gebhart/patrepeval huggingface dataset:
The convergence of embryonic & cancer signaling pathways: Role in tumor cell plasticity (2007)

Aggressive tumor cells share many characteristics with embryonic progenitors. During development, multipotent precursor cells undergo specific cell fate determination through the autocrine or paracrine delivery of signaling molecules. Similarly, during cancer progression, malignant cells release and receive cues that promote tumor growth and metastasis. In addition, the stem cell‐like plasticity of aggressive tumor cells, particularly melanoma, is suggested by their molecular signature, which defines a dedifferentiated, multipotent plastic phenotype ‐‐ that can respond to microenvironmental factors and influence other cells through epigenetic mechanisms. To address the issue of tumor cell plasticity and to understand the clinical implications of targeting this phenotype, we employed an innovative experimental approach. We used the embryonic microenvironment of the zebrafish as a biosensor for tumor‐derived signals. Using this model, we show that multipotent, aggressive melanoma cells secrete Nodal (a potent embryonic morphogen) and consequently can induce ectopic formation of the embryonic axis. Most noteworthy, we show that Nodal is present in human metastatic tumors, but not in normal skin, and thus may be involved in melanoma pathogenesis. Inhibition of Nodal signaling reduces melanoma cell invasiveness, colony formation, and tumorigenicity. Interestingly, Nodal inhibition also promotes the reversion of melanoma cells toward a melanocytic phenotype concomitant with a diminution of the plastic phenotype. These data suggest that Nodal signaling plays a key role in melanoma cell plasticity and tumorigenicity, thereby providing a previously unknown molecular target for regulating metastatic tumor cell plasticity and progression.
A software based profiling method for obtaining speedup stacks on commodity multi-cores (2014)

A key goodness metric of multi-threaded programs is how their execution times scale when increasing the number of threads. However, there are several bottlenecks that can limit the scalability of a multi-threaded program, e.g., contention for shared cache capacity and off-chip memory bandwidth; and synchronization overheads. In order to improve the scalability of a multi-threaded program, it is vital to be able to quantify how the program is impacted by these scalability bottlenecks. We present a software profiling method for obtaining speedup stacks. A speedup stack reports how much each scalability bottleneck limits the scalability of a multi-threaded program. It thereby quantifies how much its scalability can be improved by eliminating a given bottleneck. A software developer can use this information to determine what optimizations are most likely to improve scalability, while a computer architect can use it to analyze the resource demands of emerging workloads. The proposed method profiles the program on real commodity multi-cores (i.e., no simulations required) using existing performance counters. Consequently, the obtained speedup stacks accurately account for all idiosyncrasies of the machine on which the program is profiled. While the main contribution of this paper is the profiling method to obtain speedup stacks, we present several examples of how speedup stacks can be used to analyze the resource requirements of multi-threaded programs. Furthermore, we discuss how their scalability can be improved by both software developers and computer architects.
Long-Term Outcome after Pancreatic Stenting in Severe Chronic Pancreatitis (2005)

The majority (70 %) of patients with severe chronic pancreatitis who respond to pancreatic stenting maintain this response after definitive stent removal. However, a significantly higher re-stenting rate was observed in patients with chronic pancreatitis and pancreas divisum.
Tuning Structural Properties of WO3 Thin Films for Photoelectrocatalytic Water Oxidation (2021)

The preparation of tungsten oxide (WO3) thin film by direct current (DC) reactive sputtering magnetron method and its photoelectrocatalytic properties for water oxidation reaction are investigated using ultraviolet-visible radiation. The structural, morphological, and compositional properties of WO3 are fine-tuned by controlling thin film deposition time, and post-annealing temperature and environment. The findings suggest that the band gap of WO3 can be controlled by adjusting the post-annealing temperature; the band gap decreased from 3.2 to 2.7 eV by increasing the annealing temperature from 100 to 600 °C. The theoretical calculations of the WO3 bandgap and the density of state are performed by density functional theory (DFT). Following the band gap modification, the photoelectrocatalytic activity increased and the maximum photocurrent (0.9 mA/cm2 at 0.6 VSCE) is recorded with WO3 film heated at 500 °C. The WO3 film heated under air exhibits much better performance in photoelectrochemical water oxidation process than that of annealed under inert atmosphere, due to its structural variation. The change in sputtering time leads to the formation of WO3 with varying film thickness, and the maximum photocurrent is observed when the film thickness is approximately 150 nm. The electrical conductivity and charge transfer resistance are measured and correlated to the properties and the performance of the WO3 photoelectrodes. In addition, the WO3 photoelectrode exhibits excellent photoelectrochemical stability.
Identifying the Neuroanatomical Basis of Cognitive Impairment in Alzheimer's Disease by Correlation- and Nonlinearity-Aware Sparse Bayesian Learning (2014)

