135 research outputs found
Identification of an antigenic domain near the C terminus of human granulocyte-macrophage colony-stimulating factor and its spatial localization.
The goal of this study was to map an epitope on the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) at its C terminus, a region whose integrity is fundamental in maintaining the normal function of this molecule. Residues including the fourth alpha-helix (D, 103-116) were analyzed for their role in the interaction with antibodies (Abs) raised against the protein. Five peptides homologous to different segments of the C terminus of hGM-CSF were synthesized. Peptide-(102-121) included the same residues of the alpha-helix D and the next five amino acids toward the C terminus; peptide-[E108A]-(102-121) introduced the mutation E108A in order to verify the role of acidic residues; peptide-[C96A](93-110) encompassed the beta-sheet 2 and half of the alpha-helix D; peptide-[C121A]-(110-127) included the second half of the alpha-helix D and the C terminus of hGMCSF; peptide-(13-31)-Gly-Pro-Gly-(103-116) included both the alpha-helices A and D connected by the tripeptide Gly-Pro-Gly, which allows the original antiparallel orientation of the two alpha-helices to be maintained. Both anti-protein and anti-peptide-(102-121) antibodies, capable of neutralizing the stimulatory activity of hGMCSF in the bone marrow colony-forming assays, recognized a specific epitope in the C terminus of hGM-CSF. Molecular modeling estimated the surface accessibility of hGM-CSF and the stability of the synthetic peptides in aqueous solution. Altogether, our results showed that the immunogenic region includes part of the alpha-helix D and the residues 116-120, which are external to this helix and particularly exposed on the protein surface, confirming the feasible participation of this region in antibody binding
NEOSTEL: the telescope detail design program for the ESA optical ground network dedicated to NEO discovery and tracking
The Fly-Eye architecture applied for a Space Debris and NEO Surveillance and Tracking optical telescope has been originally proposed by CGS and further refined in the framework of the Space Situational Awareness (SSA) Preparatory Program studies. The high level architecture of a Telescope based on the Fly-Eye concept has been defined in the TELAD Study. Following TELAD conceptual design, the activities of NEOSTEL aim now at generating the Detailed Design of a NEO Survey Telescope based on the Fly-Eye concept. All components of the telescope are designed at detailed level to satisfy the specific requirements for the Survey and Follow Up of the Near Earth Objects. The NEO Survey Telescope detailed design generated under this Program will be directly utilized for the manufacturing of the first prototype, planned to be launched by the SSA Program in the second half of 2015. In addition, the result of the Detailed Design will produce the documentation necessary to prepare the future site that will host the NEO Survey Telescope prototype as well as the high level architecture of the data processing SW that will be required at the telescope site. The product of the prototypation activity will then constitute a full Italian key Optical Core Technology, dedicated to the NEO thematic but also extendable to the SST Segment, therefore offering possibility of application both at Civil and at Institutional level. Furthermore the Fly-Eye Telescope Technology can actively collaborate with a dedicated Space Segment, opening the way to a complete and autonomous EU System
Intersigmoid hernia. A forgotten diagnosis, a systematic review of the literature over anatomical, diagnostic, surgical, and medicolegal aspects
Introduction. Intersigmoid hernia is a hernia of the small bowel into the intersigmoid fossa. It is well known to be a rare
condition. Recent reports reveal that the preoperative differentiation of intersigmoid hernias is difficult and the diagnosis is
often confirmed during the laparotomic exploration. Due to the vague clinical manifestation in most cases, the surgical
treatment is frequently delayed. Materials and Methods. In this study, we systematically reviewed the literature up to 2019
covering 114 studies and 124 patients with an intersigmoid hernia. &e purpose of this work is to improve the understanding of
the anatomical aspects, clinical presentation, diagnosis, and treatment of intersigmoid hernia so as to assist the preoperative
differentiation of these hernias when presented as acute abdomen in the emergency department. Results. &e diameter of the
intersigmoid recess was reported with mean 2.65 cm (range 1–10 cm, SD 1.15 cm) and the length of the incarcerated small
intestine was between 3 cm (min) and 150 cm (max): mean 25.25 cm, SD 35.04 cm. &e diameter of the sigmoid recess was
greater in patients who underwent resection due to strangulation (mean 3.31 cm, SD 1.53 cm) compared to those who underwent
only reduction of the hernia (mean 2.35 cm, SD 0.74 cm). &e time from onset to operation was less in patients
undergoing resection surgery due to throttling (mean 3.03 days, SD 3.01 days) compared to those who underwent only a
reduction of hernia incarceration (mean 8.49 days, SD 6.83 days). Conclusion. Intersigmoid hernia is often a forgotten diagnosis
and a clinical challange due to its anatomical characteristics
Visual stimulation and frequency of focal neurological symptoms engage distinctive neurocognitive resources in migraine with aura patients. A study of resting-state functional networks
Introduction: Several functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks. Methods: Before and after 4 min of visual stimulation with a checkerboard pattern, we collected functional MRI in 21 migraine with aura (MwA) patients and 18 healthy subjects (HS). For each recording session, we identified independent resting-state networks in each group and correlated network connection strength changes with clinical disease features. Results: Before visual stimulation, we found reduced connectivity between the default mode network and the left dorsal attention system (DAS) in MwA patients compared to HS. In HS, visual stimulation increases functional connectivity between the independent components of the bilateral DAS and the executive control network (ECN). In MwA, visual stimulation significantly improved functional connectivity between the independent component pairs salience network and DAS, and between DAS and ECN. The ECN Z-scores after visual stimulation were negatively related to the monthly frequency of aura. Conclusions: In individuals with MwA, 4 min of visual stimulation had stronger cognitive impact than in healthy people. A higher frequency of aura may lead to a diminished ability to obtain cognitive resources to cope with transitory but important events like aura-related focal neurological symptoms
