gebhart/patrepeval huggingface dataset:
Tissue classification based on 3D local intensity structures for volume rendering (2000)

This paper describes a novel approach to tissue classification using three-dimensional (3D) derivative features in the volume rendering pipeline. In conventional tissue classification for a scalar volume, tissues of interest are characterized by an opacity transfer function defined as a one-dimensional (1D) function of the original volume intensity. To overcome the limitations inherent in conventional 1D opacity functions, we propose a tissue classification method that employs a multidimensional opacity function, which is a function of the 3D derivative features calculated from a scalar volume as well as the volume intensity. Tissues of interest are characterized by explicitly defined classification rules based on 3D filter responses highlighting local structures, such as edge, sheet, line, and blob, which typically correspond to tissue boundaries, cortices, vessels, and nodules, respectively, in medical volume data. The 3D local structure filters are formulated using the gradient vector and Hessian matrix of the volume intensity function combined with isotropic Gaussian blurring. These filter responses and the original intensity define a multidimensional feature space in which multichannel tissue classification strategies are designed. The usefulness of the proposed method is demonstrated by comparisons with conventional single-channel classification using both synthesized data and clinical data acquired with CT (computed tomography) and MRI (magnetic resonance imaging) scanners. The improvement in image quality obtained using multichannel classification is confirmed by evaluating the contrast and contrast-to-noise ratio in the resultant volume-rendered images with variable opacity values.
Tryptophan fluorescence study of the interaction of penetratin peptides with model membranes (2002)

Penetratin is a 16-amino-acid peptide, derived from the homeodomain of antennapedia, a Drosophila transcription factor, which can be used as a vector for the intracellular delivery of peptides or oligonucleotides. To study the relative importance of the Trp residues in the wild-type penetratin peptide (RQIKIWFQNRRMKWKK) two analogues, the W48F (RQIKIFFQNRRMKWKK) and the W56F (RQI KIWFQNRRMKFKK) variant peptides were synthesized. Binding of the three peptide variants to different lipid vesicles was investigated by fluorescence. Intrinsic Trp fluorescence emission showed a decrease in quantum yield and a blue shift of the maximal emission wavelength upon interaction of the peptides with negatively charged phosphatidylserine, while no changes were recorded with neutral phosphatidylcholine vesicles. Upon binding to phosphatidylcholine vesicles containing 20% (w/w) phosphatidylserine the fluorescence blue shift induced by the W56F-penetratin variant was larger than for the W48F-penetratin. Incorporation of cholesterol into the negatively charged lipid bilayer significantly decreased the binding affinity of the peptides. The Trp mean lifetime of the three peptides decreased upon binding to negatively charged phospholipids, and the Trp residues were shielded from acrylamide and iodide quenching. CD measurements indicated that the peptides are random in buffer, and become alpha helical upon association with negatively charged mixed phosphatidylcholine/phosphatidylserine vesicles, but not with phosphatidylcholine vesicles. These data show that wild-type penetratin and the two analogues interact with negatively charged phospholipids, and that this is accompanied by a conformational change from random to alpha helical structure, and a deeper insertion of W48 compared to W56, into the lipid bilayer.
Vibrio parahaemolyticusInfections in the United States, 1973–1998 (2000)

Vibrio parahaemolyticus infections are associated with consumption of raw or undercooked shellfish, contaminated food, and exposure of wounds to warm seawater. Foodborne outbreaks and sporadic infections from Vibrio species in 4 Gulf Coast states are reported routinely to the Centers for Disease Control and Prevention (CDC). Between 1988 and 1997, 345 sporadic V. parahaemolyticus infections were reported: 59% were gastroenteritis, 34% were wound infections, 5% were septicemia, and 2% were from other exposures. Forty-five percent of patients suffering from these conditions were hospitalized for their infections, and 88% of persons with acute gastroenteritis reported having eaten raw oysters during the week before their illness occurred. Between 1973 and 1998, 40 outbreaks of V. parahaemolyticus infections were reported to the CDC, and these outbreaks included >1000 illnesses. Most of these outbreaks occurred during the warmer months and were attributed to seafood, particularly shellfish. The median attack rate among persons who consumed the implicated seafood was 56%. To prevent V. parahaemolyticus infections, persons should avoid consumption of raw or undercooked shellfish and exposure of wounds to seawater.
Oligodeoxynucleotide&hyphen;based therapeutics for human leukemias (1993)

