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ObjectiveAffective disorders are associated with atypical voice patterns; however, automated voice analyses suffer from small sample sizes and untested generalizability on external data. We investigated a generalizable approach to aid clinical evaluation of depression and remission from voice using transfer learning: we train machine learning models on easily accessible non-clinical datasets and test them on novel clinical data in a different language.MethodsA Mixture-of-Experts machine learning model was trained to infer happy/sad emotional state using three publicly available emotional speech corpora in German and US English. We examined the model’s predictive ability to classify the presence of depression on Danish speaking healthy controls (N = 42), patients with first-episode major depressive disorder (MDD) (N = 40), and the subset of the same patients who entered remission (N = 25) based on recorded clinical interviews. The model was evaluated on raw, de-noised, and speaker-diarized data.ResultsThe model showed separation between healthy controls and depressed patients at the first visit, obtaining an AUC of 0.71. Further, speech from patients in remission was indistinguishable from that of the control group. Model predictions were stable throughout the interview, suggesting that 20-30 seconds of speech might be enough to accurately screen a patient. Background noise (but not speaker diarization) heavily impacted predictions.ConclusionA generalizable speech emotion recognition model can effectively reveal changes in speaker depressive states before and after remission in patients with MDD. Data collection settings and data cleaning are crucial when considering automated voice analysis for clinical purposes.Significant outcomes- Using a speech emotion recognition model trained on other languages, we predicted the presence of MDD with an AUC of 0.71.- The speech emotion recognition model could accurately detect changes in voice after patients achieved remission from MDD.- Preprocessing steps, particularly background noise removal, greatly influenced classification performance.Limitations- No data from non-remitters, meaning that changes to voice for that group could not be assessed.- It is unclear how well the model would generalize beyond Germanic languages.Data availability statementDue to the nature of the data (autobiographical interviews in a clinical population), the recordings of the participants cannot be shared publicly. The aggregated model predictions and code used to run the analyses is available athttps://github.com/HLasse/SERDepressionDetection.

Preparation and oxygen sensing properties of a luminescent composite material based on a mixed-ligand ruthenium(II) complex [Ru(phen)2DPOP]Cl2 {phen = 1, 10-phenanthroline, DPOP = 2-(11-dipyrido [3, 2-a:2′,3′-c]phenazine)-5-phenyl-1, 3, 4-oxadiazole} are reported, which are assembled in mesoporous silica MCM-41. As a result, the emission intensities of all assembly systems are sensitive to oxygen concentrations, that is to say, this material shows good oxygen-sensing properties. [Ru(phen)2DPOP]Cl2/MCM-41 (10 mg·g–1) exhibits the best sensitivity (I0/I100 = 10.8) and fast response time (2 s). These results indicate that this composite material is a promising candidate for optical oxygen sensors.

A simple and novel synthesis of polytrisubstituted-2-pyridones derivatives by the reaction of enamino esters and diethyl ethoxymethylenemalonate has been reported. The method provides a rapid synthetic route for the construction of 2-pyridones under catalyst- and solvent-free reaction conditions in moderate-to-good yields.

The light-gated cation channel channelrhodopsin-2 (ChR2) has been used in a variety of model systems to investigate the function of complex neuronal networks by stimulation of genetically targeted neurons. In slice physiology, ChR2 opens the door to novel types of experiments and greatly extends the technical possibilities offered by traditional electrophysiology. In this short review, we first consider several technical aspects concerning the use of ChR2 in slice physiology, providing examples from our own work. More specifically, we discuss differences between light-evoked action potentials and spontaneous or electrically induced action potentials. Our work implies that light-evoked action potentials are associated with increased calcium influx and a very high probability of neurotransmitter release. Furthermore, we point out the factors limiting the spatial resolution of ChR2 activation. Secondly, we discuss how synaptic transmission and plasticity can be studied using ChR2. Postsynaptic depolarization induced by ChR2 can be combined with two-photon glutamate uncaging to potentiate visually identified dendritic spines. ChR2-mediated stimulation of presynaptic axons induces neurotransmitter release and reliably activates postsynaptic spines. In conclusion, ChR2 is a powerful tool to investigate activity-dependent changes in structure and function of synapses.

