gebhart/patrepeval huggingface dataset:
Waveform presentation of seismic traces by a parallel algorithm (2008)

Seismic traces are the records of sonic wave reflections from underground. These traces can be primarily characterized by amplitude, phase, and frequency content of a given time instance at a surface bin location. Many times these attributes and their variations bear information about lithology, fluid content, and geologic structure. It is therefore a focus of many seismic interpretations. Seismic traces are generally displayed in either variable density or wiggle format. In variable density, a seismic amplitude of a given time instance at a trace is mapped to a gray scale, and a seismic section or faces of a seismic volume become images. The amplitude‐to‐gray mapping can be further extended to amplitude‐to‐color‐table. Variable density is also a commonly used presentation for seismic traces. It is perhaps the best format to reveal the abnormalities of seismic amplitude and to depict the underground structure on a section or in a volume. On the other hand, visualization of seismic traces in the form of wiggles, the most venerable method of seismogram display, is perhaps the best presentation for amplitude, phase, and frequency content, and it is a widely used visualization format on seismic interpretation workstations. Today, compared to variable density presentation, wiggles are currently more costly to produce for 2D sectional visualization and impractical for 3D perspective visualizations. In this abstract, we present a parallel algorithm for producing wiggles from seismic traces. Combined with massive parallelization of a video hardware, the algorithm produces the wiggles at the same cost as the variable density for both 2D sectional view and a 3D perspective view.
Transdifferentiation of the retinal pigment epithelia to the neural retina by transfer of the Pax6 transcriptional factor (2005)

The Pax6 gene plays an important role in eye morphogenesis throughout the animal kingdom. The Pax6 gene and its homologue could form ectopic eyes by targeted expression in Drosophila and Xenopus. Thus, this gene is a master gene for the eye morphogenesis at least in these animals. In the early development of the vertebrate eye, Pax6 is required for the instruction of multipotential progenitor cells of the neural retina (NR). Primitive retinal pigment epithelial (RPE) cells are able to switch their phenotype and differentiate into NR under exogenous intervention, including treatment with fibroblast growth factors (FGFs), and surgical removal of endogenous NR. However, the molecular basis of phenotypic switching is still controversial. Here, we show that Pax6 alone is sufficient to induce transdifferentiation of ectopic NR from RPE cells without addition of FGFs or surgical manipulation. Pax6-mediated transdifferentiation can be induced even at later stages of development. Both in vivo and in vitro studies show that the Pax6 lies downstream of FGF signaling, highlighting the central roles of Pax6 in NR transdifferentiation. Our results provide an evidence of retinogenic potential of nearly mature RPE and a cue for new therapeutic approaches to regenerate functional NR in patients with a visual loss.
Focused Value Prediction: Concepts, techniques and implementations presented in this paper are subject matter of pending patent applications, which have been filed by Intel Corporation (2020)

Value Prediction was proposed to speculatively break true data dependencies, thereby allowing Out of Order (OOO) processors to achieve higher instruction level parallelism (ILP) and gain performance. State-of-the-art value predictors try to maximize the number of instructions that can be value predicted, with the belief that a higher coverage will unlock more ILP and increase performance. Unfortunately, this comes at increased complexity with implementations that require multiple different types of value predictors working in tandem, incurring substantial area and power cost.In this paper we motivate towards lower coverage, but focused, value prediction. Instead of aggressively increasing the coverage of value prediction, at the cost of higher area and power, we motivate refocusing value prediction as a mechanism to achieve an early execution of instructions that frequently create performance bottlenecks in the OOO processor. Since we do not aim for high coverage, our implementation is light-weight, needing just 1.2 KB of storage. Simulation results on 60 diverse workloads show that we deliver 3.3% performance gain over a baseline similar to the Intel Skylake processor. This performance gain increases substantially to 8.6% when we simulate a futuristic up-scaled version of Skylake. In contrast, for the same storage, state-of-the-art value predictors deliver a much lower speedup of 1.7% and 4.7% respectively. Notably, our proposal is similar to these predictors in performance, even when they are given nearly eight times the storage and have 60% more prediction coverage than our solution.
Inhibition of p25/Cdk5 Attenuates Tauopathy in Mouse and iPSC Models of Frontotemporal Dementia (2017)

Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders, including Alzheimer's disease. Previously, we showed that replacing endogenous p35 with the noncleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial Alzheimer's disease mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double-transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δ<i>p35KI</i> mice. We observed significant reduction of phosphorylated tau and its seeding activity in the brain of double transgenic mice compared with the P301S mice. Furthermore, synaptic loss and impaired LTP at hippocampal CA3 region of <i>P301S</i> mice were attenuated by blocking p25 generation. To further validate the role of p25/Cdk5 in tauopathy, we used frontotemporal dementia patient-derived induced pluripotent stem cells (iPSCs) carrying the Tau P301L mutation and generated P301L:Δp35KI isogenic iPSC lines using CRISPR/Cas9 genome editing. We created cerebral organoids from the isogenic iPSCs and found that blockade of p25 generation reduced levels of phosphorylated tau and increased expression of synaptophysin. Together, these data demonstrate a crucial role for p25/Cdk5 in mediating tau-associated pathology and suggest that inhibition of this kinase can remedy neurodegenerative processes in the presence of pathogenic tau mutation.<b>SIGNIFICANCE STATEMENT</b> Accumulation of p25 results in aberrant Cdk5 activation and induction of numerous pathological phenotypes, such as neuroinflammation, synaptic loss, Aβ accumulation, and tau hyperphosphorylation. However, it was not clear whether p25/Cdk5 activity is necessary for the progression of these pathological changes. We recently developed the Δ<i>p35KI</i> transgenic mouse that is deficient in p25 generation and Cdk5 hyperactivation. In this study, we used this mouse model to elucidate the role of p25/Cdk5 in FTD mutant tau-mediated pathology. We also used a frontotemporal dementia patient-derived induced pluripotent stem cell carrying the Tau P301L mutation and generated isogenic lines in which p35 is replaced with noncleavable mutant Δp35. Our data suggest that p25/Cdk5 plays an important role in tauopathy in both mouse and human model systems.
Preservative-Free Triamcinolone Acetonide Suspension Developed for Intravitreal Injection (2008)

We developed a simple, reproducible method to compound stable, completely preservative-free TACA suspensions with a reasonable shelf-life, which enables to study the effect of intravitreal TACA--not biased by varying doses and toxic compounds or their residues.
Targeted gene conversion induced by triplex-directed psoralen interstrand crosslinks in mammalian cells (2009)

Correction of a defective gene is a promising approach for both basic research and clinical gene therapy. However, the absence of site-specific targeting and the low efficiency of homologous recombination in human cells present barriers to successful gene targeting. In an effort to overcome these barriers, we utilized triplex-forming oligonucleotides (TFOs) conjugated to a DNA interstrand crosslinking (ICL) agent, psoralen (pTFO-ICLs), to improve the gene targeting efficiency at a specific site in DNA. Gene targeting events were monitored by the correction of a deletion on a recipient plasmid with the homologous sequence from a donor plasmid in human cells. The mechanism underlying this event is stimulation of homologous recombination by the pTFO-ICL. We found that pTFO-ICLs are efficient in inducing targeted gene conversion (GC) events in human cells. The deletion size in the recipient plasmid influenced both the recombination frequency and spectrum of recombinants; i.e. plasmids with smaller deletions had a higher frequency and proportion of GC events. The polarity of the pTFO-ICL also had a prominent effect on recombination. Our results suggest that pTFO-ICL induced intermolecular recombination provides an efficient method for targeted gene correction in mammalian cells.
Monoclonal antibodies for the treatment of refractory asthma (2013)

In severe refractory asthma, both an understanding of the underlying pathophysiologic mechanisms driving airway inflammation and the identification of appropriate biomarkers in individual patients are critical in guiding the use of biologics and monoclonal antibodies that target the specific pathological processes.
Mechanochemical Amorphization of α-Chitin and Conversion into Oligomers of <i>N</i>-Acetyl-<scp>d</scp>-glucosamine (2017)

