Altered Spinal Homeostasis and Maladaptive Plasticity in GFAP Null Mice Following Peripheral Nerve Injury

The maladaptive response of the central nervous system (CNS) following nerve injury is primarily linked to the activation of glial cells (reactive gliosis) that produce an inflammatory reaction and a wide cellular morpho-structural and functional/metabolic remodeling. Glial acidic fibrillary protein (GFAP), a major protein constituent of astrocyte intermediate filaments (IFs), is the hallmark of the reactive astrocytes, has pleiotropic functions and is significantly upregulated in the spinal cord after nerve injury. Here, we investigated the specific role of GFAP in glial reaction and maladaptive spinal cord plasticity following sciatic nerve spared nerve injury (SNI) in GFAP KO and wild-type (WT) animals. We evaluated the neuropathic behavior (thermal hyperalgesia, allodynia) and the expression of glial (vimentin, Iba1) and glutamate/GABA system markers (GLAST, GLT1, EAAC1, vGLUT, vGAT, GAD) in lumbar spinal cord sections of KO/WT animals. SNI induced neuropathic behavior in both GFAP KO and WT mice, paralleled by intense microglial reaction (Iba1 expression more pronounced in KO mice), reactive astrocytosis (vimentin increase) and expression remodeling of glial/neuronal glutamate/GABA transporters. In conclusion, it is conceivable that the lack of GFAP could be detrimental to the CNS as it lacks a critical sensor for neuroinflammation and morpho-functional-metabolic rewiring after nerve injury. Understanding the maladaptive morpho-functional changes of glial cells could represent the first step for a new glial-based targeted approach for mechanisms of disease in the CNS

On high-speed turning of a third-generation gamma titanium aluminide

Gamma titanium aluminides are heat-resistant intermetallic alloys predestined to be employed in components suffering from high mechanical stresses and thermal loads. These materials are regarded as difficult to cut, so this makes process adaptation essential in order to obtain high-quality and defect-free surfaces suitable for aerospace and automotive parts. In this paper, an innovative approach for longitudinal external high-speed turning of a third-generation Ti-45Al-8Nb- 0.2C-0.2B gamma titanium aluminide is presented. The experimental campaign has been executed with different process parameters, tool geometries and lubrication conditions. The results are discussed in terms of surface roughness/integrity, chip morphology, cutting forces and tool wear. Experimental evidence showed that, due to the high cutting speed, the high temperatures reached in the shear zone improve chip formation, so a crack-free surface can be obtained. Furthermore, the use of a cryogenic lubrication system has been identified in order to reduce the huge tool wear, which represents the main drawback when machining gamma titanium aluminides under the chosen process condition

Understanding consumer demand for new transport technologies and services, and implications for the future of mobility

The transport sector is witnessing unprecedented levels of disruption. Privately owned cars that operate on internal combustion engines have been the dominant modes of passenger transport for much of the last century. However, recent advances in transport technologies and services, such as the development of autonomous vehicles, the emergence of shared mobility services, and the commercialization of alternative fuel vehicle technologies, promise to revolutionise how humans travel. The implications are profound: some have predicted the end of private car dependent Western societies, others have portended greater suburbanization than has ever been observed before. If transport systems are to fulfil current and future needs of different subpopulations, and satisfy short and long-term societal objectives, it is imperative that we comprehend the many factors that shape individual behaviour. This chapter introduces the technologies and services most likely to disrupt prevailing practices in the transport sector. We review past studies that have examined current and future demand for these new technologies and services, and their likely short and long-term impacts on extant mobility patterns. We conclude with a summary of what these new technologies and services might mean for the future of mobility.Comment: 15 pages, 0 figures, book chapte

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Cooling of Dark-Matter Admixed Neutron Stars with density-dependent Equation of State

We propose a dark-matter (DM) admixed density-dependent equation of state where the fermionic DM interacts with the nucleons via Higgs portal. Presence of DM can hardly influence the particle distribution inside neutron star (NS) but can significantly affect the structure as well as equation of state (EOS) of NS. Introduction of DM inside NS softens the equation of state. We explored the effect of variation of DM mass and DM Fermi momentum on the NS EOS. Moreover, DM-Higgs coupling is constrained using dark matter direct detection experiments. Then, we studied cooling of normal NSs using APR and DD2 EOSs and DM admixed NSs using dark-matter modified DD2 with varying DM mass and Fermi momentum. We have done our analysis by considering different NS masses. Also DM mass and DM Fermi momentum are varied for fixed NS mass and DM-Higgs coupling. We calculated the variations of luminosity and temperature of NS with time for all EOSs considered in our work and then compared our calculations with the observed astronomical cooling data of pulsars namely Cas A, RX J0822-43, 1E 1207-52, RX J0002+62, XMMU J17328, PSR B1706-44, Vela, PSR B2334+61, PSR B0656+14, Geminga, PSR B1055-52 and RX J0720.4-3125. It is found that APR EOS agrees well with the pulsar data for lighter and medium mass NSs but cooling is very fast for heavier NS. For DM admixed DD2 EOS, it is found that for all considered NS masses, all chosen DM masses and Fermi momenta agree well with the observational data of PSR B0656+14, Geminga, Vela, PSR B1706-44 and PSR B2334+61. Cooling becomes faster as compared to normal NSs in case of increasing DM mass and Fermi momenta. It is infered from the calculations that if low mass super cold NSs are observed in future that may support the fact that heavier WIMP can be present inside neutron stars.Comment: 24 Pages, 15 Figures and 2 Tables. Version accepted in The European Physical Journal

