gebhart/patrepeval huggingface dataset:
Circulating tumor cells in patients with castration-resistant metastatic prostate cancer (2007)

5076 Background: Blood-based assays are urgently needed to provide molecular information on the specific targets expressed in tumor cells to optimize treatment selection. Antibody-capture technologies have been applied to isolate circulating tumor cells (CTC) from small volumes of peripheral blood from patients with progressive castrate metastatic prostate cancer. It has been demonstrated previously that CTC isolated from these patients represent authentic prostate cancer cells. Methods: CTC, positive for EpCAM (epithelial cellular adhesion molecule) and nuclear DAPI, and CD45 negative, were isolated from 120 patients with clinical castrate metastatic disease. All patients had rising PSA levels and were on stable treatment regimens at the time of CTC sampling. We tested the association between CTC counts and PSA levels, and the extent of disease to bone, and soft tissue metastasis by Wilcoxon rank sum. Fluorescence in situ hybridization was performed for AR and ERBB2 genes by an adapted method in CTC. Results: The average age in this patient cohort was 69 years, and median PSA at the time when CTC were drawn was 111 ng/mL (range 0.86–12147 ng/mL). The patterns of metastatic spread included disease in soft tissue only in 12 patients (10%), in bone and soft tissue in 67 (56%), and in bone only in 41 patients (34%). CTC counts ranged from 0 to 1958 cells per 7.5 mL of blood. A large number of patients (54, 45%) had 10 or more circulating tumor cells, while only 33 patients (27.5%) had 1 or less CTC per sample of blood. Significantly higher numbers of CTC were detected in patients with bone metastasis compared to those without bone metastasis (11 vs. 2.5, p&lt;0.01). In patients with marked amplification of AR locus (five patients), tetraploidy was noted in the majority of cases (four cases). Two patients without AR amplification showed apparent tetraploidy, while no analyzed samples (nine) had amplification of ERBB2. Conclusions: The analysis of cancer-related gene alterations in CTC is feasible in a hospital-based laboratory. Further gene expression studies focused on the patients with higher numbers of CTC in correlation with clinical outcomes, as well as the investigation of CTC gene expression during specific treatments are under way. No significant financial relationships to disclose.
Hybrid nanofabrication processes utilizing diblock copolymer nanotemplate prepared by self-assembled monolayer based surface neutralization (2008)

Nanostructures including nanohole and metal dot arrays were fabricated by hybrid processes combing self-assembled diblock copolymer and conventional semiconductor processes. The interfacial energy between polystyrene-b-polymethylmetacrylate (PS-b-PMMA) diblock copolymer and substrate surface was controlled by employing a self-assembled monolayer (SAM), resulting in a polymer template with well-ordered cylindrical nanohole array. The nanohole sizes were controlled within 10 to 22 nm in diameter using block copolymers with different molecular weights. The PS nanotemplates were fabricated on various substrates, including oxides, nitrides, and poly-Si. Nanohole pattern was transferred by dry etching process, producing inorganic nanohole templates. Also, gold nanodot arrays with diameter smaller than 10 nm were fabricated through lift off process.
Autocrine IL6-Mediated Activation of the STAT3–DNMT Axis Silences the TNFα–RIP1 Necroptosis Pathway to Sustain Survival and Accumulation of Myeloid-Derived Suppressor Cells (2020)

