1,721,184 research outputs found
New mechanistic insight into replication fork reversal and restart
Full text linkAn emerging model of how stalled or damaged forks are processed is that replication
fork
s can reverse to aid repair of the damage. The first evidence that replication forks
regress in human cells came from a recent study with topoisomerase I (T
op
1) inhibitors, an
important class of anticancer drugs currently in clinical use. Their cytotoxicit
y, and thus
their efficacy, has been generally linked to their ability to cause the accumulation of DNA
nicks, which are later converted into double
-
stranded breaks (DSBs) by the collision of the
DNA replication fork with the primary lesion. The discovery
that replic
ation forks can
regress upon Top
1 inhibition provided new insight into
the molecular basis of Top
1
cytotoxicity by showing that clinically relevant
, nanomolar doses of Top
1 poisons induce
replication fork slowing and reversal in a process that c
an be uncoupled from DSB
formation
and
requires poly(ADP
-
ribose) polymerase
1
(
PARP1) activity.
However,
w
hether re
versed
forks can efficiently restart
and wh
ich
factors are
involved in this
mechanism
was
still unknown.
In this thesis
,
u
sing a combination
of biochemical and
cellular approaches, we provided the first evidence that regressed forks can restart
in vivo
and identified a key role for the human RECQ1 helicase in promoting efficient re
plication
fork restart after Top
1 inhibition
that is not shared
by other human RecQ
members
.
Our
data also provided the first insight into the molecular role of PARP1 in fork reversal by
showing that the poly(ADP
-
ribosyl)ation activity of PARP inhibits RECQ1 activity on
replication forks after Top 1 inhibition. Thus, PARP activity is not required to form, but
rather to "accumulate" reversed fork structures by maintaining/protecting them from a
counteracting activity (RECQ1), which would otherwise cause an untimely restart of
reversed forks, leading to DSB formation. The
identification of a specific and controlled
biochemical activity that drives
the
restart of reversed forks strongly supports the
physiological relevance of this DNA transaction during replication stress in human cells.
Moreover, our
studies provide new mec
hanistic insights into the roles of
RECQ1 and
PARP
1
in DNA replication and offer molecular perspectives to potentiate
chemo
therapeutic regimens based on Top
1 inhibition
Groundwater and ground displacement monitoring in the source area of the Montecchi earthflow (Northern Apennines, Italy)
No full textThe importance of pore water pressure regime for landslide activity is generally accepted. In the case of earthflows, generalized failures (reactivations) are rare and sustained slow movements can proceed for decades. The relationship between precipitation, pore water pressure responses and movement is not straightforward. We document rainfall, pore pressure regime and displacements in the source area of an active earthflow. Pressure heads at shallow depth are clearly related to infiltration from the surface and can be satisfactorily reproduced by a diffusive model while the hypothesis of gravity-dominated flow can be rejected based on the short delay between rainfall and pressure response. Displacement rates are very small to zero during the summer and increase a couple of months later than the onset of the precipitation of the wet season. Only late in the wet season, velocities attain peak values (up to 4 mm/day) and show a remarkable correlation to rainfall episodes. Higher displacement rates correspond to unexceptional pressure head values, we therefore believe that alternative mechanisms of water pressure build-up may exist. Fractures likely act as a preferential flow system and influence both the hydrological responses to rainfall and the deformation behavior of the landslide
Lithologic and morphologic controls on debris flow dynamics in the Dolomites (Italian Alps, Italy)
No full textIn high-relief landscapes, debris flows represent the most efficient mean of erosion and sediment transport across
spatial scales ranging from hectares to tens of square kilometers.
In the Dolomite region of Italy, the landscape is dominated by steep massifs mainly made of limestone and
dolostone rocks. Abundant talus and fan deposits connect the bottom of the valleys to the rocky massifs. Thick
debris talus was deposited in post-glacial climatic conditions and is actively fed by steep dolomitic rock walls.
