gebhart/patrepeval huggingface dataset:
Bcl-2 Expression Identifies an Early Stage of Myogenesis and Promotes Clonal Expansion of Muscle Cells (1998)

We show that Bcl-2 expression in skeletal muscle cells identifies an early stage of the myogenic pathway, inhibits apoptosis, and promotes clonal expansion. Bcl-2 expression was limited to a small proportion of the mononucleate cells in muscle cell cultures, ranging from approximately 1-4% of neonatal and adult mouse muscle cells to approximately 5-15% of the cells from the C2C12 muscle cell line. In rapidly growing cultures, some of the Bcl-2-positive cells coexpressed markers of early stages of myogenesis, including desmin, MyoD, and Myf-5. In contrast, Bcl-2 was not expressed in multinucleate myotubes or in those mononucleate myoblasts that expressed markers of middle or late stages of myogenesis, such as myogenin, muscle regulatory factor 4 (MRF4), and myosin. The small subset of Bcl-2-positive C2C12 cells appeared to resist staurosporine-induced apoptosis. Furthermore, though myogenic cells from genetically Bcl-2-null mice formed myotubes normally, the muscle colonies produced by cloned Bcl-2-null cells contained only about half as many cells as the colonies produced by cells from wild-type mice. This result suggests that, during clonal expansion from a muscle progenitor cell, the number of progeny obtained is greater when Bcl-2 is expressed.
Anomalous size dependence of the non-linear mobility of DNA (2000)

A strong drift velocity non-linearity of the (doublestranded) DNA molecules vs. the electric field was discovered in gel electrophoresis. The non-linear drift velocity of the longer molecules is higher than that of the short ones, depending on the molecular size in a complex fashion. This behavior contrasts with that of the ordinary, linear, drift velocity where short molecules move faster than the long ones. The molecular size dependence of the non-linear velocity or the non-linear mobility has a non-monotonous wave-like character. The non-linear mobility offers possibilities of manipulating the drift velocity at will?the DNA fragments of different size can be made to move in opposite directions in pulsed field gel electrophoresis
Determination of Radiation-induced DNA Strand Breaks in Individual Cells by Non-radioactive Labelling of 3′ OH Ends (1995)

To quantify DNA strand breaks generated by ionizing radiation in single cells with preserved morphology, the number of radiation-induced 3' OH ends of nuclear DNA was determined by enzymatic labelling. Confluent CHO-K1 cells were irradiated with doses up to 100 Gy. After fixation and permeabilization of the cell monolayer the nuclear DNA was labelled with Digoxigenin-11-dUTP using terminal transferase. The incorporated nucleotide was detected with an anti-Digoxigenin antibody conjugated with alkaline phosphatase. The phosphatase bound was quantified by a colour reaction and the integrated optical densities of the cell nuclei were measured. For doses ranging from 20 to 100 Gy a linear relationship between dose and labelling signal was obtained. Repair experiments showed a fast component of repair with a half-time of about 14 min, followed by a slower decline to background values, which were reached after 6-8 h. This method allows the measurement of radiation-induced DNA strand breaks in morphologically preserved single cells in a reproducible way, which may be of importance in the prediction of tumour response in radiotherapy.
Effects of poly(ADP-ribose) polymerase inhibition on inflammatory cell migration in a murine model of asthma. (2004)

Our results demonstrate the pathogenetic role of PARP activation in a murine model of asthma. PARP selectively regulates the production of certain chemokines and cytokines in this experimental model, which may be responsible for some of the observed protective effects seen in the current murine asthma model.
Sleep-induced breathing instability (2013)

We present a view of the neuromechanical regulation of breathing and causes of breathing instability during sleep. First, we would expect transient increases in upper airway resistance to be a major cause of transient hypopnea. This occurs in sleep because a hypotonic upper airway is more susceptible to narrowing and because the immediate excitatory increase in respiratory motor output in response to increased loads is absent in non-REM sleep. Secondly, sleep predisposes to an increased occurrence of ventilatory "overshoots", in part because abruptly changing sleep states cause transient changes in upper airway resistance and in the gain of the respiratory controller. Following these ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include: a) hypocapnia-if transient, will inhibit carotid chemoreceptors and cause hypopnea, but if prolonged will inhibit medullary chemoreceptors and cause apnea; b) a persistent inhibitory effect from lung stretch; c) baroreceptor stimulation, from a transient rise in systemic blood pressure immediately following termination of apnea or hypopnea may partially suppress the accompanying hyperpnea; d) depression of central respiratory motor output via prolonged brain hypoxia. Once apneas are initiated, reinitiation of inspiration is delayed even though excitatory stimuli have risen well above their apneic thresholds, and these prolonged apneas are commonly accompanied by tonic EMG activation of expiratory muscles of the chest wall and upper airway.
Redundant functions of B-Myb and c-Myb in differentiating myeloid cells. (1997)