As the cell and molecular biology of hematopoietic cell development becomes known in greater detail, the roles of individual genes in regulating cell proliferation and growth also become better appreciated. Some genes appear to be of particular importance in these complex processes and are therefore potential targets for molecularly based therapeutics. The rationale for such treatment is that, if the function of critical genes can be efficiently and specifically perturbed, then the ensuing disruption might lead to preferential leukemic cell death. Several technologies for carrying out targeted gene disruption now exist. One approach, the "antisense" gene strategy, appears to be particularly well suited to the treatment of human leukemia ex vivo and perhaps in vivo as well. Herein I review the experience of my laboratory in using this approach to target the c-myb and c-kit proto-oncogenes in human leukemic cells. Our results suggest that use of oligodeoxynucleotides for disrupting the function of specific genes may prove useful for both ex vivo and in vivo treatment of patients with hematopoietic malignancies.
Fault-Tolerant Quantum Computation with High Threshold in Two Dimensions (2007)

We present a scheme of fault-tolerant quantum computation for a local architecture in two spatial dimensions. The error threshold is 0.75% for each source in an error model with preparation, gate, storage, and measurement errors.
Prostaglandins and Inflammation (2011)

Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase isoenzymes, and their biosynthesis is blocked by nonsteroidal antiinflammatory drugs, including those selective for inhibition of cyclooxygenase-2. Despite the clinical efficacy of nonsteroidal antiinflammatory drugs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm.
Enhanced hepatitis C virus NS3 specific Th1 immune responses induced by co-delivery of protein antigen and CpG with cationic liposomes (2004)

Mice were immunized intramuscularly with free recombinant hepatitis C virus (HCV) NS3 (non-structural protein 3) protein, liposomes encapsulating rNS3 or rNS3 and CpG mixture, liposomes co-encapsulating rNS3 and CpG or liposomes co-encapsulating rNS3 and GpC. Liposomes co-encapsulating rNS3 and CpG induced a much higher titre of anti-HCV NS3 IgG and the dominant IgG subtype was IgG2a. Liposomes co-encapsulating rNS3 and GpC also induced high levels of anti-HCV NS3 IgG antibody, but the dominant IgG subtype was still IgG1, the same as in free HCV/NS3 immunized mice. Liposomes encapsulating rHCV NS3 and the mixture of rHCV NS3 and CpG did not increase the antibody response but switched the IgG subtype. A cytokine profile analysis revealed that the levels of Th1 cytokines in the mice immunized with liposomes co-encapsulating rHCV NS3 and CpG were significantly higher than in other mice while the levels of Th2 cytokine were significantly lower than in the mice immunized with naked rNS3. IL-12 in the mice immunized with liposome-NS3-CpG was significantly higher than in other mice. In conclusion, liposomes co-encapsulating HCV NS3 and CpG are a good candidate vaccine to induce strong Th1 immune responses against hepatitis C viruses.
Partially Folded Intermediates in Insulin Fibrillation (2003)

Native zinc-bound insulin exists as a hexamer at neutral pH. Under destabilizing conditions, the hexamer dissociates, and is very prone to forming fibrils. Insulin fibrils exhibit the typical properties of amyloid fibrils, and pose a problem in the purification, storage, and delivery of therapeutic insulin solutions. We have carried out a systematic investigation of the effect of guanidine hydrochloride (Gdn.HCl)-induced structural perturbations on the mechanism of fibrillation of insulin. At pH 7.4, the addition of as little as 0.25 M Gdn.HCl leads to dissociation of insulin hexamers into dimers. Moderate concentrations of Gdn.HCl lead to formation of a novel partially unfolded dimer state, which dissociates into a partially unfolded monomer state. High concentrations of Gdn.HCl resulted in unfolded monomers with some residual structure. The addition of even very low concentrations of Gdn.HCl resulted in substantially accelerated fibrillation, although the yield of fibrils decreased at high concentrations. Accelerated fibrillation correlated with the population of the expanded (partially folded) monomer, which existed up to >6 M Gdn.HCl, accounting for the formation of substantial amounts of fibrils under such conditions. In the presence of 20% acetic acid, where insulin exists as the monomer, fibrillation was also accelerated by Gdn.HCl. The enhanced fibrillation of the monomer was due to the increased ionic strength at low denaturant concentrations, and due to the presence of the partially unfolded, expanded conformation at Gdn.HCl concentrations above 1 M. The data suggest that under physiological conditions, the fibrillation of insulin involves both changes in the association state (with rate-limiting hexamer dissociation) and conformational changes, leading to formation of the amyloidogenic expanded monomer intermediate.
Endocrine function in sclerosteosis. (1979)

