Transcriptional profiling of belatacept and calcineurin inhibitor therapy in renal allograft recipients.

Calcineurin inhibitor (CNI) use may lead to allograft injury and compromised renal function. Gene expression profiles of 12-month kidney biopsies from a Phase 3 study of belatacept and a CNI comparator, cyclosporine (CsA), were compared with expression profiles of a set of historical, demographically matched, preimplantation control biopsies. Gene set enrichment analysis was used to test each set of differentially expressed genes (DEGs) for the enrichment of an in vitro-derived CNI toxicity (CNIT) gene set and published gene sets associated with chronic allograft injury (CAI), immune modulation and tissue remodeling. The unique set of genes differentially expressed in CNI biopsies compared with preimplantation controls was enriched for genes associated with fibrosis, early tubulointerstitial damage and in vitro CNIT. The DEGs from belatacept biopsies were not enriched for the CNIT genes but, instead, exhibited enrichment for gene sets associated with immune response and tissue remodeling. A combined analysis of DEGs across both treatment groups identified select solute transporter and cellular differentiation genes whose expression at 12 months correlated with renal function at 36 months. These results provide mechanistic insights into the reduced CAI and higher renal function observed in belatacept- versus CsA-treated patients.

Identification and classification of arrhythmic heartbeats from electrocardiogram signals using feature induced optimal extreme gradient boosting algorithm.

Arrhythmic heartbeat classification has gained a lot of attention to accelerate the detection of cardiovascular diseases and mitigating the potential cause of one-third of deaths worldwide. In this article, a computer-aided diagnostic (CAD) approach has been proposed for the automated identification and classification of arrhythmic heartbeats from electrocardiogram (ECG) signals using multiple features aided supervised learning model. For proper diagnosis of arrhythmic heartbeats, MIT-BIH Arrhythmia database has been used to train and test the proposed approach. The ECG signals, extracted from sensor leads, have undergone pre-processing via discrete wavelet transform. Three sets of features, i.e. statistical, temporal, and spectral, are extracted from the processed ECG signals followed by random forest aided recursive feature elimination strategy to select the prominent features for proper classification of arrhythmic heartbeats by the proposed optimal extreme gradient boosting (O-XGBoost) classifier. Hyperparameters such as learning rate, tree-specific parameters, and regularization parameters have been optimized to improve the performance of the XGBoost classifier. Moreover, the synthetic minority over-sampling technique has been employed for balancing the dataset in order to improve the classification performance. Quantitative results reveal the remarkable performance over state-of-the-art methods. The proposed model can be implemented in any computer-aided diagnostic system with similar topological structures.

Bis(2,S-dimethyl-dithio-carbazate-κ(2)N(3),S)(nitrato-κO)copper(II) nitrate.

The title complex, [Cu(NO(3))(C(3)H(8)N(2)S(2))(2)]NO(3), represents a low-symmetry polymorph (P-1, Z = 4) of a previously reported form [P-1, Z = 2; Ali et al. (2011 ▶). Polyhedron, 30, 542-548]. The Cu(II) atom in each independent cation is found within a distorted square-pyramidal N(2)S(2)O coordination geometry defined by two N,S-bidentate ligands and an O atom derived from a monodentate nitrate. The primary difference between the cations is found in the relative orientations of the coordinated nitrate groups, which are directed to opposite sides of the mol-ecule. Supra-molecular layers along [110] and sustained by N-H⋯O inter-actions feature in the crystal packing. These are connected along the c axis by C-H⋯O inter-actions.

Benzyl 2-methyl-3-[(E)-(thio-phen-2-yl)methyl-idene]dithio-carbazate.

In the title compound, C(14)H(14)N(2)S(3), the thione S atom and methyl group are syn, as are the two thio-ether S atoms. The mol-ecule is twisted, the dihedral angles between the central (C(2)N(2)S(2)) residue and the pendent 2-thienyl and phenyl rings being 21.57 (6) and 77.54 (3)°, respectively. In the crystal, mol-ecules assemble into a three-dimensional architecture via C-H⋯π inter-actions, involving both the five- and six-membered rings as acceptors, as well as S⋯S inter-actions [3.3406 (5) Å] between centrosymmetrically related 2-thienyl rings.

Matrix-Mediated Synthesis of Nanocrystalline ggr-Fe2O3: A New Optically Transparent Magnetic Material.

