Development of a sub-channel code for liquid metal cooled fuel assembly

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Clinical and biochemical improvements in a patient with MNGIE following enzyme replacement.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive metabolic disorder caused by a deficiency of thymidine phosphorylase (TP, EC2.4.2.4) due to mutations in the nuclear gene TYMP. TP deficiency leads to plasma and tissue accumulations of thymidine and deoxyuridine which generate imbalances within the mitochondrial nucleotide pools, ultimately leading to mitochondrial dysfunction.1 MNGIE is characterized clinically by leukoencephalopathy, external ophthalmoplegia, peripheral polyneuropathy, cachexia, and enteric neuromyopathy manifesting as gastrointestinal dysmotility. The condition is relentlessly progressive, with patients usually dying from a combination of nutritional and neuromuscular failure at an average age of 37 years.2 Allogeneic hematopoietic stem cell transplantation (AHSCT) offers a permanent cure. Clinical and biochemical improvements following AHSCT have been reported but it carries a high mortality risk and is limited by matched donor availability.3 A consensus proposal for standardizing AHSCT recommends treatment of patients without irreversible end-stage disease and with an optimally matched donor; a majority of patients are ineligible and thus there is a critical requirement for an alternative treatment

Predicting the dynamics and heterogeneity of genomic DNA content within bacterial populations across variable growth regimes

For many applications in microbial synthetic biology, optimizing a desired function requires careful tuning of the degree to which various genes are expressed. One challenge for predicting such effects or interpreting typical characterization experiments is that in bacteria such as E. coli, genome copy number varies widely across different phases and rates of growth, which also impacts how and when genes are expressed from different loci. While such phenomena are relatively well-understood at a mechanistic level, our quantitative understanding of such processes is essentially limited to ideal exponential growth. In contrast, common experimental phenomena such as growth on heterogeneous media, metabolic adaptation, and oxygen restriction all cause substantial deviations from ideal exponential growth, particularly as cultures approach the higher densities at which industrial biomanufacturing and even routine screening experiments are conducted. To meet the need for predicting and explaining how gene dosage impacts cellular functions outside of exponential growth, we here report a novel modeling strategy that leverages agent-based simulation and high performance computing to robustly predict the dynamics and heterogeneity of genomic DNA content within bacterial populations across variable growth regimes. We show that by feeding routine experimental data, such as optical density time series, into our heterogeneous multiphasic growth simulator, we can predict genomic DNA distributions over a range of nonexponential growth conditions. This modeling strategy provides an important advance in the ability of synthetic biologists to evaluate the role of genomic DNA content and heterogeneity in affecting the performance of existing or engineered microbial functions

Ultraviolet and Infrared Divergences in Implicit Regularization: a Consistent Approach

Implicit Regularization is a 4-dimensional regularization initially conceived to treat ultraviolet divergences. It has been successfully tested in several instances in the literature, more specifically in those where Dimensional Regularization does not apply. In the present contribution we extend the method to handle infrared divergences as well. We show that the essential steps which rendered Implicit Regularization adequate in the case of ultraviolet divergences have their counterpart for infrared ones. Moreover we show that a new scale appears, typically an infrared scale which is completely independent of the ultraviolet one. Examples are given.Comment: 9 pages, version to appear in Mod. Phys. Lett.

Regularization Independent Analysis of the Origin of Two Loop Contributions to N=1 Super Yang-Mills Beta Function

We present a both ultraviolet and infrared regularization independent analysis in a symmetry preserving framework for the N=1 Super Yang-Mills beta function to two loop order. We show explicitly that off-shell infrared divergences as well as the overall two loop ultraviolet divergence cancel out whilst the beta function receives contributions of infrared modes.Comment: 7 pages, 2 figures, typos correcte

