Capping Strategies for Covalent Template-Directed Synthesis of Linear Oligomers Using CuAAC.

Covalent templating provides an attractive solution to the controlled synthesis of linear oligomers because a template oligomer can be used to define the precise length and sequence of the product. If the monomer units are attached to the template using kinetically inert covalent bonds it should be possible to operate at high dilution to favor intramolecular over intermolecular reaction. However, for oligomerization reactions using copper-catalyzed azide alkyne cycloaddition (CuAAC) this is not the case. The rate-limiting step is formation of an activated copper complex, so any alkyne that is activated by copper reacts rapidly with the nearest available azide. As a result, every time a chain end alkyne is activated, rapid intermolecular reaction takes place with a different oligomer leading to the formation of higher order products. It proved possible to block these intermolecular reactions by adding an excess of an azide capping agent that intercepts the chain end of the growing oligomer on the template. By adjusting the concentration of the capping agent to compete effectively with the unwanted intermolecular reactions without interfering with the desired intramolecular reactions, it was possible to obtain quantitative yields of copy strands from covalent template-directed oligomerization reactions. Remarkably, the capping agent could also be used to control the stereochemistry of the duplex formed in the templated oligomerization reaction to give exclusively the antiparallel product.ERC-2012-AdG 320539-duplex, Herchel Smith Fun

Positive and psycho-pathological aspects between shame and shamelessness

Interpersonal relationships represent an essential aspect of mental wellbeing and social functioning. If all the symptoms contain a relational meaning, shame represents the relational affect par excellence both in terms of its origin and its purpose. This paper aims to highlight the role of shame as an affect inherent in the rhythmic nature of the encounter with the other, as well as the pathological elements of this aspect in both its conscious and unconscious dimensions. There is a heterogeneous quantitative and qualitative declination of shame, or of the defenses against this affect, among the various pathologies. We consider the fundamental needs of belonging and acceptance and the parallel abandonment anguish from various psychoanalytic and philosophical theoretical perspectives and then analyze the link between their dissatisfaction and the origin of shame. We also touch on the different interpretaions of shame based on eastern and western cultural norms. These hypotheses are closely intertwined with the beliefs of classical psychopathology. The role of the body in the encounter with the other and in the experience of shame is also examined. In particular, we study the role of this affect in schizophrenia, depression, eating disorders, and personality disorders

Labile disulfide bonds are common at the leucocyte cell surface

Redox conditions change in events such as immune and platelet activation, and during viral infection, but the biochemical consequences are not well characterized. There is evidence that some disulfide bonds in membrane proteins are labile while others that are probably structurally important are not exposed at the protein surface. We have developed a proteomic/mass spectrometry method to screen for and identify non-structural, redox-labile disulfide bonds in leucocyte cell-surface proteins. These labile disulfide bonds are common, with several classes of proteins being identified and around 30 membrane proteins regularly identified under different reducing conditions including using enzymes such as thioredoxin. The proteins identified include integrins, receptors, transporters and cell–cell recognition proteins. In many cases, at least one cysteine residue was identified by mass spectrometry as being modified by the reduction process. In some cases, functional changes are predicted (e.g. in integrins and cytokine receptors) but the scale of molecular changes in membrane proteins observed suggests that widespread effects are likely on many different types of proteins including enzymes, adhesion proteins and transporters. The results imply that membrane protein activity is being modulated by a ‘redox regulator’ mechanism

Lung segmentation and characterization in covid-19 patients for assessing pulmonary thromboembolism: An approach based on deep learning and radiomics

The COVID-19 pandemic is inevitably changing the world in a dramatic way, and the role of computed tomography (CT) scans can be pivotal for the prognosis of COVID-19 patients. Since the start of the pandemic, great care has been given to the relationship between interstitial pneumonia caused by the infection and the onset of thromboembolic phenomena. In this preliminary study, we collected n = 20 CT scans from the Polyclinic of Bari, all from patients positive with COVID-19, nine of which developed pulmonary thromboembolism (PTE). For eight CT scans, we obtained masks of the lesions caused by the infection, annotated by expert radiologists; whereas for the other four CT scans, we obtained masks of the lungs (including both healthy parenchyma and lesions). We developed a deep learning-based segmentation model that utilizes convolutional neural networks (CNNs) in order to accurately segment the lung and lesions. By considering the images from publicly available datasets, we also realized a training set composed of 32 CT scans and a validation set of 10 CT scans. The results obtained from the segmentation task are promising, allowing to reach a Dice coefficient higher than 97%, posing the basis for analysis concerning the assessment of PTE onset. We characterized the segmented region in order to individuate radiomic features that can be useful for the prognosis of PTE. Out of 919 extracted radiomic features, we found that 109 present different distributions according to the Mann–Whitney U test with corrected p-values less than 0.01. Lastly, nine uncorrelated features were retained that can be exploited to realize a prognostic signature

Agroecological practices and agrobiodiversity. A case study on organic orange in southern Italy

