Explicit kinematic equations for degree-4 rigid origami vertices, Euclidean and non-Euclidean

We derive algebraic equations for the folding angle relationships in completely general degree-4 rigid-foldable origami vertices, including both Euclidean (developable) and non-Euclidean cases. These equations in turn lead to elegant equations for the general developable degree-4 case. We compare our equations to previous results in the literature and provide two examples of how the equations can be used: in analyzing a family of square twist pouches with discrete configuration spaces, and for proving that a folding table design made with hyperbolic vertices has a single folding mode

Design and Synthesis of Hsp90 Inhibitors with B-Raf and PDHK1 Multi-Target Activity

5noopenThe design of multi-target ligands has become an innovative approach for the identification of effective therapeutic treatments against complex diseases, such as cancer. Recent studies have demonstrated that the combined inhibition of Hsp90 and B-Raf provides synergistic effects against several types of cancers. Moreover, it has been reported that PDHK1, which presents an ATP-binding pocket similar to that of Hsp90, plays an important role in tumor initiation, maintenance and progression, participating also to the senescence process induced by B-Raf oncogenic proteins. Based on these premises, the simultaneous inhibition of these targets may provide several benefits for the treatment of cancer. In this work, we set up a design strategy including the assembly and integration of molecular fragments known to be important for binding to the Hsp90, PDHK1 and B-Raf targets, aided by molecular docking for the selection of a set of compounds potentially able to exert Hsp90-B-Raf-PDHK1 multi-target activities. The designed compounds were synthesized and experimentally validated in vitro. According to the in vitro assays, compounds 4 a, 4 d and 4 e potently inhibited Hsp90 and moderately inhibited the PDHK1 kinase. Finally, molecular dynamics simulations were performed to provide further insights into the structural basis of their multi-target activity.openPinzi L.; Foschi F.; Christodoulou M.S.; Passarella D.; Rastelli G.Pinzi, L.; Foschi, F.; Christodoulou, M. S.; Passarella, D.; Rastelli, G

FROM DOCUMENTATION IMAGES TO RESTAURATION SUPPORT TOOLS: A PATHFOLLOWING THE NEPTUNE FOUNTAIN IN BOLOGNA DESIGN PROCESS

The sixteenth-century Fountain of Neptune is one of Bologna's most renowned landmarks. During the recent restoration activities of the monumental sculpture group, consisting in precious marbles and highly refined bronzes with water jets, a photographic campaign has been carried out exclusively for documentation purposes of the current state of preservation of the complex. Nevertheless, the highquality imagery was used for a different use, namely to create a 3D digital model accurate in shape and color by means of automated photogrammetric techniques and a robust customized pipeline. This 3D model was used as basic tool to support many and different activities of the restoration site. The paper describes the 3D model construction technique used and the most important applications in which it was used as support tool for restoration: (i) reliable documentation of the actual state; (ii) surface cleaning analysis; (iii) new water system and jets; (iv) new lighting design simulation; (v) support for preliminary analysis and projectual studies related to hardly accessible areas; (vi) structural analysis; (vii) base for filling gaps or missing elements through 3D printing; (viii) high-quality visualization and rendering and (ix) support for data modelling and semantic-based diagrams

Meningococcal Carriage in ‘Men Having Sex With Men’ With Pharyngeal Gonorrhoea

We assessed the characteristics of Neisseria meningitidis pharyngeal carriage in a cohort of ‘men having sex with men’, including patients with pharyngeal Neisseria gonorrhoeae infection. In the period 2017-2019, among all the oropharyngeal samples tested for gonorrhoea from MSM attending a STI Clinic in Bologna (Italy), we randomly selected 244 N. gonorrhoeae-positive samples and 403 negatives (n=647). Pharyngeal specimens were tested for N. meningitidis presence, by the detection of sodC gene. N. meningitidis-positive samples were further grouped by PCR tests for the major invasive genogroups (i.e., A, B, C, W, and Y). A molecular assay, targeting capsule transporter gene, was used to determine meningococcal capsular status. Overall, 75.8% (491/647) of samples tested positive for sodC gene, indicating a pharyngeal meningococcal carriage. Meningococcal colonisation was significantly more frequent in younger subjects (P=0.009), with no association with HIV infection. Non-groupable meningococci represented most of pharyngeal carriages (about 71%). The commonest N. meningitidis serogroup was B (23.6%), followed by C (2.1%), Y (1.8%) and W (1.1%). Meningococci were often characterized by the genetic potential of capsule production. Interestingly, a negative association between N. meningitidis and N. gonorrhoeae was found: pharyngeal gonorrhoea was significantly more present in patients without meningococcal carriage (P=0.03). Although preliminary, our data added knowledge on the epidemiology of meningococcal carriage in MSM communities at high risk of gonococcal infections, gaining new insights into the interactions/dynamics between N. meningitidis and N. gonorrhoeae

