gebhart/patrepeval huggingface dataset:
MicroRNAs Involved in Small-cell Lung Cancer as Possible Agents for Treatment and Identification of New Targets (2021)

Small-cell lung cancer, a neuro-endocrine type of lung cancers, responds very well to chemotherapy-based agents. However, a high frequency of relapse due to adaptive resistance is observed. Immunotherapy-based treatments with checkpoint inhibitors has resulted in improvement of treatment but the responses are not as impressive as in other types of tumor. Therefore, identification of new targets and treatment modalities is an important issue. After searching the literature, we identified eight down-regulated microRNAs involved in radiation- and chemotherapy-induced resistance, as well as three up-regulated and four down-regulated miRNAs with impacts on proliferation, invasion and apoptosis of small-cell lung cancer cells in vitro. Furthermore, one up-regulated and four down-regulated microRNAs with in vivo activity in SCLC cell xenografts were identified. The identified microRNAs are candidates for inhibition or reconstitution therapy. The corresponding targets are candidates for inhibition or functional reconstitution with antibody-based moieties or small molecules.
HACCLE: An Ecosystem for Building Secure Multi-Party Computations. (2020)

Cryptographic techniques have the potential to enable distrusting parties to collaborate in fundamentally new ways, but their practical implementation poses numerous challenges. An important class of such cryptographic techniques is known as secure multi-party computation (MPC). In an effort to provide an ecosystem for building secure MPC applications using higher degrees of automation, we present the HACCLE (High Assurance Compositional Cryptography: Languages and Environments) toolchain. The HACCLE toolchain contains an embedded domain-specific language (Harpoon) for software developers without cryptographic expertise to write MPC-based programs. Harpoon programs are compiled into acyclic circuits represented in HACCLE's Intermediate Representation (HIR) that serves as an abstraction for implementing a computation using different cryptographic protocols such as secret sharing, homomorphic encryption, or garbled circuits. Implementations of different cryptographic protocols serve as different backends of our toolchain. The extensible design of HIR allows cryptographic experts to plug in new primitives and protocols to realize computations.We have implemented HACCLE, and used it to program interesting algorithms and applications (e.g., secure auction, matrix-vector multiplication, and merge sort). We show that the performance is improved by using our optimization strategies and heuristics.
Measurement and Data (2001)

This chapter contains sections titled: 2.1 Introduction, 2.2 Types of Measurement, 2.3 Distance Measures, 2.4 Transforming Data, 2.5 The Form of Data, 2.6 Data Quality for Individual Measurements, 2.7 Data Quality for Collections of Data, 2.8 Conclusion, 2.9 Further Reading
Somatostatin Analogues and Multiple Receptors: Possible Physiological Roles (2007)

The availability of transfected cell lines expressing the five cloned somatostatin receptors has allowed extensive families of synthetic analogues to be screened for their binding affinities to these receptors. Cyclic octapeptides in the octreotide series have high affinity for sstr2 and low affinity for sstr1 and sstr4. Modifications to these analogues can have profound effects on their residual affinity for sstr3 and sstr5. Several linear peptides, incorporating the critical core-D-Trp-Lys-sequence of all active analogues, exhibit selectivity for either sstr3, sstr5 or both, but little affinity for the other three. From these analogues we have assembled a panel of compounds with a useful degree of specificity for sstr2, sstr3 and sstr5 and these have been used to evaluate receptor involvement in various physiological processes. Inhibition of pituitary growth hormone release correlates completely with sstr2 affinity and it appears from preliminary results that inhibition of pancreatic glucagon release is also sstr2 mediated. Effects on gastric acid secretion show a high degree of dependence on sstr2 affinity. Inhibition in vivo by somatostatin of insulin release, amylase release and binding to rat pancreatic acinar cells is highly correlated with sstr5 receptor affinity. Gastric smooth muscle cells have particularly high affinity for sstr3 receptor ligands. The availability of receptor-specific ligands is proving to be of great value in elucidating the physiological roles of each receptor. It is anticipated that these and future generations of analogues will have distinct therapeutic advantages over somatostatin itself and presently available cyclic octapeptides.
Adaptive Core Simulation Employing Discrete Inverse Theory - Part I: Theory (2005)

