gebhart/patrepeval huggingface dataset:
Cooperative, computer-aided design of scientific visualizations (1991)

While the field of scientific visualization has grown rapidly over the last decade, the task of designing graphical displays that effectively depict the data to be visualized is still a time-consuming, difficult, and essentially manual process. This paper proposes an approach to partially automating the process through cooperative computer-aided design (CCAD)--a paradigm that combines the strengths of manual and automated design by interspersing guiding design operations by the human user with the exploration of design alternatives by the computer. We demonstrate this approach in the context of the IVE design system--a CCAD environment for the design of scientific visualizations. Given a set of design requirements, the system is able to generate several alternative visualizations using a set of design rules that combine primitive visualization components in different ways. These alternatives are presented graphically to the user, who can browse through them, select the most promising visualization and refine it manually.
Design and Selection of Probes for In Vivo Molecular Targeting and Imaging (2015)

Molecular targeting with nerve-binding peptides and activatable cell penetrating peptides (ACPPs) enables site-specific delivery of imaging agents or therapeutics in vivo. Nerve binding peptides conjugated to fluorescent dyes improve intraoperative identification of nerves, which should reduce accidental transection, thus reducing patient morbidities, and enhance nerve repair in pre-existing injury, improving outcomes. To enhance in vivo nerve contrast and advance the potential clinical application of first generation nerve-highlighting peptides, such as NP41, identifying molecular binding targets, improving affinity, reducing off-target binding, and validating function in human nerve is needed. Laminins-421, -211, and collagen VI were identified as NP41's binding targets using a novel tool developed to improve the isolation of low affinity interacting molecules, termed Ligand-Proximal Photooxidation (ProxPhOx). This approach uses light activation of a singlet-oxygen generating (SOG) fluorophore conjugated to a ligand to create a highly localized area of oxidation that can be covalently tagged with biotin hydrazide for purification. A new NP41-derivatized peptide, NP713, had higher affinity, in vivo contrast, and showed higher labeling of human nerve sections than NP41. Beyond improving nerve peptides, we sought to more specifically target disease sites using ACPPs. ACPPs sensitive to matrix metalloproteinases (MMPs), particularly MMP-2/-9, have been shown to target tumors and metastases; however, improvement in the enzyme selectivity and targeting of other proteases have the potential to increase uptake and specificity of localization to these and other disease sites. Detailed characterization of the selectivity of various substrates revealed potential enzyme targets, that when coupled to their application in disease models may reveal new biological insight, as well as creating potential diagnostic and therapeutic agents. Finally, intracellular delivery of non-membrane permeable therapeutics represents a major bottleneck in molecular targeting. The development of a novel assay for cytoplasmic delivery enabled quantification of membrane translocation efficiency and may allow identification of more effective carriers. The cumulative research presented here advances the use of nerve-targeted fluorophores and of ACPP-targeted drugs and contrast agents in the clinic. These agents will allow surgeons to accomplish difficult operations more precisely and will help clinicians to better diagnose and treat many diseases.
EXPRESSION OF CYTOKERATIN 7, 20, 14 IN UROTHELIAL CARCINOMA AND SQUAMOUS CELL CARCINOMA OF THE EGYPRIAN URINARY BLADDER CANCER (2014)

