Observational critique of FIRAC as a tool for legal analysis

The most basic legal analysis requires students to identify the relevant principle and apply it to a set of facts.2 In simple terms, legal analysis entails effective and insightful reading and application of court decisions, legislation, academic writing, and transactional documents such as contracts. It is also the foundation for the process of learning legal writing.3 Legal analysis also requires that law students have a good command of the language of the discipline, mostly English in South Africa.4 Greenbaum submits that a poor command of the English language is fatal to students engaging with lecturers in a “critical or argumentative way”

Multivariate approximation: Theory and applications 2020

A summary of the main facts about the Conference ‘Multivariate Approximation: Theory and Applications’ (MATA 2020) held at the Department of Mathematics and Computer Science of the University of Perugia (Italy), on January 16-18, 2020 and the contents of the associated Special Issue appearing on Dolomites Research Notes on Approximation, are here reported

Primary umbilical endometrioma: Analyzing the pathogenesis of endometriosis from an unusual localization

Objective: This report presents a rare case of symptomatic primary umbilical endometriosis and reviews the literature on the topic with the aim to clarify some questions on the origin of endometriosis. Case Report: A 33-year-old woman with cyclic umbilical bleeding was found to have umbilical endometriosis. She had no history of pelvic or abdominal surgery. There was no past history of endometriosis or endometriosis-associated symptoms. An omphalectomy was performed after explorative laparoscopy to carefully inspect the abdominopelvic cavity and assess any coexisting pelvic endometriotic lesions. Histological examination confirmed the diagnosis of umbilical endometriosis. Conclusion: Umbilical endometriosis is a rare but under-recognized phenomenon. Primary lesions are difficult to recognize, but probably represent an independent nosological entity. The possibility of endometriosis must be considered during the evaluation of an umbilical mass despite the absence of previous surgery. Complete excision and successive histology are highly recommended

Bone marrow failure may be caused by chromosome anomalies exerting effects on RUNX1T1 gene

Background: The majority of the cases of bone marrow failure syndromes/aplastic anaemias (BMFS/AA) are non-hereditary and considered idiopathic (80-85%). The peripheral blood picture is variable, with anaemia, neutropenia and/or thrombocytopenia, and the patients with idiopathic BMFS/AA may have a risk of transformation into a myelodysplastic syndrome (MDS) and/or an acute myeloid leukaemia (AML), as ascertained for all inherited BMFS. We already reported four patients with different forms of BMFS/AA with chromosome anomalies as primary etiologic event: the chromosome changes exerted an effect on specific genes, namely RUNX1, MPL, and FLI1, leading to the disease. Results: We report two further patients with non-hereditary BM failure, with diagnosis of severe aplastic anaemia and pancytopenia caused by two different constitutional structural anomalies involving chromosome 8, and possibly leading to the disorder due to effects on the RUNX1T1 gene, which was hypo-expressed and hyper-expressed, respectively, in the two patients. The chromosome change was unbalanced in one patient, and balanced in the other one. Conclusions: We analyzed the sequence of events in the pathogenesis of the disease in the two patients, including a number of non-haematological signs present in the one with the unbalanced anomaly. We demonstrated that in these two patients the primary event causing BMFS/AA was the constitutional chromosome anomaly. If we take into account the cohort of 219 patients with a similar diagnosis in whom we made cytogenetic studies in the years 2003-2017, we conclude that cytogenetic investigations were instrumental to reach a diagnosis in 52 of them. We postulate that a chromosome change is the primary cause of BMFS/AA in a not negligible proportion of cases, as it was ascertained in 6 of these patients

Repurposing anthelmintic agents to eradicate resistant leukemia

Despite rapid progress in genomic profiling in acute lymphoblastic leukemia (ALL), identification of actionable targets and prediction of response to drugs remains challenging. To identify specific vulnerabilities in ALL, we performed a drug screen using primary human ALL samples cultured in a model of the bone marrow microenvironment combined with high content image analysis. Among the 2487 FDA-approved compounds tested, anthelmintic agents of the class of macrocyclic lactones exhibited potent anti-leukemia activity, similar to the already known anti-leukemia agents currently used in induction chemotherapy. Ex vivo validation in 55 primary ALL samples of both precursor B cell and T-ALL including refractory relapse cases confirmed strong anti-leukemia activity with IC50 values in the low micromolar range. Anthelmintic agents increased intracellular chloride levels in primary leukemia cells, inducing mitochondrial outer membrane depolarization and cell death. Supporting the notion that simultaneously targeting cell death machineries at different angles may enhance the cell death response, combination of anthelmintic agents with the BCL-2 antagonist navitoclax or with the chemotherapeutic agent dexamethasone showed synergistic activity in primary ALL. These data reveal anti-leukemia activity of anthelmintic agents and support exploiting drug repurposing strategies to identify so far unrecognized anti-cancer agents with potential to eradicate even refractory leukemia

Polymorphism in the neurofibromin gene, Nf1, is associated with antagonistic selection on wing size and development time in Drosophila melanogaster