We show in this report that the human myeloid leukemia cell line GFD8 is a useful model to compare the biological function of the structurally related c-Myb and B-Myb proto-oncogenes and to investigate the c-myb domains required for this function. GFD8 cells are dependent for growth on granulocyte-macrophage colony-stimulating factor and differentiate in response to phorbol myristate acetate (PMA). We have stably transfected this cell line with constructs constitutively expressing c-Myb or B-Myb. Deregulated expression of both c-Myb and B-Myb inhibited the differentiation observed in response to PMA and, in particular, the induction of the CD11b and CD11c antigens on the cell surface, and the induction of adherence. Furthermore, c-Myb and B-Myb enhanced expression of CD13 upon PMA treatment. Although deregulated Myb expression did not alter the growth factor dependence of the cells, it led to an increase in G2 relative to G1 arrest in cells induced to differentiate in response to PMA, whereas control vector-transfected cells were blocked mostly in G1. This decrease in G1 block took place despite normal induction of the cyclin-dependent kinase inhibitor protein p21 (CIP1/WAF1). Thus, GFD8 cells stably expressing the human B-Myb protein behaved in a manner indistinguishable from those stably expressing C-Myb for both differentiation and cell cycle parameters. In agreement with these findings and differently from most previous reports, transactivation assays show that B-myb can indeed act as a strong activator of transcription. Finally, we demonstrated that although the DNA-binding domain of c-myb is required for both the differentiation block and the shift in cell cycle after PMA treatment, phosphorylation by casein kinase II and mitogen-activated protein kinase at positions 11 and 12 or 532 of c-myb, respectively, are not. We conclude that c-Myb and B-Myb may activate a common cellular program in the GFD8 cell line involved in both differentiation and cell cycle control.
Abstract 1658: M3814, a novel investigational DNA-PK inhibitor: enhancing the effect of fractionated radiotherapy leading to complete regression of tumors in mice (2016)

Abstract Physical or chemical agents that damage DNA such as ionizing radiation are among the most widely used classes of cancer therapeutics today. Double strand breaks (DSB) generated in DNA by radiation induce multitude of cellular responses, including DNA repair, cell cycle arrest or cell death if the damage is left unrepaired. A complex set of molecular events are responsible for DNA repair via two major mechanisms - homologous recombination (HR) or non-homologous end joining (NHEJ). DNA-PKcs with its regulatory protein subunits, Ku70 and Ku80, is an integral component of NHEJ and considered an attractive intervention point to inhibit DNA repair. We have developed an orally bioavailable, highly potent, and selective inhibitor of DNA-PK, M3814, for cancer therapy in combination with DNA damaging modalities such as radiation, and radio-chemotherapy. Here, we present the preclinical characterization of M3814 using biochemical, cellular and human tumor xenograft models. M3814 sensitized multiple tumor cell lines to radiation therapy in vitro and strongly enhanced the antitumor activity of ionizing radiation in vivo with complete tumor regression applying a clinically relevant fractionated radiation regimen. These effects are due to inhibition of DNA-PK protein kinase activity as demonstrated by the levels of DNA-PK autophosphorylation in human tumor cell lines, and xenograft tumors M3814 is currently investigated in PhI clinical trials. Citation Format: Frank T. Zenke, Astrid Zimmermann, Christian Sirrenberg, Heike Dahmen, Lubo Vassilev, Ulrich Pehl, Thomas Fuchss, Andree Blaukat. M3814, a novel investigational DNA-PK inhibitor: enhancing the effect of fractionated radiotherapy leading to complete regression of tumors in mice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1658.
Adherent Cell Function in Murine T Lymphocyte Antigen Recognition. I. A Macrophage-Dependent T Cell Proliferation Assay in the Mouse (1978)