Safety and Efficacy of Erythrocyte Encapsulated Thymidine Phosphorylase in Mitochondrial Neurogastrointestinal Encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare autosomal recessive disorder of nucleoside metabolism that is caused by mutations in the nuclear thymidine phosphorylase gene (TYMP) gene, encoding for the enzyme thymidine phosphorylase. There are currently no approved treatments for MNGIE. The aim of this study was to investigate the safety, tolerability, and efficacy of an enzyme replacement therapy for the treatment of MNGIE. In this single centre study, three adult patients with MNGIE received intravenous escalating doses of erythrocyte encapsulated thymidine phosphorylase (EE-TP; dose range: 4 to 108 U/kg/4 weeks). EE-TP was well tolerated and reductions in the disease-associated plasma metabolites, thymidine, and deoxyuridine were observed in all three patients. Clinical improvements, including weight gain and improved disease scores, were observed in two patients, suggesting that EE-TP is able to reverse some aspects of the disease pathology. Transient, non-serious adverse events were observed in two of the three patients; these did not lead to therapy discontinuation and they were managed with pre-medication prior to infusion of EE-TP. To conclude, enzyme replacement therapy with EE-TP demonstrated biochemical and clinical therapeutic efficacy with an acceptable clinical safety profile

The human microbiota and prostate cancer: Friend or foe?

The human microbiome is gaining increasing attention in the medical community, as knowledge on its role not only in health but also in disease development and response to therapies is expanding. Furthermore, the connection between the microbiota and cancer, especially the link between the gut microbiota and gastrointestinal tumors, is becoming clearer. The interaction between the microbiota and the response to chemotherapies and, more recently, to immunotherapy has been widely studied, and a connection between a peculiar type of microbiota and a better response to these therapies and a different incidence in toxicities has been hypothesized. As knowledge on the gut microbiota increases, interest in the residing microbial population in other systems of our body is also increasing. Consequently, the urinary microbiota is under evaluation for its possible implications in genitourinary diseases, including cancer. Prostate cancer is the most common cancer in the male population; thus, research regarding its etiology and possible factors correlated to disease progression or the response to specific therapies is thriving. This review has the purpose to recollect the current knowledge on the relationship between the human microbiota and prostate cancer

Naturalness and theoretical constraints on the Higgs boson mass

Arbitrary regularization dependent parameters in Quantum Field Theory are usually fixed on symmetry or phenomenology grounds. We verify that the quadratically divergent behavior responsible for the lack of naturalness in the Standard Model (SM) is intrinsically arbitrary and regularization dependent. While quadratic divergences are welcome for instance in effective models of low energy QCD, they pose a problem in the SM treated as an effective theory in the Higgs sector. Being the very existence of quadratic divergences a matter of debate, a plausible scenario is to search for a symmetry requirement that could fix the arbitrary coefficient of the leading quadratic behavior to the Higgs boson mass to zero. We show that this is possible employing consistency of scale symmetry breaking by quantum corrections. Besides eliminating a fine-tuning problem and restoring validity of perturbation theory, this requirement allows to construct bounds for the Higgs boson mass in terms of $\delta m^2/m^2_H$ (where $m_H$ is the renormalized Higgs mass and $\delta m^2$ is the 1-loop Higgs mass correction). Whereas $\delta m^2/m^2_H<1$ (perturbative regime) in this scenario allows the Higgs boson mass around the current accepted value, the inclusion of the quadratic divergence demands $\delta m^2/m^2_H$ arbitrarily large to reach that experimental value.Comment: 6 pages, 4 figure

New Zinc-Based Active Chitosan Films: Physicochemical Characterization, Antioxidant, and Antimicrobial Properties

The improvement of the antioxidant and antimicrobial activities of chitosan (CS) films can be realized by incorporating transition metal complexes as active components. In this context, bioactive films were prepared by embedding a newly synthesized acylpyrazolonate Zn(II) complex, [Zn(QPhtBu)2(MeOH)2], into the eco-friendly biopolymer CS matrix. Homogeneous, amorphous, flexible, and transparent CS@Znn films were obtained through the solvent casting method in dilute acidic solution, using different weight ratios of the Zn(II) complex to CS and characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR), Raman, and scanning electron microscopy (SEM) techniques. The X-ray single-crystal analysis of [Zn(QPhtBu)2(MeOH)2] and the evaluation of its intermolecular interactions with a protonated glucosamine fragment through hydrogen bond propensity (HBP) calculations are reported. The effects of the different contents of the [Zn(QPhtBu)2(MeOH)2] complex on the CS biological proprieties have been evaluated, proving that the new CS@Znn films show an improved antioxidant activity, tested according to the DPPH method, with respect to pure CS, related to the concentration of the incorporated Zn(II) complex. Finally, the CS@Znn films were tried out as antimicrobial agents, showing an increase in antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus) with respect to pure CS, when detected by the agar disk-diffusion method