Estimating Deep Muscles Activation from High Density Surface EMG Using Graph Theory.

In the recent years important steps forward have been made in the field of signal processing on muscle signals for hand prosthetics control. At the state of the art different algorithms and techniques allow a precise estimation of hand movements. However, they mostly work exclusively on the electrode space, not seeking for any information about the currents on the contracted muscles.In this study we propose a novel simplified method to estimate the muscles currents in the forearm, along with a first experimental application on two simple movements to assess its performance. We modeled the signal propagation from muscles to electrodes using a purely resistive electrical networks and afterwards apply the graph theory to assess the muscle currents. The proposed method considerably simplify the estimation of muscle's current, decreasing the problem complexity, and therefore potentially it can be a suitable approach for future prosthetics' control.

A Simple Method to Estimate Muscle Currents from HD-sEMG and MRI using Electrical Network and Graph Theory.

In the last years the spread of hand prosthetics has fueled the research on the field of signal processing applied on physiologic data. At the state of the art there are different algorithms that allow a precise estimation of hand movements, the majority of whom work just on the electrode space. Even though there are signal processing methods that access single muscle information, they are still premature for a real application on prosthetics. We present a novel method that exploit the information extracted from a magnetic resonance image (MRI) and a single row of high-density surface electromyography (HD-sEMG) electrodes to estimate the muscles currents in the forearm, providing a first experimental application on two simple wrist movements to assess its performance. The results show that the proposed method is able to identify the correct muscle with a single muscle-contraction task, whereas for a 2 muscle task it shows a high variance in the results. The method models the signal propagation from muscles to electrodes using a simple resistive electrical network and uses the graph theory to calculate the muscle currents. It brings a considerably simpler muscle's current estimation method, significantly decreasing the problem complexity, and therefore becoming a potential effective approach for future prosthetics' control.

Musculoskeletal Simulation for Determining Influences of the Magnitude of Sensory Noise and Stiffness on the Selection of Hip or Ankle Movement Strategies.

While standing, the elderly exhibit different move- ment behaviors compared to young people. However, the causes of these differences remain clear. The purpose of this study was to verify a hypothesis that only the magnitude of sensory noise and stiffness can reproducibly determine trends in the hip or ankle movement strategies. Simulations of postural control of a musculoskeletal model for three noise conditions and three stiffness conditions were performed. Variations in the angles of the hip and ankle suggested that the sensory noise amplitude had no influence on the selection. However, the ankle strategy tended to be selected with the increase of stiffness. Strategy shifts of elderly may be derived from other components; muscle weakness, increase of neurological time delay, or learning based on other evaluation index.

Simulation-Based Rule Generation Considering Readability.

Rule generation method is proposed for an aircraft control problem in an airport. Designing appropriate rules for motion coordination of taxiing aircraft in the airport is important, which is conducted by ground control. However, previous studies did not consider readability of rules, which is important because it should be operated and maintained by humans. Therefore, in this study, using the indicator of readability, we propose a method of rule generation based on parallel algorithm discovery and orchestration (PADO). By applying our proposed method to the aircraft control problem, the proposed algorithm can generate more readable and more robust rules and is found to be superior to previous methods.

Particle velocity and sediment transport at the limit of deposition in sewers.

This paper focuses on the sediment particle while it is transported at the limit of deposition in storm sewers, i.e. as bed load at the limit of concentration that leads to sediment deposition. Although many empirical sediment transport equations are known in the literature, there is only limited knowledge concerning particle velocity. Sediment particle and sphere velocity measurements were carried out in two pipe channels and these results led to the development of a semi-theoretical equation for sediment transport at the limit of deposition in sewers. Even in the transport process without deposition, sediment movement is slower than water velocity and depends on the angle of repose of sediment with a diameter d on the roughness k of the pipe channel. Instead of classical dimensionless bed shear stress ψ, a modified dimensionless bed shear stress ψ (d/k)(2/3) was suggested, based on the angle of repose and this parameter was proved to be significant for quantifying the transport capacity. The main purpose of this article is to emphasize the importance of careful observation of experiments. Not only number of tests, but physical understanding are essential for better empirical equations.

Local photodynamic therapy for equine squamous cell carcinoma: evaluation of a novel treatment method in a murine model.

