192 research outputs found
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
Blinatumomab versus historical standard therapy in pediatric patients with relapsed/refractory Ph-negative B-cell precursor acute lymphoblastic leukemia
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 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 non-relativistic particles attracting
according to Newton's law are shown to correspond to the equations for null
geodesics in a -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 -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
-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 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 non-relativistic
gravitational dyons is also pointed out. Our results for general time-dependent
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 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 in passing from 0 to 2 for both senses of
motion. Such gravitomagnetic time shift, which is independent of the orbital
parameters of the satellites, amounts to 5 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
cm in knowing the difference between the semimajor axes of the satellites,
and the difference of the inclinations of the orbital planes which, for
, should be less than . A pair of spacecrafts
endowed with a sophisticated intersatellite tracking apparatus and drag-free
control down to 10 cm s Hz 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
- …