gebhart/patrepeval huggingface dataset:
The Gcs1 Arf-GAP Mediates Snc1,2 v-SNARE Retrieval to the Golgi in Yeast (2006)

Gcs1 is an Arf GTPase-activating protein (Arf-GAP) that mediates Golgi-ER and post-Golgi vesicle transport in yeast. Here we show that the Snc1,2 v-SNAREs, which mediate endocytosis and exocytosis, interact physically and genetically with Gcs1. Moreover, Gcs1 and the Snc v-SNAREs colocalize to subcellular structures that correspond to the trans-Golgi and endosomal compartments. Studies performed in vitro demonstrate that the Snc-Gcs1 interaction results in the efficient binding of recombinant Arf1Delta17N-Q71L to the v-SNARE and the recruitment of purified coatomer. In contrast, the presence of Snc had no effect on Gcs1 Arf-GAP activity in vitro, suggesting that v-SNARE binding does not attenuate Arf1 function. Disruption of both the SNC and GCS1 genes results in synthetic lethality, whereas overexpression of either SNC gene inhibits the growth of a distinct subset of COPI mutants. We show that GFP-Snc1 recycling to the trans-Golgi is impaired in gcs1Delta cells and these COPI mutants. Together, these results suggest that Gcs1 facilitates the incorporation of the Snc v-SNAREs into COPI recycling vesicles and subsequent endosome-Golgi sorting in yeast.
Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis (2006)

The object of this study was to monitor the safety and efficacy of long-term use of an oromucosal cannabis-based medicine (CBM) in patients with multiple sclerosis (MS). A total of 137 MS patients with symptoms not controlled satisfactorily using standard drugs entered this open-label trial following a 10-week, placebo-controlled study. Patients were assessed every eight weeks using visual analogue scales and diary scores of main symptoms, and were followed for an average of 434 days (range: 21 -814). A total of 58 patients (42.3%) withdrew due to lack of efficacy (24); adverse events (17); withdrew consent (6); lost to follow-up (3); and other (8). Patients reported 292 unwanted effects, of which 251 (86%) were mild to moderate, including oral pain (28), dizziness (20), diarrhoea (17), nausea (15) and oromucosal disorder (12). Three patients had five 'serious adverse events' between them--two seizures, one fall, one aspiration pneumonia, one gastroenteritis. Four patients had first-ever seizures. The improvements recorded and dosage taken in the acute study remained stable. Planned, sudden interruption of CBM for two weeks in 25 patients (of 62 approached) did not cause a consistent withdrawal syndrome, although 11 (46%) patients reported at least one of--tiredness, interrupted sleep, hot and cold flushes, mood alteration, reduced appetite, emotional lability, intoxication or vivid dreams. Twenty-two (88%) patients re-started CBM treatment. We conclude that long-term use of an oromucosal CBM (Sativex) maintains its effect in those patients who perceive initial benefit. The precise nature and rate of risks with long-term use, especially epilepsy, will require larger and longer-term studies.
Sensory processing in adults with autism spectrum disorders (2009)

Unusual sensory processing has been widely reported in autism spectrum disorders (ASDs); however, the majority of research in this area has focused on children. The present study assessed sensory processing in adults with ASD using the Adult/Adolescent Sensory Profile (AASP), a 60-item self-report questionnaire assessing levels of sensory processing in everyday life. Results demonstrated that sensory abnormalities were prevalent in ASD, with 94.4 percent of the ASD sample reporting extreme levels of sensory processing on at least one sensory quadrant of the AASP. Furthermore, analysis of the patterns of sensory processing impairments revealed striking within-group variability in the ASD group, suggesting that individuals with ASD could experience very different, yet similarly severe, sensory processing abnormalities. These results suggest that unusual sensory processing in ASD extends across the lifespan and have implications regarding both the treatment and the diagnosis of ASD in adulthood.
Tuning the volume of the immune response: strength and persistence of stimulation determine migration and cytokine secretion of dendritic cells (2004)

