gebhart/patrepeval huggingface dataset:
Activation of Akt (Protein Kinase B) in Mammary Epithelium Provides a Critical Cell Survival Signal Required for Tumor Progression (2001)

Activation of Akt by the phosphatidylinositol 3'-OH kinase (PI3K) results in the inhibition of proapoptotic signals and the promotion of survival signals (L. P. Kane et al., Curr. Biol. 9:601-604, 1999; G. J. Kops et al., Nature 398:630-634, 1999). Evidence supporting the importance of the PI3K/Akt signaling pathway in tumorigenesis stems from experiments with transgenic mice bearing polyomavirus middle T antigen under the control of the mouse mammary tumor virus long terminal repeat promoter. Mammary epithelium-specific expression of polyomavirus middle T antigen results in the rapid development of multifocal metastatic mammary tumors, whereas transgenic mice expressing a mutant middle T antigen decoupled from the phosphatidylinositol 3'-OH kinase (MTY315/322F) develop extensive mammary gland hyperplasias that are highly apoptotic. To directly assess the role of Akt in mammary epithelial development and tumorigenesis, we generated transgenic mice expressing constitutively active Akt (HAPKB308D473D or Akt-DD). Although expression of Akt-DD interferes with normal mammary gland involution, tumors were not observed in these strains. However, coexpression of Akt-DD with MTY315/322F resulted in a dramatic acceleration of mammary tumorigenesis correlated with reduced apoptotic cell death. Furthermore, coexpression of Akt-DD with MTY315/322F resulted in phosphorylation of the FKHR forkhead transcription factor and translational upregulation of cyclin D1 levels. Importantly, we did not observe an associated restoration of wild-type metastasis levels in the bitransgenic strain. Taken together these observations indicate that activation of Akt can contribute to tumor progression by providing an important cell survival signal but does not promote metastatic progression.
Synthesis and antitumor activity of cyclophosphamide analogs. 4. Preparation, kinetic studies, and anticancer screening of phenylketophosphamide and similar compounds related to the cyclophosphamide metabolite aldophosphamide (1986)

Phenyl ketone phosphorodiamidates [C6H5C(O)CH2CH2OP(O)NHR1NR2R3] were synthesized in conjunction with an ongoing investigation into the effects of substituents on the dynamical solution chemistry of the metabolites of cyclophosphamide (1a). In contrast to aldophosphamide (3a), which readily interconverts with its cyclic isomer 4-hydroxycyclophosphamide (2a), phenylketophosphamide (14a: R1 = H, R2 = R3 = CH2CH2Cl) exhibited an apparent "resistance" toward an intramolecular addition reaction such that 4-hydroxy-4-phenylcyclophosphamide (13a) could not be detected either spectroscopically (31P or 13C NMR) or chemically (NaCN trapping experiment). Control studies that compared the relative reactivities of 14a and methylketophosphamide [20: CH3C(O)CH2CH2OP(O)NH2N-(CH2CH2Cl)2] revealed that the factors that modulate the ring closure/opening reactions were not peculiar to the phenyl group; however, differences between phenyl and methyl profoundly influenced the rates of fragmentation of 14a and 20. 31P NMR spectroscopy was used to determine the rates at which each compound generated a cytotoxic alkylating agent. Under a standard set of reaction conditions [1 M lutidine buffer with added Me2SO (8:2), pH 7.4, 37 degrees C], the half-lives of 2a/3a, 14a, phenylketoifosfamide (14b: R1 = R2 = CH2CH2Cl, R3 = H), phenylketotrofosfamide (14c: R1 = R2 = R3 = CH2CH2Cl), and 20 were 72, 66, 63, 56, and 173 min, respectively. Analogues 14a and 14b exhibited good anticancer activity against a variety of test systems.
Synthesis, Properties, and Reactivity of (1H,1H-Perfluoroalkyl)- and (1H-Perfluoro-1-alkenyl)aryliodonium Triflates and Their Analogs (1987)

