Cobalt ferrite nanoparticles for annulation of C3-substituted nitroarenes and aryl isothiocyanates.

The synthesis of medicinally relevant N-aryl-substituted 2-aminobenzothiazoles often uses 2-aminothiophenol derivatives, which are not commercially abundant, as starting materials. Herein, we report a method for the annulation of C3-substituted nitroarenes and aryl isothiocyanates towards the synthesis of 2-aminobenzothiazoles. Reactions proceeded in the presence of cobalt ferrite nanoparticles as a catalyst, DABCO as a base, and DMF as a promoter. The cobalt ferrite nanoparticles could be recovered after each run and reused up to 3 times while the product yield was not diminished. Our method appears to be the first example of the direct use of substituted nitroarenes for yielding 2-aminobenzothiazoles.

Synthesis of 2-benzyl benzoxazoles and benzothiazoles via elemental sulfur promoted cyclization of styrenes with 2-nitrophenols and N,N-dialkyl-3-nitroanilines.

Herein we report a method for affording 2-benzyl benzoxazoles from substituted styrenes and 2-nitrophenols. The success of this method relies on the use of simple reagents, namely elemental sulfur and DABCO. A combination of identical reagents was utilized for the annulation of styrenes with N,N-dialkyl-3-nitroanilines to afford 2-benzyl benzothiazoles. Overall, benzoxazoles and benzothiazoles bearing useful functionalities such as halogens, amines, and heterocyclic groups were isolated in moderate to good yields. Our methods are a rare example of divergent transformations of substituted nitroarenes towards 2-benzyl benzoxazoles and benzothiazoles.

Acoustic speech markers for schizophrenia-spectrum disorders: a diagnostic and symptom-recognition tool.

BACKGROUND: Clinicians routinely use impressions of speech as an element of mental status examination. In schizophrenia-spectrum disorders, descriptions of speech are used to assess the severity of psychotic symptoms. In the current study, we assessed the diagnostic value of acoustic speech parameters in schizophrenia-spectrum disorders, as well as its value in recognizing positive and negative symptoms. METHODS: Speech was obtained from 142 patients with a schizophrenia-spectrum disorder and 142 matched controls during a semi-structured interview on neutral topics. Patients were categorized as having predominantly positive or negative symptoms using the Positive and Negative Syndrome Scale (PANSS). Acoustic parameters were extracted with OpenSMILE, employing the extended Geneva Acoustic Minimalistic Parameter Set, which includes standardized analyses of pitch (F0), speech quality and pauses. Speech parameters were fed into a random forest algorithm with leave-ten-out cross-validation to assess their value for a schizophrenia-spectrum diagnosis, and PANSS subtype recognition. RESULTS: The machine-learning speech classifier attained an accuracy of 86.2% in classifying patients with a schizophrenia-spectrum disorder and controls on speech parameters alone. Patients with predominantly positive v. negative symptoms could be classified with an accuracy of 74.2%. CONCLUSIONS: Our results show that automatically extracted speech parameters can be used to accurately classify patients with a schizophrenia-spectrum disorder and healthy controls, as well as differentiate between patients with predominantly positive v. negatives symptoms. Thus, the field of speech technology has provided a standardized, powerful tool that has high potential for clinical applications in diagnosis and differentiation, given its ease of comparison and replication across samples.

Cryoneurolysis' outcome on pain experience (COPE) in patients with low-back pain: study protocol for a single-blinded randomized controlled trial.

BACKGROUND: Low-back pain, including facet joint pain, accounts for up to 20 % of all sick leaves in DenmarkA proposed treatment option is cryoneurolysis. This study aims to investigate the effect of cryoneurolysis in lumbar facet joint pain syndrome. METHODS: A single-center randomized controlled trial (RCT) is performed including 120 participants with chronic facet joint pain syndrome, referred to the Department of Neurosurgery, Aarhus University Hospital. Eligible patients receive a diagnostic anesthetic block, where a reduction of pain intensity ≥ 50 % on a numerical rating scale (NRS) is required to be enrolled. Participants are randomized into three groups to undergo either one treatment of cryoneurolysis, radiofrequency ablation or placebo. Fluoroscopy and sensory stimulation is used to identify the intended target nerve prior to administrating the above-mentioned treatments. All groups receive physiotherapy for 6 weeks, starting 4 weeks after treatment. The primary outcome is the patients' impression of change in pain after intervention (Patient Global Impression of Change (PGIC)) at 4 weeks follow-up, prior to physiotherapy. Secondary outcomes are a reduction in low-back pain intensity (numeric rating scale) and quality of life (EQ-5D, SF-36) and level of function (Oswestry Disability Index), psychological perception of pain (Pain Catastrophizing Scale) and depression status (Major Depression Inventory). Data will be assessed at baseline (T0), randomization (T1), day one (T2), 4 weeks (T3), 3 (T4), 6 (T5) and 12 months (T6). DISCUSSION: This study will provide information on the effectiveness of cryoneurolysis vs. the effectiveness of radiofrequency ablation or placebo for patients with facet joint pain, and help to establish whether cryoneurolysis should be implemented in clinical practice for this patient population. TRIAL REGISTRATION: The trial is approved by the ethical committee of Central Jutland Denmark with registration number 1-10-72-27-19 and the Danish Data Protection Agency with registration number 666,852. The study is registered at Clinicaltrial.gov with the ID number NCT04786145 .

