Error in Omitting or Die after a Testamentary Gift of Income to Widow

The purpose of this essay is to consider the problems posed by a hypothetical omission of the words or dies from a typical testamentary gift of income to a surviving spouse during widowhood. While it is sincerely hoped that no one will have need of it, the writer wishes to record the products of his research and analysis just in case it may assist some blushing brother\u27s future search for the consequences of that most painful of errors-the rare, unique mistake that no one before has made

About gravitational radiation of semi local strings with non compact internal modes

In a previous work [1], given a putative vortex, it was determined whether it is non abelian or not by studying its radiation channels. The example considered there was a $SU(2)$ gauge model whose internal orientational modes are described by an sphere $S^2$. The non abelian effects presented in this reference were not very pronounced, due to the compactness of this space. In the present work, this analysis is extended for a vortex whose internal space is non compact. This situation may be realised by semi-local supersymmetric vortices [2]-[9]. As the internal space has infinite volume, a largely energetic perturbation may propagate along the object. A specific configuration is presented, when the internal space is the resolved conifold with its Ricci flat metric. The curious feature about it is that it corresponds to a static vortex, that is, the perturbation is only due to the internal modes. Even being static, the emission of gravitational radiation is in the present case of considerable order. This suggest that the presence of slowly moving objects that can emit a large amount of gravitational radiation is a hint of non abelianity.Comment: 14 pages, no figures, some irrelevant constants were set to one and the formulas are less cumbersome. Some additional numerical estimation was include

Cannabinoids in the treatment of epilepsy: current status and future prospects

Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fatcontaining meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 2C19, which it strongly inhibits. A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies’ approval was granted based on four pivotal double-blind, placebocontrolled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint (reduction in monthly seizure frequency) was met by both CBD doses. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy. The interaction between CBD and clobazam, likely due to CYP2C19 inhibition, might contribute to some AEs, especially somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the propyl analogue of CBD, showed anti-convulsant properties in pre-clinical studies, but a plant-derived, purified proprietary formulation of CBDV recently failed the Phase II RCT in patients with uncontrolled focal seizures

Characterization of Hsp70 binding and nucleotide exchange by the yeast Hsp110 chaperone Sse1.

SSE1 and SSE2 encode the essential yeast members of the Hsp70-related Hsp110 molecular chaperone family. Both mammalian Hsp110 and the Sse proteins functionally interact with cognate cytosolic Hsp70s as nucleotide exchange factors. We demonstrate here that Sse1 forms high-affinity (Kd approximately 10-8 M) heterodimeric complexes with both yeast Ssa and mammalian Hsp70 chaperones and that binding of ATP to Sse1 is required for binding to Hsp70s. Sse1.Hsp70 heterodimerization confers resistance to exogenously added protease, indicative of conformational changes in Sse1 resulting in a more compact structure. The nucleotide binding domains of both Sse1/2 and the Hsp70s dictate interaction specificity and are sufficient for mediating heterodimerization with no discernible contribution from the peptide binding domains. In support of a strongly conserved functional interaction between Hsp110 and Hsp70, Sse1 is shown to associate with and promote nucleotide exchange on human Hsp70. Nucleotide exchange activity by Sse1 is physiologically significant, as deletion of both SSE1 and the Ssa ATPase stimulatory protein YDJ1 is synthetically lethal. The Hsp110 family must therefore be considered an essential component of Hsp70 chaperone biology in the eukaryotic cell

Bisphenol A and phthalates in diet: an emerging link with pregnancy complications

