gebhart/patrepeval huggingface dataset:
An epidermal growth factor receptor variant III–targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme (2009)

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent and tumor-specific mutation widely expressed in GBMs and other neoplasms. The safety and immunogenicity of a dendritic cell (DC)-based vaccine targeting the EGFRvIII antigen was evaluated in this study. Adults with newly diagnosed GBM, who had undergone gross-total resection and standard conformal external beam radiotherapy, received three consecutive intradermal vaccinations with autologous mature DCs pulsed with an EGFRvIII-specific peptide conjugated to keyhole limpet hemocyanin. The dose of DCs was escalated in cohorts of three patients. Patients were monitored for toxicity, immune response, radiographic and clinical progression, and death. No allergic reactions or serious adverse events were seen. Adverse events were limited to grade 2 toxicities. The maximum feasible dose of antigen-pulsed mature DCs was reached at 5.7 x 10(7) +/- 2.9 x 10(7) SD without dose-limiting toxicity. EGFRvIII-specific immune responses were evident in most patients. The mean time from histologic diagnosis to vaccination was 3.6 +/- 0.6 SD months. Median time to progression from vaccination was 6.8 months [95% confidence interval (C.I.(95)), 2.5-8.8], and median survival time from vaccination was 18.7 months (C.I.(95), 14.5-25.6). Overall median survival from time of histologic diagnosis was 22.8 months (C.I.(95), 17.5-29). This study establishes the EGFRvIII mutation as a safe and immunogenic tumor-specific target for immunotherapy.
Clinical Evaluation of an Image-Guided Cochlear Implant Programming Strategy (2014)

The cochlear implant (CI) has been labeled the most successful neural prosthesis. Despite this success, a significant number of CI recipients experience poor speech understanding, and, even among the best performers, restoration to normal auditory fidelity is rare. While significant research efforts have been devoted to improving stimulation strategies, few developments have led to significant hearing improvement over the past two decades. We have recently introduced image processing techniques that open a new direction for advancement in this field by making it possible, for the first time, to determine the position of implanted CI electrodes relative to the nerves they stimulate using computed tomography images. In this article, we present results of an image-guided, patient-customized approach to stimulation that utilizes the electrode position information our image processing techniques provide. This approach allows us to identify electrodes that cause overlapping stimulation patterns and to deactivate them from a patient's map. This individualized mapping strategy yields significant improvement in speech understanding in both quiet and noise as well as improved spectral resolution in the 68 adult CI recipients studied to date. Our results indicate that image guidance can improve hearing outcomes for many existing CI recipients without requiring additional surgery or the use of 'experimental' stimulation strategies, hardware or software.
A Study of Modular AWGs for Large-Scale Optical Switching Systems (2012)

Array-waveguide grating (AWG) is a kind of passive wavelength router. It can perform nonblocking switching functions in conjunction with tunable wavelength converters (TWCs). For optical switching systems with large number of ports, however, the scalability of the AWG is restricted by coherent crosstalk. In this paper, we propose a modular method of designing arrays of AWGs for large-scale switching systems, in which a contention-free connection from an idle input to an idle output can always be established regardless of the number of existing connections in progress. The construction process of AWG networks is sometimes called AWG function decomposition. For the decomposition of an N × N AWG, we describe the modular architecture of a functionally equivalent three-stage network of smaller AWGs, and derive the necessary and sufficient conditions on the number of smaller AWG modules needed for nonblocking switching. Our results can be applied to the decomposition of any AWG components employed in an AWG-based switching network to suppress the coherent crosstalk.
Systematic analysis of yeast strains with possible defects in lipid metabolism (1999)

Lipids are essential components of all living cells because they are obligate components of biological membranes, and serve as energy reserves and second messengers. Many but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of the yeast Saccharomyces cerevisiae have been cloned and gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes or the turnover and degradation of complex lipids. To obtain more insight into lipid metabolism, regulation of lipid biosynthesis and the role of lipids in organellar membranes, a group of five European laboratories established methods suitable to screen for novel genes of the yeast Saccharomyces cerevisiae involved in these processes. These investigations were performed within EUROFAN (European Function Analysis Network), a European initiative to identify the functions of unassigned open reading frames that had been detected during the Yeast Genome Sequencing Project. First, the methods required for the complete lipid analysis of yeast cells based on chromatographic techniques were established and standardized. The reliability of these methods was demonstrated using tester strains with established defects in lipid metabolism. During these investigations it was demonstrated that different wild-type strains, among them FY1679, CEN.PK2-1C and W303, exhibit marked differences in lipid content and lipid composition. Second, several candidate genes which were assumed to encode proteins involved in lipid metabolism were selected, based on their homology to genes of known function. Finally, lipid composition of mutant strains deleted of the respective open reading frames was determined. For some genes we found evidence suggesting a possible role in lipid metabolism.
High-Resolution Quantitative Trait Locus Analysis Reveals Multiple Diabetes Susceptibility Loci Mapped to Intervals &lt;800 kb in the Species-ConservedNiddm1iof the GK Rat (2006)

