Et(h)nic Architecture in Mediterranean Area

Abstract The study of traditional built environment and the correct use of natural resources, nowadays, represent some of the multiple opportunities to product compatible structures with the environment, aimed to cope with high-energy demanding buildings and comfortless. The ethnic Mediterranean culture, purpose of the study, output of the traditional architectural knowledge, recognizes in the vernacular dwelling a symbiotic relationship between built and natural environment, respectful towards the territory thanks to the use of available raw materials that reduce human footprint. The correct use of the local raw materials and the definition of rules, archetypes and shapes are the perfect evidence of this symbiotic relationship, that ages improved achieving the perfect balance with the territory. The architectural elements, created to meet solely functional needs, changed over time, causing a rich heritage of shapes. To enhance the properties of the modern building envelopes it is necessary, preliminarily, to analyse the logic and architectural invariant of the traditional artefacts that are brought to mind, to a greater or to a lesser degree, for inspiration and to take us back on the way of harmonic planning with the place, actualizing the proposal

Apoptotic gene expression in neuropathic pain

Pain initiated or caused by a primary lesion or dysfunction in the nervous system is defined as neuropathic pain. It results from direct injury to nerves in the peripheral or central nervous system and is associated with several clinical symptoms. Neuropathic pain treatment is extremely difficult, as it is a very complex disease, involving several molecular pathways. Excitatory or inhibitory pathways controlling neuropathic pain development show altered gene expression, caused by peripheral nerve injury.
This study used several experimental pain models to demonstrate the occurrence of programmed cell death in the centers controlling pain induction and maintenance, such as spinal cord and pre-frontal cortex. We combined behavioural, molecular and morphological approaches to assess the involvement of bcl-2 gene family and caspases in neuropathic pain. Chronic constriction injury (CCI) and spared nerve injury (SNI) of rodent sciatic nerve induced the appearance of pain-like behaviours, such as hyperalgesia and allodynia. An early (2-3 days post-CCI) apoptosis appeared in the spinal cord neurons as the pro-apoptotic bax gene increased (320±19%). The incidence of apoptosis appeared to be limited to the first few days following nerve injury. Subsequently, increased expression of anti-apoptotic bcl-2 family genes may inhibit further neuron loss. SNI triggered apoptotic pathway and caspases activation in pre-frontal cortex 7, 14, and 21 days post-injury. Among the time-points analyzed, RT-PCR analysis showed increased expression of the bax/bcl-2 ratio (40±2%), bid (16±2%), caspase-1 (84±3%), caspase-8 (53±6%), caspase-9 (25±6%), caspase-12 (58±2%), TNF (32±2%) genes in the cortex by 7 days post-injury. Western blot analysis showed increased active Caspase-3 protein levels in the cortex at 3, 7, 14, and 21 post-surgery. This study shows that apoptotic genes could be an useful pharmacological target in neuropathic pain controlling.
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Chromatin remodeling agents for cancer therapy

Alterations in chromatin structure profoundly influence gene expression during normal cellular homeostasis and malignant transformation. Methylation of cytosines within CpG islands located in promoter and proximal coding regions facilitates recruitment of chromatin-remodeling proteins, which inhibits gene expression. Posttranslational modifications, such as acetylation, methylation, and phosphorylation, of core histone proteins \u27\u27mark\u27\u27 regions of chromatin for recognition by multiprotein complexes, which promote either chromatin relaxation and gene expression or chromatin compaction and repression of gene expression. Many genes become transcriptionally silenced during the development of cancer. Covalent epigenetic modifications such as DNA hypermethylation and histone post-translational modifications are an important early event during carcinogenesis and tumor development. Genes involved in key DNA damage responses pathways, apoptosis signaling and DNA repair, can frequently become methylated and epigenetically silenced in tumors. This may lead to differences in intrinsic sensitivity of tumors to chemotherapy, depending on the specific function of the gene inactivated. The fact that cancer can have an epigenetic etiology has encouraged the development of a new therapeutic option that might be termed "epigenetic therapy". The DNA methylation paradox, manifested as derepression of cancer-testis antigens and silencing of tumor suppressors during malignant transformation, provides rationale for the utilization of chromatin remodeling agents for cancer therapy. In this review, the recent advances in the understanding and clinical development of DNA methyltransferase and Histone deacetylase inhibitors, as well as their current role in cancer therapy, will be discussed

Role of Neurotrophins in Neuropathic Pain

Neurotrophins (NTs) belong to a family of structurally and functionally related proteins, they are the subsets of neurotrophic factors. Neurotrophins are responsible for diverse actions in the developing peripheral and central nervous systems. They are important regulators of neuronal function, affecting neuronal survival and growth. They are able to regulate cell death and survival in development as well as in pathophysiologic states. NTs and their receptors are expressed in areas of the brain that undergo plasticity, indicating that they are able to modulate synaptic plasticity

iMole, a web based image retrieval system from biomedical literature

iMole is a platform that automatically extracts images and captions from biomedical literature. Images are tagged with terms contained in figure captions by means of a sophisticate text-mining tool. Moreover, iMole allows the user to upload directly their own images within the database and manually tag images by curated dictionary. Using iMole the researchers can develop a proper biomedical image database, storing the images extracted from paper of interest, image found on the web repositories, and their own experimental images. In order to show the functioning of the platform, we used iMole to build a 2DE database. Briefly, tagged 2DE gel images were collected and stored in a searchable 2DE gel database, available to users through an interactive web interface. Images were obtained by automatically parsing 16,608 proteomic publications, which yielded more than 16,500 images. The database can be further expanded by users with images of interest trough a manual uploading process. iMole is available with a preloaded set of 2DE gel data at http://imole.biodigitalvalley.co

Autism Spectrum Disorders: Is Mesenchymal Stem Cell Personalized Therapy the Future?