This study estimated the expression of CK-7, CK14, and CK-20 protein in human bladder carcinoma, urothelial carcinoma (UC) in comparison to squamous cell carcinoma (SCC) and to show its possible correlation to clinicopathologic parameters (grade and stage and bilharziasis), and investigate whether cytokeratin 14 immunostaining may be useful to detect earlysquamous metaplasia in bladder biopsies and in association with UC. We evaluated the bladder tissues of 200 patients with bladder carcinoma, 150 patients had UC, and 50 patients had SCC. Imunohistochemical technique was used for detection of CK7, CK14 and CK20 monoclonal antibodies. The mean age of the patients was 55 years (range51- 70 years). The UC were classified according to grades into grade I, II and III in 20, 40 and 90 cases, respectively. Stages of UC were: Ta in 10, T1 in 60 and 90 patients with muscle-invasive T2-3. In UC cases 105 /150 (70%) were positive for over expression of CK20. In the same group of UC 120/150 (80) were positive for over expression of CK7. Negative expression was found in SCC cases. A High grades of the UC were associated with decrease expression of CK 20, there were 20 (100%) in GI, 35 (87.5%) in GII, 50 (68.6%) in GIII (P <0.01), and an increase expression of CK7 4 (20%) in GI, 26 (65%) in GII, 90(100%) in GIII (P <0.01). CK20 expression decreased as the tumor stages increased, it was 15 (100%) in Ta, 50 (83.3%) in T1, 40 (50%) in T2-3 (P <0.01), while CK7 showed increase expression in 2 cases with Ta tumor(20%), 38 (47.5%) in T1, 80 (100%) in T2-T3 (P <0.01). The present study confirmed that CK14 is expressed in SCC and in UC with squamous differentiation.
Tremor arrest with thalamic microinjections of muscimol in patients with essential tremor (1999)

Six patients undergoing stereotactic procedures for essential tremor received microinjections of muscimol (a gamma-aminobutyric acid-A [GABA(A)] agonist) into the ventralis intermedius thalamus in areas where tremor-synchronous cells were identified electrophysiologically with microelectrode recordings and where tremor reduction occurred with electrical microstimulation. Injections of muscimol but not saline consistently reduced tremor in each patient. The effect had a mean latency of 7 minutes and lasted an average of 9 minutes. We propose that GABA-mediated thalamic neuronal inhibition may represent a mechanism underlying the effectiveness of surgery for tremor and that GABA analogues could potentially be used therapeutically.
Determining the Stage of the Estrous Cycle in the Mouse by the Appearance of the Vagina (1973)

A simple method is described by which the various stages of the estrous cycle of the mouse can be easily determined by the appearance of the vagina. Data are presented which show that this method of determining estrous state is at least as accurate and reliable as the customary method of vaginal smearing. The method is faster, and less stressful to the animals than the vaginal smear procedure. Since the initial study of the estrous cycle in the guinea pig by Stockard and Papanicolaou in 1917, the vaginal smear technique has been the accepted procedure for determining the estrous state in various mammalian species. The technique involves an identification of the cell types and their relative quantities present in preparations obtained from the vagina by either scraping or swabbing the vaginal walls, or by vaginal washings. The technique is not without its disadvantages. Emery and Schwabe (1936) have reported that frequent vaginal smearing of both castrate and intact rats using cotton swabs resulted in an abnormally high incidence of cornified or estrus-like smears. Frequent smearing has also been found to result in cornification of the vaginal epithelium in mice (Wade and Doisy, 1935). Vaginal smearing, particularly during estrus, could induce pseudopregnancy and result in abnormally long cycles. Gross changes in the appearance of the
Evidence for immune selection of hepatitis C virus (HCV) putative envelope glycoprotein variants: potential role in chronic HCV infections. (1992)

E2/nonstructural protein 1, the putative envelope glycoprotein (gp72) of HCV, possesses an N-terminal hypervariable (E2 HV) domain from amino acids 384 to 414 of unknown significance. The high degree of amino acid sequence variation in the E2 HV domain appears to be comparable to that observed in the human immunodeficiency virus type 1 gp120 V3 domain. This observation and the observation that the HCV E2 HV domain lacks conserved secondary structure imply that, like the V3 loop of human immunodeficiency virus 1 gp120, the N-terminal E2 region may encode protective epitopes that are subject to immune selection. Antibody-epitope binding studies revealed five isolate-specific linear epitopes located in the E2 HV region. These results suggest that the E2 HV domain is a target for the human immune response and that, in addition to the three major groups of HCV, defined by nucleotide and amino acid sequence identity among HCV isolates, E2 HV-specific subgroups also exist. Analysis of the partial or complete E2 sequences of two individuals indicated that E2 HV variants can either coexist simultaneously in a single individual or that a particular variant may predominate during different episodes of disease. In the latter situation, we found one individual who developed antibodies to a subregion of the E2 HV domain (amino acids 396-407) specific to a variant that was predominant during one major episode of hepatitis but who lacked detectable antibodies to the corresponding region of a second variant that was predominant during a later episode of disease. The data suggest that the variability in the E2 HV domain may result from immune selection. The findings of this report could impact vaccine strategies and drug therapy programs designed to control and eliminate HCV.
Irreversible Catalyst Activation Enables Hyperpolarization and Water Solubility for NMR Signal Amplification by Reversible Exchange (2014)

