gebhart/patrepeval huggingface dataset:
Results of toxicology studies with MPC-3100, an oral HSP90 inhibitor. (2011)

e13016 Background: MPC-3100, an orally bioavailable synthetic inhibitor of HSP90, has demonstrated efficacy in animal models and is currently in a phase I clinical study in cancer patients. Toxicology studies were conducted to support the long term safety of MPC-3100. Methods: MPC-3100 was administered to rats daily by gavage at 50, 100, or 200 mg/kg for 28 consecutive days or at 25, 50, or 100 mg/kg for 117 days. In cynomolgus monkeys, MPC-3100 was given daily at 10, 25, or 50/35 mg/kg for 28 days or at 6.25, 12.5, or 25 mg/kg for 113 days. Endpoints included weight gain, food consumption, clinical chemistries, hematology, urinalysis, pathologic, and histopathologic evaluation. ECGs were performed on monkeys and ophthalmoscopic examinations were conducted on all animals. Results: Daily doses of 200 mg/kg for 28 days or 100 mg/kg for 117 days exceeded the maximum tolerated dose in rats. Clinical observations were limited to gastrointestinal effects. Generalized lymphoid depletion, mild to moderate hepatobiliary effects, mild changes in hematology, electrolytes, AST/ALT, and changes in the nonglandular stomach and intestine were noted at doses ≥100 mg/kg/day. Toxicity was greater in males. All of the observations were reversible with cessation of treatment. The no observable adverse effect level (NOAEL) after 28 or 117 days was 100 and 50 mg/kg/day, respectively. In monkeys, mortality was noted following 4 days of treatment at 50 mg/kg and 20 days of treatment with dose reduction to 35 mg/kg. Inappetance and diarrhea were associated with gastrointestinal effects. Additional effects were lymphoid depletion, decreased erythrocytes, hemoglobin, hematocrit, and mild changes in electrolytes. Reticulocytes tended to be higher. There were no drug-related effects on clinical pathology parameters at doses up to 25 mg/kg for 113 days or changes to qualitative or quantitative ECG parameters in either study. The NOAEL was 25 or 12.5 mg/kg/day for 28 or 113 days of administration. There were no ocular findings in rats or monkeys. Conclusions: Long term administration of MPC-3100 to rats or monkeys at high doses may result in lymphoid depletion and mild changes in hematology and/or electrolytes. All adverse effects appeared to be reversible upon cessation of treatment.
BFL1 modulates apoptosis at the membrane level through a bifunctional and multimodal mechanism showing key differences with BCLXL (2018)

BFL1 is a relatively understudied member of the BCL2 protein family which has been implicated in the pathogenesis and chemoresistance of a variety of human cancers, including hematological malignancies and solid tumours. BFL1 is generally considered to have an antiapoptotic function, although its precise mode of action remains unclear. By quantitatively analyzing BFL1 action in synthetic membrane models and in cells, we found that BFL1 inhibits apoptosis through three distinct mechanisms which are similar but not identical to those of BCLXL, the paradigmatic antiapoptotic BCL2 family protein. Strikingly, alterations in lipid composition during apoptosis activate a prodeath function of BFL1 that is based on noncanonical oligomerization of the protein and breaching of the permeability barrier of the outer mitochondrial membrane (OMM). This lipid-triggered prodeath function of BFL1 is absent in BCLXL and also differs from that of the apoptotic effector BAX, which sets it apart from other BCL2 family members. Our findings support a new model in which BFL1 modulates apoptosis through a bifunctional and multimodal mode of action that is distinctly regulated by OMM lipids compared to BCLXL.
Monolithic integration of an ARROW-type demultiplexer and photodetector in the shorter wavelength region (1990)

A monolithic integration of an antiresonant reflecting optical waveguide (ARROW)-type demultiplexer and photodetector is discussed. The isolation was theoretically calculated to be -21.6 dB between the wavelengths of 0.78 and 0.88 mu m, with a maximum detecting efficiency of 58% in a short demultiplexing/photodetecting length of 100 mu m. The fundamental characteristic was demonstrated experimentally. This type of device can be applied to a wavelength division multiplexing (WDM) system with comparatively wide wavelength separation, e.g. 1.3- and 1.55- mu m wavelengths.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases (2007)

