Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of MgADP on cross‐bridge kinetics: a laser flash photolysis study of guinea‐pig smooth muscle.

1. The effects of MgADP on cross‐bridge kinetics were investigated using laser flash photolysis of caged ATP (P3‐1(2‐nitrophenyl) ethyladenosine 5'‐triphosphate), in guinea‐pig portal vein smooth muscle permeabilized with Staphylococcus aureus alpha‐toxin. Isometric tension and in‐phase stiffness transitions from rigor state were monitored upon photolysis of caged ATP. The estimated concentration of ATP released from caged ATP by high‐pressure liquid chromatography (HPLC) was 1.3 mM. 2. The time course of relaxation initiated by photolysis of caged ATP in the absence of Ca2+ was well fitted during the initial 200 ms by two exponential functions with time constants of, respectively, tau 1 = 34 ms and tau 2 = 1.2 s and relative amplitudes of 0.14 and 0.86. Multiple exponential functions were needed to fit longer intervals; the half‐time of the overall relaxation was 0.8 s. The second order rate constant for cross‐bridge detachment by ATP, estimated from the rate of initial relaxation, was 0.4‐2.3 x 10(4) M‐1 s‐1. 3. MgADP dose dependently reduced both the relative amplitude of the first component and the rate constant of the second component of relaxation. Conversely, treatment of muscles with apyrase, to deplete endogenous ADP, increased the relative amplitude of the first component. In the presence of MgADP, in‐phase stiffness decreased during force maintenance, suggesting that the force per cross‐bridge increased. The apparent dissociation constant (Kd) of MgADP for the cross‐bridge binding site, estimated from its concentration‐dependent effect on the relative amplitude of the first component, was 1.3 microM. This affinity is much higher than the previously reported values (50‐300 microM for smooth muscle; 18‐400 microM for skeletal muscle; 7‐10 microM for cardiac muscle). It is possible that the high affinity reflects the properties of a state generated during the co‐operative reattachment cycle, rather than that of the rigor bridge. 4. The rate constant of MgADP release from cross‐bridges, estimated from its concentration‐dependent effect on the rate constant of the second (tau 2) component, was 0.35‐7.7 s‐1. To the extent that reattachment of cross‐bridges could slow relaxation even during the initial 200 ms, this rate constant may be an underestimate. 5. Inorganic phosphate (Pi, 30 mM) did not affect the rate of relaxation during the initial approximately 50 ms, but accelerated the slower phase of relaxation, consistent with a cyclic cross‐bridge model in which Pi increases the proportion of cross‐bridges in detached ('weakly bound') states. (ABSTRACT TRUNCATED AT 400 WORDS)
Utilizing a D-Amino Acid as a Drug Carrier for Antineoplastic Nitrogen Mustard Groups

The evaluation of an alkylating nitrogen mustard agent that utilizes D-alanine as a drug carrier for three chloroethyl substituents (ClCH2CH2-) is shown. Various important pharmacological properties were determined including polar surface area, partition coefficient, molar volume, polarizability, numbers of -OH and -NH2 groups, and aqueous solubility. The synthetic approach utilizes 1,2-dichloroethane reaction with the primary amine of D-alanine resulting in chloroethyl (ClCH2CH2-) substituents. A nitrogen mus-tard group results, and this agent showed alkylation activity in aqueous solution directed toward a nucleophilic primary amine group. Kinetics of alkylation activity is determined by placing p-chloroaniline and the nitrogen mustard agent in sodium bicarbonate buffered aqueous solution at physiological pH 7.4 and 37°C. Samples taken from the test solution are injected with fluorescamine that reacts specifically with primary amine functional groups. Absorbance measurements obtained at 400 nm by UV-Vis spectrometer indicates the relative amounts of nonalkylated p-chloroaniline in the test solution. The D-alanine nitrogen mustard agent effectively alkylated the nucleophilic primary amine of p-chloroaniline with zero-order kinetics. The rate constant was determined to be 7.445E-04 mol/l/min. Formula weight, polar surface area, Log P, molar volume, violations of Rule of 5 for D-alanine mustard agent are 276.59, 29.543 angstroms2, 1.605, 222.3 cm3, and zero violations, respectively. Cluster analysis of molecular properties showed D-alanine mustard agent to be quite similar to cyclophosphamide. This agent showed good druglikeness and zero violations of the Rule of 5, indicating good bioavailability. Molecular properties calculated for the mustard agent are numerically comparable to some clinical anticancer drugs.
Hepatic ultrastructure in the Hurler syndrome.