7noopenThe integration of Agroecological Service Crops (ASCs) into agroecosystems can provide several ecological services, such as nutrient cycling and disease and weed management. A two-year experiment on an organic orchard was carried out to compare barley (B) and horse bean (HB) ASCs with a control without ASC (Cont) in combination with fertilizers. Their effects on soil fertility and weed- and soil-borne fungi communities were evaluated by direct measurements, visual estimation, and indicators computation. A Principal Component Analysis (PCA) was used to identify latent patterns and redundancy among variables, whereas a correlation analysis was used to discriminate the compared systems within the PCA matrix. The empirical results of this study put in evidence the correlation among soil, weed, and fungal variables. A slight contribution of fertilizers on the system’s variability was observed, whereas a clear effect of ASCs was highlighted. The systems differed in weed communities, with the lowest density associated to B and the highest to Cont. B showed the highest fungal diversity, with changes in community compared to HB. HB showed a contribution on soil fertility, being associated to organic matter increase and N availability, and evidencing mixed impacts on soil quality and ecosystem functioning. Overall, the above-ground diversity and below-ground community results were inter-correlated.openCiaccia C.; La Torre A.; Ferlito F.; Testani E.; Battaglia V.; Salvati L.; Roccuzzo G.Ciaccia, C.; La Torre, A.; Ferlito, F.; Testani, E.; Battaglia, V.; Salvati, L.; Roccuzzo, G

Trends in Prescribing Oral Anticoagulants in Canada, 2008–2014

AbstractPurposeThe non–vitamin K antagonist oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban, provide several advantages over vitamin K antagonists, such as warfarin. Little is known about the trends of prescribing OACs in Canada. In this study we analyzed changes in prescription volumes for OAC drugs since the introduction of the NOACs in Canada overall, by province and by physician specialty.MethodsCanadian prescription volumes for warfarin, dabigatran, rivaroxaban, and apixaban from January 2008 to June 2014 were obtained from the Canadian Compuscript Audit of IMS Health Canada Inc and were analyzed by physician specialty at the national and provincial levels. Total prescriptions by indication were calculated based on data from the Canadian Disease and Therapeutic Index for all OAC indications and for each commonly prescribed dose of dabigatran (75, 110, and 150 mg), rivaroxaban (10, 15, and 20 mg), and apixaban (2.5 and 5 mg).FindingsThe overall number of OAC prescriptions in Canada has increased annually since 2008. With the availability of the NOACs, the proportion of total OAC prescriptions attributable to warfarin has steadily decreased, from 99% in 2010 to 67% by June 2014, and the absolute number of warfarin prescriptions has been decreasing since February 2011. The greatest decline in proportionate warfarin prescriptions was in Ontario. In general, the increase of NOAC prescriptions coincided with the introduction of provinces’ reimbursement of NOAC prescription costs. The proportion of total OAC prescriptions represented by the NOACs varied by specialty, with the greatest proportionate prescribing found among orthopedic surgeons, cardiologists, and neurologists.ImplicationsSince their approval, the NOACs have represented a growing share of total OAC prescriptions in Canada. This trend is expected to continue because the NOACs are given preference over warfarin in guidelines on stroke prevention in patients with atrial fibrillation, because of growing physician experience, and due to the emergence of potential new indications. An understanding of the current prescribing patterns will help to encourage knowledge translation and possibly influence policy/reimbursement strategies

Photon-mediated long range coupling of two Andreev level qubits

In a superconducting weak link, the supercurrent is carried by Andreev bound states (ABSs) formed by the phase-coherent reflection of electrons and their time-reversed partners. A single, highly transmissive ABS can serve as an ideal, compact two-level system, due to a potentially large energy difference to the next ABS. While the coherent manipulation of such Andreev levels qubits (ALQs) has been demonstrated, a long-range coupling between two ALQs, necessary for advanced qubit architectures, has not been achieved, yet. Here, we demonstrate a coherent remote coupling between two ALQs, mediated by a microwave photon in a novel superconducting microwave cavity coupler. The latter hosts two modes with different coupling rates to an external port. This allows us to perform fast readout of each qubit using the strongly coupled mode, while the weakly coupled mode is utilized to mediate the coupling between the qubits. When both qubits are tuned into resonance with the latter mode, we find excitation spectra with avoided-crossings, in very good agreement with the Tavis-Cummings model. Based on this model, we identify highly entangled two-qubit states for which the entanglement is mediated over a distance of six millimeters. This work establishes ALQs as compact and scalable solid-state qubits.Comment: 13 pages, 7 figure

Massive transcriptome sequencing of human spinal cord tissues provides new insights into motor neuron degeneration in als

ALS is a devastating and debilitating human disease characterized by the progressive death of upper and lower motor neurons. Although much effort has been made to elucidate molecular determinants underlying the onset and progression of the disorder, the causes of ALS remain largely unknown. In the present work, we have deeply sequenced whole transcriptome from spinal cord ventral horns of post-mortem ALS human donors affected by the sporadic form of the disease (which comprises ∼90% of the cases but which is less investigated than the inherited form of the disease). We observe 1160 deregulated genes including 18 miRNAs and show that down regulated genes are mainly of neuronal derivation while up regulated genes have glial origin and tend to be involved in neuroinflammation or cell death. Remarkably, we find strong deregulation of SNAP25 and STX1B at both mRNA and protein levels suggesting impaired synaptic function through SNAP25 reduction as a possible cause of calcium elevation and glutamate excitotoxicity. We also note aberrant alternative splicing but not disrupted RNA editing

Ectopic thymoma simulating a pericardial cyst

We present a case of a 53 year old man with a thymoma near the pericardium, a rare ectopic localisation of thymoma. A round radiodensity found at the right cardiophrenic angle was initially suspected at the echocardiography to be a pericardial cyst. The diagnosis of thymoma was made only after histopathological examination of the surgically re-sected lesion