Although ubiquitin-enriched protein inclusions represent an almost invariant feature of neurodegenerative diseases, the mechanism underlying their biogenesis remains unclear. In particular, whether the topology of ubiquitin linkages influences the dynamics of inclusions is not well explored. Here, we report that lysine 48 (K48)- and lysine 63 (K63)-linked polyubiquitination, as well as monoubiquitin modification contribute to the biogenesis of inclusions. K63-linked polyubiquitin is the most consistent enhancer of inclusions formation. Under basal conditions, ectopic expression of K63 mutant ubiquitin in cultured cells promotes the accumulation of proteins and the formation of intracellular inclusions in the apparent absence of proteasome impairment. When co-expressed with disease-associated tau and SOD1 mutants, K63 ubiquitin mutant facilitates the formation of tau- and SOD-1-positive inclusions. Moreover, K63-linked ubiquitination was found to selectively facilitate the clearance of inclusions via autophagy. These data indicate that K63-linked ubiquitin chains may represent a common denominator underlying inclusions biogenesis, as well as a general cellular strategy for defining cargo destined for the autophagic system. Collectively, our results provide a novel mechanistic route that underlies the life cycle of an inclusion body. Harnessing this pathway may offer innovative approaches in the treatment of neurodegenerative disorders.
Introduction (1992)

It is surprising how few attempts have been made to describe or to reach a consensus on current knowledge on physical activity, exercise and health. The 32 published Symposia of the Society for the Study of Human Biology, for example, do not include a title on this topic. This is unexpected for a Society now nearly 35 years old and containing many members interested in this area. Recent symposia have examined Energy and Effort (Harrison, 1982) and Capacity for Work in the Tropics (Collins & Roberts, 1988), and disease and abnormality have been a recurring interest in the Society's symposia but physical activity and health has been left to others.
Effects of endurance training on thermoregulation in females (1980)

KOBAYASHI, YOSHIO, YOSHIRO ANDO, NORIAKI OKUDA, SHOZO TAKABA, and KOKICI OHARA. Effects of endurance training on thermoregulation in females. Med. Sci. Sports Exercise, Vol. 12, No. 5, pp. 361-364, 1980. Thermoregulatory responses to heat have been evaluated at rest in 27 university students; 11 female competitive athletes, 8 male non-athletes, and 8 female non-athletes. They rested for 2 h in an ambient temperature of 32°C, 40% RH with their legs immersed up to the knees in a stirred water bath of 42°C. Sweat rates of the female athletes were higher than the female non-athletes, but lower than the male non-athletes. Core temperature threshold for sweating was significantly lower in the female athletes than in the male and female non-athletes. The slope in sweat rate/core temperature relationship of the female athletes was nearly parallel to that of the female non-athletes. The thermoregulatory responses observed in the female athletes are thought to be comparable to those produced by heat adaptation. Comparing the heat responses in male and female non-athletes, no distinct sexual differences were observed in the rise in core temperature, mean skin temperature, and the core temperature threshold for sweating. On the other hand, the slope in the sweat rate/core temperature relationship was significantly steeper in males than in females. The beneficial modifications of heat responses demonstrated in the present study in female athletes are similar to those observed in male athletes.
Microbial fuel cell as new technology for bioelectricity generation: A review (2015)

Recently, great attentions have been paid to microbial fuel cells (MFCs) due to their mild operating conditions and using variety of biodegradable substrates as fuel. The traditional MFC consisted of anode and cathode compartments but there are single chamber MFCs. Microorganisms actively catabolize substrate, and bioelectricities are generated. MFCs could be utilized as power generator in small devices such as biosensor. Besides the advantages of this technology, it still faces practical barriers such as low power and current density. In the present article different parts of MFC such as anode, cathode and membrane have been reviewed and to overcome the practical challenges in this field some practical options have been suggested. Also, this research review demonstrates the improvement of MFCs with summarization of their advantageous and possible applications in future application. Also, Different key factors affecting bioelectricity generation on MFCs were investigated and these key parameters are fully discussed.
Circulating and tumor‐infiltrating myeloid cells predict survival in human pleural mesothelioma (2011)

