gebhart/patrepeval huggingface dataset:
Role of protein kinase A and the serine-rich region of herpes simplex virus type 1 ICP4 in viral replication (1996)

Efficient expression of herpes simplex virus genes requires the synthesis of functional ICP4, a nuclear phosphoprotein that contains a prominent serine-rich region between amino acids 142 and 210. Residues in this region not only are potential sites for phosphorylation but also are involved in the functions of ICP4. By comparing the growth of a virus in which this region is deleted (d8-10) with wild-type virus (KOS) in PC12 cells or PC12 cells that are deficient in cyclic AMP-dependent protein kinase (PKA), two observations were made: (i) the growth of wild-type virus was impaired by 1 to 2 orders of magnitude in the PKA-deficient cells, indicating the involvement of PKA in the growth cycle of herpes simplex virus type 1, and (ii) while the growth of d8-10 was impaired by almost 2 orders of magnitude in wild-type cells, it was not further impaired (as was that of wild-type virus) in PKA-deficient cells, implicating the region deleted in d8-10 as a possible target for cellular PKA. In trigeminal'ganglia of mice, the d8-10 mutant virus grew poorly; however, it established latency in nearly 90% of ganglia tested. Studies of the phosphorylation of wild-type and d8-10 ICP4 proteins revealed that the serine-rich region is a major determinant for phosphorylation of ICP4 in vivo and that the phosphorylation state could change as a function of the PKA activity. Consistent with this observation, the serine-rich region of ICP4 was shown to be a target for PKA in vitro. While intact ICP4 was readily phosphorylated by ICP4 in vitro, the d8-10 mutant ICP4 was not. Moreover, a synthethic peptide representing a sequence in the serine tract that is predicted to be a substrate for PKA was phosphorylated by PKA in vitro, having a Km within the physiological range. These data suggest that PKA plays a role in viral growth through phosphorylation of one or more sites on the ICP4 molecule.
Activation of the extracellular signal‐regulated kinase pathway contributes to the behavioral deficit of fragile x‐syndrome (2012)

Fragile X syndrome (FXS) is a developmental disorder caused by the loss of Fragile X Mental Retardation 1 (FMR1) gene function because of a CGG repeat expansion (> 200 repeats) in the gene. The molecular mechanism(s) linking loss of FMR1 function to the molecular pathology and cognitive/behavioral disability remain unclear. Given the critical role of extracellular signal-regulated kinase (ERK) in synaptic plasticity and neurodevelopment, a number of recent studies have investigated ERK phosphorylation under basal conditions or upon mGluR-induction using neuronal and peripheral tissues from Fmr1 knockout mice and peripheral tissues from FXS patients. However, these reports have presented conflicting results. The current study is the first to focus on the levels of ERK phosphorylation in brain tissue from human FXS patients. In both human brain tissue and brain tissue from Fmr1 knockout mice there was significantly increased phosphorylation of MEK1/2 and ERK. Indeed, treating Fmr1 knockout mice with the MEK1/2 inhibitor SL327 abrogated audiogenic seizure activity, a feature of the Fmr1 knockout mice that replicates the symptom in patients with FXS. These findings suggest that activation of the ERK pathway results in some cardinal cognitive and clinical features in FXS patients and likely have profound translational implications.
Transcription factors : a practical approach (1993)

Part 1 The DNA mobility shift assay, C.L. Dent and D.S. Latchman: detection of DNA-binding proteins other sources of protein for use the binding assay investigation of DNA-binding specificity characterization of DNA-binding proteins study of protein-protein interactions. Part 2 Determination of DNA sequences that bind transcription factors by DNA footprinting, N.D. Lakin: preparation of DNA fragments labelled on one strand of the DNA duplex determination of a transcription factor binding site by DNase I footprinting determination of a transcription factor binding site by dimethyl sulphate protection footprinting determination of a transcription factor binding site by dimethyl sulphate interference footprinting in vivo footprinting by ligation-mediated polymerase chain reaction. Part 3 Biochemical characterization of transcription factors, Austin J. Cooney et al: determination of molecular weight of the native factor determination of the molecular weight of the denatured factor analysis of the monomer/dimer structure of the DNA-binding forms of a transcription factor identification and initial characterization of non-DNA-binding transcription factors. Part 4 Purification and cloning of transcription factors, R.H. Nichols and G.H. Goodwin: buffers and solutions preparation of nuclear extract DNA-cellulose chromatography reverse-phase chromatography production of isolated peptides design of oligonuleotides for cDNA isolation. Part 5 Cloning transcription factors from cDNA expression library, Ian G. Colwell and Helen C. Hurst: handling bacteriophage expression libraries screening methods proving the identity factor. Part 6 Cloning transcription factors by homology, Alan Ashworth: methods for cloning related transcription factors some examples of the cloning of transcription factors by homology. (part contents)
Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4 (2007)