The objective of this study was to evaluate the effect of local photodynamic therapy (PDT) with verteporfin on tumor growth inhibition of squamous cell carcinoma (SCC) in a murine model. SCC was implanted in 85 nude mice by subcutaneous injection of A-431 SCC cells. Treatment groups (10 mice/group) received an intra-tumoral injection of verteporfin dissolved in dimethyl sulfoxide (DMSO) or 5% dextrose solution at a dose of 0.01 or 0.1mg/cm3. Controls received only solvent, or no injectate. All groups received identical light illumination (100J/cm2). Relative change in tumor volume (RCTV) at day 30 was compared between groups using the Wilcoxon rank sum test (P< 0.05). Local PDT with verteporfin at a dose of 0.1mg/cm3 resulted in significantly lower RCTV at day 30 compared to controls. Choice of solvent (DMSO versus D5W) did not affect the results. Local PDT may be an effective adjunctive therapy for the treatment of periocular equine SCC.

Management of bilateral uveitis in a Toxoplasma gondii-seropositive cat with histopathologic evidence of fungal panuveitis.

A 5-year-old, neutered male Domestic Short-haired cat was referred with a 5-month history of anterior uveitis and cataract in the right eye. Clinical examination confirmed anterior uveitis and immature cataract in the right eye and chorioretinitis in the left eye. Ocular ultrasound showed a retinal detachment in the right eye. Diagnostic testing revealed elevated serum titers for Toxoplasma gondii. Anterior uveitis in the right eye and chorioretinitis in the left eye progressed, resulting in blindness despite a 21-day course of clindamycin and aggressive topical medical management of uveitis. The right eye was enucleated and histopathologic evaluation of the globe revealed panuveitis and multiple organisms morphologically consistent with Histoplasma capsulatum. Systemic treatment with itraconazole was initiated. Vision returned after 3 months of treatment and complete resolution of the retinal hemorrhages with formation of a flat chorioretinal scar was noted after 6 months of therapy. Itraconazole was discontinued 7 months after starting therapy, at which time the funduscopic appearance of the chorioretinal scar had remained static for 1 month. The cat has remained visual without evidence of disease progression for 6 months following discontinuation of itraconazole.

Xenotransplantation of cryopreserved equine squamous cell carcinoma to athymic nude and SCID mice.

Cryopreserved equine ocular squamous cell carcinoma (SCC) was inoculated subcutaneously into 15 athymic nude and 15 SCID mice. Xenotransplantation resulted in tumor growth in two athymic nude mice and 1 SCID mouse. Histological appearance and immunohistochemical characterization using cytokeratin 5/6 markers and p53 markers of the tumor grown in mice was in full accord with the original equine tumors. No evidence of metastasis was noted in any mouse. This model may serve as a relevant in vivo model for studying the biology of equine ocular SCC and for the testing of new therapeutic modalities.

DNA microarray analysis of natural killer cell-type lymphoproliferative disease of granular lymphocytes with purified CD3-CD56+ fractions.

Natural killer (NK) cell-type lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the outgrowth of CD3(-)CD16/56(+) NK cells, and can be further subdivided into two distinct categories: aggressive NK cell leukemia (ANKL) and chronic NK lymphocytosis (CNKL). To gain insights into the pathophysiology of NK cell-type LDGL, we here purified CD3(-)CD56(+) fractions from healthy individuals (n=9) and those with CNKL (n=9) or ANKL (n=1), and compared the expression profiles of >12 000 genes. A total of 15 'LDGL-associated genes' were identified, and a correspondence analysis on such genes could clearly indicate that LDGL samples share a 'molecular signature' distinct from that of normal NK cells. With a newly invented class prediction algorithm, 'weighted distance method', all 19 samples received a clinically matched diagnosis, and, furthermore, a detailed cross-validation trial for the prediction of normal or CNKL status could achieve a high accuracy (77.8%). By applying another statistical approach, we could extract other sets of genes, expression of which was specific to either normal or LDGL NK cells. Together with sophisticated statistical methods, gene expression profiling of a background-matched NK cell fraction thus provides us a wealth of information for the LDGL condition.

DNA microarray analysis of hematopoietic stem cell-like fractions from individuals with the M2 subtype of acute myeloid leukemia.

Acute myeloid leukemia (AML) may develop de novo or secondarily to myelodysplastic syndrome (MDS). Although the clinical outcome of MDS-related AML is worse than that of de novo AML, it is not easy to differentiate between these two clinical courses without a record of prior MDS. Large-scale profiling of gene expression by DNA microarray analysis is a promising approach with which to identify molecular markers specific to de novo or MDS-related AML. This approach has now been adopted with AC133-positive hematopoietic stem cell-like fractions purified from 10 individuals, each with either de novo or MDS-related AML of the M2 subtype. Sets of genes whose activity was associated with either disease course were identified. Furthermore, on the basis of the expression profiles of these genes, it was possible to predict correctly the clinical diagnosis for 17 (85%) of the 20 cases in a cross-validation trial. Similarly, different sets of genes were identified whose expression level was associated with clinical outcome after induction chemotherapy. These data suggest that, at least in terms of gene expression profiles, de novo AML and MDS-related AML are distinct clinical entities.

