gebhart/patrepeval huggingface dataset:
Desensitization of Pituitary Cells by Gonadotrophin‐Releasing Hormone or its Analogues in the Superfusion System: Different Pattern for Males and Females (1992)

The effect of a 6-h infusion of gonadotrophin-releasing hormone (GnRH) or its analogues on dispersed anterior pituitary cells from male or female rats was investigated. The cells were stimulated with 3-min pulses of K(+) and GnRH. Thereafter GnRH (1 nM) or GnRH analogues ([D-Trp(6) ]GnRH-ethylamide ([D-Trp(6) ]GnRH, 50 pM), [D-Phe(6) , Gln(8) ]GnRH-ethylamide (Folligen, 100 pM) and [Asu(6) ]GnRH-ethylamide ([Asu(6) ]GnRH, 33 pM)) were applied for 6 h. In cells from female rats this treatment resulted in a 20-fold increase in luteinizing hormone (LH) secretion during the first 90-min period of the 6-h incubation. Following this a gradual decrease in LH release occurred, and during the fourth 90-min period the amount of LH secreted was only one-third or less of the initial value. The pituitary cells of male rats responded to the same treatment with only a 7-fold rise of LH secretion during the first period. In the second 90-min of the 6-h incubation a 20% to 30% increase was observed. Even in the fourth 90-min period the amount of LH secreted was two-thirds or more greater than that of the first 90-min period. When using 10-fold greater concentrations of the same peptides in males, the increase in hormone secretion in the second 90-min was not seen and the hormone release decreased to around 50%. We found definite differences in the responses of male and female rat pituitary cells to the 6-h infusion of GnRH or its analogues: the initial amplitude of the response in females was higher but desensitization was stronger. In males, the initial response was weaker; however, even using doses one magnitude greater, the level of desensitization did not reach the values obtained in females. The results were similar both with GnRH and the analogues. The responses to 3-min K(+) and GnRH stimuli given after the 6-h incubation were strongly reduced in cells from female rats compared to the initial responses; however, in cells from male rats the reaction was higher or unchanged. The ratio of LH released by the final K(+) stimulus relative to the actual LH content of the cells decreased in females but increased in males. Our data show that the differences between the pattern of desensitization in cells from male and female rats may be caused by the differences in the amount and ratio of immediately releasable hormone and the hormone replenishment into these pools.
High-Definition Mapping of Retroviral Integration Sites Defines the Fate of Allogeneic T Cells After Donor Lymphocyte Infusion (2010)

The infusion of donor lymphocytes transduced with a retroviral vector expressing the HSV-TK suicide gene in patients undergoing hematopoietic stem cell transplantation for leukemia/lymphoma promotes immune reconstitution and prevents infections and graft-versus-host disease. Analysis of the clonal dynamics of genetically modified lymphocytes in vivo is of crucial importance to understand the potential genotoxic risk of this therapeutic approach. We used linear amplification-mediated PCR and pyrosequencing to build a genome-wide, high-definition map of retroviral integration sites in the genome of peripheral blood T cells from two different donors and used gene expression profiling and bioinformatics to associate integration clusters to transcriptional activity and to genetic and epigenetic features of the T cell genome. Comparison with matched random controls and with integrations obtained from CD34(+) hematopoietic stem/progenitor cells showed that integration clusters occur within chromatin regions bearing epigenetic marks associated with active promoters and regulatory elements in a cell-specific fashion. Analysis of integration sites in T cells obtained ex vivo two months after infusion showed no evidence of integration-related clonal expansion or dominance, but rather loss of cells harboring integration events interfering with RNA post-transcriptional processing. The study shows that high-definition maps of retroviral integration sites are a powerful tool to analyze the fate of genetically modified T cells in patients and the biological consequences of retroviral transduction.
Synthesis and Biological Evaluation of Novel 3-Isopropenyl-β-Lactams: Heterocyclic Bridged Analogues of Combretastatin A-4 as Novel Antimitotic Agents in Breast Cancer (2022)

