gebhart/patrepeval huggingface dataset:
Glucose triggers different global responses in yeast, depending on the strength of the signal, and transiently stabilizes ribosomal protein mRNAs (2003)

Glucose exerts profound effects upon yeast physiology. In general, the effects of high glucose concentrations (>1%) upon Saccharomyces cerevisiae have been studied. In this paper, we have characterized the global responses of yeast cells to very low (0.01%), low (0.1%) and high glucose signals (1.0%) by transcript profiling. We show that yeast is more sensitive to very low glucose signals than was previously thought, and that yeast displays different responses to these different glucose signals. Genes involved in central metabolic pathways respond rapidly to very low glucose signals, whereas genes involved in the biogenesis of cytoplasmic ribosomes generally respond only to glucose concentrations of> 0.1%. We also show that cytoplasmic ribosomal protein mRNAs are transiently stabilized by glucose, indicating that both transcriptional and post-transcriptional mechanisms combine to accelerate the accumulation of ribosomal protein mRNAs. Presumably, this facilitates rapid ribosome biogenesis after exposure to glucose. However, our data indicate that yeast activates ribosome biogenesis only when sufficient glucose is available to make this metabolic investment worthwhile. In contrast, the regulation of metabolic functions in response to very low glucose signals presumably ensures that yeast can exploit even minute amounts of this preferred nutrient.
PET imaging of somatostatin receptors using [68GA]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. (2001)

Imaging of somatostatin receptors (SSTRs) using [111In]diethylenetriaminepentaacetic-acid-octreotide (DTPAOC) has proven to be helpful in the differentiation of meningiomas, neurinomas or neurofibromas, and metastases as well as in the follow-up of meningiomas. A drawback of the SPECT method is its limited sensitivity in detecting small meningiomas. Because of PET's increased spatial resolution and its ability to absolutely quantify biodistribution, a PET tracer for SSTR imaging would be desirable.1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic-acid-D-Phe1-Tyr3-octreotide (DOTATOC) was labeled using the positron-emitting generator nuclide 68Ga. We acquired dynamic PET images over 120 min after intravenous injection of 175 MBq [68Ga]DOTATOC in 3 patients suffering from 8 meningiomas (WHO I degrees; 7- to 25-mm diameter). Patients' heads had been fixed using individually shaped fiber masks equipped with an external stereotactic localizer system to match PET, CT, and MRI datasets.[68Ga]DOTATOC was rapidly cleared from the blood (half-life alpha, 3.5 min; half-life beta, 63 min). Standardized uptake values (SUVs) of meningiomas increased immediately after injection and reached a plateau 60-120 min after injection (mean SUV, 10.6). No tracer could be found in the surrounding healthy brain tissue. All meningiomas (even the 3 smallest [7- to 8-mm diameter]) showed high tracer uptake and could be visualized clearly. Tracer boundaries showed a good correspondence with the matched CT and MRI images. PET provided valuable additional information regarding the extent of meningiomas located beneath osseous structures, especially at the base of the skull.According to our initial experiences, [68Ga]DOTATOC seems to be a very promising new PET tracer for imaging SSTRs even in small meningiomas, offering excellent imaging properties and a very high tumor-to-background ratio.
A Fully Integrated Fail-safe Stimulator Output Stage Dedicated to FES Stimulation (2007)

There is a great demand to reduce the volume of implantable multi-channel stimulators for functional electrical stimulation applications. Miniaturization is currently limited by the size of the large off-chip blocking capacitors that are required for safety. This paper describes a fail-safe stimulator output stage circuit utilizing the principle of high-frequency current-switching, which allows the blocking capacitors to be integrated on-chip. The proposed circuit is based on the bridge rectifier circuit, hence fully utilizing the bidirectional current through the blocking capacitor. The approach has been verified by post-layout simulations in a 1 μm CMOS SOI technology.
Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli (2008)

A low level of GOS (0.24 g/100 mL) in infant formula can improve stool frequency, decrease fecal pH, and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk.
Liver involvement in urea cycle disorders: a review of the literature (2017)

Urea cycle disorders (UCDs) are inborn errors of metabolism of the nitrogen detoxification pathway and encompass six principal enzymatic deficiencies. The aging of UCD patients leads to a better knowledge of the long-term natural history of the condition and to the reporting of previously unnoticed manifestations. Despite historical evidence of liver involvement in UCDs, little attention has been paid to this organ until recently. Hence, we reviewed the available scientific evidence on acute and chronic liver dysfunction and liver carcinogenesis in UCDs and discuss their pathophysiology. Overall, liver involvement, such as acute liver failure or steatotic-like disease, which may evolve toward cirrhosis, has been reported in all six main UCDs. Excessive glycogen storage is also a prominent histologic feature, and hypoglycemia has been reported in citrin deficiency. Hepatocarcinomas seem frequent in some UCDs, such as in citrin deficiency, and can sometimes occur in non-cirrhotic patients. UCDs may differ in liver involvement according to the enzymatic deficiency. Ornithine transcarbamylase deficiency may be associated more with acute liver failure and argininosuccinic aciduria with chronic liver failure and cirrhosis. Direct toxicity of metabolites, downstream metabolic deficiencies, impaired tricarboxylic acid cycle, oxidative stress, mitochondrial dysfunction, energy deficit, and putative toxicity of therapies combine in various ways to cause the different liver diseases reported.
Tyrosine kinase inhibitors. 5. Synthesis and structure-activity relationships for 4-[(phenylmethyl)amino]- and 4-(phenylamino)quinazolines as potent adenosine 5'-triphosphate binding site inhibitors of the tyrosine kinase domain of the epidermal growth factor receptor. (1995)

A series of 4-substituted quinazolines and related compounds have been prepared and evaluated for their ability to inhibit the tyrosine kinase activity of the epidermal growth factor receptor on a phospholipase C-gamma 1-derived substrate. The results show a narrow structure-activity relationship (SAR) for the basic ring system, with quinazoline being the preferred chromophore and benzylamino and anilino the preferred side chains. In the 4-anilino series, substitution on the 3-position of the phenyl ring with small lipophilic electron-withdrawing groups provided analogues with enhanced potency. Two series of compounds [4-(phenylmethyl)amino and 4-(3-bromophenyl)amino] were studied to determine SARs for quinazoline substituents. In the more active 4-(3-bromophenyl)amino series, electron-donating groups (NH2, OMe) at the 6- or 7-position increased activity, in a pattern consistent with a requirement for high electron density in the vicinity of the 8-position of the quinazoline ring. The 6,7-dimethoxy derivatives were the most effective in both series, with the 4-(3-bromophenyl)amino derivative (3) having an IC50 of 0.029 nM, making it by far the most potent reported inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor enzyme.
RNAi-based Analysis of CAP, Cbl, and CrkII Function in the Regulation of GLUT4 by Insulin (2004)

Stimulation of glucose transport by insulin in cultured adipocytes through translocation of intracellular GLUT4 glucose transporters to the plasma membrane has been suggested to require phosphatidylinositol (PI) 3-kinase-dependent and independent mechanisms. To test the involvement of a PI 3-kinase-independent pathway leading to activation of the TC10 GTPase, the putative intermediates CAP, c-Cbl, Cbl-b, and CrkII were selectively depleted in 3T3-L1 adipocytes using highly efficient small interfering (si) RNAs. Simultaneous depletion of the ubiquitination factors c-Cbl plus Cbl-b in cultured adipocytes had the expected effect of delaying dephosphorylation of EGF receptors upon removal of EGF. However, siRNA-mediated gene silencing of both Cbl isoforms or CAP or CrkII in these cells failed to attenuate insulin-stimulated deoxyglucose transport or Myc-tagged GLUT4-GFP translocation at either sub-maximal or maximal concentrations of insulin. The dose-response relationship for insulin stimulation of deoxyglucose transport in primary adipocytes derived from c-Cbl knock-out mice was also identical to insulin action on adipocytes from wild type mice. These data are consistent with the hypothesis that CAP, Cbl iso-forms, and CrkII are not required components of insulin signaling to GLUT4 transporters.
Surface Plasmon Characteristics of Tunable Photoluminescence in Single Gold Nanorods (2005)

Light emission resulting from two-photon excited gold nanoparticles has been proposed to originate from the radiative decay of surface plasmon resonances. In this vein, we investigated luminescence from individual gold nanorods and found that their emission characteristics closely resemble surface plasmon behavior. In particular, we observed spectral similarities between the scattering spectra of individual nanorods and their photoluminescence emission. We also measured a blueshift of the photoluminescence peak wavelength with decreasing aspect ratio of the nanorods as well as an optically tunable shape-dependent spectrum of the photoluminescence. The emission yield of single nanorods strongly depends on the orientation of the incident polarization consistent with the properties of surface plasmons.
Preparation of new classes of aliphatic, allylic, and benzylic zinc and copper reagents by the insertion of zinc dust into organic halides, phosphates, and sulfonates (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of new classes of aliphatic, allylic, and benzylic zinc and copper reagents by the insertion of zinc dust into organic halides, phosphates, and sulfonatesCarole Jubert and Paul KnochelCite this: J. Org. Chem. 1992, 57, 20, 5425–5431Publication Date (Print):September 1, 1992Publication History Published online1 May 2002Published inissue 1 September 1992https://pubs.acs.org/doi/10.1021/jo00046a026https://doi.org/10.1021/jo00046a026research-articleACS PublicationsRequest reuse permissionsArticle Views2124Altmetric-Citations116LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Vagus nerve stimulation enhances perforant path-CA3 synaptic transmission via the activation of β-adrenergic receptors and the locus coeruleus (2011)

