gebhart/patrepeval huggingface dataset:
FUS/ERG gene fusions in Ewing's tumors. (2003)

Ewing's tumors are rare pediatric neoplasms that are characterized by specific chromosomal translocations and gene rearrangements. All of the fusion genes reported to date in Ewing's tumors juxtapose the EWS gene at 22q12 to an ETS-related gene, the most common of which are FLI1 at 11q24 and ERG at 21q22. We present here four cases of Ewing's tumor, which showed no evidence of a EWS gene rearrangement, but instead contained translocations involving 16p11 and 21q22. A rearrangement involving the same chromosome bands, t(16;21)(p11;q22), is found in rare cases of acute myeloid leukemia and fuses the FUS gene at 16p11 to the ERG gene at 21q22. In two of our Ewing's tumor cases, we were able to show at the sequence level that the translocation between chromosomes 16 and 21 similarly results in a FUS/ERG fusion. In one case, exons 1-5 and most of exon 6 of FUS were fused in-frame to exon 9 of ERG; in the other case, FUS exons 1-7 were fused in-frame to ERG exons 8-9. The functional fusion transcript is expected to be expressed from the der(21)t(16;21) derivative. In the two other t(16;21)-positive Ewing's cases, we performed bacterial artificial chromosome fluorescence in situ hybridization analysis on metaphases and interphase nuclei to demonstrate colocalization of bacterial artificial chromosomes containing FUS and ERG genes, also highly suggestive of fusion gene formation. These represent the first four cases where FUS, rather than EWS, is rearranged with an ETS-family transcription factor in Ewing's tumors. Our data provide additional evidence that the transactivation domains of the TET family of RNA-binding proteins (such as EWS and FUS) are interchangeable, and suggests a novel mechanism of oncogenesis in Ewing's tumors.
Control of cell proliferation pathways by microRNAs (2008)

MicroRNAs (miRNAs) are small non-coding RNAs that regulate a large variety of cellular processes including differentiation, apoptosis and proliferation. Several miRNAs display defective expression patterns in human tumors with the consequent alteration of target oncogene or tumor suppressor genes. Many of these miRNAs modulate the major proliferation pathways through direct interaction with critical regulators such as RAS, PI3K/PTEN or ABL, as well as members of the retinoblastoma pathway, Cyclin-CDK complexes or cell cycle inhibitors of the INK4 or Cip/Kip families. A complex interplay between miRNAs and MYC or E2F family members also exists to modulate cell cycle-dependent transcription during normal or tumoral proliferation. The ability of miRNAs to modulate these proliferation pathways may have relevant implications not only in physiological or developmental processes but also in tumor progression or cancer therapy.
Down-regulation of the caffeic acid O-methyltransferase gene in switchgrass reveals a novel monolignol analog (2012)

Down-regulation of COMT activity in switchgrass resulted in the accumulation of previously undetected metabolites resembling sinapyl alcohol and its related metabolites, but that are derived from para-methylation of 5-hydroxyconiferyl alcohol, and related precursors and products; the accumulation of which suggests altered metabolism of 5-hydroxyconiferyl alcohol in switchgrass. Given that there was no indication that iso-sinapyl alcohol was integrated in cell walls, it is considered a monolignol analog. Diversion of substrates from sinapyl alcohol to free iso-sinapyl alcohol, its glucoside, and associated upstream lignin pathway changes, including increased phenolic aldehydes and acids, are together associated with more facile cell wall deconstruction, and to the observed inhibitory effect on microbial growth. However, iso-sinapyl alcohol and iso-sinapic acid, added separately to media, were not inhibitory to C. thermocellum cultures.
Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer. (2001)

