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Mega-events imply several city transformations at different scales that could be challenging to be identified and documented. The impacts of such events like Universal Exhibitions are difficult to be identified and tracked in space and over a long period of time. This paper discusses the use of open-source geospatial technologies as innovative tools in support of urban planning and management of digital cities, analysing in particular the case of an international exhibition in the urban landscape. A GIS-based approach is used to design a spatially enabled database, which is essential for implementing advanced analytics in modern smart cities. The pilot project proposes the design and implementation of such georeferenced database for monitoring the urban transformations of the area used for Expo 2015 Milano (Italy). The potential of GIS environment in the consultation process, which allows to obtain different interactive views and to make selections and queries of the data, is explored. The paper also discusses the possibility of publishing such prototype on a shared platform, allowing a larger non-technical audience to follow the urban evolution of the area in a diachronic perspective.

Streptococcus agalactiae (estreptococo grupo B de Lancefield) es el microorganismo más frecuentemente involucrado en infección neonatal por transmisión vertical madre-feto. También es responsable de infecciones en mujeres embarazadas y adultos con enfermedades de base. El objetivo de este trabajo fue conocer la prevalencia de portación de S. agalactiae en mujeres embarazadas que concurrieron al Hospital Posadas y determinar la sensibilidad a penicilina, eritromicina y clindamicina de los aislamientos. De las 1203 gestantes estudiadas, se aisló S. agalactiae en 113 muestras, con una prevalencia de 9,39%. Se realizaron las pruebas de sensibilidad a 87 de los 113 aislamientos. Todos ellos resultaron sensibles a penicilina y únicamente 2 cepas fueron resistentes a eritromicina y clindamicina (mecanismo MLS constitutivo). Resaltamos la importancia de conocer la resistencia a estos dos últimos agentes, en el caso de mujeres alérgicas a los antibióticos beta-lactámicos.Streptococcus agalactiae (Lancefield group B Streptococcus), is the most frequently microorganism involved in neonatal infections through the mother-fetus vertical transmission. It is also responsible for infections in pregnant women, and adults with underlying diseases. The objective of this work was to know the S. agalactiae carrier prevalence in pregnant women who attended to Posadas Hospital, and to study the susceptibility pattern of the isolates to penicillin, erythromycin and clindamycin. From 1203 pregnant women studied, S. agalactiae was recovered in 113, which means a prevalence of 9.39%. Antimicrobial susceptibility was tested to 87 isolates. All of them were susceptible to penicillin, and only 2 isolates were resistant to erythromycin and clindamycin (constitutive MLS mechanism). We emphasize the importance of knowing these last resistance, in the case of beta-lactam antibiotics allergic women.

Two uniqueness theorems for an isothermal mixture of two miscible fluids are proved. The mixture F is incompressible in a generalized sense and able of exerting Korteweg stresses.

Abstract Background Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. Methods A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. Results In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p

Abstract There has been a steady rise in the use of dormant propagules to study biotic responses to environmental change over time. This is particularly important for organisms that strongly mediate ecosystem processes, as changes in their traits over time can provide a unique snapshot into the structure and function of ecosystems from decades to millennia in the past. Understanding sources of bias and variation is a challenge in the field of resurrection ecology, including those that arise because often‐used measurements like seed germination success are imperfect indicators of propagule viability. Using a Bayesian statistical framework, we evaluated sources of variability and tested for zero‐inflation and overdispersion in data from 13 germination trials of soil‐stored seeds of Schoenoplectus americanus, an ecosystem engineer in coastal salt marshes in the Chesapeake Bay. We hypothesized that these two model structures align with an ecological understanding of dormancy and revival: zero‐inflation could arise due to failed germinations resulting from inviability or failed attempts to break dormancy, and overdispersion could arise by failing to measure important seed traits. A model that accounted for overdispersion, but not zero‐inflation, was the best fit to our data. Tetrazolium viability tests corroborated this result: most seeds that failed to germinate did so because they were inviable, not because experimental methods failed to break their dormancy. Seed viability declined exponentially with seed age and was mediated by seed provenance and experimental conditions. Our results provide a framework for accounting for and explaining variability when estimating propagule viability from soil‐stored natural archives which is a key aspect of using dormant propagules in eco‐evolutionary studies.