The first vasculature of the developing vertebrate embryo forms by assembly of endothelial cells into simple tubes from clusters of mesodermal angioblasts. Maturation of this vasculature involves remodeling, pruning and investment with mural cells. Hedgehog proteins are part of the instructive endodermal signal that triggers the assembly of the first primitive vessels in the mesoderm. We used a combination of genetic and in vitro culture methods to investigate the role of hedgehogs and their targets in murine extraembryonic vasculogenesis. We show that Bmps, in particular Bmp4, are crucial for vascular tube formation, that Bmp4 expression in extraembryonic tissues requires the forkhead transcription factor Foxf1 and that the role of hedgehog proteins in this process is to activate Foxf1 expression in the mesoderm. We show in the allantois that genetic disruption of hedgehog signaling (Smo(-/-)) has no effect on Foxf1 expression, and neither Bmp4 expression nor vasculogenesis are disturbed. By contrast, targeted inactivation of Foxf1 leads to loss of allantoic Bmp4 and vasculature. In vitro, the avascular Foxf1(-/-) phenotype can be rescued by exogenous Bmp4, and vasculogenesis in wild-type tissue can be blocked by the Bmp antagonist noggin. Hedgehogs are required for activation of Foxf1, Bmp4 expression and vasculogenesis in the yolk sac. However, vasculogenesis in Smo(-/-) yolk sacs can be rescued by exogenous Bmp4, consistent with the notion that the role of hedgehog signaling in primary vascular tube formation is as an activator of Bmp4, via Foxf1.
Highly scalable FBC (Floating Body Cell) with 25nm BOX structure for embedded DRAM applications (2004)

A novel FBC with 25nm-thick BOX (buried oxide) structure has been developed. A feature of new FBC is scalability in the case of thinner SOI, which promises embedded DRAM on SOI in future generations. Using 96Kbit array, the pause time distribution of FBC is demonstrated for the first time. Due to simplified structure, pause time variation of new FBC is significantly suppressed compared with conventional FBC.
Quantitative detection of T-cell activation markers by real-time PCR in renal transplant rejection and correlation with histopathologic evaluation1 (2002)

These data demonstrate that a rapid test of target gene up-regulation using real-time PCR can be used as an aid in the diagnosis of kidney allograft rejection. This is also the first report on the possible utility of HLA-DRA mRNA up-regulation as a marker for kidney transplant rejection.
Zero-Order Release Kinetics from a Self-Correcting Floatable Asymmetric Configuration Drug Delivery System (1996)

A new approach based on the three-layer matrix technology to control drug release for oral administration is presented. Polyethylene oxide polymers of various molecular weight together with theophylline as drug model and other excipients have been directly compressed into a three-layer asymmetric floatable system. The core layer contains the active drug while external layers with different thickness, composition, and erosion rates are designed to delay the hydration of the middle layer, restrict the early drug diffusion only through cylindrical side surfaces of the tablet, and provide controlled drug release. Results show that during a 16 h dissolution study drug is completely released following the zero-order kinetics with no burst effect. The release rate remains around 0.1 mg min-1 throughout the dissolution study. The release kinetics is independent of changes in pH and compression force but dependent on layer thickness and formulation components. It appears that the operating release mechanism is based on the existence of a balance between the velocities of advancing glassy/rubbery front and erosion at the swollen polymer/dissolution front.
On modeling information retrieval with probabilistic inference (1995)

