Saturation from nuclear pion dynamics

We construct an equation-of-state for nuclear matter based on the chiral Lagrangian. The relevant scales are discussed and an effective chiral power expansion scheme, which is constructed to work around the nuclear saturation density, is presented. A realistic equation-of-state is obtained by adjusting one free parameter, when the leading and subleading terms in the expansion are included. The saturation mechanism is due to correlations induced by the one-pion-exchange interaction. Furthermore, we find a substantial deviation from the Fermi-gas estimate of the quark condensate in nuclear matter already at the saturation density.Comment: revised version, with minor corrections, 13 pages, 3 Postscript figure

Angle-resolved photoemission in doped charge-transfer Mott insulators

A theory of angle-resolved photoemission (ARPES) in doped cuprates and other charge-transfer Mott insulators is developed taking into account the realistic (LDA+U) band structure, (bi)polaron formation due to the strong electron-phonon interaction, and a random field potential. In most of these materials the first band to be doped is the oxygen band inside the Mott-Hubbard gap. We derive the coherent part of the ARPES spectra with the oxygen hole spectral function calculated in the non-crossing (ladder) approximation and with the exact spectral function of a one-dimensional hole in a random potential. Some unusual features of ARPES including the polarisation dependence and spectral shape in YBa2Cu3O7 and YBa2Cu4O8 are described without any Fermi-surface, large or small. The theory is compatible with the doping dependence of kinetic and thermodynamic properties of cuprates as well as with the d-wave symmetry of the superconducting order parameter.Comment: 8 pages (RevTeX), 10 figures, submitted to Phys. Rev.

Atmospheric Muon Flux at Sea Level, Underground, and Underwater

The vertical sea-level muon spectrum at energies above 1 GeV and the underground/underwater muon intensities at depths up to 18 km w.e. are calculated. The results are particularly collated with a great body of the ground-level, underground, and underwater muon data. In the hadron-cascade calculations, the growth with energy of inelastic cross sections and pion, kaon, and nucleon generation in pion-nucleus collisions are taken into account. For evaluating the prompt muon contribution to the muon flux, we apply two phenomenological approaches to the charm production problem: the recombination quark-parton model and the quark-gluon string model. To solve the muon transport equation at large depths of homogeneous medium, a semi-analytical method is used. The simple fitting formulas describing our numerical results are given. Our analysis shows that, at depths up to 6-7 km w. e., essentially all underground data on the muon intensity correlate with each other and with predicted depth-intensity relation for conventional muons to within 10%. However, the high-energy sea-level data as well as the data at large depths are contradictory and cannot be quantitatively decribed by a single nuclear-cascade model.Comment: 47 pages, REVTeX, 15 EPS figures included; recent experimental data and references added, typos correcte

Albumin/asparaginase capsules prepared by ultrasound to retain ammonia

"Published online: 17 June 2016"Asparaginase reduces the levels of asparagine in blood, which is an essential amino acid for the proliferation of lymphoblastic malign cells. Asparaginase converts asparagine into aspartic acid and ammonia. The accumulation of ammonia in the bloodstream leads to hyperammonemia, described as one of the most significant side effects of asparaginase therapy. Therefore, there is a need for asparaginase formulations with the potential to reduce hyperammonemia. We incorporated 2 % of therapeutic enzyme in albumin-based capsules. The presence of asparaginase in the interface of bovine serum albumin (BSA) capsules showed the ability to hydrolyze the asparagine and retain the forming ammonia at the surface of the capsules. The incorporation of Poloxamer 407 in the capsule formulation further increased the ratio aspartic acid/ammonia from 1.92 to 2.46 (and 1.10 from the free enzyme), decreasing the levels of free ammonia. This capacity to retain ammonia can be due to electrostatic interactions and retention of ammonia at the surface of the capsules. The developed BSA/asparaginase capsules did not cause significant cytotoxic effect on mouse leukemic macrophage cell line RAW 264.7. The new BSA/asparaginase capsules could potentially be used in the treatment of acute lymphoblastic leukemia preventing hyperammonemia associated with acute lymphoblastic leukemia (ALL) treatment with asparaginase.Fundação para a Ciência e a Tecnologia - SFRH\BPD\98388\2013 ; UID/BIO/04469/2013 ; UID/BIA/04050/2013COMPETE 2020 (POCI-01-0145-FEDER-006684

Transculturalization of a Diabetes-Specific Nutrition Algorithm: Asian Application

