gebhart/patrepeval huggingface dataset:
Genetic counselling in the era of genomic medicine (2018)

An evidence base is necessary, incorporating implementation and outcome research, to enable health care systems, practitioners, patients and families to maximize the utility (medically and psychologically) of the new genomic possibilities.
Effects of Free Radical Scavengers on Renal Circulation after Ischaemia in the Rabbit (1983)

The intrarenal erythrocyte distribution, total renal blood flow and renal vascular resistance were studied before and during recirculation after 60 min of warm ischaemia in three groups of rabbits. One group was pretreated with superoxide dismutase, another with catalase and the third group was not pretreated at all. In non-pretreated ischaemic kidneys there was a significant trapping of labelled erythrocytes in the outer stripe of the medulla. This trapping was not seen in non-ischaemic control kidneys and was completely prevented by pretreatment with either superoxide dismutase or catalase. In non-pretreated ischaemic kidneys there was a transient increase in total renal blood flow during the first 5 min of recirculation, after which it returned to preischaemic values. After pretreatment with catalase the postischaemic increase in blood flow was more pronounced but again the blood flow returned to preischaemic values within 30 min. Pretreatment with superoxide dismutase resulted in a rapid postischaemic increase in blood flow which remained high throughout the 30 min period studied. The renal vascular resistance decreased initially during recirculation after ischaemia in both pretreated and non-pretreated kidneys. In the latter it returned to pre-ischaemic values within 10 min whereas a slower increase was observed after catalase pretreatment. After pretreatment with superoxide dismutase the resistance remained low during the 30 min recorded.
Selective Activation/Coupling of Polyhalogenated Nucleophiles in Ni/Cr-Mediated Reactions: Synthesis of C1–C19 Building Block of Halichondrin Bs (2015)

The C1-C19 building block 46 of halichondrin Bs was synthesized via a selective activation/coupling of β-bromoenone 34 with aldehyde 35 in a Ni/Cr-mediated reaction. The first phase of study was a method development to effect a coupling of a "naked" vinylogous anion with an aldehyde. The study with the coupling of 9 + 10 → 11 revealed: (1) β-bromoenone 9b is a better nucleophile than the corresponding β-iodo- and β-chloroenones 9a,c; (2) (Me)2Phen(OMe)2·NiCl2 13b is a better Ni-catalyst than (Me)2Phen(H)2·NiCl2 13a; and (3) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for an effective coupling. The second phase of study was a method development to realize a selective activation/coupling of polyhalogenated nucleophiles such as 34. The competition experiment of 10 + 9b over 10 + 31a-c revealed: (1) (Me)2Phen(OMe)2·NiCl2 13b is more effective than (Me)2Phen(H)2·NiCl2 13a for the required selective activation/coupling; (2) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for discriminating β-bromoenone 9b from the three types of vinyl iodides 31a-c. The third phase of study was an application of the developed method to execute the proposed coupling of 34 + 35 → 36. For this application, a polyether-type Ni-catalyst 37c, readily soluble in the reaction medium, was introduced to achieve the selective activation/coupling with higher efficiency. With use of ion-exchange resin-based device, the coupling product 36 was transformed to the C1-C19 building block 46 of halichondrin Bs without purification/separation of the intermediates.
Nascent RNA Sequencing Reveals Widespread Pausing and Divergent Initiation at Human Promoters (2008)

RNA polymerases are highly regulated molecular machines. We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and mapped to the genome. We show that peaks of promoter-proximal polymerase reside on approximately 30% of human genes, transcription extends beyond pre-messenger RNA 3' cleavage, and antisense transcription is prevalent. Additionally, most promoters have an engaged polymerase upstream and in an orientation opposite to the annotated gene. This divergent polymerase is associated with active genes but does not elongate effectively beyond the promoter. These results imply that the interplay between polymerases and regulators over broad promoter regions dictates the orientation and efficiency of productive transcription.
Cardiovascular development in the zebrafish I. Myocardial fate map and heart tube formation (1993)