Predicting cognitive performance of subjects from their magnetic resonance imaging (MRI) measures and identifying relevant imaging biomarkers are important research topics in the study of Alzheimer's disease. Traditionally, this task is performed by formulating a linear regression problem. Recently, it is found that using a linear sparse regression model can achieve better prediction accuracy. However, most existing studies only focus on the exploitation of sparsity of regression coefficients, ignoring useful structure information in regression coefficients. Also, these linear sparse models may not capture more complicated and possibly nonlinear relationships between cognitive performance and MRI measures. Motivated by these observations, in this work we build a sparse multivariate regression model for this task and propose an empirical sparse Bayesian learning algorithm. Different from existing sparse algorithms, the proposed algorithm models the response as a nonlinear function of the predictors by extending the predictor matrix with block structures. Further, it exploits not only inter-vector correlation among regression coefficient vectors, but also intra-block correlation in each regression coefficient vector. Experiments on the Alzheimer's Disease Neuroimaging Initiative database showed that the proposed algorithm not only achieved better prediction performance than state-of-the-art competitive methods, but also effectively identified biologically meaningful patterns.
Using Optimal Dependency-Trees for Combinatorial Optimization: Learning the Structure of the Search Space (1997)

Many combinatorial optimization algorithms have no mechanism to capture inter-parameter dependencies. However, modeling such dependencies may allow an algorithm to concentrate its sampling more effectively on regions of the search space which have appeared promising in the past. We present an algorithm which incrementally learns second-order probability distributions from good solutions seen so far, uses these statistics to generate optimal (in terms of maximum likelihood) dependency trees to model these distributions, and then stochastically generates new candidate solutions from these trees. We test this algorithm on a variety of optimization problems. Our results indicate superior performance over other tested algorithms that either (1) do not explicitly use these dependencies, or (2) use these dependencies to generate a more restricted class of dependency graphs. Scott Davies was supported by a Graduate Student Research Fellowship from the National Science Foundation. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied of the National Science Foundation. Keywords:
Calibration, terrain reconstruction and path planning for a planetary exploration system (2001)

In this paper, three important preparation tasks of a planetary exploration system are described, namely calibration, terrain reconstruction and path planning. The calibration is retrieved from the images of the planetary terrain (the same images from which the 3D measurements of the terrain are obtained). Once the system has been calibrated, the same images can be used to estimate a digital elevation map of the environment around the lander. These images are first processed pairwise using a stereo algorithm yielding sub-pixel disparity maps. In order to perform the path planning a digital elevation map is required. An algorithm is described which can generate a regular digital elevation map at any desired resolution (interpolating if necessary) and easily takes occlusions into account. The results of the calibration and reconstruction are then used by the path planning module which is capable of computing the optimal path between points of interest of the terrain. 1
Copy-on-write B-tree finally beaten (2011)

A classic versioned data structure in storage and computer science is the copy-on-write (CoW) B-tree -- it underlies many of today's file systems and databases, including WAFL, ZFS, Btrfs and more. Unfortunately, it doesn't inherit the B-tree's optimality properties; it has poor space utilization, cannot offer fast updates, and relies on random IO to scale. Yet, nothing better has been developed since. We describe the `stratified B-tree', which beats all known semi-external memory versioned B-trees, including the CoW B-tree. In particular, it is the first versioned dictionary to achieve optimal tradeoffs between space, query and update performance.
Enantiomer‐Specific Positive Allosteric Modulation of the Type 1 Cannabinoid Receptor (2015)