This article examines and extends the logical models of information retrieval in the context of probability theory. The fundamental notions of term weights and relevance are given probabilistic interpretations. A unified framework is developed for modeling the retrieval process with probabilistic inference. This new approach provides a common conceptual and mathematical basis for many retrieval models, such as the Boolean, fuzzy set, vector space, and conventional probabilistic models. Within this framework, the underlying assumptions employed by each model are identified, and the inherent relationships between these models are analyzed. Although this article is mainly a theoretical analysis of probabilistic inference for information retrieval, practical methods for estimating the required probabilities are provided by simple examples.
Trigonal warping effect of carbon nanotubes (2000)

Chirality-dependent van Hove singularities (vHs) of the one-dimensional electronic density of states (DOS) are discussed in connection with resonant Raman spectroscopy. The effect of trigonal warping on the energy dispersion relations near the Fermi energy splits the peaks of the density of states for metallic nanotubes, and the magnitude of this effect depends on the chiral angle of the carbon nanotube. The width of the peak splitting has a maximum for metallic zigzag nanotubes, and no splitting is obtained for armchair nanotubes or semiconducting nanotubes. We also find an additional logarithmic singularity in the electronic DOS for carbon nanotubes that is related to a two-dimensional singularity, which does not depend on either the diameter or the chirality.
Cell surface glycoproteins expressed on activated human T cells induce production of interleukin-1 beta by monocytic cells: a possible role of CD69. (1993)

In many immunoinflammatory diseases, macrophages, by producing interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha), stimulate protease secretion in fibroblasts, thus contributing to tissue destruction. Monocyte/macrophage activation is prompted by soluble factors released by activated T cells as well as by cell-cell contact. Indeed, previous studies have shown that monocytes exposed to paraformaldehyde (PFA)-fixed, activated T cells produced high amounts of IL-1 beta. In this report, we used the T cell line HUT-78 to further characterize the T cell factor(s) responsible for monocyte activation by cell-cell contact. After subcellular fractionation, most of the activity was found in the cellular membrane fraction of PHA/PMA-stimulated HUT-78 cells, and proved to be due to glycoproteins, following trypsin digestion and tunicamycin treatment. HUT-78 cells acquired the capacity to stimulate monocytic cells after as little as 1h of stimulation. De novo protein synthesis was required for the expression of the IL-1 beta inducing factor, as shown by cycloheximide treatment. When membrane proteins of PHA/PMA-stimulated HUT-78 cells were separated on SDS-polyacrylamide gel, a peak of stimulatory activity was observed at Mr--25-35 x 10(3). By using specific cytokine inhibitors or blocking mAbs, we ascertained that cell-associated cytokines (IL-1, IL-2, IFN gamma and GM-CSF) were not involved in monocyte activation by cell contact. Anti-CD2 and -CD11a (LFA-1) mAbs partially blocked IL-1 beta production by -25% and -35%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Localization of Tritiated Thymidine in Articular Cartilage of Rabbits (1962)

1. Tritiated thymidine autocardiography was used to study the response of articular cartilage to three types of surgically cleated wounds in the distal part of thirty-five femora of immature rabbits. The response of time cartilage was identical in each type of trauma. 2. The cartilage responded within twenty-four hours by marginal necrosis which extended four to six cells from the defect. This disappeared by three weeks in most of the animals studied. 3. An intense proliferative activity began on the first day arid extended eight to twelve cell widths from the necrotic zone on either side of the wound. This response diminished and could no longer be observed histologically or autoradiographically by two weeks. There was no evidence in the six weeks of this study that this proliferation contributed materially to wound healing. 4. Articular cartilage appears to respond to trauma in a manner identical with the response of most other body tissues, with one major exception: it undergoes necrosis and proliferation but lacks the vascular response of inflammation.
Whole genome alignments using MPI-LAGAN (2008)