A new magnetic material with appreciable optical transmission in the visible region at room temperature has been isolated as a gamma-Fe(2)O(3)/polymer nanocomposite. The synthesis is carried out in an ion-exchange resin at 60 degrees C. Magnetization and susceptibility data demonstrate loading-dependent saturation moments as high as 46 electromagnetic units per gram and superparamagnetism for lower loadings where particle sizes are less than 100 angstroms. Optical absorption studies show that the small-particle form of gamma-Fe(2)O(3) is considerably more transparent to visible light than the single-crystal form. The difference in absorption ranges from nearly an order of magnitude in the "red" spectral region to a factor of 3 at 5400 angstroms. The magnetization of the nanocomposite is greater by more than an order of magnitude than those of the strongest room-temperature transparent magnets, FeBO(3) and FeF(3).

Pentachlorophenol removal from water using surfactant-enhanced filtration through low-pressure thin film composite membranes.

Removal of pentachlorophenol from water is investigated using the surfactant-enhanced cross-flow membrane filtration technique in which anionic surfactant; sodium dodecyl sulfate (SDS) is the carrier of pentachlorophenol. The separation performances are studied by varying SDS concentrations (<

Canine transmissible venereal tumour: a review.

Canine transmissible venereal tumour (CTVT) is a contagious venereal tumour of dogs, commonly observed in dogs that are in close contact with one another, or in stray and wild dogs that exhibit unrestrained sexual activity. CTVT represents a unique, naturally transmissible, contagious tumour, where the mutated tumour cell itself is the causative agent and perpetuates as a parasitic allograft in the host. Clinical history, signalment and cytological features are often obvious for establishing a diagnosis though biopsy and histological examination may be needed in atypical cases. Most cases are curable with three intravenous injections of vincristine sulphate at weekly intervals. The role of stray and wild dogs makes the disease difficult to control and necessitates sustained animal birth control in stray dogs along with prompt therapy of the affected dogs. This review captures the manifold developments in different areas embracing this fascinating tumour, including its biology, diagnosis and therapeutic alternatives.

Shock-wave-induced enhancement of optical emission in nitrogen afterglow plasma.

This paper reports measurements of optical emission enhancement at the shock front of Mach 1.5 to Mach 3.5 shockwaves propagating in the afterglow of a 0.75 Torr nitrogen glow discharge. Electrically-generated shocks pass through the afterglow and create noticeable enhancements of the B 3Pig-A 3Sigma+u and C 3Piu-B 3Pig transitions of nitrogen. Under our discharge conditions, the electron Debye length was approximately the same magnitude as the shock thickness; this allows the possibility of a space-charge region extending beyond the neutral shockwave discontinuity. Previous researchers have measured enhancement in the B 3Pig-A 3Sigma+u optical emission at the shock front, but only in the active discharge. Fibers connected to photomultipler tubes measure the optical emission from the discharge. Laser deflection measures the shock velocity. The data reveals that the emission enhancement increases with Mach number, and also indicates that the emission enhancement decreases exponentially with time in the afterglow. Since the discharge voltage has already been shut off, the energy needed to create the emission enhancement cannot come from the power supply. We conclude that under our discharge conditions there is an increase in the already non-equilibrium energy of the electrons at the shock front via a shockwave-induced strong double layer.

Stereoelectronic effects in negatively and positively (Protonated) charged species. Ab initio studies of the gauche effect in 1,4-dioxa systems

A computational study ab initio of the conformational dependence of proton affinities of 2-methoxyethoxide (MEO), dimethoxyethane (DME), and 1,4-dioxane has been carried out at the MP2/6-31+G level of theory. The results were discussed in comparison with reference systems, from simple alkoxides and ethers to anomeric moieties, in open, cyclic, and bicyclic molecules. The COCCOC species are stronger bases than the COCOC (anomeric) ones and approach regular ethers in their strength. The gauche forms in MEO and DME are altogether stronger bases than the anti forms, and anti (equatorial) protonation is preferred over gauche (axial), unless ditopic protonation is possible, like in aga-DME or cis-tetraoxadecalin. The gauche effect plays a significant role in the formation, relative stability, and reactivity of the charged species.

Cell division, chromosomal damage and micronucleus formation in peripheral lymphocytes of healthy donors: related to donor's age.

Spontaneous baseline frequencies of chromosome aberrations, micronucleus counts and cell division were analysed in peripheral lymphocytes of 127 normal healthy individuals in vitro. Cells were subjected to culture for 48 h in serum and PHA supplemented culture medium RPMI 1640. 100 metaphases were observed for chromosome aberrations and 1000 cells each for micronucleus counts and mitotic index. Regression analyses were carried out to see the effect of age on spontaneous abnormalities. The correlation of aberrations, micronucleus formation and mitotic index with donor's age is highly significant. The elevation of abnormalities and depression of mitotic index were linear to the increase of donor's age, with a higher frequency in males. Aged males and females from the age range of 40-70 years showed larger numbers of aberrations. Individuals with the smoking habit possessed higher frequencies of abnormalities than non-smokers.

