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A study investigates the role of WDR11, a WD protein that interacts with homeodomain transcription factor EMX1, in the cause of idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS). Observations reveal that missense mutations in WDR11 reduce or eliminate the gene's interaction of EMX1, involved in the development of olfactory neurons, thereby leading to defective pubertal development in patients with IHH and KS.

The polycystic kidney disease (PKD1) gene-encoded protein, polycystin-1, is developmentally regulated, with highest expression levels seen in normal developing kidneys, where it is distributed in a punctate pattern at the basal surface of ureteric bud epithelia. Overexpression in ureteric epithelial cell membranes of an inhibitory pMyr-GFP-PKD1 fusion protein via a retroviral (VVC) delivery system and microinjection into the ureteric bud lumen of embryonic day 11 mouse metanephric kidneys resulted in disrupted branching morphogenesis. Using confocal quantitative analysis, significant reductions were measured in the numbers of ureteric bud branch points and tips, as well as in the total ureteric bud length, volume and area, while significant increases were seen as dilations of the terminal branches, where significant increases in outer diameter and volumes were measured. Microinjection of an activating 5TM-GFP-PKD1 fusion protein had an opposite effect and showed significant increases in ureteric bud length and area. These are the first studies to experimentally manipulate polycystin-1 expression by transduction in the embryonic mouse kidney and suggest that polycystin-1 plays a critical role in the regulation of epithelial morphogenesis during renal development. Keywords: Polycystic kidney disease; Polycystin-1; Kidney; Development; Ureteric bud; Branching morphogenesis; Viral transduction; Epithelial cell adhesion; Migration; Focal adhesion

Septoria leaf spot is one the most widespread disease affecting pistachio (Pistacia vera) in countries of the Mediterranean region. Traditionally, three species have been associated with pistachio, including Septoria pistaciae , Septoria pistaciarum and S. pistacina. However, recent taxonomic studies have reordered and clarified the status of Septoria and septoria-like pathogens affecting pistachio. In our study, field surveys conducted in the traditional Sicilian pistachio production area of Bronte revealed the presence of trees showing characteristic septoria-like leaf spot. Collected isolates were morphologically and molecularly characterized. Morphological characterization was based on conidia measurements and evaluation of mycelial growth on different artificial media. Tested media included CMA, MEA, OA, PDA, and SNA. Phylogenetic analysis was conducted on a multi-locus approach (ITS + tef1 + tub2) based on Maximum Parsimony and Maximum Likelihood. Results showed that our isolates clustered with S. pistaciarum. Pathogenicity test was conducted in the field using conidia suspensions in order to fulfill Koch's postulates. Presence of characteristic rounded spots and pycnidia was evaluated on the inoculated leaves 9 and 23 days after inoculation. This study represents the first update on S. pistaciarum in Italy since its first identification in 1934. [ABSTRACT FROM AUTHOR]

The identification of a candidate gene for neurofibromatosis 2 (NF2), a dominantly inherited disorder characterized by the occurrence of bilateral schwannomas and other central nervous system tumors such as multiple meningiomas, is reported. Previous studies have suggested the inactivation of a tumor suppressor gene in choromosome 22q12 as a potential cause of the disorder. The candidate NF2 gene encodes a 587-amino acid protein which is related to the membrane-organizing extension spike protein-ezrin-radixin family of proteins that link cytoskeletal proteins with proteins in the cell membrane.

Abstract This paper concerns the homogenization of the dynamic response of Euler Bernoulli's beam with random Young's modulus. Considering the eigenvalue problem, special attention is dedicated to the homogenization residuals (correctors) analysis, i.e. the difference between the random heterogeneous solution and the homogenized solution. Several correlation (mixing) laws of the Young's modulus are considered and a dimensionless characteristic scale length, based on the correlation length, is introduced. The effects of the mixing law on the residuals are analyzed using numerical approaches both for sampling the random Young' modulus and for examining the beam eigenvalue problem. Two measurements are introduced to estimate the residuals between apparent and effective solution: the normalized difference of the Young's modulus and the normalized difference of the modes' shape. The effect of the mode's order is also highlighted with reference to forced vibrations. [ABSTRACT FROM AUTHOR]

Abstract The paper deals with the differences between effective and homogeneous solution in case of dynamic of continuous media with random micro-structure. In particular, these differences, called "residuals", are considered for the dynamic linear problem of the Euler-Bernoulli's beam with random Young's modulus. The differential operator with random coefficient, that describes the eigenvalues problem, is taken into account. The convergence to the effective solution is analysed by introducing two measures: the normalized error between apparent and effective Young's moduli and between the modes shapes. The obtained results permit to highlight the dependence of the residuals from the micro-structure dimensionless length and the effect of the modes order; these aspects should be considered in the homogenization of dynamic behaviour of random heterogeneous composites. The assessment of the Rapresentative Volume Element (RVE) by convergence of the Statistical Volume Element (SVE) is also discussed. Highlights • The residuals for the dynamic behaviour of heterogeneous beams have been highlighted. • Two normalized residuals have been introduced. • The effects of the mode order have been underlined. • The convergence of SVE to RVE is discussed. [ABSTRACT FROM AUTHOR]