Use of adaptive simulation is intended to improve the fidelity and robustness of important core attribute predictions such as core power distribution, thermal margins, and core reactivity. Adaptive simulation utilizes a selected set of past and current reactor measurements of reactor observables, i.e., in-core instrumentation readings, to adapt the simulation in a meaningful way. A meaningful adaption will result in high-fidelity and robust adapted core simulator models. To perform adaption, we propose an inverse theory approach in which the multitudes of input data to core simulators, i.e., reactor physics and thermal-hydraulic data, are to be adjusted to improve agreement with measured observables while keeping core simulator models unadapted. At first glance, devising such adaption for typical core simulators with millions of input and observables data would spawn not only several prohibitive challenges but also numerous disparaging concerns. The challenges include the computational burdens of the sensitivity-type calculations required to construct Jacobian operators for the core simulator models. Also, the computational burdens of the uncertainty-type calculations required to estimate the uncertainty information of core simulator input data present a demanding challenge. The concerns however are mainly related to the reliability of the adjusted input data. The methodologies of adaptive simulation are well established in the literature of data adjustment. We adopt the same general framework for data adjustment; however, we refrain from solving the fundamental adjustment equations in a conventional manner. We demonstrate the use of our so-called Efficient Subspace Methods (ESMs) to overcome the computational and storage burdens associated with the core adaption problem. We illustrate the successful use of ESM-based adaptive techniques for a typical boiling water reactor core simulator adaption problem.
A variable eigenvalue approach to the solution of phase‐change problems (1977)

Abstract A zeroth order variable eigenvalue approach is used to solve the melting (or solidification) problem for a slab initially at a uniform temperature different from the melting temperature and two boundaries maintained at specified temperatures. The accuracy of the method is investigated by applying this approach to obtain a closed form solution for the melting of a semi‐infinite medium for which analytical solution is available and comparing both results.
A Boolean network model of the growth plate (2010)

During endochondral ossification, chondrocyte growth and differentiation is controlled by many local signalling pathways. Due to the many cross talks and feedback mechanisms, these interwoven pathways display a network like structure. In this study, a large-scale literature-based Boolean model of the growth plate network was developed. The network is able to capture the different states the chondrocytes go through as they progress through the growth plate. In a first corroboration step, the effect of mutations in various signalling pathways of the growth plate network was investigated.
The Technological Development of Minimally Invasive Spine Surgery (2014)

Minimally invasive spine surgery has its roots in the mid-twentieth century with a few surgeons and a few techniques, but it has now developed into a large field of progressive spinal surgery. A wide range of techniques are now called "minimally invasive," and case reports are submitted constantly with new "minimally invasive" approaches to spinal pathology. As minimally invasive spine surgery has become more mainstream over the past ten years, in this paper we discuss its history and development.
BMX-Mediated Regulation of Multiple Tyrosine Kinases Contributes to Castration Resistance in Prostate Cancer (2018)

