gebhart/patrepeval huggingface dataset:
Glut‐1 deficiency syndrome: Clinical, genetic, and therapeutic aspects (2004)

Impaired glucose transport across the blood-brain barrier results in Glut-1 deficiency syndrome (Glut-1 DS, OMIM 606777), characterized by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and hypoglycorrhachia. We studied 16 new Glut-1 deficiency syndrome patients focusing on clinical and laboratory features, molecular genetics, genotype-phenotype correlation, and treatment. These patients were classified phenotypically into three groups. The mean cerebrospinal fluid glucose concentration was 33.1 +/- 4.9mg/dl equal to 37% of the simultaneous blood glucose concentration. The mean cerebrospinal fluid lactate concentration was 1.0 +/- 0.3mM, which was less than the normal mean value of 1.63mM. The mean V(max) for the 3-O-methyl-D-glucose uptake into erythrocytes was 996 fmol/10(6) red blood cells per second, significantly less (54 +/- 11%; t test, p < 0.05) than the mean control value of 1,847. The mean Km value for the patient group (1.4 +/- 0.5mM) was similar to the control group (1.7 +/- 0.5mM; t test, p > 0.05). We identified 16 rearrangements, including seven missense, one nonsense, one insertion, and seven deletion mutations. Fourteen were novel mutations. There were no obvious correlations between phenotype, genotype, or biochemical measures. The ketogenic diet produced good seizure control.
Cancer-Associated Fibroblasts Derived from EGFR-TKI–Resistant Tumors Reverse EGFR Pathway Inhibition by EGFR-TKIs (2010)

Epidermal growth factor receptor (EGFR) plays a critical role in oncogenesis, which makes it an attractive target for pharmacologic inhibition. Yet, EGFR inhibition with tyrosine kinase inhibitors (TKI) does not result in a measurable and sustainable clinical benefit in a vast majority of tumors. This emphasizes the need for further investigations into resistance mechanisms against EGFR-TKIs. We previously reported the generation of an in vivo adenocarcinoma model of EGFR-TKI-acquired resistance that was devoid of the known mechanisms of resistance. Using this same xenograft model, we now show that the tumor stroma plays an important role in limiting responsiveness to EGFR-TKIs. EGFR-TKI-resistant tumors display increased surface expression of CD44(hi)/CD24(lo) and markers of epithelial to mesenchymal transition (EMT), SNAI1, and N-cadherin. An in vivo green fluorescent protein-tagging approach reveals that the tumor stroma of the EGFR-TKI-resistant tumors is distinct in that 24% of its cancer-associated fibroblast (CAF) population is composed of EMT-derived tumor cells that represent the in vivo escape from EGFR-TKIs. We further show that EMT subpopulation-harboring CAFs isolated from the EGFR-TKI-resistant tumors are tumorigenic and express the biomarker of gefitinib resistance, epithelial membrane protein-1. Finally, we provide evidence that paracrine factors secreted from the EGFR-TKI-resistant CAFs mitigate the EGFR-TKI-mediated blockade of pEGFR and pMAPK in cocultured tumor cells, regardless of their EGFR mutational status. This is the first demonstration that the tumor stroma is modified with acquisition of EGFR-TKI resistance and that it further contributes in promoting drug resistance.
BiDi Screen: A Thin, Depth-Sensing LCD for 3D Interaction using Light Fields Supplementary Appendix (2008)

In this appendix we describe how to optimize the sensor-mask (or diffuser-mask) separation, for pinhole arrays and tiled-broadband codes. As with other light field cameras, the total number of samples (given by the product of the spatial and angular resolutions) cannot exceed the number of camera pixels. In our system the LCD discretization further limits the mask resolution, restricting the total number of light field samples to be approximately equal to the total number of pixels in the display (i.e., 1680×1050 pixels). Thus, as described in Section 6.1, we achieve a spatial resolution of 73×55 samples and an angular resolution of 19×19 samples with a pinhole or MURA tile spacing of dp = 4.92 mm and a mask separation of di = 2.5 cm. However, by adjusting the spacing and separation, the spatio-angular resolution trade-off can be adjusted.
Distinct signal transduction pathways are utilized during the tube formation and survival phases of in vitro angiogenesis (1998)

Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs during development, wound healing and cancer and involves stages that orchestrate a network of cooperative interactions. Peptide growth factors and extracellular matrix (ECM) components are two major groups of angiogenesis mediators. Among the different ECM proteins, collagens have been well-associated with in vivo angiogenesis. Using human umbilical vein endothelial cells (HUVEC) grown in 3-D collagen gels we show that: (1) HUVEC do not survive well in 3-D collagen gels due to rapid induction of apoptosis. (2) VEGF, a potent in vivo angiogenic factor, fails to induce tube formation. (3) PMA was effective in inducing tube formation and survival in HUVEC dispersed in 3-D collagen gels, activating MAP kinase, phosphoinositide 3-OH kinase (PI-3-kinase) and Akt/PKB (protein kinase B) pathways. (4) VEGF was effective in preventing PMA-induced tube-like structure regression after PMA-withdrawal by (5) activating the mitogen activated protein kinase (MAPK), rather than the Akt/PKB, signaling pathway.
Activation of c‐kit is necessary for mobilization of reparative bone marrow progenitor cells in response to cardiac injury (2007)

Cardiovascular disease is the number-one cause of mortality in the developed world. The aim of this study is to define the mechanisms by which bone marrow progenitor cells are mobilized in response to cardiac ischemic injury. We used a closed-chest model of murine cardiac infarction/reperfusion, which segregated the surgical thoracotomy from the induction of cardiac infarction, so that we could study isolated fluctuations in cytokines without the confounding impact of surgery. We show here that bone marrow activation of the c-kit tyrosine kinase receptor in response to released soluble KitL is necessary for bone marrow progenitor cell mobilization after ischemic cardiac injury. We also show that release of KitL and c-kit activation require the activity of matrix metalloproteinase-9 within the bone marrow compartment. Finally, we demonstrate that mice with c-kit dysfunction develop cardiac failure after myocardial infarction and that bone marrow transplantation rescues the failing cardiac phenotype. In light of the ongoing trials of progenitor cell therapy for heart disease, our study outlines the endogenous repair mechanisms that are invoked after cardiac injury. Amplification of this pathway may aid in restoration of cardiac function after myocardial infarction.
An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. (1994)

Sequencing of two internal peptides from the putative human endothelial cell tissue plasminogen activator (t-PA) receptor identified an analog of the calcium- and phospholipid-binding protein, annexin II (Ann-II). The polymerase chain reaction-derived, full-length cDNA revealed complete sequence identity with the heavy chain of Ann-II, and ligand-precipitated receptor protein immunoreacted specifically with a monoclonal antibody to Ann-II. Transfected 293 cells bound plasminogen (Kd = 114 nM; Bmax = 347,000) as well as t-PA (Kd = 48 nM; Bmax = 380,000). Antisense oligonucleotides directed against endothelial cell Ann-II mRNA inhibited binding of both t-PA and plasminogen by 49% and 38%, respectively. The K307T mutant of Ann-II expressed on 293 cells failed to bind plasminogen, while the K328I mutant bound this ligand in a manner equivalent to the wild-type. Binding of plasminogen to both the wild-type and the K328I mutant was blocked by pretreatment of 293 cells with carboxypeptidase B. These data suggest a novel mechanism whereby a plasmin-like serine protease may cleave Ann-II at Lys307-Arg308, exposing a new carboxyl-terminal lysine residue (Lys307) for binding and efficient activation of plasminogen.
pH-Switchable, Ion-Permselective Gold Nanotubule Membrane Based on Chemisorbed Cysteine (2001)

An electroless gold plating method was used to deposit Au nanotubules within the pores of a polycarbonate template membrane. pH-switchable ion-transport selectivity was introduced by chemisorbing L-cysteine to the inside tubule walls. At low pH, where both the amino and carboxyl groups of the cysteine are protonated, these membranes preferentially reject cations and transport anions. At high pH, where both the amino and carboxyl groups are deprotonated, these membranes preferentially reject anions and transport cations. At pH = 6.0, near the isoelectric point of the chemisorbed cysteine, these membranes show neither cation nor anion transport selectivity. In addition to this electrostatically based selectivity, because of the small inside diameter of the Au nanotubules (as small as 0.9 nm), these membranes show molecular-size-based selectivity.
GUIDAGE: A FAST AUDIO QUERY GUIDED ASSEMBLAGE (2007)