Microtubule-targeted drugs are essential chemotherapeutic agents for various types of cancer. We have previously reported the synthesis of 3-vinyl-β-lactams (2-azetidinones) with potent antiproliferative activity against breast cancer MCF-7 cells. As a continuation of our research work on tubulin polymerization inhibitors, we now present the synthesis and biochemical evaluation of a series of novel 3-isopropenyl-β-lactams (2-azetidinones) that are structurally related to the colchicine binding site tubulin inhibitor and vascular targeting agent, Combretastatin A-4. The 3-isopropenyl-β-lactams in this series contain 3,4,5-trimethoxyphenyl ring A (required for CA-4), together with selected ring B substituents. These compounds showed potent activity against breast cancer in MCF-7 and triple negative MDA-MB-231 breast cancer cells and are minimally toxic to non-tumorigenic human embryonic kidney HEK-293T cells. Moreover, the compounds significantly arrested cell division during the G2/M phase and induced apoptosis in the MCF-7 cell line. Immunofluorescence studies in MCF-7 cells showed that the 3-isopropenyl-β-lactam caused mitotic catastrophe by targeting tubulin and inhibited tubulin polymerization. In conclusion, the 3-isopropenyl-2-azetidinones could be promising lead compounds for the development of anti-breast cancer drugs that target tubulin in future clinical trials.
Supplementary Figure 2 from BRCA1 Represses Amphiregulin Gene Expression (2023)

Supplementary Figure 2 from BRCA1 Represses Amphiregulin Gene Expression
Design and Synthesis of Mercaptoacetamides as Potent, Selective, and Brain Permeable Histone Deacetylase 6 Inhibitors (2017)

A series of nonhydroxamate HDAC6 inhibitors were prepared in our effort to develop potent and selective compounds for possible use in central nervous system (CNS) disorders, thus obviating the genotoxicity often associated with the hydroxamates. Halogens are incorporated in the cap groups of the designed mercaptoacetamides in order to increase brain accessibility. The indole analogue <b>7e</b> and quinoline analogue <b>13a</b> displayed potent HDAC6 inhibitory activity (IC<sub>50</sub>, 11 and 2.8 nM) and excellent selectivity against HDAC1. Both <b>7e</b> and <b>13a</b> together with their ester prodrug <b>14</b> and disulfide prodrugs <b>15</b> and <b>16</b> were found to be effective in promoting tubulin acetylation in HEK cells. The disulfide prodrugs <b>15</b> and <b>16</b> also released a stable concentration of <b>7e</b> and <b>13a</b> upon microsomal incubation. Administration of <b>15</b> and <b>16</b><i>in vivo</i> was found to trigger an increase of tubulin acetylation in mouse cortex. These results suggest that further exploration of these compounds for the treatment of CNS disorders is warranted.
Osaka Prefecture University at TRECVID 2011 (2011)

We have participated in the Content-based Copy Detection task. Our purpose for participation is to examine the performance of our image recognition method in the video retrieval. Our image recognition method utilizes local features directly, and achieves the high-speed processing, and high accuracy. We submitted 4 runs as follows. IMP.m.balanced.Uvote : uniform vote IMP.m.balanced.Wvote : weighted vote IMP.m.nofa.Uvote : uniform vote IMP.m.nofa.Wvote : weighted vote The deference between Uvote and Wvote is whether votes are weighted or not. As a result, the image recognition works better than we expected even only with a slight modification for video retrieval. However further improvements are required for achieving satisfactory results as compared to the state-of-the-art methods.
Insights into the Biology of HIV-1 Viral Protein R (2002)

HIV-1 viral protein R (Vpr) is a small, highly conserved accessory protein encoded by the HIV genome that serves many functions in the viral life cycle. Vpr induces G2 cell cycle arrest, which is thought to indirectly enhance viral replication by increasing transcription from the LTR. Vpr has also been implicated in facilitating infection of nondividing cells, most notably macrophages. Because Vpr is a nucleo-cytoplasmic shuttling protein, its role in enhancing viral replication in macrophages may be mediated through enhanced entry of the HIV preintegration complex through the limiting nuclear pore. Free Vpr is detectable in the serum of patients, and in vitro studies implicate extracellular forms of Vpr as an effector of cellular responses mediated through its ability to transduce through intact cytoplasmic membranes. We review the biologic properties of Vpr, focusing on its mechanism of action, role in HIV replication, and significance for host pathogenesis.
Bright, “Clickable” Porphyrins for the Visualization of Oxygenation under Ambient Light (2015)