Abstract (1H,1H-Perfluoroalkyl)phenyl- and -(p-fluorophenyl)iodoniurn triflates, fluorosulfate, sulfate (3)–(7) were synthesized in good yields by the oxidation of 1-iodo-1H,1H-perfluoroalkanes (RfCH2I) with trifluoroperacetic acid followed by treatment with triflic acid and benzene or fluorobenzene. (1H,1H,5H,5H-Perfluoropentane-1,5-diyl)bisphenylbisiodonium triflate was synthesized similarly. (trans-1H-Perfluoro-1-alkenyl)phenyliodonium triflates (11) were synthesized by dehydrofluorination of 3 with a base in good yields. Thermolysis of 3 produced 1H,1H-perfluoroalkyl triflate and iodobenzene, while 11 gave (Z)-1-iodo-1H-perfluoro-1-alkene and phenyl triflate. The thermolysis experiment, including (perfluoroalkyl)phenyliodonium triflate (17), demonstrated that the C–I bond strength of the trivalent iodine compounds increased in the order of RfCH2–I, Rf–I&amp;lt;Ph–I&amp;lt;RfCF=CH–I. The ionic mechanism containing RfCH2+, Ph+, and Rf+ for the thermal decomposition of 3, 11, and 17, respectively, was proposed. The reactivities of 3 and 11 to such nucleophiles as phenoxide, alkoxide, and alkanethiolate anions were studied and compared with that of 17. Remarkable changes in the reactivity were found depending on the nature of the fluoro-alkyl and -alkenyl groups. The reaction of 11 with the oxide anions yielded (2-phenoxy- and -alkoxy-1H-perfluoro-1-alkenyl)phenyliodonium triflates.
Differential DNA hypermethylation and hypomethylation signatures in colorectal cancer (2004)

Cancer cells are characterized by a generalized disruption of the DNA methylation pattern involving an overall decrease in the level of 5-methylcytosine together with regional hypermethylation of particular CpG islands. The extent of both DNA hypomethylation and hypermethylation in the tumor cell is likely to reflect distinctive biological and clinical features, although no studies have addressed its concurrent analysis until now. DNA methylation profiles in sporadic colorectal carcinomas, synchronous adenoma-carcinoma pairs and their matching normal mucosa were analyzed by using the amplification of inter-methylated sites (AIMS) method. A total of 208 AIMS generated sequences were tagged and evaluated for differential methylation. Global indices of hypermethylation and hypomethylation were calculated. All tumors displayed altered patterns of DNA methylation in reference to normal tissue. On average, 24% of the tagged sequences were differentially methylated in the tumor in regard to the normal pair with an overall prevalence of hypomethylations to hypermethylations. Carcinomas exhibited higher levels of hypermethylation than did adenomas but similar levels of hypomethylation. Indices of hypomethylation and hypermethylation showed independent correlations with patient's sex, tumor staging and specific gene hypermethylation. Hierarchical cluster analysis revealed two main patterns of DNA methylation that were associated to particular mutational spectra in the K-ras and the p53 genes and alternative correlates of hypomethylation and hypermethylation with survival. We conclude that DNA hypermethylation and hypomethylation are independent processes and appear to play different roles in colorectal tumor progression. Subgroups of colorectal tumors show specific genetic and epigenetic signatures and display distinctive correlates with overall survival.
1,2‐Epoxycarotinoide. 4. Mitteilung. Synthese, 1H‐NMR‐ und CD‐Studien von (S)‐1,2‐Epoxy‐1,2‐dihydrolycopin und (S)‐1′,2′‐Epoxy‐1′,2′‐dihydro‐γ‐carotin (1984)

1,2‐Epoxycarotenoids: Synthesis, 1 H‐NMR and CD Studies of (S) ‐1,2‐Epoxy‐1,2‐dihydrolycopene and (S) ‐1′,2′‐Epoxy‐1′, 2′ ‐dihydro‐γ‐carotene The synthesis of ( S )‐1,2‐epoxy‐1,2‐dihydrolycopene ( (S) ‐ 1 ) and ( S )‐1′, 2′ ‐epoxy‐ 1′, 2′ ‐dihydro‐γ‐carotene ( (S) ‐ 2 ) are described. The CD spectra of the (all‐ E )‐isomers and of the isomers (7Z, S )‐ 1 and (7′ Z , S )‐ 2 are discussed. The comparison of the CD spectra of the synthetic ( S )‐ 1 and the compound isolated from the tomatoes proves the ( S )‐configuration of the natural product.
PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis (2016)

PD-L1 tumor over-expression seems to be associated with higher clinical activity of anti PD-1/PD-L1 MoAbs, in pre-treated NSCLC patients, suggesting a potential role of PD-L1 expression, IHC cut-off point 1%, as predictive biomarker for the selection of patients to treat with immune-checkpoint inhibitors.
Effect of Auristatin PHE on Microtubule Integrity and Nuclear Localization in Cryptococcus neoformans (2002)