[Repair for atrioventricular valve regurgitation using autologous pericardium: report of a case].

A 13-year-old boy with [SLL] single left ventricle first underwent ventricular septation using a dacron patch at 3 years of age. Eight years after the first surgery, he presented with general fatigue on exertion as the chief complaint. Right-sided atrioventricular valve regurgitation, and dilatation of the right heart were diagnosed. Eleven years after surgery, right heart failure was uncontrollable by medicine, and 2nd surgery was performed. At operation, the right-sided heart valve leaflet was tightly adherent to the dacron septation patch, and valve plasty was judged impossible. We repaired the right-sided atrioventricular valve using an autologous pericardial valve leaflet and sub-valvular tissue. The postoperative course was uneventful, and he has been free from any complication for 33 months.

[Extracardiac fontan procedure in adult: report of a case].

We report a case of a 28-year-old female who underwent an extracardiac Fontan procedure. The subject was diagnosed as an atrioventricular septal defect (Rastelli classification: type C), a double outlet right ventricle, pulmonary artery stenosis, a hypoplasty of left ventricle, total anomalous venous return (Darling: Ib + IIb), and atrial flutter. She underwent a Blalock shunt and an aorto-pulmonary shunt at the ages of 3 and 9 years, respectively. Under a total CPB, an extracardiac total cavo-pulmonary connection (TCPC), using a 26 mm Hemashield graft, was completed. The postoperative course was uneventful. The complicated atrial anatomy and atrial arrhythmia indicated TCPC in this adult patient.

Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase.

The murine sak gene encodes a putative serine-threonine kinase which is homologous to the members of the Plk/Polo family. Although Sak protein is presumed to be involved in cell growth mechanism, efforts have failed to demonstrate its kinase activity. Little has been, therefore, elucidated how Sak is regulated and how Sak contributes to cell proliferation. Tec is a cytoplasmic protein-tyrosine kinase (PTK) which becomes activated by the stimulation of cytokine receptors, lymphocyte surface antigens, heterotrimeric G protein-linked receptors, and integrins. To clarify the in vivo function of Tec, we have tried to isolate the second messengers of Tec by using the yeast two-hybrid screening. One of such Tec-binding proteins turned out to be Sak. In human kidney 293 cells, Sak became tyrosine-phosphorylated by Tec, and the serine-threonine kinase activity of Sak was detected only under the presence of Tec, suggesting Sak to be an effector molecule of Tec. In addition, Tec activity efficiently protects Sak from the "PEST" sequence-dependent proteolysis. Internal deletion of the PEST sequences led to the stabilization of Sak proteins, and expression of these mutants acted suppressive to cell growth. Our data collectively supports a novel role of Sak acting in the PTK-mediated signaling pathway.

Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells.

Chronic myeloid leukemia (CML) is characterized by the clonal expansion of hematopoietic stem cells (HSCs). Without effective treatment, individuals in the indolent, chronic phase (CP) of CML undergo blast crisis (BC), the prognosis for which is poor. It is therefore important to clarify the mechanism underlying stage progression in CML. DNA microarray is a versatile tool for such a purpose. However, simple comparison of bone marrow mononuclear cells from individuals at different disease stages is likely to result in the identification of pseudo-positive genes whose change in expression only reflects the different proportions of leukemic blasts in bone marrow. We have therefore compared with DNA microarray the expression profiles of 3456 genes in the purified HSC-like fractions that had been isolated from 13 CML patients and healthy volunteers. Interestingly, expression of the gene for PIASy, a potential inhibitor of STAT (signal transducer and activator of transcription) proteins, was down-regulated in association with stage progression in CML. Furthermore, forced expression of PIASy has induced apoptosis in a CML cell line. These data suggest that microarray analysis with background-matched samples is an efficient approach to identify molecular events underlying the stage progression in CML.

Association of Cbl with Fms and p85 in response to macrophage colony-stimulating factor.

Tyrosine phosphorylation of Cbl and its association with signal-transducing molecules in response to macrophage colony-stimulating factor (M-CSF) were analyzed by using cell lines which express the wild-type and a mutant M-CSF receptor, Fms. We found that in a clone, F723 TF-1 cells expressing mutant Fms in which tyrosine 723 had been substituted with phenylalanine, the M-CSF stimulation-dependent association between Cbl and Fms was markedly impaired. However, phosphorylation of Cbl and its association with the p85 subunit of phosphatidylinositol 3-kinase were induced in these mutant cells as seen in the wild-type fms transfectant. These results suggest that phosphorylation of tyrosine 723 is particularly important for the recruitment of Cbl to the M-CSF receptor, but is not required for the phosphorylation and binding of Cbl to signal-transducing molecules such as p85.