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and incidence rates are continuing to rise globally. Patients often present with locally advanced disease and a staggering 50% chance of relapse following treatment. Aberrant activation of adaptive response signaling pathways, such as the cAMP/PKA pathway, induce an array of genes associated with known cancer pathways that promote tumorigenesis and drug resistance. We identified the cAMP Regulated Transcription Coactivator 2 (CRTC2) to be overexpressed and constitutively activated in HNSCCs and this confers poor prognosis. CRTCs are regulated through their subcellular localization and we show that CRTC2 is exclusively nuclear in HPV(+) HNSCC, thus constitutively active, due to non-canonical Mitogen-Activated Kinase Kinase 1 (MEKK1)-mediated activation via a MEKK1-p38 signaling axis. Loss-of-function and pharmacologic inhibition experiments decreased CRTC2/CREB transcriptional activity by reducing nuclear CRTC2 via nuclear import inhibition and/or by eviction of CRTC2 from the nucleus. This shift in localization was associated with decreased proliferation, migration, and invasion. Our results suggest that small molecules that inhibit nuclear CRTC2 and p38 activity may provide therapeutic benefit to patients with HPV(+) HNSCC.

ABSTRACT The arms race between bacteria and their bacteriophages profoundly influences microbial evolution. With an estimated 1023 phage infections occurring per second, there is strong selection for both bacterial survival and phage coevolution for continued propagation. Many phage resistance systems, including restriction-modification systems, clustered regularly interspaced short palindromic repeat-Cas (CRISPR-Cas) systems, a variety of abortive infection systems, and many others that are not yet mechanistically defined, have been described. Temperate bacteriophages are common and form stable lysogens that are immune to superinfection by the same or closely related phages. However, temperate phages collude with their hosts to confer defense against genomically distinct phages, to the mutual benefit of the bacterial host and the prophage. Prophage-mediated viral systems have been described in Mycobacterium phages and Pseudomonas phages but are predicted to be widespread throughout the microbial world. Here we describe a new viral defense system in which the mycobacteriophage Sbash prophage colludes with its Mycobacterium smegmatis host to confer highly specific defense against infection by the unrelated mycobacteriophage Crossroads. Sbash genes 30 and 31 are lysogenically expressed and are necessary and sufficient to confer defense against Crossroads but do not defend against any of the closely related phages grouped in subcluster L2. The mapping of Crossroads defense escape mutants shows that genes 132 and 141 are involved in recognition by the Sbash defense system and are proposed to activate a loss in membrane potential mediated by Sbash gp30 and gp31. IMPORTANCE Viral infection is an ongoing challenge to bacterial survival, and there is strong selection for development or acquisition of defense systems that promote survival when bacteria are attacked by bacteriophages. Temperate phages play central roles in these dynamics through lysogenic expression of genes that defend against phage attack, including those unrelated to the prophage. Few prophage-mediated viral defense systems have been characterized, but they are likely widespread both in phage genomes and in the prophages integrated in bacterial chromosomes.

BackgroundA major obstacle to using recombinant adenoviral vectors in gene therapy is the natural ability of human adenovirus to activate the classical and alternate complement pathways. These innate immune responses contribute to hepatic adenoviral uptake following systemic delivery and enhance the humoral immune responses associated with adenoviral infection.MethodsA recombinant Ad5 vector was genetically modified to display a peptide sequence ("rH17d'"), a known inhibitor of the classical complement pathway. The replication-defective vectors Ad5.HVR2-rH17d' and Ad5.HVR5-rH17d' were constructed by engineering the rH17d' peptide into the hypervariable region (HVR)-2 or HVR5 of their major capsid protein hexon. Control Ad5 vectors were created by incorporation of a 6-histidine (His6)-insert in either HVR2 or HVR5 (Ad5.HVR2-His6 and Ad5.HVR5-His6, respectively). All vectors encoded CMV promoter-controlled firefly luciferase (Luc). The four vectors were evaluated in TIB76 mouse liver cells and immunocompetent mice to compare infectivity and liver sequestration, respectively.ResultsIn vitro studies demonstrated that preincubation of all the Ad5 vectors with fresh serum significantly increased their gene transfer relative to preincubation with PBS except Ad5.HVR5-rH17d', whose infectivity of liver cells showed no serum-mediated enhancement. In line with that, mice injected with Ad5.HVR2-rH17d' or Ad5.HVR5-rH17d' showed significantly lower luciferase expression levels in the liver as compared to the respective control vectors, whereas efficiency of tumor transduction by rH17d' and His6 vectors following their intratumoral injection was similar.ConclusionsDisplaying a complement-inhibiting peptide on the Ad5 capsid surface by genetic modification of the hexon protein could be a suitable strategy for reducing Ad5 liver tropism (Ad5 sequestration by liver), which may be applicable to other gene therapy vectors with natural liver tropism.