In this article, a method is proposed for fast and automatic retrieval of factors of audio content in a large audio database based on user’s audio query. The proposed method, unlike most existing systems, takes explicit considerations of temporal morphology of audio content. This work touches upon several existing approaches and technologies for sound manipulations, such as sound texture synthesis, music and audio mosaicing on the synthesis side, and audio matching, query by audio and audio structure discovery on the analysis side. Destined for creative applications, the proposed method is modular by allowing interactive choice of search criteria. The analysis side of the proposed model features a new audio structure discovery algorithm called Audio Oracle that describes the temporal morphologies of the underlying sound as a compact state-space model. The search engine, and the main focus of this paper, features a fast and novel algorithm based on dynamic programming called Guidage that is capable of reassembling the query audio by concatenating subclips of target audio files. Demonstrated results suggest a degree of semantic-driven control for query guided applications. The article concludes with examples of two immediate applications of audio matching using Guidage on music, speech and natural sounds and a discussion on further development and use of such methods in interactive and creative environments. 1.
Prognostic factors in squamous cell carcinoma of the head and neck, with emphasis on 11q13 rearrangements and cyclin D1 overexpression. (1998)

At present, clinical outcome or response to therapy can not be fully predicted in individual cases of squamous cell carcinoma of the head and neck (SCCHN). The overall aim of the present studies was to investigate potential prognostic factors, more closely related to the malignant progression of a tumor than the established markers, such as the TNM-classification system. Tumor samples were investigated using cytogenetic analysis, immunohistochemistry (IHC), flow cytometry (FCM), slot blot hybridization, differential PCR and RT-PCR, and fluorescence in situ hybridization (FISH). The findings were compared with clinical data. Rearrangements of chromosome 11, band q13 (11q13), overexpression of the oncoprotein cyclin D1, complex karyotypes, and high histopathological malignancy scoring were all correlated to poor prognosis in SCCHN. They all yielded independent prognostic information in multivariate analysis. Cyclin D1 overexpression was correlated to partial or complete response to neoadjuvant chemotherapy. Chromosomal translocations of 11q13, together with genomic amplification, are involved in cyclin D1 oncogene (CCND1) deregulation, leading to cyclin D1 overexpression. Complex karyotypes are observed in DNA-diploid tumors, as assessed by FCM, partly explaining the low prognostic information yielded by this method in certain SCCHN. The present findings indicate 11q13 rearrange- ments and cyclin D1 overexpression, as assessed by cytogenetic analysis and IHC, respectively, to be new, independent prognostic factors in SCCHN. Furthermore, the latter parameter might predict response to induction chemotherapy. Cyclin D1 overexpression by IHC could easily be introduced to clinical work, in the hope that therapy will be brought a step closer to individualized treatment schedules.
A Novel Prostate Cancer Susceptibility Locus at 19q13 (2009)

A two-stage genome-wide association study (GWAS) of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative identified single nucleotide polymorphisms (SNP) in 150 regions across the genome that may be associated with prostate cancer (PCa) risk. We filtered these results to identify 43 independent SNPs where the frequency of the risk allele was consistently higher in cases than in controls in each of the five CGEMS study populations. Genotype information for 22 of these 43 SNPs was obtained either directly by genotyping or indirectly by imputation in our PCa GWAS of 500 cases and 500 controls selected from a population-based case-control study in Sweden [Cancer of the Prostate in Sweden (CAPS)]. Two of these 22 SNPs were significantly associated with PCa risk (P<0.05). We then genotyped these two SNPs in the remaining cases (n=2,393) and controls (n=1,222) from CAPS and found that rs887391 at 19q13 was highly associated with PCa risk (P=9.4 x 10(-4)). A similar trend of association was found for this SNP in a case-control study from Johns Hopkins Hospital (JHH), albeit the result was not statistically significant. Altogether, the frequency of the risk allele of rs887391 was consistently higher in cases than controls among each of seven study populations examined, with an overall P=3.2 x 10(-7) from a combined allelic test. A fine-mapping study in a 110-kb region at 19q13 among CAPS and JHH study populations revealed that rs887391 was the most strongly associated SNP in the region. Additional confirmation studies of this region are warranted.
Mitochondrial comparative proteomics of human ovarian cancer cells and their platinum‐resistant sublines (2010)