We have analyzed the origin of cardiac progenitors in the zebrafish embryo by injection of single blastomeres with a lineage tracer dye, and examined the formation of the zebrafish heart tube by serial sectioning of immunostained embryos. At the 512-cell stage (early blastula), most cardiac progenitors lie in a marginal zone that extends from 90 degrees longitude (midway between the future dorsal and ventral axis) through 180 degrees longitude (the future ventral axis) to 270 degrees longitude. By focusing on myocardial progenitors located at 90 degrees (and 270 degrees) longitude, we found that a single cell injected in the early blastula can contribute progeny to both the atrium and ventricle. A cell injected in the midblastula contributes progeny to either the atrium or ventricle, but not both. This analysis suggests that, at least for these myocardial progenitors, the atrial and ventricular lineages separate in the midblastula. Precardiac cells involute early during gastrulation and turn towards the animal pole with other early involuting cells. These cardiogenic cells reach the embryonic axis around the 8-somite stage, and there they coalesce to form a pair of myocardial tubular primordia on either side of the midline. By the 21-somite stage, the tropomyosin-immunoreactive myocardial tubes have moved closer to each other, and a distinct group of cells, the endocardial progenitor cells, sits medially between them. The myocardial tubes then fuse to enclose the endocardial cells and form the definitive heart tube. By 22 hours postfertilization (26-somite stage), the heart tube is clearly beating. The regionalization of cardiac myosin heavy chain expression distinguishes the cardiac chambers at this stage, although they are not morphologically delineated until 36 hours. This work shows that cardiogenic regions can be identified in the early blastula, and that chamber restriction seems to arise in the midblastula. Additionally, it provides the basis for embryological perturbation at the single cell level, as well as for the genetic analysis of heart tube formation in the zebrafish.
Enhancement of Exciton Exchange Interaction by Quantum Confinement in CdSe Nanocrystals (1995)

We have investigated the degree of linear polarization and time behaviour of photoluminescence of very small size CdSe nanocrystals under size-selective excitation. At low temperature we observe a luminescence line Stokes-shifted by a few meV and its phonon replica. The degree of linear polarization is positive at short times then becomes negative and remains constant and equal to -15%. The following model is proposed. The exciton state is split by electron-hole exchange interaction into two states with the optically forbidden state at lower energy. Laser light creates excitons in the upper energy state. The luminescence line arises from the lower energy state where excitons have relaxed after a few tens of ps. Recombination is made possible through a phonon assisted virtual transition to the confined B-exciton state. As a result the polarization degree is negative at long times. The value of the exchange energy obtained from the luminescence Stokes shift (8 meV in 40Å-diameter nanocrystals) is much larger than the bulk value (0.1 meV). The enhancement of exchange interaction by quantum confinement and the value of the degree of polarization are in good agreement with theoretical estimates.
Single image haze removal using dark channel prior (2009)

In this paper, we propose a simple but effective image prior - dark channel prior to remove haze from a single input image. The dark channel prior is a kind of statistics of the haze-free outdoor images. It is based on a key observation - most local patches in haze-free outdoor images contain some pixels which have very low intensities in at least one color channel. Using this prior with the haze imaging model, we can directly estimate the thickness of the haze and recover a high quality haze-free image. Results on a variety of outdoor haze images demonstrate the power of the proposed prior. Moreover, a high quality depth map can also be obtained as a by-product of haze removal.
Morphological characterization of cardiomyocytes isolated from a transplantable cardiac tumor derived from transgenic mouse atria (AT-1 cells). (1991)

We have developed a transplantable tumor lineage derived from transgenic mouse atrial cardiomyocytes that express the SV40 large T oncogene and have named these cardiomyocytes AT-1 cells. In this study, the transplantable tumors, freshly isolated tumor cardiomyocytes, and cultured tumor cardiomyocytes were examined using phase-contrast microscopy, autoradiography, and electron microscopy. The vast majority of the subcutaneous tumor cells, greater than 90% of the cellular mass of the tumor, exhibited sarcomeric banding. Ultrastructural characteristics typical of in vivo atrial cardiac muscle cells, including well-organized myofibrils, gap junctions, and atrial-specific cytoplasmic granules, were observed in in situ and in freshly isolated AT-1 cells. Those cells that did not contain some form of organized myofibrils were primarily vascular elements, such as endothelial cells. Labeling with [3H]thymidine indicated that greater than 90% of cultured AT-1 cells were synthesizing DNA; furthermore, many cells could be seen undergoing cell division. Electron microscopy revealed that the cultured AT-1 cardiomyocytes contained all of the above-described characteristics, including a well-developed transverse tubular system.
Methodology to Incorporate Biologically Effective Dose and Equivalent Uniform Dose in Patient-Specific 3-Dimensional Dosimetry for Non-Hodgkin Lymphoma Patients Targeted with 131I-Tositumomab Therapy (2010)

