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GeneXpert is attributed as one of the latest technical means for diagnosing Tuberculosis in very short period of time. Objectives: To evaluate the efficiency of GeneXpert and fluorescent microscopy in the detection of pulmonary tuberculosis (TB); To compare the sensitivity and specificity of GeneXpert and fluorescent microscope in the diagnosis of Mycobacterium tuberculosis Methods: In the present investigation, the diagnostic performance of GeneXpert MTB / RIF for tuberculosis was compared with the performance of light-emitting diode fluorescence microscope in TB samples from Narowal, Pakistan. For this purpose, a total of 299 TB positive specimens were obtained. Among these 54% (n = 160) were categorized to be obtained from male and 46% (n = 139) from female population. Data collected was distributed in 4 age groups; 0-20, 21-40, 41-60, and 61-80, in which the percentage and number of samples were found as 2% (n = 6), 60% (n = 179), 27% (n = 80) and 11% (n = 34), respectively. Results: The parameters including sensitivity and specificity calculated for GeneXpert were 73% and 100%, correspondingly, while the sensitivity and specificity calculated for LED-FM microscope were 43% and 100%, respectively. Conclusions: This indicates that the GeneXpert is more sensitive in detecting MTB in comparison to LED-FM technique. The GeneXpert assay was also found to detect small number of bacillus from samples in comparison to LED-FM method

Objective. Fast and accurate auto-segmentation is essential for magnetic resonance-guided adaptive radiation therapy (MRgART). Deep learning auto-segmentation (DLAS) is not always clinically acceptable, particularly for complex abdominal organs. We previously reported an automatic contour refinement (ACR) solution of using an active contour model (ACM) to partially correct the DLAS contours. This study aims to develop a DL-based ACR model to work in conjunction with ACM-ACR to further improve the contour accuracy. Approach. The DL-ACR model was trained and tested using bowel contours created by an in-house DLAS system from 160 MR sets (76 from MR-simulation and 84 from MR-Linac). The contours were classified into acceptable, minor-error and major-error groups using two approaches of contour quality classification (CQC), based on the AAPM TG-132 recommendation and an in-house classification model, respectively. For the major-error group, DL-ACR was applied subsequently after ACM-ACR to further refine the contours. For the minor-error group, contours were directly corrected by DL-ACR without applying an initial ACM-ACR. The ACR workflow was performed separately for the two CQC methods and was evaluated using contours from 25 image sets as independent testing data. Main results. The best ACR performance was observed in the MR-simulation testing set using CQC by TG-132: (1) for the major-error group, 44% (177/401) were improved to minor-error group and 5% (22/401) became acceptable by applying ACM-ACR; among these 177 contours that shifted from major-error to minor-error with ACM-ACR, DL-ACR further refined 49% (87/177) to acceptable; and overall, 36% (145/401) were improved to minor-error contours, and 30% (119/401) became acceptable after sequentially applying ACM-ACR and DL-ACR; (2) for the minor-error group, 43% (320/750) were improved to acceptable contours using DL-ACR. Significance. The obtained ACR workflow substantially improves the accuracy of DLAS bowel contours, minimizing the manual editing time and accelerating the segmentation process of MRgART.

The enzyme urease is an essential colonizing factor of the notorious carcinogenic pathogen Helicobacter pylori (H. pylori), conferring acid resistance to the bacterium. Recently, antibiotic resistant strains have emerged globally with little to no alternative treatment available. In this study we propose novel urease inhibitors capable of controlling infection by H. pylori and other pathogenic bacteria. We employed hierarchal computational approaches to screen new urease inhibitors from commercial chemical databases followed by in vitro anti-urease assays. Initially ROCS shape-based screening was performed using o-chloro-hippurohydroxamic acid followed by molecular docking studies. Out of 1.83 million compounds, 1700 compounds were retrieved based on having a ROCS Tanimoto combo score in the range of values from 1.216 to 1.679. These compounds were further screened using molecular docking simulations and the 100 top ranked compounds were selected based on their Glide score. After structural classification of the top ranked compounds, eight compounds were selected and purchased for biological assays. The plausible binding modes of the most active compounds were also confirmed using molecular dynamics (MD) simulations. Compounds 1, 2 and 3 demonstrated good urease inhibitory properties (IC50 = 0.32, 0.68 and 0.42 μM) compared to the other compounds. Enzyme kinetic studies revealed that compounds 1 and 3 are competitive inhibitors while 2 is a mixed type inhibitor of the urease enzyme. Cell based urease inhibition and MTT assay showed that these compounds blocked H. pylori urease activity, affecting bacterial growth and acid tolerance.