The heritable disorder of man known as the Hurler syndrome (lipochondrodystrophy, gargoylism, dysostosis multiplex) has in the past decade advanced from the status of a rare medical curiosity to a clinical problem of considerable research interest. It is a biochemical disorder of connective tissue metabolism, which may be transmitted either as a sex-linked recessive affecting only males, or as a simple autosomal recessive affecting both sexes.1'2 This disorder is characterized by excessive excretion in urine and excessive accumulation in liver and other tissues of the acid mucopolysaccharides, chondroitin sulfuric acid-B (/3-heparin) and heparin monosulfuric acid (heparitin). 3-7 The chemical nature of these carbohydrate polymers, which are usually complexed with proteins in their natural state, has rendered difficult their precise identification and localization by available histochemical techniques.8 Studies of Hurler liver based on histochemical and morphologic observations at the level of light microscopy have not clearly resolved the question as to whether these mucopolysaccharide-protein substances exist primarily intracellularly or extracellularly.9'13 Our earlier studies of liver ultrastructure in the Hurler syndrome clearly demonstrated the intracytoplasmic vacuolar accumulation of these glycoprotein substances. Morphologically these vacuoles appeared to be comparable to similar glycoprotein accumulations in cells of the poison glands of reptiles.14 Orizaga, Haust, Bryans and Frank,15 also observed the intracellular accumulation of this material thus confirming our initial findings. '4 They further stated, however, that all other cellular organelles, including lysosomes, appeared unaltered except for the mitochondria which were increased in density and reduced in number. Our observations on mitochondria and lysosomes1" were not in agreement with these statements. Subsequent work by Van Hoof and Hers 17 on liver ultrastructure in Hurler's syndrome confirmed our findings. In an attempt to elucidate the mechanism of mucopolysaccharide storage in the liver and to determine whether specific cellular organelles
Primary Canine and Feline Nervous System Tumors: Intraoperative Diagnosis Using the Smear Technique

The recent application of neuroimaging techniques in veterinary neurology has led to the accurate localization of many types of intracranial lesions but has also created a clinical need, particularly with brain tumors, for a specific intraoperative diagnosis. For human brain tumors, a smear technique has been used successfully for many years to provide an extremely rapid, highly accurate intraoperative diagnosis. In similar smear preparations of intracranial lesions, obtained either by computed tomography (CT)-guided stereobiopsy or from a craniotomy, we have described distinguishing cytologic features of some primary spontaneous nervous system tumors in 80 dogs and 13 cats. A final diagnosis was confirmed by evaluation of paraffin-embedded sections from the same sample and, when appropriate, by immunocytochemical staining. Preliminary findings indicate that, in dogs and cats, this procedure is useful for rapid, accurate intraoperative diagnosis of many primary nervous system tumors. The distinguishing features of the canine and feline tumors bear a remarkably close resemblance to their human counterparts.
Long‐interval T2‐weighted subtraction magnetic resonance imaging: A powerful new outcome measure in multiple sclerosis trials

To compare long‐interval T2‐weighted subtraction (T2w‐Sub) imaging with monthly gadolinium‐enhanced T1‐weighted (Gd‐T1w) imaging for (1) detection of active lesions, (2) assessment of treatment efficacy, and (3) statistical power, in a multiple sclerosis (MS), phase 2, clinical trial setting.
Comparative Analysis and Optimization of Power Loss Based on the Isolated Series/Multi Resonant Three-Port Bidirectional DC-DC Converter

Based on the loss distribution and efficiency analysis, a comparative study between a series resonant three-port bidirectional DC-DC converter (SR-TBC) and a multi-resonant three-port bi-directional DC-DC converter (MR-TBC) is reported here. By using the Fourier equivalent analysis method in hand, the resonant current, switching current expressions, zero voltage soft switching (ZVS) conditions of MR-TBC and SR-TBC are deduced. Besides, in consideration of efficiency and soft switching aspects, the loss models of main power components and resonant elements are integrated and optimized for both topologies. Their loss distributions are established, and the different effects derived from the adoption of SiC MOSFET and Si MOSFET on the converter efficiency are discussed. Finally, to verify the theoretical analyses, comparative experiments under diverse load states are conducted based on the prototypes of the MR-TBC and SR-TBC. The obtained results demonstrate that the MR-TBC successfully broadens the ZVS range and thus achieves higher efficiency along the entire load range.
Phylogeny and PCR Identification of Clinically Important Zygomycetes Based on Nuclear Ribosomal-DNA Sequence Data