The mechanism of action of the fungicidal peptide auristatin PHE was investigated in Cryptococcus neoformans. Since auristatin PHE causes budding arrest in C. neoformans (T. Woyke, G. R. Pettit, G. Winkelmann, and R. K. Pettit, Antimicrob. Agents Chemother. 45:3580-3584, 2001), microtubule integrity and nuclear localization in auristatin PHE-treated cells were examined. Iterative deconvolution in conjunction with an optimized C. neoformans microtubule immunolabeling procedure enabled detailed visualization of the microtubule cytoskeleton in auristatin PHE-treated C. neoformans. The effect of auristatin PHE on C. neoformans microtubule organization was compared with that of the tubulin-binding agent nocodazole. Both drugs produced complete disruption first of cytoplasmic and then of spindle microtubules in a time- and concentration-dependent manner. Sub-MICs of auristatin PHE caused complete microtubule disruption within 4.5 h, while 1.5 times the nocodazole MIC was required for the same effect. For both drugs, disruption of microtubules was accompanied by blockage of nuclear migration and of nuclear and cellular division, resulting in cells arrested in a uninucleate, large-budded stage. Nocodazole and the linear peptide auristatin PHE are remarkably different in structure and spectrum of activity, yet on the cellular level, they have similar effects.
Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly. (1992)

Two Saccharomyces cerevisiae genes, CIN8 and KIP1 (a.k.a. CIN9), were identified by their requirement for normal chromosome segregation. Both genes encode polypeptides related to the heavy chain of the microtubule-based force-generating enzyme kinesin. Cin8p was found to be required for pole separation during mitotic spindle assembly at 37 degrees C, although overproduced Kip1p could substitute. At lower temperatures, the activity of at least one of these proteins was required for cell viability, indicating that they perform an essential but redundant function. Cin8p was observed to be a component of the mitotic spindle, colocalizing with the microtubules that lie between the poles. Taken together, these findings suggest that these proteins interact with spindle microtubules to produce an outwardly directed force acting upon the poles.
Affinity-purified soluble Fc epsilon RII/CD23 derived from a culture supernatant of an EBV-immortalized B-cell line induced a monophasic fever in rabbits. (1991)

A soluble form of Fc epsilon RII/CD23 is spontaneously released from most lymphoblastoid cell lines established by the Epstein-Barr virus (EBV). Such a product was purified on an IgE-Sepharose column and its pyrogenic effect was investigated in rabbits. This preparation induced a monophasic fever in rabbits, with a peak response appearing 75 min after injection. Since IgE was found to be capable of abrogating such an effect, it is suggested that IgE might be involved in the control of the effectiveness of this soluble protein.
Zinc Concentration in Esophageal Biopsy Specimens Measured by X-Ray Fluorescence and Esophageal Cancer Risk (2005)

High tissue zinc concentration was strongly associated with a reduced risk of developing esophageal squamous cell carcinoma. X-ray fluorescence spectroscopy can be used to assess relationships among concentrations of both nutritional and toxic elements and disease risk in banked tissue specimens.
Implementation of GPS for location tracking (2011)

Stand alone global positioning system receivers are widely used nowadays to accurately locating one's position. By using stand alone GPS receivers the distance between two locations on earth can also be measured. This project is aim to design and implement a low cost Global Positioning System suitable to be used for hiking, climbing and sailing activities. The function of the GPS is to locate the position of user. The effects of line of sights in relation to different experimented locations are also studied. In this project, the hardware used is PIC18F4520 integrated with GPS receiver typed FV-M8. The GPS modules will generate the coordinates of latitude and longitude as well as the bearing angles between two positions. The algorithm to calculate the distance between two positions was developed by using PIC C Compiler. The written algorithm extracted the data from the GPS receiver via the RS232 communication. Microcontroller is used to parse the NMEA data sentences and execute the algorithm. Finally, the output is displayed to a LCD display unit. System testing conducted showed that for a few chosen different locations, geographical view and weather conditions, overall results give an average of 10 % different compared with ideal theoretical calculated results.
Inhibition by rapamycin of leukocyte migration and bronchial hyperreactivity induced by injection of Sephadex beads to guinea‐pigs (1993)