Conservative Treatment of Ewing’s Sarcoma of the Uterus in Young Women

Ewing sarcoma-primitive neuroectodermal tumors (ES/PNETs) constitute a family of neoplasms characterized by a continuum of neuroectodermal differentiations. ES/PNET of the uterus is rare. There are 48 cases of ES/PNET of the uterus published in the literature as far as we know. We describe a case of Ewing sarcoma of the uterus occurring in a 17-year-old woman presenting with a two-month history of pelvic pain. After surgical excision and microscopic, immunohistochemical, and electron microscopy examination, the diagnosis of Ewing sarcoma of the uterus was suggested. This report will discuss the diagnosis and surgical and clinical management of Ewing uterine sarcoma in young women, according to the available literature. In spite of the rarity of ES/PNETs, they should be taken into account in the differential diagnosis of uterine neoplasms in young women

Two chemically similar stellar overdensities on opposite sides of the plane of the Galaxy

Our Galaxy is thought to have undergone an active evolutionary history dominated by star formation, the accretion of cold gas, and, in particular, mergers up to 10 gigayear ago. The stellar halo reveals rich fossil evidence of these interactions in the form of stellar streams, substructures, and chemically distinct stellar components. The impact of dwarf galaxy mergers on the content and morphology of the Galactic disk is still being explored. Recent studies have identified kinematically distinct stellar substructures and moving groups, which may have extragalactic origin. However, there is mounting evidence that stellar overdensities at the outer disk/halo interface could have been caused by the interaction of a dwarf galaxy with the disk. Here we report detailed spectroscopic analysis of 14 stars drawn from two stellar overdensities, each lying about 5 kiloparsecs above and below the Galactic plane - locations suggestive of association with the stellar halo. However, we find that the chemical compositions of these stars are almost identical, both within and between these groups, and closely match the abundance patterns of the Milky Way disk stars. This study hence provides compelling evidence that these stars originate from the disk and the overdensities they are part of were created by tidal interactions of the disk with passing or merging dwarf galaxies.Comment: accepted for publication in Natur

An emergency clinical pathway for stroke patients – results of a cluster randomised trial (isrctn41456865)

BACKGROUND: Emergency Clinical Pathways (ECP) for stroke have never been tested in randomized controlled trials (RCTs). OBJECTIVE: To evaluate the effectiveness of an ECP for stroke patients in Latium (Italy) emergency system. METHODS: cluster-RCT designed to compare stroke patient referrals by Emergency Medical Service (EMS) and Emergency Room (ER) health professionals trained in the ECP, with those of non-trained EMS and ER controls. Primary outcome measure was the proportion of eligible (aged /= 80 and symptom onset /= 6 hours) stroke patients referred to a stroke unit (SU). Intention to treat (ITT) and per-protocol (PP) analyses were performed, and risk ratios (RR) adjusted by age, gender and area, were calculated. RESULTS: 2656 patients in the intervention arm and 2239 in the control arm required assistance; 78.3% of the former and 80.6% of the latter were admitted to hospitals, and respectively 74.8% and 78.3% were confirmed strokes. Of the eligible confirmed strokes, 106/434 (24.4%) in the intervention arm and 43/328 (13.1%) in the control arm were referred to the SU in the ITT analysis (RR = 2.01; 95% CI: 0.79-4.00), and respectively 105/243 (43.2%) and 43/311 (13.8%) in the PP analysis (RR = 3.21; 95%CI: 1.62-4.98). Of patients suitable for i.v. thrombolysis, 15/175 (8.6%) in the intervention arm and 2/115 (1.7%) in the control arm received thrombolysis (p = 0.02) in the ITT analysis, and respectively 15/99 (15.1%) and 2/107 (1.9%)(p = 0.001) in the PP analysis. CONCLUSION: Our data suggest potenti efficiency and feasibility of an ECP. The integration of EMS and ERs with SU networks for organised acute stroke care is feasible and may ameliorate the quality of care for stroke patients. TRIAL REGISTRATION: Current Controlled Trials (ISRCTN41456865)