gebhart/patrepeval huggingface dataset:
Predictive value of intratumoral signaling and immune infiltrate for response to preoperative (PO) trastuzumab (T) vs trastuzumab + everolimus (T+E) in patients (pts) with primary breast cancer (PBC): UNICANCER RADHER trial results. (2016)

606 Background: Blockade of PI3K/AKT/mTOR pathway by E combined with T in HER2+ BC pts shows promising results. It has also been reported that T acted differently when used in PO setting with a lower implication of signaling blockade and a higher induction of ADCC when used alone in chemotherapy naive pts. Additionally, mTOR blockade has been experimentally reported to activate MAPK pathway through a feed-back loop effect. We present the results of a biological integrated approach including markers of PI3K/AKT/mTOR and MAPK pathways, proliferation and immune environment in HER-2 + PBC treated with T +/- E in PO setting. Methods: Eligible pts with HER2+ PBC (IHC 3+ or FISH/SISH+) amenable to surgery were randomized to receive T (loading dose 4 mg/kg, then 2 mg/kg/W), or T+E (10 mg/d) for a 6W PO treatment. All pts had baseline core needle biopsies, tissue collected at surgery and blood samples for biomarkers and pharmacokinetic analyses. FFPE samples were used for PIK3CA mutation status and IHC (pAKT, pS6K, eIF4E, LKB1, p4EBP1, Ki67, caspase 3, PTEN, CD8, CD68). Frozen samples were used for multiplex immunoanalyses of phosphorylated PI3K/AKT/mTOR and MAPKinase signaling proteins (p-AKT, p-GSK3, p-P70S6K, p-MEK1, p-ERK1/2, p-P90RSK). Results: FFPE and frozen tumor samples (n = 80), were obtained from 82 pts randomized from July 2008 to April 2012 (41 per arm). At baseline, only PIK3CA mutation status was predictive of clinical response, whatever the arm. No difference in the expression of phosphorylated signaling kinases was induced by exposure to T while T+E induced a significant activation of MAPKinase pathway. Between baseline and surgery we observed a down regulation of pAKT pS6K, LKB1, Ki67, a lower expression of PTEN and an increase in lymphocytes (CD8+) and macrophages (CD68+) infiltrates in both arms. Conclusions: These results confirm that in PO setting, T +/- E should mostly act via the activation immune response through tumor-associated lymphocytes and macrophages infiltrates. Rapid decrease in PTEN and LKB1 may be related to early cellular mechanism of resistance to HER2 inhibition. Clinical trial information: NCT00674414.
Complex bandpass &#x0394;&#x03A3;AD modulator with noise-coupled image rejection (2009)

This paper proposes a new realization technique of image rejection function by noise-coupling architecture, which is used for a complex bandpass DeltaSigmaAD modulator. The complex bandpass DeltaSigmaAD modulator processes just input I and Q signals, not image signals, and the AD conversion can be realized with low power dissipation. It realizes an asymmetric noise-shaped spectra, which is desirable for such low-IF receiver applications. However, the performance of the complex bandpass DeltaSigmaAD modulator suffers from the mismatch between internal analog I and Q paths. I/Q path mismatch causes an image signal, and the quantization noise of the mirror image band aliases into the desired signal band, which degrades the SQNDR (Signal to Quantization Noise and Distortion Ratio) of the modulator. In our proposed modulator architecture, an extra notch for image rejection is realized by noise-coupled topology. We just add some passive capacitors and switches to the modulator; the additional integrator circuit composed of an operation amplifier in the conventional image rejection realization is not necessary. Therefore, the performance of the complex modulator can be effectively raised without additional power dissipation. We have performed simulation with MATLAB to confirm the validity of the proposed architecture. The simulation results show that the proposed architecture can achieve the realization of image-rejection effectively, and improve the SQNDR of the complex bandpass DeltaSigmaAD modulator.
The impact of non-steroid anti-inflammatory drugs and antibiotics on articular cartilage. (2001)

