gebhart/patrepeval huggingface dataset:
Genotype-Dependent Efficacy of a Dual PI3K/mTOR Inhibitor, NVP-BEZ235, and an mTOR Inhibitor, RAD001, in Endometrial Carcinomas (2012)

The PI3K (phosphatidylinositol-3-kinase)/mTOR (mammalian target of rapamycin) pathway is frequently activated in endometrial cancer through various PI3K/AKT-activating genetic alterations. We examined the antitumor effect of NVP-BEZ235--a dual PI3K/mTOR inhibitor--and RAD001--an mTOR inhibitor--in 13 endometrial cancer cell lines, all of which possess one or more alterations in PTEN, PIK3CA, and K-Ras. We also combined these compounds with a MAPK pathway inhibitor (PD98059 or UO126) in cell lines with K-Ras alterations (mutations or amplification). PTEN mutant cell lines without K-Ras alterations (n = 9) were more sensitive to both RAD001 and NVP-BEZ235 than were cell lines with K-Ras alterations (n = 4). Dose-dependent growth suppression was more drastically induced by NVP-BEZ235 than by RAD001 in the sensitive cell lines. G1 arrest was induced by NVP-BEZ235 in a dose-dependent manner. We observed in vivo antitumor activity of both RAD001 and NVP-BEZ235 in nude mice. The presence of a MEK inhibitor, PD98059 or UO126, sensitized the K-Ras mutant cells to NVP-BEZ235. Robust growth suppression by NVP-BEZ235 suggests that a dual PI3K/mTOR inhibitor is a promising therapeutic for endometrial carcinomas. Our data suggest that mutational statuses of PTEN and K-Ras might be useful predictors of sensitivity to NVP-BEZ235 in certain endometrial carcinomas.
Preparation and Properties of Polymer-Wrapped Single-Walled Carbon Nanotubes (2001)

Intimate electrical contact occurs between a substituted poly(metaphenylenevinylene) (PmPV) and bundles of single-walled nanotubes (SWNT) as evidenced by atomic force microscopy, optical, and electronic measurements carried out on single, isolated SWNT/PmPV structures (see picture). PmPV may provide a useful route toward “functionalizing” the SWNT without destroying their electrical character. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2001/z16297_s.pdf or from the author. 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.
CYCLOADDITION OF DIAZOMETHANE TO BUTADIENYLPHOSPHONATES. A NEW APPROACH TO FUNCTIONALIZED PENTADIENYLPHOSPHONATES AND PYRAZOLES (1985)

Abstract The cycloaddition reaction of diazomethane with diethyl 1,3-butadienylphosphonates containing electronegative substituents on the α-carbon atom gave diethyl (4-alkenyl-Δ1-pyrazolin-3-yl)phosphonates in high yields. Thermolysis and the base-catalyzed reaction of the pyrazolinylphosphonates produced functionalized 2,4-pentadienylphosphonates and pyrazoles, respectively, in good yields.
Long term statistics of precipitation rate return periods in the context of microwave communications (1989)

Using a 49 year point rainfall rate data bank the authors summarise the analysis and statistical modelling of the interval of time between exceedances of rain thresholds R. The study distinguishes between successive exceedances occurring within the same rain event (intra exceedances I/sub a/), and those occurring at different rain events (inter exceedances I/sub e/). The global study of both return periods or intervals I/sub i/ is also presented. The study is applied to a 49 year point rain rate data bank. It is found that the annual inter and intra intervals are well modelled by log normal distributions, and each set clusters to a single distribution when the intervals are normalized to their annual averages I/sub a/, I/sub e/.
Epitope mapping, expression and post-translational modifications of two isoforms of CD33 (CD33M and CD33m) on lymphoid and myeloid human cells (2011)

