Identification of inhibitors of the Leishmania cdc2-related protein kinase CRK3

New drugs are urgently needed for the treatment of tropical parasitic diseases such as leishmaniasis and human African trypanosomiasis (HAT). This work involved a high-throughput screen of a focussed kinase set of ~3400 compounds to identify potent and parasite-selective inhibitors of an enzymatic Leishmania CRK3-cyclin 6 complex. The aim of this study is to provide chemical validation that Leishmania CRK3-CYC6 is a drug target. Eight hit series were identified, of which four were followed up. The optimisation of these series using classical SAR studies afforded low-nanomolar CRK3 inhibitors with significant selectivity over the closely related human cyclin dependent kinase CDK2.     

In vitro-cultured wheat spikes provide a simplified alternative for studies of cadmium uptake in developing grains

BACKGROUND: An immature wheat spike culture system was used to monitor cadmium (Cd) accumulation in grains, hulls and awns of bread wheat and durum wheat. Immature spikes were cultured prior to anthesis in a medium containing 50 g L^?1 sucrose and 0.4 g L^?1 L ‐glutamine, supplemented with 0, 0.1, 0.5, 1, 2, 3, 4, 5, 10, 15, 20 or 25 mg L^?1 cadmium chloride (CdCl₂). Grains were collected at maturity and their Cd accumulation was determined using inductively coupled plasma mass spectrometry (ICP‐MS). RESULTS: Cd accumulation at CdCl₂ concentrations of 3 mg L^?1 and above was higher in grains of durum wheat compared with bread wheat. In hulls a similar trend was observed at CdCl₂ concentrations above 15 mg L^?1. Starch concentration in grains increased slightly at 3 and 4 mg L^?1 CdCl₂. Cd accumulation negatively affected grain protein concentration. Expression patterns of Cd‐related genes glutathione reductase (TaGR), metallothionein (MT) and phytochelatin synthase (PCS) in spikes cultured in media containing 0, 5, 10, 15 and 25 mg L^?1 CdCl₂ at 5 days post‐anthesis showed that TaGR and PCS expression in bread wheat was up‐regulated at 5 mg L^?1 CdCl₂ but down‐regulated at other CdCl₂ concentrations. However, in durum wheat, expression of all three genes was down‐regulated or remained unchanged. CONCLUSION: This study demonstrates that immature spike culture can be used to study Cd accumulation in grains and can delineate hyper‐accumulating durum wheat from bread wheat at CdCl₂ concentrations of 2 mg L^?1 and above. Copyright © 2011 Society of Chemical Industry     

Pollution Gradients and Chemical Characterization of Particulate Matter from Vehicular Traffic near Major Roadways: Results from the 2009 Queens College Air Quality Study in NYC

We present measurements of traffic-related pollutants made near the Long Island Expressway (LIE, I-495), in Queens, New York. The Aerodyne Research Inc. (ARI) mobile laboratory (AML) was deployed to map spatial and temporal gradients of gas-phase species and particulate matter (PM) associated with vehicular exhaust in the residential areas near the LIE. We observe that pollutant levels build up during the early morning hours under stable boundary layer conditions yet fall off quickly within 150 m downwind of the highway. An ARI soot particle aerosol mass spectrometer (SP-AMS) provided measurements of the size-resolved chemical composition of refractory black carbon (rBC) and the associated coating species. The average size distribution of the traffic related PM is characterized by a rBC mode centered at ～100 nm in vacuum aerodynamic diameter, D _va (rBC mass fraction ～50%). A second rBC mode (rBC mass fraction ～5%) more heavily coated with organic material is also observed at D _va ～500 nm. Positive matrix factorization (PMF) analyses of the traffic-related PM indicates that rBC is mostly associated with hydrocarbon-like organic (HOA) PM. These results are discussed in the context of chemically resolved size distributions and PMF analysis results performed on the SP-AMS stationary data collected at the Queens College site. Finally, we report emission indices (EI) for both fleet-average conditions and single vehicles, including several New York City Metropolitan Transit Authority (MTA) buses, sampled by the AML in “chase” mode during the study.

Copyright 2012 American Association for Aerosol Research     

Phase Characteristics of a U-22Pu-4Am-2Np-40Zr Metallic Alloy Containing Rare Earths

Metallic fuel alloys consisting of uranium (U), plutonium (Pu), and zirconium (Zr) with minor additions of americium (Am) and neptunium (Np) are under evaluation for potential use to transmute long-lived transuranic actinide isotopes in fast reactors. The current irradiation test series design, designated Advanced Fuel Cycle-2 (AFC2), includes minor additions of rare earth (RE) elements to simulate expected fission product carryover from the electrochemical molten salt reprocessing technique. The as-cast fuel alloys have been investigated for phase and thermal properties; specifically, enthalpies of transition, transition temperatures, and room temperature phase characteristics. Results and observations related to these characteristics for the “fresh” fuel alloys are provided. The alloy compositions are based on a U-22Pu-4Am-2Np-40Zr alloy, along with additions of 1.3 and 1.9 at.% RE (at the expense of uranium where RE denotes rare earth alloy of cerium, lanthanum, praseodymium, and neodymium). Phase behavior and associated transitions have been compared to available U-Pu-Zr ternary diagrams with acceptable agreement. Enthalpies of transition were deconvoluted from heating and cooling thermal traces for relatively reliable values. The RE additions to the base alloy have a minimal influence on the room temperature phases present and phase transition temperatures, but the room temperature phases present did impact the enthalpies of transition.     

