gebhart/patrepeval huggingface dataset:
HSP90 empowers evolution of resistance to hormonal therapy in human breast cancer models (2014)

The efficacy of hormonal therapies for advanced estrogen receptor-positive breast cancers is limited by the nearly inevitable development of acquired resistance. Efforts to block the emergence of resistance have met with limited success, largely because the mechanisms underlying it are so varied and complex. Here, we investigate a new strategy aimed at the very processes by which cancers evolve resistance. From yeast to vertebrates, heat shock protein 90 (HSP90) plays a unique role among molecular chaperones by promoting the evolution of heritable new traits. It does so by regulating the folding of a diverse portfolio of metastable client proteins, many of which mediate adaptive responses that allow organisms to adapt and thrive in the face of diverse challenges, including those posed by drugs. Guided by our previous work in pathogenic fungi, in which very modest HSP90 inhibition impairs resistance to mechanistically diverse antifungals, we examined the effect of similarly modest HSP90 inhibition on the emergence of resistance to antiestrogens in breast cancer models. Even though this degree of inhibition fell below the threshold for proteotoxic activation of the heat-shock response and had no overt anticancer activity on its own, it dramatically impaired the emergence of resistance to hormone antagonists both in cell culture and in mice. Our findings strongly support the clinical testing of combined hormone antagonist-low-level HSP90 inhibitor regimens in the treatment of metastatic estrogen receptor-positive breast cancer. At a broader level, they also provide promising proof of principle for a generalizable strategy to combat the pervasive problem of rapidly emerging resistance to molecularly targeted therapeutics.
Evaluating Load Generation in Virtualized Environments for Software Performance Testing (2011)

Before placing a software system into production, it is necessary to guarantee it provides users with a certain level of Quality-of-Service. Intensive performance testing is then necessary to achieve such a level and the tests require an isolated computing environment. Virtualization can therefore play an important role for saving energy costs by reducing the number of servers required to run performance tests and for allowing performance isolation when executing multiple tests in the same computing infrastructure. Load generation is an important component in performance testing as it simulates users interacting with the target application. This paper presents our experience in using a virtualized environment for load generation aimed at performance testing. We measured several performance metrics and varied system load, number of virtual machines per physical resource, and the CPU pinning schema for comparison of virtual and physical machines. The two main findings from our experiments are that physical machines produced steadier and faster response times under heavy load and that the pinning schema is an important aspect when setting up a virtualized environment for load generation.
Relations World: A Possibilistic Graphical Model (2014)

We explore the idea of using a "possibilistic graphical model" as the basis for a world model that drives a dialog system. As a first step we have developed a system that uses text-based dialog to derive a model of the user's family relations. The system leverages its world model to infer relational triples, to learn to recover from upstream coreference resolution errors and ambiguities, and to learn context-dependent paraphrase models. We also explore some theoretical aspects of the underlying graphical model.
Control of gray scale inversion in a film-compensated twisted nematic liquid crystal display using beam steering optical film (2006)

Commercially available, twisted nematic (TN), liquid crystal cells have intrinsic problems such as light leakage in the dark state, gray scale inversion, and brightness nonuniformity in gray scales when the viewing direction deviates from the normal axis. Film compensation of a TN cell has solved the first problem but the second remains unsolved, which has hindered its applications to large displays. This letter proposes the use of a beam steering film to prepare a TN cell free of gray scale inversion in wide viewing directions.
ChemInform Abstract: Synthesis of Phosphates and Phosphate Isosteres of Furanose Sugars as Potential Enzyme Inhibitors. (1988)

Abstract Various D‐fructose monosaccharides are synthesized as possible inhibitors of the gluconeogenic enzyme fructose 1,6‐bisphosphatase (FBPase).
Efficiency of a New Bioaerosol Sampler in Sampling Betula Pollen for Antigen Analyses (1987)