Higher numbers of circulating monocytes are associated with poor survival in all patients with MPM and higher densities of tumor-infiltrating macrophages are associated with poor survival in patients with nonepithelial MPM. Both may enable a novel target for immunotherapy.
Catalytic Enantioselective Alkylation of Sulfenate Anions to Chiral Heterocyclic Sulfoxides Using Halogenated Pentanidium Salts (2014)

We report halogenated pentanidiums as phase-transfer catalysts for the asymmetric alkylation of sulfenate anions to various sulfoxides with high enantioselectivities (up to 99% ee) and yields (up to 99%). This approach gives access to enantioenriched heterocyclic sulfoxides that might not be compatible with strong oxidants or organometallic reagents. Computational studies have revealed that the multiple noncovalent interactions such as halogen bonds and nonclassical hydrogen bonds are involved.
Systemic effects of Wnt signaling (2013)

Wnt signaling plays a key role in several physiological and pathological aspects. Even if Wnt signal was first described more than 20 years ago, its role in systemic effects, such as angiogenesis and vascular disorders, bone biology, autoimmune diseases, neurological diseases, and neoplastic disorders, was only recently emerged through the use of animal and in vitro models. Moreover, Wnt signaling inhibitors, such as DKK-1, may be advantageously considered targets for the treatment of several diseases, including osteoporosis, vascular diseases, inflammatory diseases, neurological diseases, and cancer. Nevertheless, further studies are required to provide a complete understanding of this complex signaling pathway, and especially of its role in human diseases, considering the possible advantageous effects of Wnt signaling inhibitors on the progression of disease conditions.
Eine neue Eisen(III)‐oxidphase: ϵ‐Fe<sub>2</sub>O<sub>3</sub> (1963)

Abstract Im Gleichstromlichtbogen bei oxydierender Atmosphäre hergestelltes Eisenoxidaerosol stellt entgegen der Literatur ein Phasengemisch dar, aus dem eine neue Phase ϵ‐Fe 2 O 3 isoliert werden konnte. ϵ‐Fe 2 O 3 ist dunkelbraun und ferrimagnetisch mit einer Magnetanomalie bei 225°C. Bei einer Temperatur ab 500°C geht es in α‐Fe 2 O 3 über. Elementarzelle: Monoklin; a 0 = 12,97 Å; b 0 = 10,21 Å; c = 8,44 Å; β = 95° 20′ Z = 20; = 4,78 g/cm 3 .
Analysis of discourse structure with syntactic dependencies and data-driven shift-reduce parsing (2009)

We present an efficient approach for discourse parsing within and across sentences, where the unit of processing is an entire document, and not a single sentence. We apply shift-reduce algorithms for dependency and constituent parsing to determine syntactic dependencies for the sentences in a document, and subsequently a Rhetorical Structure Theory (RST) tree for the entire document. Our results show that our linear-time shiftreduce framework achieves high accuracy and a large improvement in efficiency compared to a state-of-the-art approach based on chart parsing with dynamic programming.
The Ultra-Select guidewire: a new nitinol guidewire for coronary angioplasty. (1992)

The Ultra Select¿ guidewire is a solid nitinol core torque wire that recently became available for use in coronary angioplasty. This wire has near one-to-one torque with kink resistant axial strength. The wire is radioopaque and highly visible. It is effective in negotiating severe tortuosity. Nitinol (nickel-titanium alloy) has unique properties that allow for specific performance advantages for use in coronary angioplasty. This report discusses this new guidewire and its use in coronary angioplasty.
Complex Indicated Angles Applied to Unresolved Radar Targets and Multipath (1971)

The off-axis angle indicated by a conventional monopulse radar is only the real part of a "complex indicated angle." The presence of unresolved targets or multipath distorts the real part (causing an erroneous angle indication) and also produces an imaginary part, which can easily be measured by processing the normally unused quadrature-phase component of the difference signal. Under certain conditions the angles, amplitude ratio, and relative phase of two unresolved targets can theoretically be determined by meas urements of the complex indicated angle on two pulses separated by a short interval. In the special case of multipath, known relationships between the unresolved target and image theoretically permit determination of target elevation with a single pulse.
Refinement of EM restored images using adaptive POCS (1991)