The data in this report describe a T cell proliferation assay with nylon wool column-purified murine lymph node lymphocyte from animals immunized by footpad injection of antigen in CFA. It was found that the in vitro immune response of sensitized T cells to soluble protein antigens was functionally dependent on the presence of adherent cells, more specifically macrophages, at all concentrations of in vitro antigen challenge. The response was due to T cells in that cytotoxic treatment of the immune lymphocyte cells with anti-Thy 1.2 serum and complement effectively eliminated the antigen-specific DNA synthetic responses. The antigen-specific proliferation of murine lymphocytes depleted of adhereent cells could not be reconstituted with either guinea pig macrophages nor murine fibroblasts, indicating the existence of species and cell type specificity. In contrast to previous observations in the guinea pig, soluble products of cultured adherent cells could at least partially replace the function of intact macrophages in the response to antigen.
Effects of injecting growth hormone or thyroxine on milk production and blood plasma concentrations of insulin-like growth factors I and II in dairy cows (1987)

Three cows received injections of thyroxine (T4; 20 mg/day), four cows GH (40 mg/day) and three cows saline (control; 10 ml/day) on days 5-8 of a 16-day experimental period during peak lactation. Milk yield increased 13% in cows given GH (from 14.6 to 16.5 kg/day) and 15% in cows given T4 (from 15.8 to 18.2 kg/day) but did not change in control cows. Injection of T4 increased milkfat and lactose content but reduced milk protein content. Injection of GH was without effect on milk composition during the injection period but milk protein rose after injections ceased. Injection of T4 increased plasma concentrations of T4 and tri-iodothyronine six- to sevenfold, with maxima occurring on day 9. Injection of GH increased the plasma concentration of GH five- to tenfold 5 h after injection. The plasma concentration of insulin-like growth factor I (IGF-I) was increased in cows given GH in both morning (08.30 h) and afternoon (14.30 h) blood samples, the difference being greatest in afternoon samples in which plasma IGF-I content increased from 3.3 to 6.8 nmol/l. Injection of T4 reduced the plasma concentration of IGF-I in morning samples but the concentration in afternoon samples remained relatively constant throughout the 16-day experimental period. The plasma concentration of IGF-II rose in morning samples in all treatment groups to reach a maximum of 200-250 nmol/l by day 9. The galactopoietic response to injection of GH but not T4 was associated with an increase in plasma concentration of IGF-I. Changes in plasma concentration of IGF-II were not associated with changes in milk yield.
Engineered microsphere contrast agents for optical coherence tomography (2003)

Contrast agents are utilized in virtually every imaging modality to enhance diagnostic capabilities. We introduce a novel class of optical contrast agent, namely, encapsulating microspheres, that are based not on fluorescence but on scattering nanoparticles within the shell or core. The agents are suitable for reflection- or scattering-based techniques such as optical coherence tomography, light microscopy, and reflectance confocal microscopy. We characterize the optical properties of gold-, melanin-, and carbon-shelled contrast agents and demonstrate enhancement of optical coherence tomography imaging after intravenous injection of such an agent into a mouse.
Targets for Signal-transducing Protein Kinases (1988)

The transduction of signals from the external medium across the plasma membrane into the cell is a process that is essential to the functioning of multicellular organisms. There are several basic mechanisms of signal transduction, many of which involve protein phosphorylation. Protein phosphorylation is ideally suited for signal transduction, since protein kinases have an inbuilt mechanism for signal amplification, and protein phosphatases provide a means of reversing the signal when the stimulus is removed. The most common type of signal-transducing protein kinase is the family of growth factor receptor protein-tyrosine kinases (PTK), such as the epidermal growth factor (EGF) receptor. These receptors have an intrinsic signaling mechanism in which binding of ligand to an external domain activates a cytoplasmic protein kinase domain to phosphorylate target proteins in the mitogenic signal pathway. Approximately half of all known protein-tyrosine kinase genes appear to encode ligand-regulated surface receptors (Table 1).
Using starburst dendrimers as linker molecules to radiolabel antibodies (1990)

