gebhart/patrepeval huggingface dataset:
Expanding the horizon of chemotherapeutic targets: From MDM2 to MDMX (MDM4) (2011)

Alterations of p53 signalling pathway is the most frequent event in human cancers. About 50% of these, albeit showing wild-type p53, have flaws in the control mechanisms of p53 levels and activity. MDM2 and MDMX (MDM4) are the main negative regulators of p53. The relevance of MDM2 on the regulation of p53 levels and activity has fostered the development of strategies aimed at restoring p53 functions by blocking the physical interaction between MDM2 and p53. As a consequence, a number of different small molecules and peptidomimetics have been disclosed in the last decade as inhibitors of MDM2/p53 interaction. Recent studies, however, have thrust MDMX into the limelight as an additional chemotherapeutic target, suggesting the presence of a more complex relationship between MDM2, MDMX and p53. In this review article, we report key aspects of MDMX-mediated regulation of p53, recent advances in the structural characterization of the protein, and the progress made so far in the medicinal chemistry of MDMX ligands.
Dual Low Profile Detector Heads for a Restraint Free Small Animal SPECT Imaging System (2005)

A small animal single photon emission computed tomography (SPECT) system has been developed for acquiring in vivo images of the biodistribution of radiopharmaceuticals in unrestrained, awake small animal models. This system uses two dedicated gamma-ray cameras and an infrared based animal position tracking system mounted on a rotational gantry with an infrared transparent mouse burrow in the center. The original implementation of this system had two compact gamma cameras with an active area of 5 cm/spl times/5 cm. Two new gamma camera detector heads with active areas of 10 cm/spl times/20 cm have been built, tested and installed in the SPECT gantry to replace the 5 cm/spl times/5 cm detectors. The new gamma cameras are based on pixellated NaI(Tl) crystal scintillator arrays, coupled to arrays of compact position-sensitive photomultiplier tubes (PSPMT) to achieve high spatial resolution in a compact, low profile device. A novel cost-effective readout is utilized. The two detector heads are based on a 4/spl times/8 array of Hamamatsu R8520-C12 position sensitive photomultiplier tubes. Each PSPMT array is coupled to a pixellated 10 cm/spl times/20 cm NaI(Tl) scintillator crystal array with individual crystal elements of 2 mm/spl times/2 mm/spl times/15 mm in size and a septum of 0.25 mm between elements. Samples of phantom and animal studies are presented. The detectors are capable of imaging /sup 125/I and /sup 99m/Tc labeled radiopharmaceuticals in live mice.
Programmable virtual source/drain MOSFETs (2004)

We present a MOSFET structure with programmable virtual source/drain (PVS) that can be realized by the erase operation of an NVM device. Compared with the side-gate MOSFET, the proposed transistor has structural advantages, including non-external biasing and high integration density. The excellent retention performance of the fabricated twin SONOS memory (TSM) transistor that minimizes the loss of charges is also obtained. These characteristics confirm that the TSM transistor can be used for the programmable virtual source/drain device. From device simulation and experimental works, it is clearly observed that the programmable virtual source/drain, thanks to a positively charged nitride, brings about small drain leakage and well-controlled short channel effect in normal MOSFET operation. The PVS MOSFET appears to be a good candidate for low operating power appliance in the nano-scale regime.
Nuclear Hormone Receptor Medicinal Chemistry (2010)

Abstract This chapter will be focused on recent advances in the medicinal chemistry of agonist, antagonist, and modulator ligands of selected nuclear hormone receptors (NHRs) that are of special interest in the metabolic diseases therapeutic area (diabetes, obesity and dyslipidemia/atherosclerosis). These NHRs include established biological targets such as the peroxisome proliferator‐activated receptors (PPARs), the liver X receptors (LXRs), and the farnesoid X receptors (FXRs), for which ligands have reached either clinical development or have been approved for clinical usage. Other more recent targets of interest to metabolic diseases include HNF and Rev‐erb.
Supplementary Figure Legend from Hsp27 Regulates Epithelial Mesenchymal Transition, Metastasis, and Circulating Tumor Cells in Prostate Cancer (2023)

&lt;p&gt;PDF file - 94K&lt;/p&gt;
Impact of Prosthesis Length on Tympanic Membrane's and Annular Ligament's Stiffness and the Resulting Middle Ear Sound Transmission (2016)

Tension has a significant impact on the METF after middle ear reconstruction. As little tension as possible should be used to enable best sound transmission. Stabilization of prosthesis should be achieved with dislocation devices to ensure secure coupling to the ossicular remnants without creating additional tension.
Measured Haplotype Analysis of the Angiotensin-I Converting Enzyme Gene (1998)

