gebhart/patrepeval huggingface dataset:
Mechanisms of Drug Resistance in Cancer Chemotherapy (2005)

The management of cancer involves procedures, which include surgery, radiotherapy and chemotherapy. Development of chemoresistance is a persistent problem during the treatment of local and disseminated disease. A plethora of cytotoxic drugs that selectively, but not exclusively, target actively proliferating cells include such diverse groups as DNA alkylating agents, antimetabolites, intercalating agents and mitotic inhibitors. Resistance constitutes a lack of response to drug-induced tumour growth inhibition; it may be inherent in a subpopulation of heterogeneous cancer cells or be acquired as a cellular response to drug exposure. Resistance varies. Although regulatory approval may require efficacy in as few as 20% of trial cohorts, a drug may subsequently be used in unselected patients displaying resistance to the treatment. Principal mechanisms may include altered membrane transport involving the P-glycoprotein product of the multidrug resistance (MDR) gene as well as other associated proteins, altered target enzyme (e.g. mutated topoisomerase II), decreased drug activation, increased drug degradation due to altered expression of drug-metabolising enzymes, drug inactivation due to conjugation with increased glutathione, subcellular redistribution, drug interaction, enhanced DNA repair and failure to apoptose as a result of mutated cell cycle proteins such as p53. Attempts to overcome resistance mainly involve the use of combination drug therapy using different classes of drugs with minimally overlapping toxicities to allow maximal dosages and with narrowest cycle intervals, necessary for bone marrow recovery. Adjuvant therapy with P-glycoprotein inhibitors and, in specific instances, the use of growth factor and protein kinase C inhibitors are newer experimental approaches that may also prove effective in abrogating or delaying onset of resistance. Gene knockout using antisense molecules may be another effective way of blocking drug resistance genes. Conversely, drug resistance may also be used to good purpose by transplanting retrovirally transformed CD34 cells expressing the MDR gene to protect the bone marrow during high-dose chemotherapy.
Purely electrical detection of a skyrmion in constricted geometry (2016)

How to detect the skyrmion position is a crucial problem in future skyrmionics since it corresponds to the reading process of information. We propose a method to detect the skyrmion position purely electrically by measuring the Hall conductance in a constricted geometry. The Hall conductance becomes maximum when a skyrmion is at the lead position. It is possible to detect the skyrmion position even at room temperature. We find an optimized width of the sample determined by the skyrmion radius. We also investigate the effects of elastic and inelastic scatterings, and finite temperature. Our results will be a basis of future skyrmion electronics.
Fault tolerance ability analysis and evaluation of three-phase voltage source converters (2018)

201802 bcrc
<title>Measuring residual accelerations in the Spacelab environment</title> (1991)

The objective of some experiments performed in space is to study the effect of minimized convection on various processes. The Shuttle orbiter can provide long periods of microgravity for performing experiments. However, residual gravitational accelerations still remain. Accelerometers have been placed in the Spacelab to measure these accelerations. The Accelerometers are capable of measuring inputs as small as 10-6 gs. However, these levels are typically masked by the background `noise' accelerations due to crew activity and mechanical vibrations generated by the experiment facilities. In May 1985, Spacelab 3 flew on the Shuttle orbiter. The fluid experiment system (FES), a multiuser facility, was on board with the Triglycine Sulfate (TGS) crystal growth experiment. The FES is a holographic system that is capable of taking single and double exposure holograms. A series of holograms is recorded during the experiment run. The experiment is analyzed on the ground using the series of holograms taken during the run. The main purpose of the TGS experiment was to examine diffusion limited crystal growth by minimizing convection in the microgravity environment of the Spacelab. The seed crystal was attached to a platform. However, in one of the test cells, tiny crystals were found floating free in the growth solution during the experiment. Since the free crystals were in a viscous fluid, the `noise' accelerations of the Shuttle were damped out. This made it possible to measure the constant gravitational acceleration by tracking the positions of these crystals throughout the experiment. This paper presents the velocities and hence accelerations obtained by measuring the position of the free crystals from the holograms. An improved experiment is planned on IML-1 in the FES using polystyrene spheres as markers to aid in characterizing the residual accelerations present in the Spacelab.
An Electrochemical Flow Analysis System for Putrescine Using Immobilized Putrescine Oxidase and Horseradish Peroxidase (2004)