Carbonic anhydrase-9 (CA9), a transmembrane enzyme with an extracellular active site, is involved in the reversible metabolism of the carbon dioxide to carbonic acid. Up-regulation of CA by hypoxia and the hypoxia-inducible factor (HIF) pathway has been recently postulated (Wykoff et al. Cancer Res., 60: 7075-7083, 2000). In the present study we examined the expression of this enzyme in non-small cell lung cancer. Of 107 cases analyzed, 39 (36.4%) had strong membrane/cytoplasmic expression of CA9 and were grouped as positive. The staining was confined around areas of necrosis, and a significant association of CA9 expression with the extent of necrosis was noted (P = 0.004). Nevertheless, 38 of 74 cases with focal or extensive necrosis did not express CA9. CA9 expression was more frequent in the squamous cell histology (P = 0.001) and with advanced T stage (P = 0.009). A significant coexpression of CA9 with platelet-derived endothelial cell growth factor and basic fibroblast growth factor receptor expression was noted. Double staining of CA9 with anti-CD31 monoclonal antibody revealed an overall higher microvessel density in the areas expressing CA9 than in negative areas (P = 0.0005). Thirty-one of 38 CA9-positive cases were positive for HIF1a/HIF2a, but HIF positivity was a more common event (68 of 107) and their patterns of expression were diffuse (not confined in the necrotic areas). A direct association of CA9 expression with epidermal growth factor receptor, c-erbB-2, and MUC1 expression was also noted (P < 0.04). Survival analysis showed that CA9 expression is related to poor prognosis. CA9 expression in tumors with low vascularization defined a prognosis similar to the one of patients with highly angiogenic tumors. Multivariate analysis revealed that CA9 expression is a significant prognostic factor independent of angiogenesis. We conclude that CA9 is an important molecule in non-small cell lung cancer, the up-regulation of which occurs in highly hypoxic/necrotic regions of the tumors. The expression of CA9 is linked to the expression of a constellation of proteins involved in angiogenesis, apoptosis inhibition, and cell-cell adhesion disruption, which explains the strong association of CA9 with poor outcome.
Surface Modification of Base Materials for  TEOS  /  O 3 Atmospheric Pressure Chemical Vapor Deposition (1992)

Atmospheric pressure tetraethyloxysilicane chemically vapor deposited provides excellent step coverage for submicron device structures; however, the properties of the deposited films depend on the surface characteristics of the base materials being used. To illustrate this dependence, the deposition rate of nondoped silicon dioxide obtained on a thermal oxide surface is significantly lower than the deposition rate obtained on a bare silicon surface. A new method to eliminate this base material dependence involving plasma treatment has been investigated. The optimum treatment consists of exposing the base materials to a nitrogen plasma for 1 min while maintaining the base materials at 250°C. Films deposited on thermal oxide base materials which have first been treated by this new method were found to have the same deposition rate, aqueous etch rate, and surface morphology as those films deposited on untreated bare silicon. In addition to a nitrogen plasma, oxygen and argon plasmas were studied and found to produce similar results when the base material temperature was raised to 350°C. The elimination of base material dependence through the use of this new plasma treatment technique has resulted in higher integrity oxides and has also expanded the range of applications for this unique planarizing technology for very large scale integrated device fabrication.
Identification of the adult resting progenitor cell by autoradiographic tracking of oligodendrocyte precursors in experimental CNS demyelination (1998)

The new population of oligodendrocytes remyelinating an experimental demyelinating optic nerve lesion has been tracked backwards in time. Using autoradiography combined with electron microscopy and immunocytochemistry, serial sections of optic nerves from young adult cats were studied from 42 h (2 days) post-injection to 93 h (4 days) post-injection. The remyelinating oligodendrocyte lineage was found to commence with the single division of a resting progenitor cell residing in a central fascicular location outside the demyelinative lesion. The division of the founding progenitor cell occurs at 2 days post-lesion and results in two motile daughter cells. These cells, previously described by us as precursor cells, migrate to the lesion, closely appose demyelinated axons, produce axon wrapping processes and differentiate to become remyelinating oligodendrocytes. This study confirms that remyelinating oligodendrocytes originate from resting progenitor cells outside the lesion and not from mature oligodendrocytes, and implies that repeated demyelinative injury could exhaust the reparative capacity of such a region.
A single-chip optical sensor with analog memory for motion detection (1995)

