gebhart/patrepeval huggingface dataset:
A New Phase Correction Method in NMR Imaging Based on Autocorrelation and Histogram Analysis (1987)

A new statistical approach to phase correction in NMR imaging is proposed. The proposed scheme consists of first-and zero-order phase corrections each by the inverse multiplication of estimated phase error. The first-order error is estimated by the phase of autocorrelation calculated from the complex valued phase distorted image while the zero-order correction factor is extracted from the histogram of phase distribution of the first-order corrected image. Since all the correction procedures are performed on the spatial domain after completion of data acquisition, no prior adjustments or additional measurements are required. The algorithm can be applicable to most of the phase-involved NMR imaging techniques including inversion recovery imaging, quadrature modulated imaging, spectroscopic imaging, and flow imaging, etc. Some experimental results with inversion recovery imaging as well as quadrature spectroscopic imaging are shown to demonstrate the usefulness of the algorithm.
Inhibition of coated pit formation in Hep2 cells blocks the cytotoxicity of diphtheria toxin but not that of ricin toxin. (1985)

It has been recently shown (Larkin, J. M., M. S. Brown, J. L. Goldstein, and R. G. W. Anderson, 1983, Cell, 33:273-285) that after a hypotonic shock followed by incubation in a K+-free medium, human fibroblasts arrest their coated pit formation and therefore arrest receptor-mediated endocytosis of low density lipoprotein. We have used this technique to study the endocytosis of transferrin, diphtheria toxin, and ricin toxin by three cell lines (Vero, Wi38/SV40, and Hep2 cells). Only Hep2 cells totally arrested internalization of [125I]transferrin, a ligand transported by coated pits and coated vesicles, after intracellular K+ depletion. Immunofluorescence studies using anti-clathrin antibodies showed that clathrin associated with the plasma membrane disappeared in Hep2 cells when the level of intracellular K+ was low. In the absence of functional coated pits, diphtheria toxin was unable to intoxicate Hep2 cells but the activity of ricin toxin was unaffected by this treatment. By measuring the rate of internalization of [125I]ricin toxin by Hep2 cells, with and without functional coated pits, we have shown that this labeled ligand was transported in both cases inside the cells. Hep2 cells with active coated pits internalized twice as much [125I]ricin toxin as Hep2 cells without coated pits. Entry of ricin toxin inside the cells was a slow process (8% of the bound toxin per 10 min at 37 degrees C) when compared to transferrin internalization (50% of the bound transferrin per 10 min at 37 degrees C). Using the indirect immunofluorescence technique on permeabilized cells, we have shown that Hep2 cells depleted in intracellular K+ accumulated ricin toxin in compartments that were predominantly localized around the cell nucleus. Our study indicates that in addition to the pathway of coated pits and coated vesicles used by diphtheria toxin and transferrin, another system of endocytosis for receptor-bound molecules takes place at the level of the cell membrane and is used by ricin toxin to enter the cytosol.
Gastric Emptying in Healthy Subjects and in Patients with Various Malabsorptive States (1974)

Moberg, S. & Carlberger, G. Gastric emptying in healthy subjects and in patients with various malabsorptive states. Scand. J. Gastroent. 1974, 9, 17–21.Gastric emptying of a 300-ml liquid test meal containing fat, carbohydrate, and protein was measured in 7 healthy subjects and in 8 patients with steatorrhoea, 4 of whom had distal resections of the small intestine, 2 chronic pancreatitis, and 2 coeliac disease. The gastric emptying curve for the healthy subjects could be divided into a short, rapid phase and a much slower second phase, during which a constant amount of the test meal was emptied per minute. The patients who excreted 40 g or more of faecal fat daily emptied the entire volume very rapidly and without any marked change in emptying rate during the experiment. The patients with less steatorrhoea showed a lesser degree of disturbed emptying. The finding agrees with the assumption that gastric emptying of a test meal of the type used is regulated by fat absorption.
Diet and Cancer (2000)