One of the essential elements in the proper functioning of articular cartilage is the proper balance of glycosaminoglycans and collagen proteins in the extracellular matrix. Any disproportion of this balance can produce degenerative changes. Certain pharmaceutical agents can induce changes of this kind. The present article provides a review of current opinions on the impact of non-steroid anti-inflammatory drugs and antibiotics on articular cartilage.
Enantio‐ and diastereoselective syntheses of cyclic Cα‐tetrasubstituted α‐amino acids and their use to induce stable conformations in short peptides (2007)

C(alpha)-tetrasubstituted alpha-amino acids are widely used to design and prepare peptides and peptide mimics with constrained conformations. Subcategories of these compounds are cyclic C(alpha)-tetrasubstituted alpha-amino acids, in which both alpha-substituents are covalently connected. This survey presents recent advances in the synthesis and application of cyclic C(alpha)-tetrasubstituted alpha-amino acids in a systematic order beginning with cyclopropane amino acids, continuing with four, five, six membered rings, and ring structures larger than six-membered. We discuss synthetic routes to the cyclic C(alpha)-tetrasubstituted alpha-amino acids and their use as conformation determining elements in peptides.
POLCA-T: Validation of Transient Bundle Flow Predictions During an All Recirculation Pumptrip in a BWR (2006)

In this paper predicted results obtained with the POLCA-T code are compared to measurement data from an all recirculation pump trip test made at the Nuclear Power Plant Olkiluoto 1 during its commissioning in 1978. Olkiluoto 1 is one of three nuclear power plants owned by the electrical power company Teollisuuden Voima OY in Finland. The prediction is based on a best estimate reactor analysis code that incorporates a full 3D model of a reactor core into a system model. The use of a coupled code provides a means to simulate interactions between the reactor core and the plant dynamics to increase the understanding of different events and its impact on the core behaviour. The following conclusions are made based on the simulations with POLCA-T of the Olkiluoto 1 commissioning test of tripping all recirculation pumps: • POLCA-T predicts the event accurately, the flow coast down and the power decay is in good agreement with measured data. • 3D effects in channel flow can not be observed. The observed effects support the current use of a 1D approach since this is conservative with respect to power and the evaluation of Operating Limit Critical Power Ratio, (OLMCPR). This conclusion is also supported by measurement data.
Development of a general-purpose demand-side battery energy storage system (2002)

This paper presents a design and implementation of battery energy storage system (BESS) for general applications in a demand-side industrial power system. Different control modes for operating BESS to improve demand-side power supply capability is studied. The basic principle using the conventional control method is implemented to accomplish the desired control functions. The proposed methods are proved by both theoretical simulations and experimental test results on a prototype BESS.
Effect of tumor necrosis factor alpha on rabbit corneal endothelial permeability. (1996)

TNF alpha causes an increase in corneal endothelial permeability, and this increase is mediated by disruption of f-actin filaments; cAMP appears to be involved in this response.
Thermal aware cell-based full-chip electromigration reliability analysis (2005)

A hierarchical scheme with cells and modules is crucial for managing design complexity during a large integrated circuit design. We present a methodology for thermal aware cell-based electromigration analysis suitable for integrating electromigration reliability analysis into a conventional IC design flow. A block or cell is characterized for reliability while it is characterized for power and timing. Reusing cell characterization data significantly reduces computational load while analyzing a full-chip layout. During full-chip analysis, we compute a layout-level temperature profile from cell power dissipations using a Fast Fourier Transform based algorithm. The described full-chip reliability assessment methodology has been implemented in an interconnect reliability CAD tool. We have exercised the tool to demonstrate performance-reliability tradeoff and the significance of thermal-aware reliability analysis for true reliability aware design.
Accurate on-line 3D occupancy grids using Manhattan world constraints (2012)