Based on the chaos game representation, a 2D graphical representation of protein sequences was introduced in which the 20 amino acids are rearranged in a cyclic order according to their physicochemical properties. The Euclidean distances between the corresponding amino acids from the 2-D graphical representations are computed to find matching (or conserved) fragments of amino acids between the two proteins. Again, the cumulative distance of the 2D-graphical representations is defined to compare the similarity of protein. And, the examination of the similarity among sequences of the ND5 proteins of nine species shows the utility of our approach.

A novel linear trinuclear zinc(II) complex, {[ZnL(OAc)]2Zn}·CH3COCH3 (H2L: ethylenedioxybis(5-bromo-2- hydroxybenzylideneamino)), has been synthesized and structurally characterized. X-ray crystal structure of the complex reveals that three zinc(II) ions are coordinated by two tetradentate L2− units and two acetate ions acting as bridging groups. The coordination geometry around the terminal Zn(1) or Zn(1)#1 atom approaches a distorted square pyramid. The coordination sphere of the central Zn(2) atom constitutes a slightly distorted octahedral geometry. The blue-green emission from the zinc(II) complex can be observed, where the maximum emission wavelength is at 464 nm.

Background Osteosarcoma (OSA) is the most frequent type of primary malignant bone tumor and is apt to occur in children and young adults. Pulmonary metastasis (OSPM) is the major reason for its fatal outcome. Osteocalcin (OC) is a major noncollagenous bone protein whose expression is limited almost exclusively to bone marrow and osteotropic tumors. OC is also known to express in cell lines with bone metastasis feathers. Gene therapy strategies with the OC promoter directing the replication of adenovirus in a tumor-specific manner are a potential modality for OSPM therapy. Methods We detected OC mRNA expression by RNA in situ hybridization in OSA and OSPM samples from patients, and tested OC promoter transcriptional activity in OSA and non-OSA cell lines. Then we used a transcriptional replication-competent adenovirus, Ad-OC-E1a, to treat OSPM, and evaluated its tumor-specific replication and killing activities in vitro as well as anti-OSPM efficacy in vivo via systemic delivery. Results OC mRNA was detected in all types of OSA tissues, including OSPM tissues. The transcriptional activity of the OC promoter was much higher in a OSPM cell line SAOS-2LM7 and primary OSA cell line MG63 than in non-OSA cell lines, including cell lines from breast cancer, colon cancer, and liver cancer. Ad-OC-E1a expressed E1a protein only in MG63 and SAOS-2LM7, which indicated that adenovirus E1a was under strict control by the OC promoter. Ad-OC-E1a demonstrated killing and viral replication activity close to wild-type adenovirus levels in MG63 and SAOS-2LM7, but the killing and viral replication activities were attenuated significantly in cells expressing low OC transcriptional activity. To test whether Ad-OC-E1a could be used to target human OSPM in vivo, SAOS-2LM7 pulmonary metastasis models in nude mice were induced and treated by tail-vein injection with Ad-OC-E1a. Compared to tumor nodules in the lung in groups treated with PBS or control virus, the quantity of metastasized tumor nodules decreased significantly. Adenovirus-infected cells were stained immunohistochemically only inside and around the OSPM nodules but spared normal lung tissue and other organs. Conclusions These data demonstrated that OC promoter could direct adenovirus replication by controlling the E1a gene to target human OSPM in a tumor-specific manner, providing an efficient tool to develop a feasible therapeutic modality for OSPM. Copyright © 2006 John Wiley & Sons, Ltd.

Sevelamer, a phosphate-binding drug, is successfully used as catalyst in Knoevenagel reaction.