The large differences in cancer rates among countries, striking changes in these rates among migrating populations, and rapid changes over time within countries indicate that some aspect of lifestyle or environment is largely responsible for the common cancers in Western countries. Dietary fat has been hypothesized to be the key factor because national consumption is correlated with the international differences. However, detailed analyses in large prospective studies have not supported an important role of dietary fat. Instead, positive energy balance, reflected in early age at menarche and weight gain as an adult, is an important determinant of breast and colon cancers, consistent with numerous studies in animals. As a contributor to positive energy balance, and possibly by other mechanisms, physical inactivity has also been shown to be a risk factor for these diseases and in part accounts for the international differences. Although the percentage of calories from fat in the diet does not appear related to risk of colon cancer, greater risks have been seen with higher consumption of red meat, suggesting that factors other than fat per se are important. In many case-control studies, a high consumption of fruits and vegetables has been associated with reduced risks of numerous cancers, but recent prospective studies suggest these associations may have been overstated. Among the factors in fruits and vegetables that have been examined in relation to cancer risk, present data most strongly support a benefit of higher folic acid consumption in reducing risks of colon and breast cancers. These findings have been bolstered by an association between incidence of colon cancer and a polymorphism in the gene for methylenetetrahydrofolate reductase, an enzyme involved in folic acid metabolism. The benefits of folic acid appear strongest among persons who regularly consume alcohol, which itself is associated with risk of these cancers. Numerous other aspects of diet are hypothesized to influence the risks of cancers in Western countries, but for the moment the evidence is unclear.
Analysis of molecular inversion probe performance for allele copy number determination (2007)

We have developed a new protocol for using molecular inversion probes to accurately and specifically measure allele copy number. The new protocol provides for significant improvements, including the reduction of input DNA (from 2 mug) by more than 25-fold (to 75 ng total genomic DNA), higher overall precision resulting in one order of magnitude lower false positive rate, and greater dynamic range with accurate absolute copy number up to 60 copies.
LogP: towards a realistic model of parallel computation (1993)

A vast body of theoretical research has focused either on overly simplistic models of parallel computation, notably the PRAM, or overly specific models that have few representatives in the real world. Both kinds of models encourage exploitation of formal loopholes, rather than rewarding development of techniques that yield performance across a range of current and future parallel machines. This paper offers a new parallel machine model, called LogP, that reflects the critical technology trends underlying parallel computers. it is intended to serve as a basis for developing fast, portable parallel algorithms and to offer guidelines to machine designers. Such a model must strike a balance between detail and simplicity in order to reveal important bottlenecks without making analysis of interesting problems intractable. The model is based on four parameters that specify abstractly the computing bandwidth, the communication bandwidth, the communication delay, and the efficiency of coupling communication and computation. Portable parallel algorithms typically adapt to the machine configuration, in terms of these parameters. The utility of the model is demonstrated through examples that are implemented on the CM-5.
Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro (2013)

Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos together with in vitro assays we have determined the relative anti-inflammatory activity of each compound. We demonstrate that in vivo embryonic assays Pomalidomide is a significantly more potent anti-inflammatory agent than either Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known detrimental effects of Thalidomide. We found that Pomalidomide, displays a high degree of cell specificity, and has no detectable teratogenic, antiangiogenic or neurotoxic effects at potent anti-inflammatory concentrations. This is in marked contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood vessels, nerves, and embryonic development at anti-inflammatory concentrations. This work has implications for Pomalidomide as a treatment for conditions Thalidomide and Lenalidomide treat currently.
Leakage channel optical fibers with large effective area (2007)

Leakage channel fibers, where few air holes form a core, can be precisely engineered to create large leakage loss for higher-order modes, while maintaining negligible transmission loss for the fundamental mode. This unique property can be used for designing optical fibers with large effective area, which supports robust fundamental mode propagation. The large air holes in the design also enable the optical fibers to be bend resistant. The principles of design and operation regime are outlined, demonstrating the potential of this approach for optical fibers that propagate a fundamental mode in core diameter exceeding 100 μm. Performance of a fabricated passive leakage channel fiber, an ytterbium-doped double-clad leakage channel fiber, and an ytterbium-doped polarization-maintaining double-clad leakage channel fiber are also discussed.
Cache-efficient matrix transposition (2002)

We investigate the memory system performance of several algorithms for transposing an N/spl times/N matrix in-place, where N is large. Specifically, we investigate the relative contributions of the data cache, the translation lookaside buffer, register tiling, and the array layout function to the overall running time of the algorithms. We use various memory models to capture and analyze the effect of various facets of cache memory architecture that guide the choice of a particular algorithm, and attempt to experimentally validate the predictions of the model. Our major conclusions are as follows: limited associativity in the mapping from main memory addresses to cache sets can significantly degrade running time; the limited number of TLB entries can easily lead to thrashing; the fanciest optimal algorithms are not competitive on real machines even at fairly large problem sizes unless cache miss penalties are quite high: low-level performance tuning "hacks", such as register tiling and array alignment, can significantly distort the effects of improved algorithms; and hierarchical non-linear layouts are inherently superior to the standard canonical layouts (such as row- or column-major) for this problem.
Inhibitors for Novel Coronavirus Protease Identified by Virtual Screening of 687 Million Compounds (2020)

