Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents.

DNA-damaging agents are among the most frequently used anticancer drugs. However, they provide only modest benefit in most cancers. This may be attributed to a genome maintenance network, the DNA damage response (DDR), that recognizes and repairs damaged DNA.

The electronic structures of the S(2) states of the oxygen-evolving complexes of photosystem II in plants and cyanobacteria in the presence and absence of methanol.

The electronic properties of the Mn(4)O(x)Ca cluster in the S(2) state of the oxygen-evolving complex (OEC) were studied using X- and Q-band EPR and Q-band (55)Mn-ENDOR using photosystem II preparations isolated from the thermophilic cyanobacterium T. elongatus and higher plants (spinach). The data presented here show that there is very little difference between the two species.

High and low potential forms of the QA quinone electron acceptor in Photosystem II of Thermosynechococcus elongatus and spinach.

The redox potential of Q(A) in Photosystem II (PSII) from Thermosynechococcus elongatus was titrated monitoring chlorophyll fluorescence. A high potential form (E(m)=+60 ± 25 mV) was found in the absence of Mn(4)Ca, the active site for water oxidation. The low potential form (E(m)=-60 ± 48 mV), which is difficult to measure in conventional titration experiments, could be "locked in" by cross-linking the active enzyme.

Pretransplant depression, antidepressant use, and outcomes of orthotopic liver transplantation.

Depression is a common problem among patients awaiting organ transplantation, but little is known about the impact of depression and its treatment on the outcomes of liver transplantation. In this retrospective cohort analysis, we studied all patients over 18 years of age who underwent liver transplantation during a 5-year period (2004-2008) at a single center. Among 179 recipients, 65 patients had depression, as defined by a health care provider assessment, before transplantation.

Effect of Ca2+/Sr2+ substitution on the electronic structure of the oxygen-evolving complex of photosystem II: a combined multifrequency EPR, 55Mn-ENDOR, and DFT study of the S2 state.

The electronic structures of the native Mn(4)O(x)Ca cluster and the biosynthetically substituted Mn(4)O(x)Sr cluster of the oxygen evolving complex (OEC) of photosystem II (PSII) core complexes isolated from Thermosynechococcus elongatus, poised in the S(2) state, were studied by X- and Q-band CW-EPR and by pulsed Q-band (55)Mn-ENDOR spectroscopy. Both wild type and tyrosine D less mutants grown photoautotrophically in either CaCl(2) or SrCl(2) containing media were measured. The obtained CW-EPR spectra of the S(2) state displayed the characteristic, clearly noticeable differences in the hyperfine pattern of the multiline EPR signal [Boussac et al.

Peer review - a safety and quality improvement initiative in a general practice.

Background: A general practice in inner city Melbourne (Victoria), committed to ensuring quality standards of clinical care, developed a process for peer review of their doctors' performance. The aim was to ensure that there was a robust and fair process for evaluation of doctor performance from both a safety point of view, and from the perspective of contribution to team based practice.

Objective: This article describes the process and outcomes of this appraisal process.

Reducing the incidence of twins from IVF treatments: predictive modelling from a retrospective cohort.

Background: IVF treatments carry a high risk of twin pregnancy which confers a higher risk to the mother and child than singletons. Increased use of elective single embryo transfer (eSET) can reduce this twin rate. We aimed to utilize a previously published data set and statistical model based on routinely collected clinical data to predict the outcomes of policies that increase the proportion of eSET.

A high redox potential form of cytochrome c550 in photosystem II from Thermosynechococcus elongatus.

Cytochrome c(550) (cyt c(550)) is a component of photosystem II (PSII) from cyanobacteria, red algae, and some other eukaryotic algae. Its physiological role remains unclear. In the present work, measurements of the midpoint redox potential (E(m)) were performed using intact PSII core complexes preparations from a histidine-tagged PSII mutant strain of the thermophilic cyanobacterium Thermosynechococcus (T.

Effects of formate binding on the quinone-iron electron acceptor complex of photosystem II.

EPR was used to study the influence of formate on the electron acceptor side of photosystem II (PSII) from Thermosynechococcus elongatus. Two new EPR signals were found and characterized. The first is assigned to the semiquinone form of Q(B) interacting magnetically with a high spin, non-heme-iron (Fe²(+), S=2) when the native bicarbonate/carbonate ligand is replaced by formate.

Intramolecular light induced activation of a Salen-Mn(III) complex by a ruthenium photosensitizer.