ABSTRACT A molecular database for all clinically important Zygomycetes was constructed from nucleotide sequences from the nuclear small-subunit (18S) ribosomal DNA and domains D1 and D2 of the nuclear large-subunit (28S) ribosomal DNA. Parsimony analysis of the aligned 18S and 28S DNA sequences was used to investigate phylogenetic relationships among 42 isolates representing species of Zygomycetes reported to cause infections in humans and other animals, together with commonly cultured contaminants, with emphasis on members of the Mucorales. The molecular phylogeny provided strong support for the monophyly of the Mucorales, exclusive of Echinosporangium transversale andMortierella spp. , which are currently misclassified within the Mucorales. Micromucor ramannianus, traditionally classified within Mortierella, and Syncephalastrum racemosum represent the basal divergences within the Mucorales. Based on the 18S gene tree topology, Absidia corymbiferaand Rhizomucor variabilis appear to be misplaced taxonomically. A. corymbifera is strongly supported as a sister group of the Rhizomucor miehei-Rhizomucor pusillusclade, while R. variabilis is nested withinMucor. The aligned 28S sequences were used to design 13 taxon-specific PCR primer pairs for those taxa most commonly implicated in infections. All of the primers specifically amplified DNA of the size predicted based on the DNA sequence data from the target taxa; however, they did not cross-react with phylogenetically related species. These primers have the potential to be used in a PCR assay for the rapid and accurate identification of the etiological agents of mucormycoses and entomophthoromycoses.
Epigenetic induction of tissue inhibitor of matrix metalloproteinase‐3 by green tea polyphenols in breast cancer cells

Aberrant epigenetic silencing of the tissue inhibitor of matrix metalloproteinase‐3 (TIMP‐3) gene that negatively regulates matrix metalloproteinases (MMPs) activity has been implicated in the pathogenesis and metastasis of breast cancer. In the present study, we demonstrate that green tea polyphenols (GTP) and its major constituent, epigallocatechin‐3‐gallate (EGCG) mediate epigenetic induction of TIMP‐3 levels and play a key role in suppressing invasiveness and gelatinolytic activity of MMP‐2 and MMP‐9 in breast cancer cells. Treatment of MCF‐7 and MDA‐MB‐231 breast cancer cells with 20 µM EGCG and 10 µg/mL GTP for 72 h significantly induces TIMP‐3 mRNA and protein levels. Interestingly, investigations into the molecular mechanism revealed that TIMP‐3 repression in breast cancer cells is mediated by epigenetic silencing mechanism(s) involving increased activity of the enhancer of zeste homolog 2 (EZH2) and class I histone deacetylases (HDACs), independent of promoter DNA hypermethylation. Treatment of breast cancer cells with GTP and EGCG significantly reduced EZH2 and class I HDAC protein levels. Furthermore, transcriptional activation of TIMP‐3 was found to be associated with decreased EZH2 localization and H3K27 trimethylation enrichment at the TIMP‐3 promoter with a concomitant increase in histone H3K9/18 acetylation. Our findings highlight TIMP‐3 induction as a key epigenetic event modulated by GTPs in restoring the MMP:TIMP balance to delay breast cancer progression and invasion. © 2014 Wiley Periodicals, Inc.
Assessing the Quality of OpenStreetMap Data in South Africa in Reference to National Mapping Standards

The introduction and success of Volunteered Geographic Information (VGI) has gained the interest of National Mapping Agencies (NMAs). VGI is geographic information that is freely generated by non-experts and shared using VGI initiatives available on the Internet. NMAs are looking to this volunteer information to maintain their topographic databases; however, the main concern is the quality of the data. The purpose of this study is to assess whether it is feasible to use VGI to update authoritative databases, specifically in South Africa. The data from OpenStreetMap (OSM), which is one of the most successful VGI initiatives, was compared to a reference data set provided by the NMA of South Africa i.e. the Chief Directorate: National Geo-Spatial Information (CD: NGI). The results demonstrate that the OSM quality is heterogeneous across South Africa. Some of the quality measures are higher, while others are lower than that stipulated by the CD: NGI. OSM data is therefore not within CD: NGI’s national mapping requirements.
Terahertz imaging - new steps toward real-life applications