Although accumulation of myeloid-derived suppressor cells (MDSC) is a hallmark of cancer, the underlying mechanism of this accumulation within the tumor microenvironment remains incompletely understood. We report here that TNFα-RIP1-mediated necroptosis regulates accumulation of MDSCs. In tumor-bearing mice, pharmacologic inhibition of DNMT with the DNA methyltransferease inhibitor decitabine (DAC) decreased MDSC accumulation and increased activation of antigen-specific cytotoxic T lymphocytes. DAC-induced decreases in MDSC accumulation correlated with increased expression of the myeloid cell lineage-specific transcription factor IRF8 in MDSCs. However, DAC also suppressed MDSC-like cell accumulation in IRF8-deficient mice, indicating that DNA methylation may regulate MDSC survival through an IRF8-independent mechanism. Instead, DAC decreased MDSC accumulation by increasing cell death via disrupting DNA methylation of RIP1-dependent targets of necroptosis. Genome-wide DNA bisulfite sequencing revealed that the <i>Tnf</i> promoter was hypermethylated in tumor-induced MDSCs <i>in vivo</i>. DAC treatment dramatically increased TNFα levels in MDSC <i>in vitro</i>, and neutralizing TNFα significantly increased MDSC accumulation and tumor growth in tumor-bearing mice <i>in vivo</i>. Recombinant TNFα induced MDSC cell death in a dose- and RIP1-dependent manner. IL6 was abundantly expressed in MDSCs in tumor-bearing mice and patients with human colorectal cancer. <i>In vitro</i>, IL6 treatment of MDSC-like cells activated STAT3, increased expression of DNMT1 and DNMT3b, and enhanced survival. Overall, our findings reveal that MDSCs establish a STAT3-DNMT epigenetic axis, regulated by autocrine IL6, to silence TNFα expression. This results in decreased TNFα-induced and RIP1-dependent necroptosis to sustain survival and accumulation. SIGNIFICANCE: These findings demonstrate that targeting IL6 expression or function represent potentially effective approaches to suppress MDSC survival and accumulation in the tumor microenvironment.
Policy-Based Billing Architecture for Internet Differentiated Services (2000)

The Differentiated Services architecture allows a service provider to configure new services dynamically using a policy protocol. This benefit, however, may not be fully realized if the service provider need a high effort to update its billing system to charge for the services. Thus, there is a real need for a flexible billing architecture. To meet this need, a policy-based billing architecture is proposed in this paper. This architecture allows a service provider to define policies for configuring various processes of a billing system based on the charging and pricing schemes used for individual services. Definitions of policies for various charging and pricing schemes are discussed and the potential complexity of each of them is analyzed. Based on the complexity analysis four classes of services, which utilize the least complex charging schemes and require the minimum traffic metering effort, are recommended for meeting different application requirements.
Robust single-mode operation in 50μm ytterbium-doped leakage channel fibers (2007)

Leakage channel fibers, where several air holes form a core, can be precisely engineered to create large leakage loss for higher order modes, while maintain negligible transmission loss for the fundamental mode. This unique property can be used for designing optical fibers with large effective mode area, which supports robust fundamental mode propagation. The large air holes in the design also enable the optical fibers to be bend-resistant. The principles of design and operation regime are outlined in this paper. Performance of an ytterbium-doped double clad leakage channel fiber and an ytterbium-doped polarization-maintaining (PM) double clad leakage channel fiber with ~50&mgr;m core diameter is also discussed.
Voltammetric Determination of Uric Acid at a Fullerene‐C60‐Modified Glassy Carbon Electrode (2005)

Abstract Glassy carbon electrode modified by microcrystals of fullerene‐C 60 mediates the voltammetric determination of uric acid (UA) in the presence of ascorbic acid (AA). Interference of AA was overcome owing to the ability of pretreated fullerene‐C 60 ‐modified glassy carbon electrode. Based on its strong catalytic function towards the oxidation of UA and AA, the overlapping voltammetric response of uric acid and ascorbic acid is resolved into two well‐defined voltammetric peaks with lowered oxidation potential and enhanced oxidation currents under conditions of both linear sweep voltammetry (LSV) and Osteryoung square‐wave voltammetry (OSWV). At pH 7.2, a linear calibration graph is obtained for UA in linear sweep voltammetry over the range from 0.5 μM to 700 μM with a correlation coefficient of 0.9904 and a sensitivity of 0.0215 μA μM −1 . The detection limit (3 σ ) is 0.2 μM for standard solution. AA in less than four fold excess does not interfere. The sensitivity and detection limit in OSWV were found as 0.0255 μA μM −1 and 0.12 μM, for standard solution respectively. The presence of physiologically common interferents (i.e. adenine, hypoxanthine and xanthine) negligibly affects the response of UA. The fullerene‐C 60 ‐modified electrode exhibited a stable, selective and sensitive response to uric acid in the presence of interferents.
Sphingosine 1-phosphate, a specific endogenous signaling molecule controlling cell motility and tumor cell invasiveness. (1992)