The role of the extracellular matrix in cutaneous morphogenesis is poorly understood. Here, we describe the essential role of laminin-10 (alpha5beta1gamma1) in hair follicle development. Laminin-10 was present in the basement membrane of elongating hair germs, when other laminins were downregulated, suggesting a role for laminin-10 in hair development. Treatment of human scalp xenografts with antibodies to laminin-10, or its receptor beta1 integrin, produced alopecia. E16.5 Lama5 -/- mouse skin, lacking laminin-10, contained fewer hair germs compared with controls, and after transplantation, Lama5 -/- skin showed a failure of hair germ elongation followed by complete hair follicle regression. Lama5 -/- skin showed defective basement membrane assembly, without measurable increases in anoikis. Instead, Lama5 -/- skin showed decreased expression of early hair markers including sonic hedgehog and Gli1, implicating laminin-10 in developmental signaling. Intriguingly, treatment of Lama5 -/- skin with purified laminin-10 corrected basement membrane defects and restored hair follicle development. We conclude that laminin-10 is required for hair follicle development and report the first use of exogenous protein to correct a cutaneous developmental defect.

Angiogenesis is critical to wound repair. Newly formed blood vessels participate in provisional granulation tissue formation and provide nutrition and oxygen to growing tissues. In addition, inflammatory cells require the interaction with and transmigration through the endothelial basement membrane to enter the site of injury. Angiogenesis, in response to tissue injury, is a dynamic process that is highly regulated by signals from both serum and the surrounding extracellular matrix (ECM) environment. Vascular endothelial growth factor, angiopoietin, fibroblast growth factor, and transforming growth factor beta are among those most potent angiogenic cytokines in wound angiogenesis. The cooperative regulation of them is essential for wound repair. Migration of endothelial cells and development of new capillary vessels during wound repair is dependent on not only the cells and cytokines present but also the production and organization of ECM components both in granulation tissue and in endothelial basement membrane. The ECM regulates angiogenesis by providing scaffold support and signaling roles. They also serve as a reservoir and modulator for growth factors. Laminins are the major noncollagenous ECM of endothelial basement membrane. Two newly recognized laminins, 8 and 10, are the major laminins produced by human dermal microvascular endothelial cells. Laminin 10 is highly expressed in blood vessels around skin wounds. Laminin 8 promotes dermal endothelial cell attachment, migration, and tubule formation. Integrins with either beta 1 or alpha v subunits are the major cellular surface receptors for ECM molecules and mediate the interactions between cells and ECM during wound angiogenesis.

A porcine model of second-degree burn wound was used to evaluate the effect of a newly developed topical oxygen emulsion (TOE) on collagen deposition during wound repair. A total of 6 pigs were used for the study. The burn wounds were treated with air exposure (no treatment), vehicle control or TOE, which contains super-saturated oxygen and releases oxygen in sustained high level when applied topically. Skin wound samples were collected at days 0, 1, 4, 7, 10, 14 and 21 after wounding. Semi-quantitative Reverse Transcription and Polymerase Chain Reactions (RT-PCR) were used to examine the mRNA expressions for type I and type III collagens and matrix metalloprotease-1 (MMP-1). RT-PCR products were run on ethidium bromide gel and analyzed under UV light with Bio-Rad Gel Document 2000 system. The expression intensity was recorded as the mean gray value. One-way analysis of variance was used for statistical analysis. The results showed: 1). Higher mRNA expressions of collagen III and MMP-1 were observed in TOE treatment group compared with air exposure and vehicle control groups. 2). MMP-1 expression increased shortly after wounding with peak at days 4 and 7. 3). Collagen III expression increased earlier with peak at day 10 and day 14. 4). Collagen I expression level increased later than that of collagen III. Significant increase was seen after day 10 with the highest at day 21. However, there was no significant difference between vehicle control and TOE treatment groups. The data suggests that sustained high level of oxygen release by TOE may promote wound repair through the mechanism of increased expressions of type I and type III collagens. The TOE also increased the expression of MMP-1, which might accelerate clearing damaged collagens in the earlier phase of wound healing and promote collagen remodeling in the later phase. This study was supported by grants from DOD/DARPA and the Dermatology Foundation of South Florida.