Multi-timescale measurements of brain responses in visual cortex during functional stimulation using time-resolved spectroscopy

Studies of neurovascular coupling (hemodynamic changes and neuronal activation) in the visual cortex using a timedomain single photon counting system have been undertaken. The system operates in near infrared (NIR) range of spectrum and allows functional brain monitoring to be done non-invasively. The detection system employs a photomultiplier and multi-channel scaler to detect and record emerging photons with sub-microsecond resolution (the effective collection time per curve point is ~ 200 ns). Localisation of the visual evoked potentials in the brain was done using knowledge obtained from electroencephalographic (EEG) studies and previous frequency-domain optical NIR spectroscopic systems. The well-known approach of visual stimulation of the human brain, which consists of an alternating black and white checkerboard pattern used previously for the EEG study of neural responses, is applied here. The checkerboard pattern is synchronized with the multi-channel scaler system and allows the analysis of time variation in back-scattered light, at different stimulation frequencies. Slow hemodynamic changes in the human brain due to Hb- HbO2 changes in the blood flow were observed, which is evidence of the system’s capability to monitor these changes. Monocular visual tests were undertaken and compared with those done with an EEG system. In some subjects a fast optical response on a time scale commensurate with the neural activity associated with the visual cortex was detected. Future work will concentrate on improved experimental protocols and apparatus to confirm the existence of this important physiological signal

Steady State Visual Stimulation of the Brain: Optical Study of Task Related Effects

Near-infrared (NIR) and electroencephalography (EEG) systems were applied simultaneously to check a possibility of an optical brain-computer interface (BCI) based on visual protocol. A two-wavelength, two-channel NIR system using lock-in amplifiers to filter received signal was designed for monitoring of light absorption. An improved single photon-counting system based on NIR laser diodes and multichannel scaling was configured for fast one-wavelength capturing of the scatter changes in the area of the human brain corresponding to the task. Designed protocols consisted of the pattern reversed repeatedly at various frequencies. The stimulus repetition improves processing according to some behavioural measure as e.g. greater accuracy in identifying the stimulus or faster response times to make a decision about it, and often occurs under the same experimental conditions. Under certain conditions rather increased activity in the brain could be observed which results in a longer habituation time. Results of tests are presented in current article

Sphingolipid Long-Chain Base Hydroxylation Is Important for Growth and Regulation of Sphingolipid Content and Composition in \u3ci\u3eArabidopsis\u3c/i\u3e

Sphingolipids are structural components of endomembranes and function through their metabolites as bioactive regulators of cellular processes such as programmed cell death. A characteristic feature of plant sphingolipids is their high content of trihydroxy long-chain bases (LCBs) that are produced by the LCB C-4 hydroxylase. To determine the functional significance of trihydroxy LCBs in plants, T-DNA double mutants and RNA interference suppression lines were generated for the two Arabidopsis thaliana LCB C-4 hydroxylase genes Sphingoid Base Hydroxylase1 (SBH1) and SBH2. These plants displayed reductions in growth that were dependent on the content of trihydroxy LCBs in sphingolipids. Double sbh1 sbh2 mutants, which completely lacked trihydroxy LCBs, were severely dwarfed, did not progress from vegetative to reproductive growth, and had enhanced expression of programmed cell death associated–genes. Furthermore, the total content of sphingolipids on a dry weight basis increased as the relative amounts of trihydroxy LCBs decreased. In trihydroxy LCB–null mutants, sphingolipid content was ~2.5-fold higher than that in wild-type plants. Increases in sphingolipid content resulted from the accumulation of molecular species with C16 fatty acids rather than with very-long-chain fatty acids, which are more commonly enriched in plant sphingolipids, and were accompanied by decreases in amounts of C16-containing species of chloroplast lipids. Overall, these results indicate that trihydroxy LCB synthesis plays a central role in maintaining growth and mediating the total content and fatty acid composition of sphingolipids in plants

A 12-Channel, real-time near-infrared spectroscopy instrument for brain-computer interface applications

A continuous wave near-infrared spectroscopy (NIRS) instrument for brain-computer interface (BCI) applications is presented. In the literature, experiments have been carried out on subjects with such motor degenerative diseases as amyotrophic lateral sclerosis, which have demonstrated the suitability of NIRS to access intentional functional activity, which could be used in a BCI as a communication aid. Specifically, a real-time, multiple channel NIRS tool is needed to realise access to even a few different mental states, for reasonable baud rates. The 12-channel instrument described here has a spatial resolution of 30mm, employing a flexible software demodulation scheme. Temporal resolution of ~100ms is maintained since typical topographic imaging is not needed, since we are only interested in exploiting the vascular response for BCI control. A simple experiment demonstrates the ability of the system to report on haemodynamics during single trial mental arithmetic tasks. Multiple trial averaging is not required

Security and Privacy Qualities of Medical Devices: An Analysis of FDA Postmarket Surveillance

Background: Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients’ stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting. Methods: We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices. Results: Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism. Conclusions: Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware

MPK6, sphinganine and the \u3ci\u3eLCB2a\u3c/i\u3e gene from serine palmitoyltransferase are required in the signaling pathway that mediates cell death induced by long chain bases in \u3ci\u3eArabidopsis\u3c/i\u3e

