Effects of Impedance Reduction of a Robot for Wrist Rehabilitation on Human Motor Strategies in Healthy Subjects during Pointing Tasks

Studies on human motor control demonstrated the existence of simplifying strategies (namely `Donders' law') adopted to deal with kinematically redundant motor tasks. In recent research we showed that Donders' law also holds for human wrist during pointing tasks, and that it is heavily perturbed when interacting with a highly back-drivable state-of-the-art rehabilitation robot. We hypothesized that this depends on the excessive mechanical impedance of the Pronation/Supination (PS) joint of the robot and in this work we analyzed the effects of its reduction. To this end we deployed a basic force control scheme, which minimizes human-robot interaction force. This resulted in a 70% reduction of the inertia in PS joint and in decrease of 81% and 78% of the interaction torques during 1-DOF and 3-DOFs tasks. To assess the effects on human motor strategies, pointing tasks were performed by three subjects with a lightweight handheld device, interacting with the robot using its standard PD control (setting impedance to zero) and with the force-controlled robot. We quantified Donders' law as 2-dimensional surfaces in the 3-dimensional configuration space of rotations. Results revealed that the subject-specific features of Donders' surfaces reappeared after the reduction of robot impedance obtained via the force control

Genetic and phylogenetic evolution of HIV-1 in a low subtype heterogeneity epidemic: the Italian example

The Human Immunodeficiency Virus type 1 (HIV-1) is classified into genetic groups, subtypes and sub-subtypes which show a specific geographic distribution pattern. The HIV-1 epidemic in Italy, as in most of the Western Countries, has traditionally affected the Intra-venous drug user (IDU) and Homosexual (Homo) risk groups and has been sustained by the genetic B subtype. In the last years, however, the HIV-1 transmission rate among heterosexuals has dramatically increased, becoming the prevalent transmission route. In fact, while the traditional risk groups have high levels of knowledge and avoid high-risk practices, the heterosexuals do not sufficiently perceive the risk of HIV-1 infection. This misperception, linked to the growing number of immigrants from non-Western Countries, where non-B clades and circulating recombinant forms (CRFs) are prevalent, is progressively introducing HIV-1 variants of non-B subtype in the Italian epidemic. This is in agreement with reports from other Western European Countries

Conformational HIV-1 Envelope on particulate structures: a tool for chemokine coreceptor binding studies

The human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein gp120 presents conserved binding sites for binding to the primary virus receptor CD4 as well as the major HIV chemokine coreceptors, CCR5 and CXCR4

Effects of adjuvants on IgG subclasses elicited by virus-like Particles

<p>Abstract</p> <p>Background</p> <p>Virus-Like Particles (VLPs) represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C) adjuvants, has been evaluated in an animal model.</p> <p>Results</p> <p>Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced T_H2 pattern, VLPs formulated with either adjuvant elicited a T_H1-biased IgG subclasses (IgG2a and IgG3), with poly(I:C) more potent than CpG ODN1826.</p> <p>Conclusions</p> <p>The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.</p

A Compensatory Liability Regime to Promote the Exchange of Microbial Genetic Resources for Research and Benefit Sharing

Female rhesus macaques were immunized with HIV virus-like particles (HIV-VLPs) or HIV DNA administered as sequential combinations of mucosal (intranasal) and systemic (intramuscular) routes, according to homologous or heterologous prime-boost schedules. The results show that in rhesus macaques only the sequential intranasal and intramuscular administration of HIV-VLPs, and not the intranasal alone, is able to elicit humoral immune response at the systemic as well as the vaginal level.funding agencies|Simian Vaccine Evaluation Unit (SVEU) of the Division of AIDS||European Community|201433|</p

Challenges in cancer vaccine development for hepatocellular carcinoma

SummaryHepatocellular carcinoma (HCC) is the most common liver malignancy, representing the third and fifth leading cause of death from cancer worldwide in men and women, respectively.The main risk factor for the development of HCC is the hepatitis B and C virus (HBV and HCV) infection; non-viral causes (e.g., alcoholism and aflatoxin) are additional risk factors.HCC prognosis is generally poor because of the low effectiveness of available treatments and the overall 5-year survival rate is approximately 5–6%.In this framework, immunotherapeutic interventions, including cancer vaccines, may represent a novel and effective therapeutic tool. However, only few immunotherapy trials for HCC have been conducted so far with contrasting results, suggesting that improvements in several aspects of the immunotherapy approaches need to be implemented.In particular, identification of novel specific tumor antigens and evaluation of most advanced combinatorial strategies could result in unprecedented clinical outcomes with great beneficial effect for HCC patients.The state of the art in immunotherapy strategies for HCC and future perspectives are reported in the present review