Mechanochemical treatment offers great potential for environmentally sustainable processing of chitin within the context of biomass valorization. Using powder X-ray diffraction, we show that crystallinity can be reduced by 50% in 2 h in a controlled way using a ball mill. We correlate this crystallinity reduction with a decrease in interchain hydrogen bonding using infrared spectroscopy as a structural probe. Furthermore, our quantitative interpretation of the spectra reveal a decrease in glycosidic linkage content and retention of N-acetyl groups. The addition of a natural clay, kaolinite, in the ball mill leads to a significant increase in the solubility of the milled materials (up to 75.8% water-soluble products in 6 h, cf. 35.0% without kaolinite). The products of this process were characterized as oligomers of N-acetyl-d-glucosamine (chitin oligomers) with degrees of polymerization (DP) between 1 and 5 using a new quantitative matrix-assisted laser desorption-ionization (MALDI-ToF) mass spectrometric method. These data were complemented by a colorimetric assay of reducing ends and size-exclusion chromatography (SEC). N-Acetyl-d-glucosamine (the monomer) and N,N′-diacetylchitobiose (the dimer) were obtained in yields of 5.1 and 3.9 wt %, respectively, within 6 h, which is comparable with yields of glucose and cellobiose from cellulose ball milling.
Spatial resolution enhancement of images using nonlinear interpolation (2002)

A nonlinear interpolation scheme for image-resolution enhancement is presented. The algorithm is based upon a source model emphasizing edges and incorporates a hybrid local edge-fitting operator which has been developed for this application. A small neighbourhood about each pixel in the low-resolution image is first mapped to a best-fit continuous-space step-edge. This bilevel approximation serves as a local template upon which the higher-resolution sampling grid can then be superimposed. Disputed values in regions of overlap are averaged to smooth errors. The result is an image of increased resolution with noticeably sharper edges and lower reconstruction error than produced by linear techniques.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Antihypertensive therapy: special focus on drug interactions (2003)

Today, the lifetime risk of patients aged 55-65 years to receive antihypertensive drugs approaches 60%. Yet, recent trials suggest that hypertension is not adequately controlled in the majority of patients. The prevalence of hypertension increases with advancing age, as does the prevalence of comorbid conditions and the total number of medications taken. Multi-drug therapy, advancing age and comorbid conditions are also key risk factors for adverse drug reactions and drug interactions. In this review, the authors evaluate the most frequently used antihypertensive drugs (diuretics, beta-adrenergic blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor Type 1 blockers and alpha-adrenergic blockers) with special reference to pharmacodynamic and pharmacokinetic drug interactions. As the spectrum of drugs prescribed is constantly changing, safety yesterday does not imply safety today and safety today does not imply safety tomorrow. Furthermore, therapeutic efficacy should not be neglected over concerns regarding drug interactions. Many patients are at risk of clinically relevant drug interactions involving antihypertensive drugs but, presently, even more patients may be at risk of suffering from the consequences of their inadequately treated hypertension. In this respect, the authors discuss controversial viewpoints on the overall clinical relevance of drug interactions occurring at the level of cytochrome P450 metabolism.
Optimisation of pipeline route in the presence of obstacles based on a least cost path algorithm and laplacian smoothing (2017)

Subsea pipeline route design is a crucial task for the offshore oil and gas industry, and the route selected can significantly affect the success or failure of an offshore project. Thus, it is essential to design pipeline routes to be eco-friendly, economical and safe. Obstacle avoidance is one of the main problems that affect pipeline route selection. In this study, we propose a technique for designing an automatic obstacle avoidance. The Laplacian smoothing algorithm was used to make automatically generated pipeline routes fairer. The algorithms were fast and the method was shown to be effective and easy to use in a simple set of case studies.
Synergy of Daptomycin with Oxacillin and Other β-Lactams against Methicillin-Resistant <i>Staphylococcus aureus</i> (2004)