1. The effect of rapamycin (0.001 to 5 mg kg-1) on the increased leukocyte counts in bronchoalveolar lavage (BAL) fluid and hyperreactivity of isolated bronchial strips to histamine and acetylcholine (ACh) was studied following the intravenous injection of Sephadex beads to guinea-pigs. 2. The intramuscular (i.m.) injection of rapamycin (0.012 to 5 mg kg-1) dose-dependently inhibited the increase in leukocyte counts in BAL fluid. Rapamycin (5 mg kg-1) reduced the numbers of eosinophils neutrophils, macrophages and lymphocytes in BAL fluid by 64, 55, 19 and 50% respectively. In addition, rapamycin (0.012 to 5 mg kg-1) significantly inhibited the Sephadex-induced hyperreactivity of bronchial tissue to both histamine and ACh. 3. At a dose of 0.001 mg kg-1, rapamycin did not significantly reduce leukocyte infiltration or bronchial hyperreactivity. 4. Cyclosporin (5 mg kg-1) significantly reduced both lymphocyte and eosinophil numbers in BAL fluid of Sephadex-injected guinea-pigs whereas dexamethasone (1 mg kg-1) significantly reduced lymphocyte numbers. Neither drug affected the bronchial hyperreactivity to histamine and ACh. 5. It is concluded that the new immunosuppressive drug, rapamycin, is a potent inhibitor of leukocyte migration and bronchial hyperreactivity observed following the intravenous injection of Sephadex beads to guinea-pigs. Rapamycin also appears to be more effective than cyclosporin or dexamethasone in reducing leukocyte counts and bronchial hyperreactivity in this model. 6. Our results suggest that inflammatory mechanisms which are inhibited by rapamycin may be important in the induction of Sephadex-induced hyperreactivity.
Destabilization of the Epidermal Growth Factor Receptor (EGFR) by a Peptide That Inhibits EGFR Binding to Heat Shock Protein 90 and Receptor Dimerization (2013)

An eight-amino acid segment is known to be responsible for the marked difference in the rates of degradation of the EGF receptor (ErbB1) and ErbB2 upon treatment of cells with the Hsp90 inhibitor geldanamycin. We have scrambled the first six amino acids of this segment of the EGF receptor (EGFR), which lies in close association with the ATP binding cleft and the dimerization face. Scrambling these six amino acids markedly reduces EGFR stability, EGF-stimulated receptor dimerization, and autophosphorylation activity. Two peptides were synthesized as follows: one containing the wild-type sequence of the eight-amino acid segment, which we call Disruptin; and one with the scrambled sequence. Disruptin inhibits Hsp90 binding to the EGFR and causes slow degradation of the EGFR in two EGFR-dependent cancer cell lines, whereas the scrambled peptide is inactive. This effect is specific for EGFR versus other Hsp90 client proteins. In the presence of EGF, Disruptin, but not the scrambled peptide, inhibits EGFR dimerization and causes rapid degradation of the EGFR. In contrast to the Hsp90 inhibitor geldanamycin, Disruptin inhibits cancer cell growth by a nonapoptotic mechanism. Disruptin provides proof of concept for the development of a new class of anti-tumor drugs that specifically cause EGFR degradation.
Enzyme-linked immunosorbent assay in the diagnosis of kala-azar in Bhadohi (Varanasi), India (1990)

An enzyme-linked immunosorbent assay (ELISA) developed using Leishmania donovani promastigote soluble antigen gave positive responses in practically all the clinically and parasitologically diagnosed patients with kala-azar in a preliminary study. Healthy control subjects from non-endemic and endemic areas gave negative results. No cross-reaction was observed with patients having leprosy, filariasis, malaria, tuberculosis, or amoebiasis. Blood samples collected on filter paper were adequate for the test. The test appears promising in the diagnosis of kala-azar.
Understanding text corpora with multiple facets (2010)

Text visualization becomes an increasingly more important research topic as the need to understand massive-scale textual information is proven to be imperative for many people and businesses. However, it is still very challenging to design effective visual metaphors to represent large corpora of text due to the unstructured and high-dimensional nature of text. In this paper, we propose a data model that can be used to represent most of the text corpora. Such a data model contains four basic types of facets: time, category, content (unstructured), and structured facet. To understand the corpus with such a data model, we develop a hybrid visualization by combining the trend graph with tag-clouds. We encode the four types of data facets with four separate visual dimensions. To help people discover evolutionary and correlation patterns, we also develop several visual interaction methods that allow people to interactively analyze text by one or more facets. Finally, we present two case studies to demonstrate the effectiveness of our solution in support of multi-faceted visual analysis of text corpora.
Field Planning Using Integrated Surface/Subsurface Modeling (2005)

