Search

The letter addresses concerns and seeks clarification on a study titled "Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb® and Mortality in Critically Ill Patients with Hyperbilirubinemia." The authors express doubts about using mortality as the primary outcome measure in critically ill patients due to the variability in sepsis phenotypes. They also question the effectiveness of the blood purification technique, CytoSorb, in reducing bilirubin concentration and highlight the importance of mass balance calculations. The authors reference previous studies that demonstrate the capability of CytoSorb to efficiently remove bilirubin over 24 hours. They conclude that the data refute a study suggesting saturation of the CytoSorb adsorber after 6 hours. [Extracted from the article]

Worst-case analysis is a performance measure that is often too pessimistic to indicate which algorithms we should use in practice. A classical example is in the context of the Euclidean Traveling Salesman Problem (TSP) in the plane, where local search performs very well in practice even though it only achieves an Ω (log n log log n) worst-case approximation ratio. In such cases, a natural alternative approach to worst-case analysis is to analyze the performance of algorithms in semi-random models. In this paper, we propose and investigate a novel semi-random model for the Euclidean TSP. In this model, called the simultaneous semi-random model, an instance over n points consists of the union of an adversarial instance over (1 - α) n points and a random instance over α n points, for some α ∈ [ 0 , 1 ] . As with smoothed analysis, the semi-random model interpolates between distributional (random) analysis when α = 1 and worst-case analysis when α = 0 . In contrast to smoothed analysis, this model trades off allowing some completely random points in order to have other points that exhibit a fully arbitrary structure. We show that with only an α = 1 log n fraction of the points being random, local search achieves an O (log log n) approximation in the simultaneous semi-random model for Euclidean TSP in fixed dimensions. On the other hand, we show that at least a polynomial number of random points are required to obtain an asymptotic improvement in the approximation ratio of local search compared to its worst-case approximation, even in two dimensions. [ABSTRACT FROM AUTHOR]

We introduce and study a discrete multi-period extension of the classical knapsack problem, dubbed generalized incremental knapsack. In this setting, we are given a set of n items, each associated with a non-negative weight, and T time periods with non-decreasing capacities W 1 ≤ ⋯ ≤ W T . When item i is inserted at time t, we gain a profit of p it ; however, this item remains in the knapsack for all subsequent periods. The goal is to decide if and when to insert each item, subject to the time-dependent capacity constraints, with the objective of maximizing our total profit. Interestingly, this setting subsumes as special cases a number of recently-studied incremental knapsack problems, all known to be strongly NP-hard. Our first contribution comes in the form of a polynomial-time (1 2 - ϵ) -approximation for the generalized incremental knapsack problem. This result is based on a reformulation as a single-machine sequencing problem, which is addressed by blending dynamic programming techniques and the classical Shmoys–Tardos algorithm for the generalized assignment problem. Combined with further enumeration-based self-reinforcing ideas and new structural properties of nearly-optimal solutions, we turn our algorithm into a quasi-polynomial time approximation scheme (QPTAS). Hence, under widely believed complexity assumptions, this finding rules out the possibility that generalized incremental knapsack is APX-hard. [ABSTRACT FROM AUTHOR]

This study develops a new spatial correlation model for Italy using the most up-to-date and densest dataset of accelerometer and velocimeter records available. The objective is to estimate the average correlation length and assess its impact on the prediction accuracy of the Italian Shakemap compared to the global model (Loth and Baker, 2013–LB13) adopted in the default configuration of the program. We compute the spatial covariance structure using a geostatistical approach based on traditional variography applied to standardized residuals within the events of a reference ground motion model (ITA10). We observe spatial clusters of the correlation lengths and a wide variability over the Italian territory linked to the profound heterogeneity of the geological and geomorphological context. The obtained estimates are then implemented within the LB13 co-regionalization model in place of the default values while assuming the same cross-correlation coefficients among spectral parameters. Although our results are quite consistent with previous models calibrated for Italy, we find that the inclusion of the new correlation lengths in the Shakemap predictions, assessed through a leave-one-out cross-validation technique, results in a non-appreciable improvement over the global model, thus indicating that the adopted approach is not able to resolve the regional features and the corresponding spatial correlation with reference to individual scenarios. These findings may suggest the need to move towards nonergodic models in the Shakemap computing to better capture the spatial variability or to determine different co-regionalisation matrices more suitable for the regional applications. [ABSTRACT FROM AUTHOR]

Birkhoff's representation theorem (Birkhoff, Duke Math J 3(3):443–454, 1937) defines a bijection between elements of a distributive lattice and the family of upper sets of an associated poset. Although not used explicitly, this result is at the backbone of the combinatorial algorithm by Irving et al. (J ACM 34(3):532-543, 1987) for maximizing a linear function over the set of stable matchings in Gale and Shapley's stable marriage model (Gale and Shapley, Am Math Monthly 69(1):9–15 1962). In this paper, we introduce a property of distributive lattices, which we term as affine representability, and show its role in efficiently solving linear optimization problems over the elements of a distributive lattice, as well as describing the convex hull of the characteristic vectors of the lattice elements. We apply this concept to the stable matching model with path-independent quota-filling choice functions, thus giving efficient algorithms and a compact polyhedral description for this model. To the best of our knowledge, this model generalizes all those for which similar results were known, and our paper is the first that proposes efficient algorithms for stable matchings with choice functions, beyond classical extensions of the Deferred Acceptance algorithm. [ABSTRACT FROM AUTHOR]