We previously observed marked synergy between daptomycin and both rifampin and ampicillin against vancomycin-resistant enterococci (VRE). Because the synergy between daptomycin and ampicillin was observed for 100% of VRE strains with high-level ampicillin resistance (ampicillin MIC of > or =128 microg/ml), we looked for synergy between daptomycin and other beta-lactams against 18 strains of methicillin-resistant Staphylococcus aureus (MRSA) by employing a time-kill method using Mueller-Hinton broth supplemented to 50 mg of Ca2+/liter. All strains were resistant to oxacillin (16 of 18 strains were resistant at drug concentrations of > or =256 microg/ml), and all strains were susceptible to daptomycin (the MIC at which 90% of the tested isolates were inhibited was 1 microg/ml). Daptomycin was tested at concentrations of 2, 1, 0.5, 0.25, 0.125, and 0.0625 microg/ml alone or in combination with oxacillin at a fixed concentration of 32 microg/ml. Synergy was found for all 18 strains with daptomycin at one-half the MIC in combination with 32 microg of oxacillin/ml, and synergy was found for 11 of 18 strains (61%) with daptomycin at one-fourth the MIC or less in combination with oxacillin. At 24 h, the daptomycin-oxacillin combination with daptomycin at one-half the MIC showed bactericidal activity against all 18 strains, and the combination with one-fourth the daptomycin MIC showed bactericidal activity against 9 of 18 strains. We also used a novel screening method to look for synergy between daptomycin and other beta-lactams. In this approach, daptomycin was incorporated into Ca(2+)-supplemented Mueller-Hinton agar at subinhibitory concentrations, and synergy was screened by comparing test antibiotic Kirby-Bauer disks on agar with and without daptomycin. By this method, daptomycin with ampicillin-sulbactam, ticarcillin-clavulanate, or piperacillin-tazobactam showed synergy comparable to or greater than daptomycin with oxacillin. For seven of the eight strains tested, time-kill studies confirmed synergy between daptomycin and ampicillin-sulbactam with ampicillin in the range of 2 to 8 microg/ml. The combination of daptomycin and beta-lactams may be useful for the treatment of MRSA infection, but further studies are needed to elucidate the mechanisms and to determine the in vivo efficacy of the combination.
Band offsets and carrier dynamics of type-II InAs/GaSb superlattice photodetectors studied by internal photoemission spectroscopy (2013)

We use internal photoemission spectroscopy to determine the conduction band offset of a type-II InAs/GaSb superlattice (T2SL) pBp photodetector to be 0.004 (±0.004) eV at 78 K, confirming its unipolar operation. It is also found that phonon-assisted hole transport through the B-region disables its two-color detection mode around 140 K. In addition, photoemission yield shows a reduction at about an energy of longitudinal-optical phonon above the threshold, confirming carrier-phonon scattering degradation on the photoresponse. These results may indicate a pathway for optimizing T2SL detectors in addition to current efforts in material growth, processing, substrate preparation, and device passivation.
Manipulation of bacteriophages with dielectrophoresis on carbon nanofiber nanoelectrode arrays (2013)

This work describes efficient manipulation of bacteriophage virus particles using a nanostructured DEP device. The nonuniform electric field for DEP is created by utilizing a nanoelectrode array (NEA) made of vertically aligned carbon nanofibers versus a macroscopic indium tin oxide electrode in a "points-and-lid" configuration integrated in a microfluidic channel. The capture of the virus particles has been systematically investigated versus the flow velocity, sinusoidal AC frequency, peak-to-peak voltage, and virus concentration. The DEP capture at all conditions is reversible and the captured virus particles are released immediately when the voltage is turned off. At the low virus concentration (8.9 × 10(4) pfu/mL), the DEP capture efficiency up to 60% can be obtained. The virus particles are individually captured at isolated nanoelectrode tips and accumulate linearly with time. Due to the comparable size, it is more effective to capture virus particles than larger bacterial cells with such NEA-based DEP devices. This technique can be potentially utilized as a fast sample preparation module in a microfluidic chip to capture, separate, and concentrate viruses and other biological particles in small volumes of dilute solutions in a portable detection system for field applications.
Occludin Phosphorylation and Ubiquitination Regulate Tight Junction Trafficking and Vascular Endothelial Growth Factor-induced Permeability (2009)

