gebhart/patrepeval huggingface dataset:
Data from A Central Role for RAF→MEK→ERK Signaling in the Genesis of Pancreatic Ductal Adenocarcinoma (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;i&gt;KRAS&lt;/i&gt; mutation is a hallmark of pancreatic ductal adenocarcinoma (PDA) but remains an intractable pharmacologic target. Consequently, defining RAS effector pathway(s) required for PDA initiation and maintenance is critical to improve treatment of this disease. Here, we show that expression of BRAF&lt;sup&gt;V600E&lt;/sup&gt;, but not PIK3CA&lt;sup&gt;H1047R&lt;/sup&gt;, in the mouse pancreas leads to pancreatic intraepithelial neoplasia (PanIN) lesions. Moreover, concomitant expression of BRAF&lt;sup&gt;V600E&lt;/sup&gt; and TP53&lt;sup&gt;R270H&lt;/sup&gt; result in lethal PDA. We tested pharmacologic inhibitors of RAS effectors against multiple human PDA cell lines. Mitogen-activated protein (MAP)/extracellular signal–regulated (ERK) kinase (MEK) inhibition was highly effective both &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt; and was synergistic with AKT inhibition in most cell lines tested. We show that RAF→MEK→ERK signaling is central to the initiation and maintenance of PDA and to rational combination strategies in this disease. These results emphasize the value of leveraging multiple complementary experimental systems to prioritize pathways for effective intervention strategies in PDA.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; PDA is difficult to treat, in large part, due to recurrent mutations in the &lt;i&gt;KRAS&lt;/i&gt; gene. Here, we define rational treatment approaches for the disease achievable today with existing drug combinations by thorough genetic and pharmacologic dissection of the major KRAS effector pathways, RAF→MEK→ERK and phosphoinositide 3′-kinase (PI3′K)→AKT. &lt;i&gt;Cancer Discov; 2(8); 685–93. ©2012 AACR.&lt;/i&gt;&lt;/p&gt;&lt;p&gt;Read the Commentary on this article by Hanrahan et al., p. 666.&lt;/p&gt;&lt;p&gt;This article is highlighted in the In This Issue feature, p. 653.&lt;/p&gt;&lt;/div&gt;
19.1: The Most PowerEfficient 11.6” Full HD LCD Using PenTile Technology for Notebook Application (2010)

Abstract We have developed an 11.6” full high definition FHD, 1920* 1080 product with PenTile RGBW™ L6W pixel structure for notebook applications. with the increase of aperture ratio due to the reduced number of subpixels and additional white subpixel, this new product has approximately twice the brightness of comparable conventional RGB stripe products. The crosstalk that appeared when displaying a single colored pattern, which is an intrinsic problem for an even modulo subpixel repeat cell, was solved by means of a Vest feedback design. Furthermore, subpixel rendering SPR and dynamic backlight control DBLC algorithm gives us a cost effective, low power and high brightness solution.
On the bounds of the estimation error of the EOBE algorithm (2003)

Convergence analysis is performed for the extended optimal bounding ellipsoid algorithm for ARMA (autoregressive moving average) parameter estimation (with bounded but unknown inputs). Analysis shows that the residual errors are uniformly bounded. Imposition of a bound of unity on the sum of the magnitude of the MA coefficients guarantees that all the bounding ellipsoids contain the true parameter vector. With an additional persistence of excitation condition, the a priori prediction errors are shown to be bounded, and the difference between successive parameter estimates converges to zero.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Histological Localization of Phosphorothioate Oligodeoxynucleotides in Normal Rodent Tissue (1997)

Abstract The distribution of phosphorothioate oligodeoxynucleotides (P=S ODN) in rodent tissues was studied in vivo using three histological methods: direct fluorescence microscopy; immunohistochemistry; and autoradiography. All three methods gave essentially the same pattern of oligonucleotide localization in the tissues studied, and the histological results correlate well with those from radiochemical and biochemical studies of P=S ODN distribution.
Scalable numerical approach for the steady-stateab initiolaser theory (2014)