A new iterative algorithm for image restoration and point spread function (PSF) estimation is presented. The method initially restores the image with the expectation maximization (EM) algorithm. The resulting estimate is then significantly improved by using the adaptive row action projection (RAP) algorithm which is based on the theory of projection onto convex sets (POCS). The PSF is re-estimated using a least squares technique. Computer simulations show the method's competitiveness in restoring degraded images and estimating the PSF from noisy blurred images with unknown PSF.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Keratinocyte Migration, Proliferation, and Differentiation in Chronic Ulcers From Patients With Diabetes and Normal Wounds (2008)

Epithelialization of normal acute wounds occurs by an orderly series of events whereby keratinocytes migrate, proliferate, and differentiate to restore barrier function. The keratinocytes in the epidermis of chronic ulcers fail to execute this series of events. To better understand the epithelial dynamics of chronic ulcers, we used immunohistochemistry to evaluate proliferation, differentiation, adhesion, and migration in keratinocytes along the margin of chronic ulcers from patients with diabetes mellitus. We compared these features with keratinocytes from the migrating epithelial tongues of acute incisional and excisional wounds from normal volunteers. Keratinocytes at the chronic ulcer edge are highly proliferative (Ki67 proliferation marker), have an activated phenotype (K16), do not stain for keratins involved in epidermal differentiation (K10 and K2), and show a reduced expression of LM-3A32 (uncleaved, precursor of the alpha3 chain of laminin 5), a key molecule present on migrating epithelium. In contrast, keratinocytes in normal acute wound migrating epithelium do not express the proliferation marker Ki67 but do express K10, K2, and LM-3A32. A better understanding of molecular mechanisms involved in keratinocyte migration may lead to molecular targets for therapies for impaired wound healing.
Targeting Neuropeptide Receptors for Cancer Imaging and Therapy: Perspectives with Bombesin, Neurotensin, and Neuropeptide-Y Receptors (2014)

Receptors for some regulatory peptides are highly expressed in tumors. Selective radiolabeled peptides can bind with high affinity and specificity to these receptors and exhibit favorable pharmacologic and pharmacokinetic properties, making them suitable agents for imaging or targeted therapy. The success encountered with radiolabeled somatostatin analogs is probably the first of a long list, as multiple peptide receptors are now recognized as potential targets. This review focuses on 3 neuropeptide receptor systems (bombesin, neurotensin, and neuropeptide-Y) that offer high potential in the field of nuclear oncology. The underlying biology of these peptide/receptor systems, their physiologic and pathologic roles, and their differential distribution in normal and tumoral tissues are described with emphasis on breast, prostate, and lung cancers. Radiolabeled analogs that selectively target these receptors are highlighted.
ets-1 and ets-2 proto-oncogene expression in human leukemia cells and cell lines. (1989)

c-ets-1 and c-ets-2 are 2 proto-oncogenes known to be possibly involved in some human myelomonocytic leukemias. However, very few studies concern c-ets-1 and c-ets-2 RNA expression in human hematologic malignancies. We have studied 18 leukemic patients, and 10 cell lines for their ets RNA contents. c-ets-1 was strongly expressed in 5 and c-ets-2 in 8 of the 18 patients. All the cell lines expressed both c-ets-1 and c-ets-2 RNAs. This expression was highly variable from one patient to another, and from one cell line to another, regardless of the cellular leukemia subtype. The variability of this expression in patients may reflect differences in the proliferative potential of leukemic cells.
Drosophila homolog of the mammalian jun oncogene is expressed during embryonic development and activates transcription in mammalian cells. (1990)

By means of low-stringency cross-species hybridization to Southern DNA blots, human c-jun sequences were used to identify a unique Drosophila melanogaster locus (Djun). The predicted DJun protein is highly homologous to members of the mammalian Jun family in both the DNA binding and leucine zipper regions. Djun was mapped by in situ hybridization to position 46E of the second chromosome. It encodes a 1.7-kilobase transcript constitutively expressed at all developmental stages. Functionally, Djun in cooperation with mouse c-fos can trans-activate activator protein 1 DNA binding site when introduced into mammalian cells. Taken together, these data suggest that Djun, much like its mammalian homolog, may activate transcription of genes involved in regulation of cell growth, differentiation, and development. Furthermore, the identification of Djun allows one to exploit the genetics of Drosophila to identify genes in signal transduction pathways involving Djun and thus c-jun.
Plasma melatonin and insulin‐like growth factor‐1 responses to dim light at night in dairy heifers (2006)