Activation of a catalyst [IrCl(COD)(IMes)] (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene; COD = cyclooctadiene)] for signal amplification by reversible exchange (SABRE) was monitored by in situ hyperpolarized proton NMR at 9.4 T. During the catalyst-activation process, the COD moiety undergoes hydrogenation that leads to its complete removal from the Ir complex. A transient hydride intermediate of the catalyst is observed via its hyperpolarized signatures, which could not be detected using conventional nonhyperpolarized solution NMR. SABRE enhancement of the pyridine substrate can be fully rendered only after removal of the COD moiety; failure to properly activate the catalyst in the presence of sufficient substrate can lead to irreversible deactivation consistent with oligomerization of the catalyst molecules. Following catalyst activation, results from selective RF-saturation studies support the hypothesis that substrate polarization at high field arises from nuclear cross-relaxation with hyperpolarized (1)H spins of the hydride/orthohydrogen spin bath. Importantly, the chemical changes that accompanied the catalyst's full activation were also found to endow the catalyst with water solubility, here used to demonstrate SABRE hyperpolarization of nicotinamide in water without the need for any organic cosolvent--paving the way to various biomedical applications of SABRE hyperpolarization methods.
Practical Illustrations in Tissue Engineering: Surgical Considerations Relevant to the Implantation of Osteoinductive Devices (2000)

This paper provides practical illustrations in the use of osteoinductive devices (biomaterial carriers coupled with osteoinductive morphogens) for bone tissue engineering. We discuss the considerations relative to the implantation of these devices that may induce tissues that are located outside the boundaries of the osteoinductive device as well as outside boundaries of the normal skeletal envelope. Five reports of osteoinductive devices generating such tissues are reviewed. Histologic and radiographic data from a sixth example are presented and compared with histologic and radiographic findings typical of two varieties of myositis ossificans. A theory is advanced that osteoinductive implants may induce ectopic tissues that resemble fibro-osseous pathologies. Finally characteristics of tissue-engineered bone graft substitutes that may contribute to development of these pathologies and device characteristics that may obviate these ectopic tissues are considered.
Enhanced Potency of Human Sonic Hedgehog by Hydrophobic Modification (2001)

Post-translational modifications of the developmental signaling protein Sonic hedgehog (Shh) by a long-chain fatty acid at the N-terminus and cholesterol at the C-terminus greatly activate the protein in a cell-based signaling assay. To investigate the structural determinants of this activation phenomenon, hydrophobic and hydrophilic moieties have been introduced by chemical and mutagenic methods to the soluble N-terminal signaling domain of Shh and tested in both in vitro and in vivo assays. A wide variety of hydrophobic modifications increased the potency of Shh when added at the N-terminus of the protein, ranging from long-chain fatty acids to hydrophobic amino acids, with EC(50) values from 99 nM for the unmodified protein to 0.6 nM for the myristoylated form. The N-myristoylated Shh was as active as the natural form having both N- and C-terminal modifications. The degree of activation appears to correlate with the hydrophobicity of the modification rather than any specific chemical feature of the adduct; moreover, substitution with hydrophilic moieties decreased activity. Hydrophobic modifications at the C-terminus of Shh resulted in only a 2-3-fold increase in activity, and no activation was found with hydrophobic modification at other surface positions. The N-terminal modifications did not appear to alter the binding affinity of the Shh protein for the transfected receptor protein, Patched, and had no apparent effect on structure as measured by circular dichroism, thermal denaturation, and size determination. Activation of Desert Hh through modification of its N-terminus was also observed, suggesting that this is a common feature of Hh proteins.
Rosacea subtypes: a treatment algorithm. (2004)