Abstract An electrochemical flow analysis system was optimized together with immobilized putrescine oxidase and horseradish peroxidase for putrescine measurement. Four coupling agents, suberic acid bis( N ‐hydroxysuccinimide ester), γ‐maleimidobutyric N ‐hydroxysuccinimide ester, 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide and glutaraldehyde, were used for immobilizing the two enzymes on porous aminopropyl glass beads to form a bienzymic detection column. Although the glutaraldehyde crosslinking procedure offered the highest response, the immobilized bienzyme system was responsive to putrescine, spermidine (123% of the putrescine response at 250 μM) and cadaverine (98% of the putrescine response). In contrast, the enzymes immobilized on the glass beads using suberic acid bis( N ‐hydroxysuccinimide ester) offered significantly better selectivity towards putrescine at the same concentration. For comparison, cadaverine and spermidine only provoked a response of 4.7% and 27.5% of the putrescine signal. The response to cadaverine and spermidine was further suppressed by lowering the detection pH from 8 to 7. At 250 μM, the response obtained for cadaverine and spermidine was only 1.5% and 3.9%, respectively, of the signal obtained for putrescine. A linear response to putrescine was obtained from 5 to 75 μM (0.629 μAs μM −1 , R 2 =0.997) with a detection limit of 5 μM ( S/N =3). The amperometric response retained 75% of its initial value after 600 repeated injections. The immobilized PUO/HRP (putrescine oxidase/horseradish peroxidase) was successfully demonstrated for measuring putrescine in fish extracts as an indicator of fish spoilage.
HIF3A Inhibition Triggers Browning of White Adipocytes via Metabolic Rewiring (2022)

Maintenance of energy balance between intake and expenditure is a prerequisite of human health, disrupted in severe metabolic diseases, such as obesity and type 2 diabetes (T2D), mainly due to accumulation of white adipose tissue (WAT). WAT undergoes a morphological and energetic remodelling toward brown adipose tissue (BAT) and the BAT activation has anti-obesity potential. The mechanisms or the regulatory factors able to activate BAT thermogenesis have been only partially deciphered. Identifying novel regulators of BAT induction is a question of great importance for fighting obesity and T2D. Here, we evaluated the role of <i>Hif3α</i> in murine pre-adipocyte 3T3-L1 cell line, a versatile and well characterized biological model of adipogenesis, by gain- and loss-of function approaches and in thermogenesis-induced model <i>in vivo</i>. <i>HIF3A</i> is regulated by inflammation, it modulates lypolysis in adipose tissue of obese adults, but its role in energy metabolism has not previously been investigated. We characterized gene and protein expression patterns of adipogenesis and metabolic activity <i>in vitro</i> and mechanistically <i>in vivo</i>. Overexpression of <i>Hif3α</i> in differentiating adipocytes increases white fat cells, whereas silencing of <i>Hif3α</i> promotes "browning" of white cells, activating thermogenesis through upregulation of <i>Ucp1, Elovl3, Prdm16, Dio2</i> and <i>Ppargc1a</i> genes. Investigating cell metabolism, Seahorse Real-Time Cell Metabolism Analysis showed that silencing of <i>Hif3α</i> resulted in a significant increase of mitochondrial uncoupling with a concomitant increase in acetyl-CoA metabolism and Sirt1 and Sirt3 expression. The causal <i>Hif3α/Ucp1</i> inverse relation has been validated in Cannabinoid receptor 1 (CB1) knockout, a thermogenesis-induced model <i>in vivo</i>. Our data indicate that <i>Hif3α</i> inhibition triggers "browning" of white adipocytes activating the beneficial thermogenesis rewiring energy metabolism <i>in vitro</i> and <i>in vivo</i>. <i>HIF3A</i> is a novel player that controls the energy metabolism with potential applications in developing therapy to fight metabolic disorders, as obesity, T2D and ultimately cancer.
Conformational Study of an Axially Chiral Salen Ligand in Solution using Two-Photon Circular Dichroism and the Fragment-Recombination Approach (2013)