Dynamically altering protein concentration is a central activity in synthetic biology. While many tools are available to modulate protein concentration by altering protein synthesis rate, methods for decreasing protein concentration by inactivation or degradation rate are just being realized. Altering protein synthesis rates can quickly increase the concentration of a protein but not decrease, as residual protein will remain for a while. Inducible, targeted protein degradation is an attractive option and some tools have been introduced for higher organisms and bacteria. Current bacterial tools rely on C-terminal fusions, so we have developed an N-terminal fusion (Ntag) strategy to increase the possible proteins that can be targeted. We demonstrate Ntag dependent degradation of mCherry and beta-galactosidase and reconfigure the Ntag system to perform dynamic, exogenously inducible degradation of a targeted protein and complement protein depletion by traditional synthesis repression. Model driven analysis that focused on rates, rather than concentrations, was critical to understanding and engineering the system. We expect this tool and our model to enable inducible protein degradation use particularly in metabolic engineering, biological study of essential proteins, and protein circuits.

The refinement of tightly regulated prokaryotic expression systems that permit functional expression of toxic recombinant proteins is a continually evolving process. Unfortunately, the current best promoter options are either tightly repressed and produce little protein, or produce substantial protein but lack the necessary repression to avoid mutations stimulated by leaky expression in the absence ofinducer. In this report, we present three novel prokaryotic expression constructs that are tightly regulated by L-rhamnose and D-glucose. These expression vectors utilize the Escherichia coli rhaT promoter and corresponding regulatory genes to provide titratable, high-level protein yield without compromising clone integrity. Together, these components may enable the stable cloning and functional expression of otherwise toxic proteins.

BACKGROUND: Advances in the definition of the function and the mechanism of estrogen action in different tissues have come from human and animal models of estrogen insufficiency. Recently we have demonstrated that aromatase is present and biologically active in human ejaculated sperm, suggesting that autonomous estradiol sperm production may influence sperm functions. In the present study we investigate a possible physiological role for enzymatically active P450 aromatase in human ejaculated sperm. METHODS AND RESULTS: To confirm the presence of mRNA coding for P450 aromatase, total RNA isolated from human sperm underwent RT-PCR and then Southern blot analysis. In non-capacitating medium, we observed that only estradiol and aromatizable steroids were able to increase sperm motility/migration; concomitantly they enhanced protein tyrosine phosphorylation and increased p-44/42 extracellular signal-regulated kinase activity. When we tested acrosin activity, it emerged that estradiol and aromatizable androgens were also able to induce the acrosome reaction evaluated by two different cytological staining techniques (triple-stain and fluorescein isothiocyanate-Pisum sativum agglutinin). All these events were enhanced by the 2′-O-dibutyryladenosine-3′,5′-cyclic monophosphate and inhibited in the presence of the specific aromatase inhibitor, letrozole. CONCLUSIONS: From this study, it appears that a link exists between the locally produced estradiol (from ejaculated sperm), sperm capacitation and the acrosome reaction. The induction of both events by aromatizable androgens in the absence of exogenous mediators suggests that estrogen biosynthesis in ejaculated sperm is a process that may influence the intrinsic sperm fertilizing capability. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: Tantalum coated metal spacers (TCMS) have recently been utilized to fill and provide structure to large bony defects in the hindfoot. Tantalum is an appealing material due to its biocompatibility, lack of immune response generation, and structural integrity. Compared to custom printed spacers and bulk allografts, TCMS are readily available off-the-shelf implants with significantly less cost. There is currently a paucity of literature assessing the use and outcomes of TCMS in foot and ankle surgery, specifically in tibiotalocalcaneal (TTC) arthrodesis. This study serves to assess clinical outcomes and fusion rates of patients who underwent TTC arthrodesis utilizing intramedullary nailing with TCMS augmentation for large bony defects. Methods: We retrospectively identified all patients > 18 years of age who underwent TTC arthrodesis with TCMS augmentation at our tertiary care center between 2015-2021. We also identified all patients who underwent TTC arthrodesis without augmentation within that time frame. The computed tomography (CT) scans at the six-month postoperative point were reviewed by one board-certified orthopaedic foot and ankle surgeon to determine fusion status, which was defined as having at least 50% fusion mass. Patient-reported outcomes measures (PROMs) including the modified foot function index (FFI) and PROMIS Global Mental Health Score were collected for patients in both groups. Patient demographics, clinical outcomes, and PROMs were compared between groups. A multivariate logistic regression model measured the effect of TCMS augmentation on the likelihood of achieving fusion. Results: Of the 65 patients included, 21 patients (32.3%) underwent TTC with TCMS augmentation. There were no significant differences in demographics between the two groups. Patients in the TCMS group had significantly higher modified FFI (91.1 + 47.6 vs 26.3 + 48.8, p< 0.001) and PROMIS Global Mental Health (12.2 + 4.82 vs. 5.59 + 6.76, p< 0.001) scores in the postoperative period. Overall, the fusion rate was higher for the TCMS group, however the difference was not significant between groups (90.5% vs. 80.5%, p=0.472). Multivariate logistic regression identified that TCMS augmentation was a nonsignificant predictor of increased odds of fusion at the six-month postoperative point (OR=2.87, p=0.232). Conclusion: This study is the largest to date to present 6-month postoperative CT scans demonstrating successful TTC fusion with TCMS augmentation, contributing to our understanding of its utility. Given the severity of disease and bone loss in the TCMS group, it is not surprising that post-operative patient reported outcome scores differed significantly compared to the control group. TCMS augmentation can be utilized as cost effective spacers to fill large defects in TTC arthrodesis with successful union rates. Further studies are needed to evaluate the efficacy of TCMS augmented fusions as a viable substitute to custom printed cages. Figure 1: Weight-bearing anteroposterior and lateral ankle radiographs of a patient with post-traumatic ankle arthritis and previously treated chronic osteomyelitis with valgus malalignment (A). Anteroposterior and lateral ankle radiographs status post TCMS augmented TTC arthrodesis (B). Coronal and sagittal CT scans demonstrating bony union through the TCMS augment (C).