Starburst dendrimers, spherical polymers constructed from methyl acrylate and ethylenediamine, were successfully used to covalently couple synthetic porphyrins to antibody molecules. The dendrimers, as linker molecules, have great potential for increasing the specific activity of radiolabeled antibodies for tumor therapy and diagnosis.
Disassembly of Nanodiscs with Cholate (2007)

Nanodiscs are protein-lipid particles that furnish a nanometer-sized membrane environment for the investigation of membrane proteins. Nanodiscs assemble spontaneously upon the removal of cholate from an initial mixture of cholate, lipids, and engineered amphipathic proteins. A combined experimental-computational approach is applied here to study the disassembly of nanodiscs through the addition of cholate to preformed particles. For this purpose, small-angle X-ray scattering experiments and coarse-grained molecular dynamics simulations were performed and compared. The study offers a detailed view of nanodisc dynamics.
Radiation therapy in the management of cancer of the cervix. (1993)

In general, reported 5-year survival rates are 85% to 90% for stage IB, about 75% for stage IIA, 60% to 65% for IIB, 25% to 50% for stage IIIB, and 10% or less for stage IV. For bulky lesions, a combination of preoperative irradiation and hysterectomy has been tried; however, in some studies the results are no better than those noted with higher doses of irradiation alone.
The Freezing, Drying and Storage of Mammalian Skin (1952)

ABSTRACT The viability and general preservation of skin that has been subjected in vitro to freezing, drying and other procedures may be tested by transplanting it back to the animal from which it was originally removed. Rabbit’s ear skin withstands either slow or rapid freezing down to the temperature of liquid air. Slow freezing gives better preservation than rapid freezing, but impregnation with glycerol solutions protects skin against some of the harmful consequences of rapid freezing. Epidermal melanoblasts do not withstand rapid freezing unless they have been protected by glycerol solutions. Rapid thawing gives better preservation than slow thawing. Malpighian cells of the epidermis survive slow thawing after impregnation with glycerol solutions but not after impregnation with Ringer’s solution. Skin slowly frozen after impregnation with glycerol solution and stored for 4 months at—79°C. was indistinguishable, on transplantation, from a freshly removed graft. The storage of skin at—79°C. does not result in progressive deterioration during the period of storage. It is shown that the toxicity of glycerol to the various cellular constituents of skin is so slight that it may be disregarded. Isolated epidermal cells withstand exposure to 98·1 % glycerol at room temperature for half an hour. Skin does not withstand dehydration to a degree that results in a final overall water content below about 25 %. Impregnation with glycerol solutions does not increase its capacity to withstand dehydration.
Intra-articular corticosteroid injections in juvenile idiopathic arthritis (2003)

Therapeutic intervention with intra-articular steroid injections in juvenile idiopathic arthritis (JIA) has evolved from experience with adults with inflammatory joint disease, with the earliest report being published in 1951. The technique has subsequently been introduced into paediatric rheumatology practice, although much of the evidence supporting its use remains anecdotal or based on open, non-controlled studies. This review examines the body of evidence relating to many aspects of treating children with JIA with intra-articular steroids, and is approached from both a medical and a physiotherapy perspective. Where appropriate, important areas for future research are identified and discussed.
FK228 Analogues Induce Fetal Hemoglobin in Human Erythroid Progenitors (2012)

Fetal hemoglobin (HbF) improves the clinical severity of sickle cell disease (SCD), therefore, research to identify HbF-inducing agents for treatment purposes is desirable. The focus of our study is to investigate the ability of FK228 analogues to induce HbF using a novel KU812 dual-luciferase reporter system. Molecular modeling studies showed that the structure of twenty FK228 analogues with isosteric substitutions did not disturb the global structure of the molecule. Using the dual-luciferase system, a subgroup of FK228 analogues was shown to be inducers of HbF at nanomolar concentrations. To determine the physiological relevance of these compounds, studies in primary erythroid progenitors confirmed that JMA26 and JMA33 activated HbF synthesis at levels comparable to FK228 with low cellular toxicity. These data support our lead compounds as potential therapeutic agents for further development in the treatment of SCD.
CHARACTERISTICS OF YOUTHFUL BEEF CARCASSES IN RELATION TO WEIGHT, AGE AND SEX: III. MEAT QUALITY ATTRIBUTES (1971)