A 64/spl times/64-pixel image sensor with full-frame analog memory and on-chip motion processor is presented. The processor consists of a charge amplifier and an analog subtractor. It uses the switched-capacitor technique and calculates the difference between the values of the signal on each pixel in successive frames. The rate can achieve up to 60 frames/s with limited area and power overhead. The analog memory required for the storage of the previous frame is implemented using implanted capacitors placed within the sensor array. Fabricated in a 1.2-/spl mu/m standard CMOS process with an added metal 3 light-shielding layer, the circuit is fully functional and requires a total core area of 13 mm/sup 2/.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Role of Prostaglandin I2 in Airway Remodeling Induced by Repeated Allergen Challenge in Mice (2003)

Recently, we demonstrated that prostaglandin (PG)I2 has a regulatory role in allergic responses through the receptor, IP; however, the role of PGI2 in airway remodeling associated with chronic airway inflammation has not been elucidated. In the present study, we examined the role of PGI2 in allergen-induced airway remodeling using IP gene-deficient mice. Mice were sensitized to ovalbumin (OVA) with alum, and exposed daily for 3 wk to aerosolized OVA. Twenty-four hours after the final antigen inhalation, bronchoalveolar lavage, biochemical, and histopathologic examinations were performed. In wild-type mice, prolonged allergen exposure in sensitized animals induced the increases in the numbers of inflammatory leukocytes (including eosinophils and lymphocytes), levels of T helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13), levels of OVA-specific immunoglobulin (Ig)E and IgG1 in serum, and amount of hydroxyproline in the right lungs associated with transforming growth factor-beta1 levels in bronchoalveolar lavage fluid. Moreover, goblet cell hyperplasia and subepithelial fibrosis were also appreciated after repeated allergen challenge. In contrast, the disruption of IP gene significantly augmented all these parameters. These findings suggest that PGI2 has a regulatory role in allergen-induced airway remodeling as well as airway eosinophilic inflammation, Th2 cytokine production and IgE production, and that a PGI2 agonist is a therapeutic approach for the treatment of airway remodeling in allergic asthma.
Prospects of Vaccination in Autoimmune Diseases (1992)

Over the past several years, intensive efforts have been directed to define the pathogenic mechanisms and explore the potential immunotherapy of autoimmune diseases. The advances of molecular genetics and cellular immunology have now permitted select experimental immunotherapy using synthetic peptides, T cell receptor idiotypes and monoclonal antibodies. There remain many obstacles for success. First, the T cell receptor usage of autoreactive T cells in human autoimmune diseases are more heterogeneous than animal models. Clearly, there may not be an oligoclonal derivation of T cells in humans with autoimmune diseases. We foresee that the following studies might contribute to further understand pathogenic mechanisms and design feasible immunotherapy: (1) detailed characterizations of self-antigen specific T cell clones; (2) definition of interactions between MHC molecules and T cell receptors at the molecular level; (3) identification and elution of relevant disease inducing self-peptides complexed with MHC molecules and (4) identification of relevant genes that predispose to autoimmunity.
Small Pulmonary Nodules: Evaluation with Repeat CT—Preliminary Experience (1999)

Preliminary experience with early repeat CT suggests that a single repeat CT scan obtained 30 days after the first scan can depict growth in most malignant tumors as small as 5 mm.
Regulation of aromatic amino acid transport systems in Escherichia coli K-12 (1977)

The regulation of the aromatic amino acid transport systems was investigated. The common (general) aromatic transport system and the tyrosine-specific transport system were found to be subject to repression control, thus confirming earlier reports. In addition, tryosine- and tryptophan-specific transport were found to be enhanced by growth of cells with phenylalanine. The repression and enhancement of the transport systems was abolished in a strain carrying an amber mutation in the regulator gene tyrR. This indicates that the tyrR gene product, which was previously shown to be involved in regulation of aromatic biosynthetic enzymes, is also involved in the regulation of the aromatic amino acid transport systems.
Role of adenosine in tumor progression: focus on A2B receptor as potential therapeutic target (2017)

