Drosophila Spastin Regulates Synaptic Microtubule Networks and Is Required for Normal Motor Function

Nina Tang Sherwood is with California Institute of Technology, Qi Sun is with California Institute of Technology, Mingshan Xue is with UT Austin, Bing Zhang is with UT Austin, Kai Zinn is with California Institute of Technology.The most common form of human autosomal dominant hereditary spastic paraplegia (AD-HSP) is caused by mutations in the SPG4 (spastin) gene, which encodes an AAA ATPase closely related in sequence to the microtubule-severing protein Katanin. Patients with AD-HSP exhibit degeneration of the distal regions of the longest axons in the spinal cord. Loss-of-function mutations in the Drosophila spastin gene produce larval neuromuscular junction (NMJ) phenotypes. NMJ synaptic boutons in spastin mutants are more numerous and more clustered than in wild-type, and transmitter release is impaired. spastin-null adult flies have severe movement defects. They do not fly or jump, they climb poorly, and they have short lifespans. spastin hypomorphs have weaker behavioral phenotypes. Overexpression of Spastin erases the muscle microtubule network. This gain-of-function phenotype is consistent with the hypothesis that Spastin has microtubule-severing activity, and implies that spastin loss-of-function mutants should have an increased number of microtubules. Surprisingly, however, we observed the opposite phenotype: in spastin-null mutants, there are fewer microtubule bundles within the NMJ, especially in its distal boutons. The Drosophila NMJ is a glutamatergic synapse that resembles excitatory synapses in the mammalian spinal cord, so the reduction of organized presynaptic microtubules that we observe in spastin mutants may be relevant to an understanding of human Spastin's role in maintenance of axon terminals in the spinal cord.Biological Sciences, School o

The Day Ahead: IPO Today, Acquired Tomorrow?

We study the double exit phenomenon—new IPO firms get acquired quickly in the M & A market. In this paper, we attempt to discern the distinct characteristics of new public firms that made them acquired soon after their IPOs. Specifically we find that double exit firms are those backed by venture capital. Double exit firms generally have prestigious investment banks underwrite their IPOs. High technology firms are more likely to be taken over soon after their IPOs. Also, double exit firms have higher level of intangible assets. We suggest that IPO may play an important role in firms’ following acquisition incidence. First, IPO helps to reduce ex ante transaction costs between firms and financial markets, such as raising external capitals. Second, IPOs wink signals concerning the quality of the firm

Transjugular Intrahepatic Portosystemic Shunt for the Treatment of Portal Hypertension in Noncirrhotic Patients with Portal Cavernoma

Background. The purpose of this study was to evaluate the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) placement in the management of portal hypertension in noncirrhotic patients with portal cavernoma. Methods. We conducted a single institution retrospective analysis of 15 noncirrhotic patients with portal cavernoma treated with TIPS placement. 15 patients (4 women and 11 men) were evaluated via the technical success of TIPS placement, procedural complications, and follow-up shunt patency. Results. TIPS placement was technically successful in 11 out of 15 patients (73.3%). Procedure-related complications were limited to a single instance of hepatic encephalopathy in one patient. In patients with successful shunt placement, the portal pressure gradient decreased from 25.8±5.7 to 9.5±4.2 mmHg (P<0.001). TIPS dysfunction occurred in two patients during a median follow-up time of 45.2 months. Revision was not performed in one patient due to inadequate inflow. The other patient died of massive gastrointestinal bleeding in a local hospital. The remaining nine patients maintained functioning shunts through their last evaluation. Conclusions. TIPS is a safe and effective therapeutic treatment for noncirrhotic patients with symptomatic portal hypertension secondary to portal cavernoma

Identifying and decoupling many-body interactions in spin ensembles in diamond

We simulate the dynamics of varying density quasi-two-dimensional spin ensembles in solid-state systems, focusing on the nitrogen-vacancy centers in diamond. We consider the effects of various control sequences on the averaged dynamics of large ensembles of spins, under a realistic "spin-bath" environment. We reveal that spin locking is efficient for decoupling spins initialized along the driving axis, both from coherent dipolar interactions and from the external spin-bath environment, when the driving is two orders of magnitude stronger than the relevant coupling energies. Since the application of standard pulsed dynamical decoupling sequences leads to strong decoupling from the environment, while other specialized pulse sequences can decouple coherent dipolar interactions, such sequences can be used to identify the dominant interaction type. Moreover, a proper combination of pulsed decoupling sequences could lead to the suppression of both interaction types, allowing additional spin manipulations. Finally, we consider the effect of finite-width pulses on these control protocols and identify improved decoupling efficiency with increased pulse duration, resulting from the interplay of dephasing and coherent dynamics

Athermal silicon-on-insulator ring resonators by overlaying a polymer cladding on narrowed waveguides