PURPOSE: To reduce workload and inconsistencies in organ segmentation for radiation treatment planning, we developed and evaluated general and custom auto-segmentation models on CT for three major tumor sites using a well-established deep convolutional neural network (DCNN). METHODS AND MATERIALS: Five CT-based auto-segmentation models for 42 organs at risk (OARs) in head and neck (HN), abdomen (ABD) and male pelvis (MP) were developed using a full 3D DCNN architecture. Two types of DL models were separately trained using either general diversified multi-institutional datasets or custom well controlled single institution datasets. To improve segmentation accuracy, an adaptive spatial resolution approach for small and/or narrow OARs and a pseudo scan extension approach, when CT scan length is too short to cover entire organs, were implemented. The performance of the obtained models was evaluated based on accuracy and clinical applicability of the auto-segmented contours using qualitative visual inspection and quantitative calculation of dice similarity coefficient (DSC), mean distance to agreement (MDA), and time efficiency. RESULTS: The five DL auto-segmentation models developed for the three anatomical sites were found to have high accuracy (DSC ranging from 0.8 – 0.98) for 74% OARs and marginally acceptable for 26% OARs. The custom models performed slightly better than the general models, even with smaller custom datasets used for the custom model training. The organ-based approaches improved auto-segmentation accuracy for small or complex organs (e.g., eye lens, optic nerves, inner ears, and bowels). Compared with traditional manual contouring times, the auto-segmentation times, including subsequent manual editing, if necessary, were substantially reduced by 88% for MP, 80% for HN, and 65% for ABD models. CONCLUSIONS: The obtained auto-segmentation models, incorporating organ-based approaches were found to be effective and accurate for most OARs in the male pelvis, head and neck and abdomen. We have demonstrated that our multi-anatomical deep learning auto-segmentation models are clinically useful for radiation treatment planning.

Despite recent substantial improvement in autosegmentation using deep learning (DL) methods, labor-intensive and time-consuming slice-by-slice manual editing is often needed, particularly for complex anatomy (eg, abdominal organs). This work aimed to develop a fast, prior knowledge-guided DL semiautomatic segmentation (DL-SAS) method for complex structures on abdominal magnetic resonance imaging (MRI) scans.A novel application using contours on an adjacent slice as a prior knowledge informant in a 2-dimensional UNet DL model to guide autosegmentation for a subsequent slice was implemented for DL-SAS. A generalized, instead of organ-specific, DL-SAS model was trained and tested for abdominal organs on T2-weighted MRI scans collected from 75 patients (65 for training and 10 for testing). The DL-SAS model performance was compared with 3 common autocontouring methods (linear interpolation, rigid propagation, and a full 3-dimensional DL autosegmentation model trained with the same training data set) based on various quantitative metrics including the Dice similarity coefficient (DSC) and ratio of acceptable slices (ROA) using paired t tests.For the 10 testing cases, the DL-SAS model performed best with the slice interval (SI) of 1, resulting in an average DSC of 0.93 ± 0.02, 0.92 ± 0.02, 0.91 ± 0.02, 0.88 ± 0.03, and 0.87 ± 0.02 for the large bowel, stomach, small bowel, duodenum, and pancreas, respectively. The performance decreased with increased SIs from the guidance slice. The DL-SAS method performed significantly better (P.05) than the other 3 methods. The ROA values were in the range of 48% to 66% for all the organs with an SI of 1 for DL-SAS, higher than those for linear interpolation (31%-57% for an SI of 1) and DL auto-segmentation (16%-51%).The developed DL-SAS model segmented complex abdominal structures on MRI with high accuracy and efficiency and may be implemented as an interactive manual contouring tool or a contour editing tool in conjunction with a full autosegmentation process, facilitating fast and accurate segmentation for MRI-guided online adaptive radiation therapy.

