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Summary The use of Graphics Processing Units (GPUs) for scientific computing has become mainstream in the last decade. Applications ranging from deep learning to seismic modelling have benefitted from the increase in computational efficiency compared to their equivalent CPU-based implementations. Since many inverse problems in geophysics relies on similar core computations – e.g. dense linear algebra operations, convolutions, FFTs – it is reasonable to expect similar performance gains if GPUs are also leveraged in this context. In this paper we discuss how we have been able to take PyLops, a Python library for matrix-free linear algebra and optimization originally developed for singe-node CPUs, and create a fully compatible GPU backend with the help of CuPy and cuSignal. A benchmark suite of our core operators shows that an average 65x speed-up in computations can be achieved when running computations on a V100 GPU. Moreover, by careful modification of the inner working of the library, end users can obtain such a performance gain at virtually no cost: minimal code changes are required when switching between the CPU and GPU backends, mostly consisting of moving the data vector to the GPU device prior to solving an inverse problem with one of PyLops’ solvers.

The MPEG-G standardization initiative is a coordinated international effort to specify a compressed data format that enables large scale genomic data to be processed, transported and shared. The standard consists of a set of specifications (i.e., a book) describing: i) a nor-mative format syntax, and ii) a normative decoding process to retrieve the information coded in a compliant file or bitstream. Such decoding process enables the use of leading-edge com-pression technologies that have exhibited significant compression gains over currently used formats for storage of unaligned and aligned sequencing reads. Additionally, the standard provides a wealth of much needed functionality, such as selective access, data aggregation, ap-plication programming interfaces to the compressed data, standard interfaces to support data protection mechanisms, support for streaming and a procedure to assess the conformance of implementations. ISO/IEC is engaged in supporting the maintenance and availability of the standard specification, which guarantees the perenniality of applications using MPEG-G. Fi-nally, the standard ensures interoperability and integration with existing genomic information processing pipelines by providing support for conversion from the FASTQ/SAM/BAM file formats.In this paper we provide an overview of the MPEG-G specification, with particular focus on the main advantages and novel functionality it offers. As the standard only specifies the decoding process, encoding performance, both in terms of speed and compression ratio, can vary depending on specific encoder implementations, and will likely improve during the lifetime of MPEG-G. Hence, the performance statistics provided here are only indicative baseline examples of the technologies included in the standard.

Neurobasal medium (NBM) is a widely used medium for neuronal cultures, originally formulated to support survival of rat hippocampal neurons, but then optimized for several other neuronal subtypes. In the present study, the toxic effect of NBM on long-term cortical neuron cultures has been reported and investigated. A significant neuronal cell loss was observed 24 h after the total medium change performed at days in vitro 10. The neurotoxic effect was specifically because of NBM-A, a commercially derived modification of classic NBM, as neurons exposed to minimum essential medium for 24 h did not show the same mortality rate. We showed that the toxic effect was mediated by the N-methyl-D-aspartate receptor (NMDAr) as its inactivation partly prevented NBM-induced neuronal loss, and the addition of NMDAr activators, such as L-cysteine or glycine to minimum essential medium, reproduced the same toxicity rate observed in NBM. Besides the toxicity associated with NMDAr activation, the decreased antioxidative defenses also worsen (because of glutathione depletion) neuronal death, thus amplifying the effect of excitotoxic amino acids. Indeed, glutathione supplementation by the addition of its precursor N-acetyl-cysteine resulted in an increase in neuronal survival that partially prevented NBM-A toxicity. These results evidenced, on the one hand, the unsuitability of NBM-A for long-term neuronal culture, and on the other, they highlight the importance of selection of more suitable culture conditions.

Mesenchymal stem cells (MSCs) are adult bone marrow-derived stem cells actually proposed indifferently for the therapy of neurological diseases of both the Central (CNS) and the Peripheral Nervous System (PNS), as a panacea able to treat so many different diseases by their immunomodulatory ability and supportive action on neuronal survival. However, the identification of the exact mechanism of MSC action in the different diseases, although mandatory to define their real and concrete utility, is still lacking. Moreover, CNS and PNS neurons present many different biological properties, and it is still unclear if they respond in the same manner not only to MSC treatment, but also to injuries. For these reasons, in this study we compared the susceptibility of cortical and sensory neurons both to toxic drug exposure and to MSC action, in order to verify if these two neuronal populations can respond differently. Our results demonstrated that Cisplatin (CDDP), Glutamate, and Paclitaxel-treated sensory neurons were protected by the co-culture with MSCs, in different manners: through direct contact able to block apoptosis for CDDP- and Glutamate-treated neurons, and by the release of trophic factors for Paclitaxel-treated ones. A possible key soluble factor for MSC protection was Glutathione, spontaneously released by these cells. On the contrary, cortical neurons resulted more sensitive than sensory ones to the toxic action of the drugs, and overall MSCs failed to protect them. All these data identified for the first time a different susceptibility of cortical and sensory neurons, and demonstrated a protective action of MSCs only against drugs in peripheral neurotoxicity.

