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Since their launch on the market in the late 1970s, Dual Mobility Cups (DMCs) have shown encouraging results both in terms of stability and of restoration of wide hip joint amplitude. Therefore, the use of DMCs is mainly indicated for patients at risk of dislocation, such as those with neuro-muscular diseases, femoral neck fractures, or complex situations like failed hip osteosynthesis, as well as being indicated in the setting of revisions.The objective of this review is to provide indications and recommendations for orthopedic surgeons using DMCs in complex primary and revision settings. An overview of the tech- nical and theoretical requirements necessary to achieve a successful DMC implantation is presented. According to the literature, indications have been expanded thanks to the constant improvement and development of materials and implants. Nowadays, the use of DMCs is no longer limited to revision surgery alone; on the contrary, increasingly complex cases may be approached. Long-term studies are needed before any formal conclusions can be drawn an before the promising results that have been obtained in difficult cases are consolidated.

Background: The trapeziometacarpal joint is the second joint affected by osteoarthritis in the hand. The symptoms and clinical presentation are characterized by pain, limited range of motion, muscle weakness with loss of strength, bone deformities and disability. The symptomatology often is not related to the radiographic grade of osteoarthrosis. Therefore, in addition to the radiographic stage of the disease, the treatment is influenced by multiple variables such as age, functional requirement, symptoms and stability of the joint. Objective: There are several options of surgical treatments. Although trapeziectomy and its technical variation is the gold standard for treatment, prosthesis replacement can be used with good results. This case report discusses the case of a 70-year-old male who presents bilateral trapeziometacarpal osteoarthrosis treated with two different techniques with different timelines. Methods: The patient underwent a trapeziectomy on the right hand and arthroplasty with implant on the left. In both TMC the stage of the disease was grade III according to the Eaton Litter classification and the results were evaluated according to clinical and radiographic criteria. The NPRS pain scale and the Quick Dash functional scale were used in subsequent checks. The mean follow-up was 12 months. Conclusion: There were no significantly different results with respect to pain, activities of daily living, mobility or strength. No complications were observed. The patient is satisfied with the treatment having found a better and earlier resumption of daily activity of the left hand treated with prosthesis replacement.

Humeral shaft fractures represent approximately 3% of all long-bone fractures and have historically been treated successfully in a non-operative way, but surgical management is indicated in several conditions. Although there are numerous randomized clinical trials and meta-analyses that have attempted to guide surgeons, there is little evidence and no consensus as to the most suitable treatment. Every treatment has its advantages and its complications, and many factors must be considered: not only the features of the fracture, but also patient compliance and surgeon experience.

In mountain environments, landslide sediment supply is one of the main factors that can affect fluvial morphodynamics. In settings underlain by clay-rich lithologies, where earthflows are the dominant agents of hillslope sediment transfer, limited quantitative information is available on the contribution of these processes to the sediment budget. This is a critical aspect both for addressing basic scientific questions on landscape evolution, as well for tackling more applied issues on river sediment management.This study focuses on the mountain portion of the Sillaro River basin (138 km2), a fluvial system underlain by argillites and siltstones of the Ligurian domain, Northern Apennines (Italy). Here, earthflows are the most common landslide type. Through the compilation of a multi-temporal earthflow inventory (1954-2019), we aim to: (i) characterize earthflow source-to-sink sedimentary pathways, with special reference to sediment delivery to ephemeral and perennial streams; (ii) explore possible litho-topographic controls on earthflow size, frequency and recurrence; (iii) examine historical trend of earthflow activity in relation to rainfall variability and land use changes. Finally, the high and extended temporal resolution of the inventory, will offer the opportunity to test how relevant information could complement the existing inventory of the Emilia-Romagna region, for evaluating earthflow hazard and risk potential.Data collection entailed inspection of 12 sequential aerial photo sets (1954, 1969, 1976, 1988, 1996, 2000, 2006, 2008, 2011, 2014, 2016, and 2018), through which earthflows were classified and mapped in GIS environment. This remotely-based activities were complemented by confirmatory field visits on a subset of most recent events. Overall, we have mapped a total of 506 earthflows, which collectively extend over an area of 4.1 km2.Preliminary results show that earthflow size (i.e., total disturbed area) ranges from 400 m2 to 98000 m2, with frequencies peaking around 10000 m2. In terms of source-to-sink pathways, we find that earthflows chiefly tend to deliver sediment to ephemeral gully channels (61%) and perennial tributaries (25%). Whereas, 5% of the events remain on the slopes, and another 5% are buffered by roads and similar anthropogenic barriers. Only a very limited proportion of earthflows (4%) makes it directly to the Sillaro River main stem.This work, as part of the projects BEDFLOW and BEFLOW PLUS, is partially funded by Fondazione Cassa di Risparmio in Bologna.

The importance of soil moisture conditions in the initiation of landslides has been widely recognized. This study takes advantage of the distributed hydrological model to derive the soil wetness index. The derived soil wetness index is then used to determine soil wetness thresholds for landslide occurrences. In order to predict landslides based on alert zones, a zone threshold is introduced together with the soil wetness threshold to constitute the integrated threshold. We evaluate the prediction performance of the integrated thresholds with the use of skill scores and the receiver operating characteristic (ROC) curves. This study is carried out in a sub-region of the Emilia-Romagna region, Northern Italy. Results show that the derived soil wetness index could account for the hydrological process that is controlled by meteorological conditions and topographic properties. The proposed integrated threshold shows a better predictive capability than the rainfall threshold, demonstrating the effectiveness of applying the soil wetness index in landslide predictions. The optimal threshold is also determined by compromising the correct predictions and incorrect predictions, it is found that the optimal integrated threshold is more advantageous in reducing false alarms compared with the optimal rainfall threshold. This study highlights the potential of applying hydrological simulations in landslide prediction studies and provides a new way to make use of high-resolution data in zone-based landslide predictions.

