gebhart/patrepeval huggingface dataset:
Schwann cells, neurotrophic factors, and peripheral nerve regeneration (1998)

The peripheral nervous system retains a considerable capacity for regeneration. However, functional recovery rarely returns to the preinjury level no matter how accurate the nerve repair is, and the more proximal the injury the worse the recovery. Among a variety of approaches being used to enhance peripheral nerve regeneration are the manipulation of Schwann cells and the use of neurotrophic factors. Such factors include, first, nerve growth factor (NGF) and the other recently identified members of the neurotrophin family, namely, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5); second, the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF); and third, the transforming growth factors (TGFs)-beta and their distant relative, glial cell line-derived neurotrophic factor (GDNF). In this review article we focus on the roles in peripheral nerve regeneration of Schwann cells and of the neurotrophin family, CNTF and GDNF, and the relationship between these. Finally, we discuss what remains to be understood about the possible clinical use of neurotrophic factors.
Inhibition of Tumor Growth, Angiogenesis, and Microcirculation by the Novel Flk-1 Inhibitor SU5416 as Assessed by Intravital Multi-fluorescence Videomicroscopy (1999)

Vascular endothelial growth factor (VEGF) plays a fundamental role in mediating tumor angiogenesis and tumor growth. Here we investigate the direct effect of a novel small molecule inhibitor of the Flk-1-mediated signal transduction pathway of VEGF, SU5416, on tumor angiogenesis and microhemodynamics of an experimental glioblastoma by using intravital multifluorescence videomicroscopy. SU5416 treatment significantly suppressed tumor growth. In parallel, SU5416 demonstrated a potent antiangiogenic activity, resulting in a significant reduction of both the total and functional vascular density of the tumor microvasculature, which indicates an impaired vascularization as well as significant perfusion failure in treated tumors. This malperfusion was not compensated for by changes in vessel diameter or recruitment of nonperfused vessels. Analyses of the tumor microcirculation revealed significant microhemodynamic changes after angiogenesis blockage such as a higher red blood cell velocity and blood flow in remnant tumor vessels when compared with controls. Our results demonstrate that the novel antiangiogenic concept of targeting the tyrosine kinase of Flk-1/KDR by means of a small molecule inhibitor represents an efficient strategy to control growth and progression of angiogenesis-dependent tumors. This study provides insight into microvascular consequences of Flk-1/KDR targeting in vivo and may have important implications for the future treatment of angiogenesis-dependent neoplasms.
Directed Evolution Library Creation (2003)

Biological systems are very special substrates for engineering—uniquely the products of evolution, they are easily redesigned by similar approaches. A simple algorithm of iterative cycles of diversifi
Base-Calling of Automated Sequencer Traces Using Phred. II. Error Probabilities (1998)

Elimination of the data processing bottleneck in high-throughput sequencing will require both improved accuracy of data processing software and reliable measures of that accuracy. We have developed and implemented in our base-calling program phred the ability to estimate a probability of error for each base-call, as a function of certain parameters computed from the trace data. These error probabilities are shown here to be valid (correspond to actual error rates) and to have high power to discriminate correct base-calls from incorrect ones, for read data collected under several different chemistries and electrophoretic conditions. They play a critical role in our assembly program phrap and our finishing program consed.
S-Nitrosylation of DRP1 Does Not Affect Enzymatic Activity and is Not Specific to Alzheimer's Disease (2010)