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family which has been extensively studied for its roles in neural development, long-term memory, brain injury, and neurodegenerative diseases. BDNF signaling through tropomyosin receptor kinase B (TrkB) stimulates neuronal cell survival. For this reason, small molecule TrkB agonists are under pre-clinical develoment for the treatment of a range of neurodegenerative diseases and injuries. Our laboratory recently reported BDNF is secreted by pro-regenerative endothelial progenitor cells (EPCs) which support hematopoietic reconstitution following total body irradiation (TBI). Here we report BDNF-TrkB signaling plays a novel regenerative role in bone marrow and thymic regeneration following radiation injury. Exogenous administration of BDNF or TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) following myelosuppressive radiation injury promoted faster recovery of mature blood cells and hematopoietic stem cells capable of multi-lineage reconstitution. BDNF promotes hematopoietic regeneration via activation of PDGFRα+bone marrow mesenchymal stem cells (MSCs) which increase secretion of hematopoietic cytokines interleukin 6 (IL-6) and leukemia inhibitory factor (LIF) in response to TrkB activation. These data suggest pharmacologic activation of the BDNF pathway with either BDNF or 7,8-DHF may be beneficial for treatment of radiation or chemotherapy induced myelosuppression.

Study was conducted to investigate the relationship between service quality, trust and loyalty. The trust is mediating between service quality and loyalty. Service quality provided to the customer is responsibility of the restaurants. Using a convenient sampling data was collected from consumers. Service quality positively associated with trust and loyalty and trust is also positively linked with loyalty and mediates the relationship between service quality and loyalty according to our finding. This article helps the organizations to understand the importance of service quality provide and how consumers become loyal to the organization. Customer retention is higher and profitability is greater for the business over the long period of time.

Increasingly companies are focused on searching for ways to create strong brand connections with consumers. It is illustrated that such connections lead to higher levels of consumer loyalty, which increases companies’ financial performance. The main purpose of this study is to explore the impact of brand personality on brand attachment through the mediating role of trust. Also investigate the moderating role of self-congruence on the relationship between brand personality and brand trust. SPSS 23 is used to analyze the data. Data was collected through survey questionnaire technique and snow-ball sampling technique was used for data collection. Analysis reveal Brand personality have significant and positive relationship with brand trust. On the other side trust significantly enhance the brand attachment. While the results prove that self-congruence have significant moderating effect on the relationship between brand personality and brand trust.

TMEM16A is an essential component of Ca2+-activated Cl− currents in mouse vomeronasal sensory neurons., Pheromones are substances released from animals that, when detected by the vomeronasal organ of other individuals of the same species, affect their physiology and behavior. Pheromone binding to receptors on microvilli on the dendritic knobs of vomeronasal sensory neurons activates a second messenger cascade to produce an increase in intracellular Ca2+ concentration. Here, we used whole-cell and inside-out patch-clamp analysis to provide a functional characterization of currents activated by Ca2+ in isolated mouse vomeronasal sensory neurons in the absence of intracellular K+. In whole-cell recordings, the average current in 1.5 µM Ca2+ and symmetrical Cl− was −382 pA at −100 mV. Ion substitution experiments and partial blockade by commonly used Cl− channel blockers indicated that Ca2+ activates mainly anionic currents in these neurons. Recordings from inside-out patches from dendritic knobs of mouse vomeronasal sensory neurons confirmed the presence of Ca2+-activated Cl− channels in the knobs and/or microvilli. We compared the electrophysiological properties of the native currents with those mediated by heterologously expressed TMEM16A/anoctamin1 or TMEM16B/anoctamin2 Ca2+-activated Cl− channels, which are coexpressed in microvilli of mouse vomeronasal sensory neurons, and found a closer resemblance to those of TMEM16A. We used the Cre–loxP system to selectively knock out TMEM16A in cells expressing the olfactory marker protein, which is found in mature vomeronasal sensory neurons. Immunohistochemistry confirmed the specific ablation of TMEM16A in vomeronasal neurons. Ca2+-activated currents were abolished in vomeronasal sensory neurons of TMEM16A conditional knockout mice, demonstrating that TMEM16A is an essential component of Ca2+-activated Cl− currents in mouse vomeronasal sensory neurons.