Activation of the type 1 cannabinoid receptor (CB1) may be a means of treating neuropathic pain, glaucoma and neurodegenerative disorders where CB1 levels decline, such as Huntington's diseasse. Positive allosteric modulators (PAM) of CB1 enhance the potency and efficacy, and modify the signaling bias, of orthosteric ligands of CB1. Because PAMs lack inherent agonist activity, they may be safer and more therapeutically useful than orthosteric CB1 ligands that promote psychotropic side effects. The objective of this study was to characterize the activity of a novel racemic CB1 PAM – GAT211 – and its enantiomers – GAT228 and GAT229. We studied the activity of GAT211, GAT228, and GAT229 in terms of arrestin2 recruitment, PLCβ3 and ERK1/2 phosphorylation, cAMP, and 35SGTPγS in vitro. GAT211 was a modest PAM and weak partial agonist that displayed Gαi/o (ERK) bias. The R-(+)-enantiomer, GAT228, was an unbiased CB1 allosteric agonist, and the S-(+)-enantiomer, GAT229, was a potent, Gαi/o-biased CB1 PAM. In radioligand binding assays, GAT228 and GAT229 behaved as PAMs of orthosteric ligand binding, with GAT229 exhibiting higher potency and efficacy. This study demonstrated that minor changes in ligand structure, such as chirality, can completely change the pharmacodynamic properties of CB1-targetted ligands. Candidate allosteric modulators should be thoroughly screened to determine their mechanisms of action across a range of signalling pathways. Funding support provided by NIH, CIHR, Dalhousie University, and the Huntington Society of Canada.
Dysregulation of autophagy and stress granule-related proteins in stress-driven Tau pathology (2018)

Imbalance of neuronal proteostasis associated with misfolding and aggregation of Tau protein is a common neurodegenerative feature in Alzheimer's disease (AD) and other Tauopathies. Consistent with suggestions that lifetime stress may be an important AD precipitating factor, we previously reported that environmental stress and high glucocorticoid (GC) levels induce accumulation of aggregated Tau; however, the molecular mechanisms for such process remain unclear. Herein, we monitor a novel interplay between RNA-binding proteins (RBPs) and autophagic machinery in the underlying mechanisms through which chronic stress and high GC levels impact on Tau proteostasis precipitating Tau aggregation. Using molecular, pharmacological and behavioral analysis, we demonstrate that chronic stress and high GC trigger mTOR-dependent inhibition of autophagy, leading to accumulation of Tau aggregates and cell death in P301L-Tau expressing mice and cells. In parallel, we found that environmental stress and GC disturb cellular homeostasis and trigger the insoluble accumulation of different RBPs, such as PABP, G3BP1, TIA-1, and FUS, shown to form stress granules (SGs) and Tau aggregation. Interestingly, an mTOR-driven pharmacological stimulation of autophagy attenuates the GC-driven accumulation of Tau and SG-related proteins as well as the related cell death, suggesting a critical interface between autophagy and the response of the SG-related protein in the neurodegenerative potential of chronic stress and GC. These studies provide novel insights into the RNA-protein intracellular signaling regulating the precipitating role of environmental stress and GC on Tau-driven brain pathology.
Intrahepatic Cholangiocarcinoma and Acute Intermittent Porphyria: A Case Report (2023)

Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.
An effective stannic oxide/graphitic carbon nitride (SnO2 NPs@g-C3N4) nanocomposite photocatalyst for organic pollutants degradation under visible-light (2023)

Organic compounds have enhanced different industrial outputs, but many related environmental challenges, such as groundwater and surface water pollution related to these compounds, have piqued governments' and citizens' interest worldwide. Photocatalysis has recently been proven to be an effective method of eliminating these pollutants. This study investigated the photocatalytic degradation of 1-naphthyl methylcarbamate (carbaryl pesticide) and methyl orange (dye) using an efficient SnO2 [email protected]3N4 nanocomposite photocatalyst. A straightforward solid-state technique created a mesoporous SnO2 [email protected]3N4 nanocomposite photocatalyst with various SnO2 NP concentrations. Various analytical approaches were used to characterize the SnO2 [email protected]3N4 nanocomposite photocatalyst, including X-ray powder diffraction (XRD) patterns, energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared spectra (FTIR), transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy (UV-Vis). The degradation of carbaryl, as a model pesticide and methyl orange as a model dye, under visible light was tested to determine the photocatalytic activity of the SnO2 [email protected]3N4 nanocomposite with various mass percentages of SnO2 NPs. The results showed that SnO2 NPs successfully improved the photoactivity of g-C3N4. The photocatalytic activity showed that the carbaryl photodegradation rate increased from 32 % by g-C3N4 to 85 % and 96 % for methyl orange by SnO2 [email protected]3N4 nanocomposite photocatalyst (20 %), indicating that SnO2 [email protected]3N4 nanocomposite is a promising photocatalyst for pesticides and dyes. The enhanced photodegradation effectiveness of SnO2 [email protected]3N4 nanocomposite photocatalyst was related to increased surface area and improved illumination radiation ability by successfully separating charge carriers.
DG-SOI ratioed logic with symmetric DG load - a novel approach for sub 50 mn LV/LP circuit design (2004)