Mitochondrial dysfunction and synaptic loss are among the earliest events linked to Alzheimer's disease (AD) and might play a causative role in disease onset and progression. The underlying mechanisms of mitochondrial and synaptic dysfunction in AD remain unclear. We previously reported that nitric oxide (NO) triggers persistent mitochondrial fission and causes neuronal cell death. A recent article claimed that S-nitrosylation of dynamin related protein 1 (DRP1) at cysteine 644 causes protein dimerization and increased GTPase activity and is the mechanism responsible for NO-induced mitochondrial fission and neuronal injury in AD, but not in Parkinson's disease (PD). However, this report remains controversial. To resolve the controversy, we investigated the effects of S-nitrosylation on DRP1 structure and function. Contrary to the previous report, S-nitrosylation of DRP1 does not increase GTPase activity or cause dimerization. In fact, DRP1 does not exist as a dimer under native conditions, but rather as a tetramer capable of self-assembly into higher order spiral- and ring-like oligomeric structures after nucleotide binding. S-nitrosylation, as confirmed by the biotin-switch assay, has no impact on DRP1 oligomerization. Importantly, we found no significant difference in S-nitrosylated DRP1 (SNO-DRP1) levels in brains of age-matched normal, AD, or PD patients. We also found that S-nitrosylation is not specific to DRP1 because S-nitrosylated optic atrophy 1 (SNO-OPA1) is present at comparable levels in all human brain samples. Finally, we show that NO triggers DRP1 phosphorylation at serine 616, which results in its activation and recruitment to mitochondria. Our data indicate the mechanism underlying nitrosative stress-induced mitochondrial fragmentation in AD is not DRP1 S-nitrosylation.
Halide exchange reactions between aryl halides and alkali halides catalyzed by nickel metal (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHalide exchange reactions between aryl halides and alkali halides catalyzed by nickel metalS. H. Yang, C. S. Li, and C. H. ChengCite this: J. Org. Chem. 1987, 52, 4, 691–694Publication Date (Print):February 1, 1987Publication History Published online1 May 2002Published inissue 1 February 1987https://pubs.acs.org/doi/10.1021/jo00380a041https://doi.org/10.1021/jo00380a041research-articleACS PublicationsRequest reuse permissionsArticle Views2796Altmetric-Citations55LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Roles of the ankyrin repeats and C-terminal region of the mouse Notch1 intracellular region (1998)

The Notch intracellular region (RAMIC) interacts with a DNA binding protein RBP-J to activate transcription of genes that inhibit cell differentiation. The RAM domain and ankyrin (ANK) repeats of mouse Notch1 RAMIC were shown to be responsible for RBP-J binding and necessary for transactivation. The C-terminal portion of Notch1 RAMIC has also been suggested to be important for transactivation. Using GAL4 fusion constructs, we identified a novel transactivation domain (TAD) between the ANK repeats and the PEST sequence of mouse Notch1. The C-terminal half of mouse Notch2 RAMIC also exhibited TAD activity. Unexpectedly, the RBP-J chimeric protein with the Notch1 TAD failed to activate transcription but the activity was recovered by addition of either the RAM domain or ANK repeats. The results suggest that the activity of Notch1 TAD is repressed by fusion with RBP-J because of the presence of a RBP-J-associated co-repressor(s), which could be displaced by either the RAM domain or ANK repeats. Taken together, mouse Notch1 RAMIC can experimentally be separated into three functional domains: the RAM domain and ANK repeats for RBP-J binding and co-repressor displacement and the C-terminal TAD.
Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver (2014)

Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease.
Applications of synthetic oligodeoxyribonucleotides to problems in molecular biology. (1980)

The applications of synthetic oligodeoxyribonucleotides to problems in molecular biology described in this article are those where the oligodeoxyribonucleotide is a probe for a specific region of a nucleic acid. This includes the isolation of the iso-1-cytochrome c gene of yeast; the sequence determination of RNAs and DNAs including regions of double-stranded DNA; the introduction of defined site-specific point mutations into bacteriophage OX174 and in the in vitro selection of mutant DNA from a mixture with wild-type DNA.
Radiation characteristics of an electrically small MF broadcast antenna - by simulation (2001)

MF broadcast stations typically employ tall towers, heights 0.2 to 0.625 wavelength (/spl lambda/), mounted over extensive radial wire ground systems (120 radials, 0.25 to 0.4 /spl lambda/ long, buried 20 cm below the surface of the ground). In spite of the fact that MF radio broadcast services are to some extent (at least in Canada) moving to the VHF band, there is a continuing world wide interest in MF (even LF) antennas, particularly electrically short antennas, perhaps a growing interest as frequencies are vacated by some broadcasters. This paper reports on a detailed computational electromagnetic analysis of an electrically small MF umbrella antenna system, with electrically short insulated elevated radials. While an acceptable antenna radiation efficiency can be obtained, for electrically small antennas, the greater the efficiency the narrower the bandwidth of the antenna. For antenna heights less than about 0.1 /spl lambda/ the antenna bandwidth can be small, too small to meet the requirements for a MF broadcast station. The antenna system described has an acceptable operational bandwidth, as well a number of unique features.
On the Use of Metabolic Control Analysis in the Optimization of Cyanobacterial Biosolar Cell Factories (2013)