Herein we report on the conformational study of a chiral Salen ligand, AFX-155, in THF solution using two-photon absorption (TPA) and, even more importantly, two-photon circular dichroism (TPCD). The fragment-recombination approach (FRA), employed to perform computations on half-AXF-155 (AXF-169') and the center (C-AXF-155), allowed us to overcome the current computational limitations found in calculations of the TPCD spectra of large molecules. The comparative experimental-theoretical analysis of AXF-155 showed that its TPA is mainly determined by AXF-169' and validated, through TPCD, the presence of the two dominant Trans_R-Intra(NHB)//Trans_R-Extra(HB) and Trans_R-Intra(NHB)//Trans_R-Extra(NHB) structure in THF with a ΔΔ propeller chirality on the diphenylamine moieties at the end of each AXF-169'. The application of FRA for the analysis of the TPCD spectra of large chiral molecules has been proven to be effective.
Platelet activating factor‐induced neuronal apoptosis is initiated independently of its G‐protein coupled PAF receptor and is inhibited by the benzoate orsellinic acid (2007)

The bioactive lipid mediator platelet activating factor (PAF) is recognized as a key effecter of neuronal apoptosis, yet it is not clear whether its G-protein coupled receptor (PAFR) initiates or prevents PAF neurotoxicity. Using PAFR-/- and congenic wild-type mice, we show that PAF triggers caspase-3/7 activity and neuronal death in PAFR-/- but not PAFR+/+ cerebellar granule neurons. Restoring receptor expression by recombinant adenoviral infection protected cells from PAF challenge. Neuronal death was not mediated by nitric oxide or N-methyl-d-aspartate receptor signaling given that N-nitro-l-arginine methyl ester and MK-801 did not inhibit PAF-induced neuronal loss in PAFR-/- neurons. To intervene in PAFR-independent neurotoxicity, the anti-apoptotic actions of three structurally distinct PAF antagonists were compared to a panel of plant and fungal benzoic acid derivatives. We found that the PAF antagonist BN 52021 but not FR 49175 or CV 3988 inhibited PAFR-independent neurotoxicity. Orsellinic acid, a fungal-derived benzoic acid, blocked PAF-mediated neuronal apoptosis without affecting PAFR-mediated neuroprotection. These findings demonstrate that PAF can transduce apoptotic death in primary neurons independently of its G-protein coupled receptor, that PAFR activation is neuroprotective, and that orsellinic acid effectively attenuates PAFR-independent neuronal apoptosis.
A computer 3D animator based platform for teleoperation of robot systems (2002)

The 3D animated simulator emulates an actual robot manipulator in a simulation space. The simulator is intended for use in teleoperation, where the graphical image represents the actual remote manipulator. The robot is viewed from a "camera position". The motion of the tip of the manipulator can be traced out in the simulation space as a continuous 3D line. The interface has the capability to graphically display the angles of the joint. It allows for a more accurate analysis of the simulated motion. The robot trajectory is defined by either a pre-calculated trajectory file or user specified end point and orientation.
The Harmful Role of C5a on Innate Immunity in Sepsis (2010)

There is accumulating evidence in humans and in experimental sepsis that robust activation of the complement system occurs along with development of defects in the innate immune system. In this report we review evidence that the complement activation product, C5a, appears in the plasma of rodents following cecal ligation and puncture (CLP). C5a interacts with its receptors (C5aR, C5L2) on phagocytes (polymorphonuclear neutrophils, PMNs, macrophages), ultimately paralyzing the ERK1/2 pathway of the mitogen-activated protein kinase signaling pathway. C5a is also interactive with its receptors on a variety of other cell types in various organs. Interaction of C5a with receptors on PMNs results in compromised innate immunity, with intense suppression of phagocytosis, chemotaxis and the respiratory burst. Endothelial cells acquire a pro-inflammatory phenotype (increased ICAM-1 and tissue factor expression), while macrophages are primed and produce large amounts of cytokines/chemokines. All of these outcomes are C5a and C5a receptor dependent. CLP also unleashes activation of clotting (and fibrinolytic) factors in a C5a-dependent manner. Finally, thymocytes upregulate C5aR and react with C5a, resulting in apoptosis via the intrinsic (mitochondrial) pathway. Collectively, these findings suggest that interception of C5a in sepsis preserves innate immune functions and may be a strategy for treatment of septic humans.
Association of body fat with C‐reactive protein in rheumatoid arthritis (2008)

Adiposity is independently associated with CRP levels in women with RA, and thus may confound the estimation of RA disease activity when serum CRP concentration is used as a surrogate for systemic inflammation.
Stock trading decision support system using a rule selector based on sliding window (2002)