Migration to lymph nodes and secretion of cytokines are critical functions of mature dendritic cells (DCs); however, these 2 functions are not necessarily linked. This is the first report showing that quantitative differences in identical signaling pathways determine DC migration and cytokine secretion. Using different polymerized forms of CD40 ligand, we demonstrate that the strength and persistence of CD40 signaling can induce either function. Induction of monocyte-derived DC (MoDC) migration required a weak and transient CD40 signal, whereas strong and persistent CD40 signaling blocked migration and biased toward cytokine secretion. In contrast to MoDCs, CD40 activation of CD1c+ peripheral blood DCs (PBDCs) induced a nonpersistent, intracellular signaling profile resulting in migratory-type DCs unable to secrete interleukin-12p70 (IL-12p70). Extracellular signal-regulated kinase 1/2 (ERK1/2) and p38K activation synergistically mediated cytokine secretion, whereas migration was enhanced by p38K activation but reduced by persistent ERK1/2 activity. This model of signal strength and persistence also applied when stimulating DCs with intact microbes. Thus, a novel concept emerges in which the type of immune response induced by DCs is tuned by the strength and persistence of DC activating signals.
Arrays of Ultracompliant Electrochemical Dry Gel Cells for Stretchable Electronics (2010)

Ultracompliant electrochemical dry cells are connected in series powering an embedded light emitting diode in different states of mechanical stretch.
Extensibility safety and performance in the SPIN operating system (1995)

article Free Access Share on Extensibility safety and performance in the SPIN operating system Authors: B. N. Bershad Department of Computer Science and Engineering, University of Washington, Seattle, WA Department of Computer Science and Engineering, University of Washington, Seattle, WAView Profile , S. Savage Department of Computer Science and Engineering, University of Washington, Seattle, WA Department of Computer Science and Engineering, University of Washington, Seattle, WAView Profile , P. Pardyak Department of Computer Science and Engineering, University of Washington, Seattle, WA Department of Computer Science and Engineering, University of Washington, Seattle, WAView Profile , E. G. Sirer Department of Computer Science and Engineering, University of Washington, Seattle, WA Department of Computer Science and Engineering, University of Washington, Seattle, WAView Profile , M. E. Fiuczynski Department of Computer Science and Engineering, University of Washington, Seattle, WA Department of Computer Science and Engineering, University of Washington, Seattle, WAView Profile , D. Becker Department of Computer Science and Engineering, University of Washington, Seattle, WA Department of Computer Science and Engineering, University of Washington, Seattle, WAView Profile , C. Chambers Department of Computer Science and Engineering, University of Washington, Seattle, WA Department of Computer Science and Engineering, University of Washington, Seattle, WAView Profile , S. Eggers Department of Computer Science and Engineering, University of Washington, Seattle, WA Department of Computer Science and Engineering, University of Washington, Seattle, WAView Profile Authors Info & Claims ACM SIGOPS Operating Systems ReviewVolume 29Issue 5Dec. 3, 1995pp 267–283https://doi.org/10.1145/224057.224077Published:03 December 1995Publication History 650citation5,686DownloadsMetricsTotal Citations650Total Downloads5,686Last 12 Months534Last 6 weeks45 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Publisher SiteeReaderPDF
Relevance of Assembly-Activating Protein for Adeno-associated Virus Vector Production and Capsid Protein Stability in Mammalian and Insect Cells (2017)

