Smart implants for mucoperiosteal tissue expansion in cleft palate defects

Cleft lip and palate are the most common craniofacial malformations, affecting one in every 500 to 700 live births, thus accounting for about 220,000 new cases each year worldwide with tremendous variations across geographic areas, ethnic groups and socioeconomic status. Affected children have a range of both functional and aesthetic problems comprising of feeding difficulties due to incomplete oral seal, swallowing, nasal regurgitation, respiratory problems, hearing difficulties due to abnormalities in the palatal musculature, and speech impairments due to air escape and articulations problems. The surgery can solve the problems, but the two major factors which determine a good surgical outcome and its assessment are the interpretation of the actual size of the cleft and generation of periosteal tissue to close the defect. The surgeons faced a challenge to measure the cleft size due to wide diversity in methodologies employed which resulted in improper estimation of the deficient palatal tissue and thus resulted contradictory results in measuring outcomes such as occlusion or midface skeletal development. We have introduced the vomer edge for establishing a validated 3D measuring method for the width, area and height of the true cleft with reproducible landmarks for easy and accurate measurement of the outcomes in unilateral cleft lip and palate patients. The passive plate therapy provided to UCLP patients gave favourable anatomical conditions for subsequent surgical palatal repair in patients by alleviating the problems of tissue deficiency to some extent. We therefore adopted periosteal tissue distraction osteogenesis as potential treatment strategy to target the tissue deficiency while using the magnetic forces to exert necessary strain. In our study, we have assessed whether the dental magnets have the potential to act as a device to generate mucoperiosteal tissue in UCLP. We have used in-silica approach in the form of 3D FE-model and found that strain levels in the palatal segments of the cleft for the load cases do reach 1500 µstrain limit, a requirement for bone formation, according to the mild overload window of the Mechanostat theory proposed by Harold Frost. We further examined the forces, which reach threshold for regeneration of the hard and soft tissue volumes along the cleft edges in both UCLP and BCLP by means of periosteal distraction. We found that a 5N attraction force could initiate generation of soft and hard tissues along the cleft edges in in-silico model within the optimal biological limits

Comparative study of quality of life in breast cancer patients receiving two different chemotherapy regimens using European Organization for Research and Treatment of Cancer Quality of Questionnaire-Core 30 questionnaire module; for tolerability and safety

Background: Breast cancer is one of the most frequent occurring cancers in women and burgeoning worldwide. It is the second most common malignancy in India after carcinoma of the uterine cervix. In clinical trials, quality of life (QOL) outcome measurements is an important as endpoints with improving subjects physical, emotional, and social well-being.Methods: In this study, we were evaluated the comparison of the QOL in breast cancer patients on anthracycline-based regimen (six cycles of 5-fluorouracil, adriamycin, and cyclophosphamide [FAC] for a period of 18 weeks) and taxane-containing regimen (four cycles of adriamycin and cyclophosphamide [AC] followed by four cycles of paclitaxel [PTX] for a period of 24 weeks) using European Organization for Research and Treatment of Cancer Quality of Questionnaire-Core 30.Results: During first 3 months of therapy, both treatment groups exhibited a reduction in health-related QOL (HRQOL) with no clinically significant difference between them. The effect on HRQOL was less evident 3 weeks after completing chemotherapy with HRQOL of both groups returning to near baseline scores.Conclusions: Both treatment regimens (FAC and AC → PTX [AC followed by PTX]) were equally tolerated in patients

Evidence for inhibitory interaction of hyaluronan-binding protein 1 (HABP1/p32/gC1qR) with Streptococcus pneumoniae hyaluronidase

Bacterial hyaluronan lyase enzymes are the major virulence factors that enable greater microbial ingress by cleaving hyaluronan (HA) polymers present predominantly in extracellular space of vertebrates. Based on the premise that effective inhibitors may bind to and stabilize HA thereby protecting it from degradation, here we investigated inhibitory activity of human hyaluronan-binding protein 1 (HABP1) on bacterial hyaluronidase because it is highly specific to HA and localized on the cell surface. Biochemical characterization revealed that HABP1 is a competitive inhibitor of Streptococcus pneumoniae hyaluronate lyase (SpnHL) with an IC50 value of 22 μm. This is thus the first report of an endogenous protein inhibitor that may be used during natural antibacterial defense. Our findings also support a novel multipronged mechanism for the high efficacy of HABP1-mediated inhibition based on structural modeling of enzyme, substrate, and inhibitor. Evidence from docking simulations and contact interface interactions showed that the inherent charge asymmetry of HABP1 plays a key role in the inhibitory activity. This novel role of HABP1 may pave the way for peptide inhibitors as alternatives to synthetic chemicals in antibacterial research