Age-related variation in sister chromatid exchanges and cell cycle kinetics in peripheral blood lymphocytes of healthy individuals.

Sister chromatid exchanges (SCEs) and cell cycle kinetics were estimated in mitogen stimulated human lymphocytes from a selected group of healthy individuals. Data were examined to evaluate the relationship between SCE frequencies and cell cycle kinetics with donor's age, sex and smoking habit. No regular relationship was observed between the mean SCE frequencies and donor's age, although significant differences were observed between the age groups. Correlation of dispersion coefficient (H) of SCE with donor's age were significant in male and female populations. For cell cycle kinetics, a highly significant age-dependent depression in replicative index (RI) was observed. Female donors possessed a slightly higher SCE frequency and RI, although the variations between the two sexes were not significant. Smoking habit resulted in a significant enhancement of SCEs.

Bone marrow clastogenicity of trimethyltin.

Aqueous solutions of trimethyltin in four different concentrations were administered i.p. for three different treatment periods, to five Swiss albino male mice for each experimental set. Bone marrow cells were processed for somatic chromosome preparation after 6, 18 and 24 h following the usual protocol. Structural abnormalities including chromatid and chromosome breaks, dicentrics, rings and fragments were recorded. Critical assessment of the data with the one-tailed trend test revealed a significant positive trend of the dose effects in all three treatment periods. With the ANOVA test, significant variations in aberrations were observed between chemical concentrations and between treatment periods and their interaction (dose x time) was significant in aberrations and mitotic indices. Depression of mitotic index was dose- and duration-dependent.

Cytotoxicity of tin on human peripheral lymphocytes in vitro.

The comparative effects of inorganic and organic tin compounds on chromosomes were assessed in human peripheral blood lymphocytes of healthy donors 20-40 years of age. The endpoints observed were chromosomal abnormalities, sister-chromatid exchanges (SCEs) and cell cycle kinetics. The maximum concentrations which reduced the replicative index by about 50%, of stannic chloride and trimethyltin chloride were 40 micrograms and 2 micrograms per culture respectively. The tested doses were 20 micrograms and 10 micrograms of stannic chloride and 1 microgram and 0.5 microgram of trimethyltin chloride. Both doses of stannic chloride induced a much higher frequency of chromosomal abnormalities (P less than 0.05-P less than 0.001) and a greater reduction of cell cycle kinetics than the corresponding relative doses of trimethyltin chloride. The frequencies of SCEs/cell induced by the latter were, however, slightly higher than those induced by the former.

Involvement of specific chromosomes in radiation-induced rearrangements detected by fluorescence in situ hybridization (FISH).

We investigated the involvement of chromosomes in dicentrics and translocations in human peripheral blood lymphocytes exposed to X-rays in vitro. Chromosomes 2, 4, 8, 13, 15, 16, and 22 were analyzed in three cocktails of different combinations using whole chromosome probes (WCP) with the fluorescence in situ hybridization (FISH)-painting technique. The results showed overexpression of chromosomes 2, 8, and 22 in translocation, the majority being of the complete type. Chromosome 4 was underrepresented in translocation formation in both combinations, that is, 2 + 4 + 8 in cocktail I and 4 + 13 + 22 in cocktail II. Its participation in dicentric production was in good agreement with its DNA content in association with 2, 4, and 8, whereas it was underexpressed in the combination of 4 + 13 + 22. DNA-proportional involvement was noticed with chromosomes 13 and 16 in all exchange aberrations. Underexpression of chromosome 15 was observed in translocation, which is contradictory to its overexpression in dicentric formation. The participation of chromosome 22 was predominant for both translocations and dicentrics, compared with its DNA content. The overall observation of our study supports the assumption of DNA-proportional distribution of Lucas et al. However, more data are required for chromosomes 4, 8, 15, and 22 in combination with other chromosomes.

He metastable density in a double layer formed by a diameter discontinuity in a positive column.

The population density profile of triplet metastable He (2 3S1) is measured in the multiple space-charge (double) layer formed at an abrupt transition of the tube diameter in a positive column discharge. The double layer is formed at the transition from a 2.6 cm diameter to a 0.6 cm diameter tube in a static pressure discharge. The line integrated He 2 3S1 population density profile in the double-layer region is determined by diode-laser absorption. The triplet metastable density profiles are measured with discharge currents of 1, 2, and 5 mA at 1 Torr pressure for both polarity conditions: (a) when the cathode end of the discharge is in the large diameter tube and (b) when the anode end of the discharge is in the large diameter tube. The diode-laser absorption profiles show enhanced production of triplet metastable He 2 3S1 in the double-layer region as compared to the unperturbed positive column (0.6 cm diameter) with the magnitude being strongly dependent on the discharge polarity.

