gebhart/patrepeval huggingface dataset:
Undifferentiated hematopoietic cells are characterized by a genome-wide undermethylation dip around the transcription start site and a hierarchical epigenetic plasticity (2009)

Evidence for the epigenetic regulation of hematopoietic stem cells (HSCs) is growing, but the genome-wide epigenetic signature of HSCs and its functional significance remain unclear. In this study, from a genome-wide comparison of CpG methylation in human CD34(+) and CD34(-) cells, we identified a characteristic undermethylation dip around the transcription start site of promoters and an overmethylation of flanking regions in undifferentiated CD34(+) cells. This "bivalent-like" CpG methylation pattern around the transcription start site was more prominent in genes not associated with CpG islands (CGI(-)) than CGI(+) genes. Undifferentiated hematopoietic cells also exhibited dynamic chromatin associated with active transcription and a higher turnover of histone acetylation than terminally differentiated cells. Interestingly, inhibition of chromatin condensation by chemical treatment (5-azacytidine, trichostatin A) enhanced the self-renewal of "stimulated" HSCs in reconstituting bone marrows but not "steady-state" HSCs in stationary phase bone marrows. In contrast, similar treatments on more mature cells caused partial phenotypic dedifferentiation and apoptosis at levels correlated with their hematopoietic differentiation. Taken together, our study reveals that the undifferentiated state of hematopoietic cells is characterized by a unique epigenetic signature, which includes dynamic chromatin structures and an epigenetic plasticity that correlates to level of undifferentiation.
Simulation of MOSFET lifetime under AC hot-electron stress (1988)

A substrate current model and a quasistatic hot-electron-induced MOSFET degradation model have been implemented using the Substrate Current And Lifetime Evaluator (SCALE) package. It is shown that quasistatic simulation is valid for a class of waveforms that includes those encountered in inverter-based logic circuits. The validity and limitations of the model are illustrated with experimental results. SCALE is linked to SPICE externally in a pre- and postprocessor fashion to form an independent simulator. The preprocessor interprets the input deck and requests SPICE to output the transient node voltages of the user-selected devices. The postprocessor then calculates the transient substrate current and makes a lifetime prediction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Atherosclerotic Plaque Progression in Carotid Arteries: Monitoring with High-Spatial-Resolution MR Imaging—Multicenter Trial (2009)

Evaluation of results of a multicenter study indicates that quantitative evaluation of the progression of volume of extracranial carotid vessel walls is feasible with 1.5-T MR imaging despite limitations due to patient motion or habitus. In patients who had preexisting carotid disease, the rate of increase in vessel-wall volume was slower in patients receiving statin therapy.
Semen analysis and sperm function tests: How much to test? (2011)

Semen analysis as an integral part of infertility investigations is taken as a surrogate measure for male fecundity in clinical andrology, male fertility, and pregnancy risk assessments. Clearly, laboratory seminology is still very much in its infancy. In as much as the creation of a conventional semen profile will always represent the foundations of male fertility evaluation, the 5th edition of the World Health Organization (WHO) manual is a definitive statement on how such assessments should be carried out and how the quality should be controlled. A major advance in this new edition of the WHO manual, resolving the most salient critique of previous editions, is the development of the first well-defined reference ranges for semen analysis based on the analysis of over 1900 recent fathers. The methodology used in the assessment of the usual variables in semen analysis is described, as are many of the less common, but very valuable, sperm function tests. Sperm function testing is used to determine if the sperm have the biologic capacity to perform the tasks necessary to reach and fertilize ova and ultimately result in live births. A variety of tests are available to evaluate different aspects of these functions. To accurately use these functional assays, the clinician must understand what the tests measure, what the indications are for the assays, and how to interpret the results to direct further testing or patient management.
Mueller matrix imaging of human colon tissue for cancer diagnostics: how Monte Carlo modeling can help in the interpretation of experimental data (2010)