• In existing half-joints, the primary reinforcing bars are frequently widespread across multiple layers, which makes it not easy to identify the proper S&T model. • EC2 does not provide recommendations to identify the proper S&T model in half-joints with distributed reinforcement. • Two analytical methods are proposed to evaluate the ultimate capacity of half-joints with distributed reinforcement. • The actual vertical or diagonal bars involved in the ultimate resistant mechanism can be identified. • Analytical results are checked against numerical results of a nonlinear FE model, after its calibration with literature experimental results. Reinforced Concrete (RC) discontinuity regions (D-regions), such as half-joints, can represent vulnerable zones in existing RC structures since they can be affected by a quasi-brittle failure mechanism. In common design practice, the ultimate strength of D-regions is assessed through Strut and Tie (S&T) models. It is well recognized that the resistant lattice trusses suggested by the Eurocode 2 (EC2) and usually adopted in determining the resistance of new D-regions during the design phase, provide results on the safe side. Nevertheless, in existing half-joints, primary reinforcing bars are frequently distributed across multiple layers, which makes it not easy to identify the appropriate S&T model. For instance, the ultimate capacity of these half-joints could be misestimated if distributed bars are replaced by an equivalent tie passing for their centroid, as is typically done in common practice. The present paper provides two analytical methods for identifying the reinforcement bars involved in the resistant mechanism of D-regions and determining the axial forces in all of them. The proposed methods estimate the ultimate shear resistance of existing half-joints. The accuracy of the proposed procedures is checked through a comparison with numerical results. The methods, capable of identifying the weakest component in the resistant mechanisms of RC D-regions, can be adopted for the assessment of the load-carrying capacity of existing half-joints and identify the proper structural strengthening works to increase the ultimate strength and ductility. [ABSTRACT FROM AUTHOR]

During the structure lifetime, the design loads can modify because of a changing in the use destination. In common practice, any architectural change of existing buildings, which modifies the magnitude of loads, requires the evaluation of the load-carrying capacity of structural members. To this aim a nonlinear analysis considering the rotation capacity of critical regions until the failure of the structure can be advantageous compared to a simple elastic analysis. Plastic deformations of ductile elements allow for attaining a more accurate evaluation of the ultimate load, once the strength of brittle mechanisms has been averted. Exploiting the actual rotation capacity of critical regions, where plastic hinges form, this paper presents new analytical closed-form equations to evaluate the ultimate load and the failure mode of an interior span of a multi-span moment resisting frame, as impacted by the strength of beam–column joints and the elastic and post-elastic structural response of adjacent elements. Taking advantage of derived equations, a retrofitting design procedure to identify the proper structural strengthening of critical regions is proposed. The accuracy of the method is checked through a comparison with numerical results. The procedure represents a new useful tool for engineers for the local strengthening of existing reinforced concrete buildings. • The failure load and mechanism of RC multi-span moment-resisting-frames are investigated. • Ductile post-elastic response of members and brittle failure of joints are considered. • Closed-form equations, to evaluate the ultimate load, are proposed. • The approach is validated through comparisons with numerical results (FEM). • To achieve a designed safety target, the proper structural strengthening is identified. [ABSTRACT FROM AUTHOR]

Steel bracing systems are usually introduced to assure the structural stability and seismic resistance of steel storage pallet racks, whose height over the last years has increased more and more to improve warehouse efficiency. In the present paper, the axial response, under monotonic and cyclic load, of perforated cold-formed steel diagonals of concentric bracing systems is investigated through experimental tests. To satisfy the design and detailing rules required by the capacity design approach, such as the ratio between overstrength coefficients and the value of the non-dimensional slenderness, tested diagonals are equipped with additional holes at one end. Results of monotonic tests, under compression and tensile load, provide useful information about the influence of the number and shape of holes on the ultimate strength, ductility and buckling load of bracings. Cyclic tests highlight how the member slenderness and the class of its cross-section affect hysteresis loops and energy dissipation. Finally, some novel considerations are presented concerning the influence of the shape, dimensions and distance of additional holes, in addition to member geometrical features like the cross-section class, on the cyclic response of tested members. In the framework of the "Design Assisted by Testing", results could be adopted for the capacity design of perforated concentric cold formed diagonal bracings as those adopted in steel storage pallet racks. • The axial response of CFS members with holes is experimentally investigated. • The effect on the ductility of holes, member compactness and slenderness is shown. • Segment with additional holes represents a ductile fuse for investigated members. • Ductility of very slender class 3 specimens is comparable to class 2 specimens. • Energy dissipation of class 3 specimens is lower than class 2 specimens. [ABSTRACT FROM AUTHOR]

Abstract Steel storage pallet racks are used worldwide for storage of palletized goods and are popular for their ease of construction, customization, and economy. Failure of these racks can result in significant property loss and economic disruption. Ultimately, the structural behaviour of these systems can be characterized as braced systems, in the cross-aisle direction, and un-braced moment resisting frame systems, in down-aisle direction. The structural capacity of these moment resisting frames depends on the performance of beam-to-column connections. Rack connections are typically formed by beams welded to connectors with tabs and columns with perforated cross-sections to accept these tabs joining beams and columns without bolts. This paper aims to evaluate the influence on the structural response of rack connection due to the structural details, and randomness in the geometrical features and mechanical properties of connection members (beam, weld, connector and column). To explore the impact of variability in design parameters on the initial flexural stiffness and ultimate flexural capacity of rack connections, a Monte Carlo simulation was conducted, using the Component Method to model the connection. Variability in member geometrical features was determined from current design specifications, while variability in steel mechanical properties was determined via experimental tests. The results indicate that system effects reduce flexural stiffness and the variability in the response of individual components does not propagate to the overall flexural capacity. Ultimately, the work motivates accurate and thorough reporting of geometric and structural uncertainty to accurately assess rack connection performance. Highlights • Monte Carlo simulation is conducted to explore the impact of variability in design parameters on the structural behaviour of rack joints. • A mechanical model based on the Component Method is used to model the connection structural response. • Results indicate that system effects reduce connection flexural stiffness. • The variability of geometric and mechanical properties mitigates in the evaluation of the connection ultimate moment. • Connector is the most critical feature which should be controlled with greater accuracy in the manufacturing process. [ABSTRACT FROM AUTHOR]