Linkage and segregation analysis have shown that circulating angiotensin-I converting enzyme (ACE) levels are influenced by a major quantitative trait locus that maps within or close to the ACE gene. The D variant of a 287 bp insertion/deletion (I/D) polymorphism in intron 16 of the gene is associated with high ACE levels and may also be related to increased risk of cardiovascular disease. Multiple variants that are in linkage disequilibrium with the I/D polymorphism have been described, but it is unknown if any of these are directly implicated, alone or in combination with as yet undiscovered variants, in the determination of ACE levels. An analysis of 10 polymorphisms spanning 26 kb of the ACE gene revealed a limited number of haplotypes in Caucasian British families due to strong linkage disequilibrium operating over this small chromosomal region. A haplotype tree (cladogram) was constructed with three main branches (clades A-C) which account for 90% of the observed haplotypes. Clade C is most likely derived from clades A and B following an ancestral recombination event. This evolutionary information was then used to direct a series of nested, measured haplotype analyses that excluded upstream sequences, including the ACE promoter, from harbouring the major ACE-linked variant that explains 36% of the total trait variability. Residual familial correlations were highly significant, suggesting the influence of additional unlinked genes. Our results demonstrate that a combined cladistic/measured haplotype analysis of polymorphisms within a gene provides a powerful means to localize variants that directly influence a quantitative trait.
Diffuse-Adhering Escherichia coli (DAEC) as a Putative Cause of Diarrhea in Mayan Children in Mexico (1991)

Diarrhea is a major cause of infantile morbidity and mortality in developing countries. A community-based, case control study was conducted in a southern Mexican Mayan village for 3 weeks during the peak diarrhea period to prospectively identify the infectious agents associated with childhood diarrheal disease. Several enteropathogens were isolated from stools of 34 of 58 cases, although none was significantly associated with diarrhea. For the 24 cases from which no enteropathogens were isolated, diffuse-adhering Escherichia coli (DAEC) strains were significantly associated with diarrheal disease (P less than .02; odds ratio = 6; 95% confidence limit, 1.08-99.0). DAEC were highly heterogeneous with respect to plasmid content and serotype. Three DNA probes designed to differentiate E. coli exhibiting localized, diffuse, or aggregative adherence were compared with results from a standard HeLa cell binding assay to assess the utility of these probes in the field. This study provides evidence for the potential pathogenic capacity of DAEC and underscores the variety of diarrheal agents operating within a community.
Effectiveness of Iron Oxide Nanoparticles for MR Imaging and Tissue Ablation (2018)

Background: The introduction of new less invasive and non-invasive techniques for treating cardiac arrhythmias and neoplastic tissues has enhanced interest in medical imaging and iron oxide nanoparticles. The main scope of this review is to provide an overview on the usage of iron oxide nanoparticles (IONP) in magnetic resonance imaging (MRI) and thermal ablation. Methods: Several methods have been proposed to ablate abnormal growth and myocardial arrhythmia; namely surgical, radiofrequency, chemical and cryoablation. Fluoroscopy, multi-detector computed tomography, MRI as well as ultrasound are currently used for diagnosis and guiding therapies. Image-guided techniques help in visualizing the targets, precise delivering/verifying the treatment and follow up the prognosis. Results: Over one hundred papers were included in this review; the majority of the papers addressed the unique features of IONP and MRI settings. IONP have attracted special interest in MRI and thermal ablation due to their high relaxivity, biocompatibility, magnetic heating and low toxicity. The concept of ablation by magnetic nanoparticles is based on depositing magnetic nanoparticles in the tumor and their subsequent heating by an external alternating magnetic field. IONP have been used as: 1) MR contrast media for visualizing pathologic lesions before, during, and after ablation, 2) hyperthermal agents for generating heat during exposure to alternating magnetic field and 3) magnetic vectors (drugs and gene carriers) guided by magnetic field gradients to deliver therapies to pathologic lesions. IONP highlight ablated lesions in neighboring healthy tissue or organs due to improper targeting of lesions. It also enhances the vascular tree for proper catheter navigation. Conclusion: Iron oxide nanoparticles incorporate good biocompatibility and safety margin with their unique magnetic and thermic properties. IONP can be delivered locally and systemically (with caution). Furthermore, they blend diagnosis and treatment. The provision of pre-, during and post-ablation lesion characterization on IONP-contrast enhanced MRI might be helpful in complex ablation procedures and treatment. Keywords: Ablation, myocardial arrhythmia, contrast media, hyperthermia, iron oxide nanoparticles, magnetic resonance imaging, tumors.
A Quantitative Analysis of Current Practices in Optical Flow Estimation and the Principles Behind Them (2013)