Endocrine-disrupting chemicals (EDCs) are exogenous substances that are able to interfere with hormone action, likely contributing to the development of several endocrine and metabolic diseases. Among them, Bisphenol A (BPA) and phthalates contaminate food and water and have been largely studied as obesogenic agents. They might contribute to weight gain, insulin resistance and pancreatic β-cell dysfunction in pregnancy, potentially playing a role in the development of pregnancy complications, such as gestational diabetes mellitus (GDM), and adverse outcomes. Pregnancy and childhood are sensitive windows of susceptibility, and, although with not univocal results, preclinical and clinical studies have suggested that exposure to BPA and phthalates at these stages of life might have an impact on the development of metabolic diseases even many years later. The molecular mechanisms underlying this association are largely unknown, but adipocyte and pancreatic β-cell dysfunction are suspected to be involved. Remarkably, transgenerational damage has been observed, which might be explained by epigenetic changes. Further research is needed to address knowledge gaps and to provide preventive measure to limit health risks connected with exposure to EDCs

A FORTRESS BETWEEN ARTIFICE AND NATURE: THE LASER SCANNING SURVEY OF THE CASTLE OF PESCOPAGANO AS AN INSTRUMENT OF KNOWLEDGE, CONSERVATION AND ENHANCEMENT

Abstract. The castle of Pescopagano, a small village located on the border between Basilicata and Campania, is a complex of great historical and landscape value, for the inseparable combination that binds its stones to the rock where it stands. Founded perhaps in the Byzantine times, but certainly renovated and built in its current forms between the 11th and 12th century, the castle had considerable military importance under Frederick II of Swabia. Seriously damaged by the earthquake of 1694, the fortress underwent a partial reconstruction, but ended up suffering further collapses caused by the Irpinia earthquake of 1980, such as to motivate the first interventions of securing and, above all, the application of the listing process. Today the castle is still largely in ruins and is only partially accessible thanks to a limited intervention on the paths. The present research aims at deepening the knowledge of the state of conservation, the damage mechanisms and the previous restoration interventions of the castle, in order to define possible strategies for its restoration and enhancement. The analysis work uses the most advanced laser scanning and drone detection systems, in order to document, as accurately as possible, the complex patrimonial system of the castle. Thanks to the combined use of these techniques, the objective is also to define methods that can be replicated in other contexts where the relationship between geomorphology and construction is so relevant that it jeopardizes the use of any other traditional survey system

Modulation of contractility in human cardiac hypertrophy by myosin essential light chain isoforms

Cardiac hypertrophy is an adaptive response that normalizes wall stress and compensates for increased workload. It is accompanied by distinct qualitative and quantitative changes in the expression of protein isoforms concerning contractility, intracellular Ca2+-homeostasis and metabolism. Changes in the myosin subunit isoform expression improves contractility by an increase in force generation at a given Ca2+-concentration (increased Ca2+-sensitivity) and by improving the economy of the chemo-mechanical transduction process per amount of utilised ATP (increased duty ratio). In the human atrium this is achieved by partial replacement of the endogenous fast myosin by the ventricular slow-type heavy and light chains. In the hypertrophic human ventricle the slow-type β-myosin heavy chains remain unchanged, but the ectopic expression of the atrial myosin essential light chain (ALC1) partially replaces the endogenous ventricular isoform (VLC1). The ventricular contractile apparatus with myosin containing ALC1 is characterised by faster cross-bridge kinetics, a higher Ca2+-sensitivity of force generation and an increased duty ratio. The mechanism for cross-bridge modulation relies on the extended Ala-Pro-rich N-terminus of the essential light chains of which the first eleven residues interact with the C-terminus of actin. A change in charge in this region between ALC1 and VLC1 explains their functional difference. The intracellular Ca2+-handling may be impaired in heart failure, resulting in either higher or lower cytosolic Ca2+-levels. Thus the state of the cardiomyocyte determines whether this hypertrophic adaptation remains beneficial or becomes detrimental during failure. Also discussed are the effects on contractility of long-term changes in isoform expression of other sarcomeric proteins. Positive and negative modulation of contractility by short-term phosphorylation reactions at multiple sites in the myosin regulatory light chain, troponin-I, troponin-T, α-tropomyosin and myosin binding protein-C are considered in detai