We have designed a molecular system consisting of a heteroleptic [Ru(bpy)(2)L](2+) chromophore covalently linked to a Mn(III)-Salen unit. We demonstrate the light induced oxidation of the Mn(III) center in this putative photo-catalyst assembly to a Mn(IV) high spin intermediate. Both oxidation states have been characterized by transient absorption and EPR techniques.

Neuropsychological consequence of soccer play in adolescent U.K. School team soccer players.

To assess mild head injury effects in adolescent soccer players, neuropsychological performance across school team soccer players, rugby players and noncontact sport players was assessed in a quasi-experimental cross-sectional design. One hundred eighty-five males were tested (ages 13-16; response rate 55%) and 86 contributed data to the analyses after exclusion for recent concussion and overlapping sports participation. Soccer players showed lower premorbid intellectual functioning, but neither soccer players nor rugby players showed neuropsychological decrement compared with noncontact sport players.

Encoding instructions and stimulus presentation in local environmental context-dependent memory studies.

Murnane and Phelps (1993) recommend word pair presentations in local environmental context (EC) studies to prevent associations being formed between successively presented items and their ECs and a consequent reduction in the EC effect. Two experiments were conducted to assess the veracity of this assumption. In Experiment 1, participants memorised single words or word pairs, or categorised them as natural or man made.

Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro.

This study investigated the relationship between human preimplantation embryo metabolism and aneuploidy rates during development in vitro. One hundred and eighty-eight fresh and cryopreserved embryos from 59 patients (33.9 +/- 0.

How many response options? A study of remember-know testing procedures.

The remember-know procedure can be conducted in one or two steps. The one-step procedure does not include a recognition response (old-new) prior to the remember-know response. It is observed consistently that the one-step procedure leads to a more liberal placement of the response criterion, but it is unclear whether recognition accuracy is affected by the number of procedural steps.

A deterministic model of home and community care client counts in British Columbia.

In British Columbia (BC) Home and Community Care (HCC) services provide a range of health care and support services for British Columbians with acute, chronic, palliative or rehabilitative health care needs. Although it is not surprising that almost 80% of HCC clients are senior citizens (aged 65 and older), this does lead to some concern. In particular, the most recent population projections suggest that the senior population of BC will double in the next twenty years.

The semiquinone-iron complex of photosystem II: structural insights from ESR and theoretical simulation; evidence that the native ligand to the non-heme iron is carbonate.

The semiquinone-iron complex of photosystem II was studied using electron spin resonance (ESR) spectroscopy and density functional theory calculations. Two forms of the signal were investigated: 1), the native g approximately 1.9 form; and 2), the g approximately 1.

BioGateway: a semantic systems biology tool for the life sciences.

Background: Life scientists need help in coping with the plethora of fast growing and scattered knowledge resources. Ideally, this knowledge should be integrated in a form that allows them to pose complex questions that address the properties of biological systems, independently from the origin of the knowledge. Semantic Web technologies prove to be well suited for knowledge integration, knowledge production (hypothesis formulation), knowledge querying and knowledge maintenance.

Identification of the QY excitation of the primary electron acceptor of photosystem II: CD determination of its coupling environment.

Low-temperature absorption and CD spectra, measured simultaneously, are reported from Photosystem II (PS II) reduced with sodium dithionite. Spectra were obtained using PS II core complexes before and after photoaccumulation of Pheo(D1)(-), the anion of the primary acceptor. For plant PS II, Pheo(D1)(-) was generated under conditions in which the primary plastoquinone was present as an anion (Q(A)(-)) and as a modified species taken to be the neutral doubly reduced hydroquinone (Q(A)H(2)).

D1 protein variants in Photosystem II from Thermosynechococcus elongatus studied by low temperature optical spectroscopy.

In Photosystem II (PSII) from Thermosynechococcus elongatus, high-light intensity growth conditions induce the preferential expression of the psbA(3) gene over the psbA(1) gene. These genes encode for the D1 protein variants labeled D1:3 and D1:1, respectively. We have compared steady state absorption and photo-induced difference spectra at <10 K of PSII containing either D1:1 or D1:3.

The discovery of the potent aurora inhibitor MK-0457 (VX-680).

The identification of a novel series of Aurora kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modification of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (VX-680) has been assessed in Phase II clinical trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) containing the T315I mutation.

History's mysteries demystified: becoming a psychologist-historian.

More than 40 years ago, psychologist-historian Robert Watson argued that the study of history was of particular salience to psychology. In this article we explore the relationship between psychology and history and argue that the psychologist-historian plays a vital role in the discipline of psychology. We provide a brief overview of the emergence of the history of psychology as a professional subdiscipline, describe who psychologist-historians are, explain why they are needed, and detail how to join their ranks.