SUMMARY: We derived new, reversible relationships between macroseismic intensity (I), expressed in either the European Macroseismic (EMS-98) or the Mercalli–Cancani–Sieberg (MCS) scales and peak ground acceleration (PGA), peak ground velocity (PGV) and the spectral acceleration (SA) at 0.3, 1.0 and 3.0 s [SA(0.3), SA(1.0) and SA(3.0)] for Italy. We adopted the orthogonal distance regression technique to fit a quadratic function. This research aims to improve ground motion and intensity estimates for earthquake hazard applications, and for the calculation of shakemaps in Italy. To this end, the recently published INGe data set was used (https://doi.org/10.13127/inge.2). The new relations are: where PGA and SAs are expressed in cm s−2 and PGV is expressed in cm s−1. Tests performed to assess the robustness and the accuracy of the results demonstrate that adoption of quadratic relationships for this regression problem is a suitable choice within the range of values of the available data set. Comparison with similar published regressions for Italy evidences that the proposed relations provide statistically significant improved fits to the data. The new relations are also tested by inserting them in the ShakeMap system of the Italian configuration evidencing a significant improvement when compared to those implemented. [ABSTRACT FROM AUTHOR]

Since first being documented in ancient times, the relation of inflammation with injury and disease has evolved in complexity and causality. Early observations supported a cause (injury) and effect (inflammation) relationship, but the number of pathologies linked to chronic inflammation suggests that inflammation itself acts as a potent promoter of injury and disease. Additionally, results from studies over the last 25 years point to chronic inflammation and innate immune signaling as a critical link between stress (exogenous and endogenous) and adaptation. This brief review looks to highlight the role of the innate immune response in disease pathology, and recent findings indicating the innate immune response to chronic stresses as an influence in driving adaptation. [ABSTRACT FROM AUTHOR]

Sparse structures are frequently sought when pursuing tractability in optimization problems. They are exploited from both theoretical and computational perspectives to handle complex problems that become manageable when sparsity is present. An example of this type of structure is given by treewidth: a graph theoretical parameter that measures how "tree-like" a graph is. This parameter has been used for decades for analyzing the complexity of various optimization problems and for obtaining tractable algorithms for problems where this parameter is bounded. The goal of this work is to contribute to the understanding of the limits of the treewidth-based tractability in optimization. Our results are as follows. First, we prove that, in a certain sense, the already known positive results on extension complexity based on low treewidth are the best possible. Secondly, under mild assumptions, we prove that treewidth is the only graph-theoretical parameter that yields tractability for a wide class of optimization problems, a fact well known in Graphical Models in Machine Learning and in Constraint Satisfaction Problems, which here we extend to an approximation setting in Optimization. [ABSTRACT FROM AUTHOR]

An instance of the marriage problem is given by a graph G = (A ∪ B,E), together with, for each vertex of G, a strict preference order over its neighbors. A matching M of G is popular in the marriage instance if M does not lose a head-to-head election against any matching where vertices are voters. Every stable matching is a min-size popular matching; another subclass of popular matchings that always exists and can be easily computed is the set of dominant matchings. A popular matching M is dominant if M wins the head-to-head election against any larger matching. Thus, every dominant matching is a max-size popular matching, and it is known that the set of dominant matchings is the linear image of the set of stable matchings in an auxiliary graph. Results from the literature seem to suggest that stable and dominant matchings behave, from a complexity theory point of view, in a very similar manner within the class of popular matchings. The goal of this paper is to show that there are instead differences in the tractability of stable and dominant matchings and to investigate further their importance for popular matchings. First, we show that it is easy to check if all popular matchings are also stable; however, it is co-NP hard to check if all popular matchings are also dominant. Second, we show how some new and recent hardness results on popular matching problems can be deduced from the NP-hardness of certain problems on stable matchings, also studied in this paper, thus showing that stable matchings can be employed to show not only positive results on popular matchings (as is known) but also most negative ones. Problems for which we show new hardness results include finding a min-size (resp., max-size) popular matching that is not stable (resp., dominant). A known result for which we give a new and simple proof is the NP-hardness of finding a popular matching when G is nonbipartite. [ABSTRACT FROM AUTHOR]

The maximum weighted stable set problem in claw-free graphs is a well-known generalization of the maximum weighted matching problem, and a classical problem in combinatorial optimization. In spite of the recent development of fast(er) combinatorial algorithms and some progresses in the characterization of the corresponding stable set polytope, the problem of "providing a decent linear description" for this polytope (Grötschel et al. in Geometric algorithms and combinatorial optimization, Springer, New York, 1988) is still open. The main contribution of this paper is to propose an algorithmic answer to that question by providing a polynomial-time and computationally attractive separation routine for the stable set polytope of claw-free graphs, that only requires a combinatorial decomposition algorithm, the solution of (moderate sized) compact linear programs, and Padberg and Rao's algorithm for separating over the matching polytope. In particular, it is a generalization of the latter and avoids the heavy computational burden of resorting to the ellipsoid method, on which the only poly-time separation routine known so far relied. Besides, our separation routine comes with a 'small' (but not polynomial) extended linear programming formulation and a procedure to derive a linear description of the stable set polytope of claw-free graphs in the original space. [ABSTRACT FROM AUTHOR]

In this paper we present an updated and homogeneous earthquake data set for Italy compiled by joining the Italian Macroseismic Database DBMI15 and the Engineering Strong-Motion (ESM) accelerometric data bank. The database has been compiled through an extensive procedure of selection and revision based on two main steps: 1) the removal of several earthquakes in DBMI15 because the data source has been considered to be largely unreliable and 2) the extraction of all the localities reporting intensity data which are located within 3 km from the accelerograph stations that recorded the data. The final data set includes 323 recordings from 65 earthquakes and 227 stations in the time span 1972-2016. The events are characterized by magnitudes in the range 4.0-6.9 and depths in the range 0.3-45.0 km. Here, we illustrate the data collection and the properties of the database in terms of recording, event and station distributions as well as Mercalli-Cancani-Sieberg (MCS) macroseismic intensity points. Furthermore, we discuss the most relevant features of engineering interest showing several statistics with reference to the most significant metadata (such as moment magnitude, several distance metrics, style of faulting etc). The data set can be downloaded from data repository Zenodo at https://doi.org/10.13127/inge.1; (Oliveti et., 2020). [ABSTRACT FROM AUTHOR]

