Robot-aided neurorehabilitation: a robot for wrist rehabilitation.

In 1991, a novel robot, MIT-MANUS, was introduced to study the potential that robots might assist in and quantify the neuro-rehabilitation of motor function. MIT-MANUS proved an excellent tool for shoulder and elbow rehabilitation in stroke patients, showing in clinical trials a reduction of impairment in movements confined to the exercised joints. This successful proof of principle as to additional targeted and intensive movement treatment prompted a test of robot training examining other limb segments. This paper focuses on a robot for wrist rehabilitation designed to provide three rotational degrees-of-freedom. The first clinical trial of the device will enroll 200 stroke survivors. Ultimately 160 stroke survivors will train with both the proximal shoulder and elbow MIT-MANUS robot, as well as with the novel distal wrist robot, in addition to 40 stroke survivor controls. So far 52 stroke patients have completed the robot training (ongoing protocol). Here, we report on the initial results on 36 of these volunteers. These results demonstrate that further improvement should be expected by adding additional training to other limb segments.     

Electrogenerated chemiluminescence detection in paper-based microfluidic sensors

This paper describes the first approach at combining paper microfluidics with electrochemiluminescent (ECL) detection. Inkjet printing is used to produce paper microfluidic substrates which are combined with screen-printed electrodes (SPEs) to create simple, cheap, disposable sensors which can be read without a traditional photodetector. The sensing mechanism is based on the orange luminescence due to the ECL reaction of tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+)) with certain analytes. Using a conventional photodetector, 2-(dibutylamino)ethanol (DBAE) and nicotinamide adenine dinucleotide (NADH) could be detected to levels of 0.9 μM and 72 μM, respectively. Significantly, a mobile camera phone can also be used to detect the luminescence from the sensors. By analyzing the red pixel intensity in digital images of the ECL emission, a calibration curve was constructed demonstrating that DBAE could be detected to levels of 250 μM using the phone.     

A proteomics platform combining depletion, multi-lectin affinity chromatography (M-LAC), and isoelectric focusing to study the breast cancer proteome

The discovery of breast cancer associated plasma/serum biomarkers is important for early diagnosis, disease mechanism elucidation, and determination of treatment strategy for the disease. In this study of serum samples, a multidimensional fractionation platform combined with mass spectrometric analysis were used to achieve the identification of medium to lower abundance proteins, as well as to simultaneously detect glycan and abundance changes. Immuno-affinity depletion and multi-lectin chromatography (M-LAC) were integrated into an automated HPLC platform to remove high abundance protein and fractionate glycoproteins. The collected glycoproteomes were then subjected to isoelectric focusing (IEF) separation by a digital ProteomeChip (dPC), followed by in-gel digestion and LC-MS analysis using an Orbitrap mass spectrometer. As a result, the total number of identified proteins increased significantly when the IEF fractionation step was included as part of the platform. Relevant proteins with biological and disease significance were observed and the dynamic range of the serum proteome measurement was extended. In addition, potential glycan changes were indicated by comparing proteins in control and cancer samples in terms of their affinity to the multi-lectin column (M-LAC) and the pI profiles in IEF separation. In conclusion, a proteomics platform including high abundance protein depletion, lectin affinity fractionation, IEF separation, and LC-MS analysis has been applied to discover breast cancer-associated proteins. The following candidates, thrombospondin-1 and 5, alpha-1B-glycoprotein, serum amyloid P-component, and tenascin-X, were selected as promising examples of the use of this platform. They show potential abundance and glycan changes and will be further investigated in future studies.     