Occipital atrophy signature in prodromal Lewy bodies disease
Introduction: Dementia with Lewy bodies (DLB) is typically characterized by parietal, temporal, and occipital atrophy, but less is known about the newly defined prodromal phases. The objective of this study was to evaluate structural brain alterations in prodromal DLB (p-DLB) as compared to healthy controls (HC) and full-blown dementia (DLB-DEM). Methods: The study included 42 DLB patients (n = 20 p-DLB; n = 22 DLB-DEM) and 27 HC with a standardized neurological assessment and 3-tesla magnetic resonance imaging. Voxel-wise analyses on gray-matter and cortical thickness were implemented to evaluate differences between p-DLB, DLB-DEM, and HC. Results: p-DLB and DLB-DEM exhibited reduced occipital and posterior parieto-temporal volume and thickness, extending from prodromal to dementia stages. Occipital atrophy was more sensitive than insular atrophy in differentiating p-DLB and HC. Occipital atrophy correlated to frontotemporal structural damage increasing from p-DLB to DLB-DEM. Discussion: Occipital and posterior-temporal structural alterations are an early signature of the DLB continuum and correlate with a long-distance pattern of atrophy
Antigene MYCN Silencing by BGA002 Inhibits SCLC Progression Blocking mTOR Pathway and Overcomes Multidrug Resistance
: Small-cell lung cancer (SCLC) is the most aggressive lung cancer type, and is associated with smoking, low survival rate due to high vascularization, metastasis and drug resistance. Alterations in MYC family members are biomarkers of poor prognosis for a large number of SCLC. In particular, MYCN alterations define SCLC cases with immunotherapy failure. MYCN has a highly restricted pattern of expression in normal cells and is an ideal target for cancer therapy but is undruggable by traditional approaches. We propose an innovative approach to MYCN inhibition by an MYCN-specific antigene-PNA oligonucleotide (BGA002)-as a new precision medicine for MYCN-related SCLC. We found that BGA002 profoundly and specifically inhibited MYCN expression in SCLC cells, leading to cell-growth inhibition and apoptosis, while also overcoming multidrug resistance. These effects are driven by mTOR pathway block in concomitance with autophagy reactivation, thus avoiding the side effects of targeting mTOR in healthy cells. Moreover, we identified an MYCN-related SCLC gene signature comprehending CNTFR, DLX5 and TNFAIP3, that was reverted by BGA002. Finally, systemic treatment with BGA002 significantly increased survival in MYCN-amplified SCLC mouse models, including in a multidrug-resistant model in which tumor vascularization was also eliminated. These findings warrant the clinical testing of BGA002 in MYCN-related SCLC
APEIRON: A Framework for High Level Programming of Dataflow Applications on Multi-FPGA Systems
High Energy Physics (HEP) Trigger and Data Acquisition systems (TDAQs) need ever increasing throughput and real-time data analytics capabilities either to improve particle identification accuracy and further suppress background events in trigger systems or to perform an efficient online data reduction for trigger-less ones.
As for the requirements imposed by HEP TDAQs applications in the class of real-time dataflow processing, FPGA devices are a good fit inasmuch they can not only provide adequate compute, memory and I/O resources but also a smooth programming experience thanks to the availability of High-Level Synthesis (HLS) tools.
The main motivation for the design and development of the APEIRON framework is that the currently available HLS tools do not natively support the deployment of applications over multiple FPGA devices, which severely chokes the scalability of problems that this approach could tackle. To overcome this limitation, we envisioned APEIRON as an extension of the Xilinx Vitis framework able to support a network of FPGA devices interconnected by a lowlatency direct network as the reference execution platform.
Developers can define scalable applications, using a dataflow programming model inspired by Kahn Process Networks, that can be efficiently deployed on a multi-FPGAs system: the APEIRON communication IPs allow low-latency communication between processing tasks deployed on FPGAs, even if they are hosted on different computing nodes. Thanks to the use of HLS tools in the workflow, processing tasks are described in C++ as HLS kernels, while communication between tasks is expressed through a lightweight C++ API based on non-blocking send() and blocking receive() operations
Differential Associations of IL-4 With Hippocampal Subfields in Mild Cognitive Impairment and Alzheimer’s Disease
Background/Aims: We aimed to assess the association between in volumetric measures of hippocampal sub-regions – in healthy older controls (HC), subjects with mild cognitive impairment (MCI) and AD- with circulating levels of IL-4.Methods: From AddNeuroMed Project 113 HC, 101 stable MCI (sMCI), 22 converter MCI (cMCI) and 119 AD were included. Hippocampal subfield volumes were analyzed using Freesurfer 6.0.0 on high-resolution sagittal 3D-T1W MP-RAGE acquisitions. Plasmatic IL-4 was measured using ELISA assay.Results: IL-4 was found to be (a) positively associate with left subiculum volume (β = 0.226, p = 0.037) in sMCI and (b) negatively associate with left subiculum volume (β = -0.253, p = 0.011) and left presubiculum volume (β = -0.257, p = 0.011) in AD.Conclusion: Our results indicate a potential neuroprotective effect of IL-4 on the areas of the hippocampus more vulnerable to aging and neurodegeneration
mTOR: from growth signal integration to cancer, diabetes and ageing
In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy
and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France
- …