We propose a dynamic decision support system (DDSS) capable of determining a near-optimal rule-combination for each time interval (window). The system provides Buy, Hold and Sell signals from which profitable trading decisions can be made. In DDSS, an intelligent rule selector (GARS) based on genetic algorithms and a sliding window scheme is developed. Experimental results on Taiwan stock exchange weighted stock index (TSEWSI) show that DDSS outperforms its static counterpart as well as the simple buy-and-hold strategy.
Nanotubes: Chemical Sharpening, Shortening, and Unzipping of Boron Nitride Nanotubes (Adv. Funct. Mater. 28/2014) (2014)

On page 4497, Z. Chen, J. W. Connell, Y. Lin, and co-workers demonstrate a method to disperse and chemically modify the morphology of BNNTs via sonication in aqueous ammonia solutions. While BNNTs have always been considered chemically inert, the ammonia-modified BNNTs are significantly corroded and exhibit end-cap removal, tip sharpening, wall thinning, length shortening, and longitudinal unzipping. This could lead to an effective purification technique for BNNTs by removing amorphous BN fragments from production.
Stresses in a coated fiber stretched on a capstan (1990)

We developed an analytical model for the prediction of the lateral mechanical stresses in dual- and single-coated fibers stretched on a capstan during on-line proof-testing and showed that the level of these stresses in a dual-coated system is substantially higher than in a single-coated design.
Influence of Iron Deficiency on Olfactory Behavior in Weanling Rats (2012)

Chronically high occupational exposure to airborne metals like iron can impair olfactory function, but little is known about how low iron status modifies olfactory behavior. To investigate the influence of body iron status, weanling rats were fed a diet with low iron content (4 - 7 ppm) to induce iron deficiency anemia and olfactory behavior was compared to control rats fed an isocaloric diet sufficient in iron (210 - 220 ppm). Iron-deficient rats had prolonged exploratory time for attractive odorants in behavioral olfactory habituation/dis-habituation tests, olfactory preference tests and olfactory sensitivity tests compared with control rats. No significant differences were observed for aversive odorants between the two groups. These findings suggest that iron-dependent functions may be involved in controlling and processing of olfactory signal transduction via self and lateral inhibition such that odorant signal remains stronger for longer times prolonging exploratory activity on attractive odorants in the behavioral tests. These findings establish that iron deficiency can modify olfactory behavior.
The Role of Saliva and Serum inCandida albicansBiofllm Formation on Denture Acrylic Surfaces (1996)

The long term effect of either a salivary or a serum pellicle on Candida albicans biofilm formation on denture acrylic surfaces was investigated both by quantifying the ATP (adenosine triphosphate) content of the resultant biofilms and by scanning electron microscopy. When the biofilm formation on saliva-coated acrylic strips was examined, the yeasts initially colonised this surface at a slower rate than the controls although with increasing incubation time, at 72 h, the ATP content was almost ten-fold higher than the protein-free control strips. Ultrastructural studies revealed this to be due to cell aggregation and hyphal emergence, phenomena not observed in the controls. As compared with the control strips, biofilm activity of the serum-coated strips was almost 100-fold greater within 48 h incubation, and scanning electron microscopy revealed multilayer blastospore-blastospore co-adhesion, germ tube, hyphal and pseudohyphal emergence and blastospore-hyphal coadherence. Further immunocytochemical observation revealed that concanavalin-A binding material and fibronectin were involved in biofilm formation on both saliva and serum coated specimens and, in addition, mannan-binding protein and protein-A binding material also contributed to the biofilm formation on serum coated specimens. Keywords: Candida albicans , biofilm, saliva, serum, fibronectin, mannan-binding protein.
Routing and channel reservation strategies for a low Earth orbit satellite system (2002)

Routing in a low-Earth-orbit (LEO) satellite system involves the choice of inter-satellite links (ISLs) that connects two home satellites of the mobile terminals. We use a mesh model to formulate the LEO system and proposed 4 mesh-based algorithms. The objective is to minimize the new call blocking probability and the forced termination probability. Also, due to the dynamic topology of the LEO system, the route is subject to disconnection because of a route breaking event, such as a connection handover event or a link handover event. We propose a channel reservation strategy in order to safeguard the continuity of a route. Experiments are carried out to show the effectiveness of the routing algorithms and the reservation strategy.
Studies on the low pressure polymerization of propylene using catalysts containing alkali metal alkyls (1959)

