Clinical Investigation of Large Volume Subcutaneous Delivery up to 25 mL for Lean and Non-Lean Subjects.

PURPOSE: To evaluate the clinical feasibility and tolerability of large volume subcutaneous delivery at different injection depths for lean and non-lean subjects. METHODS: A single-center, randomized, subject-blinded, crossover study in 62 healthy subjects was conducted to evaluate delivery of a 10-cP solution containing hyaluronic acid. Subjects were separated into lean and non-lean cohort by SC thickness. A syringe pump was used to study the effect of different volumes (5, 12, 25 mL) of a viscous placebo solution and needle lengths (6, 9 and 12 mm) delivered at 0.5 mL/min. RESULTS: Across all treatments, injection sites were observed to have negligible leakage, ~34 kPa of back pressure, and VAS of mild pain with higher pain from needle insertion than during injection. While mild to moderate erythema was the most frequently reported ISR and edema was most prominent for 25 mL injections, all ISRs were resolved within 4 hours post injection. Subjects were unbothered by ISRs across all treatments and rated them as low distress scores (average 1.0-1.5 out of 6). CONCLUSION: SC injection of 25 mL is feasible and tolerable using a low-pain formulation for abdomen injection irrespective of subcutaneous thickness and injection depths at a delivery rate of 0.5 mL/min.

Progress of South East Asian Region countries towards achieving interim End TB strategy targets for TB incidence and mortality: a modelling study.

OBJECTIVES: In 2018, the World Health Organisation (WHO) reported that almost 10 million people worldwide had tuberculosis (TB). The majority of the TB cases were concentrated in South East Asian Region (SEAR) countries. To curb this burden, the WHO has set interim targets to reduce TB incidence by 50% and mortality by 75% by 2025 (interim targets of the 'End TB' strategy). Hence, this study was conducted to determine the progress of SEAR countries towards reaching these interim targets for TB incidence and mortality. METHODS: Secondary data analysis was performed using information from the WHO Global Health Observatory and Global Health Estimates for all SEAR countries. ARIMA modelling was used to forecast TB incidence and TB mortality from 2000 to 2025. Joinpoint regression was performed to determine the average annual percent change. RESULTS: Based on the current trend, we estimated that the incidence and mortality of TB in SEAR countries will decline to 3.7 million (4.37 million in 2018) and 495,280 (650,979 in 2016) by 2025, respectively. Projected age-standardised TB incidence showed a significant decline in only four SEAR countries, with the maximal decline in Myanmar (47.3%) followed by India (23.4%) compared with 2015 estimates. Age-standardised TB mortality showed a declining trend in six SEAR countries, with the maximum decline found in Myanmar (60.3%) followed by Thailand (39.0%). CONCLUSIONS: Current study findings show that it is highly unlikely for most SEAR countries to achieve the WHO recommended interim End TB targets of 50% reduction in incidence and 75% reduction in mortality by 2025.

Diurnal and seasonal patterns of soil CO2 efflux from the Pichavaram mangroves, India.

The diurnal and seasonal variation of soil carbon dioxide (CO2) flux was measured in the Pichavaram mangrove forest, the Southeast coast of India from February 2016 to October 2016 using an automated soil CO2 flux chamber system. Maximum soil CO2 efflux reached at 14:00 h and minimum at 00:00 h. The surface soil CO2 concentration ranged from 375 to 532 ppm with the mean 405 ± 18 ppm. The daily soil CO2 flux varied from near zero to about 7 µmol m-2 s-1 with a mean value of 2.4 ± 1.3 µmol m-2 s-1. The highest seasonal CO2 efflux from soil was during the summer and premonsoon seasons, whereas low flux values were recorded during the monsoon season. Soil CO2 efflux values were highly correlated with soil temperature. Tidal inundation during monsoon season, extreme drought condition in summer, and unusual precipitation are the major factors controlling the soil CO2 flux.

Dissecting and analyzing key residues in protein-DNA complexes.