Adenosine receptors are a family of G-coupled receptors which mediate the antiinflammatory and immune-suppressive effects of adenosine in a damaged tissue. A large number of evidence indicate that the accumulation of adenosine under hypoxic conditions favors tumor progression, helping cancer cells to evade immune responses. Tumor cells and/ or lymphoid and myeloid cells can express the adenosine-generating enzyme CD73 and/or A 2A receptor, which in turn strongly suppresses an effective T-cell-mediated response, while promotes the activity of suppressive cells such as Treg and myeloid-derived suppressor cells. CD73 inhibitors and A 2A antagonists, either as single agents, or in combination with immune-checkpoints inhibitors such as anti PD-1 monoclonal antibodies, are currently in Phase I clinical trial in cancer patients. Recent studies show that A 2B receptor plays an important role in mediating the pro-tumor effects of adenosine, since its selective blockade can inhibit tumor growth in some murine tumor models. Targeting A 2B receptor reduces immunosuppression induced by myeloid cells and inhibits the stromal cells activity within the tumor microenvironment, limiting tumor angiogenesis and metastatic processes. Here, the authors review the current data on involvement of A 2B receptor in regulating tumor progression and discuss the development of A 2B receptor inhibitors as potential therapeutic agents in cancer treatment.
Iron(0) Particles: Catalytic Hydrogenations and Spectroscopic Studies (2012)

Ironing it out: The simple pre-catalyst system FeCl3/EtMgCl was applied to the hydrogenation of various alkenes and alkynes at room temperature. Domino iron-catalyzed allylation/hydrogenation reactions were performed under 1–4 bar H2. Spectroscopic studies determined the heterogeneous nature of the active catalyst species, its oxidation state (Fe0), and the local structure and size of the formed particles. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
BamI, KpnI, and SalI restriction enzyme maps of the DNAs of herpes simplex virus strains Justin and F: occurrence of heterogeneities in defined regions of the viral DNA (1979)

We present the locations of the cleavage sites for the BamI, KpnI, and SalI restriction endonucleases within the DNA molecules of herpes simplex virus type 1 (HSV-1) strains Justin and F. These restriction enzymes cleave the HSV-1 DNA at many sites, producing relatively small fragments which should prove useful in future studies of HSV-1 gene structure and function. The mapping data revealed the occurrence of heterogeneity within three regions of the viral genome including (i) the region spanning map coordinates 0.74--0.76, (ii) the ends of the large (L) DNA component, and (iii) the junction between the large (L) and the small (S) components. The heterogeneity in the ends of L and the S-L junctions of HSV-1 (Justin) and HSV-1 (F) DNAs was grossly similar to that previously reported to occur in the ends of L and the S-L junctions of the HSV-1 (KOS) DNA (M. J. Wagner and W. C. Summers, J. Virol. 27:374--387, 1978). Thus, cleavage of these regions with restriction endonucleases yielded sets of minor fragments differing in size by constant increments. However, the various strains of HSV-1 differed with respect to the numbers, size increments, and relative molarities of the various minor fragments, suggesting that the parameters of the heterogeneity are inherited in the structural makeup of the HSV-1 genome. The strain dependence of the pattern of heterogeneity can be most easily explained in terms of variable sizes of the terminally reiterated a sequence, contained in the DNA molecules of these three strains of HSV-1.
Small Molecule Microarray Based Discovery of PARP14 Inhibitors (2016)

Poly(ADP-ribose) polymerases (PARPs) are key enzymes in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, and suffer from poor selectivity. PARP14 has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Herein, we describe a small molecule microarray-based strategy for high-throughput synthesis, screening of >1000 potential bidentate inhibitors of PARPs, and the successful discovery of a potent PARP14 inhibitor H10 with >20-fold selectivity over PARP1. Co-crystallization of the PARP14/H10 complex indicated H10 bound to both the nicotinamide and the adenine subsites. Further structure-activity relationship studies identified important binding elements in the adenine subsite. In tumor cells, H10 was able to chemically knockdown endogenous PARP14 activities.
Making Linux protection mechanisms egalitarian with UserFS (2010)

UserFS provides egalitarian OS protection mechanisms in Linux. UserFS allows any user—not just the system administrator—to allocate Unix user IDs, to use chroot, and to set up firewall rules in order to confine untrusted code. One key idea in UserFS is representing user IDs as files in a /proc-like file system, thus allowing applications to manage user IDs like any other files, by setting permissions and passing file descriptors over Unix domain sockets. UserFS addresses several challenges in making user IDs egalitarian, including accountability, resource allocation, persistence, and UID reuse. We have ported several applications to take advantage of UserFS; by changing just tens to hundreds of lines of code, we prevented attackers from exploiting application-level vulnerabilities, such as code injection or missing ACL checks in a PHP-based wiki application. Implementing UserFS requires minimal changes to the Linux kernel—a single 3,000-line kernel module—and incurs no performance overhead for most operations, making it practical to deploy on real systems. 1
Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation in Pediatric Patients and Subsequent Supportive Care (2012)