Prostate cancer responds to therapies that suppress androgen receptor (AR) activity (androgen deprivation therapy, ADT) but invariably progresses to castration-resistant prostate cancer (CRPC). The Tec family nonreceptor tyrosine kinase BMX is activated downstream of PI3K and has been implicated in regulation of multiple pathways and in the development of cancers including prostate cancer. However, its precise mechanisms of action, and particularly its endogenous substrates, remain to be established. Here, we demonstrate that BMX expression in prostate cancer is suppressed directly by AR via binding to the BMX gene and that BMX expression is subsequently rapidly increased in response to ADT. BMX contributed to CRPC development in cell line and xenograft models by positively regulating the activities of multiple receptor tyrosine kinases through phosphorylation of a phosphotyrosine-tyrosine (pYY) motif in their activation loop, generating pYpY that is required for full kinase activity. To assess BMX activity <i>in vivo</i>, we generated a BMX substrate-specific antibody (anti-pYpY) and found that its reactivity correlated with BMX expression in clinical samples, supporting pYY as an <i>in vivo</i> substrate. Inhibition of BMX with ibrutinib (developed as an inhibitor of the related Tec kinase BTK) or another BMX inhibitor BMX-IN-1 markedly enhanced the response to castration in a prostate cancer xenograft model. These data indicate that increased BMX in response to ADT contributes to enhanced tyrosine kinase signaling and the subsequent emergence of CRPC, and that combination therapies targeting AR and BMX may be effective in a subset of patients.<b>Significance:</b> The tyrosine kinase BMX is negatively regulated by androgen and contributes to castration-resistant prostate cancer by enhancing the phosphorylation and activation of multiple receptor tyrosine kinases following ADT. <i>Cancer Res; 78(18); 5203-15. ©2018 AACR</i>.
The Status of Polycyclic Group-Based Cryptography: A Survey and Open\n Problems (2016)

Polycyclic groups are natural generalizations of cyclic groups but with more\ncomplicated algorithmic properties. They are finitely presented and the word,\nconjugacy, and isomorphism decision problems are all solvable in these groups.\nMoreover, the non-virtually nilpotent ones exhibit an exponential growth rate.\nThese properties make them suitable for use in group-based cryptography, which\nwas proposed in 2004 by Eick and Kahrobaei. Since then, many cryptosystems have\nbeen created that employ polycyclic groups. These include key exchanges such as\nnon-commutative ElGamal, authentication schemes based on the twisted conjugacy\nproblem, and secret sharing via the word problem. In response, heuristic and\ndeterministic methods of cryptanalysis have been developed, including the\nlength-based and linear decomposition attacks. Despite these efforts, there are\nclasses of infinite polycyclic groups that remain suitable for cryptography.\nThe analysis of algorithms for search and decision problems in polycyclic\ngroups has also been developed. In addition to results for the aforementioned\nproblems we present those concerning polycyclic representations, group\nmorphisms, and orbit decidability. Though much progress has been made, many\nalgorithmic and complexity problems remain unsolved, we conclude with a number\nof them. Of particular interest is to show that cryptosystems using infinite\npolycyclic groups are resistant to cryptanalysis on a quantum computer.\n
Wave propagation downstream of a high power helicon in a dipolelike magnetic field (2010)

The wave propagating downstream of a high power helicon source in a diverging magnetic field was investigated experimentally. The magnetic field of the wave has been measured both axially and radially. The three-dimensional structure of the propagating wave is observed and its wavelength and phase velocity are determined. The measurements are compared to predictions from helicon theory and that of a freely propagating whistler wave. The implications of this work on the helicon as a thruster are also discussed.
AutoStitcher: An Automated Program for Efficient and Robust Reconstruction of Digitized Whole Histological Sections from Tissue Fragments (2016)

In applications involving large tissue specimens that have been sectioned into smaller tissue fragments, manual reconstruction of a "pseudo whole-mount" histological section (PWMHS) can facilitate (a) pathological disease annotation, and (b) image registration and correlation with radiological images. We have previously presented a program called HistoStitcher, which allows for more efficient manual reconstruction than general purpose image editing tools (such as Photoshop). However HistoStitcher is still manual and hence can be laborious and subjective, especially when doing large cohort studies. In this work we present AutoStitcher, a novel automated algorithm for reconstructing PWMHSs from digitized tissue fragments. AutoStitcher reconstructs ("stitches") a PWMHS from a set of 4 fragments by optimizing a novel cost function that is domain-inspired to ensure (i) alignment of similar tissue regions, and (ii) contiguity of the prostate boundary. The algorithm achieves computational efficiency by performing reconstruction in a multi-resolution hierarchy. Automated PWMHS reconstruction results (via AutoStitcher) were quantitatively and qualitatively compared to manual reconstructions obtained via HistoStitcher for 113 prostate pathology sections. Distances between corresponding fiducials placed on each of the automated and manual reconstruction results were between 2.7%-3.2%, reflecting their excellent visual similarity.
Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand (2021)