Oxygenic photosynthesis will have a key role in a sustainable future. It is therefore significant that this process can be engineered in organisms such as cyanobacteria to construct cell factories that catalyze the (sun)light-driven conversion of CO2 and water into products like ethanol, butanol, or other biofuels or lactic acid, a bioplastic precursor, and oxygen as a byproduct. It is of key importance to optimize such cell factories to maximal efficiency. This holds for their light-harvesting capabilities under, for example, circadian illumination in large-scale photobioreactors. However, this also holds for the "dark" reactions of photosynthesis, that is, the conversion of CO2, NADPH, and ATP into a product. Here, we present an analysis, based on metabolic control theory, to estimate the optimal capacity for product formation with which such cyanobacterial cell factories have to be equipped. Engineered l-lactic acid producing Synechocystis sp. PCC6803 strains are used to identify the relation between production rate and enzymatic capacity. The analysis shows that the engineered cell factories for l-lactic acid are fully limited by the metabolic capacity of the product-forming pathway. We attribute this to the fact that currently available promoter systems in cyanobacteria lack the genetic capacity to a provide sufficient expression in single-gene doses.
Induction of stem cell-like plasticity in mononuclear cells derived from unmobilised adult human peripheral blood (2003)

Undifferentiated pluripotent stem cells with flexible developmental potentials are not normally found in peripheral blood. However, such cells have recently been reported to reside in the bone marrow. Herein are reported methods of inducing pluripotency in cells derived from unmobilised adult human peripheral blood. In response to the inclusion of purified CR3/43 monoclonal antibody (mAb) to well-established culture conditions, mononuclear cells (MNC) obtained from a single blood donor are converted into pluripotent haematopoietic, neuronal and cardiomyogenic progenitor stem cells or undifferentiated stem cells. The haematopoietic stem cells are CD34+, clonogenic and have been shown to repopulate non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The neuronal precursors transcribe the primitive stem cell markers OCT-4 and nestin, and on maturation, differentially stain positive for neuronal, glial or oligodendrocyte-specific antigens. The cardiomyogenic progenitor stem cells form large bodies of asynchronously beating cells and differentiate into mature cardiomyocytes which transcribe GATA-4. The undifferentiated stem cells do not express haematopoietic-associated markers, are negative for major histocompatibility complex (MHC) class I and II antigens, transcribe high levels of OCT-4 and form embryoid body (EB)-like structures. This induction of stem cell-like plasticity in MNC may have proceeded by a process of retrodifferentiation but, in any case, could have profound clinical and pharmacological implications. Finally, the flexibility and the speed by which a variety of stem cell classes can be generated ex vivo from donor blood could potentially transfer this novel process into a less invasive automated clinical procedure.
The 2pπ*–3dπ interaction in aromatic silanes. Fluorescence from the 1(2pπ, 3dπ) intramolecular charge-transfer state (1984)

The 2pπ*–3dπ interaction in the excited state of aromatic silanes has been studied by means of absorption and emission spectroscopy. Broad and structureless fluorescence spectra of phenyldisilanes and naphthyldisilanes with large Stokes shifts have been observed and they have been attributed to the emissions from the intramolecular charge-transfer (c.t.) states with large dipole moments. Evidence that the c.t. emission originates from the 1(2pπ, 3dπ) state produced by the 2pπ*(aromatic ring)→ 3dπ(Si—Si bond) intramolecular charge transfer is given by the effect of steric twisting on the emission. It is shown that the fast formation (⩽ 1 ns) of the c.t. state from the locally excited state 1(π, π*)1B2(or 1Lb) of phenyldisilanes takes place, followed by rapid decay (⩽ 1 ns) of the intersystem crossing 1(2pπ, 3dπ)→3(π, π*). However, no c.t. emission has been observed for aromatic monosilanes and polycyclic aromatic disilanes (aromatic rings 3) even in fluid polar solvents. The 2pπ*→3dπ intramolecular c.t. mechanism is discussed in comparison with that of the twisted intramolecular charge-transfer (t.i.c.t.) state.
Immunity to Murine Prostatic Tumors: Continuous Provision of T-Cell Help Prevents CD8 T-Cell Tolerance and Activates Tumor-Infiltrating Dendritic Cells (2009)

