Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia.

Optimization of post-remission therapies to maintain complete remission and prevent relapse is a major challenge in treating patients with acute myeloid leukemia (AML). Monitoring patients for measurable residual disease (MRD) is helpful to identify those at risk for relapse. Hypomethylating agents are being investigated as post-remission therapy. Identification of recurrent genetic alterations that drive disease progression has enabled the design of new, personalized approaches to therapy for patients with AML. Emerging data suggest that targeted post-remission therapy, alone or in combination with chemotherapy, may improve outcomes. Results of ongoing clinical trials will further define potential clinical benefits

ON THE SUMMER TIME DEVELOPMENT OF THE NORTH PACIFIC SEA-LEVEL PRESSURE ANTICYCLONE

With the exception of the North Indian Ocean, subtropical ocean basins are dominated by climatological planetary-scale sea-level pressure (SLP) anticyclones. The seasonal variability of the North Pacific subtropical SLP anticyclone is examined here. The largest ERA-40 and linear diagnostic modeled Northern Hemisphere SLP seasonal variabilities are found in the mid-latitudes with relatively less change in the subtropics; this leads to the poleward boreal summer development of the North Pacific and Atlantic subtropical SLP high. Unlike the Northern Hemisphere, the Southern Hemisphere subtropical SLP highs develop equatorward. The zonal-mean Northern Hemisphere subtropical SLP and seasonal variabilities are dominated by continental seasonality - a uniform boreal winter descent changing to a zonally asymmetric continental monsoon ascent and heat lows with relatively little change over the oceans. A linear diagnostic model is used to examine the forcing of the SLP seasonal cycle. The modeled North Pacific SLP seasonal variability is forced mainly by winter stormtracks, extra-tropical North Pacific diabatic cooling, and boreal winter ITCZ. Asian monsoon forces a SLP ridge downstream, but the monsoon response is cancelled significantly by East Pacific diabatic heating and transients. North American diabatic heating and transients are also found to have a limited upstream effect. Boreal summer ITCZ forcing has limited North Pacific SLP response, and that is possibly linked to the prescribed tropical zonal-mean easterlies. ERA-40 and TRMM CSH diabatic heating is inter-compared with other independent measures of diabatic and latent heating. Zonal-mean ERA-40 ITCZ diabatic heating is nearly twice that of NCEP and ERA-15 reanalyses, which indicates a much stronger ERA-40 Hadley Circulation. The ERA-40 Walker Circulation is also stronger than of NCEP Reanalysis, which is consistent with excessive Maritime Continent diabatic heating. Largest differences are also found in the Tropical East Pacific and Atlantic. Vertically integrated TRMM CSH heating is too weak even compare with other TRMM products. However, TRMM CSH mid-tropospheric tropical heating compares well with other datasets. The largest differences appear in the upper and lower troposphere, which implies CSH limitations in handling shallow convection (a known issue) and stratiform precipitation in deep convection

Spectral Functions of the Uniform Electron Gas via Coupled-Cluster Theory and Comparison to the GWGW and Related Approximations

We use, for the first time, ab initio coupled-cluster theory to compute the spectral function of the uniform electron gas at a Wigner-Seitz radius of $r_\mathrm{s}=4$. The coupled-cluster approximations we employ go significantly beyond the diagrammatic content of state-of-the-art $GW$ theory. We compare our calculations extensively to $GW$ and $GW$-plus-cumulant theory, illustrating the strengths and weaknesses of these methods in capturing the quasiparticle and satellite features of the electron gas. Our accurate calculations further allow us to address the long-standing debate over the occupied bandwidth of metallic sodium. Our findings indicate that the future application of coupled-cluster theory to condensed phase material spectra is highly promising.Comment: 6 pages, 2 figure

Kinetic Resolution in Asymmetric Epoxidation using Iminium Salt Catalysis

The first reported examples of kinetic resolution in epoxidation reactions using iminium salt catalysis are described, providing up to 99% ee in the epoxidation of racemic cis-chromenes

The variable relationship between arm and hand use: a rationale for using finger magnetometry to complement wrist accelerometry when measuring daily use of the upper extremity.

Wrist-worn accelerometers are becoming more prevalent as a means to assess use of the impaired upper extremity in daily life after stroke. However, wrist accelerometry does not measure joint movements of the hand, which are integral to functional use of the upper extremity. In this study, we used a custom-built, non-obtrusive device called the manumeter to measure both arm use (via wrist accelerometry) and hand use (via finger magnetometry) of a group of unimpaired subjects while they performed twelve motor tasks at three intensities. We also gave the devices to four stroke subjects and asked them to wear them for six hours a day for one month. From the in-lab testing we found that arm use was a strong predictor of hand use for individual tasks, but that the slope of the relationship varied by up to a factor of ~12 depending on the task being performed. Consistent with this, in the daily use data collected from stroke subjects we found a broad spread in the relationship between arm and hand use. These results suggest that analyzing the spread of the relationship between daily hand and arm use will give more insight into upper extremity recovery than wrist accelerometry or finger magnetometry alone, because the spread reflects the nature of the daily tasks performed as well as the amount of upper extremity use

Formal synthesis of (+)-lactacystin from l-serine

A formal, stereocontrolled synthesis of lactacystin has been completed from t-Bu-O-l-serine, providing the key intermediate 13, also useful for the generation of a range of C-9 analogues

BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex.

Motor training can induce profound physiological plasticity within primary motor cortex, including changes in corticospinal output and motor map topography. Using transcranial magnetic stimulation, we show that training-dependent increases in the amplitude of motor-evoked potentials and motor map reorganization are reduced in healthy subjects with a val66met polymorphism in the brain-derived neurotrophic factor gene (BDNF), as compared to subjects without the polymorphism. The results suggest that BDNF is involved in mediating experience-dependent plasticity of human motor cortex