Deterministic protocols are well-known tools to obtain extended formulations, with many applications to polytopes arising in combinatorial optimization. Although constructive, those tools are not output-efficient, since the time needed to produce the extended formulation also depends on the number of rows of the slack matrix (hence, on the exact description in the original space). We give general sufficient conditions under which those tools can be implemented as to be output-efficient, showing applications to e.g. Yannakakis' extended formulation for the stable set polytope of perfect graphs, for which, to the best of our knowledge, an efficient construction was previously not known. For specific classes of polytopes, we give also a direct, efficient construction of extended formulations arising from protocols. Finally, we deal with extended formulations coming from unambiguous non-deterministic protocols. [ABSTRACT FROM AUTHOR]

Enabling practical utilization of layered R3̅m positive electrodes near full delithiation requires an enhanced understanding of the complex electrode-electrolyte interactions that often induce failure. Using Li[Ni0.8Co0.15Al0.05]O2 (NCA) as a model layered compound, the chemical and structural stability in a strenuous thermal and electrochemical environment was explored. Operando microcalorimetry and electrochemical impedance spectroscopy identified a fingerprint for a structural decomposition and transition-metal dissolution reaction that occurs on the positive electrode at full delithiation. Surface-sensitive characterization techniques, including X-ray absorption spectroscopy and high-resolution transmission electron microscopy, measured a structural and morphological transformation of the surface and subsurface regions of NCA. Despite the bulk structural integrity being maintained, NCA surface degradation at a high state of charge induces excessive transition-metal dissolution and significant positive electrode impedance development, resulting in a rapid decrease in electrochemical performance. Additionally, the impact of electrolyte salt, positive electrode surface area, and surface Li2CO3 content on the magnitude and character of the dissolution reaction was studied. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG), a Food and Drug Administration (FDA)-approved fluorophore with excitation and emission wavelengths inside the "optical imaging window," has been incorporated into nanocarriers (NCs) to achieve enhanced circulation time, targeting, and real-time tracking in vivo. While previous studies transferred ICG exogenously into NCs, here, a one-step rapid precipitation process [flash nanoprecipitation (FNP)] creates ICG-loaded NCs with tunable, narrow size distributions from 30 to 180 nm. A hydrophobic ion pair of ICGtetraoctylammonium or tetradodecylammonium chloride is formed either in situ during FNP or preformed then introduced into the FNP feed stream. The NCs are formulated with cores comprising either vitamin E (VE) or polystyrene (PS). ICG core loadings of 30 wt. % for VE and 10 wt. % for PS are achieved. However, due to a combination of molecular aggregation and Förster quenching, maximum fluorescence (FL) occurs at 10 wt. % core loading. The FL-per-particle scales with core diameter to the third power, showing that FNP enables uniform volume encapsulation. By varying the ICG counter-ion ratio, encapsulation efficiencies above 80% are achieved even in the absence of ion pairing, which rises to 100% with 1:1 ion pairing. Finally, while ICG ion pairs are shown to be stable in buffer, they partition out of NC cores in under 30 min in the presence of physiological albumin concentrations. [ABSTRACT FROM AUTHOR]

Phosphoinositide-phospholipase C-β1 (PLC-β1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation and osteogenesis. During myogenic differentiation of murine C2C12 myoblasts, PLC-β1 signaling pathway involves the Inositol Polyphosphate Multikinase (IPMK) and β-catenin as downstream effectors. By means of c-jun binding to cyclin D3 promoter, the activation of PLC-β1 pathway determines cyclin D3 accumulation. However, osteogenesis requires PLC-β1 expression and up-regulation but it does not affect cyclin D3 levels, suggesting that the two processes require the activation of different mediators. [ABSTRACT FROM AUTHOR]

Abstract: Combined liver and kidney transplantation (CLKT) has been increasingly used in recent years: 13 of our 19 cases were performed in the last 2 years being 3.2% of our liver transplantation (LT) and kidney transplantation (KT) activity. Only three of them were not on hemodialysis and the scheduling of a CLKT meant being at the top of the waiting list. We accepted only ideal donors and had no case of liver and only one case of kidney delayed graft function. Two deaths occurred during the first postoperative month, due to acute respiratory distress syndrome and multiorgan failure, both in patients with adult polycystic disease who were in poor nutritional condition due to a late indication for CLKT. We had two late deaths, one due to a native kidney tumor at 7 years and one at 8 years due to alcoholic cirrhosis recurrence. The late survival of our patients was 77.3% with all surviving patients showing good liver and kidney function. We planned not to do the KT in the case of a positive preoperative cross-match; but the only positive case became negative 8 hours after LT when we performed the KT. The patient is well after 2 years. The liver does not always protect the kidney if there are preformed antibodies, but we should try every possible technique not to lose the possibility of doing both transplants, because in case of LT alone the patients loses his top position on the CLKT waiting list and often waits years for a kidney. [Copyright &y& Elsevier]

Abstract: Combined transplants with the liver represent a small number of associated pathologies with little chance of resolving with a single transplant. The small case number prevents us from establishing homogeneous criteria for the procedure. The insertion of the Model for End-Stage Liver Disease in the preoperative evaluation of the patients awaiting liver transplant has definitely increased the number of combined liver-kidney transplants, which have reached more significant numbers. The number of heart-liver transplants is still too low to establish the efficacy of the measure. The multiorgan transplant with the liver represents a rare event entrusted to a series of case reports, each one of which has a history unto itself. Our experience in this field includes 14 combined liver-kidney, six combined heart-liver, and two multiorgan transplants with liver among 36 intestine transplants. We have examined the main pre-, intra-, and postsurgical problems for each one of these transplants, particularly relating to the anesthetic and intensive-care aspects. [Copyright &y& Elsevier]