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.
Perceptual basis of evolving Western musical styles (2013)

The brain processes temporal statistics to predict future events and to categorize perceptual objects. These statistics, called expectancies, are found in music perception, and they span a variety of different features and time scales. Specifically, there is evidence that music perception involves strong expectancies regarding the distribution of a melodic interval, namely, the distance between two consecutive notes within the context of another. The recent availability of a large Western music dataset, consisting of the historical record condensed as melodic interval counts, has opened new possibilities for data-driven analysis of musical perception. In this context, we present an analytical approach that, based on cognitive theories of music expectation and machine learning techniques, recovers a set of factors that accurately identifies historical trends and stylistic transitions between the Baroque, Classical, Romantic, and Post-Romantic periods. We also offer a plausible musicological and cognitive interpretation of these factors, allowing us to propose them as data-driven principles of melodic expectation.
Reciprocating Heat Engine with Superadiabatic Combustion in Porous Media. (1995)

A new method of energy conversion from combustion heat to mechanical power has been proposed on the basis of superadiabatic combustion in a porous medium. The system consists of two pistons and a thin porous medium in a cylinder ; one being a displacer piston and the other a power piston. These create reciprocating motions with a phase relation, similar to those of an ordinary Stirling engine. By means of the reciprocating flow system, the residual combustion gas enthalpy is effectively regenerated to induce enthalpy increase in the mixture through the porous medium, which served as a heat-storage medium. Due to heat recirculation, the maximum temperature is higher than the theoretical one in free space. The thermal efficiency is higher than those of the conventional Otto and diesel cycles under a range of low compression ratios.
Towards the realization of clinical extracellular vesicle diagnostics: challenges and opportunities (2015)

Extracellular vesicles (EVs) have been intensively researched in the last decade. As a result, many reports have revealed that disease-associated EVs can indeed be used as novel diagnostic tools to serve as a noninvasive 'liquid biopsy'. EVs are multi-molecular complexes and each molecule can be targeted for diagnostics. An increasing number of targetable molecules in EVs, such as miRNAs or proteins, have been identified and the accumulation of evidence will likely result in the identification of consensus EV markers. Also highlighted here are some advanced technologies that can be used as next generation assays. These technologies may overcome several challenges that continue to hinder the clinical use of EV diagnostics. A perspective is outlined for the potential contribution of EV research to develop diagnostic technologies for cancer and various other diseases.
Mapping Polyclonal Antibody Responses in Non-human Primates Vaccinated with HIV Env Trimer Subunit Vaccines (2020)

Rational immunogen design aims to focus antibody responses to vulnerable sites on primary antigens. Given the size of these antigens, there is, however, potential for eliciting unwanted, off-target responses. Here, we use our electron microscopy polyclonal epitope mapping approach to describe the antibody specificities elicited by immunization of non-human primates with soluble HIV envelope trimers and subsequent repeated viral challenge. An increased diversity of epitopes recognized and the approach angle by which these antibodies bind constitute a hallmark of the humoral response in most protected animals. We also show that fusion peptide-specific antibodies are likely responsible for some neutralization breadth. Moreover, cryoelectron microscopy (cryo-EM) analysis of a fully protected animal reveals a high degree of clonality within a subset of putatively neutralizing antibodies, enabling a detailed molecular description of the antibody paratope. Our results provide important insights into the immune response against a vaccine candidate that entered into clinical trials in 2019.
Proteome Analysis of Gastric Cancer Metastasis by Two-Dimensional Gel Electrophoresis and Matrix Assisted Laser Desorption/Ionization-Mass Spectrometry for Identification of Metastasis-Related Proteins (2004)