We present an efficient and flexible method for solving the non-linear lasing equations of the steady-state ab initio laser theory. Our strategy is to solve the underlying system of partial differential equations directly, without the need of setting up a parametrized basis of constant flux states. We validate this approach in one-dimensional as well as in cylindrical systems, and demonstrate its scalability to full-vector three-dimensional calculations in photonic-crystal slabs. Our method paves the way for efficient and accurate simulations of microlasers which were previously inaccessible.
RAS–MAPK Reactivation Facilitates Acquired Resistance in FGFR1 -Amplified Lung Cancer and Underlies a Rationale for Upfront FGFR–MEK Blockade (2018)

The FGFR kinases are promising therapeutic targets in multiple cancer types, including lung and head and neck squamous cell carcinoma, cholangiocarcinoma, and bladder cancer. Although several FGFR kinase inhibitors have entered clinical trials, single-agent clinical efficacy has been modest and resistance invariably occurs. We therefore conducted a genome-wide functional screen to characterize mechanisms of resistance to FGFR inhibition in a <i>FGFR1</i>-dependent lung cancer cellular model. Our screen identified known resistance drivers, such as MET, and additional novel resistance mediators including members of the neurotrophin receptor pathway (NTRK), the TAM family of tyrosine kinases (TYRO3, MERTK, AXL), and MAPK pathway, which were further validated in additional FGFR-dependent models. In an orthogonal approach, we generated a large panel of resistant clones by chronic exposure to FGFR inhibitors in FGFR1- and FGFR3-dependent cellular models and characterized gene expression profiles employing the L1000 platform. Notably, resistant clones had enrichment for NTRK and MAPK signaling pathways. Novel mediators of resistance to FGFR inhibition were found to compensate for FGFR loss in part through reactivation of MAPK pathway. Intriguingly, coinhibition of FGFR and specific receptor tyrosine kinases identified in our screen was not sufficient to suppress ERK activity or to prevent resistance to FGFR inhibition, suggesting a redundant reactivation of RAS-MAPK pathway. Dual blockade of FGFR and MEK, however, proved to be a more powerful approach in preventing resistance across diverse FGFR dependencies and may represent a therapeutic opportunity to achieve durable responses to FGFR inhibition in FGFR-dependent cancers. <i>Mol Cancer Ther; 17(7); 1526-39. ©2018 AACR</i>.
Optical nanoscopy of a living cell (2014)

Optical nanoscopy allows to study biological and functional processes of sub-cellular organelles. In structured illumination microscopy (SIM) the sample is illuminated with a grid-like interference pattern to encode higher spatial frequency information into observable Moiré patterns. By acquiring multiple images and a computation trick a superresolved image is obtained. SIM provides resolution enhancement of 2X in each axis as compared to conventional microscopes. For a visible light, SIM provides an optical resolution of 100 nm. The challenges associated with optical nanoscopy of a living cell are photo-toxicity, special dye requirements and artifacts due to cell movement. SIM works with conventional dyes and is a wide-field technique making it suitable for imaging living cells. In this work, we will discuss the opportunities and challenges of imaging living cells using SIM. Two applications of optical nanoscopy of living cells will be discussed; a) imaging of mitochondria in a keratinocyte cell and Optical microscopy based on fluorescence has emerged as a vital tool in modern bio-medical imaging and diagnosis. Super-resolution bio-imaging allows gathering information from sub-cellular organelles. In structured illumination microscopy (SIM) the sample is illuminated with a grid-like interference patterns to encode higher spatial frequencies information into observable images (Moiré fringes). A super-resolved image is then decoded using computational trick. In this work, we used SIM to acquired super-resolved optical images of mitochondria from a live keratinocyte cell (see Fig 1). SIM provides resolution enhancement of 2X in each axis and contrast enhancement of 8X on a projected image. Time-lapsed imaging was used to study the dynamics of mitochondria in a live cell.
Machine learning from the CARDAMON trial identifies a carfilzomib-specific mutational response signature (2023)