We are studying several novel steps toward real-life applications of terahertz and millimeter waves, such as, i) Non-destructive detection of illicit drugs using spectral fingerprints, ii) Laser-terahertz emission microscope for semiconductor device under test, iii) Real-time inspection system to detect micro-leak defects in the seal of flexible plastic packages, iv) Prism-shaped Fabry-Perot etalon for absorption measurement, v) Development of terahertz direct detector using superconducting tunnel junctions, vi) Water content measurement in plants and seeds, vii) Monitoring of water/ice state in food stuffs, viii) Non-thermal effect of millimeter wave radiation on cell membrane. In this paper, we introduce some of our recent activities.
Hull husbandry practices and biofouling management of vessels operating in California

Commercial shipping has been recognized as the primary vector for the introduction of nonindigenous species (NIS) into coastal environments in California, North America, and across the globe. These shipping-mediated introductions occur primarily through two mechanisms, ballast water and vessel biofouling (i.e. the attachment or association of organisms to a vessel's wetted surfaces). In California, vessel biofouling is believed to be responsible for up to 60% of the 257 nonindigenous species currently established in California's coastal waters. Most vessel operators manage the biofouling on their hulls because of the impact biofouling has on drag, fuel consumption, and operating costs. However, the biofouling associated with a vessel's remaining underwater surfaces, including the “niche areas” that are more susceptible to biofouling because of variable hydrodynamic flow or inadequate antifouling protection (e.g. bilge keels and sea chests), are often undermanaged or unmanaged and may pose a greater risk of species introduction. Biofouling management options vary depending on factors such as vessel type and speed. Because of this, there are many varied biofouling management strategies implemented across the global fleet of vessels. The patterns of these management schemes, along with patterns of voyage characteristics that influence biofouling accumulation, are important tools in assessing risk of species introduction. The California State Lands Commission's Marine Invasive Species Program has been collecting, on an annual basis, detailed information on these management strategies and voyage characteristics from every vessel operating in California since 2008. These data are currently being used to assess the risk of biofouling-mediated species introductions to California and to inform the development of mandatory management requirements to reduce NIS introduction risk to California.
Computation EvaBio: A Tool for Performance Evaluation in Biometrics

Performance evaluation is a key factor in biometrics. In order to assess the quality of a new biometric system, one has in general to compute the perfor- mance on a large dataset to have signiﬁcant results. It is not always an easy task as the computation complexity could be important. Moreover, the use of existing datasets is not obvious as it is represented in diﬀerent ways (datasets, directory of images) and contain multiple scenarios (single enrollment process, diﬀerent numbers of samples for the template generation for each user, etc.). We propose in this paper a new distributed-based platform facilitating the com- putation on diﬀerent datasets in biometrics. The architecture of the proposed platform is composed of a server distributing computation tasks on its available clients. Experimental results on two biometric datasets (PolyU ﬁnger knuckle print and AR face datasets) show the beneﬁt of proposed computing platform.
Control of axon–axon attraction by Semaphorin reverse signaling

Significance Bidirectional signaling between ligand and receptor facilitates cell–cell communication. Recent studies show that members of the well-known Semaphorin family proteins can mediate both forward and reverse signaling in regulating neural network formation. In this study, we identify new components of the Semaphorin reverse signaling pathway and reveal a novel mechanism by which Semaphorin reverse signaling promotes axon–axon attraction in patterning neuronal circuitry during development. Semaphorin family proteins are well-known axon guidance ligands. Recent studies indicate that certain transmembrane Semaphorins can also function as guidance receptors to mediate axon–axon attraction or repulsion. The mechanisms by which Semaphorin reverse signaling modulates axon-surface affinity, however, remain unknown. In this study, we reveal a novel mechanism underlying upregulation of axon–axon attraction by Semaphorin-1a (Sema1a) reverse signaling in the developing Drosophila visual system. Sema1a promotes the phosphorylation and activation of Moesin (Moe), a member of the ezrin/radixin/moesin family of proteins, and downregulates the level of active Rho1 in photoreceptor axons. We propose that Sema1a reverse signaling activates Moe, which in turn upregulates Fas2-mediated axon–axon attraction by inhibiting Rho1.
Solid-state characterization of Felodipine–Soluplus amorphous solid dispersions