Niddm1i, a 16-Mb locus within the major diabetes QTL in the diabetic GK rat, causes impaired glucose tolerance in the congenic NIDDM1I strain. Niddm1i is homologous to both human and mouse regions linked with type 2 diabetes susceptibility. We employed multiple QTL analyses of congenic F2 progeny selected for one recombination event within Niddm1i combined with characterization of subcongenic strains. Fine mapping located one hyperglycemia locus within 700 kb (Niddm1i4, P=5x10(-6)). Two adjacent loci were also detected, and the GK allele at Niddm1i2 (500 kb) showed a glucose-raising effect, whereas it had a glucose-lowering effect at Niddm1i3 (400 kb). Most proximally, Niddm1i1 (800 kb) affecting body weight was identified. Experimental data from subcongenics supported the four loci. Sorcs1, one of the two known diabetes susceptibility genes in the region, resides within Niddm1i3, while Tcf7l2 maps outside all four loci. Multiple-marker QTL analysis incorporating the effect of cosegregating QTL as cofactors together with genetically selected progeny can remarkably enhance resolution of QTL. The data demonstrate that the species-conserved Niddm1i is a composite of at least four QTL affecting type 2 diabetes susceptibility and that two adjacent QTL (Niddm1i2GK and Niddm1i3GK) act in opposite directions.
Structural analysis of underivatized neutral human milk oligosaccharides in the negative ion mode by nano-electrospray MS n (Part 2: Application to isomeric mixtures) (2002)

A complex mixture of isomeric neutral oligosaccharides from pooled human milk was analyzed by nano-electrospray ionization (ESI) in a quadrupole ion trap mass spectrometer (QIT-MS) in the negative ion mode. Since deprotonated molecules of neutral oligosaccharides follow distinct fragmentation rules, which have been elucidated by using model compounds (see [1]), spectra obtained from consecutive CID experiments allowed the differentiation of isomers out of this highly complex mixture. With this method new human milk oligosaccharides of previously unknown isomeric structures have been identified, e.g., the occurence of three isomeric fucosylated lacto-N-hexaoses could be determined precisely, which have not been described before: (1) Fuc (alpha1-->2) Gal (beta1-->3) GlcNac (beta1-->3) Gal (beta1-->4) GlcNac (beta1-->3) Gal (beta1-->4) Glc, (2) Gal (beta1-->4) GlcNAc [(alpha1-->3) Fuc] (beta1-->3) Gal (beta1-->4) GlcNac (beta1-->3) Gal (beta1-->4) Glc, (3) Gal (beta1-->4) GlcNAc (beta1-->3) Gal (beta1-->4) GlcNac [(alpha1-->3) Fuc] (beta1-->3) Gal (beta1-->4) Glc.
Polymer solution and fiber suspension rheology and their relationship to turbulent drag reduction (1977)

It is shown that the rheological behavior of dilute polymeric solutions can be described, at least semi-quantitatively, by means of an equation containing a single viscosity coefficient and a single time constant. This expression and the Batchelor equation for suspension rheology are used to predict the major drag-reduction phenomena observed experimentally. It is shown that mixed polymer-fiber systems may be much more effective in their drag reduction capabilities than is either kind of additive when used alone. This latter prediction finds its qualitative verification in drag coefficients which are several-fold lower than those observed at the asymptote of ’’maximum’’ drag reduction in polymer solutions.
An Unusual Cell Penetrating Peptide Identified Using a Plasmid Display-Based Functional Selection Platform (2011)

Cell penetrating peptides (CPPs) have tremendous potential for use in gene and drug delivery applications. The selection of new CPPs with desired capabilities from randomized peptide libraries is challenging, since the CPP phenotype is a complex selection target. Here we report the discovery of an unusual new CPP from a randomized peptide library using a functional selection system based on plasmid display (PD). After four rounds of screening of a 14-mer peptide library over PC12 cells, several peptides were identified and tested for their ability to deliver the green fluorescent protein (GFP). One peptide (SG3) exhibited a cell penetrating phenotype; however, unlike other well-known CPPs such as TAT or Penetratin, the newly identified peptide was not highly cationic. The PD protocol necessitated the addition of a cationic lipid (Lipofectamine2000), and in the presence of this compound, the SG3 peptide significantly outperformed the well-known TAT CPP in the delivery of GFP to PC12 cells and primary astrocytes. When the SG3 peptide was fused to the pro-apoptotic BH3 peptide from the Bak protein, significant cell death was induced in cultured primary astrocytes, indicating relevant, intracellular delivery of a functional cargo. The PD platform is a useful method for identifying functional new CPPs from randomized libraries with unique delivery capabilities.
Paramyxovirus replication and pathogenesis. Reverse genetics transforms understanding (1999)