An extended formulation of a polyhedron $$P$$ is a linear description of a polyhedron $$Q$$ together with a linear map $$\pi $$ such that $$\pi (Q)=P$$ . These objects are of fundamental importance in polyhedral combinatorics and optimization theory, and the subject of a number of studies. Yannakakis' factorization theorem (Yannakakis in J Comput Syst Sci 43(3):441-466, ) provides a surprising connection between extended formulations and communication complexity, showing that the smallest size of an extended formulation of $$P$$ equals the nonnegative rank of its slack matrix $$S$$ . Moreover, Yannakakis also shows that the nonnegative rank of $$S$$ is at most $$2^c$$ , where $$c$$ is the complexity of any deterministic protocol computing $$S$$ . In this paper, we show that the latter result can be strengthened when we allow protocols to be randomized. In particular, we prove that the base- $$2$$ logarithm of the nonnegative rank of any nonnegative matrix equals the minimum complexity of a randomized communication protocol computing the matrix in expectation. Using Yannakakis' factorization theorem, this implies that the base- $$2$$ logarithm of the smallest size of an extended formulation of a polytope $$P$$ equals the minimum complexity of a randomized communication protocol computing the slack matrix of $$P$$ in expectation. We show that allowing randomization in the protocol can be crucial for obtaining small extended formulations. Specifically, we prove that for the spanning tree and perfect matching polytopes, small variance in the protocol forces large size in the extended formulation. [ABSTRACT FROM AUTHOR]

The May 20, 2012, Emilia Ml 5.9 earthquake was followed by some major aftershocks, well recorded by a large number of temporary stations that were installed to monitor the sequence. These additional recordings allowed us a thorough testing of the performance of the ShakeMap-a procedure designed to provide rapid information on the experienced ground motion. We found that the shakemaps for the May 29, 2012, Ml 5.8 earthquake, obtained using the permanent stations only, underestimate significantly the ground motion computed with the highest station density, especially for PSA at long periods (T $$=$$ 3.0 s). This low-frequency motion is controlled primarily by the surface waves recorded in the Po plain: the observed site effects are likely not accounted properly by the site correction coefficient based on Vs30 as implemented in the ShakeMap procedure. The shakemaps determined during the seismic sequence have been included in an Italian national law that was passed after the 2012 earthquake. According to this law, the factories safety verifications were bound to the comparison between the shakemaps and the design acceleration required by the current national seismic code. We then decide to appraise the impact of the shakemap accuracy on the law provisions. Following the law recommendations, we have estimated the possible errors resulting from the incomplete evaluation of the ground shaking: our results show that, if the complete dataset were available at the time of the law approval, the number of buildings for which the safety check was required would have been significantly smaller. [ABSTRACT FROM AUTHOR]

Abstract: Lipid signalling molecules are essential components of the processes that allow one extracellular signal to be transferred inside the nucleus, where specific lipid second messengers elicit reactions capable of regulating gene transcription, DNA replication or repair and DNA cleavage, eventually resulting in cell growth, differentiation, apoptosis or many other cell functions. Nuclear inositides are independently regulated, suggesting that the nucleus constitutes a functionally distinct compartment of inositol lipids metabolism. Indeed, nuclear inositol lipids themselves can modulate nuclear processes, such as transcription and pre-mRNA splicing, growth, proliferation, cell cycle regulation and differentiation. Nuclear PI-PLCβ1 is a key molecule for nuclear inositide signalling, where it plays a role in cell cycle progression, proliferation and differentiation. Here we review the targets and possible involvement of nuclear PI-PLCβ1 in human physiology and pathology. [Copyright &y& Elsevier]

Evidence accumulated over the past 20 years has highlighted the presence of an autonomous nuclear inositol lipid metabolism, and suggests that lipid signalling molecules are important components of signalling pathways operating within the nucleus. Nuclear polyphosphoinositide ( PI) signalling relies on the synthesis and metabolism of phosphatidylinositol 4,5-bisphosphate, which can modulate the activity of effector proteins and is a substrate of signalling enzymes. The regulation of the nuclear PI pool is totally independent from the plasma membrane counterpart, suggesting that the nucleus constitutes a functionally distinct compartment of inositol lipids metabolism. Among the nuclear enzymes involved in PI metabolism, inositide specific phospholipase C ( PI- PLC) has been one of the most extensively studied. Several isoforms of PI- PLCs have been identified in the nucleus, namely PI- PLC-β1, γ1, δ1 and ζ; however, the β1 isozyme is the best characterized. In the present review, we focus on the signal transduction-related metabolism of nuclear PI- PLC and review the most convincing evidence for PI- PLC expression and activity being involved in differentiation and proliferation programmes in several cell systems. Moreover, nuclear PI- PLC is an intermediate effector and interactor for nuclear inositide signalling. The inositide cycle exists and shows a biological role inside the nucleus. It is an autonomous lipid-dependent signalling system, independently regulated with respect to the one at the plasma membrane counterpart, and is involved in cell cycle progression and differentiation. [ABSTRACT FROM AUTHOR]

Real-time seismology has made significant improvements in recent years, with source parameters now available within a few tens of minutes after an earthquake. It is likely that this time will be further reduced, in the near future, by means of increased efficiency in real-time transmission, increasing data coverage and improvement of the methodologies. In this context, together with the development of new ground motion predictive equations (GMPEs) that are able to account for source complexity, the generation of strong ground motion shaking maps in quasi-real time has become ever more feasible after the occurrence of a damaging earthquake. However, GMPEs may not reproduce reliably the ground motion in the near-source region where the finite fault parameters have a strong influence on the shaking.In this paper we test whether accounting for source-related effects is effective in better characterizing the ground motion. We introduce a modification of the GMPEs within the ShakeMap software package, and subsequently test the accuracy of the newly generated shakemaps in predicting the ground motion. The test is conducted by controlling the performance of ShakeMap as we decrease the amount of the available information. We then update ShakeMap with the GMPE modified with a corrective factor accounting for source effects, in order to better constrain these effects that likely influence the level of (near-source) ground shaking.We investigate two well-recorded earthquakes from Japan (the 2000 Tottori, Mw 6.6, and the 2008 Iwate-Miyagi, Mw7.0, events) where the instrumental coverage is as dense as needed to ensure an objective appraisal of the results. The results demonstrate that the corrected GMPE can capture only some aspects of the ground shaking in the near-source area, neglecting other multidimensional effects, such as propagation effects and local site amplification. [ABSTRACT FROM AUTHOR]