Chen et al. show that XLF functions to limit fork reversal during DNA replication. H2AX prevents MRE11-dependent replication stress in XLF-deficient cells, suggesting that H2AX prevents the resection of regressed arms at reversed forks., XRCC4-like factor (XLF) is a non-homologous end joining (NHEJ) DNA double strand break repair protein. However, XLF deficiency leads to phenotypes in mice and humans that are not necessarily consistent with an isolated defect in NHEJ. Here we show that XLF functions during DNA replication. XLF undergoes cell division cycle 7–dependent phosphorylation; associates with the replication factor C complex, a critical component of the replisome; and is found at replication forks. XLF deficiency leads to defects in replication fork progression and an increase in fork reversal. The additional loss of H2AX, which protects DNA ends from resection, leads to a requirement for ATR to prevent an MRE11-dependent loss of newly synthesized DNA and activation of DNA damage response. Moreover, H2ax−/−:Xlf−/− cells exhibit a marked dependence on the ATR kinase for survival. We propose that XLF and H2AX function in series to prevent replication stress induced by the MRE11-dependent resection of regressed arms at reversed replication forks.

Open fractures management has always been one of the main challenges in traumatologic surgery: definition of the most appropriate therapeutic protocol is a research and debate topic. Infectious risk minimisation, soft-tissue damage resolution, fracture reduction and fixation are the main objectives in order to recover anatomical and functional integrity of the involved district. Management protocols are characterized by the contrast between an early total care approach and a gradual damage control approach. Gustilo-Anderson classification is still the most widely used in order to set open fractures management, but its limitations have led to the development of other important classifications. This article, through a literature review, aims at summarising main classifications and state of the art on open fractures treatment and at highlighting latest protocols and technical solutions adopted: negative wound pression therapy, antibacterial coated nails and other innovative devices.

Landslides are widespread geological features in Italy’s Northern Apennines, with slow-moving earthflows among the most common types. They develop in fine-grained rocks and are subject to periodic rainfall-induced reactivations alternating to phases of dormancy. In this paper, we use radar interferometry (InSAR) and information about landslide activity to investigate deformation signals on an areal basis and to assess the dynamics of recently reactivated earthflows. We use traditional two-pass interferometry by taking advantage of the short revisit time of the Sentinel 1 satellite to characterize 4 years of slope deformations over the 60 km2 study area, where 186 landslides are mapped. Our results show that most intense and sustained deformation signals are associated with phenomena on the verge of reactivation, indicating that radar interferometry may have a potential for early warning purposes. By focusing on three specific earthflow reactivations, we analyze their dynamics through the years that preceded their failure. Despite inherent uncertainties, it was possible to retrieve the deformation signal’s temporal evolution, which displayed seasonally recurring accelerations, peaking during the major precipitation episodes in the area.

This casebook deals with the basic principles of the Italian business law and focuses on certain recent and pivotal cases in which important rules governing the modern public company have been applied. After a short overview of the main corporate and securities laws and regulation applicable to Italian listed companies, certain leading cases which triggered the application of such rules are analyzed. The main interrelationships between and among the economic and legal elements are scrutinized for the purpose of highlighting the economic logic underlying corporate law. In the financial markets’ dynamics, the public company plays a vital role since it attracts the public savings coming from the investors in order to finance business plans and strategies which create growth and welfare. In such a scenario, financial intermediaries must act in the interest of the investors, selecting among the potential issuers those who are the most attractive for their clients. When companies are structurally organized to attract standardized equity or debt investments, by issuing listed shares, bonds or other financial instruments, their operational and governance rules change in order to safeguard the public savings coming from the investors. In the end, what makes this branch of law so interesting to students, practitioners, and scholars alike is the open-textured relationship between corporate law and securities regulation which plays a crucial role in such context. The cases selected in the second part of this book deal with significant topics in the Italian market practice and are briefly commented making reference to an updated set of laws and references. Therefore, this book can be used also with a focus on comparative legal systems for corporations taught in Italy or abroad.

In the Dolomitic region, abundant coarse hillslope sediment is commonly found at the toe of rocky cliffs. Ephemeral channels originate where lower permeability bedrock surfaces concentrate surface runoff. Debris flows initiate along such channels following intense rainfall and determine the progressive erosion and deepening of the channels. Sediment recharge mechanisms include rock fall, dry ravel processes and channel-bank failures. Here we document debris flow activity that took place in an active debris flow basin during the year 2015. The Cancia basin is located on the southwestern slope of Mount Antelao (3264 m a.s.l.) in the dolomitic region of the eastern Italian Alps. The 2.5 km2 basin is incised in dolomitic limestone rocks. The data consist of repeated topographic surveys, distributed rainfall measurements, time-lapse (2 s) videos of two events and pore pressure measurements in the channel bed. During July and August 2015, two debris flow events occurred, following similarly intense rainstorms. We compared rainfall data to existing rainfall triggering thresholds and simulated the hydrological response of the headwater catchment with a distributed model in order to estimate the total and peak water discharge. Our data clearly illustrate how debris entrainment along the channel is the main contributor to the overall mobilized volume and that erosion is dominant when the channel slope exceeds 16°. Further downstream, sediment accumulation and depletion occurred alternately for the two successive events, indicating that sediment availability along the channel also influences the flow behaviour along the prevailing-transport reach. The comparison between monitoring data, topographical analysis and hydrological simulation allows the estimation of the average solid concentration of the two events and suggests that debris availability has a significant influence on the debris flow volume. © 2020 John Wiley & Sons, Ltd.