A total of 574 youthful beef carcasses from three sources comprising 168 steers, 147 heifers and 259 bulls were processed to study the influence of carcass weight, age and sex on beef quality. Source differences in pre-slaughter treatment were associated with differences in ultimate pH and in color of the longissimus dorsi muscle. Dark color and high pH values (pH &gt; 6.0) were characteristic of the 1. dorsi muscle from bulls subjected to the greatest pre-slaughter stress. Stress effects markedly influenced palatability factors, with dark-colored bull beef from this one source scoring significantly higher for tenderness, juiciness and flavor than beef from steers subjected to the same pre-slaughter treatment. For these bulls the correlation between tenderness and meat color score was −0.50. Comparisons within source groups indicated that in meat color and shear values at 72 hr post mortem, heifers were superior to bulls and inferior to steers. After excluding the stressed (high ultimate pH) bulls from one source there were no significant sex-source differences in shear value at 13 days. However, taste panel evaluations indicated unstressed bull beef to be less tender than beef from heifers. Heifers had significantly more marbling than comparable bulls or steers, but differences in percent ether extract were significant only for the heifer-bull comparison. Correlations between live-weight and the various quality measurements were generally insignificant. A negative relationship was indicated between tenderness and age for bull carcasses (correlations about −0.3 in terms of merit) and the amount of chemically determined intramuscular fat of bulls was positively correlated (0.3 to 0.4) with age.
Organic Field-Effect Transistors from Solution-Deposited Functionalized Acenes with Mobilities as High as 1 cm2/V·s (2005)

We present the device parameters for organic field-effect transistors fabricated from solution-deposited films of functionalized pentacene and anthradithiophenes. These materials are easily prepared in one or two steps from commercially available starting materials and are purified by simple recrystallization. For a solution-deposited film of functionalized pentacene, hole mobility of 0.17 cm2/V.s was measured. The functionalized anthradithiophenes showed behavior strongly dependent on the substituents, with hole mobilities as high as 1.0 cm2/V.s.
Reduction of Islet Amylin Expression and Basal Secretion by Adenovirus-Mediated Delivery of Amylin Antisense cDNA (1998)

Reduction of amylin content and secretion in rat islets was attempted by transduction with an adenovirus bearing a 0.2-kb fragment of rat amylin cDNA inserted in the antisense orientation (AdCMV-alpha amylin). Exposure of islets to AdCMV-alpha amylin at a multiplicity of infection (moi) of 200 (1.2 x 10(7) pfu/ml) reduced amylin mRNA levels by 37 +/- 5% (p < 0.005), whereas infection with an adenovirus expressing the reporter gene of beta-galactosidase (AdCMV-lacz) did not modify amylin expression. Transduction with the antisense construct was specifically associated with the decrease (30 +/- 6%; p < 0.001) in the amylin content. Insulin content was unaltered in AdCMV-alpha amylin islets compared to AdCMV-lacz-transduced or untransduced cells. Basal amylin secretion (2.8 mM glucose) was 36 +/- 3% (p < 0.005) lower in AdCMV-alpha amylin islets than in untransduced or AdCMV-lacz-transduced islets. In contrast, no difference in amylin secretion in response to high glucose concentrations (16.7 mM) was detected in AdCMV-alpha amylin-transduced islets. Thus, a reduction of amylin content and basal secretion in islet cells can be achieved by the adenovirus-mediated expression of antisense RNA.
Effects of microgravity and bone morphogenetic protein II on GFAP in rat brain (1998)

This study evaluated effects of bone morphogenetic protein II (BMP) on glial fibrillary acidic protein (GFAP) in the brain of female Fischer 344 rats during 14 days of spaceflight. GFAP mRNA decreased in vehicle-implanted rats flown on the space shuttle by 53 and 48% in the stratum moleculare and stratum lacunosum moleculare hippocampal subregions, respectively. GFAP mRNA was not significantly affected by BMP implantation during spaceflight. Rats returning from space exhibited a 56% increase in serum corticosterone. BMP treatment did not additively increase corticosterone elevations in microgravity but appeared to increase serum corticosterone and reduce GFAP mRNA in the stratum moleculare in control rats. These data suggest that exposure to microgravity reduces GFAP expression in hippocampal astrocytes.