude that PRL PTPs stimulate Rho signaling pathways to promote motility and invasion. Characterization of PRL activity and regulatory pathways should enhance efforts to understand and interfere with PRL-mediated events in invasion and metastasis.
The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications (2004)

Besides its role as an essential regulator of physiologic and pathologic angiogenesis, vascular endothelial growth factor (VEGF) triggers growth, survival, and migration of leukemia and multiple myeloma cells; plays a pivotal role in hematopoiesis; inhibits maturation of dendritic cells; and increases osteoclastic bone-resorbing activity as well as osteoclast chemotaxis. Dysregulation of VEGF expression and signaling pathways therefore plays an important role in the pathogenesis and clinical features of hematologic malignancies, in particular multiple myeloma. Direct and indirect targeting of VEGF and its receptors therefore may provide a potent novel therapeutic approach to overcome resistance to therapies and thereby improve patient outcome.
Cyclic capillary electrophoresis (2002)

A strategy is described here for increasing both the resolution and the flexibility of capillary electrophoresis performed in a sieving medium of ungelled polymer. This strategy is based on analysis and, sometimes, re-analysis that is done in several stages of constant-field electrophoresis. Enhancement-stages are between the analysis-stages. An enhancement-stage (i) increases the separation between peaks, while (ii) moving DNA molecules in the reverse direction. An enhancement-stage is based on an electrophoretic ratchet generated by a pulsed electrical field that can be zero-integrated. The ratchet-generating pulses are longer than the field pulses that have previously been used to improve the resolution of DNA molecules. No limit has been found to the resolution enhancement achievable. Apparently, diffusion-induced peak broadening is inhibited and, in some cases, may be reversed by the ratchet. The enhancement-stages are critically dependent on the electrical field-dependence of a plot of electrophoretic mobility as a function of DNA length. To generate the pulsed electrical field, a computer-controlled system with a time resolution of 30 microseconds has been developed. Programming is flexible enough to embed other pulses within ratchet-generating pulses. These other pulses can be either the previously used, shorter field-inversion pulses or high-frequency periodic oscillations previously found to sharpen peaks.
Pharmacokinetics Made Easy (1999)

Preface About the authors Definitions and Units of Symbols Equations Introduction 1. Clearance 2. Volume of Distribution 3. Half-life 4. How Drugs are Cleared by the Liver 5. Bioavailability and First-Pass Clearance 6. Predicting Drug Interactions and the Effects of Disease States for Metabolised Drugs 7. Clearance of Drugs by the Kidneys 8. Drug Protein Binding 9. Non-Linear Pharmacokinetics 10. How to Determine the Pharmacokinetic Parameters of a Drug 11. Pharmacodynamics-the Concentration-Effect Relationship 12. Designing Dose Regimens 13. Therapeutics Drug Monitoring Answers
60‐5: Late‐News Paper : 17‐inch Transparent AMOLED Display With Self‐Assembled Auxiliary Electrode (2019)

A novel top electrode (e.g., cathode) patterning technology using self‐assembly has been developed. The fabrication process is compatible with existing vacuum thermal evaporation techniques used in AMOLED mass production. The minimum feature size of the patterned electrode is demonstrated down to &lt;6 μm. This method can be used to fabricate an auxiliary electrode on the top of an AMOLED display with sheet resistance &lt; 1 Ω/□ and without damaging the sensitive front plane. Applications include reducing the IR drop in medium to large size panels and improving the performance of transparent AMOLED displays. A 17‐inch transparent AMOLED display panel with &gt;60% transmission and improved performance was demonstrated using this technique.
In vivo damage and recA-dependent repair of plasmid and chromosomal DNA in the radiation-resistant bacterium Deinococcus radiodurans (1994)

Deinococcus radiodurans R1 and other members of this genus share extraordinary resistance to the lethal and mutagenic effects of ionizing radiation. We have recently identified a RecA homolog in strain R1 and have shown that mutation of the corresponding gene causes marked radiosensitivity. We show here that following high-level exposure to gamma irradiation (1.75 megarads, the dose required to yield 37% of CFU for plateau-phase wild-type R1), the wild-type strain repairs > 150 double-strand breaks per chromosome, whereas a recA-defective mutant (rec30) repairs very few or none. A heterologous Escherichia coli-D. radiodurans shuttle plasmid (pMD68) was constructed and found to be retained in surviving D. radiodurans R1 and rec30 following any radiation exposure up to the highest dose tested, 3 megarads. Plasmid repair was monitored in vivo following irradiation with 1.75 megarads in both R1/pMD68 and rec30/pMD68. Immediately after irradiation, plasmids from both strains contained numerous breaks and failed to transform E. coli. While irradiation with 1.75 megarads was lethal to rec30 cultures, a small amount of supercoiled plasmid was regenerated, but it lacked the ability to transform E. coli. In contrast, wild-type cultures showed a cell division arrest of about 10 h, followed by exponential growth. Supercoiled plasmid was regenerated at normal levels, and it readily transformed E. coli. These studies show that D. radiodurans retains a heterologous plasmid following irradiation and repairs it with the same high efficiency as its chromosomal DNA, while the repair defect in rec30 prevents repair of the plasmid. Taken together, the results of this study suggest that plasmid DNA damaged in vivo in D. radiodurans is repaired by recA-dependent mechanisms similar to those employed in the repair of chromosomal DNA.
Stimulation of peripheral angiogenesis by vascular endothelial growth factor (VEGF). (1998)