Earthflows are clay-rich, slow-moving landslides subjected to periodic accelerations. During the stage of rapid movement, most earthflows exhibit a change in behavior from a solid to a fluid-like state. Although this behavior has been extensively documented in the field, the mechanism leading to the rapid acceleration of earthflows is still poorly understood. Some studies suggest that earthflows essentially behave as Coulomb plastic solids, attributing the flow-like appearance to distributed internal shearing; others believe that these landslides can be treated as viscous fluids, pointing out that the material undergoes a phase transition by increasing its moisture content. Minimal data are currently available to support these different findings. In this study, we present the results of periodic and continuous measurements of Rayleigh wave velocity carried out in an active earthflow located in the northern Apennines of Italy. Our data indicate that the material undergoes significant changes in shear stiffness and undrained strength during rapid movements. In particular, the material exhibits a substantial drop of Rayleigh wave velocity as the earthflow accelerates, followed by a slow return to predisturbance Rayleigh velocities as the landslide decelerates. Soon after a surge, the earthflow material is extremely soft and the estimated gravimetric water content is above the liquid limit. In the following months, the shear stiffness gradually increases and the water content decreases to the plastic limit following a nonlinear trend typical of a consolidation process. These data demonstrate that the earthflow transforms into a viscous fluid by softening of the material and by water entrainment.

Besides its role in homologous recombination, the tumor suppressor BRCA2 protects stalled replication forks from nucleolytic degradation. Defective fork stability contributes to chemotherapeutic sensitivity of BRCA2-defective tumors by yet-elusive mechanisms. Using DNA fiber spreading and direct visualization of replication intermediates, we report that reversed replication forks are entry points for fork degradation in BRCA2-defective cells. Besides MRE11 and PTIP, we show that RAD52 promotes stalled fork degradation and chromosomal breakage in BRCA2-defective cells. Inactivation of these factors restores reversed fork frequency and chromosome integrity in BRCA2-defective cells. Conversely, impairing fork reversal prevents fork degradation, but increases chromosomal breakage, uncoupling fork protection, and chromosome stability. We propose that BRCA2 is dispensable for RAD51-mediated fork reversal, but assembles stable RAD51 nucleofilaments on regressed arms, to protect them from degradation. Our data uncover the physiopathological relevance of fork reversal and illuminate a complex interplay of homologous recombination factors in fork remodeling and stability., BRCA2 is involved in both homologous recombination (HR) and the protection of stalled replication forks from degradation. Here the authors reveal how HR factors cooperate in fork remodeling, showing that BRCA2 supports RAD51 loading on the regressed arms of reversed replication forks to protect them from degradation.

Soil moisture is important in the triggering of many types of landslides. However, in situ soil moisture data are rarely available in hazardous zones. The advanced remote sensing technology could provide useful soil moisture information. In this study, an assessment has been carried out between the latest version of the European Space Agency Climate Change Initiative soil moisture product and the landslide events in a northern Italian region in the 14-year period 2002–2015. A clear correlation has been found between the satellite soil moisture and the landslide events, as over four-fifths of events had soil wetness conditions above the 50% regional soil moisture line. Attempts have also been made to explore the soil moisture thresholds for landslide occurrences under different environmental conditions (land cover, soil type, and slope). The results showed slope distribution could provide a rather distinct separation of the soil moisture thresholds, with thresholds becoming smaller for steeper areas, indicating dryer soil condition could trigger landslides at hilly areas than in plain areas. The thresholds validation procedure is then carried out. Forty five rainfall events between 2014 and 2015 are used as test cases. Contingency tables, statistical indicators, and receiver operating characteristic analysis for thresholds under different exceedance probabilities (1%–50%) are explored. The results have shown that the thresholds using 30% exceedance probability provide the best performance with the hitting rate at 0.92 and the false alarm at 0.50. We expect this study can provide useful information for adopting the remotely sensed soil moisture in the landslide early warnings.

International audience; Debris flows represent one of the most dangerous types of mass movements, because of their high velocities, large impact forces and long runout distances. This review describes the available debris-flow monitoring techniques and proposes recommendations to inform the design of future monitoring and warning/alarm systems. The selection and application of these techniques is highly dependent on site and hazard characterization, which is illustrated through detailed descriptions of nine monitoring sites: five in Europe, three in Asia and one in the USA. Most of these monitored catchments cover less than similar to 10 km(2) and are topographically rugged with Melton Indices greater than 0.5. Hourly rainfall intensities between 5 and 15 mm/h are sufficient to trigger debris flows at many of the sites, and observed debris-flow volumes range from a few hundred up to almost one million cubic meters. The sensors found in these monitoring systems can be separated into two classes: a class measuring the initiation mechanisms, and another class measuring the flow dynamics. The first class principally includes rain gauges, but also contains of soil moisture and pore-water pressure sensors. The second class involves a large variety of sensors focusing on flow stage or ground vibrations and commonly includes video cameras to validate and aid in the data interpretation. Given the sporadic nature of debris flows, an essential characteristic of the monitoring systems is the differentiation between a continuous mode that samples at low frequency ("non-event mode") and another mode that records the measurements at high frequency ("event mode"). The event detection algorithm, used to switch into the "event mode" depends on a threshold that is typically based on rainfall or ground vibration. Identifying the correct definition of these thresholds is a fundamental task not only for monitoring purposes, but also for the implementation of warning and alarm systems.