Vaginal and anal microbiome during chlamydia trachomatis infections

Background. Chlamydia trachomatis (CT) is the agent of the most common bacterial sexually transmitted infection worldwide, with a significant impact on women’s health. Despite the increasing number of studies about the vaginal microbiome in women with CT infections, information about the composition of the anal microbiome is still lacking. Here, we assessed the bacterial community profiles of vaginal and anal ecosystems associated or not with CT infection in a cohort of Caucasian young women. Methods. A total of 26 women, including 10 with a contemporary vaginal and anorectal CT infection, were enrolled. Composition of vaginal and anal microbiome was studied by 16S rRNA gene profiling. Co-occurrence networks of bacterial communities and metagenome metabolic functions were determined. Results. In case of CT infection, both vaginal and anal environments were characterized by a degree of dysbiosis. Indeed, the vaginal microbiome of CT-positive women were depleted in lactobacilli, with a significant increase in dysbiosis-associated bacteria (e.g., Sneathia, Parvimonas, Megasphaera), whereas the anal microbiota of CT-infected women was characterized by higher levels of Parvimonas and Pseudomonas and lower levels of Escherichia. Interestingly, the microbiome of anus and vagina had numerous bacterial taxa in common, reflecting a significant microbial ‘sharing’ between the two sites. In the vaginal environment, CT positively correlated with Ezakiella spp. while Gardnerella vaginalis co-occurred with several dysbiosis-related microbes, regardless of CT vaginal infection. The vaginal microbiome of CT-positive females exhibited a higher involvement of chorismate and aromatic amino acid biosynthesis, as well as an increase in mixed acid fermentation. Conclusions. These data could be useful to set up new diagnostic/prognostic tools, offering new perspectives for the control of chlamydial infections

Definition of a Core Collection and Construction of a Reference Set for Genome-Wide Association Studies from a Large Prunus persica Germplasm Collection

Genome-wide association studies take advantage of the natural variation present in germplasm repositories for identifying genes underlying agronomic traits, through plant molecular and phenotypic characterization. For tree crops, in vivo maintenance and phenotyping are particularly onerous and the reduction of redundancy and duplicates could help lowering management costs. In the frame of the European project FruitBreedomics, a collection of 1580 Prunus accessions from different institutions in Europe and China has been genotyped with the IPSC 9K SNP Array and phenotyped for different agronomic traits and a GWAS analysis with 4271 SNPs on 7 monogenic traits has been carried out (Micheletti et al. 2015). In the present work, the same set of 4271 SNP markers was used to identify a peach core collection by applying the maximization strategy implemented in the software PowerCore v 1.0 (Kim et al. 2007). Out of a total of 1540 a core of 72 (C72) accessions was identified, representing 4.7% sampling size. C72 contains the accessions with higher diversity representing the total allelic coverage with an efficiency index of 0.83 with respect to random sampling. In the view of setting up a genomic tool for GWAS analyses a reference subset of 150 accessions was also developed taking into account allelic and phenotypic traits representativeness through the maximization strategy, population stratification and controlled redundancy required to have enough statistical power. Preliminary PCA analysis shows population structure to explain less than 30% of variability due to the local varieties. Validation of the reference set will also be presented

Ruthenium-Catalyzed Decarboxylative Rearrangement of 4-Alkenyl-isoxazol-5-ones to Pyrrole Derivatives

Easily accessible isoxazol-5(4H)-ones are useful precursors of heterocycles. In this context, we report the ruthenium-catalyzed transformation of 4-alkenyl-substituted isoxazol-5-ones to afford 1H-pyrrole derivatives. The operative conditions were proven to be effective also on cyclohexane-fused isoxazolones giving 4,5,6,7-tetrahydroindoles. The reactions, which allow for access to tri-and tetra-substituted pyrroles in moderate to high yields, occur through decarboxylative ring-opening/ring-closure involving C-H functionalization of the alkenyl moiety

Acute stroke-like deficits associated with nonketotic hyperglycemic hyperosmolar state: an illustrative case and systematic review of literature