Protein-DNA interactions are involved in various fundamental biological processes such as replication, transcription, DNA repair, and gene regulation. To understand the interaction in protein-DNA complexes, the integrative study of binding and stabilizing residues is important. In the present study, we have identified key residues that play a dual role in both binding and stability from a nonredundant dataset of 319 protein-DNA complexes. We observed that key residues are identified in very less number of complexes (29%) and only about 4% of stabilizing/binding residues are identified as key residues. Specifically, stabilizing residues have higher preference to be key residues than binding residues. These key residues include polar, nonpolar, aliphatic, aromatic, and charged amino acids. Moreover, we have analyzed and discussed the key residues in different protein-DNA complexes, which are classified based on protein structural class, function, DNA strand, and their conformations. Especially, Ser, Thr, Tyr, Arg, and Lys residues are commonly found in most of the subclasses of protein-DNA complexes. Further, we analyzed atomic contacts, which show that polar-nonpolar is more enriched than other types of contacts. In addition, the charged contacts are highly preferred in protein-DNA complexes compared with protein-protein and protein-RNA complexes. Finally, we have discussed the sequence and structural features of key residues such as conservation score, surrounding hydrophobicity, solvent accessibility, secondary structure, and long-range order. This study will be helpful to understand the recognition mechanism and structural and functional aspects of protein-DNA complexes.

Cross-talk between clinical and host-response parameters of periodontitis in smokers.

BACKGROUND AND OBJECTIVE: Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host-response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens and oral commensal bacteria; and (iv) other variables of interest, in a population of smokers with (n = 171) and without (n = 117) periodontitis. MATERIAL AND METHODS: Bayesian network structured learning (BNSL) techniques were used to investigate potential associations and cross-talk between the four broad sets of variables. RESULTS: BNSL revealed two broad communities with markedly different topology between the populations of smokers, with and without periodontitis. Confidence of the edges in the resulting network also showed marked variations within and between the periodontitis and nonperiodontitis groups. CONCLUSION: The results presented validated known associations and discovered new ones with minimal precedence that may warrant further investigation and novel hypothesis generation. Cross-talk between the clinical variables and antibody profiles of bacteria were especially pronounced in the case of periodontitis and were mediated by the antibody response profile to Porphyromonas gingivalis.

Immune system transcriptome in gingival tissues of young nonhuman primates.

BACKGROUND AND OBJECTIVE: Young/adolescent humans harbor many microorganisms associated with periodontal disease in adults and show substantial gingival inflammatory responses. However, younger individuals do not demonstrate the soft- and hard-tissue destruction that hallmark periodontitis. MATERIAL AND METHODS: This study evaluated responses to the oral microbial ecology in gingival tissues from clinically healthy young Macaca mulatta (< 3 years of age) compared with older animals (5-23 years of age). RNA was isolated from the tissues and analyzed for the transcriptome using the Rhesus Macaque GeneChip (Affymetrix). RESULTS: Global transcriptional profiling of four age groups revealed a subset of 159 genes that were differentially expressed across at least one of the age comparisons. Correlation metrics generated a relevance network abstraction of these genes. Partitioning of the relevance network revealed seven distinct communities comprising functionally related genes associated with host inflammatory and immune responses. A group of genes was identified that were selectively increased/decreased or positively/negatively correlated with gingival profiles in the animals. A principal components analysis created metagenes of expression profiles for classifying the 23 animals. CONCLUSION: The results provide novel system-level insights into gene-expression differences in gingival tissues from healthy young animals, weighted toward host responses associated with anti-inflammatory biomolecules or those linked with T-cell regulation of responses. The combination of the regulated microenvironment may help to explain the apparent 'resistance' of younger individuals to developing periodontal disease.

EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

GAP: towards almost 100 percent prediction for ß-strand-mediated aggregating peptides with distinct morphologies.