We have tested the usefulness of several commercial anti-CD33 monoclonal antibodies (mAb) to determine the expression and localization of the two CD33 isoforms on several hematopoietic cell lines. The expression of the isoform CD33m, a CD33 transmembrane splice variant lacking the ligand-binding V immunoglobulin (Ig)-like domain, was detected by RT-polymerase chain reaction, western blot, confocal microscopy and flow cytometry on the membrane of several human cell types. CD33m was only detected by the anti-CD33 mAb HIM3-4 on the cell surface, whereas WM53, P67.6, 4D3, HIM3-4, WM54, D3HL60.251 or MY9 detected the CD33M isoform, indicating that HIM3-4 is the only mAb recognizing CD33 C(2) Ig domain. Accordingly, HIM3-4 binding to CD33 did not interfere with the binding of other antibodies against the CD33 V-domain. P67.6 mAb interfered with recognition by the rest of antibodies specific for the V domain. HIM3-4 staining could be increased after the sialidase treatment of all CD33(+) cells. However, this increase was stronger in activated T cells, suggesting a CD33 masking state in this cell population. Confocal microscopy analysis of CD33m HEK 293T-transfected cells revealed that this protein is expressed on the cell membrane and also detected in the Golgi compartment. CD33 is constitutively located outside the lipid raft domains, whereas cross-linked CD33 is highly recruited to this signaling platform. The unique ability of HIM3-4 mAb to detect the masking state of CD33 on different cell lineages makes it a good tool to improve the knowledge of the biological role of this sialic acid-binding Ig-like lectin.
Abnormal Acidification of Melanoma Cells Induces Tyrosinase Retention in the Early Secretory Pathway (2002)

In tyrosinase-positive amelanotic melanoma cells, inactive tyrosinase accumulates in the endoplasmic reticulum. Based on studies described here, we propose that aberrant vacuolar proton ATPase (V-ATPase)-mediated proton transport in melanoma cells disrupts tyrosinase trafficking through the secretory pathway. Amelanotic but not melanotic melanoma cells or normal melanocytes display elevated proton export as observed by the acidification of the extracellular medium and their ability to maintain neutral intracellular pH. Tyrosinase activity and transit through the Golgi were restored by either maintaining the melanoma cells in alkaline medium (pH 7.4-7.7) or by restricting glucose uptake. The translocation of tyrosinase out of the endoplasmic reticulum and the induction of cell pigmentation in the presence of the ionophore monensin or the specific V-ATPase inhibitors concanamycin A and bafilomycin A1 supported a role for V-ATPases in this process. Because it was previously shown that V-ATPase activity is increased in solid tumors in response to an acidified environment, the appearance of hypopigmented cells in tyrosinase-positive melanoma tumors may indicate the onset of enhanced glycolysis and extracellular acidification, conditions known to favor metastatic spread and resistance to weak base chemotherapeutic drugs.
Hereditary nonpolyposis colorectal cancer and colonic adenomas: Aggressive adenomas? (1995)

Hereditary nonpolyposis colorectal cancer (HNPCC) results from an inherited defect in one of the genes responsible for repair of errors that occur during DNA replication. Affected individuals have high risk for cancers of the colon and certain extracolonic sites. It appears that HNPCC patients form adenomas at about the same rate s the general population and there is some circumstantial evidence that adenoma is the precursor to colorectal carcinoma in the syndrome. It is hypothesized that HNPCC features accelerated progression from colonic adenoma to carcinoma, a process theoretically driven by the inability to repair DNA mismatches. Evidence in support of the "Aggressive Adenoma" in HNPCC is provided. We discuss our recommendations for colonoscopic surveillance on an annual basis for HNPCC gene-positive individuals, and for genetic counseling.
Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis (2005)

Retarded release oral phosphatidylcholine is effective in alleviating inflammatory activity caused by ulcerative colitis.
Increasing memory miss tolerance for SIMD cores (2009)

Manycore processors with wide SIMD cores are becoming a popular choice for the next generation of throughput oriented architectures. We introduce a hardware technique called "diverge on miss" that allows SIMD cores to better tolerate memory latency for workloads with non-contiguous memory access patterns. Individual threads within a SIMD "warp" are allowed to slip behind other threads in the same warp, letting the warp continue execution even if a subset of threads are waiting on memory. Diverge on miss can either increase the performance of a given design by up to a factor of 3.14 for a single warp per core, or reduce the number of warps per core needed to sustain a given level of performance from 16 to 2 warps, reducing the area per core by 35%.
Antisense PMO cocktails effectively skip dystrophin exons 45-55 in myotubes transdifferentiated from DMD patient fibroblasts (2018)