The inclusion of radiobiologic effects in the dosimetry modeling of internal emitter therapy provides a powerful platform to investigate correlations of patient outcome with planned therapy.
Light-emitting diodes based on conjugated polymers (1992)

Conjugated polymers offer, in principle, the combination of polymer processibility together with interesting electronic properties. The feasibility of controlling materials to give structures with well-defined properties has provided an important focus for the experimental work. A decade or so since the first work on the electronic properties of these materials there are now a range of polymers which provide a range of semiconducting properties, and with band-gaps from the near IR (1.5 eV) to the UV (3 eV). Some of these polymers are now sufficiently clean to allow their use as active components in semiconductor device structures. The authors discuss the developments made in this area.<
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Fc gamma receptor activation induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells. (1992)

Crosslinking of the low affinity immunoglobulin G (IgG) Fc receptor (Fc gamma R type III) on natural killer (NK) cells initiates antibody-dependent cellular cytotoxicity. During this process, Fc gamma R stimulation results in the rapid activation of phospholipase C (PLC), which hydrolyzes membrane phosphoinositides, generating inositol-1,4,5-trisphosphate and sn-1,2-diacylglycerol as second messengers. We have recently reported that PLC activation after Fc gamma R stimulation can be inhibited by a protein tyrosine kinase (PTK) inhibitor. Based on the paradigm provided by the receptor tyrosine kinases, we investigated whether PLC-gamma 1 and/or PLC-gamma 2 are expressed in NK cells, and whether the PLC-gamma isoforms are tyrosine phosphorylated in response to Fc gamma R stimulation. Immunoblotting analyses with PLC-gamma 1- and PLC-gamma 2-specific antisera demonstrate that both isoforms are expressed in human NK cells. Furthermore, Fc gamma R crosslinking triggers the tyrosine phosphorylation of both PLC-gamma 1 and PLC-gamma 2 in these cells. Phosphorylation of both isoforms is detectable within 1 min, and returns to basal level within 30 min. Pretreatment with herbimycin A, a PTK inhibitor, blocked the Fc gamma R-induced tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2, and the subsequent release of inositol phosphates. These results suggest that Fc gamma R-initiated phosphoinositide turnover in human NK cells is regulated by the tyrosine phosphorylation of PLC-gamma. More broadly, these observations demonstrate that nonreceptor PTK(s) activated by crosslinkage of a multisubunit receptor can phosphorylate both PLC-gamma isoforms.
The Development of Protein Bodies in the Storage Tissues1 (1981)

Homogenates of the developing endosperms of maize, wheat, and barley and of developing cotyledons of peas have been separated on sucrose density gradients. Protein bodies have been recognized by their content of storage proteins, their density, and their appearance under the electron microscope. The distribution of the endoplasmic reticulum was followed by measuring NADH-cytochrome &lt;it&gt;c&lt;/it&gt; reductase. Glutamate dehydrogenase, catalase, and triose phosphate dehydrogenase—respectively marker enzymes for mitochondria, microbodies, and plastids—were also present in the gradients. Differences were found between the different species with respect to the association between the endoplasmic reticulum and the storage proteins. There was no evidence for any vacuolar marker enzymes associated with the cereal protein bodies. The protein bodies of wheat and barley appear to be similar to each other but differ from maize in that the latter have much more endoplasmic reticulum associated with them. In contrast the protein bodies of peas co-sediment with vacuolar marker enzymes.
DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. III. Immunocytochemical localization (1984)