We investigated relations between geomorphic structures, movement velocity, and basal-slip surface geometry within individual kinematic domains of two large earth flows in the Apennine Mountains of southern Italy: the “Montaguto” earth flow and the “Mount Pizzuto” earth flow. Our analyses indicated that the earth flows are composed of distinct kinematic zones characterized by specific deformational patterns and longitudinal velocity profiles. Variations in velocity within individual kinematic zones is controlled by the geometry of the basal-slip surface, and, in particular by local variations in slope angle. Slip-surface geometry and slope also seem to control the density of extensional structures in driving earth-flow elements.

Chromatin ubiquitination by the ubiquitin ligase RNF168 is critical to regulate the DNA damage response (DDR). DDR deficiencies lead to cancer-prone syndromes, but whether this reflects DNA repair defects is still elusive. We identified key factors of the RNF168 pathway as essential mediators of efficient DNA replication in unperturbed S phase. We found that loss of RNF168 leads to reduced replication fork progression and to reversed fork accumulation, particularly evident at repetitive sequences stalling replication. Slow fork progression depends on MRE11-dependent degradation of reversed forks, implicating RNF168 in reversed fork protection and restart. Consistent with regular nucleosomal organization of reversed forks, the replication function of RNF168 requires H2A ubiquitination. As this novel function is shared with the key DDR players ATM, γH2A.X, RNF8, and 53BP1, we propose that double-stranded ends at reversed forks engage classical DDR factors, suggesting an alternative function of this pathway in preventing genome instability and human disease.

Following prolonged genotoxic stress, DNA2 and WRN functionally interact to degrade reversed replication forks and promote replication restart, thereby preventing aberrant processing of unresolved replication intermediates, Accurate processing of stalled or damaged DNA replication forks is paramount to genomic integrity and recent work points to replication fork reversal and restart as a central mechanism to ensuring high-fidelity DNA replication. Here, we identify a novel DNA2- and WRN-dependent mechanism of reversed replication fork processing and restart after prolonged genotoxic stress. The human DNA2 nuclease and WRN ATPase activities functionally interact to degrade reversed replication forks with a 5′-to-3′ polarity and promote replication restart, thus preventing aberrant processing of unresolved replication intermediates. Unexpectedly, EXO1, MRE11, and CtIP are not involved in the same mechanism of reversed fork processing, whereas human RECQ1 limits DNA2 activity by preventing extensive nascent strand degradation. RAD51 depletion antagonizes this mechanism, presumably by preventing reversed fork formation. These studies define a new mechanism for maintaining genome integrity tightly controlled by specific nucleolytic activities and central homologous recombination factors.

Many flow-like landslides entrain material from their paths during motion. At the flow front and along the lateral margins the sliding mass can plow into the path material pushing or entraining the existing soil. Although plowing can be a dominant mechanism for landslide mobility, little attention has been paid to this phenomenon in comparison with other entraining mechanism such as basal scouring. Therefore, establishing a suitable mathematical description is still a challenge. In this paper, a two-layer finite difference model is proposed to simulate frontal plowing. The frontal erodible mass and the sliding mass are simplified as two separate layers based on the assumption that they are immiscible in their propagation processes. The interaction (i.e., thrusting and shear) between the two layers is simulated by the normal force and shear force acting on the two-layer interface. The governing equations for the two-layer model are deduced from the mass and momentum conservations of a soil column and transformed into a finite difference form for numerical solving. Then the proposed model is tested in the back analysis of the Ximiaodian landslide which is a typical loess flow-like landslide located at the south bank of the Jing River, China. The modeling results show that frontal plowing has significant influence on the propagation of this landslide, especially on the final topography of the deposit. Without considering this effect, the thickness of the final deposit tends to be underestimated, while the propagation duration, area and distance are likely to be overestimated. The proposed model can provide more accurate and reliable simulations for rapid flow-like landslides with frontal plowing phenomenon.