Abstract The aim of the current study is to develop amorphous solid dispersion (SD) via hot melt extrusion technology to improve the solubility of a water-insoluble compound, felodipine (FEL). The solubility was dramatically increased by preparation of amorphous SDs via hot-melt extrusion with an amphiphilic polymer, Soluplus® (SOL). FEL was found to be miscible with SOL by calculating the solubility parameters. The solubility of FEL within SOL was determined to be in the range of 6.2–9.9% (w/w). Various techniques were applied to characterize the solid-state properties of the amorphous SDs. These included Fourier Transform Infrared Spectrometry spectroscopy and Raman spectroscopy to detect the formation of hydrogen bonding between the drug and the polymer. Scanning electron microscopy was performed to study the morphology of the SDs. Among all the hot-melt extrudates, FEL was found to be molecularly dispersed within the polymer matrix for the extrudates containing 10% drug, while few small crystals were detected in the 30 and 50% extrudates. In conclusion, solubility of FEL was enhanced while a homogeneous SD was achieved for 10% drug loading.
Rapid antigenic-type replacement and DNA sequence evolution of canine parvovirus

Analysis of canine parvovirus (CPV) isolates with a panel of monoclonal antibodies showed that after 1986, most viruses isolated from dogs in many parts of the United States differed antigenically from the viruses isolated prior to that date. The new antigenic type (designated CPV type 2b) has largely replaced the previous antigenic type (CPV type 2a) among virus isolates from the United States. This represents the second occurrence of a new antigenic type of this DNA virus since its emergence in 1978, as the original CPV type (CPV type 2) had previously been replaced between 1979 and 1981 by the CPV type 2a strain. DNA sequence comparisons showed that CPV types 2b and 2a differed by as few as two nonsynonymous (amino acid-changing) nucleotide substitutions in the VP-1 and VP-2 capsid protein genes. One mutation, resulting in an Asn-Asp difference at residue 426 in the VP-2 sequence, was shown by comparison with a neutralization-escape mutant selected with a non-CPV type 2b-reactive monoclonal antibody to determine the antigenic change. The mutation selected by that monoclonal antibody, a His-Tyr difference in VP-2 amino acid 222, was immediately adjacent to residue 426 in the three-dimensional structure of the CPV capsid. The CPV type 2b isolates are phylogenetically closely related to the CPV type 2a isolates and are probably derived from a common ancestor. Phylogenetic analysis showed a progressive evolution away from the original CPV type. This pattern of viral evolution appears most similar to that seen in some influenza A viruses.
Pharmacokinetics and bacteriological efficacy of cefoperazone, ceftriaxone, and moxalactam in experimental Streptococcus pneumoniae and Haemophilus influenzae meningitis

The pharmacokinetics and bacteriological efficacy of cefoperazone, cefuroxime, ceftriaxone, and moxalactam were evaluated in the experimental rabbit meningitis model of Haemophilus influenzae type b or Streptococcus pneumoniae infection. The cerebrospinal fluid penetration of these beta-lactam antibiotics was from 3 to 14% and was greater in Haemophilus-infected that in pneumococcus-infected animals. With the exception of moxalactam, the antibacterial activity in cerebrospinal fluid and change in concentration of bacteria during therapy with the test drugs were comparable to those of penicillin G in pneumococcal infection. In animals infected with H. influenzae, cefoperazone, moxalactam, and ceftriaxone were as effective as chloramphenicol in reducing the bacterial counts in cerebrospinal fluid. Moxalactam and ceftriaxone produced the largest cerebrospinal fluid bactericidal titers against this beta-lactamase-producing strain of Haemophilus. On the basis of these data, it was concluded that ceftriaxone and cefoperazone were effective against both pathogens in this meningitis model, whereas moxalactam was effective against only Haemophilus, and cefuroxime was effective against only S. pneumoniae.