Immunocytochemical studies have been carried out to determine the regional and cellular distribution of DARPP-32, a protein the phosphorylation of which can be regulated by dopamine and cAMP in intact cells. These immunocytochemical studies indicate tha DARPP-32 is localized primarily in those brain regions enriched in dopaminergic nerve terminals. Moreover, the staining pattern supports the conclusion that the DARPP-32 is present in dopaminoceptive neurons, i.e., neurons that receive a dopamine input, and that it is absent from the dopaminergic neurons themselves. Within the caudatoputamen, nucleus accumbens, olfactory tubercle, bed nucleus of the stria terminalis, and portions of the amygdaloid complex, all of which receive a strong dopamine input, DARPP-32 immunoreactivity is present in neuronal cell bodies and dendrites. In brain regions that are known to receive projections from these nuclei, puncta (presumed nerve terminals) are strongly immunoreactive for DARPP-32 but indigenous cell bodies and dendrites are not immunoreactive. These target areas include the globus pallidus, ventral pallidum, entopeduncular nucleus, and the pars reticulata of the substantia nigra. No immunoreactivity is detected in neuronal cell bodies or dendrites in any of the dopaminergic nuclei. Furthermore, nerve terminals immunoreactive for DARPP-32 do not resemble dopaminergic varicosities in either their morphology or their pattern of distribution. Many neurons are weakly immunoreactive for DARPP-32 and some of these are found in areas that apparently lack a dopaminergic input: weakly labeled neuronal cell bodies and dendrites were found throughout the neocortex, primarily in layer VI, and in the Purkinje neurons of the cerebellum. DARPP-32 immunoreactivity is also present in certain glial cells, especially in the median eminence, arcuate nucleus, and medial habenula. The present immunocytochemical studies, taken together with biochemical studies (Hemmings, H.C., Jr., A.C. Nairn, D.W. Aswad, and P. Greengard (1984) J. Neurosci. 4: 99-110; Walaas, S.I., and P. Greengard (1984) J. Neurosci. 4: 84-98) on DARPP-32, indicate that DARPP-32, is present in the subclass of dopaminoceptive neurons containing D-1 receptors (dopamine receptors coupled to adenylate cyclase). DARPP-32 may be an effective marker for certain of the actions of dopamine that are mediated through cAMP and its associated protein kinase.
Multivariate-Gaussian-based cepstral normalization for robust speech recognition (2002)

We introduce a new family of environmental compensation algorithms called multivariate gaussian based cepstral normalization (RATZ). RATZ assumes that the effects of unknown noise and filtering on speech features can be compensated by corrections to the mean and variance of components of Gaussian mixtures, and an efficient procedure for estimating the correction factors is provided. The RATZ algorithm can be implemented to work with or without the use of "stereo" development data that had been simultaneously recorded in the training and testing environments. "Blind" RATZ partially overcomes the loss of information that would have been provided by stereo training through the use of a more accurate description of how noisy environments affect clean speech. We evaluate the performance of the two RATZ algorithms using the CMU SPHINX-II system on the alphanumeric census database and compare their performance with that of previous environmental-robustness developed at CMU.
Genetic encoding of DNA nanostructures and their self-assembly in living bacteria (2016)

The field of DNA nanotechnology has harnessed the programmability of DNA base pairing to direct single-stranded DNAs (ssDNAs) to assemble into desired 3D structures. Here, we show the ability to express ssDNAs in Escherichia coli (32-205 nt), which can form structures in vivo or be purified for in vitro assembly. Each ssDNA is encoded by a gene that is transcribed into non-coding RNA containing a 3'-hairpin (HTBS). HTBS recruits HIV reverse transcriptase, which nucleates DNA synthesis and is aided in elongation by murine leukemia reverse transcriptase. Purified ssDNA that is produced in vivo is used to assemble large 1D wires (300 nm) and 2D sheets (5.8 μm(2)) in vitro. Intracellular assembly is demonstrated using a four-ssDNA crossover nanostructure that recruits split YFP when properly assembled. Genetically encoding DNA nanostructures provides a route for their production as well as applications in living cells.
Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma (2007)

NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF.
The effects of the stress caused by experimental procedures on alanine aspartate, glutamate and glutamine in rat liver (1971)

