Statistical VS Wave Realism in the Foundations of Quantum Mechanics

Different realistic attitudes towards wavefunctions and quantum states are as old as quantum theory itself. Recently Pusey, Barret and Rudolph (PBR) on the one hand, and Auletta and Tarozzi (AT) on the other, have proposed new interesting arguments in favor of a broad realistic interpretation of quantum mechanics that can be considered the modern heir to some views held by the fathers of quantum theory. In this paper we give a new and detailed presentation of such arguments, propose a new taxonomy of different realistic positions in the foundations of quantum mechanics and assess the scope, within this new taxonomy, of these realistic arguments

The relevance of recoil and free swimming in aquatic locomotion

The study of the free swimming of undulating bodies in an otherwise quiescent fluid has always encountered serious difficulties for several reasons. When considering the full system, given by the body and the unbounded surrounding fluid, the absence of external forces leads to a subtle interaction problem dominated, at least at steady state conditions, by the equilibrium of strictly related internal forces, e.g. thrust and drag, under the forcing of a prescribed deformation. A major complication has been dictated by the recoil motion induced by the non linear interactions, which may find a quite natural solution when considering as unknowns the velocity components of the body center of mass. A simplified two-dimensional model in terms of impulse equations has been used and a fruitful separation of the main contributions due to added mass and to vorticity release is easily obtained. As main results we obtain either the mean locomotion speed and the oscillating recoil velocity components which have a large effect on the overall performance of free swimming. Several constrained gaits are considered to highlight the relevance of recoil for realizing graceful and efficient trajectories and to analyze its potential means for active control

Wave-Impact in a sloshing tank: hydroelastic challenges

Wave-impact in sloshing flows is an important issue for the safety of the Liquefied Natural Gas (LNG) carriers. Although LNG tanks have filling restrictions, they must be able to operate at any filling depth. The full understanding of the physical phenomena and the accurate evaluation of the local loads in sloshing-induced slamming events occurring in completely, partially or barely filling conditions, is a challenge of the research field. Violent free-surface motions in a sloshing tank generally occur when the energy spectrum of the ship motion is focused in the frequency region close to the lowest sloshing mode of the tank. Slamming events may occur originating impulsive and large local loads that undermine the integrity of the structure. Depending on the local flow features before the impact, several and complex scenarios can characterize the physical evolutions of a wave impact in a sloshing flow. For example, when the impact angle between water and body is small, air entrapment may occur making important the compressibility of the air and its interaction with the free surface. In contrast, for an incipient breaking wave approaching a vertical wall, flip-through event may happen causing localized and large loads without any air-entrapment or flat-impact may occur. In all these cases, when the typical temporal duration of the local load is comparable with the lowest natural period of the structure, hydroelasticity matters affecting the integrity of the structure. Present research investigation pursues the experimental study about the kinematic and dynamic features of a wave impacting a rigid vertical wall of a 2D sloshing tank in shallow water conditions. Previous papers, have emphasized how the maximum pressure around the impact area is an unreliable indicator of the maximum load (with value of the standard deviation up to 50%), because of the stochastic behaviour of the impact phenomena. Here, the strain distribution along a deformable aluminum plate inserted in a rigid vertical wall of a sloshing tank has been measured to characterize the features of the local loads

Il rischio cardiovascolare e la concentrazione plasmatica del colesterolo LDL: il ruolo dei Servizi Sanitari Regionali

Cardiovascular risk and increased plasma LDL cholesterol concentration: the role of the Regional Health ServiceThe relevance of hypercholesterolemia, as a risk factor for cardiovascular (CV) disease, requires urgent actions to detect and assist high-risk citizens/patients, thus reducing and/or avoiding future complications. This goal could be achieved through more widespread awareness of the problem within the Health System of the Veneto Region, joint efforts between clinical laboratories and clinicians in transmitting and interpreting informative laboratory reports, and deeper integration of hospital and community health services. Data from recent studies, recommendations of scientific societies and political-institutional guidelines helped in determining the number of patients in the Veneto Region, which may be suffering from clinical or biochemical conditions that impact on CV risk. These include hypercholesterolemia, which is particularly addressed in this paper, with special emphasis on FH (familial hypercholesterolemia), a chronic disease associated with very high CV risk

