Mapping of the Spinal Circuitry Associated with Paw Withdrawal Learning in Spinal Mice

The overall goal of this project was to identify the neural circuitry involved in paw withdrawal learning (PaWL) in complete spinal cord transected (ST) mice. Pseudorabies virus (PRV)-Bartha 152 was injected into the tibialis anterior (TA), the primary muscle involved in this learning. The use of PRV, a transsynaptic retrograde marker, allowed labeling of the TA motoneurons and its associated interneurons in the spinal cord. By combining PRV-Bartha 152 with c-fos (an activity-dependent marker) and CaMKII (a learning-associated marker), the activated motoneurons and interneurons that were associated with spinal learning were identified. Of all PRV+ labeled neurons, 21% were motoneurons and found only on the ipsilateral side of the spinal cord (same side where learning occurred). Sixty-five percent of the labeled interneurons were found on the ipsilateral side of the spinal cord and 14% were found on the contralateral side. A majority (~60%) of the interneurons and motoneurons on the ipsilateral side were activated during PaWL. Moreover, activated PRV+ interneurons that were also positive for CaMKII were mostly located in laminae VI-VII suggesting that the neural circuitry involved in PaWL occurred in these regions

A critical assessment of viscous models of trench topography and corner flow

Stresses for Newtonian viscous flow in a simple geometry (e.g., corner flow, bending flow) are obtained in order to study the effect of imposed velocity boundary conditions. Stress for a delta function velocity boundary condition decays as 1/R(2); for a step function velocity, stress goes as 1/R; for a discontinuity in curvature, the stress singularity is logarithmic. For corner flow, which has a discontinuity of velocity at a certain point, the corresponding stress has a 1/R singularity. However, for a more realistic circular-slab model, the stress singularity becomes logarithmic. Thus the stress distribution is very sensitive to the boundary conditions, and in evaluating the applicability of viscous models of trench topography it is essential to use realistic geometries. Topography and seismicity data from northern Hoshu, Japan, were used to construct a finite element model, with flow assumed tangent to the top of the grid, for both Newtonian and non-Newtonian flow (power law 3 rheology). Normal stresses at the top of the grid are compared to the observed trench topography and gravity anomalies. There is poor agreement. Purely viscous models of subducting slables with specified velocity boundary conditions do not predict normal stress patterns compatible with observed topography and gravity. Elasticity and plasticity appear to be important for the subduction process

Using a multifrontal sparse solver in a high performance, finite element code

We consider the performance of the finite element method on a vector supercomputer. The computationally intensive parts of the finite element method are typically the individual element forms and the solution of the global stiffness matrix both of which are vectorized in high performance codes. To further increase throughput, new algorithms are needed. We compare a multifrontal sparse solver to a traditional skyline solver in a finite element code on a vector supercomputer. The multifrontal solver uses the Multiple-Minimum Degree reordering heuristic to reduce the number of operations required to factor a sparse matrix and full matrix computational kernels (e.g., BLAS3) to enhance vector performance. The net result in an order-of-magnitude reduction in run time for a finite element application on one processor of a Cray X-MP

Modeling of the surface static displacements and fault plane slip for the 1979 Imperial Valley earthquake

Synthesis of geodetic and seismological results for the 1979 Imperial Valley earthquake is approached using three-dimensional finite element modeling techniques. The displacements and stresses are calculated elastically throughout the modeled region. The vertical elastic structure in the model is derived from compressional and shear wave velocities as used in the seismic data analysis (Fuis et al., 1981) combined with a sediment density profile. Two strategies for applying initial conditions are followed in this modeling. In the first strategy, a sample seismological estimate for fault plane slip is used to predict the resultant surface motions. We show that the geodetic strain results over distances of tens of kilometer from the fault (Snay et al., 1982) are basically consistent with the model seismic fault displacements. Geodetic results from within a few kilometers of the fault trace (Mason et al., 1981) seem to require more slip at shallow depths than appears at seismic time scales. This is consistent with the occurrence of aftercreep at shallow depths in less well-consolidated material, which would bring surface displacements into line with maximum slip at depth, but not greatly affect the net moment. In the second strategy, we consider stresses on the fault plane, rather than displacements, as model variables. To constrain this part of our numerical modeling, we assume that the fault driving stress is governed by ambient tectonic stress and an opposing Coulomb friction derived from experiment. The coseismic stress drop from point to point on the failed fault is given by the difference between the tectonic shear stress and the frictional stress. After arriving at such a uniform model which adequately represents the Snay et al. results, we further modify a small region near the seismic “asperity” to make the fault plane motions qualitatively and quantitatively resemble the model of coseismic motions used in the first strategy. The observed offset on the fault trace (Sharp et al., 1982) is approximated in this final stress-driven model by removing the driving stress on the southern third of the fault. Thus, the principal features of the coseismic slip pattern are explained by a stress-driven fault model in which: (a) a spatially unresolved asperity is found equivalent to a stress drop of 18 MPa averaged over an area of 15 km^2, and (b) driving stress is essentially absent on the fault segment overlapping the 1940 earthquake rupture zone

Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component of human ketoacid dehydrogenase complexes

cDNA clones comprising the entire coding region for human dihydrolipoamide dehydrogenase (dihydrolipoamide:NAD+ oxidoreductase, EC 1.8.1.4) have been isolated from a human liver cDNA library. The cDNA sequence of the largest clone consisted of 2082 base pairs and contained a 1527-base open reading frame that encodes a precursor dihydrolipoamide dehydrogenase of 509 amino acid residues. The first 35-amino acid residues of the open reading frame probably correspond to a typical mitochondrial import leader sequence. The predicted amino acid sequence of the mature protein, starting at the residue number 36 of the open reading frame, is almost identical (greater than 98% homology) with the known partial amino acid sequence of the pig heart dihydrolipoamide dehydrogenase. The cDNA clone also contains a 3' untranslated region of 505 bases with an unusual polyadenylylation signal (TATAAA) and a short poly(A) track. By blot-hybridization analysis with the cDNA as probe, two mRNAs, 2.2 and 2.4 kilobases in size, have been detected in human tissues and fibroblasts, whereas only one mRNA (2.4 kilobases) was detected in rat tissues

Social Network Structure Is Related to Functional Improvement From Home-Based Telerehabilitation After Stroke

Objective: Telerehabilitation (TR) is now, in the context of COVID-19, more clinically relevant than ever as a major source of outpatient care. The social network of a patient is a critical yet understudied factor in the success of TR that may influence both engagement in therapy programs and post-stroke outcomes. We designed a 12-week home-based TR program for stroke patients and evaluated which social factors might be related to motor gains and reduced depressive symptoms. Methods: Stroke patients (n = 13) with arm motor deficits underwent supervised home-based TR for 12 weeks with routine assessments of motor function and mood. At the 6-week midpoint, we mapped each patient\u27s personal social network and evaluated relationships between social network metrics and functional improvements from TR. Finally, we compared social networks of TR patients with a historical cohort of 176 stroke patients who did not receive any TR to identify social network differences. Results: Both network size and network density were related to walk time improvement (p = 0.025; p = 0.003). Social network density was related to arm motor gains (p = 0.003). Social network size was related to reduced depressive symptoms (p = 0.015). TR patient networks were larger (p = 0.012) and less dense (p = 0.046) than historical stroke control networks. Conclusions: Social network structure is positively related to improvement in motor status and mood from TR. TR patients had larger and more open social networks than stroke patients who did not receive TR. Understanding how social networks intersect with TR outcomes is crucial to maximize effects of virtual rehabilitation

A Feasibility Study of Expanded Home-Based Telerehabilitation After Stroke

Introduction: High doses of activity-based rehabilitation therapy improve outcomes after stroke, but many patients do not receive this for various reasons such as poor access, transportation difficulties, and low compliance. Home-based telerehabilitation (TR) can address these issues. The current study evaluated the feasibility of an expanded TR program. Methods: Under the supervision of a licensed therapist, adults with stroke and limb weakness received home-based TR (1 h/day, 6 days/week) delivered using games and exercises. New features examined include extending therapy to 12 weeks duration, treating both arm and leg motor deficits, patient assessments performed with no therapist supervision, adding sensors to real objects, ingesting a daily experimental (placebo) pill, and generating automated actionable reports. Results: Enrollees (n = 13) were median age 61 (IQR 52–65.5), and 129 (52–486) days post-stroke. Patients initiated therapy on 79.9% of assigned days and completed therapy on 65.7% of days; median therapy dose was 50.4 (33.3–56.7) h. Non-compliance doubled during weeks 7–12. Modified Rankin scores improved in 6/13 patients, 3 of whom were \u3e3 months post-stroke. Fugl-Meyer motor scores increased by 6 (2.5–12.5) points in the arm and 1 (−0.5 to 5) point in the leg. Assessments spanning numerous dimensions of stroke outcomes were successfully implemented; some, including a weekly measure that documented a decline in fatigue (p = 0.004), were successfully scored without therapist supervision. Using data from an attached sensor, real objects could be used to drive game play. The experimental pill was taken on 90.9% of therapy days. Automatic actionable reports reliably notified study personnel when critical values were reached. Conclusions: Several new features performed well, and useful insights were obtained for those that did not. A home-based telehealth system supports a holistic approach to rehabilitation care, including intensive rehabilitation therapy, secondary stroke prevention, screening for complications of stroke, and daily ingestion of a pill. This feasibility study informs future efforts to expand stroke TR

Molecular characterization of interdigitating dendritic cell sarcoma

Interdigitating dendritic cell sarcoma is an extremely rare cancer that lacks a standard treatment approach. We report on a patient who was surgically resected and remains disease- free. The tumor was assessed for druggable targets using immunohistochemical staining to identify potential agents that could be used in the event of disease recurrence

Apoptotic Effects of Antilymphocyte Globulins on Human Pro-inflammatory CD4+CD28− T-cells

BACKGROUND: Pro-inflammatory, cytotoxic CD4(+)CD28(-) T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4(+)CD28(-) T-cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+)CD4(+)CD28(-) T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%). In vitro, ATG-F induced apoptosis even in CD4(+)CD28(-) T-cells, which was 4.3-times higher than in CD4(+)CD28(+) T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+)CD28(-) T-cells. CONCLUSION: In summary, in vivo depletion of peripheral CD3(+)CD4(+)CD28(-) T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+)CD28(-) T-cells only partly explain the underlying mechanism