The discovery that adeno-associated virus 2 (AAV2) encodes an eighth protein, called assembly-activating protein (AAP), transformed our understanding of wild-type AAV biology. Concurrently, it raised questions about the role of AAP during production of recombinant vectors based on natural or molecularly engineered AAV capsids. Here, we show that AAP is indeed essential for generation of functional recombinant AAV2 vectors in both mammalian and insect cell-based vector production systems. Surprisingly, we observed that AAV2 capsid proteins VP1 to -3 are unstable in the absence of AAP2, likely due to rapid proteasomal degradation. Inhibition of the proteasome led to an increase of intracellular VP1 to -3 but neither triggered assembly of functional capsids nor promoted nuclear localization of the capsid proteins. Together, this underscores the crucial and unique role of AAP in the AAV life cycle, where it rapidly chaperones capsid assembly, thus preventing degradation of free capsid proteins. An expanded analysis comprising nine alternative AAV serotypes (1, 3 to 9, and rh10) showed that vector production always depends on the presence of AAP, with the exceptions of AAV4 and AAV5, which exhibited AAP-independent, albeit low-level, particle assembly. Interestingly, AAPs from all 10 serotypes could cross-complement AAP-depleted helper plasmids during vector production, despite there being distinct intracellular AAP localization patterns. These were most pronounced for AAP4 and AAP5, congruent with their inability to rescue an AAV2/AAP2 knockout. We conclude that AAP is key for assembly of genuine capsids from at least 10 different AAV serotypes, which has implications for vectors derived from wild-type or synthetic AAV capsids.<b>IMPORTANCE</b> Assembly of adeno-associated virus 2 (AAV2) is regulated by the assembly-activating protein (AAP), whose open reading frame overlaps with that of the viral capsid proteins. As the majority of evidence was obtained using virus-like particles composed solely of the major capsid protein VP3, AAP's role in and relevance for assembly of genuine AAV capsids have remained largely unclear. Thus, we established a <i>trans</i>-complementation assay permitting assessment of AAP functionality during production of recombinant vectors based on complete AAV capsids and derived from any serotype. We find that AAP is indeed a critical factor not only for AAV2, but also for generation of vectors derived from nine other AAV serotypes. Moreover, we identify a new role of AAP in maintaining capsid protein stability in mammalian and insect cells. Thereby, our study expands our current understanding of AAV/AAP biology, and it concomitantly provides insights into the importance of AAP for AAV vector production.
Caveolin-1 and caveolin-2,together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis. (2003)

Thyroid cancer is common, occurring in 1% of the general population. The relative frequencies of two of the most common subtypes of thyroid carcinoma, follicular (FTC) and papillary (PTC), vary depending on the regional prevalence of iodine deficiency. Although PTC has been more extensively studied, the etiology of sporadic FTC is poorly understood. To further elucidate this, we conducted microarray expression comparison of FTC tumors and normal thyroid tissue. Three commonly down-regulated genes, caveolin-1, caveolin-2, and GDF10/BMP3b, were chosen for further study on the basis of their localization to two chromosomal regions, 7q31.1 and 10q11.1, that commonly show loss of heterozygosity in FTC. Two additional genes, glypican-3 and a novel chordin-like gene, were also analyzed in view of their involvement in bone morphogenetic protein signaling and possible interaction with GDF10. Each of these five genes was down-regulated in >or=15 of 19 FTC tumors (79%) by semiquantitative reverse transcription-PCR. Caveolin-1 showed preferential down-regulation of its beta-isoform at both the mRNA and protein level, suggesting a distinct function for this isoform. Caveolin-1 is of particular functional interest because it has been shown to interact with PTEN, the tumor suppressor gene mutated in Cowden syndrome, an inherited multiple hamartoma syndrome that includes predisposition to FTC. Immunohistochemical analysis of 141 thyroid tumors of various histological types showed significantly fewer caveolin-1-positive tumors in FTCs, including insular type tumors, and Hurthle cell carcinomas in comparison with normal thyroid. PTC and anaplastic thyroid carcinomas did not show significant down-regulation, and thus, caveolin-1 may become a useful molecular marker to differentiate the various histologies of thyroid malignancies.
Wavelength accuracy and output power of multiwavelength DFB laser arrays with integrated star couplers and optical amplifiers (1996)

In this letter, we report the static performance of multiwavelength DFB laser arrays with integrated star couplers and optical amplifiers built for the reconfigurable optical network testbed. By the use of wavelength redundancy and proximity effect, wavelength deviations of /spl plusmn/0.2 nm or less from the designated eight-wavelength comb have been achieved with high yield. Simultaneous operation of eight wavelengths has also been demonstrated. In spite of the inherent splitting loss of 13 dB, high output powers of about -13 dBm and 0 dBm per wavelength have been measured into a single-mode fiber without and with on-chip optical amplification, respectively.
Complete Meiosis from Human Induced Pluripotent Stem Cells (2011)