INTRODUCTION: Nonketotic hyperglycemic hyperosmolar state (NKHHS) is associated with a wide spectrum of neurological syndromes including acute stroke-like deficits. Clinical features and etiology have not been established yet. METHODS: Here we provide a case illustration and systematic review on non-epileptic acute neurological deficits in NKHSS. The systematic literature search followed PRISMA guidelines and a predefined protocol, including cases of NKHSS with acute stroke-like presentation. RESULTS: The database search yielded 18 cases. Hemianopia was the most common clinical presentation (73%), followed by partial or total anterior circulation syndrome (26%). Patients with symptoms of acute anterior circulation infarct were significantly older (69.5 ± 5.1 vs. 52.2 ± 13.9 years; p = 0.03) and showed higher mean glucose levels at the admission vs. those with hemianopia (674.8 ± 197.2 vs. 529.4 ± 190.8 mg/dL; p = 0.16). Brain MRI was performed in 89% of patients, resulting abnormal in 71% of them, especially hemianopic (91%). Subcortical hypointensities in T2-FLAIR MR sequences were present in all the analyzed cases. Cortical DWI hyperintensities were also common (64%). EEG showed diffuse or focal slow wave activity in 68% of patients, especially with visual hallucinations (85%). Neurological symptoms completely resolved in 78% of patients within 6 (IQR 3-10) days, following aggressive treatment and glucose normalization. CONCLUSIONS: Our results suggest neuronal dysfunction on a metabolic basis as the leading cause of acute neurological deficits in NKHHS. Despite the generally favorable prognosis, prompt identification and aggressive treatment are crucial to avoid irreversible damage. Larger cohort studies are needed to confirm our findings

Genetic Dissection of Complex Fruit Quantitative Traits in Peach Progen

Major research efforts in peach are dedicated to the discovery of genomic variants causing phenotypic effects in complex fruit traits such as: maturity date (MD), fruit size (FW), sugar (SSC) and acid content (TA), flesh texture (slow softening, SSf) and resistance to brown rot by Monilinia spp. (BRr). Five segregating progenies showing phenotypic variation for at least one of these traits are available in our experimental fields. For SSC and TA, an already validated approach based on Near-InfraRed spectroscopy (NIR), is being applied to phenotype some segregating progenies. For SSf and BRr instead, trait characterization has been performed, resulting in the identification of co-factor traits and definition of standardized phenotyping tools, which are currently applied in the characterization of segregating material (in the context of FruitBreedomics EU project). High-density linkage maps have been constructed with genotypic data obtained from IPSC Illumina 9K SNP chip (Italian Drupomics and FruitBreedomics frameworks) and Genotyping-by-Sequencing (GBS). Additionally, parents of these progenies have been re-sequenced (30-40x) and genetic variants present along their genomes have been identified. Multiple-QTL models (MQM) coupled with the use of co-factor traits is leading to the discovery of significant QTLs. Genomic variants are explored within QTL intervals on the genomes of progeny parents, in order to identify possible mutations causing phenotypic differences, and develop markers for marker-assisted selection approaches

Individualized Prediction of Drug Resistance in People with Post-Stroke Epilepsy: A Retrospective Study

Background: The study aimed to develop a model and build a nomogram to predict the probability of drug resistance in people with post-stroke epilepsy (PSE). Methods: Subjects with epilepsy secondary to ischemic stroke or spontaneous intracerebral hemorrhage were included. The study outcome was the occurrence of drug-resistant epilepsy defined according to International League Against Epilepsy criteria. Results: One hundred and sixty-four subjects with PSE were included and 32 (19.5%) were found to be drug-resistant. Five variables were identified as independent predictors of drug resistance and were included in the nomogram: age at stroke onset (odds ratio (OR): 0.941, 95% confidence interval (CI) 0.907–0.977), intracerebral hemorrhage (OR: 6.292, 95% CI 1.957–20.233), severe stroke (OR: 4.727, 95% CI 1.573–14.203), latency of PSE (>12 months, reference; 7–12 months, OR: 4.509, 95% CI 1.335–15.228; 0–6 months, OR: 99.099, 95% CI 14.873–660.272), and status epilepticus at epilepsy onset (OR: 14.127, 95% CI 2.540–78.564). The area under the receiver operating characteristic curve of the nomogram was 0.893 (95% CI: 0.832–0.956). Conclusions: Great variability exists in the risk of drug resistance in people with PSE. A nomogram based on a set of readily available clinical variables may represent a practical tool for an individualized prediction of drug-resistant PSE