Insights on the role of chemometrics and vibrational spectroscopy in fruit metabolite analysis.

The last three decades have demonstrated the ability of combining data analytics (e.g. big data, machine learning) with modern analytical instrumental techniques such as vibrational spectroscopy (VIBSPEC) (e.g. NIR, Raman, MIR) and sensing technologies (e.g. electronic noses and tongues, colorimetric sensors) to analyse, measure and monitor a wide range of properties and samples. Developments in instrumentation, hardware and software have placed VIBSPEC as a useful tool to quantify several bioactive compounds and metabolites in a wide range of fruit and plant samples. With the incorporation of hand-held and portable instrumentation, these techniques have been valuable for the development of in-field and high throughput applications, opened new frontiers of analysis in fruits and plants. This review will present and discuss some of the current applications on the use of VIBSPEC techniques combined with data analytics on the measurement bioactive compounds and plant metabolites in different fruit samples.

A spatial and temporal analysis of paediatric central nervous system infections from 2005 to 2015 in Ho Chi Minh City, Vietnam.

Central nervous system infections (CNSI) are a leading cause of death and long-term disability in children. Using ICD-10 data from 2005 to 2015 from three central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized additive mixed models (GAMM) to examine the spatial-temporal distribution and spatial and climatic risk factors of paediatric CNSI, excluding tuberculous meningitis, in this setting. From 2005 to 2015, there were 9469 cases of paediatric CNSI; 33% were ⩽1 year old at admission and were mainly diagnosed with presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of HCMC in proximity to the hospitals as well as some outer districts had the highest incidences of BI and non-BI; BI incidence was higher in the dry season. Monthly BI incidence exhibited a significant decreasing trend over the study. Both BI and non-BI were significantly associated with lags in monthly average temperature, rainfall, and river water level. Our findings add new insights into this important group of infections in Vietnam, and highlight where resources for the prevention and control of paediatric CNSI should be allocated.

Engineering a temperature sensitive tobacco etch virus protease.

Since tobacco etch virus protease (TEVp) has a high specificity and efficiency in cleaving its target substrates, many groups have attempted to engineer conditional control of its activity. Temperature induction is widely used for modulating gene function because it has fast temporal response, good penetrability and applicability to many model organisms. Here, we engineered a temperature sensitive TEVp (tsTEVp) by using N-terminal truncations to TEVp that achieved efficient proteolysis on a timescale of 4 h after 30°C induction, while remaining relatively inactive at 37°C. As demonstration, tsTEVp was used to generate temperature-induced biological responses for protein translocation, protein degradation and Ca2+-mediated cellular blebbing. Lastly, tsTEVp and their engineered target substrates could find applications in engineered synthetic biological systems.

Value of sialendoscopy-assisted transoral sublingual gland resection for a plunging ranula: case report and review.

OBJECTIVE: To highlight the value of sialendoscopy during transoral resection of the sublingual gland for a plunging ranula to prevent iatrogenic injury to the submandibular duct. METHOD AND RESULTS: The clinical course of a 20-year-old male with a plunging ranula was analysed. The patient underwent transoral resection of the affected sublingual gland and pseudocyst. Sialendoscopy was used to confirm patency of the submandibular duct with placement of a Marchal dilator to aid in preservation of the duct during sublingual gland dissection. The sublingual gland was successfully removed, with no injury to the submandibular duct or lingual nerve. During follow up, the patient had slight numbness to the tip of the tongue, which resolved after 2-3 days. Post-operative examination showed the submandibular duct to be intact and there was no swelling of the submandibular area. CONCLUSION: Sialendoscopy-assisted transoral sublingual gland resection for a plunging ranula is a safe and effective technique. Sialendoscopy aids in skeletonisation and preservation of the submandibular duct.

Relativistic quantum teleportation with superconducting circuits.

We study the effects of relativistic motion on quantum teleportation and propose a realizable experiment where our results can be tested. We compute bounds on the optimal fidelity of teleportation when one of the observers undergoes nonuniform motion for a finite time. The upper bound to the optimal fidelity is degraded due to the observer's motion. However, we discuss how this degradation can be corrected. These effects are observable for experimental parameters that are within reach of cutting-edge superconducting technology.