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky

The C. elegans sex determination protein MOG-3 functions in meiosis and binds to the CSL co-repressor CIR-1

In the germ line of the Caenorhabditis elegans hermaphrodite, nuclei either proliferate through mitosis or initiate meiosis, finally differentiating as spermatids or oocytes. The production of oocytes requires repression of the fem-3 mRNA by cytoplasmic FBF and nuclear MOG proteins. Here we report the identification of the sex determining gene mog-3 and show that in addition to its role in gamete sex determination, it is necessary for meiosis by acting downstream of GLP-1/Notch. Furthermore, we found that MOG-3 binds both to the nuclear proteins MEP-1 and CIR-1. MEP-1 is necessary for oocyte production and somatic differentiation, while the mammalian CIR-1 homolog counters Notch signaling. We propose that MOG-3, MEP-1 and CIR-1 associate in a nuclear complex which regulates different aspects of germ cell development. While FBF triggers the sperm/oocyte switch by directly repressing the fem-3 mRNA in the cytoplasm, the MOG proteins play a more indirect role in the nucleus, perhaps by acting as epigenetic regulators or by controlling precise splicing events

Drug Susceptibilities of Yeast Cells Are Affected by Membrane Lipid Composition

In the present study we have exploited isogenic erg mutants of Saccharomyces cerevisiae to examine the contribution of an altered lipid environment on drug susceptibilities of yeast cells. It is observed that erg mutants, which possess high levels of membrane fluidity, were hypersensitive to the drugs tested, i.e., cycloheximide (CYH), o-phenanthroline, sulfomethuron methyl, 4-nitroquinoline oxide, and methotrexate. Most of the erg mutants except mutant erg4 were, however, resistant to fluconazole (FLC). By using the fluorophore rhodamine-6G and radiolabeled FLC to monitor the passive diffusion, it was observed that erg mutant cells elicited enhanced diffusion. The addition of a membrane fluidizer, benzyl alcohol (BA), to S. cerevisiae wild-type cells led to enhanced membrane fluidity. However, a 10 to 12% increase in BA-induced membrane fluidity did not alter the drug susceptibilities of the S. cerevisiae wild-type cells. The enhanced diffusion observed in erg mutants did not seem to be solely responsible for the observed hypersensitivity of erg mutants. In order to ascertain the functioning of drug extrusion pumps encoding the genes CDR1 (ATP-binding cassette family) and CaMDR1 (MFS family) of Candida albicans in a different lipid environment, they were independently expressed in an S. cerevisiae erg mutant background. While the fold change in drug resistance mediated by CaMDR1 remained the same or increased in erg mutants, susceptibility to FLC and CYH mediated by CDR1 was increased (decrease in fold resistance). Our results demonstrate that between the two drug extrusion pumps, Cdr1p appeared to be more adversely affected by the fluctuations in the membrane lipid environment (particularly to ergosterol). By using 6-[(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino-hexanoyl] sphingosyl phosphocholine (a fluorescent analogue of sphingomyelin), a close interaction between membrane ergosterol and sphingomyelin which appears to be disrupted in erg mutants is demonstrated. Taken together it appears that multidrug resistance in yeast is closely linked to the status of membrane lipids, wherein the overall drug susceptibility phenotype of a cell appears to be an interplay among drug diffusion, extrusion pumps, and the membrane lipid environment

Practically Achievable Process Performance Limits for Pressure-Vacuum Swing Adsorption Based Post-Combustion CO2 Capture

Practically achievable limits for pressure-vacuum swing adsorption (PVSA)-based post-combustion carbon capture are evaluated. The adsorption isotherms of CO2 and N2 are described by competitive Langmuir isotherms. Two low-energy process cycles are considered and a machine learning surrogate-model is trained with inputs from an experimentally-validated detailed PVSA model. Several case studies are considered to evaluate two critical performance indicators, namely, minimum energy and maximum productivity. For each case study, the genetic algorithm optimizer that is coupled to the machine learning surrogate model, searches tens of thousands of combinations of isotherms and process operating conditions. The framework pairs the optimum material properties with the optimum operating conditions, hence providing the limits of achievable performance. The results indicate that very low pressures ( <~0.2 bar) may be required to achieve process constraints for low feeds with low feed compositions ($<0.15$ mol fraction), indicating that PVSA may not be favourable. At higher CO2 feed compositions, PVSA can be attractive and can be operated at practically achievable vacuum levels. Further, the gap between the energy consumption of available adsorbents and the achievable limits with a hypothetical -best adsorbent varies between 20% to 2.5% as the CO2 feed composition changes between 0.05 to 0.4. This indicates a limited potential for development of new adsorbents of PVSA-based CO2 capture. Future work for PVSA should focus on flue gas streams with high CO2 composition