Antisense-mediated exon skipping has made significant progress as a therapeutic platform in recent years, especially in the case of Duchenne muscular dystrophy (DMD). Despite FDA approval of eteplirsen-the first-ever antisense drug clinically marketed for DMD-exon skipping therapy still faces the significant hurdles of limited applicability and unknown truncated protein function. In-frame exon skipping of dystrophin exons 45-55 represents a significant approach to treating DMD, as a large proportion of patients harbor mutations within this "hotspot" region. Additionally, patients harboring dystrophin exons 45-55 deletion mutations are reported to have exceptionally mild to asymptomatic phenotypes. Here, we demonstrate that a cocktail of phosphorodiamidate morpholino oligomers can effectively skip dystrophin exons 45-55 in vitro in myotubes transdifferentiated from DMD patient fibroblast cells. This is the first report of substantive exons 45-55 skipping in DMD patient cells. These findings help validate the use of transdifferentiated patient fibroblast cells as a suitable cell model for dystrophin exon skipping assays and further emphasize the feasibility of dystrophin exons 45-55 skipping in patients.
Mobile genetic elements of the human gastrointestinal tract (2013)

The human intestine is an important location for horizontal gene transfer (HGT) due to the presence of a densely populated community of microorganisms which are essential to the health of the human superorganism. HGT in this niche has the potential to influence the evolution of members of this microbial community and to mediate the spread of antibiotic resistance genes from commensal organisms to potential pathogens. Recent culture-independent techniques and metagenomic studies have provided an insight into the distribution of mobile genetic elements (MGEs) and the extent of HGT in the human gastrointestinal tract. In this mini-review, we explore the current knowledge of mobile genetic elements in the gastrointestinal tract, the progress of research into the distribution of antibiotic resistance genes in the gut and the potential role of MGEs in the spread of antibiotic resistance. In the face of reduced treatment options for many clinical infections, understanding environmental and commensal antibiotic resistance and spread is critical to the future development of meaningful and long lasting anti-microbial therapies.
Cytotoxicity of monoclonal antibodies to a subset of Giardia isolates. (1986)

Previous studies showed that some Giardia lamblia isolates differ and can be categorized on the basis of their DNA banding patterns after digestion with endonuclease restriction enzymes, surface antigens, and excretory-secretory (E-S) products. In the present study, monoclonal antibodies (McAb) were produced that reacted with one specific group of Giardia isolates. These McAb recognized a 170,000 dalton antigen, which was present on the surface of these Giardia and released into the medium as an E-S antigen. This antigen was previously characterized and found to distinguish this subgroup of Giardia. In addition, these McAb were cytotoxic only for this subgroup of Giardia. Immobilization occurred immediately, and killing was documented by 7 min. The mechanism(s) of killing remains unknown but was shown to be complement independent and did not occur with Fab'. These McAb identifies certain isolates and can be used to type Giardia.
Online temporal pattern learning (2009)

This paper describes a biologically motivated approach, using hierarchical temporal memory (HTM), to build a high-level self-organizing visual system for a soccer bot. Meanwhile it presents two unsupervised online learning algorithms for temporal patterns in HTMs. The algorithms were implemented in a simulated soccer bot for a real-world evaluation. After a training phase, the robot was able to recognize different static objects in the soccer field. It also learned and recognized high-level objects that are composed of simpler objects, with position invariance and was also able to learn and recognize motions in the objects, all in a completely unsupervised manner.
Extracellular ATP: effects, sources and fate (1986)

ANAPP,, 3'-O-{3[N-(4-azido-2-nitrophenyl)amino]propionyl}adenosine 5'-triphosphate; APCP, adenosine 5'-[a,,8- methylene]diphosphate; APCPP, adenosine 5'-[a,
Notch signaling: its roles and therapeutic potential in hematological malignancies (2016)

Notch is a highly conserved signaling system that allows neighboring cells to communicate, thereby controlling their differentiation, proliferation and apoptosis, with the outcome of its activation being highly dependent on signal strength and cell type. As such, there is growing evidence that disturbances in physiological Notch signaling contribute to cancer development and growth through various mechanisms. Notch was first reported to contribute to tumorigenesis in the early 90s, through identification of the involvement of the Notch1 gene in the chromosomal translocation t(7;9)(q34;q34.3), found in a small subset of T-cell acute lymphoblastic leukemia. Since then, Notch mutations and aberrant Notch signaling have been reported in numerous other precursor and mature hematological malignancies, of both myeloid and lymphoid origin, as well as many epithelial tumor types. Of note, Notch has been reported to have both oncogenic and tumor suppressor roles, dependent on the cancer cell type. In this review, we will first give a general description of the Notch signaling pathway, and its physiologic role in hematopoiesis. Next, we will review the role of aberrant Notch signaling in several hematological malignancies. Finally, we will discuss current and potential future therapeutic approaches targeting this pathway.
Combined Therapy with Chemotherapeutic Agents and Herpes Simplex Virus Type 1 ICP34.5 Mutant (HSV-1716) in Human Non-Small Cell Lung Cancer (1999)