Sphingosine 1-phosphate (Sph-1-P), the initial product of Sph degradation by Sph kinase, was shown to be a strong inhibitor of cell motility and phagokinesis of B16 melanoma and other types of cells at 10-100 nM concentration. It also inhibited "chemoinvasion" of tumor cells through a thick layer of Matrigel on a filter membrane. Such inhibitory effects were produced minimally or not at all by Sph, N-methyl derivatives of Sph, or other related sphingolipids and phospholipids. Sph-1-P did not inhibit cell proliferation or protein kinase C (PKC) activity, in contrast to Sph and N-methyl-Sph, which inhibit PKC activity and cell growth in general. Radiolabeled [3H]Sph and [14C]N-methyl-Sph were rapidly incorporated into B16 melanoma cells. However, [14C]N-methyl-Sph was not metabolically converted into other compounds, whereas [3H]Sph was efficiently converted within 10 min to Sph-1-P, followed by conversion to other sphingolipids and phospholipids. The inhibitory effect of Sph-1-P on cell motility and tumor cell invasiveness could be a specific phenomenon independent of PKC and other known transmembrane signaling mechanisms, based on an unknown mechanism. It may directly affect organizational assembly of actin filaments. Since exogenous Sph is rapidly converted into Sph-1-P, some reported effects of Sph may be ascribable to such conversion.
Current-controlled nanotube growth and zone refinement (2005)

We describe methods by which the growth of a single carbon nanotube (CNT) can be precisely controlled by an electrical current. In one method a CNT is grown to a predetermined geometry inside another nanotube, which serves as a reaction chamber. Another method allows a preexisting marginal-quality multiwall CNT to be zone refined into a higher-quality multiwall CNT by driving a catalytic bead down the length of the nanotube. In both methods, the speed of nanotube formation is adjustable, and the growth can be stopped and restarted at will.
Dielectric Solid-State Planar Waveguide Lasers: A Review (2007)

This review takes a look at the historical development of the dielectric planar waveguide laser leading to key state-of-the-art technologies that fall within this broad subject area. Discussed herein are many of the advantages offered by the waveguide geometry such as high optical gain, and thus, low threshold-power requirements, suitability for quasi-three-level laser transitions, integration with functional devices on single substrates, guided spatial-mode control, and its considerable immunity to thermal effects and external environmental conditions. A detailed snapshot is made of many active host media for which there has been reported laser action in the planar waveguide geometry, covering many of the major rare-earth-ion transitions. Several fabrication techniques are highlighted and appraised for their applicability to different host media, touching on their benefits and drawbacks. Challenges and future prospects for these lasers are considered.
3D printing antagonistic systems of artificial muscle using projection stereolithography (2015)

The detailed mechanical design of a digital mask projection stereolithgraphy system is described for the 3D printing of soft actuators. A commercially available, photopolymerizable elastomeric material is identified and characterized in its liquid and solid form using rheological and tensile testing. Its capabilities for use in directly printing high degree of freedom (DOF), soft actuators is assessed. An outcome is the ∼40% strain to failure of the printed elastomer structures. Using the resulting material properties, numerical simulations of pleated actuator architectures are analyzed to reduce stress concentration and increase actuation amplitudes. Antagonistic pairs of pleated actuators are then fabricated and tested for four-DOF, tentacle-like motion. These antagonistic pairs are shown to sweep through their full range of motion (∼180°) with a period of less than 70 ms.
Heparanase: a target for drug discovery in cancer and inflammation (2007)

The remodelling of the extracellular matrix (ECM) has been shown to be highly upregulated in cancer and inflammation and is critically linked to the processes of invasion and metastasis. One of the key enzymes involved in specifically degrading the heparan sulphate (HS) component of the ECM is the endo-beta-glucuronidase enzyme heparanase. Processing of HS by heparanase releases both a host of bioactive growth factors anchored within the mesh of the ECM as well as defined fragments of HS capable of promoting cellular proliferation. The finding that heparanase is elevated in a wide variety of tumor types and is subsequently linked to the development of pathological processes has led to an explosion of therapeutic strategies to inhibit its enzyme activity. So far only one compound, the sulphated oligosaccharide PI88, which both inhibits heparanase activity and has effects on growth factor binding has reached clinical trials where it has shown to have promising efficacy. The scene has clearly been set however for a new generation of compounds, either specific to the enzyme or with dual roles, to emerge from the lab and enter the clinic. The aim of this review is to describe the current drug discovery status of small molecule, sugar and neutralising antibody inhibitors of heparanase enzyme activity. Potential strategies will also be discussed on the selection of suitable biomarker strategies for specific monitoring of in vivo heparanase inhibition which will be crucial for both animal model and clinical trial testing.
Contextual Animation of Gestural Commands (1994)