Abstract A new group of “clickable” and brightly emissive metalloporphyrins has been developed for the visualization of oxygenation under ambient light with the naked eye. These alkynyl‐terminated compounds permit the rapid and facile synthesis of oxygen‐sensing dendrimers through azide–alkyne click chemistry. With absorption maxima overlapping with the wavelengths of common commercial laser sources, they are readily applicable to biomedical imaging of tissue oxygenation. An efficient synthetic methodology, featuring the stable trimethylacetyl (pivaloyl) protecting group, is described for their preparation. A paint‐on liquid bandage containing a new, click‐synthesized porphyrin dendrimer has been used to map oxygenation across an ex vivo porcine skin burn model.
An interview with Michael Rabin (2010)

Michael O. Rabin, co-recipient of the 1976 ACM A.M. Turing Award, discusses his innovative algorithmic work with Dennis Shasha.
Experiences in the Development and Usage of a Privacy Requirements Framework (2016)

Any reasonable implementation of privacy requirements can not be made through legal compliance alone. The belief that a software system can be developed without privacy being an integral concept, or that a privacy policy is sufficient as requirements or compliance check is at best dangerous for the users, customers and business involved. While requirements frameworks exist, the specialisation of these into the privacy domain have not been made in such a manner that they unify both the legal and engineering domains. In order to achieve this one must develop ontological structures to aid communication between these domains, provide a commonly acceptable semantics and a framework by which requirements expressed at different levels of abstractness can be linked together and support refinement. An effect of this is to almost completely remove the terms 'personal data' and 'PII' from common usage and force a deeper understanding of the data and information being processed. Once such a structure is in place - even if just partially or sparsely populated - provides a formal framework by which not only requirements can be obtained, their application (or not) be justified and a proper risk analysis made. This has further advantages in that privacy requirements and their potential implementations can be explored through the software development process and support ideas such as agile methods and 'DevOps' rather than being an 'add-on' exercise - a privacy impact assessment - poorly executed at inappropriate times.
Statistical Properties Of Light Scattered By A Turbulent Layer (1988)

We report measurements of the spatial coherence properties of light scattered by a turbulent layer - in particular, the dependence of the spatial coherence function of intensity fluctuations on propagation distance is compared with theoretical predictions.
Purification and characterization of a casein‐kinase‐II‐type enzyme from Xenopus laevis ovary (1988)

A casein kinase of type II has been highly purified from Xenopus laevis ovary. A new experimental protocol has been developed for the purification, consisting in four chromatographic steps: hydrophobic on tyrosine-agarose, ion exchange on DEAE-Sepharose, affinity on heparin-Sepharose and fast protein liquid on Mono Q. The purification was greater than 20,000, taking into account an inhibitor present in the starting material which masked the activity in the crude fraction. The overall yield was greater than 20%. Full-grown Xenopus oocytes contain 64 milliunits per oocyte corresponding to an intracellular concentration in the nanomolar range. The enzyme shares the following features with the mammalian casein kinase II: (a) comparable subunit composition (42-kDa doublet, 38 kDa and 26 kDa), (b) autophosphorylation of the 26-kDa subunit, (c) ability to use GTP as well as ATP as phosphate donor, (d) inability to use Mn2+ instead of Mg2+ to support the activity, (e) phosphorylation of both threonine and serine residues of casein, (f) inhibition by low doses of heparin. Biological effects of the highly purified enzyme have been investigated upon microinjection into Xenopus full-grown oocytes. At nanomolar concentrations (approximately 3 nM) the enzyme inhibited progesterone induction of meiotic cell division whereas it facilitates meiotic maturation at the level of maturation-promoting factor. These results suggest a role for the kinase in the phosphorylation cascade involved during the prophase/metaphase transition of meiotic cell division, both in the mechanism of the meiotic prophase arrest and in the activity of the cytoplasmic factor maturation-promoting factor. When microinjected into oocytes above 45 nM, the kinase provoked complex changes in the profile of the in ovo 32P-labelled proteins indicating that its targets could be other kinase/phosphatase regulatory proteins.
Native point defects in low-temperature-grown GaAs (1995)