Vascular endothelial growth factor (VEGF) alters tight junctions (TJs) and promotes vascular permeability in many retinal and brain diseases. However, the molecular mechanisms of barrier regulation are poorly understood. Here we demonstrate that occludin phosphorylation and ubiquitination regulate VEGF-induced TJ protein trafficking and concomitant vascular permeability. VEGF treatment induced TJ fragmentation and occludin trafficking from the cell border to early and late endosomes, concomitant with increased occludin phosphorylation on Ser-490 and ubiquitination. Furthermore, both co-immunoprecipitation and immunocytochemistry demonstrated that VEGF treatment increased the interaction between occludin and modulators of intracellular trafficking that contain the ubiquitin interacting motif, including Epsin-1, epidermal growth factor receptor pathway substrate 15 (Eps15), and hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs). Inhibiting occludin phosphorylation by mutating Ser-490 to Ala suppressed VEGF-induced ubiquitination, inhibited trafficking of TJ proteins, and prevented the increase in endothelial permeability. In addition, an occludin-ubiquitin chimera disrupted TJs and increased permeability without VEGF. These data demonstrate a novel mechanism of VEGF-induced occludin phosphorylation and ubiquitination that contributes to TJ trafficking and subsequent vascular permeability.
Method for the quantitative measurement of collecting lymphatic vessel contraction in mice (2014)

Collecting lymphatic vessels are critical for the transport of lymph and its cellular contents to lymph nodes for both immune surveillance and the maintenance of tissue-fluid balance. Collecting lymphatic vessels drive lymph flow by autonomous contraction of smooth muscle cells that cover these vessels. Here we describe methods using intravital microscopy to image and quantify collecting lymphatic vessel contraction in mice. Our methods allow for the measurement of the strength of lymphatic contraction of an individual lymphangion in a mouse, which has not yet been demonstrated using other published methods. The ability to study murine collecting lymphatic vessel contraction-using the methods described here or other recently published techniques-allows the field to dissect the molecular mechanisms controlling lymphatic pumping under normal and pathological conditions using the wide variety of molecular tools and genetic models available in the mouse. We have used our methods to study lymphatic contraction in physiological and inflammatory conditions. The methods described here will facilitate the further study of lymphatic function in other pathological conditions that feature lymphatic complications.
AI Feynman 2.0: Pareto-optimal symbolic regression exploiting graph modularity (2020)

We present an improved method for symbolic regression that seeks to fit data to formulas that are Pareto-optimal, in the sense of having the best accuracy for a given complexity. It improves on the previous state-of-the-art by typically being orders of magnitude more robust toward noise and bad data, and also by discovering many formulas that stumped previous methods. We develop a method for discovering generalized symmetries (arbitrary modularity in the computational graph of a formula) from gradient properties of a neural network fit. We use normalizing flows to generalize our symbolic regression method to probability distributions from which we only have samples, and employ statistical hypothesis testing to accelerate robust brute-force search.
Reciprocal secretion of proteins by the bacterial type III machines of plant and animal pathogens suggests universal recognition of mRNA targeting signals (1999)

Bacterial pathogens of both animals and plants use type III secretion machines to inject virulence proteins into host cells. Although many components of the secretion machinery are conserved among different bacterial species, the substrates for their type III pathways are not. The Yersinia type III machinery recognizes some secretion substrates via a signal that is encoded within the first 15 codons of yop mRNA. These signals can be altered by frameshift mutations without affecting secretion of the encoded polypeptides, suggesting a mechanism whereby translation of yop mRNA is coupled to the translocation of newly synthesized polypeptide. We report that the type III machinery of Erwinia chrysanthemi cloned in Escherichia coli recognizes the secretion signals of yopE and yopQ. Pseudomonas syringae AvrB and AvrPto, two proteins exported by the recombinant Erwinia machine, can also be secreted by the Yersinia type III pathway. Mapping AvrPto sequences sufficient for the secretion of reporter fusions in Yersinia revealed the presence of an mRNA secretion signal. We propose that 11 conserved components of type III secretion machines may recognize signals that couple mRNA translation to polypeptide secretion.