Peptide-based vaccine for cancer therapies

Different strategies based on peptides are available for cancer treatment, in particular to counter-act the progression of tumor growth and disease relapse. In the last decade, in the context of therapeutic strategies against cancer, peptide-based vaccines have been evaluated in different tumor models. The peptides selected for cancer vaccine development can be classified in two main type: tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs), which are captured, internalized, processed and presented by antigen-presenting cells (APCs) to cell-mediated immunity. Peptides loaded onto MHC class I are recognized by a specific TCR of CD8+ T cells, which are activated to exert their cytotoxic activity against tumor cells presenting the same peptide-MHC-I complex. This process is defined as active immunotherapy as the host’s immune system is either de novo activated or restimulated to mount an effective, tumor-specific immune reaction that may ultimately lead to tu-mor regression. However, while the preclinical data have frequently shown encouraging results, therapeutic cancer vaccines clinical trials, including those based on peptides have not provided satisfactory data to date. The limited efficacy of peptide-based cancer vaccines is the consequence of several factors, including the identification of specific target tumor antigens, the limited immunogenicity of peptides and the highly immunosuppressive tumor microenvironment (TME). An effective cancer vaccine can be developed only by addressing all such different aspects. The present review describes the state of the art for each of such factors

Tackling hepatocellular carcinoma with individual or combinatorial immunotherapy approaches.

Abstract Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer globally. Indeed, there is a single drug approved as first-line systemic therapy in advanced unresectable HCC, providing a very limited survival benefit. In earlier stages, 5-year survival rates after surgical and loco-regional therapies are extremely variable depending on the stage of disease. Nevertheless, HCC is considered an immunogenic tumor arising in chronically inflamed livers. In such a scenario, immunotherapy strategies for HCC, in particular combinations including cancer vaccines, may represent a key therapeutic tool to improve clinical outcome in HCC patients. However, a lot of improvement is needed given the disappointing results obtained so far

<i>‘Je sais et tout mais...’</i> might the general extenders in European French be changing?

This paper addresses contemporary trends in the use of general extenders in two recent corpora of spontaneous French stratified by age. In these corpora, certain variants (e.g. et tout) are highly prevalent in the speech of young people compared to older speakers, while others are not. Other studies have shown that general extenders’ form as well as frequency tends to vary with respect to speakers’ age, while some extenders may also undergo grammaticalisation. The present study includes a comparison with a late 20th-century corpus of spoken French, and finds that not only age grading but also generational change might be occurring. This conclusion is supported by qualitative and quantitative analysis of the contemporary data, showing that the forms most frequent among young people appear to have acquired new pragmatic functions

Immature monocyte derived dendritic cells gene expression profile in response to Virus-Like Particles stimulation

We have recently developed a candidate HIV-1 vaccine model based on HIV-1 Pr55gag Virus-Like Particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from an Ugandan HIV-1 isolate of the clade A (HIV-VLP(A)s). The HIV-VLP(A)s induce in Balb/c mice systemic and mucosal neutralizing Antibodies as well as cytotoxic T lymphocytes, by intra-peritoneal as well as intra-nasal administration. Moreover, we have recently shown that the baculovirus-expressed HIV-VLPs induce maturation and activation of monocyte-derived dendritic cells (MDDCs) which, in turn, produce Th1- and Th2-specific cytokines and stimulate in vitro a primary and secondary response in autologous CD4+ T cells. In the present manuscript, the effects of the baculovirus-expressed HIV-VLP(A)s on the genomic transcriptional profile of MDDCs obtained from normal healthy donors have been evaluated. The HIV-VLP(A )stimulation, compared to both PBS and LPS treatment, modulate the expression of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. The results of gene profiling analysis here presented are highly informative on the global pattern of gene expression alteration underlying the activation of MDDCs by HIV-VLP(A)s at the early stages of the immune response and may be extremely helpful for the identification of exclusive activation markers