A replication-selective herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) has shown efficacy both in vitro and in vivo against human non-small cell lung cancer (NSCLC) cell lines but complete eradication of tumor has not been accomplished with a single viral treatment in our murine xenograft models. Therefore, strategies to enhance the efficacy of this treatment were investigated. We determined the oncolytic activity of HSV-1716 in NCI-H460 cells in combination with each of four chemotherapeutic agents: mitomycin C (MMC), cis-platinum II (cis-DDP), methotrexate (MTX), or doxorubicin (ADR). Isobologram analysis was performed to evaluate the interaction between the viral and chemotherapeutic agents. The oncolytic effect of HSV-1716 in combination with MMC was synergistic in two of five NSCLC cell lines. In the other three cell lines, the combined effect appeared additive. No antagonism was observed. The in vivo effect of this combination was then examined in a murine xenograft model. NCI-H460 flank tumors were directly injected with HSV-1716 (4 x 106 PFU) followed by intravenous MMC administration (0.17 mg/kg) 24 hr later. After 3 weeks, the mean tumor weight in the combined treatment group was significantly less than either individual treatment in an additive manner. The synergistic dose of MMC neither augmented nor inhibited viral replication in vitro and HSV-1716 infection did not upregulate DT-diaphorase, which is the primary enzyme responsible for MMC activation. In summary, the combination of HSV-1716 with common chemotherapeutic agents may augment the effect of HSV-based therapy in the treatment of NSCLC.
Combined biological nitrification and denitrification of high-salinity wastewater (1997)

The focusing on the discharge of nitrogen compounds to aquifers has put pressure on power plants to look into removal of nitrogen compounds from the gas scrubbing liquors (DESOx and DENOx). The scrubber liquor has a high salinity, a high chloride content and a temperature of about 40°. Initial laboratory tests to evaluate the possibility of performing biological nitrification and denitrification showed promise and a pilot-scale test unit was established at one of the Danish coal-fired combined heat and power plant (AVEDØRE 1). The pilot plant was operated under varying conditions with regard to temperature and chloride concentration. Maximum nitrification and denitrification rates were measured. At 30°C and 20 g Cl−/l, maximum nitrification and denitrification rates of 2 and 3 mg N/g VSS·h respectively were measured. In the effluent, concentrations of inorganic nitrogen were below 8 mg N/l. Twice during the test period, inhibition of the biomass activity was caused by high concentrations of heavy metals. The high content of heavy metals was due to malfunction of pH control in the heavy metal removal plant. The nitrification process was more sensitive to heavy metals than the denitrification process, and during the two toxic events the nitrification rate decreased to zero. The influence of rapid changes in the chloride and nitrite contents on nitrification was also examined. The results from the performed tests can be applied on other wastewaters with similar characteristics as these scrubber liquors i.e. with salinity. As an example fertilizer and pharmaceutical industries can be mentioned.
Effect of lipid peroxidation inhibition on retinal ganglion cell death. (1996)

The lipid peroxidation blocker tirilazad mesylate inhibits retinal ganglion cell death in vitro. Because irreversible loss of retinal ganglion cells is the final common pathway in a variety of optic neuropathies, this or similar agents may be useful in animal models of optic neuropathies.
Silicone Rubber Substrata: A New Wrinkle in the Study of Cell Locomotion (1980)

When tissue cells are cultured on very thin sheets of cross-linked silicone fluid, the traction forces the cells exert are made visible as elastic distortion and wrinkling of this substratum. Around explants this pattern of wrinkling closely resembles the "center effects" long observed in plasma clots and traditionally attributed to dehydration shrinkage.
Evidence for lack of enhanced hedgehog target gene expression in common extracutaneous tumors. (2003)