Many biological assays require the ability to isolate and process single cells. Some research fields, such as the characterization of rare cells, the in vitro processing of stem cells, and the study of early stage cell differentiation, call for the additional and typically unmet ability to work with extremely low-count cell populations. In all these cases, efficient single-cell handling must be matched with the ability to work on a limited number of cells with a low cell loss rate. In this paper, we present a platform combining flow-through processing with deterministic (nonstatistical) patterning of cells coming from extremely small cell populations. We describe here modules using dielectrophoresis to control the position of cells flowing in microchannels and to pattern them in open microwells where cells were further analyzed. K562 cells continuously flowing at a speed of up to 100 µm/s were tridimensionally focused, aligned, and patterned inside microwells. A high-patterning yield and low cell loss rate were demonstrated experimentally: 15uL drops, containing an average of 15 cells, were transferred to the microchannel with an 83% yield, and cells were then patterned into microwells with a 100% yield. The deterministic patterning of cells was demonstrated both by isolating single cells in microwells and by creating clusters composed of a predetermined number of cells. Cell proliferation was assessed by easily recovering cells from open microwells, and a growth rate comparable to the control was obtained. [ABSTRACT FROM AUTHOR]

Abstract: We deal with some generalizations of the graph coloring problem on classes of perfect graphs. Namely we consider the -coloring problem (upper bounds for the color on each vertex), the precoloring extension problem (a subset of vertices colored beforehand), and a problem generalizing both of them, the -coloring problem (lower and upper bounds for the color on each vertex). We characterize the complexity of all those problems on clique-trees of different heights, providing polynomial-time algorithms for the cases that are easy. These results have interesting corollaries. First, one can observe on clique-trees of different heights the increasing complexity of the chain -coloring, -coloring, -coloring, and list-coloring. Second, clique-trees of height 2 are the first known example of a class of graphs where -coloring is polynomial-time solvable and precoloring extension is NP-complete, thus being at the same time the first example where -coloring is polynomially solvable and -coloring is NP-complete. Last, we show that the-coloring problem on unit interval graphs is NP-complete. These results answer three questions from Bonomo et al. [F. Bonomo, G. Durán, J. Marenco, Exploring the complexity boundary between coloring and list-coloring, Annals of Operations Research 169 (1) (2009) 3–16]. [Copyright &y& Elsevier]

Phosphoinositide-phospholipase C β1 (PLCβ1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation. We previously demonstrated that nuclear PLCβ1 activates the cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLCβ1 is essential for cyclin D3 promoter activation and gene transcription, through c-jun/AP1. Myotonic dystrophy (DM) is the most prevalent form of muscular dystrophy in adults. DM type 1 (DM1) and type 2 (DM2) are dominantly inherited multisystem disorders. DM1 is triggered by the pathological expansion of a (CTG)(n) triplet repeat in the gene coding for DMPK, the dystrophia myotonica-protein kinase, whereas a (CCTG)(n) tetranucleotide repeat expansion in the ZNF9 gene, encoding a CCHC-type zinc finger protein, causes DM2. We found that, unlike in normal myotubes, the level of expression of PLCβ1 in DM1 and DM2 cells was already elevated in proliferating cells. Treatment with insulin induced a dramatic decrease in the amount of PLCβ1. During differentiation, cyclin D3 and myogenin were elevated in normal myotubes, whereas differentiating DM1 and DM2 cells did not increase these proteins. Forced expression of PLCβ1 in DM1 and DM2 cells increased the expression of differentiation markers, myogenin and cyclin D3, and enhanced fusion of DM myoblasts. These results highlight again that PLCβ1 expression is a key player in myoblast differentiation, functioning as a positive regulator in the correction of delayed differentiation of skeletal muscle in DM human myoblasts. [ABSTRACT FROM AUTHOR]

SUMMARY We present the results of the regression analyses between Mercalli-Cancani-Sieberg (MCS) intensity and the spectral acceleration (SA) at 0.3, 1.0 and 2.0 s (SA03, SA10 and SA20). In Italy, the MCS scale is used to describe the level of ground shaking suffered by manufactures or perceived by the people, and it differs to some extent from the Mercalli Modified scale in use in other countries. We have assembled a new SA/MCS-intensity data set from the DBMI04 intensity database and the ITACA accelerometric data bank. The SA peak values are calculated in two ways-using the maximum among the two horizontal components, and using the geometrical mean among the two horizontal components. The regression analysis has been performed separately for the two kinds of data sets and for the three target periods. Since both peak ground parameters and intensities suffer of appreciable uncertainties, we have used the orthogonal distance regression technique. Also, tests designed to assess the robustness of the estimated coefficients have shown that single-line parametrizations for the regressions are sufficient to model the data within the model uncertainties. For the maximum horizontal component, SA xxhm, the new relations are [ABSTRACT FROM AUTHOR]