Resistance to platinum-based chemotherapy is the major obstacle to successful treatment of ovarian cancer. It is evident that mitochondrial defects and the dysfunctions of oxidative phosphorylation and energy production in ovarian cancer cells were directly related to their resistance to platinum drugs. Using 2-D DIGE, we compared mitochondrial proteins from two platinum-sensitive human ovarian cancer cell lines (SKOV3 and A2780) with that of four platinum-resistant sublines (SKOV3/CDDP, SKOV3/CBP, A2780/CDDP, and A2780/CBP). Among the 236 differentially expressed spots, five mitochondrial proteins (ATP-α, PRDX3, PHB, ETF, and ALDH) that participate in the electron transport respiratory chain were identified through mass spectrometry. All of them are downregulated in one or two of the platinum-resistant cell lines. Three proteins (ATP-α, PRDX3, and PHB) were validated by using western blot and immunohistochemistry. There is a significant decrease of PHB in tumor tissues from ovarian cancer patients who were resistant to platinum-based chemotherapies. This is the first direct mitochondrial proteomic comparison between platinum-sensitive and resistant ovarian cancer cells. These studies demonstrated that 2-D DIGE-based proteomic analysis could be a powerful tool to investigate limited mitochondrial proteins, and the association of PHB expression with platinum resistance indicates that mitochondria defects may contribute to platinum resistance in ovarian cancer cells.
Studies on the Biosynthesis of Paraherquamide A and VM99955. A Theoretical Study of Intramolecular Diels−Alder Cycloaddition (2003)

Intramolecular Diels-Alder reactions of 2-azadiene models have been studied quantum chemically at the B3LYP/6-31G level in order to elucidate the stereochemical features of the cyclization step involved in the biosynthesis of paraherquamide A and VM99955. These cycloadditions take place through concerted transition states associated with [4 + 2] processes. Analysis of the energies along the competitive paths reveals that while the cycloadditions of the oxindoles present a large anti selectivity, the indoles show a low syn selectivity for the formation of the C20 stereogenic center that is larger for the reduced tertiary amide form. The presence of the C14 methyl of the beta-methylproline ring produces a low hindrance along the reaction coordinate for the syn approach of the isoprene framework, in agreement with the low facial selectivity found experimentally. An analysis of the electrophilicity and activation parameters for experimental models of the inter- and intramolecular Diels-Alder reactions reveals several significant factors controlling these biosynthetic cyclizations. The results are in reasonable agreement with the available experimental data.
Atoxic Derivative of Botulinum Neurotoxin A as a Prototype Molecular Vehicle for Targeted Delivery to the Neuronal Cytoplasm (2014)

We have previously described genetic constructs and expression systems that enable facile production of recombinant derivatives of botulinum neurotoxins (BoNTs) that retain the structural and trafficking properties of wt BoNTs. In this report we describe the properties of one such derivative, BoNT/A ad, which was rendered atoxic by introducing two amino acid mutations to the light chain (LC) of wt BoNT/A, and which is being developed as a molecular vehicle for delivering drugs to the neuronal cytoplasm. The neuronal binding, internalization, and intracellular trafficking of BoNT/A ad in primary hippocampal cultures was evaluated using three complimentary techniques: flow cytometry, immunohistochemistry, and Western blotting. Neuronal binding of BoNT ad was significantly increased when neurons were incubated in depolarizing medium. Flow cytometry demonstrated that BoNT/A ad internalized into neurons but not glia. After 24 hours, the majority of the neuron-bound BoNT/A ad became internalized, as determined by its resistance to pronase E-induced proteolytic degradation of proteins associated with the plasma membrane of intact cells. Significant amounts of the atoxic LC accumulated in a Triton X-100-extractable fraction of the neurons, and persisted as such for at least 11 days with no evidence of degradation. Immunocytochemical analysis demonstrated that the LC of BoNT/A ad was translocated to the neuronal cytoplasm after uptake and was specifically targeted to SNARE proteins. The atoxic LC consistently co-localized with synaptic markers SNAP-25 and VAMP-2, but was rarely co-localized with markers for early or late endosomes. These data demonstrate that BoNT/A ad mimics the trafficking properties of wt BoNT/A, confirming that our platform for designing and expressing BoNT derivatives provides an accessible system for elucidating the molecular details of BoNT trafficking, and can potentially be used to address multiple medical and biodefense needs.
Activated regulatory T cells suppress effector NK cell responses by an IL-2-mediated mechanism during an acute retroviral infection (2015)