Clinically significant behavior problems during the initial 18 months following early childhood traumatic brain injury.

Objective: This study looked at the emergence of clinically significant problems in behavior, executive function skills, and social competence during the initial 18 months following traumatic brain injury (TBI) in young children relative to a cohort of children with orthopedic injuries (OI) and the environmental factors that predict difficulties postinjury. Participants: Children, ages 3–7 years, hospitalized for severe TBI, moderate TBI, or OI were seen shortly after their injury (M = 40 days) and again 6 months, 12 months, and 18 months postinjury. Design: Behavioral parent self-reports, demographic data, family functioning reports, and home environment reports were collected at injury baseline and each time point postinjury. Results: Results suggest that, compared with the OI group, the severe TBI group developed significantly more externalizing behavior problems and executive function problems following injury that persisted through the 18-month follow-up. Minimal social competence difficulties appeared at the 18-month follow-up, suggesting a possible pattern of emerging deficits rather than a recovery over time. Conclusions: Predictors of the emergence of clinically significant problems included permissive parenting, family dysfunction, and low socioeconomic status. The findings are similar to those found in school-age children. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repetition priming of nonwords in young and older adults.

In 3 experiments, a pronunciation task was used to examine repetition priming of novel nonwords in young and older adults. The contributions of item and associative priming to the total repetition priming effect were assessed. In Experiment 1, age consistency was found in both components of repetition priming after 9 repetitions of nonwords. Experiment 2 established that young and older adults were similar in item and associative priming after as few as 2 repetitions of nonwords. Finally, Experiment 3 demonstrated that associative priming persists for at least 3 min and that it is dissociable from cued recall. The overall pattern of results strongly argues that elaborative processing is not necessary to obtain associative priming in indirect memory tasks and that young and older adults show similar magnitudes of associative priming. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive interventions to improve face-name recall: The role of personality trait differences.

To explore the relationship of personality trait differences to the ability of older adults to benefit from an intervention to improve face–name recall, 3 previously validated methods of intervention were used in conjunction with the NEO Personality Inventory. Ss were 156 community-dwelling elderly. The 3 treatment conditions all included a standard imagery mnemonic for remembering names and faces but differed in the method of nonmnemonic training (imagery, relaxation, and imagery?+?judgment) administered before teaching the mnemonic device. As in prior studies, there was an overall improvement in the number of face–name pairs remembered after the intervention. In the group of Ss as a whole, Ss who scored higher on the openness factor of the NEO scored significantly higher on all face–name outcome measures regardless of training conditions. Furthermore, there was a significant interaction between treatment condition and scores on Subfactor O1 (fantasy) of the openness factor. Higher scores on the fantasy subfactor were related to greater improvements in the imagery condition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of Infant Car Seat grip orientations and lift strategies

The rear-facing Infant Car Seat (ICS) is designed to meet federal requirements for transporting children less than 1 year old. Typical use includes transfer in and out of a vehicle, which is shown to be a difficult lift. Despite the frequency of this lift, manufacturers provide little guidance for users. Review of relevant literature suggested an ICS featuring an angled handle, promoting a neutral wrist posture, would increase grip stability and decrease lifting effort. Popular press suggested a foot-in-car stance for the ICS lift would do the same. An experiment was conducted in which wrist deviations from neutral posture were recorded along with lifting muscle activation levels (multiple flexor muscles and biceps brachii) and overall perceived exertion for straight versus a new bent handle design and conventional stance versus foot-in-car. Foot position was examined to test the recommendations in the popular press. Surprisingly, wrist deviation was not significantly affected by the new bent handle design (due to compensatory behavior with the straight handle) but was related to foot placement (p=0.04). Results revealed the bent handle to significantly reduce flexor activation compared with the straight handle (p=0.0003); however, the level of biceps activation increased. Biceps activation also significantly increased for foot-in-car stance (p=0.035) but not flexor activation. In general, the bent handle enabled the user to lift the ICS with a steadier grip and less effort.     

Remote virtual whiteboard assistance for improving task performance during lunar surface operations

Virtual Reality - During extravehicular activities (EVAs), astronauts are heavily dependent on the Mission Center (MCC) and their Intra-Vehicular Astronaut (IVA) counterparts. Each procedure step...