Over the last few years the therapeutic approach to demyelinating diseases has radically changed, strategies having been developed aimed at partnering the classic symptomatic treatments with the most advanced regenerative medicine tools. At first, the transplantation of myelinogenic cells, Schwann cells or oligodendrocytes was suggested, but the considerable technical difficulties, (poor availability, difficulties in harvesting and culturing, and the problem of rejection in the event of non-autologous sources), shifted attention towards more versatile cellular types, such as Mesenchymal Stem Cells (MSCs). Recent studies have already demonstrate both in vitro and in vivo that glially-primed MSCs (through exposure to chemical cocktails) have myelogenic abilities. In spite of a large number of papers on glially-differentiated MSCs, little is known about the ability of undifferentiated MSCs to myelinate axons and processes. Here we have demonstrated that also undifferentiated MSCs have the ability to myelinate, since they induce the myelination of rat DRG neuron processes after direct co-culturing. In this process a pivotal role is performed by the p75 receptor. © 2013 Elsevier Inc.

An appropriate complexity analysis stage is the first and fundamental step for any methodology aiming at the implementation of today's (complex) multimedia algorithms. Such a stage may have different final implementation goals such as defining a new architecture dedicated to the specific multimedia standard under study, or defining an optimal instruction set for a selected processor architecture, or to guide the software optimization process in terms of control-flow and data-flow optimization targeting a specific architecture. The complexity of nowadays multimedia standards, in terms of number of lines of codes and cross-relations among processing algorithms that are activated by specific input signals, goes far beyond what the designer can reasonably grasp from the "pencil and paper" analysis of the (software) specifications. Moreover, depending on the implementation goal different measures and metrics are required at different steps of the implementation methodology or design flow. The process of extracting the desired measures needs to be supported by appropriate automatic tools, since code rewriting, at each design stage, may result resource consuming and error prone. This paper reviews the state of the art of complexity analysis methodologies oriented to the design of multimedia systems and presents an integrated tool for automatic analysis capable of producing complexity results based on rich and customizable metrics. The tool is based on a C virtual machine that allows extracting from any C program execution the operations and data-flow information, according to the defined metrics. The tool capabilities include the simulation of virtual memory architectures. This paper shows some examples of complexity analysis results that can be yielded with the tool and presents how the tools can be used at different stages of implementation methodologies.

The clinical usability of pancreatic islet transplantation for the treatment of type I diabetes, despite some encouraging results, is currently hampered by the short lifespan of the transplanted tissue. In vivo studies have demonstrated that co-transplantation of Mesenchymal Stem Cells (MSCs) with transplanted pancreatic islets is more effective with respect to pancreatic islets alone in ensuring glycemia control in diabetic rats, but the molecular mechanisms of this action are still unclear. The aim of this study was to elucidate the molecular mechanisms of the positive effect of MSCs on pancreatic islet functionality by setting up direct, indirect and mixed co-cultures. MSCs were both able to prolong the survival of pancreatic islets, and to directly differentiate into an "insulin-releasing" phenotype. Two distinct mechanisms mediated these effects: i) the survival increase was observed in pancreatic islets indirectly co-cultured with MSCs, probably mediated by the trophic factors released by MSCs; ii) MSCs in direct contact with pancreatic islets started to express Pdx1, a pivotal gene of insulin production, and then differentiated into insulin releasing cells. These results demonstrate that MSCs may be useful for potentiating pancreatic islets' functionality and feasibility.