Colon samples with both healthy and cancerous regions have been imaged in diffuse light and backscattering geometry by using a Mueller imaging polarimeter. The tumoral parts at the early stage of cancer are found to be less depolarizing than the healthy ones. This trend clearly shows that polarimetric imaging may provide useful contrasts for optical biopsy. Moreover, both types of tissues are less depolarizing when the incident polarization is linear rather than circular. However, to really optimize an optical biopsy technique based on polarimetric imaging a realistic model is needed for polarized light scattering by tissues. Our approach to this goal is based on numerical Monte-Carlo simulations of polarized light propagation in biological tissues modeled as suspensions of monodisperse spherical scatterers representing the cell nuclei. The numerical simulations were validated by comparison with measurements on aqueous polystyrene sphere suspensions, which are commonly used as tissue phantoms. Such systems exhibit lower depolarization for incident linear polarization in the Rayleigh scattering regime, i.e. when the sphere diameters are smaller than the wavelength, which is obviously not the case for cell nuclei. In contrast, our results show that this behaviour can also be seen for "large" scatterers provided the optical index contrast between the spheres and the surrounding medium is small enough, as it is likely to be the case in biological tissues.
The TAK1-NF-κB axis as therapeutic target for AML (2014)

Development and maintenance of leukemia can be partially attributed to alterations in (anti)-apoptotic gene expression. Genome-wide transcriptome analyses revealed that 89 apoptosis-associated genes were differentially expressed between patient acute myeloid leukemia (AML) CD34(+) cells and normal bone marrow (NBM) CD34(+) cells. Among these, transforming growth factor-β activated kinase 1 (TAK1) was strongly upregulated in AML CD34(+) cells. Genetic downmodulation or pharmacologic inhibition of TAK1 activity strongly impaired primary AML cell survival and cobblestone formation in stromal cocultures. TAK1 inhibition was mainly due to blockade of the nuclear factor κB (NF-κB) pathway, as TAK1 inhibition resulted in reduced levels of P-IκBα and p65 activity. Overexpression of a constitutive active variant of NF-κB partially rescued TAK1-depleted cells from apoptosis. Importantly, NBM CD34(+) cells were less sensitive to TAK1 inhibition compared with AML CD34(+) cells. Knockdown of TAK1 also severely impaired leukemia development in vivo and prolonged overall survival in a humanized xenograft mouse model. In conclusion, our results indicate that TAK1 is frequently overexpressed in AML CD34(+) cells, and that TAK1 inhibition efficiently targets leukemic stem/progenitor cells in an NF-κB-dependent manner.
Pedagogy Meets PowerPoint: A Research Review of the Effects of Computer-Generated Slides in the Classroom (2006)

Abstract The present essay offers a comprehensive review of the effects of computer-generated slides in the classroom, beginning with an overview of the ongoing debate over whether. To date, much of this debate has been testimonial in nature; in an effort to move beyond testimonials, this essay will attempt to ground the pedagogical debate over PowerPoint in various learning theories. Extant research on such slides is examined in four subcategories: (1) student reactions; (2) learning outcomes; (3) learning styles; and (4) slide variation effects. This essay closes with a discussion of how various research findings help inform (but by no means settle) the debate over PowerPoint and pedagogy. Notes 1. Studies examining the pedagogical effects of "multimedia" have incorporated a variety of educational technologies. Some studies using the term "multimedia" have simply looked at the effects of computer-generated slides. These studies, since they isolate the effects of such slides, are included in the present review. 2. The Butler and Mautz (1996) study actually contrasted standard black and white (text only) computer-generated slides with multimedia slides (computer-generated slides containing text, graphics, color, and motion). In the study, the researchers classified the former slides as "traditional" visual aids since these visuals merely replicated overhead transparencies. 3. The Ahmed study results contain no test of statistical significance. However, the reported data clearly reveal that computer-generated slides did not improve student learning outcomes; students in the overhead condition outperformed their counterparts in the computer-generated slide condition on most of the test questions serving as the dependent variable. 4. The Lowry (1999) study may serve as the exception due to a unique feature in this particular experiment. This study not only involved adding PowerPoint to course lectures, it also added PowerPoint as a non-lecture problem-solving tool; in non-lecture settings, students attended timed PowerPoint presentations demonstrating step-by-step solutions to course problems. Additional informationNotes on contributorsDavid G. Levasseur David G. Levasseur (Ph.D., 1994) is Associate Professor in the Department of Communication Studies at West Chester University J. Kanan Sawyer J. Kanan Sawyer (Ph.D., 2004) is Assistant Professor in the Department of Communication Studies at West Chester University
Beam converging laser diode by taper ridge waveguide (1988)

