A brain-computer interface with vibrotactile biofeedback for haptic information

<p>Abstract</p> <p>Background</p> <p>It has been suggested that Brain-Computer Interfaces (BCI) may one day be suitable for controlling a neuroprosthesis. For closed-loop operation of BCI, a tactile feedback channel that is compatible with neuroprosthetic applications is desired. Operation of an EEG-based BCI using only <it>vibrotactile feedback</it>, a commonly used method to convey haptic senses of contact and pressure, is demonstrated with a high level of accuracy.</p> <p>Methods</p> <p>A Mu-rhythm based BCI using a motor imagery paradigm was used to control the position of a virtual cursor. The cursor position was shown visually as well as transmitted haptically by modulating the intensity of a vibrotactile stimulus to the upper limb. A total of six subjects operated the BCI in a two-stage targeting task, receiving only vibrotactile biofeedback of performance. The location of the vibration was also systematically varied between the left and right arms to investigate location-dependent effects on performance.</p> <p>Results and Conclusion</p> <p>Subjects are able to control the BCI using only vibrotactile feedback with an average accuracy of 56% and as high as 72%. These accuracies are significantly higher than the 15% predicted by random chance if the subject had no voluntary control of their Mu-rhythm. The results of this study demonstrate that vibrotactile feedback is an effective biofeedback modality to operate a BCI using motor imagery. In addition, the study shows that placement of the vibrotactile stimulation on the biceps ipsilateral or contralateral to the motor imagery introduces a significant bias in the BCI accuracy. This bias is consistent with a drop in performance generated by stimulation of the contralateral limb. Users demonstrated the capability to overcome this bias with training.</p

On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

<p>Abstract</p> <p>Background</p> <p>Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM) patients. Treatment effects with improved left ventricular (LV) ejection fraction (EF) have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful.</p> <p>Methods</p> <p>This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR) to the relative risk (RR) of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM) and 63-70% (lower half of the normal range for TM).</p> <p>Results</p> <p>A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p < 0.001) and the higher EF stratum (EF 63-70%, RR 0.893 p = 0.001).</p> <p>Conclusion</p> <p>These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.</p

Results of measurement of the night corpuscular flux on the MR-12 rockets in the JASPIC project (Soviet part of the program)

In June 1978, a joint Soviet-American project (JASPIC) was conducted, the goals of which were: (1) the study of the flows of spilling electrons which act upon the middle-latitude ionosphere under nocturnal conditions (nocturnal corpuscular source of ionization); and (2) the mutual comparison of procedures for recording corpuscular radiations in the upper atmosphere, using meteorological and geophysical rockets

Evaluation of the NRF1-proteasome axis as a therapeutic target in breast cancer

Abstract Proteasomes are multi-subunit complexes that specialize in protein degradation. Cancer cells exhibit a heightened dependence on proteasome activity, presumably to support their enhanced proliferation and other cancer-related characteristics. Here, a systematic analysis of TCGA breast cancer datasets revealed that proteasome subunit transcript levels are elevated in all intrinsic subtypes (luminal, HER2-enriched, and basal-like/triple-negative) when compared to normal breast tissue. Although these observations suggest a pan-breast cancer utility for proteasome inhibitors, our further experiments with breast cancer cell lines and patient-derived xenografts (PDX) pointed to triple-negative breast cancer (TNBC) as the most sensitive subtype to proteasome inhibition. Finally, using TNBC cells, we extended our studies to in vivo xenograft experiments. Our previous work has firmly established a cytoprotective role for the transcription factor NRF1 via its ability to upregulate proteasome genes in response to proteasome inhibition. In further support of this notion, we show here that NRF1 depletion significantly reduced tumor burden in an MDA-MB-231 TNBC xenograft mouse model treated with carfilzomib. Taken together, our results point to TNBC as a particularly vulnerable breast cancer subtype to proteasome inhibition and provide a proof-of-principle for targeting NRF1 as a viable means to increase the efficacy of proteasome inhibitors in TNBC tumors

High-Throughput Sorting and Placement of One-Bead–One-Compound (OBOC) Libraries from Bulk to Single Wells in Organic Solvent

One-bead–one-compound (OBOC) solid-phase combinatorial chemistry has been used extensively in drug discovery. However, a major bottleneck has been the sorting of individual beads, while still swollen in organic solvent, into individual wells of a microwell plate. To solve this problem, we have constructed an automated bead sorting system with integrated quality control that is capable of sorting and placing large numbers of beads in bulk to single wells of a 384-well plate, all in an organic solvent. The bead sorter employs a unique, reciprocating fluidic design capable of depositing 1 bead every 1.5 s, with an average accuracy of 97%. We quantified the performance of this instrument by sorting over 8500 beads, followed by cleaving the conjugated compound and confirming the chemical identity of each by liquid chromatography/mass spectrometry (LC/MS). This instrument should enable more efficient screening of combinatorial small molecule libraries without the need to dry beads or otherwise change the chemical environment