Highlights • The rotation required by structural elements to perform a plastic design is evaluated. • The proposed approach allows to the failure mode of the structure to be predicted. • Information on the more efficient configuration of additional bolts are provided. • Theoretical results are applied to rack joints tested in an experimental campaign. Abstract The structural behaviour of beam-column joints plays a critical role in the seismic response of frame structures. In the case of steel rack systems, uprights (columns) are usually 3rd or 4th class open thin-walled cold-formed steel members according to Eurocode 3, as such, local buckling occurs before the plastic moment resistance (in the case of the 3rd class) or yield stress (4th class) is achieved. Beams are usually 1st or 2nd class, so they can form a plastic hinge with the rotation capacity required from plastic analysis without reduction of the resistance (1st class) or with a limitation on the rotation capacity due to local buckling (2nd class). For this reason, only beams and connections, which can be easily equipped with additional bolts to increase their structural performance, can provide a post-elastic behaviour with energy dissipation. This paper presents and develops a method capable of evaluating the rotational capacity, or ductility, required by beams and connections to perform a plastic design. The proposed approach allows for the failure mode of the structure to be predicted starting from mechanical properties of structural members, and it is valid for both service and seismic loads. The analytical method could be applied to different structural systems and materials; in the present work it is presented with reference to industrial pallet racks. Theoretical assessment herein of the required plastic rotation for beams and connections provides useful information for bolted connection design to increase capacity of the racks with minimal additional cost. [ABSTRACT FROM AUTHOR]

In this work we analyze the convergence of the elastic coefficients in terms of the residuals as the dimensions of the sample of a random two-dimensional medium vary. In particular, the case of the masonry material which can be considered a heterogeneous solid with two phases (stones or bricks and mortar) is taken into account. In particular, we consider a masonry which presents a quasi-periodic micro-structure. A procedure of numerical generation of wall portions has been developed which takes into account not only the scale ratio but also the mechanical ratio and the geometrical ratio. The convergence of residuals has been highlighted in terms of probability density function and statistical moments, up to the second order, of the stiffness coefficients and of the log-Euclidean distance between the masonry samples and the closest isotropic material. [ABSTRACT FROM AUTHOR]

Steel storage pallet racks are characterised by the extensive use of thin-walled cold-formed steel members and boltless beam-column connections, whose structural behavior plays a key role in the seismic response of rack systems. Due to the great variety of connector types and member geometries, the current design codes require experimental tests on rack connections to obtain their mechanical characteristics. The drawback is that these experimental procedures are expensive and time-consuming. In this paper a theoretical mechanical model, based on the application of the Component Method (CM), is proposed with the aim to assess the flexural resistance and initial elastic stiffness of rack connections. Results are compared with experimental data collected in an experimental campaign carried out on several full-scale joints, belonging to different types produced by the same manufacturing company. The comparison highlights the accuracy of the proposed model that permits the weakest component of the joint and its failure mode to be evaluated. The CM provides fundamental information about the influence of structural details on the joint behavior, and it could be used in the design of rack connections to improve their structural response. The proposed mechanical model appears appropriate for predicting features of studied connections and especially for analyzing main components, which influence the initial rotational stiffness and the ultimate bending moment of rack connections. Finally the proposed model can be easily modified to be used in the analysis of other connector types, as only a limited number of structural and geometrical data are required for its definition. [ABSTRACT FROM AUTHOR]

Pallet racks are characterized by boltless beam-column connections and the extensive use of thin-walled cold-formed steel members. Due to the great number of beam-end connector types and member geometries, a reliable evaluation of their structural behavior, especially under seismic loads, requires a thorough modeling of beam-column joints, whose moment-rotation curves can be reliably assessed only through experimental tests. In this paper, the authors present results of monotonic and cyclic tests on four different types of industrial rack joints. Tested joints differ from one another in the type of beam-connector, which is obtained by folding the beam end or is welded to the beam-end section with different welding layouts. Moreover, joints differ in the number of tabs and the relative thickness of the upright and the beam-end connector. Experimental results from cyclic tests allows for moment-rotation curves of joints to be accurately identified, confirming that they are significantly different from traditional steel framed buildings due to pinching in hysteresis loops. Obtained curves can be used for reliable modeling of joints in seismic analyses of steel pallet racks. As producers of steel rack structures are interested in reducing the total welding length of beam-end connectors for time efficiency and cost saving, the influence of the welding layout of beam-end connectors on the structural response and failure mode of joints has also been investigated. Finally, some joints have also been equipped with additional bolts to evaluate their influence on the bearing capacity, initial elastic stiffness and dissipated energy per cycle. [ABSTRACT FROM AUTHOR]