A new bioaerosol sampler consisting of Liu-type atmospheric aerosol sampling inlet, coarse particle inertial impactor, two-stage high-efficiency virtual impactor (aerodynamic particle sizes respectively in diameter: greater than or equal to 8 microns, 8-2.5 microns, and 2.5 microns; sampling on filters) and a liquid-cooled condenser was designed, fabricated and field-tested in sampling birch (Betula) pollen grains and smaller particles containing Betula antigens. Both microscopical (pollen counts) and immunochemical (enzyme-linked immunosorbent assay) analyses of each stage were carried out. The new sampler was significantly more efficient than Burkard trap e.g. in sampling particles of Betula pollen size (ca. 25 microns in diameter). This was prominent during pollen peak periods (e.g. May 19th, 1985, in the virtual impactor 9482 and in the Burkard trap 2540 Betula p.g. X m-3 of air). Betula antigens were detected also in filter stages where no intact pollen grains were found; in the condenser unit the antigen concentrations instead were very low.
Novel millimeter-wave gas sensor using dielectric resonator with sensitive layer on TiO<inf>2</inf> (2009)

A new generation of gas sensors that operates in millimeter-wave frequency range is presented. The sensor uses a dielectric resonator operating with whispering-gallery modes. Here the dielectric resonator is covered by TiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> thin film as sensitive layer. A gas or humidity adsorption makes the TiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> dielectric permittivity changing and such changing modifies the resonant frequencies of high-Q whispering-gallery modes within the dielectric resonator. From the measurement of these resonant frequencies the humidity concentration is derived. Here, the proof of concept is demonstrated through full wave electromagnetic simulations. This humidity (gas) sensor can be remotely interrogated and has great potential for wireless sensors network applications.
Optical free-carrier generation in silicon nano-waveguides at 1550 nm (2018)

We report on time-resolved pump and probe characterization of linear and nonlinear optical generation of free carriers in a silicon strip nano-waveguide at the 1550 nm communication band. Analytical expressions were developed to extract the carrier density averaged along the waveguide length from the measured free-carrier absorption for different input pump power levels. This allows us to discriminate the contributions from two-photon absorption (TPA) and single-photon absorption (SPA), obtaining TPA and SPA coefficients of (1.5 ± 0.1) cm/GW and (1.9 ± 0.1) m−1, respectively. Our results reveal that the effective TPA within the waveguide is higher than the value reported for bulk silicon. In addition, we find that for the waveguide under test, the carrier generation via SPA plays an important role up to ∼300 mW, and therefore, it must be taken into account to correctly assess free-carrier effects in silicon photonic devices.
Paxos replicated state machines as the basis of a high-performance data store (2011)

Conventional wisdom holds that Paxos is too expensive to use for high-volume, high-throughput, data-intensive applications. Consequently, fault-tolerant storage systems typically rely on special hardware, semantics weaker than sequential consistency, a limited update interface (such as append-only), primary-backup replication schemes that serialize all reads through the primary, clock synchronization for correctness, or some combination thereof. We demonstrate that a Paxos-based replicated state machine implementing a storage service can achieve performance close to the limits of the underlying hardware while tolerating arbitrary machine restarts, some permanent machine or disk failures and a limited set of Byzantine faults. We also compare it with two versions of primary-backup. The replicated state machine can serve as the data store for a file system or storage array. We present a novel algorithm for ensuring read consistency without logging, along with a sketch of a proof of its correctness.
Evidence for an infectious etiology in autism (1997)

Objective: Cyclical trends in birth rates that vary from general population patterns have been reported for several neuropsychiatric disorders. These data are used to test etiological hypotheses. Monthly and seasonal variations have been demonstrated for Autism possibly implicating an environmental pathogenic factor. We analyse data from Israel, focusing on viral epidemics. Method: Data covering a 30 year period (1960–1989), including general population live births, autistic births, and incidence of viral encephalitis, viral meningitis, rubella, measles, and poliomyelitis were collected from Israel's Ministry of Health, Central Bureau of Statistics and National League for Autism. Periodicity and correlations between variables were analyzed. Results: Over the period studied, 290 autistic births were evaluated. Spectral analysis using the cosine function demonstrated a significant periodicity (tau) of 17.6 years (P=0.011) and near-significant periodicities of 3.2 years (P=0.07) and 4.1 years (P=0.27). Superposition of these three periods showed a highly significant fit to the annual autistic birth pattern (r=0.749, P=0.042). Multiple regression analysis of variables (encephalitis, meningitis, rubella, measles and poliomyelitis), yielded two significant findings: (a) during the period 1968–1989 the incidence of measles correlated with the rhythmicity of Autistic births (r=0.49, P=0.036); (b) during the entire study period the incidence of viral meningitis correlated with this rhythmicity (r=0.37, P=0.042). It is note worthy that the only risk factor demonstrating a cyclical trend was viral meningitis (tau=3.0 years, P=0.032). Conclusions: Cyclical trends are significant in Autistic births in Israel. Autistic birth patterns are partially explained by the rates of measles and viral meningitis in the general population. There is a statistically significant environmental association between autism and both viral meningitis and measles that should be further investigated.
Transfection of Bone Marrow Cells In Vitro or In Vivo Prior to Cryopreservation with Manganese Superoxide Dismutase (MnSOD-PL) Protects Frozen Cells from Ionizing Irradiation. (2006)