A Bayesian hierarchical correlation model for fMRI cluster analysis

Data-driven cluster analysis is potentially suitable to search for, and discriminate between, distinct response signals in blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), which appear during cerebrovascular disease. In contrast to model-driven methods, which test for a particular BOLD signal whose shape must be given beforehand, data-driven methods generate a set of BOLD signals directly from the fMRI data by clustering voxels into groups with correlated time signals. Here, we address the problem of selecting only the clusters that represent genuine responses to the experimental stimulus by modeling the correlation structure of the clustered data using a Bayesian hierarchical model. The model is empirically justified by demonstrating the hierarchical organization of the voxel correlations after cluster analysis. BOLD signal discrimination is demonstrated using: 1) simulations that contain multiple pathological BOLD response signals; and 2) fMRI data acquired during an event-related motor task. These demonstrations are compared with results from a model-driven method based on the general linear model. Our simulations show that the data-driven method can discriminate between the BOLD response signals, while the model-driven method only finds one signal. For fMRI, the data-driven method distinguishes between the BOLD signals appearing in the sensorimotor cortex and those in basal ganglia and putamen, while the model-driven method combines these signals into one activation map. We conclude that the proposed data-driven method provides an objective framework to identify and discriminate between distinct BOLD response signals.     

The Effects of Microstructure and Confinement on the Compressive Fragmentation of an Advanced Ceramic

We investigate the rate‐dependent compressive failure and fragmentation of a hot‐pressed boron carbide, under both uniaxial and confined biaxial compression, using quantitative fragment analysis coupled with quantitative microstructural analysis. Two distinct fragmentation regimes are observed, one of which appears to be more sensitive to the microstructural length scales in the material, while the second is more sensitive to the structural character and boundary conditions of the compressed sample. The first regime, which we refer to as “microstructure‐dependent,” appears to be associated with smaller fragments arising from the coalescence of fractures initiating from graphitic inclusions. This regime appears to become more dominant as the strain rate is increased and as the stress‐state becomes more confined. The second regime generates larger fragments with the resulting fragment size distribution dependent on the specific structural mechanisms that are activated during macroscopic failure (e.g., buckling of local columns developed during the compression). The average fragment size in the latter regime appears to be reasonably predicted by current fragmentation models. This improved understanding of the effects of microstructure and confinement on fragmentation then provides new insights into prior ballistic studies involving boron carbide.     

Efficacy of immunization with ferric citrate receptor FecA from Escherichia coli on induced coliform mastitis

The effects of immunization with the ferric citrate receptor FecA on antibody responses and on experimentally induced mastitis following intramammary challenge were investigated. Twenty-one cows were assigned to seven blocks of three cows based on expected parturition. Cows within block were randomly assigned to one of three treatments: 1) FecA immunization, 2) Escherichia coli J5 immunization, and 3) unimmunized controls. Challenge was by infusion of approximately 60 cfu of E. coli 727 into one uninfected mammary gland between 13 and 31 d after parturition. Cows within block were challenged on the same day. Cows immunized with FecA had higher immunoglobulin (Ig)G titers against FecA in serum and in mammary secretions at calving, immediately before challenge, and 7 d after challenge than did cows immunized with E. coli J5 or control cows. Immunization with FecA also increased IgG titers against whole-cell E. coli 727 in serum and in mammary secretions at calving. Serum IgM titers against FecA were higher in FecA immunized cows than in other treatment groups immediately before challenge. Bacterial counts in milk, duration of bacterial isolation in milk, rectal temperature, and milk somatic cell counts following intramammary challenge were similar among treatments. Milk production and dry matter intake did not differ among treatments. The ferric citrate receptor FecA was immunogenic in cows, but immunization had minimal effect on the clinical severity of experimentally induced E. coli mastitis.     

