This scientific statement is intended for use by physicians and allied health personnel caring for patients with transient ischemic attacks. Formal evidence review included a structured literature ...search of Medline from 1990 to June 2007 and data synthesis employing evidence tables, meta-analyses, and pooled analysis of individual patient-level data. The review supported endorsement of the following, tissue-based definition of transient ischemic attack (TIA): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. Patients with TIAs are at high risk of early stroke, and their risk may be stratified by clinical scale, vessel imaging, and diffusion magnetic resonance imaging. Diagnostic recommendations include: TIA patients should undergo neuroimaging evaluation within 24 hours of symptom onset, preferably with magnetic resonance imaging, including diffusion sequences; noninvasive imaging of the cervical vessels should be performed and noninvasive imaging of intracranial vessels is reasonable; electrocardiography should occur as soon as possible after TIA and prolonged cardiac monitoring and echocardiography are reasonable in patients in whom the vascular etiology is not yet identified; routine blood tests are reasonable; and it is reasonable to hospitalize patients with TIA if they present within 72 hours and have an ABCD(2) score >or=3, indicating high risk of early recurrence, or the evaluation cannot be rapidly completed on an outpatient basis.
The large Trp gene family encodes transient receptor potential (TRP) proteins that form novel cation-selective ion channels. In mammals, 28 Trp channel genes have been identified. TRP proteins ...exhibit diverse permeation and gating properties and are involved in a plethora of physiologic functions with a strong impact on cellular sensing and signaling pathways. Indeed, mutations in human genes encoding TRP channels, the so-called "TRP channelopathies," are responsible for a number of hereditary diseases that affect the musculoskeletal, cardiovascular, genitourinary, and nervous systems. This review gives an overview of the functional properties of mammalian TRP channels, describes their roles in acquired and hereditary diseases, and discusses their potential as drug targets for therapeutic intervention.
A Reverse Shock in GRB 181201A Laskar, Tanmoy; Eerten, Hendrik van; Schady, Patricia ...
The Astrophysical journal,
10/2019, Letnik:
884, Številka:
2
Journal Article
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We present comprehensive multiwavelength radio to X-ray observations of GRB 181201A spanning from 150 s to 163 days after the burst, comprising the first joint ALMA-VLA-GMRT observations of a ...gamma-ray burst (GRB) afterglow. The radio and millimeter-band data reveal a distinct signature at 3.9 days, which we interpret as reverse-shock (RS) emission. Our observations present the first time that a single radio-frequency spectral energy distribution can be decomposed directly into RS and forward shock (FS) components. We perform detailed modeling of the full multiwavelength data set, using Markov Chain Monte Carlo sampling to construct the joint posterior density function of the underlying physical parameters describing the RS and FS synchrotron emission. We uncover and account for all discovered degeneracies in the model parameters. The joint RS-FS modeling reveals a weakly magnetized ( 3 × 10−3), mildly relativistic RS, from which we derive an initial bulk Lorentz factor of Γ0 103 for the GRB jet. Our results support the hypothesis that low-density environments are conducive to the observability of RS emission. We compare our observations to other events with strong RS detections and find a likely observational bias selecting for longer lasting, nonrelativistic RSs. We present and begin to address new challenges in modeling posed by the present generation of comprehensive, multifrequency data sets.
Transient stability (TS) and electromagnetic transient (EMT) programs are widely used simulation tools in power systems, with distinct applications but competing requirements. TS programs are fast ...which makes them suitable for handling large-scale networks, however, the modeling is not sufficiently detailed. On the other hand, EMT simulators are highly detailed, but limited in speed; consequently, they are used to simulate only small portions of the network. Integrating these two types of simulators generates a hybrid simulator which inherits the merits of both programs. A hybrid simulator can fulfill the modeling requirements of a large network by providing a fast as well as a detailed simulation. Establishing a connection between two different programs brings up several important issues which have been addressed, classified, and explained in this paper. An alternative integrated modeling of TS and EMT is also discussed using the concept of frequency shifting.
Gut microbiota has been suggested to play a role in almost all major diseases including cardio- and cerebrovascular diseases. A possible mechanism is the transformation of dietary choline and ...l-carnitine into trimethylamine by gut bacteria. This metabolite is further oxidized into trimethylamine-N-oxide (TMAO) in liver and promotes atherogenesis. Nevertheless, little is known about gut microbial diversity and blood TMAO levels in stroke patients.
We performed a case-control study of patients with large-artery atherosclerotic ischemic stroke and transient ischemic attack. TMAO was determined with liquid chromatography tandem mass spectrometry. Gut microbiome was profiled using Illumina sequencing of the 16S rRNA V4 tag. Within the asymptomatic control group, participants with and without carotid atherosclerotic plaques showed similar levels of TMAO without a significant difference in gut microbiota; however, the gut microbiome of stroke and transient ischemic attack patients was clearly different from that of the asymptomatic group. Stroke and transient ischemic attack patients had more opportunistic pathogens, such as Enterobacter, Megasphaera, Oscillibacter, and Desulfovibrio, and fewer commensal or beneficial genera including Bacteroides, Prevotella, and Faecalibacterium. This dysbiosis was correlated with the severity of the disease. The TMAO level in the stroke and transient ischemic attack patients was significantly lower, rather than higher, than that of the asymptomatic group.
Participants with asymptomatic atherosclerosis did not exhibit an obvious change in gut microbiota and blood TMAO levels; however, stroke and transient ischemic attack patients showed significant dysbiosis of the gut microbiota, and their blood TMAO levels were decreased.