Abstract Overexpression of MnSOD in IL-3 dependent murine hematopoietic progenitor cell line 32D cl 3 protects against apoptosis induced by ionizing irradiation, TNF-α, IL-3 withdrawal or other inducers of cytotoxic stress. Cryopreservaton of bone marrow is routinely used in clinical marrow transplantation with the necessary cytotoxic loss of a fraction of cells from the stress of thawing. To determine if overexpression of MnSOD protected marrow from the stress of thawing and also whether frozen cells resisted ionizing irradiation, 32D cl 3 and subclone 2C6 stably transfected and overexpressing MnSOD were tested. Exponentially growing cells 2C6 cells demonstrate increased irradiation survival with an increased shoulder on the survival curve n = 4.95 ± 0.1 compared to 32D cl 3 n = 2.77 ± 0.1 (p = 0.011), with no significant change in the Do = 2.11 ± 0.08 vs. Do = 2.36 ± 0.10 Gy. Cells from 32D cl 3 and 2C6 were frozen in liquid nitrogen in 50% DMSO and stored at a −140°C for a minimum of 24 hrs and irradiated to doses ranging from 0 to 800 cGy while frozen. The cells were thawed 24 hr later, plated in methylcellulose and colonies of greater than 50 cells counted seven days later. The data was analyzed using linear quadratic and single-hit, multi-target models. Cells from 2C6 were more resistant to thawing with survival of 24.3 ± 0.6% compared to 20.9 ± 0.8% for 32D cl 3 (p = 0.018) and to irradiation as shown by an increase in the Do of 2.036 ± 0.225 compared to 1.455 ± 0.149 Gy for frozen 32D cl 3 cells (p= 0.0287). The frozen 2C6 cells resisted the stress of thawing with an increased plating efficiency compared to the frozen 32D cl 3 cells (121.4 ± 3.2 colonies for 2C6 cells and 104.3 ± 3.9 colonies for 32D cl 3 per 500 cells plated, p=0.0018). To determine whether fresh bone marrow transfected in vivo, or in vitro, then frozen and irradiated, also was protected, C57BL/6NHsd mice were injected with MnSOD-PL (100 ug plasmid DNA in 100 μl). Twenty-four hours later, bone marrow was isolated from MnSOD-PL injected mice as well as control mice (a subpopulation transfected with MnSOD-PL in vitro) and frozen in aliquots of 1 × 106 cells. The cells were irradiated while frozen to doses ranging from 0 to 800 cGy, plated in methylcellulose and colonies of greater than 50 cells counted 7 days later. The colonies were divided between nonadherent and adherent in the methylcellulose. The Do was calculated for the adherent colonies, nonadherent colonies and total colonies. In all three cases the Do for the bone marrow treated with MnSOD-PL in vitro or in vivo was higher than the Do of the control bone marrow. The percent HA-epitope tagged total transfected cells was 22.1 ± 3.7%. The data indicates that MnSOD overexpression protects frozen bone marrow perhaps important to increasing preservation efficiency.
Codebook design and link level performance of closed-loop 4&#x00D7;2 MIMO in HSDPA (2013)