A recent breakthrough in the field of nonsegmented negative strand RNA viruses (Mononegavirales), including paramyxoviruses, is the establishment of a system to recover an infectious virus entirely from complementary DNA and hence allow reverse genetics. Mutations can now be introduced into viral genomes at will and the resulting phenotypes studied as long as the introduced mutations are not lethal. This technology is being successfully applied to answer outstanding questions regarding the roles of viral components in replication and their contribution to pathogenicity, which are difficult to address using conventional virology. For instance, how the paramyxovirus accessory proteins V and C contribute to actual viral replication and pathogenesis has remained unanswered since their first description more than 20 years ago. Using Sendai virus, which causes fatal pneumonia in mice, it has been shown that the V protein is completely dispensable for viral replication in cell cultures but encodes a luxury function required for pathogenesis in vivo. The Sendai virus C proteins were also defined to be nonessential gene products which greatly contributed to replication both in vitro and in vivo. It is also now possible to design live vaccines by introducing predetermined or plausible attenuating mutations. In addition, the use of paramyxoviruses to express foreign genes has also become feasible. Paramyxovirus reverse genetics is thus renovating our understanding of viral replication and pathogenesis and will further mark an era in recombinant technology for disease prevention and gene therapy.
Spermine oxidase maintains basal skeletal muscle gene expression and fiber size and is strongly repressed by conditions that cause skeletal muscle atrophy (2014)

Skeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fasting, muscle denervation, and aging) strongly reduced expression of the enzyme spermine oxidase. Importantly, a reduction in spermine oxidase was sufficient to induce muscle fiber atrophy. Conversely, forced expression of spermine oxidase increased muscle fiber size in multiple models of muscle atrophy (immobilization, fasting, and denervation). Interestingly, the reduction of spermine oxidase during muscle atrophy was mediated by p21, a protein that is highly induced during muscle atrophy and actively promotes muscle atrophy. In addition, we found that spermine oxidase decreased skeletal muscle mRNAs that promote muscle atrophy (e.g., myogenin) and increased mRNAs that help to maintain muscle mass (e.g., mitofusin-2). Thus, in healthy skeletal muscle, a relatively low level of p21 permits expression of spermine oxidase, which helps to maintain basal muscle gene expression and fiber size; conversely, during conditions that cause muscle atrophy, p21 expression rises, leading to reduced spermine oxidase expression, disruption of basal muscle gene expression, and muscle fiber atrophy. Collectively, these results identify spermine oxidase as an important positive regulator of muscle gene expression and fiber size, and elucidate p21-mediated repression of spermine oxidase as a key step in the pathogenesis of skeletal muscle atrophy.
An Intact Zinc Ring Finger Is Required for Tumor Necrosis Factor Receptor-associated Factor-mediated Nuclear Factor-κB Activation but Is Dispensable for c-Jun N-terminal Kinase Signaling (1998)

The diverse biological effects of the tumor necrosis factor (TNF) receptor superfamily are believed to be mediated in part through TNF receptor-associated factors (TRAFs), a family of cytoplasmic adaptor proteins which can activate intracellular signaling pathways, including the nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK) pathways. TRAFs 2, 5, and 6 strongly activate both pathways when overexpressed; however, TRAF 3 (a close homologue of TRAF 5) does not significantly activate either pathway. The current study addresses the structural basis for this difference by substituting corresponding domains of TRAF 5 into TRAF 3 and testing activation of both pathways. A small region of TRAF 5 (the first zinc finger and 10 residues of the second zinc finger) is sufficient to convert TRAF 3 into an activator of both pathways. Also, an intact zinc ring finger is required for NF-kappaB activation but not JNK activation. In agreement with this finding, TRAF 2A, a TRAF 2 splice variant with an altered ring finger, is a specific activator of JNK. These findings suggest that different domains of TRAFs may be involved in NF-kappaB and JNK signaling. Also, alternative splicing of TRAFs may represent a novel mechanism whereby TNF family receptors can mediate distinct downstream effects in different tissues.
Asthma diagnosis, monitoring and control : paediatrics (2007)

Asthma is an inflammatory disease and the standard of therapy is the use of regular anti-inflammatory drugs, often, but not always, inhaled. Diagnosis of asthma often rests on clinical parameters in young children and it should be remembered that in these children wheeze is not always due to asthma. In older children objective diagnostic tests should be employed. Attention to regular use of therapy (adherence) as well as inhaler technique is of paramount importance in children.
Modification of enzymatic-ally amplified DNA for the detection of point mutations (1989)