Advances in sequencing technologies have substantially increased the number of fully sequenced genomes. Alignment algorithms play a crucial rule in analyzing whole genomes, identifying similar and conserved regions between pairs of genomes, leading to annotation of genomes with site-specific properties and functions.\n\nIn this work we introduce a parallel algorithm for a widely used whole genome alignment method called LAGAN. We use the MPI-based protocol, to develop parallel solutions for two phases of the algorithm which take up a significant portion of the total runtime, and also have a high memory requirement. The serial LAGAN program uses CHAOS to quickly determine initial anchor or seeds, which are extended using a sparse dynamic programming based longest-increasing subsequence method. Our work involves parallelizing the CHAOS and LIS phases of the algorithm using a one-dimensional block cyclic partitioning of the computation. This leads to development of an efficient algorithm that utilizes the processors in a balanced way. We also ensure minimum time spent in communication or transfer of information across processors.\n\n\nWe also report experimental evaluation of our parallel implementation using pairs of human contigs of varying lengths. We discuss and illustrate the challenges faced in parallelizing a sparse dynamic programming formulation as in this work, and show equivalent to theoretical speedups for our parallelized phases of the LAGAN algorithm.
Femtosecond distributed soliton spectrum in fibers (1989)

By pumping a fiber in the anomalous group-velocity dispersion regime with a color-center laser, we generate a femtosecond distributed soliton spectrum with τ ≳ 100 fsec covering a wide spectral range between 1.55 &lt; λ &lt; 1.85 μm. We present a theory to explain the spectrum and use autocorrelations and cross correlations to verify the results experimentally. Modulation instability and the soliton self-frequency shift effect initiate a multisoliton collision process that results in narrow, high-intensity solitons. An ensemble average over these solitons, which start from noise and frequency shift by different amounts, yields the observed broad spectra. We use the fiber output in pump–probe experiments, measuring the exciton ionization time in InGaAs/InP multiple quantum wells for the first time to our knowledge.
Hierarchical Self-Assembly: Well-Defined Supramolecular Nanostructures and Metallohydrogels via Amphiphilic Discrete Organoplatinum(II) Metallacycles (2013)

Metallacyclic cores provide a scaffold upon which pendant functionalities can be organized to direct the formation of dimensionally controllable nanostructures. Because of the modularity of coordination-driven self-assembly, the properties of a given supramolecular core can be readily tuned, which has a significant effect on the resulting nanostructured material. Herein we report the efficient preparation of two amphiphilic rhomboids that can subsequently order into 0D micelles, 1D nanofibers, or 2D nanoribbons. This structural diversity is enforced by three parameters: the nature of the hydrophilic moieties decorating the parent rhomboids, the concentration of precursors during self-assembly, and the reaction duration. These nanoscopic constructs further interact to generate metallohydrogels at high concentrations, driven by intermolecular hydrophobic and π-π interactions, demonstrating the utility of coordination-driven self-assembly as a first-order structural element for the hierarchical design of functional soft materials.
The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. (1994)

Water-soluble ingredients of the herbal medicine sho-saiko-to dose-dependently inhibited the proliferation of a human hepatocellular carcinoma cell line (KIM-1) and a cholangiocarcinoma cell line (KMC-1). Fifty % effective doses on day 3 of exposure to sho-saiko-to were 353.5 +/- 32.4 micrograms/ml for KIM-1 and 236.3 +/- 26.5 micrograms/ml for KMC-1. However, almost no suppressive effects were detected in normal human peripheral blood lymphocytes or normal rat hepatocytes. Sho-saiko-to suppressed the proliferation of the carcinoma cell lines significantly more strongly than did each of its major ingredients, i.e., saikosaponin a, c, and d, ginsenoside Rb1 and Rg1, glycyrrhizin, baicalin, baicalein, and wogonin, or another herbal medicine, juzen-taiho-to (P < 0.05 or 0.005). Because such ingredients are barely soluble in water, there could be synergistic or additive effects of the ingredients in sho-saiko-to. Morphological, DNA, and cell cycle analyses revealed two possible modes of action of sho-saiko-to to suppress the proliferation of carcinoma cells; (a) it induces apoptosis in the early period of exposure and (b) it induces arrest at the G0/G1 phase in the late period of exposure.
A Protein Kinase Cε-Anti-apoptotic Kinase Signaling Complex Protects Human Vascular Endothelial Cells against Apoptosis through Induction of Bcl-2 (2007)