The feedback quantization has a considerable impact on the performance of precoded four branch High Speed Downlink Packet Access (HSDPA) MIMO. As the number of transmit antennas is increased, constructing an efficient quantization scheme becomes more important, and compared to the case of two transmit antennas, more quantization loss needs to be tolerated. In this paper, the performance of four branch dual-codeword single-user MIMO is evaluated assuming two different types of compact codebooks. First of the studied codebooks is similar to the 4-Tx codebook used in Long Term Evolution (LTE) system and the second is a novel multi-granular codebook that tries to address the different short and long term correlation properties of the radio channel. An extension to the multi-granular codebook is also proposed in this paper to further improve the performance. Simulation results are presented assuming cross-polarized antenna configuration. The link performance is compared to Release 7 2×2 MIMO and 4×2 MIMO with singular value decomposition based unquantized feedback. The studies show link throughput gains up to 66% for the LTE codebook and up to 79% for the multi-granular codebook compared to the 2×2 MIMO. The relative gains are highest at low geometries where rank 1 transmission is dominant.
Initial Experience with Full-Length Metal Stent to Relieve Malignant Ureteral Obstruction (2006)

Ureteral obstruction caused by extrinsic compression by a malignancy generally can be overcome initially with a ureteral stent. However, the long-term failure rate is high, usually necessitating placement of a nephrostomy tube. Herein, we present the initial case, in this country, of intractable ureteral obstruction managed successfully with the newly developed all-metal Resonance stent (Cook Ireland Ltd., Limerick, Ireland) constructed of MP35N alloy, a composite of nonmagnetic nickel-cobalt-chromium-molybdenum. The patient is a 64-year-old woman with metastatic breast cancer causing retroperitoneal fibrosis and ureteral obstruction diagnosed laparoscopically. The obstruction failed to respond to placement of a single 7F double-J stent and then of two 6F double-J stents in the left ureter. As a last resort, in order to avoid nephrostomy-tube placement, the 6F metal stent was placed; this provided unobstructed flow of urine, as documented on a subsequent Whitaker test and, most recently, on a renal scan, 4 months after initial stent placement.
Mechanical activation of mitochondrial energy metabolism during cell differentiation (2022)

Abstract In multicellular lives, differentiation of many types of stem and progenitor cells is often accompanied by a metabolic transition from glycolysis to mitochondrial oxidative phosphorylation. The mechanisms driving this metabolic transition in vivo are largely unknown. Here, we show that, during differentiation of the Drosophila female germline cyst, the surrounding somatic cells compress the cyst and increase the tension of cyst cells’ membranes. Transmembrane channel-like, an evolutionarily conserved ion channel involved in mechanosensation, maintains cytosolic Ca 2+ levels in compressed differentiating cysts. Cytosolic Ca 2+ induces transcriptional activation of oxidative phosphorylation through a CaMKI-Fray-JNK signaling relay. Our findings demonstrate a molecular link between cell mechanics and mitochondrial energy metabolism, with implications in other developmentally orchestrated metabolic transitions in mammals.
Posthypercapnic syndrome (2023)

Hypercapnic respiratory failure is a common cause of hospitalization and death in patients with chronic obstructive pulmonary disease (COPD). The aim of this work was to analyze the pathophysiological mechanisms and clinical picture of hypercapnic respiratory failure and to discuss the tactics of managing a patient with COPD and posthypercapnic alkalosis that developed during treatment using a clinical case as an example. Conclusion. To date, the search for new treatments for posthypercapnic alkalosis is still relevant, but there are few published studies on this topic. Acute problems in mixed metabolic disorders can be solved with an integrated therapeutic approach that includes the use of medical gases.
Analytical method for optimal design of RF dual-band rat-race couplers for arbitrary frequency ratios (2012)

This article presents an analytical method to design a hybrid structure dual-band rat-race coupler at microwave frequencies. The proposed structure uses six identical cells of which each is engineered to work as a quarter wavelength transmission line with proper characteristic impedance at two distinct frequencies having arbitrary frequency ratio. The performances of the π- and T-cells are studied to assess their ability to provide the required electrical parameters for dual-band operation. It is demonstrated that the single-section π-topology can only lead to a suboptimal design for a dual-band rat-race cell at two nonharmonic frequencies. In contrast, the proposed double-section π-cell structure allows achieving an optimal dual-band cell design. A dual-band rat-race coupler designed at 2.14 and 3.6 GHz has been simulated and fabricated in hybrid microstrip technology. Measurement results agree well with analytically based simulation results, which demonstrate the effectiveness of the proposed structure for dual-band operation. © 2012 Wiley Periodicals, Inc. Int J RF and Microwave CAE 22: 690–700, 2012.
In Situ TEM Imaging of Defect Dynamics under Electrical Bias in Resistive Switching Rutile-TiO2 (2014)