Abstract Drawing a mark can be an efficient command input technique when using a pen‐based computer. However, marks are not intrinsically self‐explanatory as are other interactive techniques such as buttons and menus. We present design principles for interaction mechanisms which make marks self explanatory for novices but still allow experts to use efficient command marks. The key notion is that use of the explanation mechanism physically trains a novice to use the efficient command marks. Two novel interaction mechanisms we have developed using these principles are presented.
Identification of a large bent DNA domain and binding sites for serum response factor adjacent to the NFI repeat cluster and enhancer region in the major IE94 promoter from simian cytomegalovirus (1993)

The major immediate-early (MIE) transactivator proteins of cytomegaloviruses (CMV) play a pivotal role in the initiation of virus-host cell interactions. Therefore, cis- and trans-acting factors influencing the expression of these proteins through their upstream promoter-enhancer regions are important determinants of the outcome of virus infection. S1 nuclease analysis and in vitro transcription assays with the MIE (or IE94) transcription unit of simian CMV (SCMV) (Colburn) revealed a single prominent mRNA start site associated with a canonical TATATAA motif. This initiator region lies adjacent to a 2,400-bp 5'-upstream noncoding sequence that encompasses a newly identified 1,000-bp (A+T)-rich segment containing intrinsically bent DNA (domain C), together with the previously described proximal cyclic AMP response element locus (domain A) and a tandemly repeated nuclear factor I binding site cluster (domain B). Deleted MIE reporter gene constructions containing domain A sequences only yield up to 4-fold stronger basal expression in Vero cells than the intact simian virus 40 promoter-enhancer region, and sequences from position -405 to -69 (ENH-A1) added to a minimal heterologous promoter produced a 50-fold increase of basal expression in an enhancer assay. In contrast, neither the nuclear factor I cluster nor the bent DNA region possessed basal enhancer properties and neither significantly modulated the basal activity of the ENH-A1 segment. A second segment of domain A from position -580 to -450 was also found to possess basal enhancer activity in various cell types. This ENH-A2 region contains three copies of a repeated element that includes the 10-bp palindromic sequence CCATATATGG, which resembles the core motif of serum response elements and proved to bind specifically to the cellular nuclear protein serum response transcription factor. Reporter gene constructions containing four tandem copies of these elements displayed up to 13-fold increased basal enhancer activity and 18-fold tetradecanoyl phorbol acetate responsiveness in U937 cells, but an ENH-A2 DNA segment encompassing two of the core serum response transcription factor binding sites failed to respond to serum induction in NIH 3T3 cells. Although there are overall similarities in the organizations of both the MIE enhancers and MIE transcription units among human CMV, SCMV, and murine CMV, the specific arrangements of repetitive motifs are quite different, and the bent DNA and ENH-A2 domains appear to be unique to SCMV.
Direct urine polymerase chain reaction for chlamydia and gonorrhoea: a simple means of bringing high-throughput rapid testing to remote settings? (2013)

The results of this study show that the simplified PCR strategy may be a feasible approach for rapid screening and improving chlamydia and gonorrhoea treatment in remote settings.
Conservative volumetric visibility with occluder fusion (2000)

Visibility determination is a key requirement in a wide range of graphics algorithms. This paper introduces a new approach to the computation of volume visibility, the detection of occluded portions of space as seen from a given region. The method is conservative and classifies regions as occluded only when they are guaranteed to be invisible. It operates on a discrete representation of space and uses the opaque interior of objects as occluders. This choice of occluders facilitates their extension into adjacent opaque regions of space, in essence maximizing their size and impact. Our method efficiently detects and represents the regions of space hidden by such occluders. It is the first one to use the property that occluders can also be extended into empty space provided this space is itself occluded from the viewing volume. This proves extremely effective for computing the occlusion by a set of occluders, effectively realizing occluder fusion. An auxiliary data structure represents occlusion in the scene and can then be queried to answer volume visibility questions. We demonstrate the applicability to visibility preprocessing for real-time walkthroughs and to shadow-ray acceleration for extended light sources in ray tracing, with significant acceleration in both cases.
Evidence for Attachment Pheromones in the Cayenne Tick (Acari: Ixodidae) (1997)