In this paper, the effect of geometric irregularities on the dynamic response of circular masonry arches is considered. Irregular geometries are obtained through a random generation of the key geometric parameters, and the effect of these irregularities is shown by modelling the dynamic response to ground motion. The masonry arch is modelled as a four-link mechanism, i.e., a system made of three rigid blocks hinged at their ends, where the position of the hinges at the instant of activation of the motion is determined through limit analysis. Lagrange’s non-linear equations of motion have been solved through numerical integration. The results show that geometrical uncertainties produce an alteration of the mechanical features of the rigid blocks which may reduce the seismic capacity. [ABSTRACT FROM AUTHOR]

Accurate and reliable predictions of the dynamic behaviour of dams is essential to ensure their correct management and the safety of the downstream population. In this context, structural monitoring and testing procedures for their dynamic characterization are essential tools for the calibration of numerical models of dams. This paper presents some results of an ongoing research program aimed at an accurate definition of the geometric and structural properties of a large arch-gravity dam: the Ridracoli dam in the Emilia-Romagna region, Italy. In the first part of the research, a detailed survey carried out by an Unmanned Aerial Vehicle has allowed the detailed reconstruction of the three-dimensional geometry of the structure. The dense point cloud, as provided by the aerial survey, has been the base for the definition of a high-fidelity finite element model, including the dam, the surrounding rock mass, with a detailed reconstruction of the site topography, and the reservoir water, whose dynamic interaction with the structure is modelled by means of acoustic elements. A large program of structural monitoring, including a number of vibration tests, has been performed on the Ridracoli dam during the last thirty years. The dynamic monitoring system includes accelerometers, located in the structure and in the foundation rock mass, strain gauges and hydrodynamic pressure cells. The forced vibration tests were carried out in correspondence to the maximum water level, in order to identify the dynamic characteristics of the dam. The mechanical properties of the dam material and of the foundation rock are calibrated by comparing model predictions with the results obtained from vibration tests and from acceleration recordings acquired under recent seismic events, considering the actual water levels registered during the tests. The finite element model obtained will allow the simulation of the seismic performance of the dam under different design earthquakes. The assessment of the effects of the reservoir level and of the vertical joints on the dynamic response of the structure will be analysed. [ABSTRACT FROM AUTHOR]

This paper aims to evaluate the effect of the geometrical uncertainties on the collapse condition of the circular masonry arch in presence of horizontal actions. Adopting Heyman’s hypotheses about the material, a limit analysis based procedure has been developed in order to evaluate the horizontal loads multiplier, taking into account the uncertainties related to the imprecisions of construction, the shape defects of the voussoirs or the deterioration level. The collapse state has been determined in terms of horizontal loads multiplier, whose statistical moments up to second order and probability density functions have been evaluated versus a stereometry parameter. The comparison between the obtained results and those related to the nominal geometry highlighted that the uncertainties effects could reduce significantly the nominal bearing capacity of the structure. Within this context, a safety factor, which takes into account such effects, is introduced. [ABSTRACT FROM AUTHOR]

• A steel bracing system dissipates the seismic energy through moment-rotation hysteresis loops of a fuse. • Cyclic tests and numerical analyses are performed to investigate the behaviour of the proposed system. • The influence of design parameters on the energy dissipation capacity of the system is investigated. • The easily replaceability of the fuse, while ensuring ductile system response, is assessed. • The fulfilment of limitations on the overstrength coefficient by simply changing the fuse cross-section is highlighted. According to the capacity design method, earthquake-resistant structures should be able to dissipate energy through dissipative regions, which are expected to yield while the other structural members remain in the elastic field during seismic excitation. The non-linear response of a bracing system, in which energy dissipation relies on a fuse, is investigated through experimental tests and numerical analyses. Loading on the fuse is a combination of bending moment, axial, and shear load. Results provide valuable information on the influence of several design parameters, such as the member cross-section compactness, shape, and member slenderness. The stability of the moment-rotation hysteresis loops and the energy dissipation are assessed through cyclic tests. To promote the utilization of the proposed bracing system in earthquake resistant steel structures, the work concludes by highlighting that the fuses are easily replaceable while ensuring ductile system response. [ABSTRACT FROM AUTHOR]

This paper aims to evaluate the limit equilibrium condition and the minimum thickness of masonry arches in presence of horizontal loads. The analysis fits into the frame of limit analysis referring to Heyman's theory. Two types of arches are analysed, the circular and pointed one. The loading system consists of vertical and horizontal loads, which refer respectively to the self-weight of the voussoirs and to the seismic actions. The collapse mechanism and the corresponding horizontal load multiplier are determined, in the condition of rigid abutments, as functions of the geometrical features of the structure. The results are supported by some simple experimental tests and a sensitivity analysis, which considers the effect of geometrical irregularities on the load multiplier. [ABSTRACT FROM AUTHOR]

In order to evaluate seismic vulnerability of existing reinforced concrete buildings, a simplified approach is proposed to take into account the beam-column joints shear collapse. This collapse is described by a link element which is introduced between column and beam. To develop and verify this element, several comparisons have been performed with experimental results of laboratory test and numerical results obtained by a two-dimensional finite element model specifically carried out for this check. The link element uses a tri-linear moment–rotation law, compatible with standard Italian and European codes, whose features can be estimated by limited structural and geometrical information, which is a typical situation on older existing structures, and by standard code recommendations. In order to give a preliminary evaluation of the seismic capacity for existing R.C. frames, taking into account the beam-column joints behaviour, this link element has been introduced in a one-dimensional model of bearing structure of the Unit N.1 of the Santa Maria Annunziata Hospital in Florence (Italy) and pushover analyses have been carried out. [ABSTRACT FROM AUTHOR]