0000-0002-2032-8930 WOS: 000404578800016 Two coordination polymers, {[Ln(2-stp)(4,4 '-bipy)(H2O)]center dot(H2O)}, [Ln = Dy (1) and Eu (2), 2-stp = 2-sulfoterephthalate and 4,4 '-bipy = 4,4 '-bipyridine] have been characterized by solid state UV-vis, FTIR spectra, X-ray single crystal diffraction and solid state photoluminescence. Variable-temperature magnetic susceptibility and isothermal magnetization as function of external magnetic field is also studied for both complexes. After ligand-mediated excitation, both complexes show the characteristic visible and NIR luminescence of the corresponding Ln(III) ions (Ln = Dy, Eu) which is due to efficient energy transfer from the ligands to the central Ln(III) ions via an antenna effect. The indirect energy transfer in both complexes has been investigated and discussed in detail. Research Funds of Balikesir UniversityBalikesir University [BAP-2015/128]; Mugla Sitki Kocman UniversityMugla Sitki Kocman University [BAP-2017/035] The authors are grateful to the Research Funds of Balikesir University (BAP-2015/128) and Mugla Sitki Kocman University (BAP-2017/035) for the financial support.

The present study focuses on the dynamic magnetic behaviour of exchange coupled 3d-4f complexes containing the scarcely investigated non-Kramers Tm3+ center, the 3d metal ions being either the low-spin Fe3+ (1) or the diamagnetic Co3+ (2) ion. Both complexes display field-induced slow relaxation of magnetization. The field and temperature dependences of the relaxation rate provided indication of relevant contributions from quantum tunnelling, direct, Orbach and Raman processes, with only minor effects from exchange coupling interactions. Furthermore, the aged sample of 2 exhibited an additional relaxation process, possibly due to structural modifications accompanied by solvent loss, highlighting the importance of a careful consideration of this factor when analysing the magnetization dynamics in solvated systems.

Hydrothermal reactions of lanthanide metal salts with 2-sulfoterephthalate (2-stp) and 4,4'-bipyridine (4,4'-bipy) led to three coordination polymers, {[Ln(2-stp)(4,4'-bipy)(H2O)]center dot(H2O)), [Ln = Gd (1), Ho (2) and Sm (3)]. Their structures have been established by X-ray single crystal diffraction. Complexes 1-3 are isostructural with 2D framework in which all Ln(III) atoms are nine-coordinated. All these 2D layers are further interlinked via hydrogen bonds resulting in 3D architecture. The solid-state photoluminescence measurements display the characteristic luminescence of Ho (2) and Sm (3), which is due to efficient energy transfer from the ligands to the central Ln(III) ions via an "antenna effect". Variable temperature magnetic susceptibility and isothermal magnetization as function of external magnetic field for 1-3 is studied which reveal mainly the presence of antiferromagnetic interactions and the thermal depopulation of Stark sublevels together with crystal field affects. (C) 2016 Elsevier B.V. All rights reserved.

A novel water-stable (t1/2 ∼ 6.8 days) mononuclear manganese(IV) complex of a hexacoordinating non-Schiff-base ligand (H4L) with N2O4-donor atoms has been synthesized and characterized crystallographically. High-frequency electron paramagnetic resonance experiments performed on a single crystal reveal a manganese(IV) ion with an S = 3/2 ground spin state that displays a large single-ion anisotropy, setting the record of mononuclear manganese(IV) complexes reported so far. In addition, spin-echo experiments reveal a spin-spin relaxation time T2 ∼ 500 ns.

An electron paramagnetic resonance (EPR) study of a single crystal of Co II -based single-chain magnets (SCM) is presented. Discrete resonant absorptions are associated to the presence of magnetic domains within the chains of finite lengths determined by a competition between intra-chain exchange interactions and thermally excited single spin fluctuations. The results are interpreted as a transition from single spin dynamics at high temperature ( T ∼20 K), associated to the Kramers doublet ground state of the individual Co II ions, to archetypical SCM dynamics at low temperatures, where intra-chain correlations form long magnetic domains, whose average length is imposed by the concentration of defects in the sample.