MOTIVATION: Distinguishing between amyloid fibril-forming and amorphous ß-aggregating aggregation-prone regions (APRs) in proteins and peptides is crucial for designing novel biomaterials and improved aggregation inhibitors for biotechnological and therapeutic purposes. RESULTS: Adjacent and alternate position residue pairs in hexapeptides show distinct preferences for occurrence in amyloid fibrils and amorphous ß-aggregates. These observations were converted into energy potentials that were, in turn, machine learned. The resulting tool, called Generalized Aggregation Proneness (GAP), could successfully distinguish between amyloid fibril-forming and amorphous ß-aggregating hexapeptides with almost 100 percent accuracies in validation tests performed using non-redundant datasets. CONCLUSION: Accuracies of the predictions made by GAP are significantly improved compared with other methods capable of predicting either general ß-aggregation or amyloid fibril-forming APRs. This work demonstrates that amino acid side chains play important roles in determining the morphological fate of ß-mediated aggregates formed by short peptides. AVAILABILITY AND IMPLEMENTATION: http://www.iitm.ac.in/bioinfo/GAP/.

Differential Gene Expression Profiles Reflecting Macrophage Polarization in Aging and Periodontitis Gingival Tissues.

Recent evidence has determined a phenotypic and functional heterogeneity for macrophage populations. This plasticity of macrophage function has been related to specific properties of subsets (M1 and M2) of these cells in inflammation, adaptive immune responses and resolution of tissue destructive processes. This investigation hypothesized that targeted alterations in the distribution of macrophage phenotypes in aged individuals, and with periodontitis would be skewed towards M1 inflammatory macrophages in gingival tissues. The study used a non-human primate model to evaluate gene expression profiles as footprints of macrophage variation in healthy and periodontitis gingival tissues from animals 3-23 years of age and in periodontitis tissues in adult and aged animals. Significant increases in multiple genes reflecting overall increases in macrophage activities were observed in healthy aged tissues, and were significantly increased in periodontitis tissues from both adults and aged animals. Generally, gene expression patterns for M2 macrophages were similar in healthy young, adolescent and adult tissues. However, modest increases were noted in healthy aged tissues, similar to those seen in periodontitis tissues from both age groups. M1 macrophage gene transcription patterns increased significantly over the age range in healthy tissues, with multiple genes (e.g. CCL13, CCL19, CCR7 and TLR4) significantly increased in aged animals. Additionally, gene expression patterns for M1 macrophages were significantly increased in adult health versus periodontitis and aged healthy versus periodontitis. The findings supported a significant increase in macrophages with aging and in periodontitis. The primary increases in both healthy aged tissues and, particularly periodontitis tissues appeared in the M1 phenotype.

Novel approach for selecting the best predictor for identifying the binding sites in DNA binding proteins.

Protein-DNA complexes play vital roles in many cellular processes by the interactions of amino acids with DNA. Several computational methods have been developed for predicting the interacting residues in DNA-binding proteins using sequence and/or structural information. These methods showed different levels of accuracies, which may depend on the choice of data sets used in training, the feature sets selected for developing a predictive model, the ability of the models to capture information useful for prediction or a combination of these factors. In many cases, different methods are likely to produce similar results, whereas in others, the predictors may return contradictory predictions. In this situation, a priori estimates of prediction performance applicable to the system being investigated would be helpful for biologists to choose the best method for designing their experiments. In this work, we have constructed unbiased, stringent and diverse data sets for DNA-binding proteins based on various biologically relevant considerations: (i) seven structural classes, (ii) 86 folds, (iii) 106 superfamilies, (iv) 194 families, (v) 15 binding motifs, (vi) single/double-stranded DNA, (vii) DNA conformation (A, B, Z, etc.), (viii) three functions and (ix) disordered regions. These data sets were culled as non-redundant with sequence identities of 25 and 40% and used to evaluate the performance of 11 different methods in which online services or standalone programs are available. We observed that the best performing methods for each of the data sets showed significant biases toward the data sets selected for their benchmark. Our analysis revealed important data set features, which could be used to estimate these context-specific biases and hence suggest the best method to be used for a given problem. We have developed a web server, which considers these features on demand and displays the best method that the investigator should use. The web server is freely available at http://www.biotech.iitm.ac.in/DNA-protein/. Further, we have grouped the methods based on their complexity and analyzed the performance. The information gained in this work could be effectively used to select the best method for designing experiments.