The positive effect of adult undifferentiated mesenchymal stem cells (MSCs) on neuronal survival has already been reported, although the mechanisms by which MSCs exert their effect are still a matter of debate. Here we have demonstrated that MSCs are able to prolong the survival of dorsal root ganglion (DRG) neurons mainly by inhibiting some proteolytic enzymes, and in particular the pathway of metalloproteinases (MMPs), a family of proteins that are involved in many neuronal processes, including survival. The inhibition of MMPs was both direct, by acting on MT-MMP1, and indirect, by acting on those proteins that regulate MMPs' activation, such as Timp-1 and Sparc. The importance of the MMPs' down-regulation for neuronal survival was also demonstrated by using N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycyl hydroxamic acid (NNGH), a wide range inhibitor of metalloproteinases, which was able to increase the survival of DRG neurons in a significant manner. The down-regulation of MMPs, obtained both by MSC contact and by chemical inhibition, led to the inactivation of caspase 3, the executor of apoptotic death in DRG neurons cultured alone, while caspase 7 was found to be irrelevant for the apoptotic process. The capacity of MSCs to prevent apoptosis mainly by inactivating the metalloproteinase pathway is an important finding that sheds light on MSCs' mechanism of action, making undifferentiated MSCs a promising tool for the treatment of many different neurodegenerative pathologies.

The involvement of the Mitogen-Activated Protein Kinases (MAPKs) family in platinum derivative-induced peripheral neuropathy has already been demonstrated. In particular, it has been evidenced that in Dorsal Root Ganglion (DRG) neurons prolonged exposure to oxaliplatin (OHP) induces early activation of p38 and ERK1/2, which mediate neuronal apoptosis, while the neuroprotective action of JNK/Sapk is downregulated by the drug treatment. In this study, the exposure of OHP-treated neurons to a neuroprotective stimulus, represented by a high dose of NGF, counteracts OHP-induced neuronal mortality. This effect was achieved by restoring the MAPK activation existing in untreated control cells. Increased viability occurred also after the administration of retinoic acid (RA), a pro-differentiative agent able to activate both JNK/Sapk and ERK1/2. The use of specific chemical inhibitors of MAPKs confirms the importance of this class of proteins for the neuroprotective pathway, since they reverse the protective effect. In summary, our findings assess the validity of MAPKs as the target of neuroprotective therapies during chemotherapeutic treatment. Moreover they also describe a double role for ERK1/2, depending on cellular stimulation, since it mediates neuronal apoptosis after OHP exposure. However, it is also important, as is JNK/Sapk, in preserving the correct cellular differentiation that is pivotal for neuronal survival.

An unsolved question is how platinum derivatives used for solid cancer therapy cause peripheral neuropathy in patients and apoptosis in "in vitro" models of chemotherapy-induced peripheral neuropathy. DRG neurons from E15 rat embryos were treated with toxic doses of oxaliplatin or cisplatin. Here, the role of MAPKs in neuronal apoptosis was studied. Both oxaliplatin and cisplatin induced a dose-dependent neuronal apoptosis, modulated by the proteins of Bcl-2 family. Regarding MAPKs, platinum derivatives activated p38 while they reduced the active form and the total amount of JNK/Sapk. Both oxaliplatin and cisplatin activated ERKs at early stages, although they behaved differently at later stages. By using specific inhibitors of the various MAPKs it was demonstrated that the platinum-induced neuronal apoptosis is mediated by early p38 and ERK1/2 activation, while JNK/Sapk has a neuroprotective role. These results suggest a role for the different MAPKs in peripheral neuropathies characterized by apoptosis of DRG neurons.

Mesenchymal stem cells (MSCs) have been found to be useful in the management of different models of neurological diseases. In the present study, we tested the possible protective effect of MSCs on sensory dorsal root ganglia (DRG) explants exposed to the toxic effect of CDDP, a widely used anticancer drug. DRG explants cultured on a collagen layer and exposed to NGF for 2 h (differentiating neurons) or for 5 days (fully differentiated neurons) were treated with CDDP and subsequently co-cultured with MSCs. MSCs were able to support the survival of both differentiating and fully differentiated DRG neurons up to 2 months after the drug treatment, reducing the CDDP-induced death of DRG neurons. MSCs were, however, unable to restore the correct length of DRG neurites compromised by CDDP treatment. The positive effect on neuronal survival was exerted through the contact between DRG and MSCs, and not mediated by neurotrophic factors released by the MSCs. Our observations could represent a starting point for designing a neuroprotective strategy to limit CDDP induced neuropathy without interfering with its anticancer properties.