Abnormal hedgehog signaling, most commonly caused by loss of PTCH1 inhibitor activity,drives tumorigenesis of basal cell carcinomas (BCCs). To assess whether other tumors also have abnormal hedgehog signaling, we have assayed RNA from common cancers at nine different sites for levels of expression of hedgehog target genes that are up-regulated uniformly in BCCs. We report here that such dysregulation appears not to be common in the types of non-BCC cancers studied, indicating that the molecular pathogenesis of BCCs, like their frequency and behavior, differs markedly from that of most other cancers.
GNSS Error Sources (2018)

This chapter discusses the most serious sources of error affecting global navigation satellite systems (GNSS) signals, classifying these in a new way, according to their nature and/or effects. For instance, errors due to clock bias or drift are grouped together. Errors related to the signal propagation medium, too, are treated in the same way. GNSS errors need to be corrected to achieve accepted positioning and navigational accuracy. We provide a theoretical description for each source, supporting these with diagrams and analytical figures where possible. Some common metrics to measure the magnitude of GNSS errors, including the user equivalent range error (UERE) and the dilution of precision (DOP), are also presented. The chapter concludes with remarks on the significance of the sources of error.
Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin. (1996)

Huntington's disease (HD) is an inherited neurodegenerative disorder associated with expansion of a CAG repeat in the IT15 gene. The IT15 gene is translated to a protein product termed huntingtin that contains a polyglutamine (polyGln) tract. Recent investigations indicate that the cause of HD is expansion of the polyGln tract. However, the function of huntingtin and how the expanded polyGln tract causes HD is not known. We investigate potential protein-protein interactions of huntingtin using affinity resins. Huntingtin from brain extracts is retained on calmodulin(CAM)-Sepharose in a calcium-dependent fashion. We purify rat huntingtin to apparent homogeneity using a combination of DEAE-cellulose column chromatography, ammonium sulfate precipitation, and preparative SDS/PAGE. Purified rat huntingtin does not interact with CAM directly as revealed by 125I-CAM overlay. Huntingtin forms a large CAM-containing complex of over 1,000 kDa in the presence of calcium, which partially disassociates in the absence of calcium. Furthermore, an increased amount of mutant huntingtin from HD patient brains is retained on CAM-Sepharose compared to normal huntingtin from control patient brains, and the mutant allele is preferentially retained on CAM-Sepharose in the absence of calcium. These results suggest that huntingtin interacts with other proteins including CAM and that the expansion of polyGln alters this interaction.
Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay (1988)

An enzyme-linked immunosorbent assay for plasminogen activator inhibitor-1 (PAI-1) in biologic fluids was developed on the basis of two murine monoclonal antibodies raised against PAI-1 purified from HT-1080 fibrosarcoma cells. The lower limit of sensitivity of the assay in plasma is 2 ng/mL. The assay is 12 times less sensitive toward the PAI-1/human tissue-type plasminogen activator (t-PA) complex as compared with free PAI-1. The intraassay, interassay, and interdilution coefficients of variation are 5.2%, 8.0%, and 7.1%, respectively. The level of PAI-1 in platelet-poor plasma of healthy subjects is 18 +/- 10 ng/mL (mean +/- SD, n = 45). In platelet-rich plasma after freezing and thawing, 92% of PAI-1 antigen is released from platelets, whereas only 8% is found in the corresponding platelet-poor plasma. In platelet-poor plasma from healthy subjects, a linear correlation (r = 0.80) was found between PAI activity and PAI-1 antigen. In plasma approximately two thirds of the PAI-1 antigen was functionally active, whereas only 5% of the PAI-1 antigen released from platelets was active. During pregnancy a progressive increase of PAI-1 antigen levels up to three- to sixfold the control value was observed. In plasma of patients with recurrent deep vein thrombosis, PAI-1 levels were 44 +/- 20 ng/mL (mean +/- SD, n = 7), during a clinically silent phase. Four of these patients had a level above 38 ng/mL (mean +/- 2 SD of normal). The present assay, based on stable and reproducible reagents, allows the specific determination of PAI-1 antigen in biologic fluids. It may facilitate interlaboratory comparisons and be useful for further investigations of the role of PAI-1 in clinical conditions associated with impaired fibrinolysis and/or a tendency to thrombosis and investigations of the role of PAI-1 in platelets.