Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2.

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics

Extending the limits of globule detection -- ISOPHOT Serendipity Survey Observations of interstellar clouds

A faint $I_{\rm 170}=4$ MJysr$^{-1}$ bipolar globule was discovered with the ISOPHOT 170 $\mu$m Serendipity Survey (ISOSS). ISOSS J 20246+6541 is a cold ($T_{\rm d}\approx 14.5$ K) FIR source without an IRAS pointsource counterpart. In the Digitized Sky Survey B band it is seen as a 3\arcmin size bipolar nebulosity with an average excess surface brightness of $\approx 26$ mag/$\square$\arcsec . The CO column density distribution determined by multi-isotopic, multi-level CO measurements with the IRAM-30m telescope agrees well with the optical appearance. An average hydrogen column density of $\approx 10^{21}$cm$^{-2}$ was derived from both the FIR and CO data. Using a kinematic distance estimate of 400 pc the NLTE modelling of the CO, HCO$^+$, and CS measurements gives a peak density of $\approx 10^4$cm$^{-3}$. The multiwavelength data characterise ISOSS 20246+6541 as a representative of a class of globules which has not been discovered so far due to their small angular size and low 100$\mu$m brightness. A significant overabundance of $^{13}$CO is found $X(^{13}CO) \ge 150\times X(C^{18}O)$. This is likely due to isotope selective chemical processes.Comment: 5 pages, 3 figure

Conductivity of Strongly Coupled Striped Superconductor

We study the conductivity of a strongly coupled striped superconductor using gauge/gravity duality (holography). The study is done analytically, in the large modulation regime. We show that the optical conductivity is inhomogeneous but isotropic at low temperatures. Near but below the critical temperature, we calculate the conductivity analytically at small frequency \omega, and find it to be both inhomogeneous and anisotropic. The anisotropy is imaginary and scales like 1/\omega. We also calculate analytically the speed of the second sound and the thermodynamic susceptibility.Comment: 32 page

A surrogate model for the economic evaluation of renewable hydrogen production from biomass feedstocks via supercritical water gasification

Supercritical water gasification is a promising technology for renewable hydrogen production from high moisture content biomass. This work produces a machine learning surrogate model to predict the Levelised Cost of Hydrogen over a range of biomass compositions, processing capacities, and geographic locations. The model is published to facilitate early-stage economic analysis (doi.org/10.6084/m9.figshare.22811066). A process simulation using the Gibbs reactor provided the training data using 40 biomass compositions, five processing capacities (10–200 m3/h), and three geographic locations (China, Brazil, UK). The levelised costs ranged between 3.81 and 18.72 $/kgH2 across the considered parameter combinations. Heat and electricity integration resulted in low process emissions averaging 0.46 kgCO2eq/GJH2 (China and Brazil), and 0.37 kgCO2eq/GJH2 (UK). Artificial neural networks were most accurate when compared to random forests and support vector regression for the surrogate model during cross-validation, achieving an accuracy of MAPE: 0.99 on the test set

Three-dimensional scapular morphology is associated with rotator cuff tears and alters the abduction moment arm of the supraspinatus.

BACKGROUND: Numerous studies have reported an association between rotator cuff injury and two-dimensional measures of scapular morphology. However, the mechanical underpinnings explaining how these shape features affect glenohumeral joint function and lead to injury are poorly understood. We hypothesized that three-dimensional features of scapular morphology differentiate asymptomatic shoulders from those with rotator cuff tears, and that these features would alter the mechanical advantage of the supraspinatus. METHODS: Twenty-four individuals with supraspinatus tears and twenty-seven age-matched controls were recruited. A statistical shape analysis identified scapular features distinguishing symptomatic patients from asymptomatic controls. We examined the effect of injury-associated morphology on mechanics by developing a morphable model driven by six degree-of-freedom biplanar videoradiography data. We used the model to simulate abduction for a range of shapes and computed the supraspinatus moment arm. FINDINGS: Rotator cuff injury was associated with a cranial orientation of the glenoid and scapular spine (P = .011, d = 0.75) and/or decreased subacromial space (P = .001, d = 0.94). The shape analysis also identified previously undocumented features associated with superior inclination and subacromial narrowing. In our computational model, warping the scapula from a cranial to a lateral orientation increased the supraspinatus moment arm at 20° of abduction and decreased the moment arm at 160° of abduction. INTERPRETATIONS: Three-dimensional analysis of scapular morphology indicates a stronger relationship between morphology and cuff tears than two-dimensional measures. Insight into how morphological features affect rotator cuff mechanics may improve patient-specific strategies for prevention and treatment of cuff tears