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and depression and has cognition-enhancing effects in patients with Alzheimer's disease. The hippocampus is widely recognized to be related to epilepsy, depression, and Alzheimer's disease. One possible mechanism of VNS involves its effect on the hippocampus; i.e. it increases the release of noradrenaline in the hippocampus. However, the effect of VNS on synaptic transmission in the hippocampus is unknown. To determine whether VNS modulates neurotransmission in the hippocampus, we examined the effects of VNS on perforant path (PP)-CA3 synaptic transmission electrophysiologically in anaesthetized rats. VNS induces a persistent enhancement of PP-CA3 field excitatory post-synaptic potentials (fEPSPs). Arc, an immediate early gene, was used to identify active brain regions after VNS. The locus coeruleus (LC), which contains the perikarya of noradrenergic projections, harboured more Arc-positive cells, as measured by in-situ hybridization, after 10-min VNS. In addition, electrical lesions of LC neurons or intraventricular administration of the β-adrenergic receptor antagonist timolol prevented the enhancement of PP-CA3 responses by VNS. In conclusion, the protracted increase in PP-CA3 synaptic transmission that is induced by VNS entails activation of the LC and β-adrenergic receptors. Our novel findings suggest that information from the periphery modulates synaptic transmission in the CA3 region of the hippocampus.
Persisting Viral Sequences Shape Microbial CRISPR-based Immunity (2012)

Well-studied innate immune systems exist throughout bacteria and archaea, but a more recently discovered genomic locus may offer prokaryotes surprising immunological adaptability. Mediated by a cassette-like genomic locus termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), the microbial adaptive immune system differs from its eukaryotic immune analogues by incorporating new immunities unidirectionally. CRISPR thus stores genomically recoverable timelines of virus-host coevolution in natural organisms refractory to laboratory cultivation. Here we combined a population genetic mathematical model of CRISPR-virus coevolution with six years of metagenomic sequencing to link the recoverable genomic dynamics of CRISPR loci to the unknown population dynamics of virus and host in natural communities. Metagenomic reconstructions in an acid-mine drainage system document CRISPR loci conserving ancestral immune elements to the base-pair across thousands of microbial generations. This 'trailer-end conservation' occurs despite rapid viral mutation and despite rapid prokaryotic genomic deletion. The trailer-ends of many reconstructed CRISPR loci are also largely identical across a population. 'Trailer-end clonality' occurs despite predictions of host immunological diversity due to negative frequency dependent selection (kill the winner dynamics). Statistical clustering and model simulations explain this lack of diversity by capturing rapid selective sweeps by highly immune CRISPR lineages. Potentially explaining 'trailer-end conservation,' we record the first example of a viral bloom overwhelming a CRISPR system. The polyclonal viruses bloom even though they share sequences previously targeted by host CRISPR loci. Simulations show how increasing random genomic deletions in CRISPR loci purges immunological controls on long-lived viral sequences, allowing polyclonal viruses to bloom and depressing host fitness. Our results thus link documented patterns of genomic conservation in CRISPR loci to an evolutionary advantage against persistent viruses. By maintaining old immunities, selection may be tuning CRISPR-mediated immunity against viruses reemerging from lysogeny or migration.
Fibroblast seeding and culture in biodegradable porous substrates (1995)

A natural poly(hydroxybutyrate-co-9% hydroxyvalerate) copolyester was processed into a three-dimensional porous foam structure by salt leaching/solvent casting with previously sieved sodium chloride salts. Laboratory-built P(HB-9% HV) foams and commercial collagen sponges were cut into small rectangular specimens, sterilized, and prewetted using ethanol, rinsed with Dulbecco's minimum essential medium + 10% serum culture media, and seeded with fibroblasts isolated from canine anterior cruciate ligaments. The fibroblast cultures into such porous substrates were performed from 0 to 35 days by incubation (5% CO2) at 37 degrees C. It demonstrated that the P(HB-HV) sustained a cell proliferation rate similar to that observed in collagen sponges, up to at least 35 days, with a maximal cell density on the day 28 in culture. On the other hand, the P(HB-HV) materials kept their structural integrity during the culture period while the collagen foams contracted greatly. Further, the total protein production after 4 weeks in culture was found to be twice as high (190 +/- 10%) in the P(HB-9% HV) foam than in the collagen foam. Porous P(HB-HV) materials appear to be adequate polymeric substrates for cell cultures. However, further evaluations are still required to confirm such preliminary results.
Platelet-dependent primary hemostasis promotes selectin- and integrin- mediated neutrophil adhesion to damaged endothelium under flow conditions (1996)