Landscape evolution in active mountain chains can be dominated by gravitational slope movements. This is observed in a large portion of the Reno river catchment, Apennines, Italy, where weak rocks, such as clayshales, are subject to earthflows that control hillslope morphology and supply sediments to the channel network. In this paper, we evaluate the sediment flux generated by earthflows and compare it with Holocene-averaged deposition rates to assess the contribution of mass movements to landscape evolution. Present-day hillslope sediment flux is estimated by combining measured displacement rates (72 inclinometers) and spatial attributes of earthflows and historical frequency of reactivations. Averaged sediment yield (~ 1.6 x 10 3 t/km 2 /yr) compares well with similar studies on earthflow-dominated landscapes, despite notable differences in methodology. In the study area, the connectivity between hillslopes and the stream network is well developed and no significant sediment sinks influence the sediment transport processes. We document best estimates of regional sediment fluxes and related uncertainties, based on available data. Coarse limestone fragments, present in the clayshales, are used as a natural sediment tracer to allow a comparison with sedimentation rates taking place at the mouth of the intramontane catchment. Here, available borehole logs, 14 C datings and stratigraphic correlations of the alluvial fan are used to obtain an estimate of the deposition that took place during Holocene times. Taking also into account the role of solute transport, sedimentation rates are compared to earthflow sediment production rates. Results show a good agreement and demonstrate that earthflows are the primary mass wasting process in these weak rock lithologies. We document best estimates of regional sediment fluxes and related uncertainties. Present earthflow sediment production outpaces Holocene-averaged sedimentation rates by a factor of two. The gap between sediment production and deposition can be partly justified by uncertainties associated with our estimates and by time-scale differences. With this respect, the dynamic equilibrium between erosion and deposition, is likely affected by intra-Holocene oscillations at a short time scale (10 to 1 ky) attributable to climate variability. Terraced deposits documenting sedimentary episodes would also support such interpretation.

A method proposed for delineating lahar-hazard zones in volcanic valleys is adapted to debris flows. The original method is based on two predictive equations that relate the lahar volume to the cross-sectional inundated area and to the planimetric inundated area. These predictive equations were derived by combining a scaling analysis of lahar kinematics with the statistical analysis of data for 27 historical lahars. This paper tests the applicability of this approach to debris flow fans. Forty debris flow basins in the Italian Alps were surveyed, and data on 27 historical debris flow events were collected in the field or by means of aerial-photo analysis. Collected data reveal that the flow area ( A ) and the planimetric area ( B ) of a debris flow are linearly correlated to the debris flow volume ( V ) on a logarithmic scale, with high statistical significance. Moreover, the computed regression equations are very similar to those obtained from other published datasets on debris flows, leading to the global fitting equations A = 0.08 V 2 / 3 and B = 17 V 2 / 3 . These predictive equations are then implemented in an automated code (DFLOWZ) that delineates the inundated area on a debris flow fan on the basis of a user-specified debris flow volume, taking the statistical uncertainty in the prediction into account. DFLOWZ is simple reproducible, and it can handle both confined and unconfined flow. The model is tested against 10 historical debris flow events, providing a satisfactory agreement between observed and computed inundated areas. In spite of the limitations due to DEM accuracy and statistical uncertainty of the regression parameters, test results show that the method can be useful for practical applications.

RecQ helicases are a widely conserved family of ATP-dependent motors with diverse roles in nearly every aspect of bacterial and eukaryotic genome maintenance. However, the physical mechanisms by which RecQ helicases recognize and process specific DNA replication and repair intermediates are largely unknown. Here, we solved crystal structures of the human RECQ1 helicase in complexes with tailed-duplex DNA and ssDNA. The structures map the interactions of the ssDNA tail and the branch point along the helicase and Zn-binding domains, which, together with reported structures of other helicases, define the catalytic stages of helicase action. We also identify a strand-separating pin, which (uniquely in RECQ1) is buttressed by the protein dimer interface. A duplex DNA-binding surface on the C-terminal domain is shown to play a role in DNA unwinding, strand annealing, and Holliday junction (HJ) branch migration. We have combined EM and analytical ultracentrifugation approaches to show that RECQ1 can form what appears to be a flat, homotetrameric complex and propose that RECQ1 tetramers are involved in HJ recognition. This tetrameric arrangement suggests a platform for coordinated activity at the advancing and receding duplexes of an HJ during branch migration.

Genotoxic treatments in human cells consistently induce uncoupling of replication forks and their remodeling into four-way junctions by the RAD51 recombinase., Replication fork reversal protects forks from breakage after poisoning of Topoisomerase 1. We here investigated fork progression and chromosomal breakage in human cells in response to a panel of sublethal genotoxic treatments, using other topoisomerase poisons, DNA synthesis inhibitors, interstrand cross-linking inducers, and base-damaging agents. We used electron microscopy to visualize fork architecture under these conditions and analyzed the association of specific molecular features with checkpoint activation. Our data identify replication fork uncoupling and reversal as global responses to genotoxic treatments. Both events are frequent even after mild treatments that do not affect fork integrity, nor activate checkpoints. Fork reversal was found to be dependent on the central homologous recombination factor RAD51, which is consistently present at replication forks independently of their breakage, and to be antagonized by poly (ADP-ribose) polymerase/RECQ1-regulated restart. Our work establishes remodeling of uncoupled forks as a pivotal RAD51-regulated response to genotoxic stress in human cells and as a promising target to potentiate cancer chemotherapy.

The replication-stress response enables the DNA replication machinery to overcome DNA lesions or intrinsic replication-fork obstacles, and it is essential to ensure faithful transmission of genetic information to daughter cells. Multiple replication stress–response pathways have been identified in recent years, thus raising questions about the specific and possibly redundant functions of these pathways. Here, we review the emerging mechanisms of the replication-stress response in mammalian cells and consider how they may influence the dynamics of the core DNA replication complex.