Low-temperature magnetometry, ac susceptibility, and calorimetry have been employed to study Co-based single-chain magnets (SCMs) organized through halogen bonding. Magnetic hysteresis and maxima in the dc and ac susceptibilities, respectively, confirm the SCM behavior of the system. Several characteristic magnetic relaxation regimes are observed at different temperatures, which can be associated with both intra- and interchain exchange interactions. Remarkably, tweaking the rate at which an external magnetic field is swept along the axis of the chains enables a controlled transition between the one- and three-dimensional dynamics. Experiments on an isostructural Co-based SCM system crystallized with different halogens do not show three-dimensional dynamics, illustrating the importance of halogen bonding on the control of interchain interactions.

We report the synthesis, structure, and spectroscopic and dynamic magnetic properties of a series of heterodinuclear complexes, [ZnLn(LH4 )2 ](NO3 )3 ⋅6 H2 O (Ln=Nd, Tb, Dy, Ho, Er, and Yb), with the singly deprotonated form of a new compartmentalized Schiff-base ligand, LH5 . The Ln(III) ions in these systems show a distorted square-antiprism geometry with an LnO8 coordination sphere. EPR spectroscopy and DC magnetic studies have shown that the anisotropic nature of the complexes is far more complicated than predicted on the basis of a simple electrostatic model. Among the investigated systems, only the Dy(III) derivative showed single-ion magnet behavior, in zero and an applied magnetic field, both in pure polycrystalline samples and in a series of polycrystalline samples with different degrees of dilution at the single-crystal level in the isostructural Y(III) derivative. The rich dynamics observed as functions of frequency, field, and temperature reveals that multiple relaxation mechanisms are at play, resulting in a barrier of 189 cm(-1) , which is among the highest reported for a dinuclear Zn-Dy system. Analysis of the dynamic behavior as a function of dilution degree further evidenced the persistence of non-negligible intermolecular interactions, even at the lowest concentration of 1 %.

The hydrothermal reaction of CrCl3·6H2O and Ln(NO3)3·xH2O in the presence of di(2-pyridil)ketone, and sodium acetate in water leads to the formation of a series of [Cr4Ln(CH3COO)(pyCOO)((py)2COO)4]·(NO3)2·nH2O complexes (with Ln = Gd(III), Tb(III), Dy(III), and n = 19 or 20). The four newly synthesized complexes were characterized by single crystal X-ray diffraction technique and their magnetic properties were fully investigated by dc (direct current) and ac (alternating current) magnetic susceptibility measurements. Single crystal X-ray studies revealed that the dysprosium derivative crystallizes as two different structural forms: a triclinic P form and a monoclinic P21/n form. The gadolinium and the terbium derivatives were isostructural to the dysprosium monoclinic form. Surprisingly, full static and dynamic magnetic studies revealed that none of the synthesized complexes exhibit single molecule magnet behaviour, while the gadolinium derivative displays a magnetocaloric effect (MCE).

The rodent vomeronasal organ plays a crucial role in several social behaviors. Detection of pheromones or other emitted signaling molecules occurs in the dendritic microvilli of vomeronasal sensory neurons, where the binding of molecules to vomeronasal receptors leads to the influx of sodium and calcium ions mainly through the transient receptor potential canonical 2 (TRPC2) channel. To investigate the physiological role played by the increase in intracellular calcium concentration in the apical region of these neurons, we produced localized, rapid, and reproducible increases in calcium concentration with flash photolysis of caged calcium and measured calcium-activated currents with the whole cell voltage-clamp technique. On average, a large inward calcium-activated current of −261 pA was measured at −50 mV, rising with a time constant of 13 ms. Ion substitution experiments showed that this current is anion selective. Moreover, the chloride channel blockers niflumic acid and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid partially inhibited the calcium-activated current. These results directly demonstrate that a large chloride current can be activated by calcium in the apical region of mouse vomeronasal sensory neurons. Furthermore, we showed by immunohistochemistry that the calcium-activated chloride channels TMEM16A/anoctamin1 and TMEM16B/anoctamin2 are present in the apical layer of the vomeronasal epithelium, where they largely colocalize with the TRPC2 transduction channel. Immunocytochemistry on isolated vomeronasal sensory neurons showed that TMEM16A and TMEM16B coexpress in the neuronal microvilli. Therefore, we conclude that microvilli of mouse vomeronasal sensory neurons have a high density of calcium-activated chloride channels that may play an important role in vomeronasal transduction.