We present structural and electronic data which indicate that the dominant defects in GaAs grown at low temperatures (LT GaAs) by molecular beam epitaxy (MBE) are As antisites (AsGa) and Ga vacancies (VGa), with negligible amounts of As interstitials (Asi). We show that the change of lattice parameter correlates with the concentration of AsGa, and that AsGa alone can account for the lattice expansion. We also show that the total concentration of AsGa has a characteristic second power dependence on the concentration of AsGa in the positive charge state for the material grown at different temperatures. This can be understood provided that VGa defects are the acceptors responsible for the carrier compensation. Our results are consistent with most experimental results and the theoretical expectation from the calculation of defect formation energies. We find that the conclusion may also be true in As-rich bulk GaAs.
Evidence of Hermaphroditism and Sex Ratio Distortion in the Fungal Feeding Nematode Bursaphelenchus okinawaensis (2014)

Nematodes have many different reproductive strategies along with their divergent life histories; the ability of hermaphrodite to self- and cross-fertilize is useful for genetic manipulation. Here, we demonstrate the hermaphroditism of the fungal feeding nematode Bursaphelenchus okinawaensis, which was formerly described as a parthenogenetic nematode, and we show its other unique sexual characteristics. To determine that it is hermaphroditic, we performed the following experiments: observation of the pronuclear and chromosome behavior during oogenesis and early embryogenesis; observation of spermatogenesis during the fourth larval stage; investigation of sperm utilization; and investigation of phenotypic segregation after cross-mating using a chemically induced visible mutant. We then investigated the mating preferences and spermatid size difference between males and hermaphrodites. B. okinawaensis males successfully mated only with sperm-depleted old hermaphrodites, and the spermatid sizes of males were almost the same as those of hermaphrodites. Moreover, the sex ratio of cross-fertilized progeny was highly skewed toward hermaphrodites. B. okinawaensis is phylogenetically distant from established model nematodes such as C. elegans and is more closely related to some economically relevant parasitic nematodes. This newly discovered hermaphroditic nematode has great potential for evolutionary and parasitological research.
Brain ganglioside biosynthesis and function (2008)

Gangliosides, sialylated glycosphingolipids, are the major sialoglycans in the brain. The same four ganglioside structures, GM1, GD1a, GD1b and GT1b, comprise most of the brain gangliosides in mammals (~97% in humans). The functions of brain gangliosides are not fully known. Two major brain gangliosides, GD1a and GT1b, are implicated in myelin-axon interactions based on their ability to act as receptors for the brain lectin MAG (myelin-associated glycoprotein). These two gangliosides share the same terminal MAG-binding determinant, NeuAc(α 2-3)Gal(β 1-3)GalNAc. GD1a and GT1b are synthesized from GM1 and GD1b (respectively) by addition of terminal α 2-3-linked sialic acid. We used mouse genetics to block sialylation of GM1 and GD1b in vivo. Gangliosides were extracted from brains of mice engineered to lack each of four different α 2-3 sialyltransferase genes: St3gal1, St3gal2, St3gal3 and St3gal4. A significant, but partial (~50%) block of GD1a and GT1b synthesis was found only in St3gal2-null mice. However, expression of GD1a and GT1b was robustly blocked in St3gal2 and Stgal3 double null mice, with commensurate increases in their precursors, GM1 and GD1b. Impaired GD1a and GT1b expression was confirmed in St3gal2 and Stgal3 double null mice by thin layer chromatography, multi-dimensional mass spectroscopy and ganglioside immunohistochemistry. Preliminary phenotypic characterization indicates that these animals are runted, short-lived, and have early motor deficits reflected by impaired hind limb reflexes. These data identify St3gal2 and St3gal3 as the key sialyltransferase genes responsible for terminal ganglioside sialylation, and further implicate GD1a and GT1b in nervous system function.
Statistical Tools for Analyzing Measurements of Charge Transport (2012)