We reported previously that tumor-specific CD8(+) T cells (TcR-I) become tolerant in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. In this study, we show that CD4(+) TcR transgenic (TcR-II) T cells transferred into TRAMP mice became activated in lymph nodes, trafficked to the prostate, and initially functioned as T(H)1 cells. Although a single cotransfer of TcR-II cells delayed TcR-I cell tolerization, repeated transfer of TcR-II cells was required to prevent TcR-I cell tolerization and significantly slowed progression of TRAMP prostate tumors. After transfer of TcR-II cells, dendritic cells within the tumor expressed higher levels of costimulatory molecules and displayed an enhanced ability to stimulate proliferation of naive T cells. Blockade of CD40-CD40L interactions during TcR-II transfer resulted in a profound reduction in dendritic cell stimulatory capacity and a partial loss of TcR-I effector functions and tumor immunity. These data show that sustained provision of activated tumor-specific CD4(+) T cells alters the immunosuppressive tumor microenvironment, ultimately leading to the control of tumor growth. These findings will assist in the design of more effective immunotherapeutic approaches for cancer.
Mammalian Tumor Xenografts Induce Neovascularization in Zebrafish Embryos (2007)

The zebrafish (Danio rerio)/tumor xenograft model represents a powerful new model system in cancer. Here, we describe a novel exploitation of the zebrafish model to investigate tumor angiogenesis, a pivotal step in cancer progression and target for antitumor therapies. Human and murine tumor cell lines that express the angiogenic fibroblast growth factor (FGF) 2 and/or vascular endothelial growth factor (VEGF) induce the rapid formation of a new microvasculature when grafted close to the developing subintestinal vessels of zebrafish embryos at 48 h postfertilization. Instead, no angiogenic response was exerted by related cell clones defective in the production of these angiogenic growth factors. The newly formed blood vessels sprout from the subintestinal plexus of the zebrafish embryo, penetrate the tumor graft, and express the transcripts for the zebrafish orthologues of the early endothelial markers Fli-1, VEGF receptor-2 (VEGFR2/KDR), and VE-cadherin. Accordingly, green fluorescent protein-positive neovessels infiltrate the graft when tumor cells are injected in transgenic VEGFR2:G-RCFP zebrafish embryos that express green fluorescent protein under the control of the VEGFR2/KDR promoter. Systemic exposure of zebrafish embryos immediately after tumor cell injection to prototypic antiangiogenic inhibitors, including the FGF receptor tyrosine kinase inhibitor SU5402 and the VEGFR2/KDR tyrosine kinase inhibitor SU5416, suppresses tumor-induced angiogenesis without affecting normal blood vessel development. Accordingly, VE-cadherin gene inactivation by antisense morpholino oligonucleotide injection inhibits tumor neovascularization without affecting the development of intersegmental and subintestinal vessels. These data show that the zebrafish/tumor xenograft model represents a novel tool for investigating the neovascularization process exploitable for drug discovery and gene targeting in tumor angiogenesis.
Fourier Transform Spectrometry with a Near-Infrared Supercontinuum Source (2009)

Optical fiber based supercontinuum light sources combine the brightness of lasers with the broad bandwidth of incandescent lamps and thus are promising candidates for sources in spectroscopic applications requiring high brightness and broad bandwidth. Herein, near-infrared (IR) Fourier transform (FT) spectrometry with a supercontinuum (SC) light source is investigated. The efficient, collimated propagation of broad bandwidth SC light through an 18 m path length multipass cell is demonstrated. A normalized spectral difference is calculated for the SC spectrum on consecutive FT mirror scans and is found to vary by less than 0.5%, indicating excellent spectral stability. The rms noise on zero absorbance lines is obtained as a function of the number of mirror scans at 0.125, 2, and 16 cm(-1) resolution for both the SC and conventional tungsten lamp source. The SC source has approximately a factor of ten times more noise than the lamp under comparable conditions for each resolution and data acquisition time. This clearly indicates that spectral acquisition with the SC source is not detector noise limited. NIR-FT spectra of methane and methyl salicylate, acquired with both the SC and lamp source, are reported. These spectra illustrate the advantage the SC source has over the incandescent source in that it can efficiently traverse long path lengths, thus providing a sensitivity advantage. The spectra also demonstrate the disadvantage of the SC source with respect to the lamp in the increased level of amplitude noise. Prospects for the future use of SC sources in absorption spectroscopy, including possible noise mitigation strategies, are briefly discussed.
Microfluidic Encapsulation of Cells in Polymer Microgels (2012)

In this Concept article, recent advances in microfluidic platforms for the generation of cell-laden hydrogel particles (microgels) are reported. Advances in the continuous microfluidic encapsulation of cells in droplets and microgels are critically reviewed, and currently used methods for the encapsulation of cells in polymer microgels are discussed. An outlook on current applications and future directions in this field of research are also presented. This article will be of interest to chemists, materials scientists, cell biologists, bioengineers, and pharmacologists.