To converge a laser beam parallel to the junction plane, a taper ridged waveguide is fabricated at the tip of the laser diode cavity. The beam converging effect is observed, and the beamwidth parallel to the junction plane is reduced to 1μm
High-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing (2011)

RNA interference (RNAi) screening is a state-of-the-art technology that enables the dissection of biological processes and disease-related phenotypes. The commercial availability of genome-wide, short hairpin RNA (shRNA) libraries has fueled interest in this area but the generation and analysis of these complex data remain a challenge. Here, we describe complete experimental protocols and novel open source computational methodologies, shALIGN and shRNAseq, that allow RNAi screens to be rapidly deconvoluted using next generation sequencing. Our computational pipeline offers efficient screen analysis and the flexibility and scalability to quickly incorporate future developments in shRNA library technology.
The cloning and expression of an anti-peptide antibody: a system for rapid analysis of the binding properties of engineered antibodies (1986)

The cloning of the light and heavy chain genes of an antilysozyme monoclonal antibody is described and the application of site-directed mutagenesis for reconstruction of complete cDNAs from incomplete cDNA clones is discussed. The behaviour of the RNA transcripts produced from these cDNAs after their subcloning into an appropriate Salmonella typhimurium, SP6, vector and subsequent injection into Xenopus oocytes has been analysed. The antibody secreted by oocytes after RNA injection has been quantitated and its antigen-binding properties compared with wild-type hybridoma antibody. The results show that this route for expression of antibodies, though limited in its capacity to produce more than a few micrograms of protein, is potentially a means for rapid evaluation of the antigen-binding properties of engineered antibodies.
Particulate Contrast Media (1980)

Particulate contrast agents, when compared to water-soluble media, offer the advantage of allowing the administration of high doses without creating hypertonicity gradients and ionic imbalances. Since these radiopaque particles are accumulated in the reticuloendothelial system, they could be ideal hepatic CT contrast agents. We have developed a method for making particles of 2 +/- 1 microns by precipitating from an organic solvent. Preincubation of these particles in human serum albumin overcomes the very serious problem of in vivo particle aggregation and embolization. The ethyl esters of iothalamic and iodipamic acid have been injected intravenously into mice, rats, and rabbits. Radiopacification of the liver is maximal within 2-3 hours postinfusion, with radiopaque material subsequently clearing through the biliary system. Elimination from the organism seems to be complete within a few days postinfusion. Efforts to decrease the subacute toxicity of these agents are underway.
Alpha 2 -Adrenergic Receptor–Induced Vascular Constriction in Blacks and Whites (2003)

