Charge Transfer in Partition Theory

The recently proposed Partition Theory (PT) [J.Phys.Chem.A 111, 2229 (2007)] is illustrated on a simple one-dimensional model of a heteronuclear diatomic molecule. It is shown that a sharp definition for the charge of molecular fragments emerges from PT, and that the ensuing population analysis can be used to study how charge redistributes during dissociation and the implications of that redistribution for the dipole moment. Interpreting small differences between the isolated parts' ionization potentials as due to environmental inhomogeneities, we gain insight into how electron localization takes place in H2+ as the molecule dissociates. Furthermore, by studying the preservation of the shapes of the parts as different parameters of the model are varied, we address the issue of transferability of the parts. We find good transferability within the chemically meaningful parameter regime, raising hopes that PT will prove useful in chemical applications.Comment: 12 pages, 16 figure

Conceptualising quality of life for older people with aphasia

Background: There is an increasing need in speech and language therapy for clinicians to provide intervention in the context of the broader life quality issues for people with aphasia. However, there is no descriptive research that is explicitly focused on quality of life (QoL) from the perspectives of older people with aphasia. Aims: The current study explores how older people with chronic aphasia who are living in the community describe their QoL in terms of what contributes to and detracts from the quality in their current and future lives. The study is descriptive in nature, and the purpose is to conceptualize the factors that influence QoL. Methods & Procedures: Thirty older participants (16 women, 14 men) with mild to moderate aphasic impairment took part. All participants had adequate communication skills to participate: demonstrating reliable yes/no response and moderate auditory comprehension ability. Participants were interviewed in their own homes using six brief unprompted open questions about QoL, in a structured interview. The first five questions were drawn from previous gerontological research (Farquhar, 1995), and a sixth question specifically targeting communication was added. Content analysis was used, identifying discrete units of data and then coding these into concepts and factors. Additional demographic information was collected, and participants’ mood on day of interviewing was assessed using the Geriatric Depression Scale (Sheikh & Yesavage, 1986). Outcomes & Results: Activities, verbal communication, people, and body functioning were the core factors in QoL for these participants, and they described how these factors both contributed quality in life as well as detracted from life quality. Other factors that influenced QoL included stroke, mobility, positive personal outlook, in/dependence, home and health. Whilst the findings are limited by the lack of probing of participants’ responses, the study does present preliminary evidence for what is important in QoL to older people with aphasia. Conclusions: Quality of life for older people with predominantly mild to moderate chronic aphasia who are living in the community is multifactorial in nature. Some factors lie within the remit of speech and language therapy, some lie beyond the professional role, but all are relevant for consideration in rehabilitation and community practice. Further qualitative research is implicated to better understand QoL with aphasia, using in-depth interviewing with a broader range of people with aphasia

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis

Chromosome segregation and genome maintenance require the removal of DNA bridges that link chromosomes just before cells divide. Here the authors show that the LEM-3/Ankle1 nuclease processes DNA bridges before cells divide and define a previously undescribed genome integrity mechanism

Alternative splicing of the n-terminal cytosolic and transmembrane domains of P2X7 controls gating of the ion channel by ADP-ribosylation

P2X7 is a homotrimeric ion channel with two transmembrane domains and a large extracellular ATP-binding domain. It plays a key role in the response of immune cells to danger signals released from cells at sites of inflammation. Gating of murine P2X7 can be induced by the soluble ligand ATP, as well as by NAD(+)-dependent ADP-ribosylation of arginine 125, a posttranslational protein modification catalyzed by the toxin-related ecto-enzymes ART2.1 and ART2.2. R125 is located at the edge of the ligand-binding crevice. Recently, an alternative splice variant of P2X7, designated P2X7(k), was discovered that differs from the previously described variant P2X7(a) in the N-terminal 42 amino acid residues composing the first cytosolic domain and most of the Tm1 domain. Here we compare the two splice variants of murine P2X7 with respect to their sensitivities to gating by ADP-ribosylation in transfected HEK cells. Our results show that the P2X7(k) variant is sensitive to activation by ADP-ribosylation whereas the P2X7(a) variant is insensitive, despite higher cell surface expression levels. Interestingly, a single point mutation (R276K) renders the P2X7(a) variant sensitive to activation by ADP-ribosylation. Residue 276 is located at the interface of neighboring subunits approximately halfway between the ADP-ribosylation site and the transmembrane domains. Moreover, we show that naive and regulatory T cells preferentially express the more sensitive P2X7(k) variant, while macrophages preferentially express the P2X7(a) variant. Our results indicate that differential splicing of alternative exons encoding the N-terminal cytosolic and transmembrane domains of P2X7 control the sensitivity of different immune cells to extracellular NAD(+) and ATP

Understanding Heavy Tails of Flood Peak Distributions

Statistical distributions of flood peak discharge often show heavy tail behavior, that is, extreme floods are more likely to occur than would be predicted by commonly used distributions that have exponential asymptotic behavior. This heavy tail behavior may surprise flood managers and citizens, as human intuition tends to expect light tail behavior, and the heaviness of the tails is very difficult to predict, which may lead to unnecessarily high flood damage. Despite its high importance, the literature on the heavy tail behavior of flood distributions is rather fragmented. In this review, we provide a coherent overview of the processes causing heavy flood tails and the implications for science and practice. Specifically, we propose nine hypotheses on the mechanisms causing heavy tails in flood peak distributions related to processes in the atmosphere, the catchment, and the river system. We then discuss to which extent the current knowledge supports or contradicts these hypotheses. We also discuss the statistical conditions for the emergence of heavy tail behavior based on derived distribution theory and relate them to the hypotheses and flood generation mechanisms. We review the degree to which the heaviness of the tails can be predicted from process knowledge and data. Finally, we recommend further research toward testing the hypotheses and improving the prediction of heavy tails

Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5′-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells

*S Supporting Information ABSTRACT: Two nicotinamide adenine dinucleotide (NAD +) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD + (6-N-methyl nicotinamide adenosine 5′-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5′-diphosphoribose, 11), whereas 6-thio NHD + (nicotinamide 6-mercaptopurine 5′-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5′-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5′-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1cIDPR-induced Ca 2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5′-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling