On the approximation of the Minimum Disturbance p-Facility Location Problem

AbstractAn n×m non-negative integer matrix D={dij} is given, representing the disturbance that customer i receives by a facility at location j. We consider the problem of finding p facilities so that the maximum, over the n customers, of the sums of their disturbances is minimized. We show that this problem can be deterministically approximated within O(ρ(logn+logp)), where ρ is the ratio between the biggest and the smallest positive entry of D. We obtain this result by first taking a randomized rounding approach to the problem and then by derandomizing the algorithm by the method of conditional probabilities

Approximation algorithms for maximum cut with limited unbalance

AbstractWe consider the problem of partitioning the vertices of a weighted graph into two sets of sizes that differ at most by a given threshold B, so as to maximize the weight of the crossing edges. For B equal to 0 this problem is known as Max Bisection, whereas for B equal to the number n of nodes it is the maximum cut problem. We present polynomial time randomized approximation algorithms with non trivial performance guarantees for its solution. The approximation results are obtained by extending the methodology used by Y. Ye for Max Bisection and by combining this technique with another one that uses the algorithm of Goemans and Williamson for the maximum cut problem. When B is equal to zero the approximation ratio achieved coincides with the one obtained by Y. Ye; otherwise it is always above this value and tends to the value obtained by Goemans and Williamson as B approaches the number n of nodes

Randomized Algorithms over Finite Fields for the Exact Parity Base Problem

AbstractWe present three randomized pseudo-polynomial algorithms for the problem of finding a base of specified value in a weighted represented matroid subject to parity conditions. These algorithms, the first two being an improved version of those presented by P. M. Camerini et al. (1992, J. Algorithms13, 258–273) use fast arithmetic working over a finite field chosen at random among a set of appropriate fields. We show that the choice of a best algorithm among those presented depends on a conjecture related to the best value of the so-called Linnik constant concerning the distribution of prime numbers in arithmetic progressions. This conjecture, which we call the C-conjecture, is a strengthened version of a conjecture formulated in 1934 by S. Chowla. If the C-conjecture is true, the choice of a best algorithm is simple, since the last algorithm exhibits the best performance, either when the performance is measured in arithmetic operations, or when it is measured in bit operations and mild assumptions hold. If the C-conjecture is false we are still able to identify a best algorithm, but in this case the choice is between the first two algorithms and depends on the asymptotic growth of m with respect to those of U and n, where 2n, 2m, U are the rank, the number of elements, and the maximum weight assigned to the elements of the matroid, respectively

DON GIULIO TARRA, EDUCATORE DEI SORDOMUTI. BIOBIBLIOGRAFIA ESSENZIALE

La presente scheda ripercorre la biobibliografia di Don Giulio Tarra nei suoi tratti essenziali.   Don Giulio Tarra, educator for the deaf and dumb. Essential bio-bibliography This document retraces the essential bio-bibliography of Don Giulio Tarra

Metabolic connectivity of resting-state networks in alpha synucleinopathies, from prodromal to dementia phase

Previous evidence suggests that the derangement of large-scale brain networks reflects structural, molecular, and functional mechanisms underlying neurodegenerative diseases. Although the alterations of multiple large-scale brain networks in Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are reported, a comprehensive study on connectivity reconfiguration starting from the preclinical phase is still lacking. We aimed to investigate shared and disease-specific changes in the large-scale networks across the Lewy Bodies (LB) disorders spectrum using a brain metabolic connectivity approach. We included 30 patients with isolated REM sleep behavior disorder (iRBD), 28 with stable PD, 30 with DLB, and 30 healthy controls for comparison. We applied seed-based interregional correlation analyses (IRCA) to evaluate the metabolic connectivity in the large-scale resting-state networks, as assessed by [18F]FDG-PET, in each clinical group compared to controls. We assessed metabolic connectivity changes by applying the IRCA and specific connectivity metrics, such as the weighted and unweighted Dice similarity coefficients (DC), for the topographical similarities. All the investigated large-scale brain resting-state networks showed metabolic connectivity alterations, supporting the widespread involvement of brain connectivity within the alpha-synuclein spectrum. Connectivity alterations were already evident in iRBD, severely affecting the posterior default mode, attentive and limbic networks. Strong similarities emerged in iRBD and DLB that showed comparable connectivity alterations in most large-scale networks, particularly in the posterior default mode and attentive networks. Contrarily, PD showed the main connectivity alterations limited to motor and somatosensory networks. The present findings reveal that metabolic connectivity alterations in the large-scale networks are already present in the early iRBD phase, resembling the DLB metabolic connectivity changes. This suggests and confirms iRBD as a risk condition for progression to the severe LB disease phenotype. Of note, the neurobiology of stable PD supports its more benign phenotype