Angiogenic growth factors constitutes a potentially novel form of therapy for patients with ischemic vascular disease. The feasibility of using recombinant formulations of angiogenic growth factors to augment collateral artery development by stimulation of capillary growth in animal models of myocardial and hindlimb ischemia has now been well established. In the case of vascular endothelial growth factor (VEGF) similar results may be achieved by gene transfer. Further laboratory and clinical studies may yield promising insights into the fundamental basis for native as well as therapeutic angiogenesis, and at the same time more explicitly define the manner in which therapeutic angiogenesis may be successfully incorporated into clinical practice.
Retinal–Salinixanthin Interactions in a Thermophilic Rhodopsin (2018)

In microbial rhodopsins (also called retinal proteins), the retinal chromophore is used for harvesting light. A carotenoid molecule has been reported to complement the retinal as light harvesting antenna in bacterial retinal proteins, although examples are scarce. In this paper, we present the formation of a novel antenna complex between thermophilic rhodopsin (TR) and the carotenoid salinixanthin (Sal). The complex formation and its structure were studied using UV-visible absorption as well as circular dichroism (CD) spectroscopies. Our studies indicate that the complex is formed in both the trimeric and monomeric forms of TR. CD spectroscopy suggests that excitonic coupling takes place between retinal and Sal. The binding of Sal with artificial TR pigments derived from synthetic retinal analogues further supports the contribution of the retinal chromophore to the CD spectrum. These studies further support the possibility of interaction between the 4-keto ring of the Sal and the retinal in TR-Sal complexes. Temperature-dependent CD spectra indicate that the positive band (ca. 482 nm) of the bisignate CD spectra of the studied complexes originates from the contribution of excitonic coupling and induced chirality of Sal in the protein binding site. The presence of a relatively smaller glycine residue in the vicinity of the retinal chromophore in TR is proposed to be crucial for binding with Sal. The results are expected to shed light on the mechanism of retinal-carotenoid interactions in other biological systems.
Approved and Experimental Small‐Molecule Oncology Kinase Inhibitor Drugs: A Mid‐2016 Overview (2016)

Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult-even for those working in the field-easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation. The purpose of this review is thus to provide an overview of the biomedical rationales for the kinases being targeted on the one hand, and the design principles, as well as chemical, pharmacological, pharmaceutical, and toxicological kinase inhibitor properties, on the other hand. Two issues that are especially important in kinase inhibitor research, target selectivity and drug resistance, as well as the underlying structural concepts, are discussed in general terms and in the context of relevant kinases and their inhibitors.
Mutants in the Exo I motif of Escherichia coli dnaQ: defective proofreading and inviability due to error catastrophe. (1996)

The Escherichia coli dnaQ gene encodes the proofreading 3' exonuclease (epsilon subunit) of DNA polymerase III holoenzyme and is a critical determinant of chromosomal replication fidelity. We constructed by site-specific mutagenesis a mutant, dnaQ926, by changing two conserved amino acid residues (Asp-12-->Ala and Glu-14-->Ala) in the Exo I motif, which, by analogy to other proofreading exonucleases, is essential for the catalytic activity. When residing on a plasmid, dnaQ926 confers a strong, dominant mutator phenotype, suggesting that the protein, although deficient in exonuclease activity, still binds to the polymerase subunit (alpha subunit or dnaE gene product). When dnaQ926 was transferred to the chromosome, replacing the wild-type gene, the cells became inviable. However, viable dnaQ926 strains could be obtained if they contained one of the dnaE alleles previously characterized in our laboratory as antimutator alleles or if it carried a multicopy plasmid containing the E. coli mutL+ gene. These results suggest that loss of proofreading exonuclease activity in dnaQ926 is lethal due to excessive error rates (error catastrophe). Error catastrophe results from both the loss of proofreading and the subsequent saturation of DNA mismatch repair. The probability of lethality by excessive mutation is supported by calculations estimating the number of inactivating mutations in essential genes per chromosome replication.
Association of RHAMM with E2F1 promotes tumour cell extravasation by transcriptional up‐regulation of fibronectin (2014)

Dissemination of cancer cells from primary to distant sites is a complex process; little is known about the genesis of metastatic changes during disease development. Here we show that the metastatic potential of E2F1-dependent circulating tumour cells (CTCs) relies on a novel function of the hyaluronan-mediated motility receptor RHAMM. E2F1 directly up-regulates RHAMM, which in turn acts as a co-activator of E2F1 to stimulate expression of the extracellular matrix protein fibronectin. Enhanced fibronectin secretion links E2F1/RHAMM transcriptional activity to integrin-β1-FAK signalling associated with cytoskeletal remodelling and enhanced tumour cell motility. RHAMM depletion abolishes fibronectin expression and cell transmigration across the endothelial layer in E2F1-activated cells. In a xenograft model, knock-down of E2F1 or RHAMM in metastatic cells protects the liver parenchyma of mice against extravasation of CTCs, whereas the number of transmigrated cells increases in response to E2F1 induction. Expression data from clinical tissue samples reveals high E2F1 and RHAMM levels that closely correlate with malignant progression. These findings suggest a requirement for RHAMM in late-stage metastasis by a mechanism involving cooperative stimulation of fibronectin, with a resultant tumourigenic microenvironment important for enhanced extravasation and distant organ colonization. Therefore, stimulation of the E2F1-RHAMM axis in aggressive cancer cells is of high clinical significance. Targeting RHAMM may represent a promising approach to avoid E2F1-mediated metastatic dissemination.