Don’t Feel Threatened by Law

The idea that legal systems conditionally threaten citizens is taken by most legal and political philosophers as ’reasonably uncontroversial,’ obvious,’ or as portraying ’a large part of how law operates.’ This paper clarifies and ultimately rejects this idea: our legal systems, it is argued, rarely address citizens via conditional threats. If correct, the conclusion defended in this paper might force us to re-examine core debates in legal and political philosophy that rely on the assumption that legal systems often threaten citizens: debates about the justification of the state, global justice, and the coerciveness of law

Diagnostic investigation to support the restoration of the polychrome terracotta relief "Madonna and Child" in Piove di Sacco (Padova, Italy)

Restoration procedures of the polychrome terracotta relief “Madonna and Child” with papier-mâché inserts from a shrine in Piove di Sacco (Padova, orthern Italy) were assisted by analytical investigations, contributing to identify the chemical composition of the pigments, fractures and internal damages, additions and retouchings, which strongly modified the original manufact. In particular, energy dispersive X-ray fluorescence, Raman spectroscopy and FT-IR spectroscopy were employed to determine the chemical composition of pigments on the original layer and on the overpaintings and to understand the artistic techniques. Moreover, X-ray planar radiography and computed tomography were used to understand the structure and its conservative state. Finally, the relief, stylistically dated to the 17th century, turned out to be a Renaissance terracotta artefact. The polychrome blue traces of lapis lazuli highlighted a valuable artwork and the resemblance with the style of Donatello and his apprentices have recently led to further studies, as an initial part of a larger research on polychrome terracotta in Veneto

Conscientious objection to abortion in the developing world: The correspondence argument.

In this paper we extend Heidi Hurd's "correspondence thesis" to the termination of pregnancy debate and argue that the same reasons that determine the permissibility of abortion also determine the justifiability of acts involving conscientious objection against its performance. Essentially, when abortion is morally justified, acts that prevent or obstruct it are morally unjustified. Therefore, despite conscientious objection being legally permitted in some global south countries, we argue that such permission to conscientiously object would be morally wrong in cases of morally justifiable termination of pregnancy. After presenting and defending our "correspondence argument" we suggest that conscientious objection should be denied as a matter of public health policy in developing counties, even in cases where adequate referral services are possible. Towards the end, we extend our argument to midwives, nurses, and prospective students in the field. Given their essential position in resource-poor contexts; they too have no claim to conscientious objection

In vitro efficacy of alphacypermethrin on the buffalo louse Haematopinus tuberculatus (Burmeister, 1839).

In Italy buffalo farms adopted intensive breeding techniques, however the high density of animals in intensive breeding favours the diffusion of ectoparasites, such as louse. The aim of this study was to determine the in vitro efficacy of the insecticide alphacypermethrin (ACYP) against the buffalo louse, Haematopinus tuberculatus. The study was performed by using louse collected from animals in a commercial buffalo farm located in the Campania region of Southern Italy. Lice (adults and nymphs) were collected from highly infested buffaloes. The ACYP was diluted with physiological solution to different concentrations: 1.5%, 0.75%, 0.37%. A volume of 600 μl of the diluted sample was spread evenly over a filter paper held in the lower half of Petri dish. Ten adult lice and ten nymphs were placed on the top of each filter paper disc. The control groups were treated with physiological solution. Seven replicates were used for each concentration. The louse vitality was assessed at different time intervals: 1, 2, 4, 8, 10, 15, 20, 30, 40, 50, 60 minutes, after every 10 min until 240 min or at the louse death. After 240 min the louse vitality was examined each 60 min until 540 min. In vitro bioassays revealed that the lousicidal efficacy of ACYP improved as the concentration and the exposure time increased. The results of this in vitro study confirm that ACYP at 1.5% concentration can also be used in buffalo for the control of lice, as already in use in cattle. Further field trials will need to be conducted to confirm the safety, the dosage and the in vivo parasitological efficacy of this drug on buffaloes

Treatment of Hepatitis C virus genotype 3 infection with direct-acting antiviral agents