The Evolutionary Scenario of Pediatric Unclassified Primary Antibody Deficiency to Adulthood

background: unclassified primary antibody deficiency (unPAD) is a relatively novel inborn error of immunity (IEI) condition that can vary with time to more defined entities. since long-term follow-up (FU) studies are scarce, we aimed to provide insight into the evolutionary clinical and immunological scenario of unPAD children to adulthood and identification of biomarkers of primary immune deficiency (PID) persistence. methods: a total of 23 pediatric unPAD patients underwent clinical and immunological FU for a mean time of 14 years (range 3-32 years, median 16 years). results: UnPAD diagnosis may change over time. at the last FU, 10/23 (44%) children matched the diagnosis of transient hypogammaglobulinemia of infancy and 13/23 (56%) suffered from a persistent PID. In detail, an unPAD condition was confirmed in 7/23 (30%) patients, whereas 3/23 (13%), 2/23 (9%), and 1/23 (4%) were reclassified as common variable immunodeficiency, selective IgA deficiency, and isolated IgM deficiency, respectively. Low IgA, low specific antibody response to pneumococcus, and lower respiratory tract infections at diagnosis were independently associated with IEI persistence. conclusions: long-term monitoring of unPAD patients is required to define their outcome and possible evolution towards a definitive IEI diagnosis

Identification of the pyridoxal 5′‐phosphate allosteric site in human pyridox(am)ine 5′‐phosphate oxidase

Adequate levels of pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6 , and its proper distribution in the body are essential for human health. The PLP recycling pathway plays a crucial role in these processes and its defects cause severe neurological diseases. The enzyme pyridox(am)ine 5'-phosphate oxidase (PNPO), whose catalytic action yields PLP, is one of the key players in this pathway. Mutations in the gene encoding PNPO are responsible for a severe form of neonatal epilepsy. Recently, PNPO has also been described as a potential target for chemotherapeutic agents. Our laboratory has highlighted the crucial role of PNPO in the regulation of PLP levels in the cell, which occurs via a feedback inhibition mechanism of the enzyme, exerted by binding of PLP at an allosteric site. Through docking analyses and site-directed mutagenesis experiments, here we identified the allosteric PLP binding site of human PNPO. This site is located in the same protein region as the allosteric site we previously identified in the Escherichia coli enzyme homologue. However, the identity and arrangement of the amino acid residues involved in PLP binding are completely different and resemble those of the active site of PLP-dependent enzymes. The identification of the PLP allosteric site of human PNPO paves the way for the rational design of enzyme inhibitors as potential anti-cancer compounds

A gene-nutrient interaction between vitamin B6 and serine hydroxymethyltransferase (SHMT) affects genome integrity in Drosophila

Pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6, participates as a cofactor to one carbon (1C) pathway that produces precursors for DNA metabolism. The concerted action of PLP-dependent serine hydroxymethyltransferase (SHMT) and thymidylate synthase (TS) leads to the biosynthesis of thymidylate (dTMP), which plays an essential function in DNA synthesis and repair. PLP deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, rising the hypothesis that an altered 1C metabolism may be involved. To test this hypothesis, we used Drosophila as a model system and found, firstly, that in PLP deficient larvae SHMT activity is reduced by 40%. Second, we found that RNAi-induced SHMT depletion causes chromosome damage rescued by PLP supplementation and strongly exacerbated by PLP depletion. RNAi-induced TS depletion causes severe chromosome damage, but this is only slightly enhanced by PLP depletion. dTMP supplementation rescues CABs in both PLP-deficient and PLP-proficient SHMTRNAi . Altogether these data suggest that a reduction of SHMT activity caused by PLP deficiency contributes to chromosome damage by reducing dTMP biosynthesis. In addition, our work brings to light a gene-nutrient interaction between SHMT decreased activity and PLP deficiency impacting on genome stability that may be translated to human