Black Americans have a reduced hypotensive response to the alpha2-adrenergic receptor agonist clonidine compared with whites, despite similar central sympathoinhibition. This reduced hypotensive response might be explained by greater postsynaptic vascular alpha2-adrenergic receptor vasoconstrictive response. However, clonidine has a low alpha2/alpha1 selectivity ratio. Therefore, to determine the role of altered alpha2-adrenergic receptor vascular sensitivity in ethnic differences in vascular response, we compared local vascular responses with the highly selective alpha2-adrenergic receptor agonist dexmedetomidine in healthy black (n=18) and white (n=19) subjects. Increasing doses of dexmedetomidine (0.001 to 1000 ng/min) were infused into a dorsal hand vein, and the local response was measured with a linear variable differential transformer. Dexmedetomidine caused pronounced venoconstriction, with an average (+/-SD) maximum response of 74.5+/-17.72% but with no difference between blacks and whites. There was substantial intersubject variability in the sensitivity to dexmedetomidine; the dose resulting in 50% (ED50) of maximum vasoconstriction ranged from 0.08 ng/min to 256 ng/min. The geometric mean ED50 was 2.28 ng/min (95% CI, 0.02 to 271.6 ng/min) in blacks and 1.58 ng/min (95% CI, 0.11 to 24.55 ng/min) in whites (P=0.59). Our data indicate that alpha2-adrenergic receptor-induced venoconstriction is similar in blacks and whites. These findings do not support the hypothesis that altered alpha2-adrenergic receptor sensitivity is the explanation for the decreased blood pressure response to systemic administration of clonidine in blacks. The response to dexmedetomidine provides a model that will allow further study of the regulation of alpha2-adrenergic receptor-mediated vascular responses
<title>Video browsing using clustering and scene transitions on compressed sequences</title> (1995)

This paper describes a new technique for extracting a hierarchical decomposition of a complex video selection for browsing purposes. The technique combines visual and temporal information to capture the important relations within a scene and between scenes in a video, thus allowing the analysis of the underlying story structure with no a priori knowledge of the content. We define a general model of hierarchical scene transition graph, and apply this model in an implementation for browsing. Video shots are first identified and a collection of key frames is used to represent each video segment. These collections are then classified according to gross visual information. A platform is built on which the video is presented as directed graphs to the user, with each category of video shots represented by a node and each edge denotes a temporal relationship between categories. The analysis and processing of video is carried out directly on the compressed videos. Preliminary tests show that the narrative structure of a video selection can be effectively captured using this technique.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Tyrosyl-tRNA Synthetase: A Housekeeping Protein and an Attractive Harbinger of Cellular Death (1999)

Cytokine-type activities are observed for the human tyrosyl-tRNA synthetase, largely considered as an essential enzyme for protein synthesis, only after cleavage into two fragments. These peptide fragments are novel elements in the orchestration of the tissue response to a cellular suicide program and should be viewed as highly differentiated adaptions of peptide modules with biological activity in more than one kind of environment.
The TCR is an allosterically regulated macromolecular machinery changing its conformation while working (2019)

The αβ T-cell receptor (TCR) is a multiprotein complex controlling the activation of T cells. Although the structure of the complete TCR is not known, cumulative evidence supports that the TCR cycles between different conformational states that are promoted either by thermal motion or by force. These structural transitions determine whether the TCR engages intracellular effectors or not, regulating TCR phosphorylation and signaling. As for other membrane receptors, ligand binding selects and stabilizes the TCR in active conformations, and/or switches the TCR to activating states that were not visited before ligand engagement. Here we review the main models of TCR allostery, that is, ligand binding at TCRαβ changes the structure at CD3 and ζ. (a) The ITAM and proline-rich sequence exposure model, in which the TCR's cytoplasmic tails shield each other and ligand binding exposes them for phosphorylation. (b) The membrane-ITAM model, in which the CD3ε and ζ tails are sequestered inside the membrane and again ligand binding exposes them. (c) The mechanosensor model in which ligand binding exerts force on the TCR, inducing structural changes that allow signaling. Since these models are complementary rather than competing, we propose a unified model that aims to incorporate all existing data.
First full-beam PET acquisitions in proton therapy with a modular dual-head dedicated system (2013)