Based on various signs and symptoms, the National Rosacea Society (NRS) Expert Committee has divided the syndrome of rosacea into 4 major subtypes: erythematotelangiectatic, papulopustular (inflammatory), phymatous, and ocular. Each of the subtypes can be divided further into more specific subgroups. For example, sensory rosacea is an additional subtype that can be recognized and treated. Signs and symptoms may direct therapy. This article proposes an overview of common treatments based on subtypes. Treatments that have been validated by randomized controlled trials are reviewed. However, many excellent treatments have not been validated by double-blind randomized trials.
'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data (1999)

(1999). 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica: Vol. 29, No. 11, pp. 1181-1189.
Effect of aging on respiratory system physiology and immunology (2006)

With the looming expansion of the elderly population of the US, a thorough understanding of "normal" aging-related changes on the respiratory system is paramount. The respiratory system undergoes various anatomical, physiological and immunological changes with age. The structural changes include chest wall and thoracic spine deformities which impairs the total respiratory system compliance leading to increase work of breathing. The lung parenchyma loses its supporting structure causing dilation of air spaces: "senile emphysema". Respiratory muscle strength decreases with age and can impair effective cough, which is important for airway clearance. The lung matures by age 20-25 years, and thereafter aging is associated with progressive decline in lung function. The alveolar dead space increases with age, affecting arterial oxygen without impairing the carbon dioxide elimination. The airways receptors undergo functional changes with age and are less likely to respond to drugs used in younger counterparts to treat the same disorders. Older adults have decreased sensation of dyspnea and diminished ventilatory response to hypoxia and hypercapnia, making them more vulnerable to ventilatory failure during high demand states (ie, heart failure, pneumonia, etc) and possible poor outcomes.
Characterization of the cellular uptake and metabolic conversion of acetylated N‐acetylmannosamine (ManNAc) analogues to sialic acids (2004)

"Sialic acid engineering" refers to the strategy where cell surface carbohydrates are modified by the biosynthetic incorporation of metabolic intermediates, such as non-natural N-acetylmannosamine (ManNAc) analogues, into cellular glycoconjugates. While this technology has promising research, biomedical, and biotechnological applications due to its ability to endow the cell surface with novel physical and chemical properties, its adoption on a large scale is hindered by the inefficient metabolic utilization of ManNAc analogues. We address this limitation by proposing the use of acetylated ManNAc analogues for sialic acid engineering applications. In this paper, the metabolic flux of these "second-generation" compounds into a cell, and, subsequently, into the target sialic acid biosynthetic pathway is characterized in detail. We show that acetylated ManNAc analogues are metabolized up to 900-fold more efficiently than their natural counterparts. The acetylated compounds, however, decrease cell viability under certain culture conditions. To determine if these toxic side effects can be avoided, we developed an assay to measure the cellular uptake of acetylated ManNAc from the culture medium and its subsequent flux into sialic acid biosynthetic pathway. This assay shows that the majority ( > 80%) of acetylated ManNAc is stored in a cellular "reservoir" capable of safely sequestering this analogue. These results provide conditions that, from a practical perspective, enable the acetylated analogues to be used safely and efficaciously and therefore offer a general strategy to facilitate metabolic substrate-based carbohydrate engineering efforts. In addition, these results provide fundamental new insights into the metabolic processing of non-natural monosaccharides.
Escherichia coli iron superoxide dismutase targeted to the mitochondria of yeast cells protects the cells against oxidative stress. (1995)