In this paper we present an algorithm for constructing nearly drift-free 3D occupancy grids of large indoor environments in an online manner. Our approach combines data from an odometry sensor with output from a visual registration algorithm, and it enforces a Manhattan world constraint by utilizing factor graphs to produce an accurate online estimate of the trajectory of a mobile robotic platform. We also examine the advantages and limitations of the octree data structure representation of a 3D environment. Through several experiments in environments with varying sizes and construction we show that our method reduces rotational and translational drift significantly without performing any loop closing techniques.
Model Checking MDPs with a Unique Compact Invariant Set of Distributions (2011)

The semantics of Markov Decision Processes (MDPs), when viewed as transformers of probability distributions, can described as a labeled transition system over the probability distributions over the states of the MDP. The MDP can be seen as defining a set of executions, where each execution is a sequence of probability distributions. Reasoning about sequences of distributions allows one to express properties not expressible in logics like PCTL, examples include expressing bounds on transient rewards and expected values of random variables, as well as comparing the probability of being in one set of states at a given time with another set of states. With respect to such a semantics, the problem of checking that the MDP never reaches a bad distribution is undecidable [1]. In this paper, we identify a special class of MDPs called semi-regular MDPs that have a unique non-empty, compact, invariant set of distributions, for which we show that checking any ω-regular property is decidable. Our decidability result also implies that for semi-regular probabilistic finite automata with isolated cut-points, the emptiness problem is decidable.
Single-photon and multiphoton processes causing resonance in the transmission of electrons by a single potential barrier in a radiation field (1999)

Simulations of electrons tunneling in a barrier for which the height varies sinusoidally with time show resonances increasing the transmitted current. For square barriers, these resonances occur when electrons are promoted above the barrier by absorbing quanta from the barrier oscillations, and the barrier length is an integer multiple of one-half of the de Broglie wavelength. For several barriers having other profiles, we find that there is a single broad resonance centered at a wavelength equal to 0.9 times the wavelength for a photon having the energy to take the particle exactly to the top of the barrier. We attribute this difference to the fact that quanta may only be exchanged at the ends of a square barrier, whereas quanta are exchanged throughout the full length of barriers having other profiles—especially in regions of high electric field intensity. A Floquet expansion is used to examine the change in transmission caused by barrier modulation for electrons at the different energies caused by the exchange of quanta. We find that the wavelengths for resonance are proportional to the number of quanta absorbed by the particles, and attribute this observation to the requirement that specific values of absorbed energy are necessary for resonance. The increase in transmission caused by absorbing M quanta is proportional to the Mth power of the power flux density of the radiation causing barrier modulation. Thus, as the power is increased, the total transmission (including all energies) shows greater structure due to multiphoton processes. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 75: 417–427, 1999
Parechoviruses in children: understanding a new infection (2010)

The recently discovered HPeV3 has been shown to play an important role in severe neonatal infections, observations possibly linked to its very recent emergence or possibly different cellular tropism that underlie its targeting of the most susceptible individuals. HPeV infections are currently under-diagnosed and should be considered in the clinical and diagnostic evaluation of severe neonatal disease presentations.
Modelling optical fibre cable (1996)

Optical fibre cables are made by placing optical fibres inside a loose tube packed with a water based gel, and then winding these loose tubes on to a central strength member in helically wound sections of alternating twist separated by reversing sections. The length of the loose tubes and their position on the strength member was modelled along with an analysis of where the optical fibres lie in the loose tubes.
Cytosine-5 RNA methylation links protein synthesis to cell metabolism (2019)

Posttranscriptional modifications in transfer RNA (tRNA) are often critical for normal development because they adapt protein synthesis rates to a dynamically changing microenvironment. However, the precise cellular mechanisms linking the extrinsic stimulus to the intrinsic RNA modification pathways remain largely unclear. Here, we identified the cytosine-5 RNA methyltransferase NSUN2 as a sensor for external stress stimuli. Exposure to oxidative stress efficiently repressed NSUN2, causing a reduction of methylation at specific tRNA sites. Using metabolic profiling, we showed that loss of tRNA methylation captured cells in a distinct catabolic state. Mechanistically, loss of NSUN2 altered the biogenesis of tRNA-derived noncoding fragments (tRFs) in response to stress, leading to impaired regulation of protein synthesis. The intracellular accumulation of a specific subset of tRFs correlated with the dynamic repression of global protein synthesis. Finally, NSUN2-driven RNA methylation was functionally required to adapt cell cycle progression to the early stress response. In summary, we revealed that changes in tRNA methylation profiles were sufficient to specify cellular metabolic states and efficiently adapt protein synthesis rates to cell stress.
Kriging: applying geostatistical techniques to the genetic study of complex diseases (2020)