Gamete failure-derived infertility affects millions of people worldwide; for many patients, gamete donation by unrelated donors is the only available treatment. Embryonic stem cells (ESCs) can differentiate in vitro into germ-like cells, but they are genetically unrelated to the patient. Using an in vitro protocol that aims at recapitulating development, we have achieved, for the first time, complete differentiation of human induced pluripotent stem cells (hiPSCs) to postmeiotic cells. Unlike previous reports using human ESCs, postmeiotic cells arose without the over-expression of germline related transcription factors. Moreover, we consistently obtained haploid cells from hiPSCs of different origin (keratinocytes and cord blood), produced with a different number of transcription factors, and of both genetic sexes, suggesting the independence of our approach from the epigenetic memory of the reprogrammed somatic cells. Our work brings us closer to the production of personalized human gametes in vitro.
Spinal Instrumentation in the Management of Degenerative Disorders of the Lumbar Spine (1997)

The use of spinal instrumentation as an adjunct to fusion for the treatment of degenerative disorders of the lumbar spine is controversial. Instrumented lumbar fusions, in specific instances, may improve patient outcomes. For patients undergoing single level primary lumbar arthrodesis, the available data do not conclusively support the efficacy of spinal instrumentation. However, in the setting of previous failed lumbar surgery, iatrogenic or degenerative lumbar spondylolisthesis, spinal instrumentation may be useful as an adjunct to fusion. Possible advantages associated with the use of instrumentation include: correction of deformity in frontal and sagittal planes; decreased pseudarthrosis rates; prevention of progression of spondylolisthesis, and provision of spinal stability in the absence of intact posterior elements. Complications associated with the use of instrumentation include: increased cost; increased operative times; increased infection rate; increased reoperation rate; and a steep learning curve. Therefore, when instrumentation is to be used, the benefits must outweigh the risks. These risks can be minimized by the judicious use of instrumentation by experienced surgeons, for specific indications as supported by the literature.
Dengue Viremia Titer, Antibody Response Pattern, and Virus Serotype Correlate with Disease Severity (2000)

Viremia titers in serial plasma samples from 168 children with acute dengue virus infection who were enrolled in a prospective study at 2 hospitals in Thailand were examined to determine the role of virus load in the pathogenesis of dengue hemorrhagic fever (DHF). The infecting virus serotype was identified for 165 patients (DEN-1, 46 patients; DEN-2, 47 patients; DEN-3, 47 patients, DEN-4, 25 patients). Patients with DEN-2 infections experienced more severe disease than those infected with other serotypes. Eighty-one percent of patients experienced a secondary dengue virus infection that was associated with more severe disease. Viremia titers were determined for 41 DEN-1 and 46 DEN-2 patients. Higher peak titers were associated with increased disease severity for the 31 patients with a peak titer identified (mean titer of 107.6 for those with dengue fever vs. 108.5 for patients with DHF, P=.01). Increased dengue disease severity correlated with high viremia titer, secondary dengue virus infection, and DEN-2 virus type.
An iteratively-trained segmentation-free phrase translation model for statistical machine translation (2007)

Attempts to estimate phrase translation probablities for statistical machine translation using iteratively-trained models have repeatedly failed to produce translations as good as those obtained by estimating phrase translation probablities from surface statistics of bilingual word alignments as described by Koehn, et al. (2003). We propose a new iteratively-trained phrase translation model that produces translations of quality equal to or better than those produced by Koehn, et al.'s model. Moreover, with the new model, translation quality degrades much more slowly as pruning is tightend to reduce translation time.
Analysis of the killing of spores of Bacillus subtilis by a new disinfectant, SteriloxR (2001)

This work provides information on the mechanism of spore resistance to and spore killing by a new disinfectant.
Effects of nutritional status on wound healing. (1993)

Malnutrition causes an array of metabolic alterations that affect wound healing. Stressed starvation, in which essential protein stores in lean body mass and viscera are utilized, is of utmost concern. Hospital-related malnutrition usually presents as a combination of both protein and energy malnutrition. Key nutrients play specific roles in wound healing. For example, vitamin C is essential for collagen synthesis, vitamin A enhances epithelialization, and zinc is necessary for cell mitosis and cell proliferation. Modern methods are available to determine an array of serum nutrient levels; however, these investigations are often inadequate, because serum levels of specific nutrients frequently do not reflect the total body content. Therefore the common association between generalized malnutrition and deficiencies of specific nutrients must be recognized. By using current nutritional techniques such as anthropometrics, albumin, transferrin, and immune status, one could determine nutritional deficiencies and thereby could replete all nutrients, including protein, carbohydrate, fat, vitamins, and minerals, through either parenteral or enteral support.
Isoform I (mdr3) is the major form of P-glycoprotein expressed in mouse brain capillaries. Evidence for cross-reactivity of antibody C219 with an unrelated protein (1995)