Athermal silicon ring resonators are experimentally demonstrated by overlaying a polymer cladding on narrowed silicon wires. The ideal width to achieve athermal condition for the TE mode of 220nm-height SOI waveguides is found to be around 350nm. After overlaying a polymer layer, the wavelength temperature dependence of the silicon ring resonator is reduced to less than 5 pm/degrees C, almost eleven times less than that of normal silicon waveguides. The optical loss of a 350-nm bent waveguide (with a radius of 15 mu m) is extracted from the ring transmission spectrum. The scattering loss is reduced to an acceptable level of about 50dB/cm after overlaying a polymer cladding. (C) 2009 Optical Society of Americ

Zero-forcing Oriented Power Minimization for Multi-cell MISO-NOMA Systems: A Joint User Grouping, Beamforming and Power Control Perspective

International audienceFuture wireless communication systems have been imposed high requirement on power efficiency for operator's profitability as well as to alleviate information and communication technology (ICT) global carbon emission. To meet these challenges, the power consumption minimization problem for a generic multi-cell multiple input and single output non-orthogonal multiple access (MISO-NOMA) system is studied in this work. The associated joint user grouping, beamforming (BF) and power control problem is a mixed integer non-convex programming problem, which is tackled by an iterative distributed methodology. Towards this end, the near-optimal zero-forcing (ZF) BF is leveraged, wherein the semiorthogonal user selection (SUS) strategy is applied to select BF users. Based on these, the BF vectors and BF users are determined for each cell using only local information. Then, two distributed user grouping strategies are proposed. The first one, called channel condition based user clustering (CCUC), performs user grouping in each cell based on the channel conditions. This is conducted independently of the power control part and has low computational complexity. Another algorithm, called power consumption based user clustering (PCUC), uses both the channel conditions and inter-cell interference information to minimize each cell's power consumption. In contrary to CCUC, PCUC is optimized jointly with the power control. Finally, with the obtained user grouping and BF vectors, the resultant power allocation problem is optimally solved via an iterative algorithm, whose convergence is mathematically proven given that the problem is feasible. We perform Monte-Carlo simulation and numerical results show that the proposed resource management methods outperform various conventional MISO schemes and the non-clustered MISO-NOMA strategy in several aspects, including power consumption, outage probability, energy efficiency, and connectivity efficiency

Preclinical evaluation of the ROCK1 inhibitor, GSK269962A, in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with high mortality that urgently requires new treatments. ROCK1 plays an essential role in regulating growth and survival in AML cells. In this study, we evaluated GSK269962A, a selective ROCK1 inhibitor, in preclinical models of AML. Compared with solid tumors, GSK269962A selectively inhibited cell growth and clonogenicity of AML cells. Furthermore, GSK269962A arrested AML cells in the G2 phase and induced apoptosis by regulating multiple cell cycle- and apoptosis-associated proteins. Strikingly, GSK269962A could eliminate leukemia cells from bone marrow, liver, and spleen in an animal model of AML and significantly prolong mouse survival. Mechanistically, GSK269962A could inhibit the growth of AML by blocking ROCK1/c-Raf/ERK signaling pathway. Notably, a correlation was found between the expression levels of ROCK1 protein and the sensitivity of GSK269962A in AML. These data highlight the potential role of ROCK1 as an attractive target for treating AML, as well as the potential of GSK269962A for use in clinical trials of AML

Evolutionary characteristics and genetic transmission patterns of predominant HIV-1 subtypes among men who have sex with men in China.

OBJECTIVES: Men who have sex with men (MSM) represent one of the major risk groups for HIV-1 infection in China, and the predominant subtypes among this population has changed over the last two decades. The objective of this study was to determine the evolutionary characteristics and transmission patterns of the dominant HIV-1 strains in the Chinese MSM population. METHODS: A total of 4980 published HIV-1 pol gene sequences from MSM in China were retrieved and comprehensive evolutionary and transmission analyses were then conducted. Bayesian coalescent-based methods and selection pressure analyses were used to reconstruct the time-scale and demographic history and to estimate other evolutionary parameters. Transmission patterns were characterized using network analyses. RESULTS: There were 2546 (51.12%) CRF01_AE, 1263 (25.36%) CRF07_BC, and 623 (12.51%) subtype B, accounting for 88.99% of the total sequences. From 2000 to 2016, the prevalence of CRF01_AE was stable, comprising nearly half of all sequences over time (58.33-45.38%, p=0.071). CRF07_BC increased slightly from 13.3% to 22.49% (p<0.001), while subtype B decreased dramatically from 41.67% to 9.04% (p<0.001). Demographic reconstruction showed that the greatest expansion of the HIV epidemic occurred between 1999 and 2005. CRF01_AE had a higher estimated evolutionary rate (2.97×10-3 substitutions/site/year) and exhibited more sites under positive selection (25/351 codons) compared to the other subtypes. Network analyses showed that CRF07_BC (68.29%, 84/123) had a higher proportion of cross-region networks than CRF01_AE (49.1%, 174/354) and subtype B (36.46%, 35/96) (p<0.001). CONCLUSIONS: The predominant subtypes of HIV-1 in Chinese MSM have different evolutionary characteristics and transmission patterns, which poses a significant challenge to HIV treatment and disease prevention