Cognitive Reserve in Isolated Rapid Eye-Movement Sleep Behavior Disorder

Isolated rapid-eye-movement sleep behaviour disorder (RBD) is considered the prodromal stage of α-synucleinopathies (e.g., Parkinson’s disease and dementia with Lewy bodies); however, iRBD patients show a wide variety in the progression timing (5–15 years). The model of cognitive reserve (CR) might contribute to explaining this phenomenon. Our exploratory study aimed to evaluate, for the first time, the impact of CR level on cognitive performance in polysomnography-confirmed iRBD patients. Fifty-five iRBD patients (mean age ± SD: 66.38 ± 7.51; M/F 44/11) underwent clinical and neuropsychological evaluations at the time of diagnosis. The CR Index questionnaire was part of the clinical assessment. We found that iRBD patients with high levels of CR showed: (i) the lowest percentage of mild cognitive impairment (10%), and (ii) the best performance in visuo-constructive and verbal memory functions (i.e., the recall of the Rey–Osterrieth complex figure test). Our results suggest that CR might help iRBD patients better cope with the cognitive decline related to the neurodegenerative process, providing the first preliminary findings supporting CR as a possible protective factor in this condition. This might pave the way for future longitudinal studies to evaluate the role of CR as a modulating factor in the timing of iRBD conversion and cognitive deterioration development.</p

Back from the underworld: the exploitation of spring habitats by stygobiont species

Stygobionts, namely animals with strong adaptations to subterranean environments that are unable to complete their life cycles outside groundwater, can be observed in spring ecotones, but their occurrence is generally considered accidental. The aim of this paper is to assess if stygobiont occurrence in springs is linked to specific environmental conditions or if it is random, irrespective of their features. For three years, we surveyed 59 spring sites recording the occurrence of vertebrate and invertebrate stygobiont species and assessing if spring features were related to their distribution. Moreover, we recorded the escape reactions of two easily identifiable stygobiont species. We detected six taxa usually considered as strictly stygobiont based on their troglomorphic features. Two of them were quite widespread: the salamander Proteus anguinus and the shrimp Troglocaris planinensis. Environmental characteristics were significantly related to the distribution of stygobionts. Hydroperiod and occurrence of flooding were the factors that played the strongest role in affecting occurrence. Our study suggests that the occurrence of stygobionts in springs is linked to specific habitat features rather than being a random mechanism and that the exploitation of ecotones can be important for the lifecycle of some species usually assumed to be strictly associated to caves

The small heat shock protein B8 (HSPB8) efficiently removes aggregating species of dipeptides produced in C9ORF72-related neurodegenerative diseases

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two neurodegenerative diseases in which similar pathogenic mechanisms are involved. Both diseases associate to the high propensity of specific misfolded proteins, like TDP-43 or FUS, to mislocalize and aggregate. This is partly due to their intrinsic biophysical properties and partly as a consequence of failure of the neuronal protein quality control (PQC) system. Several familial ALS/FTD cases are linked to an expansion of a repeated G4C2 hexanucleotide sequence present in the C9ORF72 gene. The G4C2, which localizes in an untranslated region of the C9ORF72 transcript, drives an unconventional repeat-associated ATG-independent translation. This leads to the synthesis of five different dipeptide repeat proteins (DPRs), which are not âclassicalâ misfolded proteins, but generate aberrant aggregation-prone unfolded conformations poorly removed by the PQC system. The DPRs accumulate into p62/SQSTM1 and ubiquitin positive inclusions. Here, we analyzed the biochemical behavior of the five DPRs in immortalized motoneurons. Our data suggest that while the DPRs are mainly processed via autophagy, this system is unable to fully clear their aggregated forms, and thus they tend to accumulate in basal conditions. Overexpression of the small heat shock protein B8 (HSPB8), which facilitates the autophagy-mediated disposal of a large variety of classical misfolded aggregation-prone proteins, significantly decreased the accumulation of most DPR insoluble species. Thus, the induction of HSPB8 might represent a valid approach to decrease DPR-mediated toxicity and maintain motoneuron viability

Tdp-25 Routing to Autophagy and Proteasome Ameliorates its Aggregation in Amyotrophic Lateral Sclerosis Target Cells

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motoneurons, while non-neuronal cells may contribute to disease onset and progression. Most ALS cases are characterized by the mislocalization and aggregation of the TAR DNA binding protein 43 (TDP-43) in affected cells. TDP-43 aggregates contain C-terminal TDP-43 fragments of 35 kDa (TDP-35) and 25 kDa (TDP-25) and have been mainly studied in motoneurons, while little is currently known about their rate of accumulation and clearance in myoblasts. Here, we performed a comparative study in immortalized motoneuronal like (NSC34; i-motoneurons) cells and stabilized myoblasts (C2C12; s-myoblasts) to evaluate if these two cell types differentially accumulate and clear TDP forms. The most aggregating specie in i-motoneurons is the TDP-25 fragment, mainly constituted by the \u201cprion-like\u201d domain of TDP-43. To a lower extent, TDP-25 also aggregates in s-myoblasts. In both cell types, all TDP species are cleared by proteasome, but TDP-25 impairs autophagy. Interestingly, the routing of TDP-25 fragment to proteasome, by overexpressing BAG1, or to autophagy, by overexpressing HSPB8 or BAG3 decreased its accumulation in both cell types. These results demonstrate that promoting the chaperone-assisted clearance of ALS-linked proteins is beneficial not only in motoneurons but also in myoblasts