This paper investigates the possibility of using SDG (symmetric double gate) device intrinsically on structure as a load device for DG-SOI based ratioed logic, To establish the feasibility and superiority of this approach an inverter and a NOR gate were designed, which exhibits considerable advantages. The work is then extented to show how the approach can also be used to built NAND and XOR gates to create a complete logic family. All the simulations are done for 50 nm gate length devices using SILVACO tools. Voltage transfer characteristics are studied for both SDG load and ADG (asymmetric double gate) inverter. The transient characteristics obtained with a 1.25 GHz pulse on the n/sup +/-poly gate and a 500 MHz on the p/sup +/-poly gate are also studied.
Saving energy with just in time instruction delivery (2002)

Just-In-Time instruction delivery is a general method for saving energy in a microprocessor by dynamically limiting the number of in-flight instructions. The goal is to save energy by (1) fetching valid instructions no sooner than necessary, avoiding cycles stalled in the pipeline - especially the issue queue, and (2) reducing the number of fetches and subsequent processing of mis-speculated instructions. A simple algorithm monitors performance and adjusts the maximum number of in-flight instructions at fairly long intervals, 100 K instructions in this study. The proposed JIT instruction delivery scheme provides the combined benefits of more targeted schemes proposed previously. With only a 3% performance degradation, energy savings in the fetch, decode pipe, and issue queue are 10%, 12%, and 40%, respectively.
Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets (2021)

To interrogate particular neuronal pathways in nonhuman primates under natural and stress-free conditions, we applied designer receptors exclusively activated by designer drugs (DREADDs) technology to common marmosets. We injected adeno-associated virus vectors expressing the excitatory DREADD hM3Dq into the unilateral substantia nigra (SN) in four marmosets. Using multi-tracer positron emission tomography imaging, we detected DREADD expression in vivo, which was confirmed in nigrostriatal dopamine neurons by immunohistochemistry, as well as by assessed activation of the SN following agonist administration. The marmosets rotated in a contralateral direction relative to the activated side 30-90 min after consuming food containing the highly potent DREADD agonist deschloroclozapine (DCZ) but not on the following days without DCZ. These results indicate that non-invasive and reversible DREADD manipulation will extend the utility of marmosets as a primate model for linking neuronal activity and natural behavior in various contexts.
Multi-channel, high-density, ultra-low capacitance arrays for ESD and surge protection (2008)

A novel protection device providing ultra-low line capacitance and improved ESD (J. E. Vinson et al., 2003) and surge capability is presented. Applications include stand-alone protection arrays and integrated protection in baseband- or RF-filters. A proprietary epitaxial layer and isolation capability enable high levels of surge power handling capability, while keeping line capacitance low and reducing device footprint. The response of the device to ESD and surge stresses is investigated at wafer- and package-level. Process condition variations and derived structures are studied, along with a consideration of issues related to the measurement of capacitance, ESD and surge capability.
Frequent disc photography and computerized perimetry in eyes with optic disc haemorrhage (1986)

Two patients (one with glaucoma with field loss, one with ocular hypertension) with previously known optic disc haemorrhage were followed with frequent disc photography, computerized perimetry and tonometry for a period of one year. Nine haemorrhages were seen in three of the four eyes studied. Three bleedings showed sudden enlargements, interpreted as re-bleedings, during the absorption phase. Haemorrhages were not associated with any stepwise localized or general worsening of the visual field, nor did the fields deteriorate during the period of the study. No structural changes of the optic nerve head were seen after the bleedings during the observation time of one year. The duration of the haemorrhages varied, but no bleeding lasted less than one week. Before disappearing they were often so small that they could only be detected when series of photographs were examined in chronological order. Haemorrhages large enough to be discernible on isolated slides were present in 20% of the disc photographs. Thus disc haemorrhages are transient and easy to overlook. Many careful observations may be necessary before the first haemorrhage is seen. Each individual bleeding is a minor vascular incident which usually leaves no measurable functional or structural trace.
High Efficiency and ESD of GaN-Based LEDs With Patterned Ion-Damaged Current Blocking Layer (2014)

This letter examined the use of a patterned ion-damaged current blocking layer (patterned-IDCBL). A 50-Å-InGaN layer grown as the top epitaxial layer was transformed into an insulator fabricated by oxygen plasma treatment, in which the dot patterns are regularly arranged over the active areas of the light-emitting diode (LED) and inserted beneath the p-electrode. The results showed that the light output power increased by 16.8% at 60 mA compared with the conventional LEDs, and that the electrostatic discharge resistance is effectively improved by the patterned-IDCBL.