Biweekly Hizentra® in Primary Immunodeficiency: a Multicenter, Observational Cohort Study (IBIS)

Immunoglobulin G (IgG) replacement therapy is a standard treatment for patients with primary immunodeficiency diseases (PIDs). Hizentra®, a 20% human subcutaneous IgG (SCIG), is approved for biweekly administration for PIDs. The aim of the multicenter IBIS study was to prospectively investigate the efficacy of biweekly Hizentra® compared with previous IVIG or SCIG treatment regimens in patients with PIDs. The study consisted of a 12-month retrospective period followed by 12-month prospective observational period. The main endpoints included pre-infusion IgG concentrations, proportion of patients with serious bacterial infections (SBIs), other infections, hospitalizations due to PID-related illnesses, and days with antibiotics during the study periods. Of the 36 patients enrolled in the study, 35 patients continued the study (mean age 26.1 ± 14.4 years; 68.6% male). The mean pre-infusion IgG levels for prior immunoglobulin regimens during the retrospective period (7.84 ± 2.09 g/L) and the prospective period (8.55 ± 1.76 g/L) did not show any significant variations (p = 0.4964). The mean annual rate of SBIs/patient was 0.063 ± 0.246 for both prospective and retrospective periods. No hospitalizations related to PIDs were reported during the prospective period versus one in the retrospective period. All patients were either very (76.5%) or quite (23.5%) satisfied with biweekly Hizentra® at the end of the study. In conclusion, the IBIS study provided real-world evidence on the efficacy of biweekly Hizentra® in patients with PIDs, thus verifying the data generated by the pharmacometric modeling and simulation study in a normal clinical setting

Functional and structural properties of pyridoxal reductase (PdxI) from Escherichia coli. A pivotal enzyme in the vitamin B6 salvage pathway

Pyridoxine 4-dehydrogenase (PdxI), a NADPH-dependent pyridoxal reductase, is one of the key players in the Escherichia coli pyridoxal 5'-phosphate (PLP) salvage pathway. This enzyme, which catalyses the reduction of pyridoxal into pyridoxine, causes pyridoxal to be converted into PLP via the formation of pyridoxine and pyridoxine phosphate. The structural and functional properties of PdxI were hitherto unknown, preventing a rational explanation of how and why this longer, detoured pathway occurs, given that, in E. coli, two pyridoxal kinases (PdxK and PdxY) exist that could convert pyridoxal directly into PLP. Here, we report a detailed characterisation of E. coli PdxI that explains this behaviour. The enzyme efficiently catalyses the reversible transformation of pyridoxal into pyridoxine, although the reduction direction is thermodynamically strongly favoured, following a compulsory-order ternary-complex mechanism. In vitro, the enzyme is also able to catalyse PLP reduction and use NADH as an electron donor, although with lower efficiency. As with all members of the aldo-keto reductase (AKR) superfamily, the enzyme has a TIM barrel fold; however, it shows some specific features, the most important of which is the presence of an Arg residue that replaces the catalytic tetrad His residue that is present in all AKRs and appears to be involved in substrate specificity. The above results, in conjunction with kinetic and static measurements of vitamins B6 in cell extracts of E. coli wild-type and knockout strains, shed light on the role of PdxI and both kinases in determining the pathway followed by pyridoxal in its conversion to PLP, which has a precise regulatory function

Systemic amyloidosis due to unknown multiple myeloma in small bowel pseudo-obstruction: case report

Amyloidosis is a pathologic diagnosis characterized by extracellular deposition of insoluble protein fibrils in various organs and tissues. There are two main forms of amyloidosis, primary amyloidosis, and secondary amyloidosis. Gastrointestinal involvement is common in both amyloidosis forms. We describe the case of a 78-year-old woman taken to the operating room for small bowel obstruction, found to have pseudo-obstruction and enteritis. Exploratory laparotomy revealed gastric mass and histological examen showed extensive amyloid deposition consistent with amyloidosis. Hematological evaluation revealed unknown multiple myeloma. This case report and literature data suggest to perform a hematological examination in patients with amyloidosis diagnosis to exclude a multiple myeloma or other plasma cell disorder