• Long chain bases (LCBs) are sphingolipid intermediates acting as second messengers in programmed cell death (PCD) in plants. Most of the molecular and cellular features of this signaling function remain unknown. • We induced PCD conditions in Arabidopsis thaliana seedlings and analyzed LCB accumulation kinetics, cell ultrastructure and phenotypes in serine palmitoyltransferase (spt), mitogen-activated protein kinase (mpk), mitogenactivated protein phosphatase (mkp1) and lcb-hydroxylase (sbh) mutants. • The lcb2a-1 mutant was unable to mount an effective PCD in response to fumonisin B1 (FB1), revealing that the LCB2a gene is essential for the induction of PCD. The accumulation kinetics of LCBs in wild-type (WT) and lcb2a-1 plants and reconstitution experiments with sphinganine indicated that this LCB was primarily responsible for PCD elicitation. The resistance of the null mpk6 mutant to manifest PCD on FB1 and sphinganine addition and the failure to show resistance on pathogen infection and MPK6 activation by FB1 and LCBs indicated that MPK6 mediates PCD downstream of LCBs. • This work describes MPK6 as a novel transducer in the pathway leading to LCBinduced PCD in Arabidopsis, and reveals that sphinganine and the LCB2a gene are required in a PCD process that operates as one of the more effective strategies used as defense against pathogens in plants

Sphingolipids in the Root Play an Important Role in Regulating the Leaf Ionome in \u3ci\u3eArabidopsis thaliana\u3c/i\u3e

Sphingolipid synthesis is initiated by condensation of Ser with palmitoyl-CoA producing 3-ketodihydrosphinganine (3-KDS), which is reduced by a 3-KDS reductase to dihydrosphinganine. Ser palmitoyltransferase is essential for plant viability. Arabidopsis thaliana contains two genes (At3g06060/TSC10A and At5g19200/TSC10B) encoding proteins with significant similarity to the yeast 3-KDS reductase, Tsc10p. Heterologous expression in yeast of either Arabidopsis gene restored 3-KDS reductase activity to the yeast tsc10D mutant, confirming both as bona fide 3-KDS reductase genes. Consistent with sphingolipids having essential functions in plants, double mutant progeny lacking both genes were not recovered from crosses of single tsc10A and tsc10B mutants. Although the 3-KDS reductase genes are functionally redundant and ubiquitously expressed in Arabidopsis, 3-KDS reductase activity was reduced to 10% of wild-type levels in the loss-of-function tsc10a mutant, leading to an altered sphingolipid profile. This perturbation of sphingolipid biosynthesis in the Arabidopsis tsc10a mutant leads an altered leaf ionome, including increases in Na, K, and Rb and decreases in Mg, Ca, Fe, and Mo. Reciprocal grafting revealed that these changes in the leaf ionome are driven by the root and are associated with increases in root suberin and alterations in Fe homeostasis

Inverse M-matrices, II

AbstractThis is an update of the 1981 survey by the first author. In the meantime, a considerable amount has been learned about the very special structure of the important class of inverse M-matrices. Developments since the earlier survey are emphasized, but we have tried to be somewhat complete; and, some results have not previously been published. Some proofs are given where appropriate and references are given for others. After some elementary preliminaries, results are grouped by certain natural categories

Suicide tourism in Manhattan, New York City, 1990-2004

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61257/1/gross_suicide_toursism_2007.pd

Identification of metabolic pathways influenced by the G-protein coupled receptors GprB and GprD in Aspergillus nidulans

Heterotrimeric G-protein-mediated signaling pathways play a pivotal role in transmembrane signaling in eukaryotes. Our main aim was to identify signaling pathways regulated by A. nidulans GprB and GprD G-protein coupled receptors (GPCRs). When these two null mutant strains were compared to the wild-type strain, the DeltagprB mutant showed an increased protein kinase A (PKA) activity while growing in glucose 1% and during starvation. In contrast, the DeltagprD has a much lower PKA activity upon starvation. Transcriptomics and (1)H NMR-based metabolomics were performed on two single null mutants grown on glucose. We noted modulation in the expression of 11 secondary metabolism gene clusters when the DeltagprB and DeltagprD mutant strains were grown in 1% glucose. Several members of the sterigmatocystin-aflatoxin gene cluster presented down-regulation in both mutant strains. The genes of the NR-PKS monodictyphenone biosynthesis cluster had overall increased mRNA accumulation in DeltagprB, while in the DeltagprD mutant strain the genes had decreased mRNA accumulation. Principal component analysis of the metabolomic data demonstrated that there was a significant metabolite shift in the DeltagprD strain. The (1)H NMR analysis revealed significant expression of essential amino acids with elevated levels in the DeltagprD strain, compared to the wild-type and DeltagprB strains. With the results, we demonstrated the differential expression of a variety of genes related mainly to secondary metabolism, sexual development, stress signaling, and amino acid metabolism. We propose that the absence of GPCRs triggered stress responses at the genetic level. The data suggested an intimate relationship among different G-protein coupled receptors, fine-tune regulation of secondary and amino acid metabolisms, and fungal development