Cytotoxicity of TiO2 nanoparticles towards freshwater sediment microorganisms at low exposure concentrations.

There is a persistent need to assess the effects of TiO2 nanoparticles on the aquatic ecosystem owing to their increasing usage in consumer products and risk of environmental release. The current study is focused on TiO2 nanoparticle-induced acute toxicity at sub-ppm level (≤1ppm) on the three different freshwater sediment bacterial isolates and their consortium under two different irradiation (visible light and dark) conditions. The consortium of the bacterial isolates was found to be less affected by the exposure to the nanoparticles compared to the individual cells. The oxidative stress contributed considerably towards the cytotoxicity under both light and dark conditions. A statistically significant increase in membrane permeability was noted under the dark conditions as compared to the light conditions. The optical and fluorescence microscopic images showed aggregation and chain formation of the bacterial cells, when exposed to the nanoparticles. The electron microscopic (SEM, TEM) observations suggested considerable damage of cells and bio-uptake of nanoparticles. The exopolysaccrides (EPS) production and biofilm formation were noted to increase in the presence of the nanoparticles, and expression of the key genes involved in biofilm formation was studied by RT-PCR.

Vertical distribution of heavy metals in soil profile in a seasonally waterlogging agriculture field in Eastern Ganges Basin.

The accumulation of heavy metals in soil and water is a serious concern due to their persistence and toxicity. This study investigated the vertical distribution of heavy metals, possible sources and their relation with soil texture in a soil profile from seasonally waterlogged agriculture fields of Eastern Ganges basin. Fifteen samples were collected at ~0.90-m interval during drilling of 13.11 mbgl and analysed for physical parameters (moisture content and grain size parameters: sand, silt, clay ratio) and heavy metals (Fe, Mn, Cr, Cu, Pb, Zn, Co, Ni and Cd). The average metal content was in the decreasing order of Fe > Mn > Cr > Zn > Ni > Cu > Co > Pb > Cd. Vertical distribution of Fe, Mn, Zn and Ni shows more or less similar trends, and clay zone records high concentration of heavy metals. The enrichment of heavy metals in clay zone with alkaline pH strongly implies that the heavy metal distributions in the study site are effectively regulated by soil texture and reductive dissolution of Fe and Mn oxy-hydroxides. Correlation coefficient analysis indicates that most of the metals correlate with Fe, Mn and soil texture (clay and silt). Soil quality assessment was carried out using geoaccumulation index (I(geo)), enrichment factor (EF) and contamination factor (CF). The enrichment factor values were ranged between 0.66 (Mn) and 2.34 (Co) for the studied metals, and the contamination factor values varied between 0.79 (Mn) and 2.55 (Co). Results suggest that the elements such as Cu and Co are categorized as moderate to moderately severe contamination, which are further confirmed by I(geo) values (0.69 for Cu and 0.78 for Co). The concentration of Ni exceeded the effects-range median values, and the biological adverse effect of this metal is 87%. The average concentration of heavy metals was compared with published data such as concentration of heavy metals in Ganga River sediments, Ganga Delta sediments and upper continental crust (UCC), which apparently revealed that heavy metals such as Fe, Mn, Cr, Pb, Zn and Cd are influenced by the dynamic nature of flood plain deposits. Agricultural practice and domestic sewage are also influenced on the heavy metal content in the study area.

Modulation of 3D Bioprintability in Polysaccharide Bioink by Bioglass Nanoparticles and Multiple Metal Ions for Tissue Engineering.