Abstract Integrated surface/subsurface modeling has been shown to have a critical impact on field development. Integrated modeling aims to capture the interaction between the surface facilities, the production/injection system, and the reservoir(s). Among other issues, an integrated surface/subsurface model addresses the following: Pressure interaction between a reservoir and a surface facility network model.Pressure interaction between different reservoirs in the case of multiple reservoirs sharing a surface facility.Improved calculation of pressure and temperature gradients in the wellbore.Influence of facility constraints and equipment on a set of reservoirs sharing a surface facility.Mixing of fluids from reservoirs with different fluid descriptions sharing a common production network.Applying global production and injection constraints to the coupled system (including the transfer of reinjection fluids between reservoirs). In this paper, a set of examples is presented illustrating the use of the above surface/subsurface modeling capabilities and their impact on field planning. The study mainly focuses on the following issues: Multiple reservoirs coupling in a compositional mode involving black oil delumping. Reservoir/network coupling takes place at both the well bottomhole and tubinghead.Integrated surface/subsurface system response to various network choke-setting scenarios.Field events scheduling in response to the behavior of the integrated surface/subsurface system. The results presented in this paper complement those presented in a previous study.[1]
Low temperature synthesis of nanocrystalline Y3Al5O12 (YAG) and Ce-doped Y3Al5O12 via different sol–gel methods (1999)

Nanocrystalline yttrium aluminium garnet (YAG, Y3Al5O12) and Ce-doped YAG ceramics were synthesized by two ‘soft chemistry' sol–gel processes using (i) mixtures of inorganic salts or oxides and (ii) mixtures of alkoxides of the respective elements. In the first approach the metal ions, generated by dissolving metal oxides or nitrates in acetic acid and/or water, were complexed by ethylene glycol to obtain the precursors for pure and doped YAG samples. In the alkoxide route monolithic gels were obtained by hydrolysis and condensation of a compositional mixture of Al, Y and Ce alkoxides in a PriOH solution. The molecular level mixing and the tendency of partially hydrolysed alkoxide species to form extended networks of cross-linked metal centers facilitates the structure evolution thereby lowering the crystallization temperature, in the latter case. The X-ray diffraction (XRD) patterns of the ceramic sintered at 700 °C were identical with the stoichiometric YAG composition which is the lowest temperature reported for the synthesis of crystalline and single phase Y3Al5O12 while well developed YAG phases in the non-alkoxide synthesis were obtained only at 1000 °C. Cerium doped YAG powders (CeO2 + Y3Al5O12) were synthesized using [NH4]2[Ce(NO3)6] (8 mol%) and [Ce3(OBut)9(ButOH)2] (5 mol%), as dopants. A homogeneous distribution of cerium in the YAG lattice was achieved in both cases. The thermal behaviour, phase transformations, composition and microstructural features in the gels and polycrystalline samples were studied by TG/DTA, XRD, FT-IR, solid-state 27Al MAS NMR spectroscopy, SEM, TEM, energy dispersive X-ray analysis and high resolution electron microscopy studies. The quality of the resulting products (homogeneity, crystallization temperature, grain size, grain size distribution, etc.) and economical aspects (synthetic skill, cost of precursors, etc.) of the two approaches are discussed.
Load Balancing Servers, Firewalls, and Caches (2002)

From the Publisher:
Owing to their ability to scale server farms and improve the security and availability of networked applications, load balancers are expected to grow into a multibillion-dollar market in the next few years. Written from the unique perspective of an industry insider, this book explains how this critical technology can be used to solve several challenges in managing today's server farms, Web sites, firewalls, and caches. Chandra Kopparapu offers you a close look at how load balancers work and explores the ability of load balancers to solve a multitude of network and server bottlenecks in the Internet age -- from dramatic improvements in server farm scalability to removing the firewall as a network bottleneck. This book provides a technical discussion of this fast-growing market, covering the full spectrum of topics, from server and firewall load balancing to transparent cache switching to global server load balancing. In the process, he delivers insight into the way new technologies are deployed in network infrastructure and how they work.
Conserved and Variant Epitopes of Target Antigens of Transmission-Blocking Antibodies among Isolates of Plasmodium falciparum from Malaysia (1991)

Monoclonal antibodies (MAbs) directed against different epitope regions on three sexual stage-specific gamete surface proteins of Plasmodium falciparum, Pfs 25, Pfs 230, and Pfs 48/45, were used to study the genetic diversity of these epitopes among fresh isolates of P. falciparum from Malaysia, using immunofluorescence microscopy (IFA). Among 45 Malaysian isolates, one epitope of Pfs 25, designated region I, showed evidence of variable reactivity with MAbs among different isolates; the Pfs 25 epitope, region II, was universally recognized by MAbs in all isolates. Two apparently distinct epitope regions of Pfs 230 were defined by MAbs, one of which was universally recognized by MAbs among the 45 isolates; the other was conserved in all but three isolates. The epitope regions of gamete-surface protein Pfs 48/45, designated regions I, IIa, IIb, IIc, III, and IV, were examined for reactivity by IFA in 33 isolates. Epitope regions I, IIb, III, and IV were conserved in all isolates; regions IIa and IIc existed in variant forms.