Raman scattering study of delafossite magnetoelectric multiferroic compounds: CuFeO2 and CuCrO2.

Ultrasonic velocity measurements on the magnetoelectric multiferroic compound CuFeO(2) reveal that the antiferromagnetic transition observed at T(N1) = 14 K might be induced by an R3m --> pseudoproper ferroelastic transition. In that case, the group theory states that the order parameter associated with the structural transition must belong to a two-dimensional irreducible representation E(g) (x(2) - y(2), xy). Since this type of transition can be driven by a Raman E(g) mode, we performed Raman scattering measurements on CuFeO(2) between 5 and 290 K. Considering that the isostructural multiferroic compound CuCrO(2) might show similar structural deformations at the antiferromagnetic transition T(N1) = 24.3 K, Raman measurements have also been performed for comparison. At ambient temperature, the Raman modes in CuFeO(2) are observed at ω(E(g)) = 352 cm(-1) and ω(A(1g)) = 692 cm(-1), while these modes are detected at ω(E(g)) = 457 cm(-1) and ω(A(1g)) = 709 cm(-1) in CuCrO(2). The analysis of the temperature dependence of the modes in both compounds shows that the frequencies of all modes increase with decreasing temperature. This typical behavior is attributed to anharmonic phonon-phonon interactions. These results clearly indicate that none of the Raman active modes observed in CuFeO(2) and CuCrO(2) drive the pseudoproper ferroelastic transitions observed at the Néel temperature T(N1). Finally, a broad band at about 550 cm(-1) observed in the magnetoelectric phase of CuCrO(2) below T(N2) could be associated with magnons.

A hybrid zone and bidirectional introgression between two catadromous species: Australian bass Macquaria novemaculeata and estuary perch Macquaria colonorum.

The presence and distribution of hybrid individuals and the existence of a hybrid zone between the catadromous Australian bass Macquaria novemaculeata and estuary perch Macquaria colonorum were investigated throughout the range of both species in Australia. Bayesian analyses and genotypic simulations identified 140 putative hybrids (11·5% of the total sample) with varying levels of introgression. Most hybrids were observed in an area extending from the Snowy River to the Albert River suggesting a hybrid zone in the eastern Bass Strait region. Sixteen hybrids, however, were found outside this zone, possibly reflecting the movement of hybrid offspring between estuaries or their inadvertent release during fish stocking programmes. Biparental backcrossing was found to occur suggesting that hybrids were fertile. These results have implications for the management of the extensive stocking programme in M. novemaculeata and for understanding the potential role of habitat degradation and reduced water flow in facilitating hybridization in species with migratory life histories.

Investigation of phonon behavior in Pr(2)NiMnO(6) by micro-Raman spectroscopy.

The temperature dependence of phonon excitations and the presence of spin-phonon coupling in polycrystalline Pr(2)NiMnO(6) samples were studied using micro-Raman spectroscopy and magnetometry. Magnetic properties show a single ferromagnetic-to-paramagnetic transition at 228 K and a saturation magnetization close to 4.95 µ(B)/f.u. Three distinct Raman modes at 657, 642, and 511 cm( - 1) are observed. The phonon excitations show a clear hardening due to anharmonicity from 300 down to 10 K. Further, the temperature dependence of the 657  cm( - 1) mode shows only a small softening. This reflects the presence of a relatively weak spin-phonon coupling in Pr(2)NiMnO(6) contrary to the case for other double perovskites previously studied.

Local linear discriminant analysis (LLDA) for group and region of interest (ROI)-based fMRI analysis.

A post-processing method for group discriminant analysis of fMRI is proposed. It assumes that the fMRI data have been pre-processed and analyzed so that each voxel is given a statistic specifying task-related activation(s), and that individually specific regions of interest (ROIs) have been drawn for each subject. The method then utilizes Local Linear Discriminant Analysis (LLDA) to jointly optimize the individually-specific and group linear combinations of ROIs that maximally discriminates between groups (or between tasks, if using the same subjects). LLDA tries to linearly transform each subject's voxel-based activation statistics within ROIs to a common vector space of ROI combinations, enabling the relative similarity of different subjects' activation to be assessed. We applied the method to data recorded from 10 normal subjects during a motor task expected to activate both cortical and subcortical structures. The proposed method detected activation in multiple cortical and subcortical structures that were not present when the data were analyzed by warping the data to a common space. We suggest that the method be applied to group fMRI data when warping to a common space may be ill-advised, such as examining activation in small subcortical structures susceptible to mis-registration, or examining older or neurological patient populations.

Mott transition, compressibility divergence, and the P-T phase diagram of layered organic superconductors: an ultrasonic investigation.