Evidence is presented for the existence of male-produced attachment pheromones in the tick Amblyomma cajennense (F). Unfed males and females attached significantly faster to shaved sides on bovine hosts where preattached males were present than did adult ticks released in control areas. Attached ticks did not form clusters around the preattached males as described for other species of Amblyomma. They attached in areas under bags where they had been released, but were not necessarily close to the feeding males. Males apparently required at least 4 d of feeding before producing the pheromones. Males that fed for < 3 d failed to induce attachment. A significant increase in attachment of newly introduced males and females was observed only on day 4 after the feeding of the preattached male started. This response increased on days 5 and 6 after feeding had commenced. An evolutionary trend in the production of tick pheromones was suggested.
Significant Impact of Single N-Glycan Residues on the Biological Activity of Fc-based Antibody-like Fragments (2012)

Recent studies have demonstrated that IgG-Fc fragments (Fcabs) can be engineered to form antigen-binding sites with antibody properties. Thus they may serve as an attractive alternative to conventional antibodies in therapeutic applications. The critical influence of Fc glycosylation on effector functions of IgGs is well documented; however, whether this applies to Fcabs is not known. Here we used human cells, wild type, and glycoengineered plants to generate four different glycoforms of H10-03-6, an Fcab with engineered HER2/neu-binding sites. Plant-derived H10-03-6 differed in the presence/absence of single oligosaccharide residues, i.e., core fucose and xylose, and terminal galactose. All of the glycoforms had similar binding to HER2/neu expressed on human tumor cells. By contrast, glycoforms that lacked core oligosaccharide modifications (i.e., core α1,3-fucose and β1,2-xylose) showed significantly enhanced binding to the Fcγ receptor IIIa, irrespective of whether plant or human expression systems were used. Consistent with this finding, plant-derived H10-03-6 glycoforms lacking core N-glycan residues mediated higher antibody-dependent cellular cytotoxicity against human tumor cells. No alteration in γ-receptor binding and antibody-dependent cellular cytotoxicity activity was observed upon decoration of N-glycans by terminal galactose. The results point to a significant impact of distinct N-glycan residues on effector functions of Fcabs. Moreover, the outcomes imply that the effector functions mediated by H10-03-6 can be optimized by altering the N-glycosylation profile. Biasing vaccine-induced immune responses toward optimal Fc glycosylation patterns could result in improved vaccine efficacy.
Rationale and study design of the Adaptive study of IL-2 dose on regulatory T cells in type 1 diabetes (DILT1D): a non-randomised, open label, adaptive dose finding trial (2014)

NCT01827735, ISRCTN27852285, DRN767.
Influence of dopants and substrate material on the formation of Ga vacancies in epitaxial GaN layers (2001)

We have applied a low-energy positron beam and secondary ion mass spectrometry to study defects in homoepitaxial and heteroepitaxial GaN layers. Positron experiments reveal high concentrations of Ga vacancies in nominally undoped n-type GaN, where the conductivity is due to unintentional oxygen incorporation. Ga vacancies are observed in both homoepitaxial and heteroepitaxial layers, indicating that their formation is independent of the dislocation density. No Ga vacancies are detected in p-type or semi-insulating samples doped with Mg, as predicted by the theoretical formation energies. In samples where n-type conductivity is due to Si doping and the incorporation of oxygen impurities is suppressed, the concentration of Ga vacancies is much lower than in n-type samples containing oxygen. This indicates that the presence of oxygen donor in GaN promotes the formation of Ga vacancy. We suggest that this effect is due to the creation of ${\mathrm{V}}_{\mathrm{Ga}}{\ensuremath{-}\mathrm{O}}_{\mathrm{N}}$ complexes during the epitaxial growth.