The rapid outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China followed by its spread around the world poses a serious global concern for public health with almost 90000 people infected and thousands of fatalities. To conquer viral infections, the inhibition of proteases essential for proteolytic processing of viral polyproteins is a conventional therapeutic strategy. To this date, no specific drugs or vaccines are available to treat SARS-CoV-2 despite its close relation to the SARS-CoV-1 virus that caused a similar epidemic in 2003. Thus, there remains an urgent need for the development of specific antiviral therapeutics to conquer SARS-CoV-2. In order to find novel inhibitors, we computationally screened a compound library of over 687 million compounds for binding at the recently solved crystal structure of the main protease of SARS-CoV-2. A screening of such a vast chemical space for SARS-CoV-2 protease inhibitors has not been reported before. After shape screening, two docking protocols were applied followed by the determination of pharmacokinetically relevant molecular descriptors to narrow down the initial hits. Next, molecular dynamics simulations were conducted to validate the stability of docked binding modes and comprehensively quantify ligand binding energies. After evaluation of off-target binding, we report a list of 11 drug-like compounds with improved binding free energy to the target protease in contrast to the cocrystallized peptidomimetic lead compound that suffers from poor pharmacokinetic properties. Furthermore, we identified one potent binder with comparable properties from the natural compound library.
Θ/spl Rfr/-string: A geometry-based representation for efficient and effective retrieval of images by spatial similarity (1998)

A spatial similarity algorithm assesses the degree to which the spatial relationships among the domain objects in a database image conform to those specified in the query image. In this paper, we propose a geometry-based structure for representing the spatial relationships in the images and an associated spatial similarity algorithm. The proposed algorithm recognizes both translation, scale, and rotation variants of an image, and variants of the image generated by an arbitrary composition of translation, scale, and rotation transformations. The algorithm has /spl Theta/(n log n) time complexity in terms of the number of objects common to the database and query images. The retrieval effectiveness of the proposed algorithm is evaluated using the TESSA image collection.
Neuroimaging predictors of cognitive performance across a standardized neurocognitive battery. (2013)

The feasibility of administering a comprehensive neuropsychological battery in the scanner was established, and task-specific brain activation patterns improved prediction beyond demographic information. This benchmark index of performance-associated brain activation can be applied to link brain activation with neurocognitive performance during standardized testing. This first step in standardizing a neurocognitive battery for use in fMRI may enable quantitative assessment of patients with brain disorders across multiple cognitive domains. Such data may facilitate identification of neural dysfunction associated with poor performance, allow for identification of individuals at risk for brain disorders, and help guide early intervention and rehabilitation of neurocognitive deficits.
Encapsulating Elastically Stretchable Neural Interfaces: Yield, Resolution, and Recording/Stimulation of Neural Activity (2011)

A high resolution elastically stretchable microelectrode array (SMEA) to interface with neural tissue is described. The SMEA consists of an elastomeric substrate, such as poly(dimethylsiloxane) (PDMS), elastically stretchable gold conductors, and an electrically insulating encapsulating layer in which contact holes are opened. We demonstrate the feasibility of producing contact holes with 40 µm × 40 µm openings, show why the adhesion of the encapsulation layer to the underlying silicone substrate is weakened during contact hole fabrication, and provide remedies. These improvements result in greatly increased fabrication yield and reproducibility. An SMEA with 28 microelectrodes was fabricated. The contact holes (100 µm × 100 µm) in the encapsulation layer are only ~10% the size of the previous generation, allowing a larger number of microelectrodes per unit area, thus affording the capability to interface with a smaller neural population per electrode. This new SMEA is used to record spontaneous and evoked activity in organotypic hippocampal tissue slices at 0% strain before stretching, at 5 % and 10 % equibiaxial strain, and again at 0% strain after relaxation. The noise of the recordings increases with increasing strain. The frequency of spontaneous neural activity also increases when the SMEA is stretched. Upon relaxation, the noise returns to pre-stretch levels, while the frequency of neural activity remains elevated. Stimulus-response curves at each strain level are measured. The SMEA shows excellent biocompatibility for at least two weeks.
The Diabetic Foot (2006)

Foot pathology remains the leading diabetic complication requiring hospitalization (). Because the incidence of diabetes in the general population is expected to rise, the prevalence of diabetic foot complications will follow. The resulting cost to society can be measured in direct costs attributed to treatment, as well as indirect costs in lost productivity. The total cost of diabetic foot complications in the United States has been estimated to approach $4 billion annually, as extrapolated from the costs of ulcer care and amputations (). However the costs are measured, diabetic foot problems represent a major public health challenge of growing proportions.
Visiblity Streaming for Network-based Walkthroughs. (1998)