BACKGROUND: Bioglasses are used in applications related to bone rehabilitation and repair. The mechanical and bioactive properties of polysaccharides like alginate and agarose can be modulated or improved using bioglass nanoparticles. Further essential metal ions used as crosslinker have the potential to supplement cultured cells for better growth and proliferation. METHOD: In this study, the alginate bioink is modulated for fabrication of tissue engineering scaffolds by extrusion-based 3D bioprinting using agarose, bioglass nanoparticles and combination of essential trace elements such as iron, zinc, and copper. Homogeneous bioink was obtained by in situ mixing and bioprinting of its components with twin screw extruder (TSE) based 3D bioprinting, and then distribution of metal ions was induced through post-printing diffusion of metal ions in the printed scaffolds. The mechanical and 3d bioprinting properties, microscopic structure, biocompatibility of the crosslinked alginate/agarose hydrogels were analyzed for different concentrations of bioglass. The adipose derived mesenchymal stem cells (ADMSC) and osteoblast cells (MC3T3) were used to evaluate this hydrogel's biological performances. RESULTS: The porosity of hydrogels significantly improves with the incorporation of the bioglass. More bioglass concentration results in improved mechanical (compressive, dynamic, and cyclic) and 3D bioprinting properties. Cell growth and extracellular matrix are also enhanced with bioglass concentration. CONCLUSION: For bioprinting of the bioinks, the advanced TSE head was attached to 3D bioprinter and in situ fabrication of cell encapsulated scaffold was obtained with optimized composition considering minimal effects on cell damage. Fabricated bioinks demonstrate a biocompatible and noncytotoxic scaffold for culturing MC3T3 and ADMSC, while bioglass controls the cellular behaviors such as cell growth and extracellular matrix formation.

Characteristics of a Spray-Dried Porcine Blood Meal for Aedes aegypti Mosquitoes.

Research into mosquito-borne illnesses faces hurdles because feeding fresh animal blood to rear female mosquitoes presents logistical, economic, and safety challenges. In this study, a shelf-stable additive (spray-dried porcine blood; SDPB) hypothesized to supply accessible hemoglobin was evaluated within an alternative meal (AM) containing whey powder and PBS for rearing the yellow fever mosquito Aedes aegypti. LC-MS/MS proteomics, microbial assays, and particle reduction techniques confirmed and characterized the functionality of hemoglobin in SDPB, while engorgement, fecundity, egg viability, and meal stability bioassays assessed AM performance. Chemical assays supported hemoglobin as the phagostimulant in SDPB with aggregates partially solubilized in the AM that can be more accessible via particle reduction. Unpaired two-tailed t-tests indicate that the AM stimulates oogenesis (t11 = 13.6, p = 0.003) and is stable under ambient (1+ y; t12 = 0.576, p = 0.575) and aqueous (14 d; t12 = 0.515, p = 0.639) conditions without decreasing fecundity. Egg hatch rates for the ninth generation of AM-reared Ae. aegypti were 50-70+%. With further development, this meal may serve as a platform for mass rearing or studying effects of nutritional additives on mosquito fitness due to its low cost and stability. Future work may examine tuning spray drying parameters and resulting impacts on hemoglobin agglomeration and feeding.

Proton magnetic resonance spectroscopy of human cervical spondylosis at 3T.

STUDY DESIGN: A single-center magnetic resonance imaging and spectroscopic study involving 21 patients with advanced cervical spondylosis and 11 healthy controls. OBJECTIVE: We assessed the utility of magnetic resonance spectroscopy (MRS) to quantify biochemical changes within the spinal cord and serve as a potential biomarker in patients with cervical spondylosis with or without T2 hyperintensity within the cord. SETTING: Los Angeles, California, USA. METHODS: Twenty-one patients with cervical spondylosis and eleven healthy controls were evaluated. Single-voxel MRS was performed in the cervical cord. Morphometry of the spinal canal space was measured. N-Acetyl aspartylglutamic acid (NAA), choline (Cho), myo-inositol (Myo-I), glutamine-glutamate complex (Glx) and lactate metabolite concentration ratios with respect to total creatine (Cr) were quantified using an LC model algorithm and compared between healthy controls and spondylosis patients. Correlation of MRS metabolites with modified Japanese Orthopaedic Association (mJOA) score was also performed. RESULTS: The spinal canal space was significantly different between patients and controls (analysis of variance (ANOVA), P<0.0001). Total Cho-to-Cr ratio was significantly elevated in patients with spondylosis and T2-hyperintensity compared with healthy controls (ANOVA, P<0.01). A significantly higher Cho-to-NAA ratio was observed in spondylosis patients compared with healthy controls (ANOVA, P<0.01). Slightly elevated Glx and Myo-I were encountered in patients with stenosis without T2 hyperintensity. A linear correlation between Cho-NAA ratio and mJOA was also observed (P<0.01). CONCLUSION: MRS appears sensitive to biochemical changes occurring in advanced cervical spondylosis patients. The Cho/NAA ratio was significantly correlated with the mJOA score, providing a potentially clinically useful radiographical biomarker for the management of advanced cervical spondylosis patients.