P-glycoprotein (P-gp) is expressed in various non-cancerous tissues such as the endothelial cells of the blood-brain barrier. We used several monoclonal antibodies (mAbs) and isoform-specific polyclonal antibodies to establish which P-gp isoforms are expressed in isolated mouse brain capillaries. P-gp class I isoform was detected in capillaries with a Western immunoblotting procedure using a specific antiserum. No immunoreactivity was observed with either class II- or class III-specific antisera. Immunoreactivity was observed with mAb C219. However, this antibody detected two distinct immunoreactive proteins (155 and 190 kDa) in the isolated brain capillaries. These two proteins comigrated as a broad band when the samples were submitted to heat prior to gel electrophoresis. The glycoprotein nature of these two antigens was evaluated by their sensitivity to N-glycanase treatment. Following this treatment, the size of the proteins was reduced from 190 and 155 kDa to 180 and 120 kDa, respectively. Triton X-114 phase-partitioning studies showed that the 190 kDa immunoreactive protein was poorly solubilized by Triton X-114, while the 155 kDa protein was partitioned in the detergent-rich phase. In labelling experiments, only the 155 kDa protein was photolabelled with [125I]iodoarylazidoprazosin. These results show that a 190 kDa protein detected by antibody C219 is an antigen unrelated to the three P-gp isoforms presently known. Cross-reactivity of C219 with an unrelated protein emphasizes the fact that more than one antibody should be used in the assessment of P-gp expression in cell lines and tissues.
Edge and Tip Diffraction Imaging in Three Dimensions (2011)

The dimensionality of the diffracted wave is related to the dimensionality of the diffractor: a surface reflected ray is uniquely determined, edge diffracted rays strike out a one-parameter pencil, tip diffracted rays a two-parameter pencil of rays. These topological notions are important to analyse the effect of diffraction imaging by specularity suppression. In diffraction imaging reflectivity is fully suppressed, edge diffractivity partly suppressed, while tip diffractivity stands out unsuppressed. These observations have a significant impact on the structural interpretation of three-dimensional diffraction images. Edges constitute the skeleton of a structural model and tips indicate the joints of the skeleton.
Imaging Microvasculature with Contrast Enhanced Ultraharmonic Ultrasound (2013)

Purpose: Atherosclerotic plaque neovascularization was shown to be one of the strongest predictors of future cardiovascular events [1]. Yet, the clinical tools for coronary wall microvasculature detection in vivo are lacking. Here we report a contrast-enhanced ultrasound pulse sequence capable of detecting microvasculature invisible in conventional intracoronary imaging.
Circulating Adiponectin and Leptin in Relation to Myelodysplastic Syndrome: A Case-Control Study (2007)

Circulating adiponectin and leptin may play an important role in MDS etiopathogenesis. Future studies are needed to confirm these associations and to explore underlying mechanisms.
Tumor Progression Despite Efficient Tumor Antigen Cross-Presentation and Effective “Arming” of Tumor Antigen-Specific CTL (2001)

To determine whether APC function or "arming" of CTL for lytic function are the points at which Ags from a nonimmunogenic tumor fail to induce an effective immune response, we established a murine tumor model that expressed intracellular OVA and selected a clone (cOVA-9) that remained susceptible to lysis by specific CD8(+) T cells throughout tumor growth. Viable cOVA-9 tumor cells grew in normal mice at a rate similar to the parental tumor, and vaccination with irradiated cOVA-9 cells did not induce protection against itself or the parental line, confirming its nonimmunogenic status. In vivo evaluation during tumor growth demonstrated persisting tumor Ag cross-presentation accompanied by the generation of potent, specific CTL which were detectable when tumors were barely palpable. Despite the presence of highly active CTL in the tumor-draining lymph nodes, there was no apparent lysis of tumor-associated APC. These data show that tumor-draining APC are not dysfunctional with regard to two crucial processes, in vivo tumor Ag cross-presentation and specific CTL arming, and that failure to prevent tumor growth is not in the induction phase, but in the effector phase and occurs within the tumor itself before the tumor matrix is established.