Hepatitis C virus (HCV) genotype 3 is responsible for 30.1% of chronic hepatitis C infection cases worldwide. In the era of directacting antivirals, these patients have become one of the most challenging to treat, due to fewer effective drug options, higher risk of developing cirrhosis and hepatocellular carcinoma and lower sustained virological response (SVR) rates. Currently there are 4 recommended drugs for the treatment of HCV genotype 3: pegylated interferon (PegIFN), sofosbuvir (SOF), daclatasvir (DCV) and ribavirin (RBV). Treatment with PegIFN, SOF and RBV for 12 weeks has an overall SVR rate of 83-100%, without significant differences among cirrhotic and non-cirrhotic patients. However, this therapeutic regimen has several contra-indications and can cause significant adverse events, which can reduce adherence and impair SVR rates. SOF plus RBV for 24 weeks is another treatment option, with SVR rates of 82-96% among patients without cirrhosis and 62-92% among those with cirrhosis. Finally, SOF plus DCV provides 94-97% SVR rates in non-cirrhotic patients, but 59-69% in those with cirrhosis. The addition of RBV to the regimen of SOF plus DCV increases the SVR rates in cirrhotic patients above 80%, and extending treatment to 24 weeks raises SVR to 90%. The ideal duration of therapy is still under investigation. For cirrhotic patients, the optimal duration, or even the best regimen, is still uncertain. Further studies are necessary to clarify the best regimen to treat HCV genotype 3 infection491

2D Zernike polynomial expansion: finding the protein-protein binding regions

We present a method for efficiently and effectively assessing whether and where two proteins can interact with each other to form a complex. This is still largely an open problem, even for those relatively few cases where the 3D structure of both proteins is known. In fact, even if much of the information about the interaction is encoded in the chemical and geometric features of the structures, the set of possible contact patches and of their relative orientations are too large to be computationally affordable in a reasonable time, thus preventing the compilation of reliable interactome. Our method is able to rapidly and quantitatively measure the geometrical shape complementarity between interacting proteins, comparing their molecular iso-electron density surfaces expanding the surface patches in term of 2D Zernike polynomials. We first test the method against the real binding region of a large dataset of known protein complexes, reaching a success rate of 0.72. We then apply the method for the blind recognition of binding sites, identifying the real region of interaction in about 60% of the analyzed cases. Finally, we investigate how the efficiency in finding the right binding region depends on the surface roughness as a function of the expansion order

Identificação e análise de promotores de desidrinas no genoma da macieira.

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Predictors Of Early Treatment Discontinuation And Severe Anemia In A Brazilian Cohort Of Hepatitis C Patients Treated With First-generation Protease Inhibitors

The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin <= 8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.49

Increased mitophagy in the skeletal muscle of spinal and bulbar muscular atrophy patients

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by polyglutamine expansion in the androgen receptor (AR) and characterized by the loss of lower motor neurons. Here we investigated pathological processes occurring in muscle biopsy specimens derived from SBMA patients and, as controls, age-matched healthy subjects and patients suffering from amyotrophic lateral sclerosis (ALS) and neurogenic atrophy. We detected atrophic fibers in the muscle of SBMA, ALS and neurogenic atrophy patients. In addition, SBMA muscle was characterized by the presence of a large number of hypertrophic fibers, with oxidative fibers having a larger size compared with glycolytic fibers. Polyglutamine-expanded AR expression was decreased in whole muscle, yet enriched in the nucleus, and localized to mitochondria. Ultrastructural analysis revealed myofibrillar disorganization and streaming in zones lacking mitochondria and degenerating mitochondria. Using molecular (mtDNA copy number), biochemical (citrate synthase and respiratory chain enzymes) and morphological (dark blue area in nicotinamide adenine dinucleotide-stained muscle cross-sections) analyses, we found a depletion of the mitochondria associated with enhanced mitophagy. Mass spectrometry analysis revealed an increase of phosphatidylethanolamines and phosphatidylserines in mitochondria isolated from SBMA muscles, as well as a 50% depletion of cardiolipin associated with decreased expression of the cardiolipin synthase gene. These observations suggest a causative link between nuclear polyglutamine-expanded AR accumulation, depletion of mitochondrial mass, increased mitophagy and altered mitochondrial membrane composition in SBMA muscle patients. Given the central role of mitochondria in cell bioenergetics, therapeutic approaches toward improving the mitochondrial network are worth considering to support SBMA patients

Dormancy-related transcript accumulation of the dehydrin gene family in apple buds.

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