The accuracy of optical flow estimation algorithms has been improving steadily as evidenced by results on the Middlebury optical flow benchmark. The typical formulation, however, has changed little since the work of Horn and Schunck. We attempt to uncover what has made recent advances possible through a thorough analysis of how the objective function, the optimization method, and modern implementation practices influence accuracy. We discover that “classical” flow formulations perform surprisingly well when combined with modern optimization and implementation techniques. One key implementation detail is the median filtering of intermediate flow fields during optimization. While this improves the robustness of classical methods it actually leads to higher energy solutions, meaning that these methods are not optimizing the original objective function. To understand the principles behind this phenomenon, we derive a new objective function that formalizes the median filtering heuristic. This objective function includes a non-local smoothness term that robustly integrates flow estimates over large spatial neighborhoods. By modifying this new term to include information about flow and image boundaries we develop a method that can better preserve motion details. To take advantage of the trend towards video in wide-screen format, we further introduce an asymmetric pyramid downsampling scheme that enables the estimation of longer range horizontal motions. The methods are evaluated on the Middlebury, MPI Sintel, and KITTI datasets using the same parameter settings.
Fundamentals of Digital Document Enhancement and Restoration (1997)

Digital document resolution conversion and enhancement is a field of image processing with two specific goals that define the field and its problems. One goal is to enable document portability by processing a document bit map in a manner that enables its displayed or printed form to be consistent in appearance when rendered by various devices. A second goal is to arrive at documents with an enhanced appearance over that attainable by directly printing the given bit map. The goals are typically achieved through spatial resolution conversion and quantization range conversion. For the image processing problems encountered, the image class and the processing setting tend to be well defined. Also, a significant legacy has been developed that defines the language of this technology. This chapter provides a general description of the field, and defines the basic terms and methods that are examined in detail in subsequent chapters.
Reconfigurable computing in the era of post-silicon scaling [panel discussion] (2013)

Summary form only given, as follows. Although transistor densities continue to scale exponentially, the failure of Dennard Scaling prevents us from maximally utilizing die area in future power-constrained multicore processors-a phenomenon referred to as "Dark Silicon". Alternative energy-efficient architectures based on FPGAs, GPGPUs, ASICs, MPPAs, etc. are likely to continue on an exponential scaling trajectory while outperforming conventional architectures by an order-of-magnitude or more. With the impending threat of dark silicon, there is a critical window of opportunity for reconfigurable computing to become a mainstream ingredient and driver of future, scalable computer architectures. Before this can happen, major challenges and opportunities must be addressed: (1) how to gracefully integrate reconfigurable computing into existing software and hardware ecosystems, (2) how to build tools, languages, and compilers for agile application development and debugging, (3) how to identify and exploit emerging applications in datacenters and in energy-constrained form factors, (4) how to train and educate students and practitioners to use these systems in sustainable ways, and (5) how to define new and stable boundaries between software and hardware that make it easier to exploit reconfigurable computing. This panel brings together pioneers and experts in computer architecture and reconfigurable computing to discuss opportunities and challenges in the wake of dark silicon.
Automated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia (2017)

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications.
Advancing photonic design and measurements with artificial intelligence (2021)

Discovering novel, unconventional optical designs in combination with advanced machine-learning assisted data analysis techniques can uniquely enable new phenomena and breakthrough advances in many areas including imaging, sensing, energy, and quantum information technology. It demonstrated that compared to other inverse-design approaches that require extreme computation power to undertake a comprehensive search within a large parameter space, machine learning assisted topology optimization can expand the design space while improving the computational efficiency. This talk will highlight our most recent findings on 1) merging topology optimization with artificial-intelligence-assisted algorithms and 2) integrating machine-learning based analysis with photonic design and quantum optical measurements.
Design, synthesis, anticancer, and docking of some S‐ and/or N‐heterocyclic derivatives as VEGFR‐2 inhibitors (2021)