Sclerosteosis is a rare autosomal recessive condition which is characterized by excessive skeletal overgrowth, distortion of the facies, cranial nerve abnormalities and raised intracranial pressure. Syndactyly and digital malformation are associated features. Radiological examination reveals thickened sclerotic bone maximally involving the skull, including the pituitary fossa. Sclerosis and hyperostosis are present throughout the skeleton. Biochemical and endocrine tests were carred out on 3 patients with sclerosteosis in an attempt to detect any dysfunction of calcium regulation of the pituitary. Results revealed no abnormality of basal parathyroid or calcitonin secretion. Histological examination revealed quantitatively increased bone resorption in comparison with normal subjects, although the pattern resembled osteosclerosis. Regulation of growth hormone, adrenocorticotrophin, gonadotrophin and thyrotrophin function were intact. We conclude that pituitary function and calcium 'homeostasis' are normal in this disorder.
Measuring bacterial ectoenzyme activities in marine waters using mercuric chloride as a preservative and a control (1995)

Investigations of bacterial ectoenzymes in seawater using fluorogenic substrate analogues such as 4-methylumbelliferone (4MUF) and P-naphthylamine (BNAPH) are made more efficient and feasible in a greater range of environments if samples can be preserved and analyzed at a later date. Preservation by freezing has been shown to be feasible. However, activity will persist in the liquid phase until the samples are completely frozen and will commence again upon thawing. Addition of mercuric chloride (HgC12] is an excellent means of terminating enzymatic activity, as well as providing a negative control for autofluorescence and autohydrolysis without the need to boil or autoclave seawater. HgC12 causes relatively little inhibition of fluorescence 4MUF (-5 %) and BNAPH (-30 %) in seawater. Furthermore, the effects are linear over a wide range of concentrations and consistent across the excltation and emission spectra. Inhibition of 4MUF fluorescence by Hg2+ in solutions of low ionic strength is reversible by addition of NaCl or other salts, so this method of preservation may be useful in fresh waters as well. 4MUF fluorescence in Hg2'-poisoned seawater is stable for long periods (>l yr! when stored in the dark at -20C; BNAPH, however, loses fluorescence over time.
SiO 2 -enhanced synthesis of Si nanowires by laser ablation (1998)

Si nanowires with uniform size have been synthesized by laser ablation of highly pure Si powder targets mixed with SiO2. A bulk quantity of Si nanowires was successfully obtained by mixing 30%–70% of SiO2 into the Si powder target. SiO2 played a crucial role in enhancing the formation and growth of the Si nanowires. The morphology and microstructure of the Si nanowire tips have been systematically characterized by means of high-resolution transmission electron microscopy. No evidence of metal was found at the tips. The results suggest that Si oxide is more important than metal in catalyzing the formation of Si nanowires.
Kinetics of the Oxidation of Heterocyclic Aldehydes by Quinolinium Dichromate (2002)

Abstract Quinolinium dichromate in sulfuric acid oxidizes heterocyclic aldehydes (2-furaldehyde, 2-pyrrolecarbaldehyde, 2-thiophenecarbaldehyde) to the corresponding acids in a 50% (v/v) acetic acid–water medium. The kinetic data on the rates of oxidation of the substrates have been discussed with reference to the aldehyde hydration equilibria. The kinetic results support a mechanistic pathway proceeding via a rate-determining oxidative decomposition of the chromate ester of the aldehyde hydrate.
Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study (1998)