Co-localization of blood platelets and granulocytes at sites of hemostasis and inflammation has triggered an intense interest in possible interactions between these cellular processes and induction of vessel wall injury. Leukocyte adhesion to endothelial cells decreases with increasing shear and is dependent on an initial rolling phase mediated by selectins. We hypothesized that flow-dependent platelet adhesion at an injured vessel wall will lead to P-selectin expression by platelets, thus mediating leukocyte co-localization. A perfusion chamber was used in which flowing whole blood induced platelet adhesion to a subendothelial matrix (ECM) of cultured human umbilical vein endothelial cells (HUVEC). We compared neutrophil (polymorphonuclear leukocyte [PMN]) interactions with HUVEC and their ECM with and without adhered platelets. PMNs adhered predominantly to ECM-adhered platelets and not to endothelial cells. ECM alone did not support PMN adhesion under flow conditions. PMN adhesion to unstimulated HUVEC was only substantial at low shear (up to 200 cells/mm2 at shear stress 80 mPa). In marked contrast, PMN adhesion to ECM-adhered platelets was dramatically increased, and adhesion was demonstrated at much higher shear stress (up to 640 mPa). Studies with specific antibodies showed that the platelet-dependent neutrophil adhesion was selectin-mediated. Inhibition of P-selectin caused a marked inhibition of adhesion at high shear stress, whereas the role of leukocyte L-selectin was less pronounced. beta2-Integrin-blocking antibodies inhibited static neutrophil adhesion. fMLP induced L-selectin shedding from leukocytes, resulting in decreased leukocyte adhesion. In conclusion, platelet-dependent hemostasis at the ECM appears to be a powerful intermediate in neutrophil-vessel wall interactions at shear stresses that normally do not allow neutrophil adhesion to intact endothelium.
Near Infrared Spectroscopy for Intraoperative Monitoring of the Spinal Cord (2002)

This near infrared spectroscopy technique monitors changes in oxygenation of the spinal cord, and therefore appears capable of intraoperative warning about impending vascular compromise of the spinal cord.
Comparative MR analysis of the entorhinal cortex and hippocampus in diagnosing Alzheimer disease. (1999)

The volumetric measurements of both the entorhinal cortex and hippocampus have comparably high discriminative power in diagnosing Alzheimer disease. In clinical practice, hippocampal volumetry may be more feasible, because the method is easier to use and has less variability.
Regulation of cell signaling induced by the cell adhesion molecule, E-cadherin (1999)

Cell adhesion is important in the regulation of many cellular behaviors including cell growth, differentiation, migration, cell survival and cell transformation. Adherens-type junctions are a specific type of cell-cell adhesion that are stabilized by the actin cytoskeleton. These adhesions are initiated by the homotypic binding of cadherin extracellular domains on neighboring cells and are linked to the actin cytoskeleton through a complex of proteins that includes the catenins. Recently, these sites of cell adhesion have been implicated in cell signaling. Here, we characterize novel signaling pathways activated by aggregation of E-cadherin. We show that during adherens-type junction formation, a rapid burst in epidermal growth factor receptor (EGFR) signaling occurs. This signaling represents a new alternative mechanism of EGFR activation. We propose a mechanism in which E-cadherin aggregation promotes oligomerization of both EGFR and a repressive phosphatase. Thus, oligomerization of the phosphatase results in its inactivation and allows activation of oligomerized EGFR. During colony formation, non-transformed epithelial cells form cell-cell contacts and decrease their cell-extracellular matrix adhesions called focal adhesions. Transformed cells are unable to form stable cell-cell adhesions and maintain their focal adhesions. We examined whether E-cadherin-mediated cell signaling influenced cell-extracellular matrix adhesion. Indeed, aggregation of E-cadherin in cells devoid of cell-cell contacts, stimulates the loss of focal adhesions. Inhibition of EGFR activity prevents E-cadherin induced focal adhesion disassembly. Preliminary examination of E-cadherin signaling in Ras transformed cells suggests that E-cadherin mediated signaling is non-functional. These results suggest a mechanism of coordinating soluble growth factor and cell-cell adhesion induced signaling to affect cell-extracellular matrix adhesion. Furthermore, these results implicate defects in cellular signaling in transformed cells that have altered cell adhesion.
Alaska's first American century: the view ahead (1968)

Alaska and Canada have recently been celebrating the one hundredth anniversary of those separate events, both occurring in 1867, which gave birth to their modern political alignment. Because of its geographical position, Alaska's history, more than that of any other state of the union, developed in response to international events. Its original Russian occupation, and its acquisition by the United States a century ago, emerge from the history of eastern Siberia, and are related to events in the region of the river Amur, once a part of the ancient Chinese empire. Its purchase also carried with it a boundary dispute merging Alaska's history with that of western Canada.