Abstract Precision medicine holds great promise to improve outcomes in cancer, including haematological malignancies. However, there are few biomarkers that influence choice of chemotherapy in clinical practice. In particular, multiple myeloma requires an individualized approach as there exist several active therapies, but little agreement on how and when they should be used and combined. We have previously shown that a transcriptomic signature can identify specific bortezomib- and lenalidomide-sensitivity. However, gene expression signatures are challenging to implement clinically. We reasoned that signatures based on the presence or absence of gene mutations would be more tractable in the clinical setting, though examples of such signatures are rare. We performed whole exome sequencing as part of the CARDAMON trial, which employed carfilzomib-based therapy. We applied advanced machine learning approaches to discover mutational patterns predictive of treatment outcome. The resulting model accurately predicted progression-free survival (PFS) both in CARDAMON patients and in an external validation set of patients from the CoMMpass study who had received carfilzomib. The signature was specific for carfilzomib therapy and was strongly driven by genes on chromosome 1p36. Importantly, patients predicted to be carfilzomib-sensitive had a longer PFS when treated with carfilzomib/lenalidomide/dexamethasone than with bortezomib/carfilzomib/dexamethasone. However, in those predicted to be carfilzomib-insensitive, the latter therapy may have been capable of eradicating carfilzomib-resistant clones. We propose that the signature can be used to make rational therapeutic decisions and could be incorporated into future clinical trials.
Transfer and Green functions based on modal analysis for Lamb waves generation (2000)

This work presents an easy way to deduce the tensorial transfer and Green functions for Lamb waves generated in isotropic elastic plates. These functions could be applied to obtain the response of each propagating mode in the ensemble of excited modes arising from any sort of pulsed excitation (wedge transducers, lasers, etc.). The transfer function is based on modal analysis development. Not only is it easy to manipulate but also allows the avoidance of laborious calculations for each kind of Lamb waves source. Theoretical predictions are compared with those of Viktorov [I. A. Viktorov, Rayleigh and Lamb Waves (Plenum, New York, 1967)] and with experimental measurements of Lamb waves generated by the wedge-transducer method.
Relationship of quality goals and measurement performance to the selection of quality control procedures for multi‐channel haematology analysers (1990)

An approach is described for selecting QC procedures based on goals for analytical quality, the performance characteristics of the measurement procedure (imprecision, bias, frequency of errors), and the performance characteristics of the control procedure (probabilities for error detection and false rejection). Performance characteristics of stable sample QC procedures and patient data QC procedures (retained patient specimens, Bull's single-rule algorithm, Bull's multi-rule algorithm) are compared to determine when to apply these different QC procedures to multichannel hematology analysers. Precise, stable methods may be controlled using Bull's single-rule algorithm; less precise, less stable methods require Bull's multi-rule algorithm, retained patient specimens, or stable sample QC procedures; imprecise and unstable methods are best controlled using stable sample QC procedures. "Multi-stage" designs may employ stable samples for "startup" testing, retained patient specimens for short term monitoring, and Bull's single-rule algorithm for long term monitoring.
Optimization of droplet routing for an n-plex bioassay on a digital microfluidic lab-on-chip (2009)

The multiplexed in-vitro measurement of glucose and other metabolites in human physiological fluids is of great importance for the clinical diagnosis of metabolic disorders. We present a design technique for optimizing an n-plex bioassay on an electrowetting-based digital microfluidic lab-on-chip. The n product droplets of the n-plex bioassay are detected using a photomultiplier tube located at the transport bus of the lab-on-chip. We optimize the routing of the droplets and prove that this approach minimizes the assay completion time. The effectiveness of the proposed droplet-routing schedule is shown via an on-chip experiment for a 3-plex assay. We compare the completion time of the proposed routing schedule to an unoptimized baseline schedule for the n-plex assay.
Hyperparameter Optimization in Binary Communication Networks for\n Neuromorphic Deployment (2020)

Training neural networks for neuromorphic deployment is non-trivial. There\nhave been a variety of approaches proposed to adapt back-propagation or\nback-propagation-like algorithms appropriate for training. Considering that\nthese networks often have very different performance characteristics than\ntraditional neural networks, it is often unclear how to set either the network\ntopology or the hyperparameters to achieve optimal performance. In this work,\nwe introduce a Bayesian approach for optimizing the hyperparameters of an\nalgorithm for training binary communication networks that can be deployed to\nneuromorphic hardware. We show that by optimizing the hyperparameters on this\nalgorithm for each dataset, we can achieve improvements in accuracy over the\nprevious state-of-the-art for this algorithm on each dataset (by up to 15\npercent). This jump in performance continues to emphasize the potential when\nconverting traditional neural networks to binary communication applicable to\nneuromorphic hardware.\n
Data from A Novel Orally Active Small Molecule Potently Induces G<sub>1</sub> Arrest in Primary Myeloma Cells and Prevents Tumor Growth by Specific Inhibition of Cyclin-Dependent Kinase 4/6 (2023)