The phase diagram of the organic superconductor kappa-(BEDT-TTF)(2)Cu[N(CN)(2)]Cl has been investigated by ultrasonic velocity measurements under helium gas pressure. Different phase transitions were identified through several elastic anomalies characterized from isobaric and isothermal sweeps. Our data reveal two crossover lines that end on the critical point terminating the first-order Mott transition line. When the critical point is approached along these lines, we observe a dramatic anomaly of the sound velocity which is consistent with a diverging compressibility of the electronic degrees of freedom.

Regulation of trophoblastic gelatinases by proto-oncogenes.

During the first trimester of pregnancy, certain cytotrophoblastic cells (CTB) of anchoring villi invade the underlying decidua. Regulation of this invasive behaviour depends on cytokines and growth factors secreted by decidua and trophoblast, which modulate metalloproteinase (MMP) secretion of CTB. Since MMP-9 expression by CTB is a prerequisite for matrigel invasion and since the promoter region of the MMP-9 gene contains two AP-1 binding sites, we hypothesized, that transient activation of c-jun and c-fos oncogenes (which bind to form AP-1) by tumour necrosis factor (TNFalpha), or the phorbol ester TPA will promote the invasive phenotype of CTB and induce the production of MMP-9.TNFalpha or TPA when added to primary cultures of CTB increase MMP-9 activity and MMP-9 mRNA. This effect is inhibited by cycloheximide indicating the necessity of protein synthesis. TPA or TNFalpha induces also the binding of nuclear proteins (extracted from treated CTB) to a radiolabelled oligonucleotide corresponding to the consensus sequence of the TPA responsive element. Antibodies to Jun and Fos can displace this binding. Transient transfection of antisense mRNA to jun or fos into CTB inhibits the immunoreactivity and gelatinolytic activity of MMP-9. We conclude that AP-1 is necessary but may not be sufficient for transactivation of the MMP-9 gene in human CTB.

FRET-based in vivo Ca2+ imaging by a new calmodulin-GFP fusion molecule.

Intracellular Ca2+ acts as a second messenger that regulates numerous physiological cellular phenomena including development, differentiation and apoptosis. Cameleons, a class of fluorescent indicators for Ca2+ based on green fluorescent proteins (GFPs) and calmodulin (CaM), have proven to be a useful tool in measuring free Ca2+ concentrations in living cells. Traditional cameleons, however, have a small dynamic range of fluorescence resonance energy transfer (FRET), making subtle changes in Ca2+ concentrations difficult to detect and study in some cells and organelles. Using the NMR structure of CaM bound to the CaM binding peptide derived from CaM-dependent kinase kinase (CKKp), we have rationally designed a new cameleon that displays a two-fold increase in the FRET dynamic range within the physiologically significant range of cytoplasmic Ca2+ concentration of 0.05-1 microM.

Platelet glycoprotein IIb/IIIa-receptor inhibitors in patients with acute coronary syndromes or undergoing percutaneous coronary interventions: a review.

BACKGROUND: Over 12.2 million Americans are affected by acute coronary syndromes (ACS) resulting from arterial thrombosis after atherosclerotic plaque rupture. The mechanism of thrombosis is based on the platelet activation pathway, facilitated by expression of the platelet glycoprotein (GP) lIb/Illa receptors. The platelet GP IIb/IIIa-receptor inhibitors represent a new class of drugs, of which abciximab, eptifibatide, and tirofiban have been approved for use in the medical management of ACS and as adjunctive therapy in percutaneous coronary interventions (PCIs). OBJECTIVE: This article reviews the results of published multicenter, randomized, placebo-controlled, double-blind trials of the efficacy and safety of platelet GP IIb/IIIa-receptor inhibitors in patients with coronary artery disease. METHODS: To identify articles for this review, a search of MEDLINE for the years 1994 through 2000 was conducted using the key words myocardial ischemia, unstable angina, angioplasty, stent, abciximab, eptifibatide, tirofiban, lamifiban, and platelet aggregation inhibitors. Relevant review articles were consulted as well as reports of clinical studies. CONCLUSIONS: Three GP IIb/IIIa-receptor inhibitors--abciximab, eptifibatide, and tirofiban-are approved by the US Food and Drug Administration as adjunctive therapy in patients undergoing PCI. Eptifibatide and tirofiban 'are also indicated for the medical management of patients with unstable angina and non-ST-segment-elevation myocardial infarction. The use of GP IIb/IIIa-receptor inhibitors as a component of management with fibrinolytic agents is under investigation. Studies comparing the efficacy of tirofiban and abciximab in patients undergoing planned PCI with intracoronary stent placement are in progress. Until data are available from long-term trials and head-to-head comparisons of these agents, it is not possible to generalize about their overall or comparative efficacy.