In network-based walkthroughs the server transmits online only the primitives which are potentially visible from the client’s current viewpoint (visibility streaming). To reduce the bandwidth requirements it is necessary to minimize the set of view-dependent potentially visible primitives using occlusion culling techniques. However, even a slight change in the viewpoint might require the computation and transmission of many new primitives and thus latency is inevitable. In this paper we present an algorithm for determining a conservative superset of an -neighborhood of a given viewpoint. Having such an -superset, the client is free to render the model independently of the server as long as he moves within that -neighborhood.
Innervation Territories of Mechanically Activated C Nociceptor Units in Human Skin (1997)

Innervation territories of mechanically activated C nociceptor units in human skin. J. Neurophysiol. 78: 2641-2648, 1997. Innervation territories of single mechanically activated C nociceptors in the skin of the leg and foot were explored in normal human subjects. Microneurographic recordings were obtained in the peroneal nerve from 70 mechano-heat responsive (CMH) and 7 mechano-(but not heat) responsive (CM) units. Units were identified by their constant long-latency response to intracutaneous electrical stimulation of their terminals. Responsiveness to mechanical, heat, or transcutaneous electrical stimuli was verified by transient slowing of conduction velocity after activation by such stimuli. We determined their thresholds to mechanical stimuli (mean 33.7 mN, median 30 mN, range 3-750 mN) and heat (mean 42.5 degrees C, median 42.5 degrees C, range 37-49 degrees C). Most mechano-receptive fields (mRFs) were found on the foot dorsum (60 units) and some on the lower leg (14 units) and toes (3 units). Most units had one continuous mRF, but 10 units had more complex fields. Areas of mRFs mapped with a von Frey filament (750 mN) ranged from 10 to 363 mm2 (mean, 106 mm2). The mRFs were oval or irregularly shaped with greatest diameters ranging from 3 to 45 mm. Mean areas of mRFs were largest on the lower leg (198 mm2), smaller on the foot dorsum (88 mm2), and smallest on the toes (35 mm2). Forty-nine of the 77 units had identical mRFs and electro-receptive fields (eRFs). Twenty-six units had larger eRFs than mRFs, whereas the opposite was found for two units only. Areas of eRFs ranged from 16 to 511 mm2 (mean 121 mm2). An estimate of the innervation density based on the present data and the presumed number of C fibers in cutaneous fascicles of the peroneal nerve suggests a considerable overlap of nociceptive endings in the skin. Such overlapping nociceptor innervation in the skin allows for substantial spatial summation in response to punctate noxious stimuli, which may be a prerequisite for high accuracy in localizing painful events from a C-fiber input. The reduction in size of innervation territories distally allows for finer discrimination of spatial dimensions of noxious stimuli distally as compared with proximal regions of the extremities. Mean maximal diameters of the mechano-receptive fields of CMH and CM units on the lower leg (22.3 mm) and foot (15.3 mm) are of similar size as the radius of axon reflex flares evoked by noxious mechanical stimuli in these regions.
Preclinical Evaluation of Radiation and Perifosine in a Genetically and Histologically Accurate Model of Brainstem Glioma (2010)

Brainstem gliomas (BSG) are a rare group of central nervous system tumors that arise mostly in children and usually portend a particularly poor prognosis. We report the development of a genetically engineered mouse model of BSG using the RCAS/tv-a system and its implementation in preclinical trials. Using immunohistochemistry, we found that platelet-derived growth factor (PDGF) receptor alpha is overexpressed in 67% of pediatric BSGs. Based on this observation, we induced low-grade BSGs by overexpressing PDGF-B in the posterior fossa of neonatal nestin tv-a mice. To generate high-grade BSGs, we overexpressed PDGF-B in combination with Ink4a-ARF loss, given that this locus is commonly lost in high-grade pediatric BSGs. We show that the likely cells of origin for these mouse BSGs exist on the floor of the fourth ventricle and cerebral aqueduct. Irradiation of these high-grade BSGs shows that although single doses of 2, 6, and 10 Gy significantly increased the percent of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive nuclei, only 6 and 10 Gy significantly induce cell cycle arrest. Perifosine, an inhibitor of AKT signaling, significantly induced TUNEL-positive nuclei in this high-grade BSG model, but in combination with 10 Gy, it did not significantly increase the percent of TUNEL-positive nuclei relative to 10 Gy alone at 6, 24, and 72 hours. Survival analysis showed that a single dose of 10 Gy significantly prolonged survival by 27% (P = 0.0002) but perifosine did not (P = 0.92). Perifosine + 10 Gy did not result in a significantly increased survival relative to 10 Gy alone (P = 0.23). This PDGF-induced BSG model can serve as a preclinical tool for the testing of novel agents.