A well-described animal model was used to understand the molecular mechanisms of carcinogenesis and metastasis of gastric cancer at the protein level. Gastric cancer was induced in 12 Wistar rats by oral administration of N-methyl-N'-Nitro-N-Nitrosoguanidine (MNNG). The protein expression patterns of normal gastric tissue, gastric cancer, and corresponding metastases were analyzed by proteomics in matched tissues of 3 rats. Proteins in the region of molecular masses of 15-75 kDa and an isoelectric point of 3-7 were separated by two-dimensional electrophoresis (2-DE) and identified by peptide fingerprinting with matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). Twenty-seven spots corresponding to 25 different proteins served as landmarks for comparison between tissues. The identified proteins included cytoskeletal proteins, stress associated proteins, proteins involved in signal transduction, cell proliferation and differentiation, and metabolism. Eleven proteins were up-regulated and 2 proteins were down-regulated in tumor tissue when compared with normal tissue. Twelve proteins were up-regulated and 8 proteins were down-regulated in the metastases when compared with the primary tumor. The overexpression of HSP27 in gastric cancer was confirmed by immunohistochemical analysis of human gastric cancer specimens. Combining well-defined animal models with proteome analysis will improve our understanding of the fundamental changes that contribute to the process of carcinogenesis and the formation of metastases in gastric cancer.
Design and Implementation of a Large Scale Tree-Based QR Decomposition Using a 3D Virtual Systolic Array and a Lightweight Runtime (2014)

A systolic array provides an alternative computing paradigm to the von Neumann architecture. Though its hardware implementation has failed as a paradigm to design integrated circuits in the past, we are now discovering that the systolic array as a software virtualization layer can lead to an extremely scalable execution paradigm. To demonstrate this scalability, in this paper, we design and implement a 3D virtual systolic array to compute a tile QR decomposition of a tall-and-skinny dense matrix. Our implementation is based on a state-of-the-art algorithm that factorizes a panel based on a tree-reduction. Freed from the constraint of a planar layout, we present a three-dimensional virtual systolic array architecture for this algorithm. Using a runtime developed as a part of the Parallel Ultra Light Systolic Array Runtime (PULSAR) project, we demonstrate on a Cray-XT5 machine how our virtual systolic array can be mapped to a large-scale machine and obtain excellent parallel performance. This is an important contribution since such a QR decomposition is used, for example, to compute a least squares solution of an overdetermined system, which arises in many scientific and engineering problems.
New Hemodynamic Parameters in Peri-Operative and Critical Care—Challenges in Translation (2023)

Hemodynamic monitoring technologies are evolving continuously-a large number of bedside monitoring options are becoming available in the clinic. Methods such as echocardiography, electrical bioimpedance, and calibrated/uncalibrated analysis of pulse contours are becoming increasingly common. This is leading to a decline in the use of highly invasive monitoring and allowing for safer, more accurate, and continuous measurements. The new devices mainly aim to monitor the well-known hemodynamic variables (e.g., novel pulse contour, bioreactance methods are aimed at measuring widely-used variables such as blood pressure, cardiac output). Even though hemodynamic monitoring is now safer and more accurate, a number of issues remain due to the limited amount of information available for diagnosis and treatment. Extensive work is being carried out in order to allow for more hemodynamic parameters to be measured in the clinic. In this review, we identify and discuss the main sensing strategies aimed at obtaining a more complete picture of the hemodynamic status of a patient, namely: (i) measurement of the circulatory system response to a defined stimulus; (ii) measurement of the microcirculation; (iii) technologies for assessing dynamic vascular mechanisms; and (iv) machine learning methods. By analyzing these four main research strategies, we aim to convey the key aspects, challenges, and clinical value of measuring novel hemodynamic parameters in critical care.