Recent advances in multi-temporal Differential Synthetic Aperture Radar (SAR) Interferometry (DInSAR) have greatly improved our capability to monitor geological processes. Ground motion studies using DInSAR require both the availability of good quality input data and rigorous approaches to exploit the retrieved Time Series (TS) at their full potential. In this work we present a methodology for DInSAR TS analysis, with particular focus on landslides and subsidence phenomena. The proposed methodology consists of three main steps: (1) pre-processing, i.e., assessment of a SAR Dataset Quality Index (SDQI) (2) post-processing, i.e., application of empirical/stochastic methods to improve the TS quality, and (3) trend analysis, i.e., comparative implementation of methodologies for automatic TS analysis. Tests were carried out on TS datasets retrieved from processing of SAR imagery acquired by different radar sensors (i.e., ERS-1/2 SAR, RADARSAT-1, ENVISAT ASAR, ALOS PALSAR, TerraSAR-X, COSMO-SkyMed) using advanced DInSAR techniques (i.e., SqueeSAR(TM), PSInSAR(TM), SPN and SBAS). The obtained values of SDQI are discussed against the technical parameters of each data stack (e.g., radar band, number of SAR scenes, temporal coverage, revisiting time), the retrieved coverage of the DInSAR results, and the constraints related to the characterization of the investigated geological processes. Empirical and stochastic approaches were used to demonstrate how the quality of the TS can be improved after the SAR processing, and examples are discussed to mitigate phase unwrapping errors, and remove regional trends, noise and anomalies. Performance assessment of recently developed methods of trend analysis (i.e., PS-Time, Deviation Index and velocity TS) was conducted on two selected study areas in Northern Italy affected by land subsidence and landslides. Results show that the automatic detection of motion trends enhances the interpretation of DInSAR data, since it provides an objective picture of the deformation behaviour recorded through TS and therefore contributes to the understanding of the on-going geological processes.

During the October 2014 alluvial event in Parma province, which also caused the city of Parma to be partially flooded, several debris flows affected the upper Val Parma and Val Baganza (northern Apennines, Italy) causing severe and widespread damages to check-dams, roads and other infrastructures. The meteorological event reached intensities as high as 80 mm/hour, which is well above the thresholds presented in literature for the alpine area. The result was the occurrence of tens of debris flow along the Mt. Cervellino – Mt. Vitello relief, which were triggered in zones of failure of slope debris coverage along the streams, remobilized and scoured debris along the track and destroyed several check dams and damaged roads that were overflown by debris. Since debris flows in the northern Apennines are considered quite rare events, their hazard is generally underestimated or overlooked. The event in the Parma province, at the opposite, warns against this potentially destructive events that, in a changing meteorological framework, might result much more frequent and widespread than expected also in the northern Apennines.

Three tunnels for hydraulic purposes were excavated by tunnel-boring machines (TBM) in mostly hard metamorphic rocks in Northern Italy. A total of 14 km of tunnel was surveyed almost continually, yielding over 700 sets of data featuring rock mass characteristics and TBM performance. The empirical relations between rock mass rating and penetration rate clearly show that TBM performance reaches a maximum in the rock mass rating (RMR) range 40–70 while slower penetration is experienced in both too bad and too good rock masses. However, as different rocks gives different penetrations for the same RMR, the use of Bieniawski's classification for predictive purpose is only possible provided one uses a normalized RMR index with reference to the basic factors affecting TBM tunneling. Comparison of actual penetrations with those predicted by the Innaurato and Barton models shows poor agreement, thus highlighting the difficulties involved in TBM performance prediction.

The financial support for this Article was not fully acknowledged. The Acknowledgements should have included the following: This study was in part supported by the Swiss National Foundation Grant No.: 31003A-156023 to Alessandro Sartori.

We present an automated time series analysis of InSAR data for the characterization of ground subsidence induced by longwall mining at Metropolitan mine (New South Wales, Australia). The dataset derives from SqueeSAR™ processing of two Envisat radar data stacks of 44 images acquired from the ascending orbit and 43 from a descending orbit, acquired on a 35-day repeat interval in the period June 2006 to September 2010. Automated time series classification was carried out with PSTime, a specifically designed software that employs a sequence of statistical tests to classify the time series into the six different classes: uncorrelated, linear, quadratic, bilinear, discontinuous without constant velocity and discontinuous with change in velocity. Results highlight a cluster of bilinear trends with acceleration at the front of longwall panel progression and a cluster of bilinear trends with deceleration at the back. Linear trends are found at the centre of the subsidence bowl while outside most trends are uncorrelated. This picture is consistent with the evidence of acceleration in deformation trend when mining is approaching and a deceleration after extraction is completed and an essentially constant while mining takes place just underneath a specific point. Thus, time series analysis proved to be valuable for subsidence dynamics characterization, constraining in space and time the patterns of deformation trend in mining applications.

n n n n n n n n n n n n n LandSLIdE MonItorIng In thE EMILIa roMagna aPEnnInES Alberto Rosi, Matteo Berti, Nicola Bicocchi, Gabriella Castelli, Alessandro Corsini, Marco Mamei, and Franco Zambonelli Universita di Modena e Reggio Emilia Matteo Berti Universita di Bologna I taly’s Emilia Romagna Apennines are characterized by widespread landslide phenomena that pose a potential danger to villages and infrastructures. Existing monitoring technologies are coarse-grained, discontinuous, and costly. To overcome these limitations, we’ve started an interdisciplinary collaboration to study wireless sensor networks in this context. We’ve developed and deployed the first prototype in a steep landslide area near the village of Calita. The network’s infrastructure was first deployed in late 2008, and it’s been working ever since. It currently exploits 13 Crossbow Micaz motes with TinyOS software and covers a surface of approximately 500 square meters. The nodes embed accelerometer boards to capture slope movements and environmental boards to monitor ambient parameters such as temperature, pressure, humidity, and light depth. In-node processing and eventbased data delivery minimize communications and save energy. A base station delivers data to a central server every 15 minutes to support near-realtime analysis (see Figure 1). Analysis of the data collected so far proves the system’s capability to detect slope movements with high accuracy. In fact, comparisons between the sensor-network data and the data collected from the preexisting instrument sensors, such as strain gauges and inclinometers, show a good match. The wireless networks could therefore potentially act as an effective compleEnvironmental Monitoring and Task-Driven Computing

