Modular and Recursive Kinematics and Dynamics for Parallel Manipulators

Constrained multibody systems typically feature multiple closed kinematic loops that constrain the relative motions and forces within the system. Typically, such systems possess far more articulated degrees-of-freedom (within the chains) than overall end-effector degrees-of-freedom.Thus, actuation of a subset of the articulations creates mixture of active and passive joints within the chain.The presence of such passive joints interferes with the effective modular formulation of the dynamic equations-of-motion in terms of a minimal set of actuator coordinates as well the subsequent recursivesolution for both forward and inverse dynamics applications. Thus, in this paper, we examine the development of modular and recursive formulations of equations-of-motion in terms of a minimal set of actuated-joint-coordinates for an exactly-actuated parallel manipulators. The 3 RRR planar parallel manipulator, selected to serve as a case-study, is an illustrative example of a multi-loop, multi-degree-of-freedom system with mixtures of active/passive joints. The concept of decoupled natural orthogonal complement (DeNOC) is combined with the spatial parallelism inherent in parallel mechanisms to develop a dynamics formulation that is both recursive and modular. An algorithmic approach to the development of both forward and inverse dynamics is highlighted. The presented simulation studies highlight the overall good numerical behavior of the developed formulation, both in terms of accuracy and lack of formulation stiffness.     

Endogenous production of beta-chemokines by CD4+, but not CD8+, T-cell clones correlates with the clinical state of human immunodeficiency virus type 1 (HIV-1)-infected individuals and may be responsible for blocking infection with non-syncytium-inducing HIV-1 in vitro

Recent studies have demonstrated that the beta-chemokines RANTES, MIP-1alpha, and MIP-1beta suppress human immunodeficiency virus type 1 (HIV-1) replication in vitro and may play an important role in protecting exposed but uninfected individuals from HIV-1 infection. However, levels of beta-chemokines in AIDS patients are comparable to and can exceed levels in nonprogressing individuals, indicating that global beta-chemokine production may have little effect on HIV-1 disease progression. We sought to clarify the role of beta-chemokines in nonprogressors and AIDS patients by examination of beta-chemokine production and HIV-1 infection in patient T-lymphocyte clones established by herpesvirus saimiri immortalization. Both CD4+ and CD8+ clones were established, and they resembled primary T cells in their phenotypes and expression of activated T-cell markers. CD4+ T-cell clones from all patients had normal levels of mRNA-encoding CCR5, a coreceptor for non-syncytium-inducing (NSI) HIV-1. CD4+ clones from nonprogressors and CD8+ clones from AIDS patients secreted high levels of RANTES, MIP1alpha, and MIP-1beta. In contrast, CD4+ clones from AIDS patients produced no RANTES and little or no MIP-1alpha or MIP-1beta. The infection of CD4+ clones with the NSI HIV-1 strain ADA revealed an inverse correlation to beta-chemokine production; clones from nonprogressors were poorly susceptible to ADA replication, but clones from AIDS patients were highly infectable. The resistance to ADA infection in CD4+ clones from nonprogressors could be partially reversed by treatment with anti-beta-chemokine antibodies. These results indicate that CD4+ cells can be protected against NSI-HIV-1 infection in culture through endogenously produced factors, including beta-chemokines, and that beta-chemokine production by CD4+, but not CD8+, T cells may constitute one mechanism of disease-free survival for HIV-1-infected individuals.     

Molecular and structural characterization of five novel mutations in the Bruton's tyrosine kinase gene from patients with X-linked agammaglobulinemia