Endothelial cell apoptosis is associated with vascular injury and predisposes to atherogenesis. Endothelial cells express anti-apoptotic genes including Bcl-2, Bcl-XL and survivin, which also contribute to angiogenesis and vascular remodeling. We report a central role for protein kinase Cepsilon (PKCepsilon) in the regulation of Bcl-2 expression and cytoprotection of human vascular endothelium against apoptosis. Using myristoylated inhibitory peptides, a predominant role for PKCepsilon in vascular endothelial growth factor-mediated endothelial resistance to apoptosis was revealed. Immunoblotting of endothelial cells infected with an adenovirus expressing a constitutively active form of PKCepsilon (Adv-PKCepsilon-CA) or control Adv-beta-galactosidase demonstrated a 3-fold, PKCepsilon-dependent increase in Bcl-2 expression, with no significant change in Bcl-XL, Bad, Bak, or Bax. The induction of Bcl-2 inhibited apoptosis induced by serum starvation or etoposide, and PKCepsilon activation attenuated etoposide-induced caspase-3 cleavage. The functional role of Bcl-2 was confirmed with Bcl-2 antagonist HA-14-1. Inhibition of phosphoinositide 3-kinase attenuated vascular endothelial growth factor-induced protection against apoptosis, and this was rescued by overexpression of constitutively active PKCepsilon, suggesting PKCepsilon acts downstream of phosphoinositide 3-kinase. Co-immunoprecipitation studies demonstrated a physical interaction between PKCepsilon and Akt, which resulted in formation of a signaling complex, leading to optimal induction of Bcl-2. This study reveals a pivotal role for PKCepsilon in endothelial cell cytoprotection against apoptosis. We demonstrate that PKCepsilon forms a signaling complex and acts co-operatively with Akt to protect human vascular endothelial cells against apoptosis through induction of the anti-apoptotic protein Bcl-2 and inhibition of caspase-3 cleavage.
Introduction of All-Hydrocarbon i,i+3 Staples into α-Helices via Ring-Closing Olefin Metathesis (2010)

The introduction of all-hydrocarbon i,i+3 staples into alpha-helical peptide scaffolds via ring-closing olefin metathesis (RCM) between two alpha-methyl,alpha-pentenylglycine residues incorporated at i and i+3 positions, which lie on the same face of the helix, has been investigated. The reactions were found to be highly dependent upon the side-chain stereochemistry of the amino acids undergoing RCM. The i,i+3 stapling system established here provides a potentially useful alternative to the well-established i,i+4 stapling system now in widespread use.
Derivation and Characterization of a Dengue Type 1 Host Range-Restricted Mutant Virus That Is Attenuated and Highly Immunogenic in Monkeys (2002)

We recently described the derivation of a dengue serotype 2 virus (DEN2mutF) that exhibited a host range-restricted phenotype; it was severely impaired for replication in cultured mosquito cells (C6/36 cells). DEN2mutF virus had selected mutations in genomic sequences predicted to form a 3' stem-loop structure (3'-SL) that is conserved among all flavivirus species. The 3'-SL constitutes the downstream terminal similar95 nucleotides of the 3' noncoding region in flavivirus RNA. Here we report the introduction of these same mutational changes into the analogous region of an infectious DNA derived from the genome of a human-virulent dengue serotype 1 virus (DEN1), strain Western Pacific (DEN1WP). The resulting DEN1 mutant (DEN1mutF) exhibited a host range-restricted phenotype similar to that of DEN2mutF virus. DEN1mutF virus was attenuated in a monkey model for dengue infection in which viremia is taken as a correlate of human virulence. In spite of the markedly reduced levels of viremia that it induced in monkeys compared to DEN1WP, DEN1mutF was highly immunogenic. In addition, DEN1mutF-immunized monkeys retained high levels of neutralizing antibodies in serum and were protected from challenge with high doses of the DEN1WP parent for as long as 17 months after the single immunizing dose. Phenotypic revertants of DEN1mutF and DEN2mutF were each detected after a total of 24 days in C6/36 cell cultures. Complete nucleotide sequence analysis of DEN1mutF RNA and that of a revertant virus, DEN1mutFRev, revealed that (i) the DEN1mutF genome contained no additional mutations upstream from the 3'-SL compared to the DEN1WP parent genome and (ii) the DEN1mutFRev genome contained de novo mutations, consistent with our previous hypothesis that the defect in DEN2mutF replication in C6/36 cells was at the level of RNA replication. A strategy for the development of a tetravalent dengue vaccine is discussed.