A triplet repeat expansion leading to transcriptional silencing of the FMR1 gene results in fragile X syndrome (FXS), which is a common cause of inherited intellectual disability and autism. Phenotypic variation requires personalized treatment approaches and hampers clinical trials in FXS. We searched for microRNA (miRNA) biomarkers for FXS using deep sequencing of urine and identified 28 differentially regulated miRNAs when 219 reliably identified miRNAs were compared in dizygotic twin boys who shared the same environment, but one had an FXS full mutation, and the other carried a premutation allele. The largest increase was found in miR-125a in the FXS sample, and the miR-125a levels were increased in two independent sets of urine samples from a total of 19 FXS children. Urine miR-125a levels appeared to increase with age in control subjects, but varied widely in FXS subjects. Should the results be generalized, it could suggest that two FXS subgroups existed. Predicted gene targets of the differentially regulated miRNAs are involved in molecular pathways that regulate developmental processes, homeostasis, and neuronal function. Regulation of miR-125a has been associated with type I metabotropic glutamate receptor signaling (mGluR), which has been explored as a treatment target for FXS, reinforcing the possibility that urine miR-125a may provide a novel biomarker for FXS.

M Gentile, E Vigna, C Mazzone, E Lucia, AG Recchia, L Morabito2, MG Bisconte, C Gentile, F Morabito1UOC di Ematologia, Azienda Ospedaliera di Cosenza, Italy; 2Servicio de Hematología y Hemoterapia, Hospital Universitario de Canarias, La Laguna, Tenerife, SpainAbstract: Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder that originates from antigen-experienced B lymphocytes that do not die and hence accumulate due to external survival signals or undergo apoptosis and are replenished by proliferating precursors. These neoplastic lymphocytes exhibit a characteristic immunophenotype of CD5+/CD19+/CD20+/HLA-DR+/CD23+/sIgdim. Thus, the CD20 antigen has been an appealing target for therapy. The introduction of the monoclonal antibody rituximab (anti-CD20) enabled an outstanding advance in CLL treatment. The introduction of this monoclonal antibody into chemotherapy regimens has dramatically improved complete response rates and progression-free survival in patients with both untreated and relapsed CLL. Although only preliminary data from phase III confirmatory trials have been reported, the FCR regimen, which combines fludarabine and cyclophosphamide with rituximab, is currently the most effective treatment regimen for CLL patients, and has also been demonstrated to significantly improve overall survival . The success of rituximab and the identification of other CLL lymphocyte surface antigens have spurred the development of a multitude of monoclonal antibodies targeting distinct proteins and epitopes in an attempt to target CLL cells more effectively.Keywords: rituximab, chronic lymphocytic leukemia, chemotherapy