Systemic treatment of psoriasis with fumaric acid esters (FAE) has been found effective by empirical means. In recent years clinical studies have confirmed the antipsoriatic activity of a defined mixture of different FAE. The aim of the present prospective multicentre study was to investigate further the efficacy and safety of FAE therapy in a large number of patients with severe psoriasis vulgaris. From 101 patients included in the study 70 completed the treatment period of 4 months. Discontinuation was due to adverse events in seven, lack of efficacy in two, and other reasons, such as non-attendance for scheduled visits, in 22 patients. Evaluation of overall efficacy showed a decrease in psoriasis area and severity index of 80% after 4 months of FAE therapy. Laboratory investigations revealed a slight overall decrease of lymphocytes during the treatment period which was more than 50% below baseline in 10 patients. During weeks 4 and 8 mean eosinophil counts were above the normal range. At the end of FAE therapy elevated eosinophil counts had returned to normal values. None of the patients showed changes in renal function parameters throughout the study. Adverse events were reported in 69% of the patients mainly consisting of gastrointestinal complaints (56%) and flushing (31%). In five patients gastrointestinal complaints and in two patients flushing led to withdrawal from the study. Taken together the results of this multicentre study showed in a large number of patients that systemic FAE treatment is effective in severe psoriasis vulgaris. Transient eosinophilia seems to be a characteristic feature of FAE therapy, while lymphocytopenia is usually mild. Adverse effects are dose-related and consist mainly of gastrointestinal complaints and flushing.
GAD65, GAD67, and GABAT Immunostaining in Human Brain and Apparent GAD65 Loss in Alzheimer's Disease (2013)

The GABAergic system is the main inhibitory neurotransmitter system in the vertebrate brain. Although it is well established that the GABAergic system is affected in neuropsychiatric disorders, in Alzheimer's disease (AD) it has been considered to be relatively spared. In this study we describe the immunohistochemical localization of the main enzymes of the GABAergic system; glutamate decarboxylase 65 (GAD65), GAD67, and GABA transferase (GABAT) in human brain. In neocortex, hippocampus, basal ganglia, and cerebellum, GAD65 and GAD67 immunoreactivity were found in neuropil granules, possibly axonal boutons or terminals, and in a subset of small to midsized neurons. GAD65 preferentially stained neuropil granules, while GAD67 preferentially stained neuronal cell bodies. GABAT intensely labeled many types of neurons and glia cells. While GAD65 and GAD67 stained the cytoplasm of cells homogeneously, GABAT labeling appeared irregular and granular. GAD65 immunoreactivity of neurons and neuropil was severely reduced in AD middle temporal gyrus, hippocampus, and putamen as determined by fluorescence and light microscopic immunohistochemistry. Western blotting revealed a similar reduction of GAD65, but not GAD67, protein levels in the middle temporal gyrus of AD. Our results suggest that the GABAergic system is more severely affected in AD than previously reported. This deficit may contribute to AD pathogenesis by loss of GABAergic inhibitory activity.
The NLRP3 Inflammasome: A Sensor for Metabolic Danger? (2010)

Interleukin-1beta (IL-1beta), reactive oxygen species (ROS), and thioredoxin-interacting protein (TXNIP) are all implicated in the pathogenesis of type 2 diabetes mellitus (T2DM). Here we review mechanisms directing IL-1beta production and its pathogenic role in islet dysfunction during chronic hyperglycemia. In doing so, we integrate previously disparate disease-driving mechanisms for IL-1beta, ROS, and TXNIP in T2DM into one unifying model in which the NLRP3 inflammasome plays a central role. The NLRP3 inflammasome also drives IL-1beta maturation and secretion in another disease of metabolic dysregulation, gout. Thus, we propose that the NLRP3 inflammasome contributes to the pathogenesis of T2DM and gout by functioning as a sensor for metabolic stress.
The NMDA-to-AMPA Ratio at Synapses Onto Layer 2/3 Pyramidal Neurons Is Conserved Across Prefrontal and Visual Cortices (2003)