Factors associated with alcohol reduction in harmful and hazardous drinkers following alcohol brief intervention in Scotland: a qualitative enquiry

Background: Alcohol Brief Intervention (ABI) uses a motivational counselling approach to support individuals to reduce excessive alcohol consumption. There is growing evidence on ABI’s use within various health care settings, although how they work and which components enhance success is largely unknown. This paper reports on the qualitative part of a mixed methods study. It explores enablers and barriers associated with alcohol reduction following an ABI. It focuses on alcohol’s place within participants’ lives and their personal perspectives on reducing consumption. There are a number of randomised controlled trials in this field though few ABI studies have addressed the experiences of hazardous/harmful drinkers. This study examines factors associated with alcohol reduction in harmful/hazardous drinkers following ABI. Methods: This qualitative study was underpinned by a realist evaluation approach and involved semistructured interviews with ten harmful or hazardous alcohol drinkers. Participants (n = 10) were from the intervention arm of a randomised controlled trial (n = 124). All had received ABI, a 20 min motivational counselling interview, six months previously, and had reduced their alcohol consumption. Interviews were recorded, transcribed verbatim and thematically analysed. Results: Participants described their views on alcohol, its’ place in their lives, their personal perspectives on reducing their consumption and future aspirations. Conclusions: The findings provide an insight into participants’ views on alcohol, ABI, and the barriers and enablers to change. Participants described a cost benefit analysis, with some conscious consideration of the advantages and disadvantages of reducing intake or abstaining from alcohol. Findings suggest that, whilst hospital admission can act as a catalyst, encouraging individuals to reflect on their alcohol consumption through ABI may consolidate this, turning this reflective moment into action. Sustainability may be enhanced by the presence of a ‘significant other’ who encourages and experiences benefit. In addition having a purpose or structure with activities linked to employment and/or social and leisure pursuits offers the potential to enhance and sustain reduced alcohol consumption. Trial registration: Trial registration number TRN NCT00982306 September 22nd 200

Ultra-strong Adhesion of Graphene Membranes

As mechanical structures enter the nanoscale regime, the influence of van der Waals forces increases. Graphene is attractive for nanomechanical systems because its Young's modulus and strength are both intrinsically high, but the mechanical behavior of graphene is also strongly influenced by the van der Waals force. For example, this force clamps graphene samples to substrates, and also holds together the individual graphene sheets in multilayer samples. Here we use a pressurized blister test to directly measure the adhesion energy of graphene sheets with a silicon oxide substrate. We find an adhesion energy of 0.45 \pm 0.02 J/m2 for monolayer graphene and 0.31 \pm 0.03 J/m2 for samples containing 2-5 graphene sheets. These values are larger than the adhesion energies measured in typical micromechanical structures and are comparable to solid/liquid adhesion energies. We attribute this to the extreme flexibility of graphene, which allows it to conform to the topography of even the smoothest substrates, thus making its interaction with the substrate more liquid-like than solid-like.Comment: to appear in Nature Nanotechnolog

Male germ cell-specific protein Trs4 binds to multiple proteins

Temperature-related sequence 4 (Trs4) has been identified as a testis-specific gene with expression sensitive to the abdominal temperature changes induced by artificial cryptorchidism. In murine testes, Trs4 mRNA was detected in round spermatids and its protein was localized mainly in the elongating spermatids as well as in the acrosomes and tails of mature spermatozoa. Using a yeast two-hybrid screening system, we identified Rshl-2, Gstmu1, and Ddc8 as putative binding partners of the Trs4 protein in mouse testes. Their interactions were confirmed by in vivo and in vitro binding assays. Further studies demonstrated that Ddc8, a newly identified gene with unknown functions, displayed a similar expression pattern with Trs4 in mouse testes. In particular, Trs4, Ddc8, and Rshl-2 proteins were co-localized to the tails of mature spermatozoa. These results suggested that Trs4 might be involved in diverse processes of spermiogenesis and/or fertilization through interactions with its multiple binding partners. © 2009 Elsevier Inc.postprin