BACKGROUND: The Btk (Bruton's tyrosine kinase) gene has been shown to be mutated in the human immunodeficiency disease, XLA (X-linked agammaglobulinemia). Btk is a member of the Tec family of cytosolic protein tyrosine kinases with distinct functional domains PH, TH, SH3, SH2, and kinase. Mutations have been observed in each of the Btk subdomains in XLA. We have analyzed the Btk gene in six XLA patients from five unrelated families. MATERIALS AND METHODS: DNA was prepared from the patients peripheral blood. The Btk exons including the junctional sequences were analyzed by single-strand conformation polymorphism (SSCP) followed by direct nucleotide sequencing after PCR-amplification. For structural analysis, the missense mutations were introduced into three-dimensional models of the PH and kinase domains of Btk and the outcome was predicted based on the knowledge of the protein function. RESULTS: Five novel mutations and two novel polymorphisms, all of which resulted from single-base alterations, were identified. Three of the five mutations were in the PH domain and two were in the kinase domain of Btk. Three of these mutations were of the missense type, two of which altered the same codon in the PH domain; the third one was located in the kinase domain. The fourth mutation was a point deletion in the PH domain causing a frameshift followed by premature termination. The fifth mutation was a splice donor-site mutation within the kinase domain which could result in an exon skipping. In four of the five instances, mothers of the patients were shown to be obligate carriers. In one instance, a sibling sister was identified as a heterozygote establishing her as a carrier. CONCLUSIONS: Functional consequences of the mutations causing frameshifts and altered splicing can be inferred directly. Functional consequences of the missense mutations were interpreted by 3-dimensional structural modeling of Btk domains. It is proposed that the two PH domain mutations will interfere with membrane localization while the kinase domain mutation will interfere with the enzymatic function of Btk. This study provides further insight into the role of Btk in XLA.     

A modification of split-skin graft

Although acine cell neoplasms have for a long time been regarded as benign tumors, they are presently considered to represent the carcinomas. These rare tumors mainly affect the parotid glands, and only exceptionally involve other salivary glands. Clinically, acic cell carcinoma present as isolated tumors simulating a pleomorphic adenoma. The diagnosis is histopathological, and complete surgical removal of the tumor is the treatment of choice, with cervical lymphatic voiding and/or postoperative radiotherapy in selected cases. A prolonged patient follow-up is required, for the tumor may recur many years after surgery. We report a case of acinic cell carcinoma in submaxillary gland.     

Conflicts of values and biodefense measures

Today, we are faced with an enemy that blends into the fabric of our society and has connections internationally with friends and foes alike. Such an enemy can exploit the nature of our free and open society with impunity. We freely disclose information regarding much of our technology and we have an open government answerable to the public to a degree rarely seen anywhere else in the world This certainly suggests a need to close the gates to protect ourselves from those who would infiltrate us for ill will. We must suffer imposed restrictions on ourselves in order to do so as there are no simple methods to distinguish the enemy from our own in a variety of settings. After September 11, 2001, the anthrax scare, the concern over small pox, and other bioterrorist tactics, we can easily conclude that our concern is not exaggerated.     

Fetal ECG extraction from single-channel maternal ECG usingsingular value decomposition

The extraction of fetal electrocardiogram (ECG) from the composite maternal ECG signal obtained from the abdominal lead is discussed. The proposed method employs singular value decomposition (SVD) and analysis based on the singular value ratio (SVR) spectrum. The maternal ECG (M-ECG) and the fetal ECG (F-ECG) components are identified in terms of the SV-decomposed modes of the appropriately configured data matrices, and elimination of the M-ECG and determination of F-ECG are achieved through selective separation of the SV-decomposed components. The unique feature of the method is that only one composite maternal ECG signal is required to determine the P-ECG component. The method is numerically robust and computationally efficient     

Expression pattern and cellular distribution of the murine homologue of AF10

The microbiologists use the term corynebacteria to describe aerobically growing, asporogenous, irregularly sharped gram-positive rods. They comprise strictly aerobic bacteria isolated from environment as well as preferentially anaerobic bacteria found in clinical specimens. A large part of these bacteria is considered as commensal of skin and mucous membranes. This group of organisms has recently been subjected to considerable taxonomic revisions, which have resulted in the proposal of several new species, many of them representing previous Centers for Diseases Control coryneform groups. Moreover, recent investigations demonstrated the existence of a pathogenic role for some of them. These bacteria comprise well-known pathogens such as C. diphtheriae responsible for diphtheria, Actinomyces spp. responsible for actinomycosis and Arcanobacterium haemolyticum recovered from pharyngitis, but other corynebacteria were related to particular infections. For example, the lipophilic and antibiotics multiresistant species Corynebacterium urealyticum and C. jeikeium were found to be responsible for urinary tract infections and septicemias, respectively. The recently described species Turicella otitidis was found to be implicated in otitis media and C. seminale were recovered from genital specimens of male patients. Implantation of material devices, use of broad-spectrum antibiotics led to an increase of sepsis due to the species C. jeikeium and C. amycolatum. Many of the new Actinomyces species grow well under aerobic conditions and are often implicated in various abscesses. Moreover an increase of immunocompromised patients led to the development of infections due to the aerobic actinomycete Rhodococcus equi. The association of some corynebacteria with particular diseases should prompt the microbiologist to identify these bacteria when they are encountered in a pathogenic situation. Identification of the major part of corynebacteria isolated from clinical specimens can now be achieved by using recent schemes.     