To better understand regulation of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor complements across the cortex, and to investigate NMDA receptor (NMDAR)-based models of persistent activity, we compared NMDA/AMPA ratios in prefrontal (PFC) and visual cortex (VC) in rat. Whole cell voltage-clamp responses were recorded in brain slices from layer 2/3 pyramidal cells of the medial PFC and VC of rats aged p16-p21. Mixed miniature excitatory postsynaptic currents (mEPSCs) having AMPA receptor (AMPAR)- and NMDAR-mediated components were isolated in nominally 0 Mg2+ ACSF. Averaged mEPSCs were well-fit by double exponentials. No significant differences in the NMDA/AMPA ratio (PFC: 27 +/- 1%; VC: 28 +/- 3%), peak mEPSC amplitude (PFC: 19.1 +/- 1 pA; VC: 17.5 +/- 0.7 pA), NMDAR decay kinetics (PFC: 69 +/- 8 ms; VC: 67 +/- 6 ms), or degree of correlation between NMDAR- and AMPAR-mediated mEPSC components were found between the areas (PFC: n = 27; VC: n = 28). Recordings from older rats (p26-29) also showed no differences. EPSCs were evoked extracellularly in 2 mM Mg2+ at depolarized potentials; although the average NMDA/AMPA ratio was larger than that observed for mEPSCs, the ratio was similar in the two regions. In nominally 0 Mg2+ and in the presence of CNQX, spontaneous activation of NMDAR increased recording noise and produced a small tonic depolarization which was similar in both areas. We conclude that this basic property of excitatory transmission is conserved across PFC and VC synapses and is therefore unlikely to contribute to differences in firing patterns observed in vivo in the two regions.
Diazo Compounds: Versatile Tools for Chemical Biology (2016)

Diazo groups have broad and tunable reactivity. That and other attributes endow diazo compounds with the potential to be valuable reagents for chemical biologists. The presence of diazo groups in natural products underscores their metabolic stability and anticipates their utility in a biological context. The chemoselectivity of diazo groups, even in the presence of azido groups, presents many opportunities. Already, diazo compounds have served as chemical probes and elicited novel modifications of proteins and nucleic acids. Here, we review advances that have facilitated the chemical synthesis of diazo compounds, and we highlight applications of diazo compounds in the detection and modification of biomolecules.
Usual Interstitial Pneumonia (2002)

The pathologic findings in biopsy and subsequent explant specimens from 20 patients with usual interstitial pneumonia (UIP) were reviewed to refine histologic criteria for diagnosis, to identify factors that may confound diagnosis, and to assess the relationship of UIP and nonspecific interstitial pneumonia (NSIP). One case of NSIP was also identified and included for comparison. Surgical biopsies from 15 of the 20 UIP cases were diagnosed as UIP, whereas 5 showed only nondiagnostic changes. An important new observation is that areas resembling nonspecific interstitial pneumonia (NSIP-like areas) are present in the majority of UIP cases in both biopsy and explant specimens, and they are extensive in some. Ten of the 15 UIP biopsies were considered straightforward, with typical patchy interstitial fibrosis, honeycomb change, and fibroblast foci. Five cases were considered difficult because of prominent NSIP-like areas in two, extensive honeycomb change in one, superimposed diffuse alveolar damage in one, and superimposed bronchiolitis obliterans-organizing pneumonia in one. The most helpful feature for diagnosing UIP in difficult cases was the presence of a distinct patchwork appearance to the characteristic uneven or variegated parenchymal involvement along with evidence of architectural derangement. No explant showing UIP was preceded by biopsy findings of NSIP, and the one NSIP case appeared similar at biopsy and explant. NSIP or NSIP-like areas and UIP may reflect different mechanisms of fibrosis related either to different severity of injury or to different injuries.
Protective effect of muramyl dipeptide analogs against infections of Pseudomonas aeruginosa or Candida albicans in mice (1981)

Two analogs of N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) were found to give better protection than muramyl dipeptide against intraperitoneal Pseudomonas aeruginosa infection or intravenous Candida albicans infection in mice. The analogs tested were N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and N-acetylmuramyl-L-alpha-amino-butyryl-D-isoglutamine. The optimum treatment was 80 mg/kg per day given once daily for 4 consecutive days before infection by the intraperitoneal, intravenous, or subcutaneous route. Dose response was limited. The compounds were not orally active. Synergism was seen between N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine and gentamicin. No postinfection protection was observed. A nonspecific stimulation of macrophage cells by muramyl dipeptide analogs may contribute to the protection because antiinfective activity against Listeria monocytogenes given intraperitoneally was achieved with CBA mice.