Abstract The low pressure polymerization of propylene was investigated using catalysts prepared from alkali metal alkyls and titanium tetrachloride. In all cases the efficiency of the catalysts depended on the molecular ratio of the metal alkyl to the titanium tetrachloride. In general the polymerization conditions were similar to those for ethylene although the propylene polymerized much more slowly. With n ‐butyllithium–titanium tetrachloride, optimum molecular ratios were found between 1.8–2.5, with sharp drops on both sides. With amylsodium–titanium tetrachloride the optimum extended over a wide range (5.7–15), the activity decreasing sharply with lower molecular ratios. The catalysts prepared from sodium alkyls were more active than those prepared from lithium alkyls. Increasing yield was obtained on lowering the concentration of the catalyst. Up to a pressure of about 3 atmospheres, increase in the rate of polymerization was observed with increase in pressure; above this no influence of the pressure was observed. Isotactic polymers were isolated from the polymerization products by successive fractionation of the crude polymers in acetone, ether, and isooctane which dissolved the atactic polymers. With butyllithium–titanium tetrachloride catalysts, at and above optimum ratios, the isotactic fractions were about 60%. At lower ratios there was a great increase in atactic polymers. With amylsodium–titanium tetrachloride catalysts the isotactic fractions were about 70%. Phenylsodium–titanium tetrachloride catalysts were found to be very weak in the polymerization of propylene.
Macrocrystalline Colloidal Assemblies in an Electric Field (2001)

Macrocrystalline colloidal assemblies with tunable non-spherical shapeare fabricated through colloidal crystallization under an AC electric field. Also, by field-induced drop breakup, uniform micrometer-sized macrocrystalline particles can be synthesized (see Figure). Interestingly, the electrical field promotes infiltration of the suspending oil, which can be used for fabricating photonic crystals with high refractive index mismatch.
Ki-67 assessment in early breast cancer: SAKK28/12 validation study on the IBCSG VIII and IBCSG IX cohort (2019)

The assessment of Ki-67 in early-stage breast cancer has become an important diagnostic tool in planning adjuvant therapy, particularly for the administration of additional chemotherapy to hormone-responsive patients. An accurate determination of the Ki-67 index is of the utmost importance; however, the reproducibility is currently unsatisfactory. In this study, we addressed the predictive/prognostic value of Ki-67 index assessed by using the most reproducible methods, which were identified in the pilot phase. Paraffin blocks obtained from patients with moderately differentiated, estrogen receptor (ER)-positive early-stage breast cancer in Switzerland, who were originally randomized to the treatment arms with and without chemotherapy in the IBCSG VIII-IX trials, were retrieved. Of these 344 randomized patients, we identified 158 patients (82 treated with and 76 treated without chemotherapy) for whom sufficient tumour tissue was available. The presence of Ki-67 was assessed visually by counting 2000 cells at the periphery (A) and estimating the number of positive cells in five different peripheral regions (C), which was determined to be the most reproducible method identified the pilot phase. The prognostic and predictive value was assessed by calculating the breast cancer-free interval (BCFI) and overall survival (OS) rate. Ki-67 was considered a numerical and categorical variable when different cut-off values were used (10%, 14%, 20% and 30%). An mRNA-based subtyping by using the MammaTyper kit with the application of a 20% Ki-67 immunohistochemistry (IHC) cut-off equivalent was also performed. 158 of 344 randomized patients could be included in the Ki-67 analysis. The mean Ki-67 values obtained by using the two methods differed (A: 21.32% and C: 16.07%). Ki-67 assessed by using method A with a cut-off of 10% was a predictive marker for OS, as the hazard ratio (>10% vs. <=10%) in patients with chemotherapy was 0.48 with a 95% confidence interval of [0.19-1.19]. Further, the HR of patients treated without chemotherapy was 3.72 with a 95% confidence interval of [1.16-11.96] (p<sub>interaction</sub>=0.007). Higher Ki-67 index was not associated with outcome and using the 10% Ki-67 cut-off there was an opposite association for patients with and without chemotherapy. Ki-67 assessments with IHC significantly correlated with MammaTyper results (p=0.002). The exact counting method (A) performed via a light-microscope revealed the predictive value of Ki-67 assessment with a 10% cut-off value. Further analyses employing image analyses and/or mRNA-based-assessments in larger populations are warranted.