Higher derivatives and brane-localised kinetic terms in gauge theories on orbifolds

We perform a detailed analysis of one-loop corrections to the self-energy of the (off-shell) gauge bosons in six-dimensional N=1 supersymmetric gauge theories on orbifolds. After discussing the Abelian case in the standard Feynman diagram approach, we extend the analysis to the non-Abelian case by employing the method of an orbifold-compatible one-loop effective action for a classical background gauge field. We find that bulk higher derivative and brane-localised gauge kinetic terms are required to cancel one-loop divergences of the gauge boson self energy. After their renormalisation we study the momentum dependence of both the higher derivative coupling h(k^2) and the {\it effective} gauge coupling g_eff(k^2). For momenta smaller than the compactification scales, we obtain the 4D logarithmic running of g_eff(k^2), with suppressed power-like corrections, while the higher derivative coupling is constant. We present in detail the threshold corrections to the low energy gauge coupling, due to the massive bulk modes. At momentum scales above the compactification scales, the higher derivative operator becomes important and leads to a power-like running of g_eff(k^2) with respect to the momentum scale. The coefficient of this running is at all scales equal to the renormalised coupling of the higher derivative operator which ensures the quantum consistency of the model. We discuss the relation to the similar one-loop correction in the heterotic string, to show that the higher derivative operators are relevant in that case too, since the field theory limit of the one-loop string correction does not commute with the infrared regularisation of the (on-shell) string result.Comment: 1+45 pages, 2 figures, JHEP style file, version to be published in JHE

Segmented forefoot plate in basketball footwear: Does it influence performance and foot joint kinematics and kinetics?

This study examined the effects of shoes’ segmented forefoot stiffness on athletic performance and ankle and metatarsophalangeal joint kinematics and kinetics in basketball movements. Seventeen university basketball players performed running vertical jumps and 5-msprints atmaximumeffort with 3 basketball shoes of various forefoot plate conditions (medial plate, medial + lateral plates, and no-plate control). One-way repeated measures ANOVAs were used to examine the differences in athletic performance, joint kinematics, and joint kinetics among the 3 footwear conditions (α = .05). Results indicated that participants wearing medial + lateral plates shoes demonstrated 2.9% higher jump height than those wearing control shoes (P = .02), but there was no significant differences between medial plate and control shoes (P \u3e .05). Medial plate shoes produced greater maximum plantar flexion velocity than the medial + lateral plates shoes (P \u3c .05) during sprinting. There were no significant differences in sprint time. These findings implied that inserting plates spanning both the medial and lateral aspects of the forefoot could enhance jumping, but not sprinting performances. The use of a medial plate alone, although induced greater plantar flexion velocity at the metatarsophalangeal joint during sprinting, was not effective in improving jump heights or sprint times

A biological function based biomarker panel optimization process.

Implementation of multi-gene biomarker panels identified from high throughput data, including microarray or next generation sequencing, need to be adapted to a platform suitable in a clinical setting such as quantitative polymerase chain reaction. However, technical challenges when transitioning from one measurement platform to another, such as inconsistent measurement results can affect panel development. We describe a process to overcome the challenges by replacing poor performing genes during platform transition and reducing the number of features without impacting classification performance. This approach assumes that a diagnostic panel reflects the effect of dysregulated biological processes associated with a disease, and genes involved in the same biological processes and coordinately affected by a disease share a similar discriminatory power. The utility of this optimization process was assessed using a published sepsis diagnostic panel. Substitution of more than half of the genes and/or reducing genes based on biological processes did not negatively affect the performance of the sepsis diagnostic panel. Our results suggest a systematic gene substitution and reduction process based on biological function can be used to alleviate the challenges associated with clinical development of biomarker panels

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

Cascaded Local Implicit Transformer for Arbitrary-Scale Super-Resolution

Implicit neural representation has recently shown a promising ability in representing images with arbitrary resolutions. In this paper, we present a Local Implicit Transformer (LIT), which integrates the attention mechanism and frequency encoding technique into a local implicit image function. We design a cross-scale local attention block to effectively aggregate local features. To further improve representative power, we propose a Cascaded LIT (CLIT) that exploits multi-scale features, along with a cumulative training strategy that gradually increases the upsampling scales during training. We have conducted extensive experiments to validate the effectiveness of these components and analyze various training strategies. The qualitative and quantitative results demonstrate that LIT and CLIT achieve favorable results and outperform the prior works in arbitrary super-resolution tasks

Novel technique of neovagina creation with uterine serosa in the treatment of vaginal agenesis associated with mullerian agenesis

AbstractObjectiveOur aim was to create a neovagina with the least surgical morbidity and the best functional outcome.Materials and methodsWe hereby describe a new technique (Lee's neovaginoplasty) using a combined laparoscopic and vaginal approach in the creation of a neovagina using the uterine serosa layer from the rudimentary uterus and the peritoneum as a graft to line the vagina. This procedure was performed in three patients who were followed-up for a duration of 4 months to 2 years. Vaginal dilation was maintained with a vaginal mold daily for 3 months and three to four times a week thereafter.ResultsAdequate vaginal length of 6-7 cm and width of 2.5 cm was achieved postoperatively. There were no surgical complications and postoperative recovery was fast. Vaginal examination 1 month later showed healthy vaginal tissue with no necrosis or infection. Long-term follow-up did not show any shortening or stenosis of the vagina. Patients were able to have satisfactory sexual intercourse with no pain.ConclusionThe laparoscopic-vaginal approach of using a uterine serosa and peritoneal graft for creation of a neovagina is a simple and effective approach with minimal surgical morbidity that can create a passageway for satisfactory intercourse

Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.

UnlabelledAlthough adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP-Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite-coated poly(lactic-coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP-based therapeutics.SignificanceAlthough stem cell-based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics

Investigation and identification of protein γ-glutamyl carboxylation sites

<p>Abstract</p> <p>Background</p> <p>Carboxylation is a modification of glutamate (Glu) residues which occurs post-translation that is catalyzed by γ-glutamyl carboxylase in the lumen of the endoplasmic reticulum. Vitamin K is a critical co-factor in the post-translational conversion of Glu residues to γ-carboxyglutamate (Gla) residues. It has been shown that the process of carboxylation is involved in the blood clotting cascade, bone growth, and extraosseous calcification. However, studies in this field have been limited by the difficulty of experimentally studying substrate site specificity in γ-glutamyl carboxylation. <it>In silico</it> investigations have the potential for characterizing carboxylated sites before experiments are carried out.</p> <p>Results</p> <p>Because of the importance of γ-glutamyl carboxylation in biological mechanisms, this study investigates the substrate site specificity in carboxylation sites. It considers not only the composition of amino acids that surround carboxylation sites, but also the structural characteristics of these sites, including secondary structure and solvent-accessible surface area (ASA). The explored features are used to establish a predictive model for differentiating between carboxylation sites and non-carboxylation sites. A support vector machine (SVM) is employed to establish a predictive model with various features. A five-fold cross-validation evaluation reveals that the SVM model, trained with the combined features of positional weighted matrix (PWM), amino acid composition (AAC), and ASA, yields the highest accuracy (0.892). Furthermore, an independent testing set is constructed to evaluate whether the predictive model is over-fitted to the training set.</p> <p>Conclusions</p> <p>Independent testing data that did not undergo the cross-validation process shows that the proposed model can differentiate between carboxylation sites and non-carboxylation sites. This investigation is the first to study carboxylation sites and to develop a system for identifying them. The proposed method is a practical means of preliminary analysis and greatly diminishes the total number of potential carboxylation sites requiring further experimental confirmation.</p