Debris flows are widespread over the territory. They are commonly triggered by water discharge concentrated on
steep headwater catchments and delivered to talus slopes. Headwater catchments are typically very steep (45°-60°
on the average) and mostly consist of exposed bedrock with no vegetation and sparse to none soil cover. Debris
flow fans are relatively steep (10 to 30°)
Our study area extends over 250 km2 and includes about one-hundred debris flow catchments. We take advantage
of the remarkable morphological similarities of the catchments to characterize their lithology, morphometry and
investigate scale-relationships. We use LiDAR, field surveys and aerial photo interpretation to describe the
principal topographic conditions associated with debris-flow initiation, transportation, and deposition. Debris
flow-prone catchments associated to recent activity has been selected to investigate the role of geology and
morphology as influencing factor at basin scale. They display a decreasing specific sediment yield with increasing
size. Depending on the abundance of loose debris deposits, volumes of sediment delivered to the fan span about
one order of magnitude. Dependence of deposited sediment volumes on the basin scale is clear and translates into
an inverse proportionality when specific yield is considered
High intensity convective rainfalls and corresponding hydrological response in rocky head water basins
No full textThe influence of preferential flow on pressure propagation and landslide triggering of the Rocca Pitigliana landslide
No full textThe fast pore water pressure response to rain events is an important triggering factor for slope instability. The fast pressure response may be caused by preferential flow that bypasses the soil matrix. Currently, most of the hydro-mechanical models simulate pore water pressure using a single-permeability model, which cannot quantify the effects of preferential flow on pressure propagation and landslide triggering. Previous studies showed that a model based on the linear-diffusion equation can simulate the fast pressure propagation in near-saturated landslides such as the Rocca Pitigliana landslide. In such a model, the diffusion coefficient depends on the degree of saturation, which makes it difficult to use the model for predictions. In this study, the influence of preferential flow on pressure propagation and slope stability is investigated with a 1D dual-permeability model coupled with an infinite-slope stability approach. The dual-permeability model uses two modified Darcy-Richards equations to simultaneously simulate the matrix flow and preferential flow in hillslopes. The simulated pressure head is used in an infinite-slope stability analysis to identify the influence of preferential flow on the fast pressure response and landslide triggering. The dual-permeability model simulates the height and arrival of the pressure peak reasonably well. Performance of the dual-permeability model is as good as or better than the linear-diffusion model even though the dual-permeability model is calibrated for two single pulse rain events only, while the linear-diffusion model is calibrated for each rain event separately. In conclusion, the 1D dual-permeability model is a promising tool for landslides under similar conditions
Deformation responses of slow moving landslides to precipitation in the Northern Apennines (Italy).
No full textSlow moving landslides are a frequent feature in the Northern Apennines of Italy and one of the main landscape forming agents. Among the most common landslide types are complex earth flows that occur in chaotic clayshales and complex rock slides in highly fractured flysch. We present the results of an InSAR-based survey in the Reno and Panaro river catchments, which are located South of Bologna and Modena in the Northern Apennines of Italy. We processed Envisat and Cosmo-SkyMed radar data using the Stanford Method of Persistent Scatterers (StaMPS) and documented movement on 62 deep-seated landslides. These landslides were compared to theregional landslide inventory that contains information about the type of landslide, its state of activity and the lithological characteristics of the host rock. Of the landslides found using InSAR, 42 % correspond to active landslide bodies in the regional inventory, while 48 % are mapped as dormant and 10% are not previously mapped. InSAR derived landslides often do not correspond to the exact extent of mapped landslide bodies. InSAR results show two recurring styles of deformation: (1) earthflows involving chaotic clay-shale units that exhibit steady state displace ment, or exhibit long-term (multi-annual) accelerations and decelerations, or (2) complex landslides in flysch units that are characterized by distinct increases in displacement rate following periods (weeks-to-months) of intense precipitation. Such differences in behavior might be due to inherent differences in the mechanical and hydraulic characteristics of the material in relation to the specific climatic forcing experienced during the observation period (2003 and 2015). Flysch units are relatively more fragile and have higher permeability when compared to clayshale units. Hence the deformation response to the precipitation is likely faster and characterized by more abrupt accelerations and decelerations
Debris flows in Val Parma and Val Baganza (northern Apennines) During the October 2014 alluvial event in Parma Province (Italy)
No full textDuring 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
Measurements of runoff discharges at the feet of a rocky channel incised on the Dimai Peak (Venetian Dolomites, Northeast Italy)
No full textAn advanced SPH model for protective constructions of debris flows adopting the modified HBP constitutive law
Full text linkIn many catchments prone to debris flows, prevention
structures such as check dams and retention basins have been
installed to prevent debris flows from impacting the nearby
infrastructures. The SPH model adopting the Herschel–Bulkley–
Papanastasiou (HBP) constitutive law has shown good potential
in modeling the interaction between debris flow and prevention
structures. However, the accuracy of this model is not fully
satisfactory when modeling the deposition process of debris flow,
because the original HBP law is a viscoplastic model which does
not consider frictional dissipation. Therefore, in this paper, we
proposed a novel SPH model for analyzing the interaction between
debris flow and prevention structures, by incorporating a modified
HBP law with frictional dissipation into the original SPH model.
The proposed model is validated by column collapse and flume
benchmark experiments first and then utilized to analyze a real
debris flow and its interaction with the prevention structures in
the Cancia catchment in northern Italian Alps. The results of the
column collapse experiment show that our model exhibits a better
performance in simulating the collapse process compared with the
original SPH model, and the simulation results of the sand flume
test illustrate that the proposed model can accurately predict
the impact force of debris flow on the prevention structure. The
simulation results of the Cancia debris flow demonstrate that the
check dams can dramatically diminish the discharge and the frontal
flow velocity of the debris flow, and the peak impact force of debris
flow generally decreases with gentler channel slope. Furthermore,
various prevention structures show different interaction
mechanisms with debris flows: the flat deposition platform mainly
dissipates the kinetic energy of the flow, the check dam mainly
reduces the peak discharge of the debris flow and intercepts the
debris mass, and the retention basin at the outlet contributes to
the deposition of debris flow. The proposed novel SPH model is
helpful for guiding the optimization design of multiple prevention
structures in debris flow gullies
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