In many invertebrates, body size shows genetically based clines, with size increasing in colder climates. Large body size is typically associated with prolonged development times. We consider variation in the CNS-specific gene neurofibromin 1 (Nf1) and its association with body size and development time. We identified two major Nf1 haplotypes in natural populations, Nf1-insertion-A and Nf1-deletion-G. These haplotypes are characterized by a 45-base insertion/deletion (INDEL) in Nf1 intron 2 and an A/G synonymous substitution (locus L17277). Linkage disequilibrium (LD) between the INDEL and adjacent sites is high but appears to be restricted within the Nf1 gene interval. In Australia, the frequency of the Nf1-insertion-A haplotype increases with latitude where wing size is larger, independent of the chromosomal inversion In(3R)Payne. Unexpectedly, the Nf1-insertion-A haplotype is negatively associated with wing size. We found that the Nf1-insertion-A haplotype is enriched in females with shorter development time. This suggests that the Nf1 haplotype cline may be driven by selection for development time rather than size; females from southern (higher latitude) D. melanogaster populations maintain a rapid development time despite being relatively larger, and the higher incidence of Nf1-insertion-A in Southern Australia may contribute to this pattern, whereas the effects of the Nf1 haplotypes on size may be countered by other loci with antagonistic effects on size and development time. Our results point to the potential complexity involved in identifying selection on genetic variants exhibiting pleiotropic effects when studies are based on spatial patterns or association studies

Stochastic motion of test particle implies that G varies with time

The aim of this letter is to propose a new description to the time varying gravitational constant problem, which naturally implements the Dirac's large numbers hypothesis in a new proposed holographic scenario for the origin of gravity as an entropic force. We survey the effect of the Stochastic motion of the test particle in Verlinde's scenario for gravity\cite{Verlinde}. Firstly we show that we must get the equipartition values for $t\rightarrow\infty$ which leads to the usual Newtonian gravitational constant. Secondly,the stochastic (Brownian) essence of the motion of the test particle, modifies the Newton's 2'nd law. The direct result is that the Newtonian constant has been time dependence in resemblance as \cite{Running}.Comment: Accepted in International Journal of Theoretical Physic

Celestial Mechanics, Conformal Structures, and Gravitational Waves

The equations of motion for $N$ non-relativistic particles attracting according to Newton's law are shown to correspond to the equations for null geodesics in a $(3N+2)$-dimensional Lorentzian, Ricci-flat, spacetime with a covariantly constant null vector. Such a spacetime admits a Bargmann structure and corresponds physically to a generalized pp-wave. Bargmann electromagnetism in five dimensions comprises the two Galilean electro-magnetic theories (Le Bellac and L\'evy-Leblond). At the quantum level, the $N$-body Schr\"odinger equation retains the form of a massless wave equation. We exploit the conformal symmetries of such spacetimes to discuss some properties of the Newtonian $N$-body problem: homographic solutions, the virial theorem, Kepler's third law, the Lagrange-Laplace-Runge-Lenz vector arising from three conformal Killing 2-tensors, and motions under inverse square law forces with a gravitational constant $G(t)$ varying inversely as time (Dirac). The latter problem is reduced to one with time independent forces for a rescaled position vector and a new time variable; this transformation (Vinti and Lynden-Bell) arises from a conformal transformation preserving the Ricci-flatness (Brinkmann). A Ricci-flat metric representing $N$ non-relativistic gravitational dyons is also pointed out. Our results for general time-dependent $G(t)$ are applicable to the motion of point particles in an expanding universe. Finally we extend these results to the quantum regime.Comment: 26 pages, LaTe

On the Possibility of Measuring the Gravitomagnetic Clock Effect in an Earth Space-Based Experiment

In this paper the effect of the post-Newtonian gravitomagnetic force on the mean longitudes $l$ of a pair of counter-rotating Earth artificial satellites following almost identical circular equatorial orbits is investigated. The possibility of measuring it is examined. The observable is the difference of the times required to $l$ in passing from 0 to 2$\pi$ for both senses of motion. Such gravitomagnetic time shift, which is independent of the orbital parameters of the satellites, amounts to 5$\times 10^{-7}$ s for Earth; it is cumulative and should be measured after a sufficiently high number of revolutions. The major limiting factors are the unavoidable imperfect cancellation of the Keplerian periods, which yields a constraint of 10$^{-2}$ cm in knowing the difference between the semimajor axes $a$ of the satellites, and the difference $I$ of the inclinations $i$ of the orbital planes which, for $i\sim 0.01^\circ$, should be less than $0.006^\circ$. A pair of spacecrafts endowed with a sophisticated intersatellite tracking apparatus and drag-free control down to 10$^{-9}$ cm s$^{-2}$ Hz$^{-{1/2}}$ level might allow to meet the stringent requirements posed by such a mission.Comment: LaTex2e, 22 pages, no tables, 1 figure, 38 references. Final version accepted for publication in Classical and Quantum Gravit