Strong double-layer formation by shock waves in nonequilibrium plasmas.

Strong double-layer formation by acoustic shock wave (

Cell division, chromosomal aberration, and micronuclei formation in human peripheral blood lymphocytes. Effect of stannic chloride on donor's age.

Age related cytotoxicity of stannic chloride was evaluated in human lymphocytes considering mitotic index (MI), damaged cell (DC), chromosome aberration (CA), and micronuclei formation (MNC) as endpoints. Significant elevation of DCs, CAs, MNCs, and reduction of MI were observed in all classified age groups compared to each control set. The mean frequencies of abnormalities show a statistically significant increase with subject's age. Linearity of the effect of age was common for both untreated and treated lymphocytes of both sexes.

Identification of voltage-sensitive calcium channels in Setaria cervi (Nematoda: Filarioidea) and their role in regulation of spontaneous motility.

Whole worm of Setaria cervi and its nerve muscle preparation exhibit rhythmical movements when suspended in modified Ringer's solution in an isolated organ bath. Deprivation of calcium from the bathing fluid results in gradual reduction in the amplitude and rate of contraction till the movements ceased completely. Similar results were obtained by adding EDTA (5 micrograms/ml) to the bath. The effect was concentration related and was evident early with higher concentration of EDTA. Acetylcholine which increases spontaneous movements of the whole worm as well as N.M. preparation failed to do so when the movements were inhibited either in calcium free solution or in the presence of EDTA. Addition of calcium channel blocker, Nifedipine to the bathing fluid also resulted in concentration related reduction of movements of the preparation of Setaria. Further, the stimulant response of Ach was also reduced by Nifedipine and this too was related to the concentration of calcium channel blocker in the bath. The evidence clearly indicates that presence of calcium is essential for the stimulant response of Ach on S. cervi, which like mammalian tissues contain calcium channels that can be blocked by specific blocking agents.

Regulation of cholinomimetic action of pyrantel pamoate by calcium channels in Setaria cervi.

Nerve muscle preparation of Setaria cervi (Nematoda:Filarioidea) exhibits spontaneous rhythmical movements when suspended in isolated organ bath containing modified Ringer's solution. Pyrantel pamoate (50 ng/ml) when applied caused initial short lasting stimulation followed by irreversible paralysis. When suspended in calcium free bathing fluid the movements of n.m. preparation showed a gradual decrease both in amplitude and rate of contraction til the movements ceased completely. The effect was similar when EDTA was added to the bath fluid. The stimulant effect of Pyrantel pamoate was blocked in calcium free solution and in bath applied EDTA. Calcium channel blocker Nifedipine in a concentration of 500 ng/ml blocked the effect of Pyrantel pamoate (50 ng/ml). Neither stimulation nor depression of movements was evident with higher concentration of PP (250 mg/ml) the stimulant effect of Pyrantel pamoate was blocked while the depressant effect characterized by decrease in amplitude of calcium is essential for the stimulant effect of Pyrantel pamoate and its response on n.m. preparation is similar to Acetylcholine.

Comparison of efficacy and safety of two parenteral iron preparations in pregnant women.

OBJECTIVE: To compare the efficacy and safety with a fixed dose of two parenteral iron preparations, iron sucrose complex and iron sorbitol citric acid as per the current practice. MATERIALS AND METHODS: A prospective randomized open label study was conducted. In this study, 60 pregnant women with hemoglobin less than 8.5 g/dl received a fixed dose of either IV iron sucrose or IM iron sorbitol citric acid therapy. The efficacy of the therapy was assessed by laboratory parameters such as hemoglobin, hematocrit, MCV, MCH, and serum ferritin level after 14 and 28 days. To assess the safety, adverse drug reactions with both the therapies were recorded. RESULTS: Hemoglobin concentration increased significantly (P < 0.001) with respect to time in both the groups. The rise in the hemoglobin level in third and fourth weeks was significantly higher in iron sucrose (0.92 g/dl) than iron sorbitol citric acid therapy (0.56 g/dl). There was no significant change in the rise of the serum ferritin level after both the therapies. Adverse events were common with iron sorbitol citric acid therapy. However, no serious adverse drug reactions were observed. CONCLUSIONS: No significant difference in the efficacy of both of the therapy. However, adverse events and dropout rates were much more common in the group of pregnant women who received iron sorbitol citric acid.