Industrial cold-formed steel pallet racks are constructed of upright frames bolted to braces in the cross-aisle direction. The flexibility and resistance of these brace-to-upright joints play a key role in the structural behavior of pallet racks in the cross-aisle direction. In this paper, the behavior of these joints has been evaluated through monotonic and cyclic experimental tests to determine the dominant failure modes and the stiffness. The resultant cyclic structural response is pinched, which suggests that upright frame connections are non-dissipative. An analytical model based on the Component Method has been developed to evaluate the ultimate resistance and the flexibility of these bolted connections, with braces oriented flange-to-flange. The model is capable of identifying the influence of each component on the connection structural response. A comparison with results obtained by a Finite Element numerical model, typically used in common practice, in which members are modelled by elastic frame elements and connections are assumed rigid is conducted. The numerical model overestimates the effective stiffness by nearly 14 times. The same model, when modified with a linear link with a force-displacement response determined from the analytical model, provides reliable results in agreement with the experiments. The developed modelling approach is recommended for adoption by practitioners for the design of steel storage pallet racks. • The flexibility and resistance of brace-to-upright joints is investigated. • Monotonic and cyclic experimental tests are performed. • Upright frame connections are non-dissipative. • An analytical model based on the Component Method has been developed. • The modelling approach is recommended for the design of steel racks. [ABSTRACT FROM AUTHOR]

Summary Background During recent years scientific research has demonstrated a growing interest in elastic and anaelastics adhesive taping techniques. However, only a few studies investigating the principles behind the effects of taping. At present, the action mechanisms of kinesiology taping remain speculative. Objectives To investigate the effects of taping application on the tone of the pectoralis major muscle at rest, in absence of any relevant pathologies. Methods and measures The study involved a prospective, randomised and blinded clinical trial on healthy individuals and a repeated measures study design. Two different taping techniques (facilitatory and inhibitory) were applied over the pectoralis major of 24 healthy volunteers. The outcome measure was passive range of motion of external rotation of the glenohumeral joint. Results Facilitatory taping significatively enhanced the activity of the underlying muscle. Results showed a negative correlation between facilitatory taping application and the contralateral pectoralis major length, indicating a possible effect on the muscle tone of areas outside the site of direct application. The inhibitory taping application did not produce significant results. Conclusions effects on ipsilateral and contralateral muscle physiology could be interpreted through the initial hypothesis of taping inducing changes in fascial stiffness. These could be transmitted along the continuing system. Further studies are needed to inform the possible uses of taping in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: In this paper the estimation of residuals for the homogenized solution in elastic problem is taken into account. The case of the beam with Young's modulus randomly varying along the axis is considered. The analysis is performed by means of numerical simulation which is validated by comparison with particular solutions reported in the literature. The convergence to the homogenized solution and the behavior of the residuals are studied in terms of the parameter ɛ, which represents the ratio between the microscopic and the macroscopic scale. After validation with the literature results, the procedure is used to analyze the influence on the convergence of the correlation law of Young's modulus with log-normal distribution. Moreover the particular case of the two-phase beam is considered. The effect of different boundary conditions is also investigated. [Copyright &y& Elsevier]

• The required rotation to perform a plastic analysis is analytically evaluated. • The effective rotational capacity of RC beams is analytically assessed. • The impact of the rotation uncertainty is highlighted by the Monte Carlo simulation. • The rotation ductility has a greater dispersion than the ultimate moment. • The reliability of the Eurocode moment redistribution procedure is investigated. Design codes allow the moment redistribution in reinforced concrete (RC) beams through the moment redistribution factor. The advantages of performing a moment redistribution are to prevent the congestion of rebars at critical sections along the beams, to allow a more even distribution of rebars along the length and to increase the load carrying-capacity, exploiting the plastic rotation of RC sections. The redistribution requires that sections, in which plastic hinges form, provide the required rotation ductility. The required rotation to perform a plastic analysis with complete moment redistribution and the effective rotational capacity of RC sections are both analytically evaluated with the related load-carrying capacity. A probabilistic analysis by means of the Monte Carlo simulation is performed to assess as the rotation ductility is impacted by the uncertainty in mechanical and geometric parameters and its influence on the ultimate load. The probabilistic analysis shows a greater dispersion in predicting both the rotational capacity and related ultimate load than the member ultimate moment. A reliability analysis on the evaluation of the load carrying-capacity of a RC frame according to the Eurocode moment redistribution procedure is performed. Results highlight the Eurocode to be nonconservative suggesting of reviewing the limit on the normalized neutral axis depth to perform a plastic analysis without explicit verification. [ABSTRACT FROM AUTHOR]