A debris flow event occurred in June 1997 in the Dolomites (Eastern Alps, Italy). The phenomenon was directly observed in the field and recorded by a video camera near its initiation area. The debris flow originated shortly after an intense rainstorm (25 mm in 30 min) whose runoff mobilised the loose coarse debris that filled the bottom of the channel in its upper part. The analysis of the steep headwater basin indicates a very short concentration time (9–14 min) that fits the quick hydrological response observed in the field. The debris flow mobilisation was not contemporaneous with the arrival of the peak water discharge in the initiation area probably due to the time required for the saturation of the highly conductive channel-bed material. Channel cross-section measurements taken along the flow channel indicate debris flow peak velocity and discharge ranging from 3.1 to 9.0 m/s and from 23 to 71 m3/s, respectively. Samples collected immediately after deposition were used to determine the water content and bulk density of the material. Channel scouring, fines enrichment and transported volume increase testify erosion and entrainment of material along the flow channel. Field estimates of the rheological properties based on open channel flow of Bingham fluid indicate a yield strength of 5000±400 Pa and relatively low viscosity (60–326 Pa s), probably due to a high percentage of fines (approx. 30%).

This paper illustrates research addressing the subject of the earthquake-induced surface effects by means of a multidisciplinary approach: tectonics, neotectonics, seismology, geology, hydrogeology, geomorphology, soil/rock mechanics have been considered. The research is aimed to verify in areas affected by earthquake-triggered landslides a methodology for the identification of potentially unstable areas. The research was organized according to regional and local scale studies. In order to better emphasise the complexity of the relationships between all the parameters affecting the stability conditions of rock slopes in static and dynamic conditions a new integrated approach, Rock Engineering Systems (RES), was applied in the Northern Apennines. In the paper, the different phases of the research are described in detail and an example of the application of RES method in a sample area is reported. A significant aspect of the study can be seen in its attempt to overcome the exclusively qualitative aspects of research into the relationship between earthquakes and induced surface effects, and to advance the idea of beginning a process by which this interaction can be quantified.

Topoisomerase I (TOP1) inhibitors are an important class of anticancer drugs. The cytotoxicity of TOP1 inhibitors can be modulated by replication fork reversal through a process that requires poly(ADP-ribose) polymerase (PARP) activity. Whether regressed forks can efficiently restart and what factors are required to restart fork progression after fork reversal are still unknown. We have combined biochemical and EM approaches with single-molecule DNA fiber analysis to identify a key role for human RECQ1 helicase in replication fork restart after TOP1 inhibition that is not shared by other human RecQ proteins. We show that the poly(ADP-ribosyl)ation activity of PARP1 stabilizes forks in the regressed state by limiting their restart by RECQ1. These studies provide new mechanistic insights into the roles of RECQ1 and PARP in DNA replication and offer molecular perspectives to potentiate chemotherapeutic regimens based on TOP1 inhibition.

RecQ helicases have attracted considerable interest in recent years due to their role in the suppression of genome instability and human diseases. These atypical helicases exert their function by resolving a number of highly specific DNA structures. The crystal structure of a truncated catalytic core of the human RECQ1 helicase (RECQ1(49-616)) shows a prominent β-hairpin, with an aromatic residue (Y564) at the tip, located in the C-terminal winged-helix domain. Here, we show that the β-hairpin is required for the DNA unwinding and Holliday junction (HJ) resolution activity of full-length RECQ1, confirming that it represents an important determinant for the distinct substrate specificity of the five human RecQ helicases. In addition, we found that the β-hairpin is required for dimer formation in RECQ1(49-616) and tetramer formation in full-length RECQ1. We confirmed the presence of stable RECQ1(49-616) dimers in solution and demonstrated that dimer formation favours DNA unwinding; even though RECQ1 monomers are still active. Tetramers are instead necessary for more specialized activities such as HJ resolution and strand annealing. Interestingly, two independent protein-protein contacts are required for tetramer formation, one involves the β-hairpin and the other the N-terminus of RECQ1, suggesting a non-hierarchical mechanism of tetramer assembly.

[1] The hydrologic behavior of shallow weathered soils commonly determines the propensity for slope failure. Here we use laboratory data and field data collected by an automated monitoring system to assess the character of pore water pressure responses in a natural clay slope subject to intermittent rainfall. Although we did not measure pore pressure distributions that triggered slope failure, we obtained three years of field data that provided reliable and largely reproducible documentation of transient pore pressure responses. At depths of tens of centimeters to a few meters below the ground surface, moisture and pressure sensors recorded relatively fast, transient responses to precipitation. The speeds of pore pressure pulses advancing downward in the saturated zone were much larger than those of advective fronts driven by gravity, and the amplitudes of the pulses attenuated with depth. Statistical assessment of 129 pressure head responses demonstrates that this behavior is consistent with predictions of a linear, one-dimensional pore pressure diffusion model. However, the model best simulates measurements if diffusivity is treated as a calibration parameter and if initial moisture conditions match model assumptions. For regional assessment of slope stability, the predictive accuracy of the linear-diffusion model is limited by inherent uncertainties in defining the initial conditions and in assigning the values of hydraulic parameters.