Nuclear inositide signaling is nowadays a well-established issue and a growing field of investigation, even though the very first evidence came out at the end of the 1980's. The understanding of its biological role is supported by the recent acquisitions dealing with pathology and namely hematological malignancies. Here, we review this issue highlighting the main achievements in the last years. J. Cell. Physiol. 226: 14-20, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In Italy, the Mercalli–Cancani–Sieberg (MCS) is the intensity scale in use to describe the level of earthquake ground shaking, and its subsequent effects on communities and on the built environment. This scale differs to some extent from the Mercalli Modified scale in use in other countries and adopted as standard within the USGS-ShakeMap procedure to predict intensities from observed instrumental data. We have assembled a new PGM/MCS-intensity data set from the Italian database of macroseismic information, DBMI04, and the Italian accelerometric database, ITACA. We have determined new regression relations between intensities and PGM parameters (acceleration and velocity). Since both PGM parameters and intensities suffer of consistent uncertainties we have used the orthogonal distance regression technique. The new relations are and Tests designed to assess the robustness of the estimated coefficients have shown that single-line parametrizations for the regression are sufficient to model the data within the model uncertainties. The relations have been inserted in the Italian implementation of the USGS-ShakeMap to determine intensity maps from instrumental data and to determine PGM maps from the sole intensity values. Comparisons carried out for earthquakes where both kinds of data are available have shown the general effectiveness of the relations. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this paper is to characterize the spatio-temporal distribution of Central-Europe seismicity. Specifically, by using a non-parametric statistical approach, the proportional hazard model, leading to an empirical estimation of the hazard function, we provide some constrains on the time behavior of earthquake generation mechanisms. The results indicate that the most conspicuous characteristics of M W 4.0+ earthquakes is a temporal clustering lasting a couple of years. This suggests that the probability of occurrence increases immediately after a previous event. After a few years, the process becomes almost time independent. Furthermore, we investigate the cluster properties of the seismicity of Central-Europe, by comparing the obtained result with the one of synthetic catalogs generated by the epidemic type aftershock sequences (ETAS) model, which previously have been successfully applied for short term clustering. Our results indicate that the ETAS is not well suited to describe the seismicity as a whole, while it is able to capture the features of the short- term behaviour. Remarkably, similar results have been previously found for Italy using a higher magnitude threshold. [Copyright &y& Elsevier]

Abstract: Here we report that PLC-β1 catalytic activity plays a role in the increase of cyclin D3 levels and induces the differentiation of C2C12 skeletal muscle cells. PLC-β1 mutational analysis revealed the importance of His331 and His378 for the catalysis. The expression of PLC-β1 and cyclin D3 proteins is highly induced during the process of skeletal myoblast differentiation. We have previously shown that PLC-β1 activates cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLC-β1 is a crucial regulator of the mouse cyclin D3 gene. We show that after insulin treatment cyclin D3 mRNA levels are lower in cells overexpressing the PLC-β1 catalytically inactive form in comparison to wild type cells. We describe a novel signalling pathway elicited by PLC-β1 that modulates AP-1 activity. Gel mobility shift assay and supershift performed with specific antibodies indicate that the c-jun binding site is located in a cyclin D3 promoter region specifically regulated by PLC-β1 and that c-Jun binding activity is significantly increased by insulin and PLC-β1 overexpression. Mutation of AP-1 site decreased the basal cyclin D3 promoter activity and eliminated its induction by insulin and PLC-β1. These results hint at the fact that PLC-β1 catalytic activity signals a c-jun/AP-1 target gene, i.e. cyclin D3, during myogenic differentiation. [Copyright &y& Elsevier]

Abstract: On all kidney waiting lists the 10% to 20% of patients who have antibodies against more than 80% of a panel of HLA antigens (panel reactive antibody [PRA] >80%) are difficult to transplant. The best solution for these patients is to find a compatible donor, ideally a full match, who yields a negative crossmatch test (CMX). If this is not possible, desensitization treatment (high-dose) intravenous immunoglobulin (IVIG) or plasmapheresis (PP) + low-dose IVIG is possible with good results in living donor kidney transplantation mainly if the antibody titer is low. It may also be offered to patients awaiting cadaveric donors too after a long waiting time; however, when applied for several months, it has the obvious disadvantage of giving the patient the risk for long-lasting immunologic weakness without the certitude of finding a kidney. In one of our recent cases of combined liver plus kidney transplantation, a positive CMX became negative 8 hours after the liver operation; the kidney was transplanted with a good result which lasted over 3 years. This observation suggested the possibility of a quick desensitization protocol in selected patients with a large (but not strong) immunization who probably are the majority. Patients sensitized to IVIG and with low titer PRA could be given a single PP + low-dose IVIG (what can be done within the time limit of cadaveric donor kidney transplantation) with good probability of turning an initial positive CMX to negative with the possibility of performing the operation and the advantage of giving the immunosuppression only when the kidney is present. [Copyright &y& Elsevier]

Abstract: The aim of this paper is to provide some constrains on the time behavior of earthquake generation mechanism, through the usage of a non-parametric statistics that leads up to the empirical estimation of the hazard function. The results indicate that the most characterizing temporal feature for large (M 7.0+) worldwide shallow earthquake occurrence is a clustering lasting few years, indicating that the probability of earthquake occurrence is higher immediately after the occurrence of an event. After that, the process becomes almost time independent, as in a Poisson process. Remarkably, this time clustering is very similar to what previously found for different spatio-magnitude windows, and it does not seem to depend on the tectonic style of the region. This may support the hypothesis of an universal law for earthquake occurrence. [Copyright &y& Elsevier]

The time-dependence of earthquake occurrence is mostly ignored in standard seismic hazard assessment even though earthquake clustering is well known. In this work, we attempt to quantify the impact of more realistic dynamics on the seismic hazard estimations. We include the time and space dependences between earthquakes into the hazard analysis via Monte Carlo simulations. Our target region is the Lower Rhine Embayment, a low seismicity area in Germany. Including aftershock sequences by using the epidemic type aftershock-sequence (ETAS) model, we find that on average the hypothesis of uncorrelated random earthquake activity underestimates the hazard by 5–10 per cent. Furthermore, we show that aftershock activity of past large earthquakes can locally increase the hazard even centuries later. We also analyse the impact of the so-called long-term behaviour, assuming a quasi-periodic occurrence of main events on a major fault in that region. We found that a significant impact on hazard is only expected for the special case of a very regular recurrence of the main shocks. [ABSTRACT FROM AUTHOR]