Abstract: Background: We conducted a multicenter prospective trial to assess tolerability and activity of pegylated liposomal doxorubicin (PLD) in women ≥70years with locally-advanced or metastatic breast cancer. Patients and Methods: All patients underwent Multidimensional Geriatric Assessment (MGA). Frail patients were excluded. Normal cardiac function was required for inclusion. A bi-weekly schedule of PLD at 20mg/mq was adopted. Results: Thirty-two patients were enrolled with a median age of 78years, 78.1% with visceral involvement, and 37.6% previously treated with chemotherapy for advanced disease. A mean of 7.8cycles were delivered (range 1 to 20), with a median cumulative dose intensity of 8.9mg/m2/week. Grade 3–4 toxicities were anemia (6.3%), palmar–plantar erythrodysesthesia (6.3%), mucositis (6.3%), infection (3.1%), and pulmonary embolism (3.1%). No cardiac events were registered. Causes of treatment interruption were maximal response (15.6%), progression (40.6%), refusal/loss to follow-up (28.1%), toxicities (9.4%), or other (6.3%). Response was obtained in 33.3% of 27 evaluable patients; median time to progression (TTP) was 10.3months. MGA status (vulnerable vs. fit) did not have an impact on response, progression, and toxicity. Conclusions: Bi-weekly PLD is well tolerated in both fit and vulnerable patients, with an apparently fairly good response rate and TTP (possibly biased by subsequent endocrine therapy and loss to follow-up). Close observation of patients is recommended in order to avoid early refusal/loss to follow-up. [Copyright &y& Elsevier]

Abstract: In this paper the results of experimental tests in a boundary layer wind tunnel aimed at direct comparison of the two main methods used to estimate the wind loads acting on tall buildings are presented. The tests were performed on two different models of tall buildings: a regular one with a prismatic shape; an irregular one whose external shape was inspired by that of Bank of China Tower in Hong Kong. The two models have the same square footprint and height. The two methods used to measure the wind effects were: the high frequency force balance, which allows to directly measure the global base reactions (two forces in the plane of the base, the two overturning moments and the torsional moment around the vertical axis); the synchronous multi-pressure sensing system, which measures the pressure in several points on the surface of the model, and allows, by means of numerical integration, to estimate both the floor loads and the base reactions. In order to perform a comparison between the results obtained by the high frequency force balance and synchronous multi-pressure sensing system a statistical analysis of the results was carried out; in particular, higher order moments were investigated. Moreover the spectra and the correlation structure of the loads were studied. [Copyright &y& Elsevier]

The introduction of the Japanese beetle (Popillia japonica Newman) in Italy raised concerns for its control in herbaceous and perennial crops, nurseries and landscape plants. During the early stages of spread of an invasive pest, the availability of effective insecticides is essential to sustain the immediate needs of plant protection. Here, we screened the effects of 20 active ingredients representative of chemical and organic insecticides registered in Europe for adult beetle management on high-value crops (grapevine, peach and corn) and landscape plants (willow and Virginia creeper) by field trials carried out in 2019 and 2020. Plant parts suitable for spraying were sleeved and beetles were caged before the application (contact effect), after the application but on the same day (residual, short-term effect), and 7–8 days after the application (residual, long-term effect). Among the 20 active ingredients tested, only four broad-spectrum (acetamiprid, deltamethrin, lambda-cyhalothrin and phosmet) were effective in killing beetles under all the experimental conditions, while other broad-spectrum and selective ingredients were mainly effective only on contact and as short-term residual. The organic active ingredients were much less effective under any condition. The data provide a valid support to update the European guidelines aimed at controlling P. japonica for growers, landscape managers and homeowners. The low selectivity of the most effective insecticides requires the integration into management strategies that envisage their use only whether strictly necessary, and in combination with other containment measures. [Display omitted] • Contact and residual effects of chemical and organic insecticides were tested on Popillia japonica adults. • Broad-spectum chemical insecticides were effective in killing beetles on contact and residual application. • Selective and organic insecticides did not always result in a significant beetle mortality under all conditions tested. [ABSTRACT FROM AUTHOR]

Abstract: A numerical model was developed to analyze the main characteristics of the dynamic behavior of cables under wind loading. The model accounted for non-linear geometrical effects and it was developed using the finite element method, performing the analysis in the time-domain by a direct integration method. The results obtained from the numerical model were compared to those derived from several wind-tunnel experimental tests on a scale model of the cable. The tests were performed both in laminar and in turbulent flow, and the axial force at the supports and the overall drag force, together with mid-span displacements, were logged. Moreover, the data by experimental tests allowed an estimate of the wind action on the cable, which was used to load the numerical model. The analysis was performed considering both wind mean action and dynamic effects due to wind fluctuations. The comparison between numerical and experimental results was made. [Copyright &y& Elsevier]

Abstract: This paper presents a parametric investigation of the axial fatigue performance of suspended cables subjected to lateral wind-induced vibrations. An up-to-date literature review of cable fatigue is followed by numerical analysis of the total axial fatigue damage produced by different out-of-plane wind excitations on cables with different initial sags. The fatigue damage is calculated in the time domain through an adequate cycles counting method. A discussion of the influence of the Irvine parameter on the total fatigue damage is then performed. The results may be adopted to compare the risk of fatigue ruptures occurring in suspended cables (such as transmission power lines) with different Irvine parameters. The numerical simulations are conducted using a tridimensional geometric nonlinear finite element model, experimentally validated in previous works. The turbulent wind field is simulated as a multivariate mono-dimensional Gaussian process. The investigation first explores the case of uncorrelated nodal drag forces and it is then extended to statistically correlated ones. A stochastic analysis of the cable responses under different wind loads is also proposed to discuss the hypothesis of Gaussian distribution. [Copyright &y& Elsevier]