The prevalence of type 2 diabetes (T2D) in Asia is growing at an alarming rate, posing significant clinical and economic risk to health care stakeholders. Commonly, Asian patients with T2D manifest a distinctive combination of characteristics that include earlier disease onset, distinct pathophysiology, syndrome of complications, and shorter life expectancy. Optimizing treatment outcomes for such patients requires a coordinated inclusive care plan and knowledgeable practitioners. Comprehensive management starts with medical nutrition therapy (MNT) in a broader lifestyle modification program. Implementing diabetes-specific MNT in Asia requires high-quality and transparent clinical practice guidelines (CPGs) that are regionally adapted for cultural, ethnic, and socioeconomic factors. Respected CPGs for nutrition and diabetes therapy are available from prestigious medical societies. For cost efficiency and effectiveness, health care authorities can select these CPGs for Asian implementation following abridgement and cultural adaptation that includes: defining nutrition therapy in meaningful ways, selecting lower cutoff values for healthy body mass indices and waist circumferences (WCs), identifying the dietary composition of MNT based on regional availability and preference, and expanding nutrition therapy for concomitant hypertension, dyslipidemia, overweight/obesity, and chronic kidney disease. An international task force of respected health care professionals has contributed to this process. To date, task force members have selected appropriate evidence-based CPGs and simplified them into an algorithm for diabetes-specific nutrition therapy. Following cultural adaptation, Asian and Asian-Indian versions of this algorithmic tool have emerged. The Asian version is presented in this report

PR1-Specific T Cells Are Associated with Unmaintained Cytogenetic Remission of Chronic Myelogenous Leukemia After Interferon Withdrawal

Interferon-alpha (IFN) induces complete cytogenetic remission (CCR) in 20-25% CML patients and in a small minority of patients; CCR persists after IFN is stopped. IFN induces CCR in part by increasing cytotoxic T lymphocytes (CTL) specific for PR1, the HLA-A2-restricted 9-mer peptide from proteinase 3 and neutrophil elastase, but it is unknown how CCR persists after IFN is stopped.We reasoned that PR1-CTL persist and mediate CML-specific immunity in patients that maintain CCR after IFN withdrawal. We found that PR1-CTL were increased in peripheral blood of 7/7 HLA-A2+ patients during unmaintained CCR from 3 to 88 months after IFN withdrawal, as compared to no detectable PR1-CTL in 2/2 IFN-treated CML patients not in CCR. Unprimed PR1-CTL secreted IFNgamma and were predominantly CD45RA+/-CD28+CCR7+CD57-, consistent with functional naïve and central memory (CM) T cells. Similarly, following stimulation, proliferation occurred predominantly in CM PR1-CTL, consistent with long-term immunity sustained by self-renewing CM T cells. PR1-CTL were functionally anergic in one patient 6 months prior to cytogenetic relapse at 26 months after IFN withdrawal, and in three relapsed patients PR1-CTL were undetectable but re-emerged 3-6 months after starting imatinib.These data support the hypothesis that IFN elicits CML-specific CM CTL that may contribute to continuous CCR after IFN withdrawal and suggest a role for T cell immune therapy with or without tyrosine kinase inhibitors as a strategy to prolong CR in CML

New insights regarding HCV-NS5A structure/function and indication of genotypic differences

<p>Abstract</p> <p>Background</p> <p>HCV is prevalent throughout the world. It is a major cause of chronic liver disease. There is no effective vaccine and the most common therapy, based on Peginterferon, has a success rate of ~50%. The mechanisms underlying viral resistance have not been elucidated but it has been suggested that both host and virus contribute to therapy outcome. Non-structural 5A (NS5A) protein, a critical virus component, is involved in cellular and viral processes.</p> <p>Methods</p> <p>The present study analyzed structural and functional features of 345 sequences of HCV-NS5A genotypes 1 or 3, using <it>in silico </it>tools.</p> <p>Results</p> <p>There was residue type composition and secondary structure differences between the genotypes. In addition, second structural variance were statistical different for each response group in genotype 3. A motif search indicated conserved glycosylation, phosphorylation and myristoylation sites that could be important in structural stabilization and function. Furthermore, a highly conserved integrin ligation site was identified, and could be linked to nuclear forms of NS5A. ProtFun indicated NS5A to have diverse enzymatic and nonenzymatic activities, participating in a great range of cell functions, with statistical difference between genotypes.</p> <p>Conclusion</p> <p>This study presents new insights into the HCV-NS5A. It is the first study that using bioinformatics tools, suggests differences between genotypes and response to therapy that can be related to NS5A protein features. Therefore, it emphasizes the importance of using bioinformatics tools in viral studies. Data acquired herein will aid in clarifying the structure/function of this protein and in the development of antiviral agents.</p

Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society