Transient receptor potential mucolipin 1 (TRPML1) is a cation channel located within endosomal and lysosomal membranes. Ubiquitously expressed in mammalian cells, its loss-of-function mutations are ...the direct cause of type IV mucolipidosis, an autosomal recessive lysosomal storage disease. Here we present the single-particle electron cryo-microscopy structure of the mouse TRPML1 channel embedded in nanodiscs. Combined with mutagenesis analysis, the TRPML1 structure reveals that phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P
) binds to the N terminus of the channel-distal from the pore-and the helix-turn-helix extension between segments S2 and S3 probably couples ligand binding to pore opening. The tightly packed selectivity filter contains multiple ion-binding sites, and the conserved acidic residues form the luminal Ca
-blocking site that confers luminal pH and Ca
modulation on channel conductance. A luminal linker domain forms a fenestrated canopy atop the channel, providing several luminal ion passages to the pore and creating a negative electrostatic trap, with a preference for divalent cations, at the luminal entrance. The structure also reveals two equally distributed S4-S5 linker conformations in the closed channel, suggesting an S4-S5 linker-mediated PtdInsP
gating mechanism among TRPML channels.
Under fault conditions, virtual synchronous generators (VSGs) are prone to lose transient stability, similar to synchronous generators. However, the existing studies on VSG transient stability are ...not comprehensive. The transient characteristics of VSGs are highly affected by control parameters, but the transient models of VSGs in existing studies are overly simplified. In addition, the critical clearing angle (CCA) and critical clearing time (CCT) are two indices used to measure the transient stability of a system, but there are few studies that consider both CCA and CCT. In this article, we analyze the CCA and CCT quantitatively to describe the transient stability boundary of a VSG under different control parameters and fault conditions. Then, an equal proportional area criterion is proposed to provide guidance for the control of virtual inertia in the VSG. Based on a theoretical analysis, a transient control method for a VSG is proposed, which can improve the transient stability of the VSG in terms of both CCA and CCT. Finally, simulation and experimental tests are performed to validate the correctness of the theoretical analysis and the proposed method.
As a prevalent vertigo disease in the clinic, isolated transient vertigo can present as a vertigo episode without focal signs and always free of symptoms on presentation. Previous studies showed a ...part of isolated transient vertigo events had a high risk of stroke during follow-up. However, how to discern posterior circulation ischemia become a great challenge for clinicians, especially in emergency, neurology, and ENT departments. Routine besides, hematological, and imaging examinations are often difficult provide a clear etiological diagnosis. Hence, this article reviews current knowledge about the epidemiology, risk factors, offending lesions, and clinical manifestation of transient ischemic attack (TIA) presenting as isolated transient vertigo. In addition, we summarize several advances in besides examinations, serum biomarkers, and imaging technologies to better identify stroke events. Finally, the current situation of therapy was briefly retrospected. Here we present a critical clinical puzzle that needs to be solved in the future. Of note, there is a still lack of high-quality studies in this field. The article reviews the keys to the diagnosis of isolated transient vertigo due to TIA and provides us with more methods to screen for high-risk stroke populations.
Driven by the large-scale integration of distributed power resources, grid-connected voltage-source converters (VSCs) are increasingly required to operate as grid-forming units to regulate the system ...voltage/frequency and emulate the inertia. While various grid-forming control schemes have been reported, their transient behaviors under large-signal disturbances are still not fully explored. This article addresses this issue by presenting a design-oriented transient stability analysis of the grid-forming VSCs. First, four typical grid-forming control schemes, namely, the power-synchronization control (PSC), the basic droop control, the droop control with low-pass filters (LPFs), and the virtual synchronous generator (VSG) control, are systematically reviewed, whose dynamics are characterized by a general large-signal model. Based on this model, a comparative analysis on the transient stabilities of different control schemes is then carried out. It reveals that the PSC and the basic droop control can retain a stable operation as long as there are equilibrium points, due to their noninertial transient responses, while the droop control with LPFs and the VSG control can be destabilized even if the equilibrium points exist, due to the lack of damping on their inertial transient responses. With the phase portrait, the underlying stability mechanism is explicitly elaborated, and the quantitative impacts of the controller gains and the virtual inertia are clearly identified. Subsequently, controller design guidelines are proposed to enhance the system damping as well as the transient stability. Finally, experimental results are provided to verify the theoretical analysis.
Sensory TRP Channels in Three Dimensions Diver, Melinda M; Lin King, John V; Julius, David ...
Annual review of biochemistry,
06/2022, Letnik:
91
Journal Article
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Transient receptor potential (TRP) ion channels are sophisticated signaling machines that detect a wide variety of environmental and physiological signals. Every cell in the body expresses one or ...more members of the extended TRP channel family, which consists of over 30 subtypes, each likely possessing distinct pharmacological, biophysical, and/or structural attributes. While the function of some TRP subtypes remains enigmatic, those involved in sensory signaling are perhaps best characterized and have served as models for understanding how these excitatory ion channels serve as polymodal signal integrators. With the recent resolution revolution in cryo-electron microscopy, these and other TRP channel subtypes are now yielding their secrets to detailed atomic analysis, which is beginning to reveal structural underpinnings of stimulus detection and gating, ion permeation, and allosteric mechanisms governing signal integration. These insights are providing a framework for designing and evaluating modality-specific pharmacological agents for treating sensory and other TRP channel-associated disorders.
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