Abstract: Genetic analysis aims to identify the variations in DNA sequence whose functional consequences produce heritable variations in phenotype. In one of the first successes of unbiased molecular genetic analysis in human disease, the Huntington''s disease (HD) gene was mapped and cloned without any prior knowledge of the nature of its protein product or of the molecular defect that underlies the characteristic phenotype of the disorder. However, while the cloning of HD and recognition of its trinucleotide repeat expansion spawned a plethora of approaches to investigating HD through its distinctive neuropathology, the role for genetic strategies in HD research did not end there. The use of genetic analysis has remained a critical tool for defining the characteristics of the mechanism that triggers the pathogenic process, permitting the investigation of early events that occur long before traditionally recognized pathology. Delineation of these events can reveal molecular targets for development of therapies that prevent onset of HD. Most recently, an extension of genetic analysis to the identification of non-linked genetic variations that alter the course of HD pathogenesis has offered the promise of identifying modifier genes to reveal biological pathways active throughout the disease process and to provide valid targets for pharmacological intervention. Thus, unbiased genetic strategies have not only provided a crucial entrée into molecular investigation of HD via a root cause that was previously unsuspected, they also represent a continuing route to accelerate the ultimate goal of developing an effective treatment for HD. [Copyright &y& Elsevier]

Thirteen years ago, the culmination of genetic rather than biochemical strategies resulted in the identification of the root cause of Huntington''s disease: an expanded CAG trinucleotide repeat that leads to an elongated polyglutamine tract in the huntingtin protein. Since then, biochemical and cell biological attempts to elucidate pathogenesis have largely focused on N-terminal polyglutamine-containing huntingtin fragments. However, continued application of genetic strategies has suggested that the disease process is, in fact, triggered by the presence of expanded polyglutamine in intact huntingtin. An increased emphasis on the earliest presymptomatic stages of the disease, facilitated by incorporating genetic lessons from human patients into the search for biochemical targets, could provide a route to a rational treatment to prevent or slow the onset of this devastating neurodegenerative disorder. [Copyright &y& Elsevier]

Experimental tests were performed to evaluate forces and aerodynamic coefficients on a typical cable-stayed mast used for removable base stations (so-called raw land sites). The results were obtained using the wind tunnel facility at the University of Perugia. Different prototype-scale models (1:1) representing portions of the structural system were tested, varying the oncoming wind direction and measuring the drag and lift forces. The drag and lift coefficients were calculated in order to obtain a reliable wind load model on the whole structure. The structural response of the raw land site was estimated by numerical calculations using the experimental load model and the results were compared to those obtained using code prescriptions. Finally, a sensitivity analysis was performed varying the incoming wind direction to evaluate the effect of the lift forces on the structural response. [Copyright &y& Elsevier]

A homogenization approach to assess the mechanical characteristics of masonry structures is presented in this paper. In order to analyze an actual masonry, the concept of periodic cell, used in literature for periodic masonry, is replaced with that of representative volume element. This volume is found by employing a formulation based on finite size test-windows. The homogenized medium stiffness tensor is obtained by considering the hierarchy of estimates relative to essential and natural boundary conditions. Moreover an ensemble average is performed on space taking into account different test-windows location on the given structure. An application shows the effectiveness of the proposed approach. [Copyright &y& Elsevier]

Familial dysautonomia is a developmental disorder of the sensory and autonomic nervous system. Recent studies have shown that two mutations in the gene IKBKAP are responsible for the disease. IKAP, the IKBKAP-encoded protein, is a member of the recently identified human Elongator complex. The major FD mutation is a splice mutation that results in aberrant tissue-specific mRNA splicing. [Copyright &y& Elsevier]

In vivo gene transfer to kidney by lentiviral vector. Background. The growing understanding of the molecular basis of renal diseases makes the development of gene therapy for kidney disorders a potential treatment alternative. Work aimed at determining the feasibility and the efficiency of gene transfer to the kidney using different viral and nonviral transduction systems is a necessary component to understanding the full potential. Lentiviral vectors have been shown to transduce stably different tissues and cell types that are refractory to other gene transfer approaches. To date, the potential of lentiviral vectors to transfer genes in kidney has not been investigated. The scope of this work was to analyze the efficiencies of in vivo transduction of kidney by a lentiviral vector. Methods. A pseudotyped lentiviral vector carrying the gene for the enhanced green fluorescent protein (EGFP) was delivered into one kidney of experimental mice by retrograde infusion through the ureter. The presence of the virus and the expression of the reporter protein were monitored over time. Results. Both viral DNA and EGFP expression were measurable in the kidney infused with the lentiviral vector but not in the contralateral kidney. Protein expression was detected by immunostaining, as EGFP fluorescence was masked by the high background fluorescence of the kidney. Expression of EGFP persisted for the entire two-month duration of the experiments. Conclusions. Lentiviral vectors can effectively deliver exogenous genes to the kidney in vivo, resulting in persistent expression of the introduced gene. [ABSTRACT FROM AUTHOR]

• Three-point bending tests to investigate the behaviour of steel beams are performed. • The influence of design parameters on the member energy dissipation is investigated. • The effect of the cross-section compactness and member slenderness is explored. • Different cross-sections belonging to class 1 show different rotation and failure mode. • The seismic performance and adequacy of tested beams as braces is highlighted. In the capacity design method, earthquake resistant structures should have the ability to dissipate energy in plastic mechanisms through dissipative zones, which are expected to yield while the others remain in the elastic range during seismic excitation. In this paper, the elastoplastic response of different steel beams in three-point bending, under monotonic and cyclic loads, is investigated through experimental tests and theoretical analysis to investigate their efficacy to be used as fuses in an innovative bracing system. Results provide useful information on the influence of several design parameters such as the geometrical properties of members, the steel strength-strain behavior, the connection structural details and the geometric non-linearity. The stability of the moment-rotation hysteretic loops and the energy dissipation is assessed through cyclic tests. The influences of the cross-section compactness and member slenderness are also investigated. Within the "Design Assisted by Testing" framework, the results highlight the role of member cross-section shape. Double channel sections have a greater rotation capacity than rectangular hollow sections with the same elastic section modulus and of the same section class. Moreover, the influence of the connection details is explored. To promote the utilization of the proposed bracing system, the work concludes with design recommendations. [ABSTRACT FROM AUTHOR]