Background Several studies report increased minor neurodevelopment dysfunctions in children born very low birth weight (VLBW). Usefulness of preventive early intervention programs to improve neurodevelopment outcome of VLBW infants is still under investigation. Aims To evaluate the effects of an early post-discharge developmental mother–child intervention program on neurodevelopment outcome at 36 months in VLBW infants. Study design Prospective study. Subjects 36 VLBW infants ([mean (S.D.)] birthweight = 864 g (204 g); gestational age = 27.9 weeks (2.4 weeks)), consecutively born January–August 2001, randomized in intervention and control groups. Outcome measures Neurodevelopment assessment at 36 months of chronological age with use of the Griffiths Mental Development Scale and related subscales. Results At 36 months of chronological age, as compared to controls, children in intervention group exhibited higher scores in personal–social subscales ([mean (S.D.)] = 101.4 (9.3) vs. 92.9 (12.1), P = 0.02), eye–hand coordination (92.7 (4.5) vs. 87.1 (9.9), P = 0.041), practical reasoning (98.6 (8.2) vs. 89.4 (10.1), P = 0.01). Development Scale were 97.6 (5.5) and 92.4 (9.9), respectively, in intervention and control groups (P = 0.074). Conclusions Early post-discharge developmental mother–child intervention program may have a positive effect on later neurodevelopment outcome of VLBW children.

The complexity of nowadays, algorithms in terms of number of lines of codes and cross-relations among processing algorithms that are activated by specific input signals, goes far beyond what the designer can reasonably grasp from the "pencil and paper" analysis of the (software) specifications. Moreover, depending on the implementation goal different measures and metrics are required at different steps of the implementation methodology or design flow of SoC. The process of extracting the desired measures needs to be supported by appropriate automatic tools, since code rewriting, at each design stage, may result resource consuming and error prone. This paper presents an integrated tool for automatic analysis capable of producing complexity results based on rich and customizable metrics. The tool is based on a C virtual machine that allows extracting from any C program execution the operations and data-flow information, according to the defined metrics. The tool capabilities include the simulation of virtual memory architectures.

This paper presents some examples of architectures for the implementation of wavelet codecs. Compared to previous works, the novelty of the approach is based on a joint optimization of both the algorithmic and architectural features, according to the overall system hardware and software strategy. The results of the analysis, although general for the different considered architectures, allow specific optimization of system performance for both dedicated ASIC design and embedded software implementation based on available system resources, such as execution speed and cache performance, while minimizing power consumption.

The increasing complexity of processing algorithms has lead to the need of more and more intensive specification and validation by means of software implementations. As the complexity grows, the intuitive understanding of the specific processing needs becomes harder. Hence, the architectural implementation choices or the choices between different possible software/hardware partitioning become extremely difficult tasks. Automatic tools for complexity analysis at high abstraction level are nowadays a fundamental need. This paper describes a new automatic tool for high-level algorithmic complexity analysis, the Software Instrumentation Tool (SIT), and presents the results concerning the complexity analysis and design space exploration for the implementation of a JPEG2000 encoder using a hardware/software co-design methodology on a Xilinx Virtex-IITM platform FPGA. The analysis and design process for the implementation of a video surveillance application example is described.

A series of esters and ethers of N-alkylmorpholin-2-ols, and their methiodides, which can be considered cyclic analogues of acetylcholine, were synthesized. The amines were obtained by acylation or etherification of morpholinols with the appropriate acyl chlorides and alcohols. All compounds were tested for their ability to interact with the muscarinic receptor M2 (guinea-pig atria) or M3 (rat ileum and urinary bladder) subtype. Some compounds, although endowed with relatively low potency, proved interesting for their organ selectivity. Some considerations on the structure-activity relationship are made and the results obtained with reference agonists and antagonists are also shown.

Burn and Rand1 demonstrated that some spastic effects of nicotine on aortic strips can be abolished by a prophylactic treatment with reserpine. The present investigation was conducted in order to study how reserpine or other drugs are able to prevent the spastic activity of nicotine on this blood vessel.

The increasing complexity of processing algorithms has led to the need of more and more intensive specification and validation by means of software implementations. As the complexity grows, the intuitive understanding of the specific processing needs becomes harder and harder. Hence, the architectural implementation choices or the choices between different possible software/hardware partitioning become extremely difficult tasks. Moreover, it is also desirable to understand and measure the algorithm complexity at the highest possible level near to the algorithmic level so as to be able to take the more appropriate actions. Automatic tools to perform such analysis become nowadays a fundamental need.In this paper, the requirements of a suitable algorithmic complexity evaluation technology are discussed, with a particular emphasis to the problem of the analysis of multimedia systems and signal processing algorithms. A brief review about limitations and weaknesses of existing tools is given, specifying the characteristics of ideal "complexity evaluation systems". A new approach is described, called here Software Instrumentation Tool, SIT, yielding an automatic software tool able to extract information not depending on the simulation platform, keeping into account specific input data and resulting in a good and useful measure of the desired high-level algorithmic complexity.