This paper applies statistical methods to analyze the large, noisy data sets produced in measurements of tunneling current density (J) through self-assembled monolayers (SAMs) in large-area junctions. It describes and compares the accuracy and precision of procedures for summarizing data for individual SAMs, for comparing two or more SAMs, and for determining the parameters of the Simmons model (β and J0). For data that contain significant numbers of outliers (i.e., most measurements of charge transport), commonly used statistical techniques—e.g., summarizing data with arithmetic mean and standard deviation and fitting data using a linear, least-squares algorithm—are prone to large errors. The paper recommends statistical methods that distinguish between real data and artifacts, subject to the assumption that real data (J) are independent and log-normally distributed. Selecting a precise and accurate (conditional on these assumptions) method yields updated values of β and J0 for charge transport across both odd and even n-alkanethiols (with 99% confidence intervals) and explains that the so-called odd–even effect (for n-alkanethiols on Ag) is largely due to a difference in J0 between odd and even n-alkanethiols. This conclusion is provisional, in that it depends to some extent on the statistical model assumed, and these assumptions must be tested by future experiments.
3,6-Anhydro-L-galactonate cycloisomerase fromVibriosp. strain EJY3: crystallization and X-ray crystallographic analysis (2017)

3,6-Anhydro-L-galactonate cycloisomerase (ACI), which is found in the marine bacterium Vibrio sp. strain EJY3, converts 3,6-anhydro-L-galactonate into 2-keto-3-deoxygalactonate. ACI is a key enzyme in the metabolic pathway of 3,6-anhydro-L-galactose (AHG). Study of AHG metabolism is important for the efficient fermentation of agar and biofuel production, because AHG is a sugar that is non-fermentable by commercial microorganisms. The aci gene from Vibrio sp. strain EJY3 was cloned, and the recombinant protein was overexpressed and crystallized in order to determine the structure and understand the function of the protein. The crystals diffracted to 2.2 Å resolution and belonged to space group P4<sub>1</sub>2<sub>1</sub>2 or P4<sub>3</sub>2<sub>1</sub>2, with unit-cell parameters a = b = 87.9, c = 143.5 Å. The Matthews coefficient was 2.3 Å<sup>3</sup> Da<sup>-1</sup>, with a solvent content of 47%.
Markov Chain based Method for In-Domain and Cross-Domain Sentiment Classification (2015)

Sentiment classification of textual opinions in positive, negative or neutral polarity, is a method to understand people thoughts about products, services, persons, organisations, and so on. Interpreting and labelling opportunely text data polarity is a costly activity if performed by human experts. To cut this labelling cost, new cross domain approaches have been developed where the goal is to automatically classify the polarity of an unlabelled target text set of a given domain, for example movie reviews, from a labelled source text set of another domain, such as book reviews. Language heterogeneity between source and target domain is the trickiest issue in cross-domain setting so that a preliminary transfer learning phase is generally required. The best performing techniques addressing this point are generally complex and require onerous parameter tuning each time a new source-target couple is involved. This paper introduces a simpler method based on the Markov chain theory to accomplish both transfer learning and sentiment classification tasks. In fact, this straightforward technique requires a lower parameter calibration effort. Experiments on popular text sets show that our approach achieves performance comparable with other works.
Differential functional coupling in Gp130-JAK complexes expands the plasticity of the interleukin-6 signaling axis (2023)

ABSTRACT Cytokines dimerize/oligomerize surface receptors to activate signaling. While cytokine receptors preferentially bind only one member of the JAK family, ancestral cytokine receptors, such as Gp130, promiscuously recruit different JAKs to elicit their activities. Here, we have explored how the identity of JAKs in Gp130 signaling complexes can regulate functional outcomes. Using a synthetic biology approach, we show that Gp130 bound to different JAKs propagates distinct STAT activation profiles. While Gp130-JAK1 complexes activated both, STAT1 and STAT3 very potently, Gp130-JAK2 complexes exhibited a clear preference for STAT3 activation. Gp130-TYK2 complexes triggered overall weaker signaling but with diminished STAT specificity. The three JAKs competed for binding to Gp130 and led to differential activation of phospho-Tyr in the Gp130 intracellular domain. JAK1, JAK2 and to a lower extent TYK2 bound with comparable affinities to Gp130, and in response to IL-6 stimulation efficiently drove Gp130 dimerization. However, the three JAKs differentially affected Gp130 surface expression, identifying JAK-dependent receptor trafficking as a critical determinant of signaling plasticity. Our results provide new mechanistic insights into how differential functional coupling in Gp130-JAK complexes translates into unique signaling signatures that likely contribute to its large functional diversity.