[A case of supravalvular mitral ring].

A two-year-old girl with supravalvular mitral ring successfully underwent the excision of the ring. The preoperative echocardiogram showed supravalvular mitral ring and almost normal mitral leaflets. We paid attention not to injury mitral valve at the excision of the ring because supravalvular mitral ring adhered to the mitral valve.

[A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer: a cooperative study group trial (group B)].

A late phase II clinical study of RP56976 (docetaxel) in patients with advanced or recurrent gastric cancer was performed to evaluate the anti-tumor activity and clinical toxicity as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of 72 patients enrolled, 63 patients were eligible and 59 patients were evaluable for response. The anti-tumor effects obtained complete response (CR) in one patient partial response (PR) in 13, minor response (MR) in 3, no change (NC) in 20, and progressing disease (PD) in 22 patients. The overall response rate in 59 patients was 23.7% (14/59). For 14 CR or PR cases, a response appeared 10 to 107 days (median 33.5 days) and 1 to 8 (median 2) times of dosing after the initial administration. The response rate was 9.5% in the primary tumor, 31.3% livers, 50.0% abdominal tumor, and 24.1% lymph nodes, respectively. The major adverse reactions were gastrointestinal symptoms including nausea/vomiting, anorexia, fatigue, alopecia and fever. Leukocytopenia and neutrocytopenia were also observed with a high incidence, but they recovered after 8 days from the nadir. The results show that docetaxel is an effective anti-tumor agent for advanced or recurrent gastric cancer. It is necessary to conduct another clinical trial by concomitant administration with other anti-tumor agents.

Association of CrkL with STAT5 in hematopoietic cells stimulated by granulocyte-macrophage colony-stimulating factor or erythropoietin.

CrkL is an adapter protein comprising Src homology (SH) 2 and SH3 domains. We investigated the molecule(s) associated with CrkL in factor-dependent cell lines. In the granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell lines TF-1 and UT-7, an approximately 95-kDa tyrosine-phosphorylated protein was precipitated along with CrkL after GM-CSF stimulation. The same protein was also observed when we used the erythropoietin (EPO)-dependent cell line UT-7/EPO, in an EPO stimulation-dependent manner. We identified it as STAT5 (signal transducer and activator of transcription 5, 96 kDa) by STAT5-specific antibodies. The direct binding of the SH2 domain of CrkL to STAT5 was demonstrated in far Western blotting and pull-down experiments using the glutathione S-transferase (GST) fusion construct CrkL-SH2. The addition of the oligopeptide containing phosphotyrosine 694 in STAT5A impaired the association between GST-CrkL-SH2 and STAT5. Furthermore, in a gel shift assay using prolactin-inducible element (PIE) as the probe, the DNA binding activity of STAT5 was inhibited by the interaction with GST-CrkL-SH2 in vitro. Finally, we found that STAT5 associated with CrkL did not bind to PIE sequence. These results suggest that CrkL participates in the Janus kinase (JAK)-STAT pathway by direct association with STAT5.

[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent gastric cancer: a Japanese Cooperative Study Group trial (group A)].

A late phase II clinical study of RP56976 (docetaxel) was conducted in patients with advanced/recurrent gastric cancer as a multicenter cooperative trial. Docetaxel was administered intravenously at a dose of 60 mg/m2 every 3-4 weeks. Of the 76 patients enrolled, 66 patients were eligible and 59 patients were evaluable for response. One patient showed complete response (CR), 13 patients partial response (PR), 1 patient minor response (MR), 19 patients no change (NC) and 25 patients had progressive disease (PD). The overall response rate in 59 evaluable patients was 23.7% (95% CI = 13.6-36.6%). The primary tumor showed a 4.3% (1/23) response, while the metastatic lesions in the abdomen, pelvic mass, lung, liver, and lymph nodes showed response rates of 62.5% (5/8), 33.3% (1/3), 33.3% (1/3), 14.8% (4/27), and 13.9% (5/26), respectively. About hematological toxicity, severe (Grade 3 or more) leukopenia was observed in 36 patients (56.3%) and neutropenia in 52 patients (81.3%). Other major toxicity (Grade 3 or more) included nausea/vomiting in 11 patients (17.2%), anorexia in 9 patients (14.1%), fatigue in 5 patients (7.8%), and alopecia in 7 patients (10.9%), all which were tolerable. The results show that docetaxel is an effective anticancer agent for advanced/recurrent gastric cancer.