The current study demonstrates that virus-induced Tregs indeed inhibit antiviral NK cell responses and describes a targeted immunotherapy that can abrogate the suppression of NK cells by Tregs.
Non-destructive stress measurement in double ion-exchanged glass using optical guided-waves and scattered light (2017)

A non-destructive method is developed to determine the stress profile in double ion-exchanged lithium aluminosilicate glass. In this method, the steep compressive stress distribution from the surface to a depth of 10 µm is evaluated by the optical guided-wave method. The stress distribution from a depth of 50 to 413 µm is determined by the scattered light technique, where the scattered light intensity observed normal to an incident polarized beam is recorded and the phase shift is calculated from it. The stress profile combined with the optical guided-wave and the scattered light methods is presented and its comparison with the sodium and potassium concentration distributions and the Raman peak shift is discussed.
Life without Perlecan Has Its Problems (1999)

Perlecan plays an important tole in basement membranes and other extracellular matrices. Mice with a knockout gene for perlecan die at or before birth with severe defects in the brain, heart, and skeleton.
The Galley parallel file system (1997)

Most current multiprocessor file systems are designed to use multiple disks in parallel, using the high aggregate bandwidth to meet the growing I/O requirements of parallel scientific applications. Many multiprocessor file systems provide applications with a conventional Unix-like interface, allowing the application to access multiple disks transparently. This interface conceals the parallelism within the file system, increasing the ease of programmability, but making it difficult or impossible for sophisticated programmers and libraries to use knowledge about their I/O needs to exploit that parallelism. In addition to providing an insufficient interface, most current multiprocessor file systems are optimized for a different workload than they are being asked to support. We introduce Galley, a new parallel file system that is intended to efficiently support realistic scientific multiprocessor workloads. We discuss Galley's file structure and application interface, as well as the performance advantages offered by that interface.
Arabidopsis thaliana ethylene-responsive element binding protein (AtEBP), an ethylene-inducible, GCC box DNA-binding protein interacts with an ocs element binding protein (1997)

Ocs elements are a group of promoter sequences required for the expression of both pathogen genes in infected plants and plant defense genes. Genes for ocs element binding factors (OBFs), belonging to a specific class of basic-region leucine zipper (bZIP) transcription factors, have been isolated in a number of plants. Using protein-protein interaction screening with OBF4 we have isolated AtEBP, an Arabidopsis protein that contains a novel DNA-binding domain, the AP2/EREBP domain. One class of proteins that contain this domain are the tobacco ethylene-responsive element binding proteins (EREBPs). The EREBPs bind the GCC box that confers ethylene responsiveness to a number of pathogenesis related (PR) gene promoters. AtEBP expression is inducible by exogenous ethylene in wild-type plants and AtEBP transcripts are increased in the ctr1-1 mutant, where ethylene-regulated pathways are constitutively active. Electrophoretic mobility-shift assay and DNase I footprint analysis revealed that AtEBP can specifically bind to the GCC box. Interestingly, the highest level of AtEBP expression was detected in callus tissue, where ocs elements are very active. Synergistic effects of the GCC box with ocs elements or the related G-box sequence have been previously observed, for example, in the ethylene-induced expression of a PR gene promoter. Our results suggest that cross-coupling between EREBP and bZIP transcription factors occurs and may therefore be important in regulating gene expression during the plant defense response.
Probiotics for the treatment of eczema: a systematic review (2009)

Currently, probiotics cannot be recommended for treating eczema. The heterogeneity between studies may be attributable to probiotic strain-specific effects, which means that novel probiotic strains may still have a role in eczema management.