In this study, in situ electrical biasing was combined with transmission electron microscopy (TEM) in order to study the formation and evolution of Wadsley defects and Magnéli phases during electrical biasing and resistive switching in titanium dioxide (TiO2). Resistive switching devices were fabricated from single-crystal rutile TiO2 substrates through focused ion beam milling and lift-out techniques. Defect evolution and phase transformations in rutile TiO2 were monitored by diffraction contrast imaging inside the TEM during electrical biasing. Reversible bipolar resistive switching behavior was observed in these single-crystal TiO2 devices. Biased induced reduction reactions created increased oxygen vacancy concentrations to such an extent that shear faults (Wadsley defects) and oxygen-deficient phases (Magnéli phases) formed over large volumes within the TiO2 TEM specimen. Nevertheless, the observed reversible formation/dissociation of Wadsley defects does not appear to correlate to resistive switching phenomena at these length scales. These defect zones were found to reversibly reconfigure in a manner consistent with charged oxygen vacancy migration responding to the applied bias polarity.
Micro-optical coherence tomography catheter for endomicroscopy of the human cochlea (2022)

To address the unmet need to study the microstructure changes in the cochlea that occur with sensorineural hearing loss, we have constructed a miniature flexible micro-OCT catheter that can be inserted into the human cochlea and acquire images with cellular-level resolution. The OCT catheter was designed, fabricated, and characterized. Crucial mechanical properties (flexibility, insertion force) were measured and found to be comparable to those of commercial cochlear implants. These early results suggest that this new device may provide a viable approach for diagnosing SNHL and selecting the most appropriate treatments on an individual patient basis.
Structures of three DNA cross-linking agents, ethane-1,2-di(methylsulfonate), propane-1,3-di(methylsulfonate) and n-butane-1,4-di(methylsulfonate) (1989)

(I): C4H10O6S2, Mr = 218.25, P2(1)/c, a = 7.2611 (9), b = 5.8726 (4), c = 10.6628 (19) A, beta = 103.95 (1) degree, V = 441.3 (2) A3, Z = 2, Dm = 1.65, Dx = 1.642 Mg m-3, lambda(Cu K alpha) = 1.54184 A, mu = 5.43 mm-1, F(000) = 228, R = 0.0336 and wR = 0.0346 for 745 unique reflections with F greater than or equal to 3 sigma (F), T = 298 K. (II): C5H12O6S2, Mr = 232.28, P2(1)/c, a = 11.030 (1), b = 8.452 (1), c = 11.162 (1) A, beta = 104.65 (1) degree, V = 1006.8 (3) A3, Z = 4, Dm 1.54, Dx = 1.532 Mg m-3, lambda(Cu K alpha) = 1.54184 A, mu = 4.79 mm-1, F(000) = 488, R = 0.0418 and wR = 0.0430 for 1666 unique reflections with F greater than or equal to 3 sigma(F), T = 298 K. (III): C6H14O6S2, Mr = 246.30, P1, a = 5.6147 (9), b = 6.8343 (6), c = 7.5434 (6) A, alpha = 110.61 (1), beta = 92.08 (1), gamma = 76.15 (1) degree, V = 262.7 (3) A3, Z = 1, Dm = 1.56, Dx = 1.557 Mg m-3, lambda(Cu K alpha) = 1.54184 A, mu = 4.79 mm-1, F(000) = 130, R = 0.0397 and wR = 0.0425 for 907 unique reflections with F greater than or equal to 3 sigma(F), T = 298 K. All three compounds have a common conformation in the C.O.SO2.CH3 part of the molecules due to weak O...H interactions. Compounds (I) and (III) have a trans conformation about the central C--C bond, whereas (II) is cis.