The effect of dim (5, 10 and 50 1x) light at night on night plasma melatonin level (NML) and night plasma insulin-like growth factor-1 (IGF-1) level was determined in 12 prepubertal Holstein heifers (245 +/- 16 days age) using a 4 x 4 Latin Square design with 14-day treatment and 14-day recovery periods. Blood samples were collected at 23:00 hr (prior to the 8 hr night treatment which commenced at mid-night) on days 0, 3 and 13, and throughout the night at 01:00, 02:00, 03:00, 04:00, 06:00 and 08:00 hr on days 1, 4 and 14 of treatment. Plasma was analysed by radioimmunoassay for melatonin (all samples) and IGF-1 (samples for day 14, 04:00 hr only). Treatment (P = 0.03) and treatment x time (P = 0.02) were significant for NML. Exposure to 50 lx suppressed NML by 50% during the initial 2 hr of the night, but not thereafter. Exposure to 5 and 10 lx had no effect on NML. The NML response to 50 lx was found on all treatment days studied (treatment x time x day; P = 0.99). There was no treatment effect on plasma IGF-1 level (P = 0.89), but plasma IGF-1 level was higher (P = 0.001) during period 4. Plasma IGF-1 level and NML tended (P = 0.10) to be negatively correlated. Light intensities of 10 lx or less appear safe for use at night in dairy barns where darkness is recommended.
Dynamic Viscoelastic Properties of Cholesteric Liquid Crystals (1975)

Abstract Propagation of ultrasonic shear waves at frequencies from 2.4 to 18 MHz was studies in three 18-carbon unsaturated fatty acid esters of cholesterol, cholesteryl obleate (CO), cholesteryl linoleacte (CL), and cholesteryl linolenate (CLn), and three mixtures of the esters, 80% CL-20% CO, 95% CL-5% CO, and 80% CLn-20% CO. The oleate and linoleate esters are of biological importance because they comprise about 70–80% of the cholesteryl esters contained in atherosclerotic plaque. A shear wave pulse superposition technique was used to obtain the complex shear mechanical impedance and, hence, the dynamic shear viscosity and dynamic shear rigidity. The reflectance technique permits the study of liquid crystals whose long axes are oriented, in the plane of shear, with respect to the shearing direction of the ultrasonic wave. Falling ball viscosity measurements using a Hoeppler precision viscosimeter were made as a function of temperature from 35 tc 55°C. Shear wave measurements of dynamic shear rigidity and dynamic shear viscosity are shown as functions of temperature. This work represents the first measurement of both the dynamic viscosity and rigidity in a liquid crystalline substance. In the smectic phase, a dynamic shear rigidity is exhibited in all systems studied. The shear mechanical impedance of cholesteryl linoleate is found to be independent or orientation of the long axis of the molecule with respect to the direction of shear in agreement with the prediction of Brochard which is based on Leslie's hydrodynamic theory of the cholesteric state. The dynamic shear viscosity is found to be dependent on the shear rate. This may be explained in terms of a relaxation in the short range order present in the isotropic phase of both nematic and cholesteric compounds, as recently discussed by De Gennes.
Heterocyclic Ortho-Aminocarbonyl Compounds in the Friedländer Reaction Promoted by Chlorotrimethylsilane (2007)

A possibility of introduction of heterocyclic ortho-aminoketones into promoted by TMSCl Friedländer reaction with a wide set of α-methylenecarbonyl compounds was studied.A convenient synthetical method to obtain heterofused pyridine systems was elaborated; its scope and limitations were established as well.A set of derivatives of thieno [2,3-b] 5H-chromeno[2,3-b]pyridin-5-ones, pyrido[2,3-d]pyrimidin-2,4(1H,3H)-diones was obtained in high preparative yields.