Abstract: We present two examples of statistical analysis of seismicity conducted by integrating geological, geophysical and seismological data with the aim to characterize the active stress field and to define the spatio-temporal distribution of large earthquakes. Moreover, our data will help to improve the knowledge of the “seismogenic behavior” of the areas and to provide useful information for seismic hazard evaluation. The earthquakes are described by two non-parametric statistical procedures integrating also tectonic-physical parameters to study the spatio-temporal variability. The results show that the areas are characterized by: 1) a stress regime with mainly extensional kinematics; 2) tectonic structures mainly oriented with the active stress field (S hmin =N44°±18° in the southern Apennines and S hmin =N50°±17° in the central Apennines); 3) cluster distribution of seismicity and 4) a high probability of earthquake occurrence (M >5.5) in the next 10 years. [Copyright &y& Elsevier]

Abstract: Background: Metabolic syndrome (MS) includes some risk factors for development of diabetes and cardiovascular disease, obesity (BMI > 30), high triglycerides, low HDL cholesterol, hypertension and impaired glucose tolerance. Following the definition of the Adult Treatment Panel III criteria, a diagnosis of MS was established when 3 or more factors were present. In renal transplan patients MS has been reported to negatively influence both patient and graft survivals. The present study sought to verify the effect of MS among our cases. Methods: 298 cadaveric renal transplant recipients operated between January 1, 1996 and December 31, 2001 with absence of diabetes before transplantation, stable renal function 1 year posttransplantation and at least 4 years follow up were retrospectively evaluated from the end of the first post-operative year. Results: 50 patients out of 298 (16,7%) had MS at the beginning of the study, including 37 of them with 3 and 13 with 4 risk factors. Only one patient with MS died of cardiovascular disease. Graft failure was observed in 23.5% MS patients versus 9,7% patients without the Syndrome (p:n.s.) Only Creatinine and the incidence of Cardiovascular Diseases at 4 years were statistically higher in MS patients (P < .001). Conclusions: These results suggested that MS is a risk factor for increasing CVD morbidity and decreased graft function, but early treatment of risk factors as soon as they become apparent can limit the adverse effects on patient and graft survival. [Copyright &y& Elsevier]

Abstract: Lipid second messengers, particularly those derived from the polyphosphoinositide metabolism, play a pivotal role in multiple cell signaling networks. Phosphoinositide 3-kinase (PI3K) generate 3′-phosphorylated inositol lipids that are key players in a multitude of cell functions. One of the best characterized targets of PI3K lipid products is the serine/threonine protein kinase Akt (protein kinase B, PKB). Recent findings have implicated the PI3K/Akt pathway in tumorigenesis because it stimulates cell proliferation and suppresses apoptosis. However, it was thought that this signal transduction network would exert its carcinogenetic effects mainly by operating in the cytoplasm. Evidence accumulated over the past 15 years has highlighted the presence of an autonomous nuclear inositol lipid cycle, and strongly suggests that lipid molecules are important components of signaling pathways operating at the nuclear level. PI3K, its lipid product phosphatidylinositol (3,4,5) trisphosphate (PtdIns(3,4,5)P3), and Akt have been identified within the nucleus and recent data suggest that they counteract apoptosis also by operating in this cell compartment through a block of caspase-activated DNase and inhibition of chromatin condensation. In this review, we shall summarize the most updated and intriguing findings about nuclear PI3K/PtdIns(3,4,5)P3/Akt in relationship with tumorigenesis and suppression of apoptotic stimuli. [Copyright &y& Elsevier]

Abstract: Over the last years, evidence has suggested that phosphoinositides, which are involved in the regulation of a large variety of cellular processes both in the cytoplasm and in the plasma membrane, are present also within the nucleus. A number of advances has resulted in the discovery that phosphoinositide-specific phospholipase C signalling in the nucleus is involved in cell growth and differentiation. Remarkably, the nuclear inositide metabolism is regulated independently from that present elsewhere in the cell. Even though nuclear inositol lipids hydrolysis generates second messengers such as diacylglycerol and inositol 1,4,5-trisphosphate, it is becoming increasingly clear that in the nucleus polyphosphoinositides may act by themselves to influence pre-mRNA splicing and chromatin structure. Among phosphoinositide-specific phospholipase C, the β1 isoform appears to be one of the key players of the nuclear lipid signaling. This review aims at highlighting the most significant and up-dated findings about phosphoinositide-specific phospholipase C β1 in the nucleus. [Copyright &y& Elsevier]

Abstract: Background: Prolonged mechanical ventilation and the consequently long stay in the intensive care unit (ICU) appear to be important infection risk factors in patients undergoing liver transplant. Methods: We analyzed the data relating to 70 liver transplants performed on 67 patients during the past year’s activities. For each patient we have considered the presence of preoperative pulmonary alterations, the first radiological result of the postoperative thorax, the PaO2/FiO2 ratio recorded in the peroperative phase immediately after induction of general anesthesia (T0), and arrival at the ICU at the end of the operation (T1). We also considered the enzyme trend (glutamate-oxalacetic transaminase [GOT] and glutamate-pyruvate transaminase [GPT]) recorded every 6 hours for the first 42 hours of the postoperative period (times T1 to T7). Results: There was an evident correspondence between the values of PaO2/FiO2 ≤ 300 ratio at time T1 and the subsequent duration of mechanical ventilation (P = .001). There was also a correlation between the PaO2/FiO2 ≤ 300 ratio at time T1 and the trend of the GPT in the first 24 hours postsurgery (P = .021; P = .026; P = .018; P = .048) or GOT trend over the same span of time (P = .027; P = .035; P = .048). Conclusions: Graft malfunction as expressed by the enzyme trend affects both the duration of mechanical ventilation and the postoperative PaO2/FiO2 ratios. This metric may be useful to reinforce infection surveillance and to perform an early percutaneous tracheostomy in these patients. [Copyright &y& Elsevier]