The paper proposes an approach to model the geometrical uncertainty in case of curves in space. After highlighting the importance of the geometrical uncertainty in various fields of mechanics, the random set of "irregular or imperfect curves" is analysed in the natural or intrinsic reference system by the formulas of Serret–Frenet. It is shown that the Riccati's random differential operator, in complex domain, describes this random set. The curvature and torsion are modelled by weakly homogeneous random functions with discrete spectrum. Numerical results show the application of the proposed approach. [ABSTRACT FROM AUTHOR]

Lattice structures can provide high strength with modest weight. For this reason, they are found in many natural systems at the microscopic level and have also been adopted in engineering at many scales. Assessment of the load-bearing capacity of such structures is crucial and cannot ignore considerations of imperfections, whether due to natural factors if the material exists naturally or to manufacturing defects if it is created artificially. Defects can affect many geometrical aspects of the lattice such as the shape of cells and the thickness and the waviness of trusses. In this paper, we will focus on the first aspect, investigating the effect of variation of the shape of the cells by applying a perturbation to the periodic configuration for common geometries. The failure load of these systems is evaluated by means of an upper bound limit analysis through linear programming, varying the relative density of the lattice and the intensity of imperfections. The failure load is addressed by statistical moments and probability density functions. • Statistical analysis on bearing capacity of geometrically imperfect lattices. • Several periodic lattice patterns are considered with different relative densities. • Most lattice structures are weaker with imperfections, except the rhomboidal lattice. • The probability density function best suited to represent the samples is discussed. [ABSTRACT FROM AUTHOR]

Summary Most human cancers arise from stem and progenitor cells by the sequential accumulation of genetic and epigenetic alterations, while cancer modeling typically requires simultaneous multiple oncogenic events. Here, we show that a single p53 mutation, despite causing no defect in the mouse brain, promoted neural stem and progenitor cells to spontaneously accumulate oncogenic alterations, including loss of multiple chromosomal (chr) regions syntenic to human chr10 containing Pten , forming malignant gliomas with PI3K/Akt activation. Rictor/mTORC2 loss inhibited Akt signaling, greatly delaying and reducing glioma formation by suppressing glioma precursors within the subventricular zone stem cell niche. Rictor/mTORC2 loss delayed timely differentiation of granule cell precursors (GCPs) during cerebellar development, promoting sustained GCP proliferation and medulloblastoma formation, which recapitulated critical features of TP53 mutant sonic hedgehog (SHH) medulloblastomas with GLI2 and/or N-MYC amplification. Our study demonstrates that Rictor/mTORC2 has opposing functions in neural stem cells and GCPs in the adult and the developing brain, promoting malignant gliomas and suppressing SHH-medulloblastoma formation, respectively. [ABSTRACT FROM AUTHOR]

Highlights • The collapse condition of the masonry arch on spreading support is investigated. • An incremental numerical procedure is developed in finite displacement field. • Geometrical uncertainties of the masonry arch are described by random variables. • Masonry arch with irregularities has lower displacement capacity than nominal arch. • The results obtained by numerical analyses are in agreement with experimental tests. Abstract This work is aimed at evaluating the collapse displacement of masonry arch subjected to spreading supports. This is achieved through a general application of the virtual works principle. The problem is described in a finite displacements formulation and investigated with a probabilistic approach, also considering the effects of the geometrical uncertainties. This aspect is related to the imperfections of the voussoirs, which affect the structural shape. The comparison between the numerical and experimental results, derived both by the literature and laboratory tests, confirms that the geometrical irregularities can significantly affect the results obtained on the nominal structural geometry. Moreover, the disagreement observed in the experimental tests is explained. [ABSTRACT FROM AUTHOR]

Background: Unlike other neurodegenerative disorders, Huntington''s disease, with its motor, behavioral, and cognitive deficits and early loss of neurons in the striatum, has a single cause: expanded versions of a polymorphic CAG repeat in the HTT gene (previously HD) of ≥35 units. This uniform starting point permits the development of therapeutics based solely upon the features of the HTT CAG repeat. Methods, Results, and Discussion: We are applying global methods, such as genome-wide gene expression levels, to discover dominant and CAG length-dependent genes and pathways, using cells and tissues bearing the full-range of HTT CAG allele sizes. These phenotypes can potentially point to small molecule or gene modifiers and can be converted into cell-, pathway- or gene-based assays suitable for high-throughput screens to find modifiers of HTT CAG size-dependent effects in models and humans. This genetic approach to therapeutic target discovery has demonstrated that the HTT CAG repeat is a functional polymorphism that, over the non-HD and the HD ranges, affects energy, RNA metabolism, and the cytoskeleton. These HTT CAG size-dependent signatures provide an unbiased read-out for assays with which to find compounds or genes that may slow or halt the earliest phase of the HD disease process. [Copyright &y& Elsevier]