In the framework of the WISELAND project, funded by MIUR, we tested the integration between LiDAR and hyperspectral methodologies in the Valoria landslide (Modena province, Italy), a high risk area with vulnerable elements, subjected to periodic and abrupt reactivations. Multitemporal LiDAR Digital Terrain Models (DTMs) allowed the calculation of a differential surface, highlighting absolute height variations, recognizing the main landslide components and identifying depletion and accumulation zones. Hyperspectral data helped in the landslide terrain roughness characterization, performing the Principal Component Analysis (PCA) and correlating the results with Flatness and Organization geomorphometric parameters derived from LiDAR DTM.

Patients with hereditary spastic paraplegia (HSP) often resemble patients with mild spastic diplegia (SD), although their motor limitations differ. The aim of this study was to analyse quantitatively the gait of HSP and SD subjects in order to define the gait pattern in HSP and the differences between the two conditions. Fifteen subjects with HSP, 40 patients with SD and 20 healthy subjects underwent gait analysis (GA). The spatio-temporal and kinematic parameters at the proximal joints were found to be similar in HSP and SD, whereas the most significant differences were found at the knee and ankle joints. Both groups displayed a tendency for knee hyperextension in the midstance phase, but the duration of this hyperextension was longer in the HSP patients. This study shows that GA complements traditional clinical evaluations, making it possible to distinguish, clearly, between motor ability in HSP and in SD patients; the duration of the knee hyperextension during midstance was found to discriminate between the two gait patterns.

Background RecQ helicases play an essential role in the maintenance of genome stability. In humans, loss of RecQ helicase function is linked with predisposition to cancer and/or premature ageing. Current data show that the specific depletion of the human RECQ1 helicase leads to mitotic catastrophe in cancer cells and inhibition of tumor growth in mice. Results Here, we show that RECQ1 is highly expressed in various types of solid tumors. However, only in the case of brain gliomas, the high expression of RECQ1 in glioblastoma tissues is paralleled by a lower expression in the control samples due to the poor expression of RECQ1 in non-dividing tissues. This conclusion is validated by immunohistochemical analysis of a tissue microarray containing 63 primary glioblastomas and 19 perilesional tissue samples, as control. We also show that acute depletion of RECQ1 by RNAi results in a significant reduction of cellular proliferation, perturbation of S-phase progression, and spontaneous γ-H2AX foci formation in T98G and U-87 glioblastoma cells. Moreover, RECQ1 depleted T98G and U-87 cells are hypersensitive to HU or temozolomide treatment. Conclusions Collectively, these results indicate that RECQ1 has a unique and important role in the maintenance of genome integrity. Our results also suggest that RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas.

Fault and fracture planes (FFP) that cut through multilayer sequences can be significantly refracted at layer-layer interfaces due to the different mechanical properties of the contiguous layers, such as shear strength, friction coefficient and grain size. Detailed studies of different but coexisting and broadly coeval failure modes (tensile, hybrid and shear) within multilayers deformed in extensional settings have led to infer relatively low confinement and differential stress as the boundary stress conditions at which FFP refraction occurs. Although indeed widely recognized and studied in extensional settings, the details of FFP nucleation, propagation and refraction through multilayers remain not completely understood, partly because of the common lack of geological structures documenting the incipient and intermediate stages of deformation. Here we present the results of a study on strongly refracted strike-slip FFP within the mechanically layered turbidites of the Marnoso Arenacea Formation (MAF) of the Italian Northern Apennines. The MAF is characterized by the alternation of sandstone (strong) and carbonate mudstone (weak) layers. The studied refracted FFP formed at the front of the regional-scale NE-verging Palazzuolo anticline and post-date almost any other observed structure except for a set of late extensional faults. The studied faults display coexistence of shear and hybrid (tensile-shear) failure modes and we suggest that they initially nucleated as shear fractures (mode III) within the weak layers and, only at a later stage, propagated as dilatant fractures (mode I-II) within the strong layers. The tensile fractures within the strong layers invariably contain blocky calcite infills, which are, on the other hand, almost completely absent along the shear fracture planes deforming the weak layers. Paleostress analysis was performed to constrain the NNE-SSW compressional stress field that produced the refracted FFP and to exclude the possibility that the present attitude of these structures may result from the rotation through time of faults with an initial orientation. Slip tendency analysis was also performed to infer the relative slip and dilation potentials of the observed structures. Mesoscopic analysis of preserved structures from the incipient and intermediate stages of development and evolution of the refracted FFP allowed us to build an evolutionary scheme wherein: a) Nucleation of refracted FFP occurs within weak layers; b) Refraction is primarily controlled by grain size and clay mineral content and variations thereof at layer-layer interfaces but also within individual layers; c) Propagation within strong layers occurs primarily by fluid-assisted development ahead of the FFP tip of a “process zone” defined by a network of hybrid and tensile fractures; d) The process zone causes the progressive weakening and fragmentation of the affected rock volume to eventually allow the FFP to propagate through the strong layers; e) Enhanced suitable conditions for the development of tensile and hybrid fractures can be also achieved thanks to the important role played by pressured fluids.