&lt;div&gt;Abstract&lt;p&gt;Cell cycle deregulation is central to the initiation and fatality of multiple myeloma, the second most common hematopoietic cancer, although impaired apoptosis plays a critical role in the accumulation of myeloma cells in the bone marrow. The mechanism for intermittent, unrestrained proliferation of myeloma cells is unknown, but mutually exclusive activation of cyclin-dependent kinase 4 (Cdk4)-cyclin D1 or Cdk6-cyclin D2 precedes proliferation of bone marrow myeloma cells &lt;i&gt;in vivo&lt;/i&gt;. Here, we show that by specific inhibition of Cdk4/6, the orally active small-molecule PD 0332991 potently induces G&lt;sub&gt;1&lt;/sub&gt; arrest in primary bone marrow myeloma cells &lt;i&gt;ex vivo&lt;/i&gt; and prevents tumor growth in disseminated human myeloma xenografts. PD 0332991 inhibits Cdk4/6 proportional to the cycling status of the cells independent of cellular transformation and acts in concert with the physiologic Cdk4/6 inhibitor p18&lt;sup&gt;INK4c&lt;/sup&gt;. Inhibition of Cdk4/6 by PD 0332991 is not accompanied by induction of apoptosis. However, when used in combination with a second agent, such as dexamethasone, PD 0332991 markedly enhances the killing of myeloma cells by dexamethasone. PD 0332991, therefore, represents the first promising and specific inhibitor for therapeutic targeting of Cdk4/6 in multiple myeloma and possibly other B-cell cancers. (Cancer Res 2006; 66(15): 7661-7)&lt;/p&gt;&lt;/div&gt;
Calmodulin Expression During Rat Liver Regeneration (1994)

We have investigated the messenger RNAs expressed from the three calmodulin genes during rat liver regeneration. The results revealed that all the calmodulin transcripts increased from 8 hr after a partial hepatectomy, although differences in the timing and the level of expression from the three genes were observed. Calmodulin I transcripts peaked at 16 hr, whereas calmodulin II and calmodulin III progressively increased from 8 to 24 hr. At 24 hr after surgery, calmodulin I, calmodulin II and the 2.3 kb calmodulin III transcripts reached values of a 6-fold increase, whereas the 0.8 kb product of calmodulin III increased 25-fold. At 30 hr the levels of all the calmodulin transcripts were similar to those observed at 24 hr. The transcription rates of the three calmodulin genes augmented after hepatectomy (calmodulin I and calmodulin II twofold and calmodulin III fourfold), indicating that the elevation of the calmodulin transcripts could be, at least partially, the result of this increase in the transcription rates. The total calmodulin concentration also increased twofold at 24 hr after hepatectomy. We also report that the administration of the beta-adrenergic blocker, D,L-propranolol inhibited the accumulation of calmodulin protein without significantly affecting the increase of the messenger RNAs. These results indicate that the expression of calmodulin observed during liver regeneration could be regulated by cyclic AMP at the translational or posttranslational level.
Practical RFID + sensor convergence toward context-aware X-reality (2009)

Second Life is a representative virtual world accessible via the Internet. One can live in Second Life as a Resident, represented as an avatar. Now an important question is a raise that is, What if virtual world reflects real world (almost) exactly in the same way and vice versa? RFID and sensor technologies can drive life into virtual world i.e., RFID + Sensor technology augments user's experiences in the virtual world and enables real world synchronous response toward the virtual world. Furthermore, these two worlds can cross over to extend human life space (called cross-reality). However, the main challenge of using RFID + Sensor technology in real world is the heterogeneity of RFID + Sensor devices and the sensing data. Ubiquitous Sensor Network (USN) middleware has emerged as the key technology to propel the innovative paradigm (i.e., cross-reality) realization because USN middleware provides solution to heterogeneity and more. This paper describes USN middleware (COSMOS) which intermediates between various USN applications and diverse physical resources such as RFID reader networks, sensor and actuator networks, etc. and shows how it functions as a part of cross-reality platform.
Broadly tunable carrier envelope phase stable optical parametric amplifier pumped by a monolithic ytterbium fiber amplifier (2009)