Novel heterocyclic derivatives (4-22) were designed, synthesized, and evaluated against hepatocellular carcinoma type (HepG2) and breast cancer (MCF-7) cells, targeting the VEGFR-2 enzyme. Compounds 18, 10, 13, 11, and 14 were found to be the most potent derivatives against both the HepG2 and MCF-7 cancer cell lines, with GI<sub>50</sub> = 2.11, 2.54 µM, 3.16, 3.64 µM, 3.24, 6.99 µM, 7.41, 6.49 µM and 8.08, 10.46 µM, respectively. Compounds 18 and 10 showed higher activities against both HepG2 and MCF-7 cells than sorafenib (GI<sub>50</sub> = 9.18, 5.47 µM, respectively) and doxorubicin (GI<sub>50</sub> = 7.94, 8.07 µM, respectively). Compounds 13, 11, and 14 showed higher activities than sorafenib against HepG2 cancer cells, but lower activities against MCF-7 cells. Compounds 18, 13, and 10 were more potent than sorafenib, inhibiting vascular endothelial growth factor receptor-2 (VEGFR-2) at GI<sub>50</sub> values of 0.05, 0.06, and 0.08 µM, respectively. Compound 11 inhibited VEGFR-2 at an IC<sub>50</sub> value of 0.10 µM, which is equipotent to sorafenib. Compound 14 inhibited VEGFR-2 at an IC<sub>50</sub> value of 0.11 µM, which is nearly equipotent to sorafenib. The tested compounds have more selectivity against cancer cell lines. Compounds 18, 10, 13, 11, and 14 are, respectively, 16.76, 9.24, 6.06, 2.78, and 2.85 times more toxic in HePpG2 cancer cells than in VERO normal cells. Also, compounds 18, 10, 13, 11, and 14 are, respectively, 14.07, 8.02, 2.81, 3.18, and 2.20 times more toxic in MCF-7 than in VERO normal cells. The most active compounds, 10, 13, and 18, showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile.
Experiences with approximating queries in Microsoft's production big-data clusters (2019)

With the rapidly growing volume of data, it is more attractive than ever to leverage approximations to answer analytic queries. Sampling is a powerful technique which has been studied extensively from the point of view of facilitating approximation. Yet, there has been no large-scale study of effectiveness of sampling techniques in big data systems. In this paper, we describe an in-depth study of the sampling-based approximation techniques that we have deployed in Microsoft's big data clusters. We explain the choices we made to implement approximation, identify the usage cases, and study detailed data that sheds insight on the usefulness of doing sampling based approximation.
New applications of the infrared CCD camera (1996)

In Japan, two dimensional IRCCD cameras such as Nikon's LAIRD 3 have been sold by various manufacturers. In addition to the staring type IR cameras, there are mechanical scanning type IR cameras which are also receiving much attention in the market. The primary applications of the IR camera market have been night-time security surveillance, non-destructive testing and/or process control in the industrial environment. In such applications, infrared radiation emitted from the observed object is seen as heat. Thus, many IR cameras have been designed to maximize the amount of IR radiation collected from an observed object. One new application for the LAIRD3 camera is to observe the spectral signature of an object over a specific spectral band in order to determine the presence and location of a specific gas. This paper described the results of using this method to detect the presence and location of methane in an observed environment.
Analogue of the van Cittert–Zernike theorem for statistically homogeneous wave fields (1990)

A theorem is presented that expresses a correspondence between the degree of spatial coherence of statistically homogeneous fields and the complex amplitude in certain monochromatic fields. The theorem is illustrated by an example that shows the behavior of the degree of spatial coherence of certain partially coherent fields throughout a three-dimensional volume region.
0.125 Terawatt Kilohertz Laser System (2005)

Recently there has been significant progress in the development of high-repetition-rate, high-peak-power Ti:sapphire systems.1
Optical Verification of Microbubble Response to Acoustic Radiation Force in Large Vessels With In Vivo Results (2015)

This study provides the first optical observation of microbubble-binding dynamics in large blood vessel environments with application of a modulated acoustic radiation force beam sequence. With targeted adhesion, secondary radiation forces were unable to produce large aggregates of adherent microbubbles. Additionally, the new phenomenon called control peak was observed both in vitro and in vivo in a murine model for the first time. The findings in this study provide us with a better understanding of microbubble behaviors in large blood vessel environments with application of acoustic radiation force and could potentially guide future beam sequence designs or signal processing routines for enhanced ultrasound molecular imaging.
Education in image sciences and engineering at the Technion (2002)

The departments of electrical engineering and computer science at Technion offer a broad spectrum of courses in digital and optical signals and imaging systems, and a research environment most suitable for specialization in image system engineering. We describe a few of the courses and discuss some issues related to their teaching.
Temperature and stress dependence of creep life of welded joints in strength enhanced high Cr ferritic steels (2009)

Overestimation of creep life is a serious problem that happens in long term creep of welded joints made of 9–12%Cr ferritic steels. Creep rupture data of welded joints made of grades 91, 92 and 122 steels were subjected to multiregion analyses paying attention to change in activation energy Q for creep rupture life. A region with a low Q value was found in long term creep of the welded joints. Therefore, long term creep rupture life of the welded joints can be overestimated when it is evaluated by temperature acceleration tests based on a high Q value of short term data. The decrease in activation energy was closely related to the change in fracture location from base metal to heat affected zone. Activation energy and stress exponent for creep rupture life take similar values both in base metal and in the welded joint, though the transition to the low Q region starts at shorter time in cross-welded joints. This fact suggests that creep rupture life can be formulated in a unified manner irrespective of base metal or welded joint. Weld strength factor of high Cr ferritic steels should have a lower limit insensitive to service temperature.