Rats were stressed by intravenous injection, tail-warming or moderate restraint for 30s, i.e. by stresses imposed by normal handling during experiment. Liver glutamate concentrations were greatly affected. The results were substantially the same in two varieties of rat (Wistar and Sprague-Dawley), in two laboratories, in experiments carried out by two sets of workers, and after all three stresses. The following detailed results refer to Wistar rats. 1. In starved rats at 20 degrees C and 30 degrees C and in post-absorptive rats at 20 degrees C stress by injection raised liver glutamate concentrations from 1.54, 1.57 and 1.88mumol/g wet wt. 30s after injection to 3.4, 2.7 and 3.6mumol/g wet wt. respectively a few minutes later. In starved rats at 20 degrees C the concentration then fell slowly to 2.3mumol/g wet wt., in starved rats at 30 degrees C it remained steady, and in post-absorptive rats at 20 degrees C it rose slowly to about 4.3mumol/g wet wt. The final values seemed fairly steady and corresponded to an ;alert' state. 2. In starved rats at 20 degrees C anaesthesia, with or without injection or cannulation during it, raised glutamate concentrations to the ;alert' values, which were maintained for 2-3h. 3. Liver alanine concentration in post-absorptive rats initially fell from 1.5 to 0.8mumol/g, and then stayed fairly constant. 4. Aspartate and glutamine concentrations altered only in starved rats, and proportionately much less than those of glutamate. 5. The necessity for knowing the time-dependence of glutamate concentrations after experimental handling is emphasized. 6. There is no wholly satisfactory explanation of the observations.
Novel Therapies for Metastatic Renal Cell Carcinoma: Efforts to Expand beyond the VEGF/mTOR Signaling Paradigm (2012)

With six agents approved for metastatic renal cell carcinoma (mRCC) within the past 5 years, there has undoubtedly been progress in treating this disease. However, the goal of cure remains elusive, and the agents nearest approval (i.e., axitinib and tivozanib) abide by the same paradigm as existing drugs (i.e., inhibition of VEGF or mTOR signaling). The current review will focus on investigational agents that diverge from this paradigm. Specifically, novel immunotherapeutic strategies will be discussed, including vaccine therapy, cytotoxic T-lymphocyte antigen 4 (CTLA4) blockade, and programmed death-1 (PD-1) inhibition, as well as novel approaches to angiogenesis inhibition, such as abrogation of Ang/Tie-2 signaling. Pharmacologic strategies to block other potentially relevant signaling pathways, such as fibroblast growth factor receptor or MET inhibition, are also in various stages of development. Although VEGF and mTOR inhibition have dramatically improved outcomes for patients with mRCCs, a surge above the current plateau with these agents will likely require exploring new avenues.
The effect of aclidinium bromide 400 µg on sleep quality in COPD: A pilot study (2016)

<b>Background:</b> Aclidinium bromide 400 µg (AB) is known to improve lung function and symptoms in moderate to severe COPD; however, sleep disturbances are common in patients with COPD. <b>Aim:</b> This study investigated the effects of AB on symptoms and sleep quality. <b>Methods:</b> This was a Phase IV, 21-day, randomized, double-blind, placebo (PBO)-controlled, two-period, crossover pilot study (NCT02153489). Assessments included FEV<sub>1</sub>, symptoms (cough, wheeze, sputum, dyspnoea, chest tightness, congestion), physical activity, polysomnography and adverse events (AEs). <b>Results:</b> Patients (n=30; mean age: 64.4 y; male: 50%; mean pre-bronchodilator FEV<sub>1</sub> ±standard deviation: 1.3±0.4 L) received AB or PBO twice daily (BID). Patients with obstructive sleep apnoea were excluded. After 21 days, AB improved both trough and peak FEV<sub>1</sub> vs PBO (p&lt;0.05). AB improved evening symptoms (p&lt;0.01) vs PBO and showed numerical improvements in morning (p=0.06) and nighttime (p=0.08) symptoms. AB increased rapid eye movement sleep by 2.53% (p&lt;0.05) and decreased oxygen desaturation index by 2.5 (p&lt;0.05) vs PBO. AB numerically improved total sleep time by 19 min (p=0.11), sleep efficiency by 3.6% (p=0.12), moderate physical activity by 18 min/day (p=0.06) and number of steps by 246 steps/day (p=0.59) vs PBO. AEs were similar across groups; the most frequent were erythema (10.0%), nasopharyngitis (6.7%) and rhinitis (6.7%). <b>Conclusions:</b> In this pilot study, aclidinium 400 µg BID significantly improved lung function. Improvements were also observed in sleep quality, physical activity and symptoms in patients with moderate COPD. These changes may be clinically important and therefore require confirmation in adequately powered studies.