For nurses to correctly educate their patients and family members, and to aid nurses in anticipating patient's needs, an understanding of the potential different acute toxicities and supportive care between pediatric patients undergoing RIC- versus MAC-AlloHSCT is vital.
Acetaminophen Hepatotoxicity: The First 35 Years (2002)

The acetaminophen nomogram including its uses and limitations is discussed as well as the development of the N-acetylcysteine protocol. While it has taken many years to elucidate the genetic variability and true multiplicity of the cytochrome P450 "mixed function oxidase system" many publications early on looked at the enzyme system as a single entity. Numerous articles indicated that barbiturates, anticonvulsants, and others could induce "P450" and add to the toxicity of acetaminophen. It rapidly became apparent that just because "P450" was induced when measured as a whole, not all other substrates would have changed metabolic activity. The role of diet and ethanol induction and inhibition on CYP2E1, the enzyme of greatest interest for acetaminophen is multifaceted. The lack of enhancement of acetaminophen toxicity by phenytoin and in fact, the potential for reduction of toxicity with that agent is a good example of the evolution of our knowledge. Further complicating our understanding is the introduction of misleading terms such as "therapeutic misadventure" and other expressions of molecular intent. A critical understanding of the literature makes it clear that therapeutic doses of acetaminophen either alone or in the presence of inducers do not produce toxicity. While the community of clinical toxicologists is small, it needs to be more aggressive in making sure that physicians from other specialties and non-clinical toxicology colleagues understand the significance and implications of this science.
Oncogenic transformation alters cisplatin‐induced apoptosis in rat embryo fibroblasts (1995)

We have investigated whether cellular transformation by different oncogenes alters their responsiveness to the chemotherapeutic agent cis-diamminedichloroplatinum(II) (cDDP). Rat-6 (R6) embryo fibroblasts transformed by v-myc, rc-mos (rearranged mouse c-mos), v-src and activated c-H-ras oncogenes displayed differential sensitivities to cDDP, and the IC50 values of cDDP decreased by approximately 3.0-, 1.2-, 2.0- and 1.5-fold, respectively. Over-expression of myc, but not ras, src or mos, induced apoptosis in R6 cells. Nevertheless, all oncogenes influenced cellular susceptibility to apoptosis triggered by cDDP as judged by the appearance of condensed chromatin, formation of apoptotic bodies and internucleosomal cleavage of genomic DNA to 180 bp multimers, yielding a "laddered" electrophoretic profile on agarose gel. There was a correlation between the time- and concentration-dependent enhancement of cDDP-induced DNA fragmentation and potentiation of cDDP sensitivity by various oncogenes. Oncogenic transformation led to a decrease in expression of the PKC epsilon isoform, and stable transfection of PKC epsilon in R6 cells prevented cDDP-induced apoptosis and protected cells against cDDP cytotoxicity. Our results indicate that the differential sensitivity of oncogene-transformed cells to cDDP may be associated with the ability of various oncogenes to influence cDDP-induced apoptosis.
Nucleotide sequence of the cDNAs encoding the variable region heavy and light chains of a myeloma protein specific for the terminal nonreducing end of alpha(1----6)dextran. (1987)

The complete nucleotide sequences of the cDNAs encoding the heavy- and light-chain variable regions (VH and VL) of myeloma protein W3129, an anti-alpha(1----6)-dextran with a unique combining site, have been determined. The VH region is encoded by a germ-line gene highly homologous to VH441, which also appears to be used in some anti-galactans and anti-levans. W3129 VH uses a diversity region that is not found in any of the galactan- or levan-specific antibodies and whose germ-line counterpart is unknown. The W3129 light chain differs from complete light-chain sequences thus far reported but is identical in the first 23 amino acids with NZB IgA myeloma PC118.