Trend and Determinants of Fertility in a Declining Fertility Regime: A Study of Rural Uttar Pradesh.

This study is an attempt to examine the socio-economic and demographic differentials in children ever born and desire for additional child in rural Uttar Pradesh using the empirical data set. Two stage stratified random sampling procedure was applied to select the respondents from ten villages of rural Raebareli district. Total 460 women having with at least one child below ten years of age were interviewed during September 2016 to February 2017. Children ever born (CEB) and desire for another child were the main outcome variables of the study. One-way ANOVA and chi-square test were used in the bi-variate analysis. Poisson regression and logistic regression were used in multivariate analysis. The mean children ever born in the study area was 2.7 children per women and 64.7 per cent of fecund women who had two children and not currently pregnant had no desire for another child. Women's education, economic status of the household, autonomy index and higher caste group were significantly negatively associated with the children ever born in the study area. The desire for another child was significantly higher among those who had only daughters (OR = 1.99; p < 0.01). In conclusion, more emphasis needs to be placed on messages conveyed through the mass media, addressing the benefits of small family size and family planning, and programs that focus on reduction in newborn mortality could also be considered, which would also help to reduce fertility.

Geochemical fractionation, mobility of elements and environmental significance of surface sediments in a Tropical River, Borneo.

Miri River is a tropical river in Borneo that drains on flat terrain and urbanised area and debauches into the South China Sea. This paper documents the environmental status of this river, and provides an insight into the provenance using bulk chemistry of the sediments, and brings out the geochemical mobility, bioavailability, and potential toxicity of some critical elements based on BCR sequential extraction. The sediments are intense to moderately weathered and recycled products of Neogene sedimentary rocks. The hydrodynamic characteristics of the river favoured an upstream section dominated by fine sand, while the downstream sediments are medium silt. Based on the bulk geochemistry, the Miri River sediments are moderate to considerably contaminated by Cu, Mo, and As in the upstream and by Sb, As and Cu in the downstream. The potential ecological risk values are low except Cu and a significant biological impact is expected in downstream due to Cu, As, Zn and Cr. The mobility, bioavailability and Risk Assessment Code values for Zn and Mn are higher and thus may pose moderate to very high risk to aquatic organisms. Though a high bulk concentration of Cu is observed, the association of Cu with the bioavailable fraction is low.

3D bioprinting of complex tissue scaffolds with in situ homogeneously mixed alginate-chitosan-kaolin bioink using advanced portable biopen.

Control of in situ 3D bioprinting of hydrogel without toxic crosslinker is ideal for tissue regeneration by reinforcing and homogeneously distributing biocompatible reinforcing agent during fabrication of large area and complex tissue engineering scaffolds. In this study, homogeneous mixing, and simultaneous 3D bioprinting of a multicomponent bioink based on alginate (AL)-chitosan (CH), and kaolin was obtained by an advanced pen-type extruder to ensure structural and biological homogeneity during the large area tissue reconstruction. The static, dynamic and cyclic mechanical properties as well as in situ self-standing printability significantly improved with the kaolin concentration for AL-CH bioink-printed samples due to polymer-kaolin nanoclay hydrogen bonding and cross-linking with less amount of calcium ions. The Biowork pen ensures better mixing effectiveness for the kaolin-dispersed AL-CH hydrogels (evident from computational fluid dynamics study, aluminosilicate nanoclay mapping and 3D printing of complex multilayered structures) than the conventional mixing process. Two different cell lines (osteoblast and fibroblast) introduced during large area multilayered 3D bioprinting have confirmed the suitability of such multicomponent bioinks for in vitro even tissue regeneration. The effect of kaolin to promote uniform growth and proliferation of the cells throughout the bioprinted gel matrix is more significant for this advanced pen-type extruder processed samples.