A gene encoding a fusion protein consisting of Escherichia coli iron superoxide dismutase (FeSOD) with the mitochondrial targeting presequence of yeast manganese superoxide dismutase (MnSOD) was cloned and expressed in E. coli and in Saccharomyces cerevisiae DL1Mn- yeast cells deficient in MnSOD. In the yeast cells the fusion protein was imported into the mitochondrial matrix. However, the presequence was not cleaved. In a control set of experiments, the E. coli FeSOD gene without the yeast MnSOD leader sequence was also cloned and expressed in S. cerevisiae DL1Mn- cells. In this case the FeSOD was located in the cytosol and was not imported into the mitochondrial matrix. E. coli FeSOD, with and without the yeast MnSOD presequence, proved to be active in yeast, but, whereas the FeSOD targeted to the mitochondria of yeast cells deficient in MnSOD protected the cells from the toxic effects of oxidative stress, FeSOD without the yeast MnSOD presequence did not protect the yeast cells deficient in MnSOD against oxidative stress.
Spectrophotometric Determination of Nitrate with a Single Reagent (2003)

Abstract A spectrophotometric procedure for determination of nitrate in water, soil extracts, and a variety of other sample types is described using one reagent solution which is easily prepared and stored. Sample and equipment requirements are minimal. Reduced chemical hazard, simplicity, and versatility represent improvements over existing methods. Limit of detection is 0.01 µg N mL−1 (0.72 μM ) or less, depending on the matrix.
Background-minimized cassette mutagenesis by PCR using cassette-specific selection markers: a useful general approach for studying structure-function relationships of multisubstrate enzymes. (1995)

An efficient protocol, termed background-minimized cassette mutagenesis (BMCM) by PCR, has been developed for multiple mutagenesis of DNA. This method uses suitable extension primers for incorporating various mutation(s) and is not limited by either the nature of the mutation or the size and spatial location of mutational loci. Minimization of the wild type background clone and mutant selection at very high frequency were easily achieved through a two-step process. First, a deletion of a unique restriction site within the cassette was introduced through additional silent mutation(s). Then, the recombinant clones were digested with the corresponding enzyme followed by transformation when selective linearization of wild-type clone led to its near total removal leaving the mutant clones as the only practicable transformants. Because it is generally possible to design several such cassette-specific unique background minimization markers for any gene, for multiple mutagenesis involving distally located portions of the gene the present protocol is superior to other currently available methods. The efficiency of BMCM-PCR has been demonstrated here by using the multisubstrate enzyme 5-enolpyruvyl-shikimate-3-phosphate synthase (EPSPs) of Bacillus subtilis as a model system. Three different sets of cassettes of varying sizes were generated to encompass the three putative active/binding regions in the beginning, middle, and the end of the gene encoding EPSPs. Very high efficiency of mutation incorporation and selection were obtained in all cases. Furthermore, by taking advantage of the unique cassette-specific background elimination markers, it was possible to generate a nested set of double and/or triple mutants. The mutant enzymes were overexpressed in Escherichia coli and purified to near homogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)
Standardization of a Hierarchical Transactive Control System (2010)

resources, load control The authors describe work they have conducted toward the generalization and standardization of the transactive control approach that was first demonstrated in the Olympic Peninsula Project for the management of a transmission constraint. The newly generalized approach addresses several potential shortfalls of the prior approach: First, the authors have formalized a hierarchical node structure which defines the nodes and the functional signal pathways between these nodes. Second, by fully generalizing the inputs, outputs, and functional responsibilities of each node, the authors make the approach available to a much wider set of responsive assets and operational objectives. Third, the new, generalized approach defines transactive signals that
The Role of a Prescription in Anxiety Medication Use, Abuse, and Dependence (2010)

These results indicate that prescription for anxiety medications is associated with nonmedical use of these medications, although the direction of causality cannot be determined in this study. Although anxiety medications have clinical utility, greater clinical attention should be given to the potential for their abuse among patients at particular risk.