In an effort to develop a robust and efficient front end for a chirped-pulse parametric amplification chain, we demonstrate a broadband difference-frequency converter driven by a monolithic femtosecond Yb-doped-fiber amplifier and emitting carrier-envelope-offset-free pulses with the energy of tens of nanojoules tunable in the wavelength range from 1200 nm to beyond 2 mum. Next to providing these seed pulses, the system enables direct optical synchronization of Nd- and Yb-doped pump lasers for subsequent parametric amplification.
Quantitative characterization of the excavation damaged zone fracture network in the Meuse/Haute-Marne Underground Research Laboratory: in situ experiment and numerical interpretation of helium injection test (2016)

Abstract In the underground laboratory of Meuse/Haute-Marne (Bure) in France, different fracture types have been intensively investigated. Within a co-operative project between BGR and ANDRA, geophysical measurements and borehole gas tests were conducted in three well-designed boreholes in the gallery GRM to characterize the fracture structure and to determine the gas tracer velocity within fracture networks. On the basis of seismic measurements and nitrogen gas interference tests, helium was injected into an interval of borehole OHZ3003, where an unloading joint has been identified. The injection took place in the form of a 10 min ‘pulse’ with an injection pressure of 2 bar. The other two boreholes, OHZ3002, where an upper part of the shear-mode fractures (‘chevron’ pattern) dominate, and OHZ3001, where shear-mode fractures (subvertical ‘oblique’ fractures and ‘chevron’ pattern) exist, served as observation holes. To maintain the pressure gradient between the injection hole and the observation holes, nitrogen gas was subsequently flushed into the injection hole. Two breakthrough curves of helium concentration and pressure developments in the two observation holes were continuously monitored using two helium leakage detectors and pressure gauges. To interpret the measured pressure and concentration data, numerical models were constructed. A 3D model was used to simulate nitrogen gas flow and 2D models were applied to simulate a helium transport process. The real volume of the injection interval was considered in the model and the experimental process was simulated. Using the calibrated transport parameter data for a helium tracer from previous studies in the Mont Terri Rock Laboratory, the calculated breakthrough curves agreed well with those obtained from measuring the variation in permeability. The permeability derived from the helium tracer test agrees well with the estimation obtained from the nitrogen gas tests.
Hardware support for spin management in overcommitted virtual machines (2006)

Multiprocessor operating systems (OSs) pose several unique and conflicting challenges to System Virtual Machines (System VMs). For example, most existing system VMs resort to gang scheduling a guest OS's virtual processors (VCPUs) to avoid OS synchronization overhead. However, gang scheduling is infeasible for some application domains, and is inflexible in other domains.In an overcommitted environment, an individual guest OS has more VCPUs than available physical processors (PCPUs), precluding the use of gang scheduling. In such an environment, we demonstrate a more than two-fold increase in runtime when transparently virtualizing a chip-multiprocessor's cores. To combat this problem, we propose a hardware technique to detect several cases when a VCPU is not performing useful work, and suggest preempting that VCPU to run a different, more productive VCPU. Our technique can dramatically reduce cycles wasted on OS synchronization, without requiring any semantic information from the software.We then present a case study, typical of server consolidation, to demonstrate the potential of more flexible scheduling policies enabled by our technique. We propose one such policy that logically partitions the CMP cores between guest VMs. This policy increases throughput by 10-25% for consolidated server workloads due to improved cache locality and core utilization, and substantially improves performance isolation in private caches.
Radiation Damage Analysis of a commercial optical CMOS Image Sensor (2007)

Detectors used with an intense radiation source, such as synchrotron require the need to study the damage which has occurred to the detector. This paper concentrates on understanding the effect of radiation damage on signal quality and examines a method to reduce such a damage.