Abstract: The Prometheus system is a plasma filtration treatment coupling adsorption and hemodialysis (FPSA) aimed to blood purification in liver failure. After separation through an albumin-permeable membrane, plasma enters a secondary circuit where protein-bound toxic substances are removed by two adsorbers; p01, a neutral resin, and p02, an anion exchanger. Plasma is then returned to the venous line, where a high-flux hemodialyzer removes water-soluble substances. We used the Prometheus system in 12 patients with acute or acute-on-chronic liver insufficiency: eight cirrhosis, one posttransplant dysfunction, and three secondary liver insult (two cardiogenic shock and one rhabdomyolysis). All patients were severely hyperbilirubinemic, hypercholemic, and hyperammonemic. Twenty-eight sessions each lasting 340 ± 40 minutes were performed (2.5/patient). The mean total bilirubin decreased from 33.6 ± 20 to 22.2 ± 13.6 mg/dL (P < .001); the reduction ratios for cholic acid and ammonia were 48.6% and 51.6%, respectively. The pre- to postsession urea reduction was 57.6% ± 9.5% and creatinine 42.7% ± 10%. A significant reduction was observed in the circulating levels of soluble interleukin (IL) 2 receptor (pre: 2687.2 ± 1434.7; post: 1977.1 ± 602 Ul/ml; P < .001) and in IL 6 (pre: 56.1 ± 11.1; post: 35.9 ± 10.3 pg/mL, P = .05). During treatments the hemodynamics were stable. Two patients received liver transplantations. The secondary liver insult was completely overcome in all three patients. The overall survival at 30 days was 41.6% (5/12 patients). Prometheus, based on FPSA, produced high clearance for protein-bound and water soluble markers, which resulted in high treatment efficacy. [Copyright &y& Elsevier]

Abstract: The complications concerning liver and intestinal transplant surgery have relevance for the field of intensive care because they share some characteristics with those following complex long-term surgery. Thus, in this article we shall try to describe complications that are specific to liver and multivisceral transplants. A review of the existing literature on this topic reveals a large number of studies dedicated to early as well as late surgical complications, and immunosuppressive treatment, while there are far fewer contributions describing complications exclusively concerning intensive care. We shall thus attempt to focus on certain aspects where, besides the literature data, we have personal experience. In particular we want to underline the implications of failure in the functional recovery of the graft; alterations in water, electrolyte, and glycemic balance; as well as neurological, respiratory, renal, nutritional, and infective complications. [Copyright &y& Elsevier]

Inositide-specific phospholipase C (PLC) β1 is a key enzyme in nuclear lipid signal transduction affecting cell cycle progression and may be directly involved in regulation of gene expression and hematopoiesis. By microarrays, we compared the effect of nuclear PLCβ1 overexpression with that of PLC M2b cytoplasmatic mutant, which is exclusively located in the cytoplasm, in murine erythroleukemia cells. Out of 9000 genes analyzed, the CD24 gene, coding for an antigen involved in differentiation and hematopoiesis as well, was up-regulated in cells overexpressing nuclear PLCβ1 as compared with both cells overexpressing the M2b cytoplasmatic mutant and the wild type cells. Here we show that nuclear PLCβ1 up-regulated the expression of CD24. The correlation was strengthened by the observation that when PLCβ1 expression was silenced by means of small interfering RNA, CD24 expression was down-regulated. We also demonstrated that PLCβ1-dependent upmodulation of CD24 was mediated, at least in part, at the transcriptional level, in that PLCβ1 affected the CD24 promoter activity. Moreover, the up-regulation of CD24 was higher during erythroid differentiation of murine erythroleukemia cells. Altogether our findings, obtained by combining microarrays, phenotypic analysis, and small interfering RNA technology, identify CD24 as an molecular effector of nuclear PLCβ1 signaling pathway in murine erythroleukemia cells and strengthen the contention that nuclear PLCβ1 constitutes a key step in erythroid differentiation in vitro. [ABSTRACT FROM AUTHOR]

In the present work, we have analyzed the expression and subcellular localization of all the members of inositide-specific phospholipase C (PLCβ) family in muscle differentiation, given that nuclear PLCβ1 has been shown to be related to the differentiative process. Cell cultures of C2C12 myoblasts were induced to differentiate towards the phenotype of myotubes, which are also indicated as differentiated C2C12 cells. By means of immunochemical and immunocytochemical analysis, the expression and subcellular localization of PLCβ1, β2, β3, β4 have been assessed. As further characterization, we investigated the localization of PLCβ isoenzymes in C2C12 cells by fusing their cDNA to enhanced green fluorescent protein (GFP). In myoblast culture, PLCβ4 was the most expressed isoform in the cytoplasm, whereas PLCβ1 and β3 exhibited a lesser expression in this cell compartment. In nuclei of differentiated myotube culture, PLCβ1 isoform was expressed at the highest extent. A marked decrease of PLCβ4 expression in the cytoplasm of differentiated C2C12 cells was detected as compared to myoblasts. No relevant differences were evidenced as regards the expression of PLCβ3 at both cytoplasmatic and nuclear level, whilst PLCβ2 expression was almost undetactable. Therefore, we propose that the different subcellular expression of these PLC isoforms, namely the increase of nuclear PLCβ1 and the decrease of cytoplasmatic PLCβ4, during the establishment of myotube differentiation, is related to a spatial-temporal signaling event, involved in myogenic differentiation. Once again the subcellular localization appears to be a key step for the diverse signaling activity of PLCβs. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A new non-parametric multivariate model is provided to characterize the spatio-temporal distribution of large earthquakes. The method presents several advantages compared to other more traditional approaches. In particular, it allows straightforward testing of a variety of hypotheses, such as any kind of time dependence (i.e. seismic gap, cluster, and Poisson hypotheses). Moreover, it may account for tectonics/physics parameters that can potentially influence the spatio-temporal variability, and tests their relative importance. The method has been applied to the Italian seismicity of the last four centuries. The results show that large earthquakes in Italy tend to cluster; the instantaneous probability of occurrence in each area is higher immediately after an event and decreases until it reaches, in few years, a constant value representing the average rate of occurrence for that zone. The results also indicate that the clustering is independent of the magnitude of the earthquakes. Finally, a map of the probability of occurrence for the next large earthquakes in Italy is provided. [ABSTRACT FROM AUTHOR]