During particle therapy irradiation, positron emitters with half-lives ranging from 2 to 20 min are generated from nuclear processes. The half-lives are such that it is possible either to detect the positron signal in the treatment room using an in-beam positron emission tomography (PET) system, right after the irradiation, or to quickly transfer the patient to a close PET/CT scanner. Since the activity distribution is spatially correlated with the dose, it is possible to use PET imaging as an indirect method to assure the quality of the dose delivery. In this work, we present a new dedicated PET system able to operate in-beam. The PET apparatus consists in two 10 cm × 10 cm detector heads. Each detector is composed of four scintillating matrices of 23 × 23 LYSO crystals. The crystal size is 1.9 mm × 1.9 mm × 16 mm. Each scintillation matrix is read out independently with a modularized acquisition system. The distance between the two opposing detector heads was set to 20 cm. The system has very low dead time per detector area and a 3 ns coincidence window, which is capable to sustain high single count rates and to keep the random counts relatively low. This allows a new full-beam monitoring modality that includes data acquisition also while the beam is on. The PET system was tested during the irradiation at the CATANA (INFN, Catania, Italy) cyclotron-based proton therapy facility. Four acquisitions with different doses and dose rates were analysed. In all cases the random to total coincidences ratio was equal or less than 25%. For each measurement we estimated the accuracy and precision of the activity range on a set of voxel lines within an irradiated PMMA phantom. Results show that the inclusion of data acquired during the irradiation, referred to as beam-on data, improves both the precision and accuracy of the range measurement with respect to data acquired only after irradiation. Beam-on data alone are enough to give precisions better than 1 mm when at least 5 Gy are delivered.
Autophosphorylation of Smooth Muscle Myosin Light Chain Kinase at Its Regulatory Domain (1995)

Autophosphorylation of smooth muscle myosin light chain kinase was initially reported by Foyt et al. [Foyt, H. L., & Means, A. R. (1985) J. Cyclic Nucleotide Protein Phosphorylation Res. 260, 8978-8983], however, the effects of autophosphorylation on the kinase activity as well as the location of the sites have not been elucidated. Here we demonstrate that MLCK is autophosphorylated at three sites, Thr 803, Ser 815, and Ser 823, and this phosphorylation alters MLCK activity. Two phosphorylation sites are located in the regulatory domain of the kinase, the threonine site toward the autoinhibitory region and the serine site (Ser 815) in close proximity to the calmodulin anchoring site. The autophosphorylation was significantly inhibited by the binding of calmodulin. The autophosphorylation at Thr 803 is an intramolecular process, and the alignment of the basic amino acid residues nearby Thr 803 was highly homologous to the phosphorylation site of myosin light chain, suggesting that the regulatory site is in close proximity to the catalytic site in the three-dimensional structure. The phosphorylation at the threonine site activated the calmodulin-independent activity while the phosphorylation at the serine site inhibited the calmodulin-dependent activity due to a decrease in the affinity for calmodulin. This finding shows another example of the activation of calmodulin-dependent kinases by autophosphorylation at its autoinhibitory region and provides a new clue for understanding the calmodulin/MLCK signalling pathway.
Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 immediate early protein VP175 (1980)

Herpes simplex virus (HSV)-specific proteins fall into at least three kinetic classes whose synthesis is sequentially and coordinaely regulated. Temperature-sensitive (ts) mutants of one complementation group (1-2) are defective in the transition from immediate early to early and late protein synthesis. To elucidate the function of the 1-2 gene product in the HSV type 1 replicative cycle, nine ts mutants in this group were mapped by fine-structure analysis and characterized members of the group lie within the terminally repeated sequences of the S region of the genome. Fine-structure genetic and physical mapping permitted the mutations to be ordered within these sequences. Because it has been shown that the message for VP175 and the DNA template specifying this protein extend beyond the limits of the physical map of the mutations, it follows that the mutations must lie within the structural gene for VP175. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that most members of the group overproduced the immediate early proteins VP175, -136, -110, and -63 and markedly underproduced early and late proteins at the nonpermissive temperature. In temperature shiftup experiments, it was fund that the synthesis of early and late proteins ceased, whereas the synthesis of immediate early proteins began again. Thus, it is postulated that VP175 is (i) involved in the transition from immediate early to early protein synthesis, (ii) requird continuously to maintain early protein synthesis, (iii) autoregulated, acting to inhibit immediate early protein synthesis.