Complex diseases often display geographic distribution patterns. Therefore, the integration of genetic and environmental factors using geographic information systems (GIS) and specific statistical analyses that consider the spatial dimension of data greatly assist in the research of their gene-environment interactions (GxE). The objectives of the present work were to assess the application of a geostatistical interpolation technique (kriging) in the study of complex diseases with a distinct heterogeneous geographic distribution and to test its performance as an alternative to conventional genetic imputation methods. Using multiple sclerosis as a case study, kriging demonstrated to be a flexible and valuable tool for integrating information from various sources and at a different spatial resolution into a model that easily allowed to visualize its heterogeneous geographic distribution in Europe and to explore the intertwined interactions between several known genetic and environmental risk factors. Even though the performance of kriging did not surpass the results obtained with current imputation techniques, this pilot study revealed a worse performance of the latter for rare variants in chromosomal regions with a low density of markers.
Hepatitis A infections in men who have sex with men using HIV PrEP in Paris (2018)

The current hepatitis A outbreak in Europe is largely involving men having sex with multiple male partners. The objective of the present report was to warn teams dealing against the persistent risk of viral and bacterial sexually transmitted infection (STIs) in patients receiving HIV pre-exposure prophylaxis (PrEP). We have notified and investigated three cases of acute hepatitis A virus (HAV) infection in people receiving HIV PrEP in our clinic between December 2016 and March 2017. The patients were not epidemiologically related, had no recent travel history to HAV endemic areas, reported multiple STIs during this period and had not been vaccinated against HAV. They were all identified as genotype A, strain VRD_521_2016 virus.Large-scale vaccination against viral hepatitis is recommended in men having sex with men, especially in those using PrEP, as PrEP is used by people who have high-risk sexual behaviour.
Non-surgical management of stress urinary incontinence: ambulatory treatments for leakage associated with stress (ATLAS) trial (2007)

This trial will provide useful information to help counsel women with stress and mixed incontinence about the relative efficacy and satisfaction with pessary, behavioral therapy and both treatments combined.
Toward noninvasive assessment of stroke risk in pediatric cerebrovascular disease (2021)

Abstract Background and Purpose Moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disease leading to recurrent stroke. There is a lack of reliable biomarkers to identify unilateral stroke MMD patients who are likely to progress to bilateral disease and experience subsequent contralateral stroke(s). We hypothesized that local hemodynamics are predictive of future stroke and set out to noninvasively assess this stroke risk in pediatric MMD patients. Methods MR and X-ray angiography imaging were utilized to reconstruct patient-specific models of the circle of Willis of 6 pediatric MMD patients who had previous strokes, along with a control subject. Blood flow simulations were performed by using a Navier-Stokes solver within an isogeometric analysis framework. Vascular regions with a wall shear rate (WSR) above the coagulation limit (&gt; 5000 s −1 ) were identified to have a higher probability of thrombus formation, potentially leading to ischemic stroke(s). Two metrics, namely, “critical WSR coverage” and “WSR score”, were derived to assess contralateral stroke risk and compared with clinical follow-up data. Results In two patients that suffered a contralateral stroke within two months of the primary stroke, critical WSR coverages exceeding 50% of vessel surface and WSR scores greater than 6x the control were present in multiple contralateral vessels. These metrics were not as conclusive in two additional patients with 3-to-5-year gaps between primary and contralateral strokes. However, a longitudinal study of one of these two cases, where a subsequent timepoint was analyzed, accurately predicted disease stabilization on the primary stroke side and an elevated contralateral stroke risk, thus indicating that post-stroke follow-up at regular intervals might be warranted for secondary stroke prevention. Conclusions WSR-based metrics could be predictive of future stroke risk after an initial stroke in MMD patients. In addition, more accurate predictions may be possible by performing patient-specific hemodynamic analysis at multiple timepoints during patient follow-up to monitor changes in the WSR-based metrics.
Gamma radiation nose system based on In/sub 2/O/sub 3//SiO thick film pn-junctions (2006)