Integral Manufacturing of Composite Skin-Stringer Assembly and Their Stability Analyses

Stiffened composite constructions are increasingly being used in the primary structures of aircraft. One key component in these structures is the assembly between the skin and the stringer. The purpose of the stringers sandwiched between two separate layers of skin is to provide structural integrity to a relatively weak skin-structure. Current practice is to fabricate the skin and the stringer separately, assemble them with adhesively bonded joints, and then co-cure the entire assembly in an autoclave. However, the reliability of the joint manufactured in this fashion is not dependable and hence requires riveting of the skin with the stringer by hundreds of mechanical fasteners. Although the mechanical fastener improves the joint reliability, it certainly increases the weight and reduces the strength of the structure by introducing stress concentration points around the rivet holes. In order to eliminate these disadvantages, an innovative low cost manufacturing technique has been developed. The technique utilizes the vacuum assisted resin transfer molding (VARTM) process to co-inject both the skin and the stringer in one integral step. Furthermore, the skin and the stringer are now part of one continuous fabric preform which by default eliminates any adhesive bonding. Several skin-stringer assemblies with plain weave carbon fabric and SC-15 epoxy resin have been manufactured following this procedure. Stability of the manufactured skin-stringer assembly has been investigated experimentally. The extensive analysis focused on the determination of the critical load corresponding to the instability of the structure, failure load and study of the failure mechanisms. Details of manufacturing procedures and experimental investigations are presented in the paper.     

A report of diphtheria surveillance from a rural medical college hospital

A 5-year sentinel surveillance of diphtheria from 1989 to 1993 was undertaken at a rural medical college hospital. No significant change in the number of diphtheria cases was observed in spite of sustained high level of diphtheria, pertussis, tetanus vaccine-3 doses (DPT3) coverage. Most of the diphtheria cases occurred during July to November. Age distribution of diphtheria cases showed that more than 75% occurred above 2 years age (except in 1989) and around 65% cases above 3 years age. The age shift in diphtheria signified success of primary diphtheria immunisation, as well as indicated the lack of coverage with booster doses at appropriate ages. Because of high coverage with primary diphtheria immunisation there was decrease in circulating toxigenic C diphtheriae resulting in less natural boosting of antibody titre. Thus, in absence of booster immunisation, the older children and adults were more vulnerable to diphtheria. The findings of the study justified the need of emphasising importance of booster diphtheria immunisation at appropriate ages for effective control of diphtheria.     

Acute phase proteins in male Chinese schizophrenic patients in Singapore

The effects of orientating pairs of synergistic monoclonal antibodies (mAb) on binding of human chorionic gonadotropin (hCG) was studied by radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR). Antibody synergy towards hCG required two functionally intact antibodies located adjacent to each other and with different epitope specificities. We investigated whether immobilization procedures avoiding protein denaturation, increasing proper orientation and promoting higher molecular flexibility of the synergistic mAb resulted in significantly enhanced antigen, binding. Synergistic mAb pairs captured through their Fc-region by protein G or a polyclonal serum against the Fc-part of mouse IgG could be used at 10-fold lower coating concentrations to achieve maximal binding of the analyte as compared with the same mAb pairs coated directly onto polystyrene. The synergistic effect observed with protein A used as capture varied greatly with the subclasses of the two synergistic antibodies employed. Scatchard analysis revealed that the number of functionally synergistic antibody sites participating in the binding of hCG for one mAb pair was about 10 times higher for the protein G-captured as compared with the directly coated synergistic pair. Biotinylated synergistic mAb pairs, coated directly or captured by streptavidin, did not display any enhanced antigen binding when tested in SPR or ELISA. With SPR, synergy was only observed when the synergistic mAb had been captured through their Fc-region. Using protein G or a polyclonal rabbit anti-IgG1 serum as capture reagents in SPR, synergistic triple mAb combinations against hCG were demonstrated.