Hexagonally ordered KLaF4 host: phase-controlled synthesis and luminescence studies.

Experiments resulting in the successful synthesis of hexagonally ordered KLaF(4) have been described for the first time. Syntheses from three different lanthanum precursors and KF under nonaqueous conditions and at atmospheric pressure are presented. The temperature, time of the fluorination reactions, and lanthanum precursor influenced the formation of hexagonal KLaF(4). While La(O(i)Pr)(3) and La(acac)(3) yielded hexagonal KLaF(4) by their reaction with KF in methanol at 65 °C, LaCl(3) favored only the formation of cubic KLaF(4) at 25 °C (room temperature). Size-induced phase transformation from cubic KLaF(4) to its hexagonal polymorph has been proposed for the reactions involving La(acac)(3) and La(O(i)Pr)(3) and KF. Rietveld refinement of the powder X-ray diffraction pattern of the hexagonally ordered KLaF(4) was successfully carried out in space group P6̅2m (No. 189) with lattice constants a = 6.5842(3) Å and c = 3.8165(3) Ǻ. A relatively lower effective phonon energy of 262 cm(-1) observed for the hexagonally ordered KLaF(4) (determined from its Raman spectrum) suggests its potential as a host for optically active elements with the possibility of minimized nonradiative processes. The hexagonal KLaF(4) sample was doped with Er(3+) ion (3 mol %) and systematically investigated by diffuse reflectance, normal emission, and upconversion studies. Strong green emission ((4)S(3/2), (2)H(11/2) → (4)I(15/2)) has been observed upon 980 and 460 nm excitation. A highly transparent light-emitting polymer [poly(methyl methacrylate)] composite containing hexagonal KLaF(4):Er(3+) phosphor has also been effectively demonstrated for many potential applications.

The electronic spectrum of Si3 I: triplet D(3h) system.

We report the measurement of a jet-cooled electronic spectrum of the silicon trimer. Si(3) was produced in a pulsed discharge of silane in argon, and the excitation spectrum examined in the 18 000-20 800 cm(-1) region. A combination of resonant two-color two-photon ionization (R2C2PI) time-of-flight mass spectroscopy, laser-induced fluorescence/dispersed fluorescence, and equation-of-motion coupled-cluster calculations have been used to establish that the observed spectrum is dominated by the 1(3)A(1)" - ã (3)A(2)' transition of the D(3h) isomer. The spectrum has an origin transition at 18,600 ± 4 cm(-1) and a short progression in the symmetric stretch with a frequency of ∼445 cm(-1), in good agreement with a predicted vertical transition energy of 2.34 eV for excitation to the 1(3)A(1)" state, which has a calculated symmetric stretching frequency of 480 cm(-1). In addition, a ∼505 cm(-1) ground state vibrational frequency determined from sequence bands and dispersed fluorescence is in agreement with an earlier zero-electron kinetic energy study of the lowest D(3h) state and with theory. A weaker, overlapping band system with a ∼360 cm(-1) progression, observed in the same mass channel (m/z = 84) by R2C2PI but under different discharge conditions, is thought to be due to transitions from the (more complicated) singlet C(2v) ground state ((1)A(1)) state of Si(3). Evidence of emission to this latter state in the triplet dispersed fluorescence spectra suggests extensive mixing in the excited triplet and singlet manifolds. Prospects for further spectroscopic characterization of the singlet system and direct measurement of the energy separation between the lowest singlet and triplet states are discussed.