In/sub 2/O/sub 3/ and SiO mixtures, in thick film pn-junction form, were investigated for /spl gamma/-radiation dosimetry purposes. Results show that the current increased with an increase in radiation dose to a certain level, exceeding this level resulted in device damage. The performance parameters of the devices, such as sensitivity to /spl gamma/-radiation exposure and working dose region, were found to be highly dependant on the composition of the materials used. To cover a wider range of radiation, the approach of using sensor arrays was utilized, where the sections of the radiation nose system differ in material composition. A dynamic selection of the multiple sensors of various sensitivity and accuracy range was implemented by applying an error and pattern recognition analysis, which maximizes measurement accuracy. The algorithm was optimized for efficiency, which allows its use it in small devices, like handheld computers.
Sensitive Assay for Mycoplasma Detection in Mammalian Cell Culture (2012)

Mycoplasma contamination in mammalian cell cultures is often overlooked yet is a serious issue which can induce a myriad of cellular changes leading to false interpretation of experimental results. Here, we present a simple and sensitive assay to monitor mycoplasma contamination (mycosensor) based on degradation of the Gaussia luciferase reporter in the conditioned medium of cells. This assay proved to be more sensitive as compared to a commercially available bioluminescent assay in detecting mycoplasma contamination in seven different cell lines. The Gaussia luciferase mycosensor assay provides an easy tool to monitor mammalian cell contaminants in a high-throughput fashion.
Transductive Optimization of Top k Precision (2015)

Consider a binary classification problem in which the learner is given a labeled training set, an unlabeled test set, and is restricted to choosing exactly $k$ test points to output as positive predictions. Problems of this kind---{\it transductive precision@$k$}---arise in information retrieval, digital advertising, and reserve design for endangered species. Previous methods separate the training of the model from its use in scoring the test points. This paper introduces a new approach, Transductive Top K (TTK), that seeks to minimize the hinge loss over all training instances under the constraint that exactly $k$ test instances are predicted as positive. The paper presents two optimization methods for this challenging problem. Experiments and analysis confirm the importance of incorporating the knowledge of $k$ into the learning process. Experimental evaluations of the TTK approach show that the performance of TTK matches or exceeds existing state-of-the-art methods on 7 UCI datasets and 3 reserve design problem instances.
Enamine Approach for Versatile and Reversible Functionalization on Cellulose Related Porous Sponges (2018)

A readily modifiable cellulose sponge was prepared from cellulose acetoacetate (CAA). Facile postsynthetic modification with primary amino-containing modifiers such as octadecyl amine (ODA), cysteine (CYS), and l-glutamic acid (GLU) could be achieved demonstrating the ease of anchoring a broad selection of functional groups to the surface of the sponges. This postsynthetic modification process was systematically characterized by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, which confirmed the formation of the enamine bonds. Besides, the microstructures and mechanical properties of the sponges were well preserved throughout the postsynthetic modification process. The enamine bonds, as one of the dynamic covalent bonds, were easily formed under mild and neutral conditions and broken under exposure to a low pH stimulus. The enamine bonds were used to modify the CAA sponges, which can achieve the versatility and recycling of cellulose porous materials. Therefore, the resulting sponges could serve as a versatile precursor to a broad spectrum of multifunctional porous materials, paving a new way for constructing smart sponges through the postsynthetic modification strategy.