Effects of adjuvants on safety and efficacy of an Escherichia coli J5 bacterin

The effects of using a water-soluble adjuvant or an emulsified oil-based adjuvant on the safety, antibody titer, and clinical responses of an Escherichia coli J5 bacterin were tested in an experimental infection trial. Fifty-one cows were assigned to 17 blocks of 3. Two cows within each block of 3 were vaccinated with a commercially prepared E. coli J5 bacterin containing either a water-soluble adjuvant or the same bacterin preparation emulsified in oil. One cow in each block was an unvaccinated control. Cows were immunized at drying off and 42 d later. The right or left front mammary quarter of each experimental cow was challenged by intramammary infusion of E. coli 727 between 14 and 35 DIM. Areas of inflammation at the primary injection site were greater 1, 2, and 3 d following primary vaccination for bacterin containing oil-in-water adjuvant compared with bacterin containing water-soluble adjuvant. Whey anti-E. coli J5 IgG titers were higher at calving for cows vaccinated with bacterin containing oil-in-water adjuvant than for cows either vaccinated with bacterin containing water-soluble adjuvant or unvaccinated controls. Serum x-E. coli J5 IgG titers were higher at calving for vaccinated cows than for unvaccinated controls. Peak bacterial counts in milk from challenged quarters were greater for unvaccinated controls than for cows vaccinated with bacterin containing water-in-oil adjuvant. Bacterial counts in milk from challenged quarters and clinical score both were greater in unvaccinated controls than cows vaccinated with bacterin containing water-in-oil adjuvant between 12 and 24 h postchallenge. Clinical responses were similar between unvaccinated controls and cows vaccinated with bacterin containing water-soluble adjuvant.     

Opsonic activity of bovine serum and mammary secretion after Escherichia coli J5 vaccination.

Six pairs of cows were used to determine the effects of immunization with an Escherichia coli (O111:B4) J5 bacterin on in vitro opsonization of a smooth heterologous strain of E. coli. One cow in each pair was either immunized with the vaccine or sham-immunized at drying off, 30 d after drying off, and at calving. Opsonizing bacteria with serum collected from vaccinated cows 21 d after calving resulted in higher mean number of intracellular bacteria per phagocytosing neutrophil than opsonizing bacteria with serum collected from control cows. Phagocytic parameters using serum collected at drying off and calving did not differ between treatment groups. A trend for enhanced opsonic activity of colostrum from vaccinates was noted. Enhanced opsonization by serum from vaccinated cows coincided with higher serum IgM titer to E. coli J5 whole cell antigen compared with controls. Serum IgG titers to E. coli J5 did not differ between groups. Colostrum IgG titers to E. coli J5 were greater at calving in vaccinated than in control cows. Colostrum and milk collected 21 d after calving from vaccinated cows had higher IgM titers to E. coli J5 than did mammary secretions from control cows. Numbers of intracellular bacteria per phagocytizing neutrophil were correlated positively with IgM titers to E. coli J5 in both serum and colostrum.     

Efficacy of intramammary immunization with an Escherichia coli J5 bacterin

Intramammary immunization was investigated as a procedure to reduce the clinical signs of coliform mastitis. Twenty-four cows were equally distributed to the following Escherichia coli J5 immunization schedules: 1) Subcutaneous injection 14 d prior to the end of lactation, intramammary immunization 7 d after drying off, and subcutaneous injection 30 d into the dry period; 2) subcutaneous injections at drying off, at 30 d into the dry period, and within 12 h after calving; and 3) unimmunized controls. Intramammary immunizations were the infusion of vaccine via the teat canal into each of the four mammary glands. Cows were challenged by infusion of E. coli 727 into one uninfected mammary quarter at approximately 30 d after calving. Intramammary immunization enhanced antibody titers against E. coli J5 and E. coli 727 compared with subcutaneous immunization. Immunoglobulin G titers against E. coli J5 and E. coli 727 in whey were greater at the time of challenge and 7 d after challenge for cows that received the intramammary immunization than for cows immunized by only subcutaneous injections. Serum IgG titers against E. coli 727 were enhanced at 7 d after challenge for cows receiving intramammary immunizations compared with conventionally immunized cows. Serum IgM titers against E. coli 727 were higher at calving for cows receiving intramammary immunization compared with conventionally immunized cows. Immunization schedule had minimal effect on systemic and local signs of clinical mastitis following challenge.