The present study discusses the magnetic dynamics of a previously reported cyanide bridged 3d-4f dinuclear DyIIICoIII complex. Following the axial anisotropy suggested by previous Electron Paramagnetic Resonance spectroscopy (EPR) analysis, the complex turned out to show slow relaxation of the magnetization at cryogenic temperature, and this was studied in different temperature and field regimes. The existence of multichannel relaxation pathways that reverse the magnetization was clearly disclosed: a tentative analysis suggested that these channels can be triggered and controlled as a function of applied static magnetic field and temperature. Persistent evidence of a temperature independent process even at higher fields, attributable to quantum tunneling, is discussed, while the temperature dependent dynamics is apparently governed by an Orbach process. The broad distribution of relaxation rates evidenced by the ac susceptibility measurements suggest a relevant role of the intermolecular interactions in this system.

Recently, various triangular [Mn${}^{\mathrm{III}}$]${}_{3}$ molecules have been extensively studied due to the fact that one can modulate the magnitude and the sign of the inter-ion exchange, thereby giving rise to very simple clusters that constitute some of the cleanest and best examples of so-called single-molecule magnets. However, magnetic and electron paramagnetic resonance (EPR) characterizations of low-spin antiferromagnetic [Mn${}^{\mathrm{III}}$]${}_{3}$ complexes have been problematic due to the significant spin frustration that exists for this topology. We show that this frustration is relieved in the highly distorted [NEt${}_{4}$]${}_{3}$Mn${}_{3}$Zn${}_{2}$(salox)${}_{3}$O(N${}_{3}$)${}_{8}$]\ifmmode\cdot\else\textperiodcentered\fi{}MeOH molecule: Susceptibility data suggest a well isolated S = 2 ground state; EPR spectroscopy and high-field torquemetry support this conclusion and further indicate the presence of a very significant zero-field-splitting (zfs) separating the lowest-lying ${m}_{S}$ = \ifmmode\pm\else\textpm\fi{}2 states from the excited levels within the same S = 2 multiplet. Remarkably, this zfs is sufficient to give rise to magnetic bistability, as evidenced through the observation of low-temperature magnetization hysteresis.

Calcium calmodulin dependent kinase II (CaMKII) is sequestered in dendritic spines within seconds upon synaptic stimulation. The program Smoldyn was used to develop scenarios of single molecule CaMKII diffusion and binding in virtual dendritic spines. We first validated simulation of diffusion as a function of spine morphology. Additional cellular structures were then incorporated to simulate binding of CaMKII to the post-synaptic density (PSD); binding to cytoskeleton; or their self-aggregation. The distributions of GFP tagged native and mutant constructs in dissociated hippocampal neurons were measured to guide quantitative analysis. Intra-spine viscosity was estimated from fluorescence recovery after photo-bleach (FRAP) of red fluorescent protein. Intra-spine mobility of the GFP-CaMKII? constructs was measured, with hundred-millisecond or better time resolution, from FRAP of distal spine tips in conjunction with fluorescence loss (FLIP) from proximal regions. Different FRAP \ FLIP profiles were predicted from our Scenarios and provided a means to differentiate binding to the PSDs from self-aggregation. The predictions were validated by experiments. Simulated fits of the Scenarios provided estimates of binding and rate constants. We utilized these values to assess the role of self-aggregation during the initial response of native CaMKII holoenzymes to stimulation. The computations revealed that self-aggregation could provide a concentration-dependent switch to amplify CaMKII sequestration and regulate its activity depending on its occupancy of the actin cytoskeleton.

We prepared three structurally related Mn(3)(III)Mn(2)(II) complexes that possess S approximately 1-11 spin ground states as a result of variations in the geometry and identity of mu(2)-eta(1):eta(1) bridging groups. These complexes function as single-molecule magnets yet demonstrate other interesting behavior such as quasi-classical magnetization hysteresis and comparable magnetization reversal barriers (U(eff)).