Autism and autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental disorders. They are enigmatic conditions that have their origins in the interaction of genes and environmental factors. ASDs are characterized by dysfunctions in social interaction and communication skills, in addition to repetitive and stereotypic verbal and nonverbal behaviours. Immune dysfunction has been confirmed with autistic children. There are no defined mechanisms of pathogenesis or curative therapy presently available. Indeed, ASDs are still untreatable. Available treatments for autism can be divided into behavioural, nutritional, and medical approaches, although no defined standard approach exists. Nowadays, stem cell therapy represents the great promise for the future of molecular medicine. Among the stem cell population, mesenchymal stem cells (MSCs) show probably best potential good results in medical research. Due to the particular immune and neural dysregulation observed in ASDs, mesenchymal stem cell transplantation could offer a unique tool to provide better resolution for this disease

Long-Lasting Effects of Human Mesenchymal Stem Cell Systemic Administration on Pain-Like Behaviors, Cellular, and Biomolecular Modifications in Neuropathic Mice

Background: Neuropathic pain (NP) is an incurable disease caused by a primary lesion in the nervous system. NP is a progressive nervous system disease that results from poorly defined neurophysiological and neurochemical changes. Its treatment is very difficult. Current available therapeutic drugs have a generalized nature, sometime acting only on the temporal pain properties rather than targeting the several mechanisms underlying the generation and propagation of pain. Methods: Using biomolecular and immunohistochemical methods, we investigated the effect of the systemic injection of human mesenchymal stem cells (hMSCs) on NP relief. We used the spared nerve injury (SNI) model of NP in the mouse. hMSCs were injected into the tail vein of the mouse. Stem cell injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored every 10 days starting from day 11 until 90 days after surgery. Results: hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once injected into the tail vein. An anti-nociceptive effect was detectable from day 11 post surgery (7 days post cell injection). hMSCs were mainly able to home in the spinal cord and pre-frontal cortex of neuropathic mice. Injected hMSCs reduced the protein levels of the mouse pro-inflammatory interleukin IL-1β and IL-17 and increased protein levels of the mouse anti-inflammatory interleukin IL-10, and the marker of alternatively activated macrophages CD106 in the spinal cord of SNI mice. Conclusion: As a potential mechanism of action of hMSCs in reducing pain, we suggest that they could exert their beneficial action through a restorative mechanism involving: (i) a cell-to-cell contact activation mechanism, through which spinal cord homed hMSCs are responsible for switching pro-inflammatory macrophages to anti-inflammatory macrophages; (ii) secretion of a broad spectrum of molecules to communicate with other cell types. This study could provide novel findings in MSC pre-clinical biology and their therapeutic potential in regenerative medicine

Capacitive Displacement Sensor for a Self-Sensing Shock-Absorber Piston-Cylinder Mechanism

Measurement of piston displacement is a common problem for any pneumatic or hydraulic device, like shock-absorber. Direct measurements are not always feasible because of mechanical constraints; most recent techniques rely on magnetic phenomena, introducing considerable complexity. In an attempt to achieve an economical and feasible solution, an intrinsic capacitive sensor is developed. Such sensors measure the capacitance between piston and cylinder, which is directly proportional to displacement. It is developed an oscillator stage to measure the unknown capacitance. The oscillator’s output is acquired by a microcontroller, conditioned and transformed into the estimated displacement. This paper focuses on the design methodology of the measurement stage, highlighting tradeoffs and optimizations. The sensor was developed for an automotive application in a commercial shock absorber: however, it can be extended to other devices where proper electrical isolation between cylinder and piston is provided. Mathematical models and experimental results are reported compared to a commercial position sensor

Enlightening the Darknets: Augmenting Darknet Visibility with Active Probes

Darknets collect unsolicited traffic reaching unused address spaces. They provide insights into malicious activities, such as the rise of botnets and DDoS attacks. However, darknets provide a shallow view, as traffic is never responded. Here we quantify how their visibility increases by responding to traffic with interactive responders with increasing levels of interaction. We consider four deployments: Darknets, simple, vertical bound to specific ports, and, a honeypot that responds to all protocols on any port. We contrast these alternatives by analyzing the traffic attracted by each deployment and characterizing how traffic changes throughout the responder lifecycle on the darknet. We show that the deployment of responders increases the value of darknet data by revealing patterns that would otherwise be unobservable. We measure Side-Scan phenomena where once a host starts responding, it attracts traffic to other ports and neighboring addresses. uncovers attacks that darknets and would not observe, e.g. large-scale activity on non-standard ports. And we observe how quickly senders can identify and attack new responders. The “enlightened” part of a darknet brings several benefits and offers opportunities to increase the visibility of sender patterns. This information gain is worth taking advantage of, and we, therefore, recommend that organizations consider this option