Design of a robotic hand with a biologically-inspired parallel actuation system for prosthetic applications

Trabajo presentado al 34th Annual Mechanisms and Robotics Conference celebrado en Quebec del 15 al 18 de agosto de 2010.This paper presents the design of a robotic hand for prosthetic applications. The main characteristic of this robotic hand is its biologically-inspired parallel actuation system, which is based on the behavior/strength space of the Flexor Digitorum Profundus (FDP) and the Flexor Digitorum Superficialis (FDS) muscles. The design separates the strength space of the FDS and FDP muscles into a lighter strength region where finer manipulation and general approach tasks are executed, and a higher strength region where the more robust grasps are achieved. Two parallel actuator types and kinematic structures are designed to complement the requirements of both strength space regions.This research was performed under an award/contract from Telemedicine Advanced Technology Research Center (TATRC), of the U.S. Army Medical Research and Materiel Command (USAMRMC) of the U.S. Department of Defense.Peer Reviewe

Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens and 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive and 209 HPV-negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c-myc, LAGE-1, MAGE-A1, -A3, -A4, NY-ESO-1, SpanX-a1 and p53. AR to MAGE-A3, MAGE-A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue-sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV-positive and HPV-negative HNSCC

Identification and Characterization of Peripheral T-Cell Lymphoma-Associated SEREX Antigens

Peripheral T-cell lymphomas (PTCL) are generally less common and pursue a more aggressive clinical course than B-cell lymphomas, with the T-cell phenotype itself being a poor prognostic factor in adult non-Hodgkin lymphoma (NHL). With notable exceptions such as ALK+ anaplastic large cell lymphoma (ALCL, ALK+), the molecular abnormalities in PTCL remain poorly characterised. We had previously identified circulating antibodies to ALK in patients with ALCL, ALK+. Thus, as a strategy to identify potential antigens associated with the pathogenesis of PTCL, not otherwise specified (PTCL, NOS), we screened a testis cDNA library with sera from four PTCL, NOS patients using the SEREX (serological analysis of recombinant cDNA expression libraries) technique. We identified nine PTCL, NOS-associated antigens whose immunological reactivity was further investigated using sera from 52 B- and T-cell lymphoma patients and 17 normal controls. The centrosomal protein CEP250 was specifically recognised by patients sera and showed increased protein expression in cell lines derived from T-cell versus B-cell malignancies. TCEB3, BECN1, and two previously uncharacterised proteins, c14orf93 and ZBTB44, were preferentially recognised by patients' sera. Transcripts for all nine genes were identified in 39 cancer cell lines and the five genes encoding preferentially lymphoma-recognised antigens were widely expressed in normal tissues and mononuclear cell subsets. In summary, this study identifies novel molecules that are immunologically recognised in vivo by patients with PTCL, NOS. Future studies are needed to determine whether these tumor antigens play a role in the pathogenesis of PTCL

Chemotherapy-induced alopecia in mice. Induction by cyclophosphamide, inhibition by cyclosporine A, and modulation by dexamethasone

We introduce cyclophosphamide-induced alopecia (CYP-IA) in C57BL-6 mice as a clinically relevant model for studying the biology of chemotherapy-induced alopecia and for developing anti-alopecia drugs. One injection of CYP to mice with all back skin follicles in anagen VI induces severe alopecia that strikingly reproduces the follicle response, recovery, and histopathology seen in human CYP-IA. CYP dose-dependently induces abnormal follicular melanogenesis and dystrophic anagen or, in more severely damaged follicles, dystrophic catagen. Both dystrophy forms are followed by an extremely shortened telogen phase, but differ in the associated hair loss and in recovery patterns, which determines hair regrowth. This follicular response to CYP can be manipulated pharmacologically: systemic cyclosporine A shifts it toward a mild form of dystrophic anagen, thus retarding CYP-IA and prolonging "primary recovery". Topical dexamethasone, in contrast, forces follicles into dystrophic catagen, which augments CYP-IA, but accelerates the regrowth of normally pigmented hair ("secondary recovery")

Transforming growth factor-beta receptor type I and type II expression during murine hair follicle development and cycling

Although the TGF-β family of growth factors probably regulates skin and hair follicle development, its exact role is still quite ill-defined. Here, we characterize the correlative expression pattern of the interdependent high affinity receptor proteins for TGF-β1 and TGF-β3, TGF-β3 receptor type I (TGF-βRI) and TGF-β receptor type II (TGF-βR11), during hair follicle development and cycling in C57BL/6 mice. During neonatal follicle development, TGF-βRII immunoreactivity is confined to epithelial cells. Focal epidermal TGF-βRII expression is seen even before actual hair placode formation. In contrast to the TGF-βRlI immunoreactivity in the outer root sheath, precortical hair matrix and inner root sheath cells were TGF-βRII negative during hair bulb morphogenesis. TGF-βRI (Alk-5) immunoreactivity largely overlapped the TGF-βR11 expression pattern, but was more wide-spread. During hair follicle cycling in adolescent mice, TGF-βRlI immunoreactivity was restricted to follicles, and was strikingly hair cycle dependent (maximal immunoreactivity: anagen VI and early catagen). Again, TGF-βRI (Alk-5) immunoreactivity co-localized with TGF-βRII immunoreactivity, but was more extensive. Reverse transcriptase polymerase chain reaction analysis of TGF-βRII mRNA confirmed peak transcript levels in back skin with most hair follicles in the anagen VI-catagen transformation. mRNA levels of TGF-βRI (Alk-5) did not vary significantly during the hair cycle, whereas those of TGF-βRI (threonine-serine kinase 7L) declined during early anagen, and were maximal during the anagen-catagen transition. THis provides a basis for defining the choreography of TGF-β-related signalling during hair follicle morphogenesis and cycling, introduces intraepidermal TGF-βRII immunoreactivity as a marker for imminent follicle development, and supports the concept that both TGF-βRII and TGF-βRI stimulation is involved in, but not restricted to, the control of catagen induction