Journal Article Modification of enzymatic-ally amplified DNA for the detection of point mutations Get access A. Haliassos, A. Haliassos Institut de Pathologie Moléculaire, CHU Cochin 24 rue du F bS St Jacques, F-75014, Pans, France Search for other works by this author on: Oxford Academic PubMed Google Scholar J.C. Chomel, J.C. Chomel Institut de Pathologie Moléculaire, CHU Cochin 24 rue du F bS St Jacques, F-75014, Pans, France Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Tesson, L. Tesson Institut de Pathologie Moléculaire, CHU Cochin 24 rue du F bS St Jacques, F-75014, Pans, France Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Baudis, M. Baudis Institut de Pathologie Moléculaire, CHU Cochin 24 rue du F bS St Jacques, F-75014, Pans, France Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Kruh, J. Kruh Institut de Pathologie Moléculaire, CHU Cochin 24 rue du F bS St Jacques, F-75014, Pans, France Search for other works by this author on: Oxford Academic PubMed Google Scholar J.C. Kaplan, J.C. Kaplan Institut de Pathologie Moléculaire, CHU Cochin 24 rue du F bS St Jacques, F-75014, Pans, France Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Kitzis A. Kitzis * Institut de Pathologie Moléculaire, CHU Cochin 24 rue du F bS St Jacques, F-75014, Pans, France * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 17, Issue 9, 11 May 1989, Page 3606, https://doi.org/10.1093/nar/17.9.3606 Published: 11 May 1989 Article history Received: 04 April 1989 Published: 11 May 1989
A Cell's Sense of Direction (1999)

In eukaryotic cells directional sensing is mediated by heterotrimeric guanine nucleotide-binding protein (G protein)-linked signaling pathways. In Dictyostelium discoideum amoebae and mammalian leukocytes, the receptors and G-protein subunits are uniformly distributed around the cell perimeter. Chemoattractants induce the transient appearance of binding sites for several pleckstrin homology domain-containing proteins on the inner face of the membrane. In gradients of attractant these sites are persistently present on the side of the cell facing the higher concentration, even in the absence of a functional actin cytoskeleton or cell movement. Thus, the cell senses direction by spatially regulating the activity of the signal transduction pathway.
The role of cell culture vaccines in the control of the next influenza pandemic (2004)

Pandemic influenza A viruses of avian origin are of particular concern and have crossed the species barrier several times in recent years, giving rise to illness and occasionally death in humans. This situation could become dramatically worse if the infectivity of avian viruses for humans were increased by reassortment between the genes of human and avian viruses. Co-infection of humans or an intermediate host with an avian strain and an existing human strain could produce new viruses of unknown pathogenicity to which the entire population would be susceptible. Inactivated vaccines against influenza have been prepared for many years using viruses grown in embryonated chicken eggs. However, the use of eggs presents difficulties when vaccine supplies need to be expanded at short notice. It seems likely that future vaccines will be prepared in high-yielding cell cultures from continuous lines that are preferably anchorage-independent. At present, only certain preparations of the Vero and Madin-Darby canine kidney cell lines, grown and maintained in serum-free medium, are acceptable to all regulatory authorities. However, this situation is likely to change with increasing need for non-pandemic and pandemic vaccines.
Modelling enhanced spherical diffraction and troposcattering on a transhorizon path with the aid of the parabolic equation and ray tracing methods (1996)

The parabolic equation is applied to model the effect of an evaporation duct and high k-factor simultaneously present in a multilink path of 11.6 GHz over the sea. In addition, the ray tracing method is extended to the calculation of the common volume and, in conjunction with the radar equation, to estimating the scatter power and delay spreads. The results are compared with experimental observations and provide an explanation on transhorizon propagation phenomena.
Increasing power efficiency of multi-core network processors through data filtering (2002)

We propose and evaluate a data filtering method to reduce the power consumption of high-end processors with multiple execution cores. Although the proposed method can be applied to a wide variety of multi-processor systems including MPPs, SMPs and any type of single-chip multiprocessor, we concentrate on Network Processors. The proposed method uses an execution unit called Data Filtering Engine that processes data with low temporal locality before it is placed on the system bus. The execution cores use locality to decide which load instructions have low temporal locality and which portion of the surrounding code should be off-loaded to the data filtering engine.Our technique reduces the power consumption, because a) the low temporal data is processed on the data filtering engine before it is placed onto the high capacitance system bus, and b) the conflict misses caused by low temporal data are reduced resulting in fewer accesses to the L2 cache. Specifically, we show that our technique reduces the bus accesses in representative applications by as much as 46.8% (26.5% on average) and reduces the overall power by as much as 15.6% (8.6% on average) on a single-core processor. It also improves the performance by as much as 76.7% (29.7% on average) for a processor with 16 execution cores.