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

Priprava i vrednovanje biorazgradljivih implantata s kontroliranim oslobađanjem za postoperativnu primjenu

Biodegradable implants of ciprofloxacin hydrochloride for post operative site delivery were prepared using glyceryl monostearate and different concentrations of polyethylene glycol (PEG 6000) glycerol and Tween 80 as erosion enhancers by compression and molding technique. Formulations were subjected to in vitro drug release by the USP dissolution method, while promising formulations were subjected to in vitro drug release by the agar gel method and also to stability studies. It was observed that glyceryl monostearate formed hydrophobic matrix and delayed the drug delivery. Antibiotic release profile was controlled by using different combinations of erosion enhancers. The formulation prepared by compression method showed more delayed release as compared to formulations prepared by molding method.Biorazgradljivi implantati ciprofloksacin hidroklorida za postoperativnu primjenu pripravljeni su pomoću gliceril monostearata (GMS) i različitih koncentracija polietilen glikola (PEG 6000), glicerola i Tween 80 kao promotora erozije metodom kompresije i lijevanja. Oslobađanje ljekovite tvari iz pripravaka praćeno je in vitro prema USP metodi. Pripravci koji su dali dobre rezultate ispitani su i in vitro metodom s agarom te su podvrgnuti testovima stabilnosti. Primijećeno je da gliceril monostearat tvori hidrofobni matriks i usporava oslobađanje lijeka. Koristeći različite kombinacije promotora erozije postignuto je kontrolirano oslobađanje antibiotika. Oslobađanje iz implantata dobivenih metodom kompresije sporije je od implantata dobivenih metodom lijevanja

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

When is a hydrological model sufficiently calibrated to depict flow preferences of riverine species?

Riverine species have adapted to their environment, particularly to the hydrological regime. Hydrological models and the knowledge of species preferences are used to predict the impact of hydrological changes on species. Inevitably, hydrological model performance impacts how species are simulated. From the example of macroinvertebrates in a lowland and a mountainous catchment, we investigate the impact of hydrological model performance and the choice of the objective function based on a set of 36 performance metrics for predicting species occurrences. Besides species abundance, we use the simulated community structure for an ecological assessment as applied for the Water Framework Directive. We investigate when a hydrological model is sufficiently calibrated to depict species abundance. For this, we postulate that performance is not sufficient when ecological assessments based on the simulated hydrology are significantly different (analysis of variance, p < .05) from the ecological assessments based on observations. The investigated range of hydrological model performance leads to considerable variability in species abundance in the two catchments. In the mountainous catchment, links between objective functions and the ecological assessment reveal a stronger dependency of the species on the discharge regime. In the lowland catchment, multiple stressors seem to mask the dependence of the species on discharge. The most suitable objective functions to calibrate the model for species assessments are the ones that incorporate hydrological indicators used for the species prediction

iPrevent

Curso de Especial InterésLa siguiente propuesta, contiene la información necesaria para poder asesorar y brindar una mejor atención a los procesos que son inherentes a la sexualidad del ser humano. El diseño de la creación de una aplicación llamada iPrevent, usada en aparatos tecnológicos como los móviles con sistema Android y Apple. Esta aplicación está encaminada a presentar y a exponer los distintos métodos anticonceptivos que se encuentran en el mercado, así mismo brindar un marco de conocimiento de cada uno, para facilitar la toma de decisiones de los adolescentes; de esta manera teniendo una correlación con la salud pública y mitigar los embarazos no deseados y posibles interrupciones voluntarias del embarazo (IVE) y uso de Métodos Anticonceptivos de emergencia en esta población.101 p.1. Resumen 2. Justificación 3. Marco teórico 4. Objetivos 5. Metodología 6. Estudio de mercadeo 7. Resultados 8. Discusión 9. Conclusiones y recomendaciones 10. Referencias 11. ApéndicesPregradoPsicólog

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

Nap1 regulates proper CENP-B binding to nucleosomes

CENP-B is a widely conserved centromeric satellite DNA-binding protein, which specifically binds to a 17-bp DNA sequence known as the CENP-B box. CENP-B functions positively in the de novo assembly of centromeric nucleosomes, containing the centromere-specific histone H3 variant, CENP-A. At the same time, CENP-B also prevents undesired assembly of the CENP-A nucleosome through heterochromatin formation on satellite DNA integrated into ectopic sites. Therefore, improper CENP-B binding to chromosomes could be harmful. However, no CENP-B eviction mechanism has yet been reported. In the present study, we found that human Nap1, an acidic histone chaperone, inhibited the non-specific binding of CENP-B to nucleosomes and apparently stimulated CENP-B binding to its cognate CENP-B box DNA in nucleosomes. In human cells, the CENP-B eviction activity of Nap1 was confirmed in model experiments, in which the CENP-B binding to a human artificial chromosome or an ectopic chromosome locus bearing CENP-B boxes was significantly decreased when Nap1 was tethered near the CENP-B box sequence. In contrast, another acidic histone chaperone, sNASP, did not promote CENP-B eviction in vitro and in vivo and did not stimulate specific CENP-B binding to CENP-A nucleosomes in vitro. We therefore propose a novel mechanism of CENP-B regulation by Nap1

Small molecule antagonists of NAADP-induced Ca2+ release in T-lymphocytes suggest potential therapeutic agents for autoimmune disease

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca2+-releasing second messenger known to date, but the precise NAADP/Ca2+ signalling mechanisms are still controversial. We report the synthesis of small-molecule inhibitors of NAADP-induced Ca2+ release based upon the nicotinic acid motif. Alkylation of nicotinic acid with a series of bromoacetamides generated a diverse compound library. However, many members were only weakly active or had poor physicochemical properties. Structural optimisation produced the best inhibitors that interact specifically with the NAADP/Ca2+ release mechanism, having no effect on Ca2+ mobilized by the other well-known second messengers D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] or cyclic adenosine 5′-diphospho-ribose (cADPR). Lead compound (2) was an efficient antagonist of NAADP-evoked Ca2+ release in vitro in intact T lymphocytes and ameliorated clinical disease in vivo in a rat experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Compound (3) (also known as BZ194) was synthesized as its bromide salt, confirmed by crystallography, and was more membrane permeant than 2. The corresponding zwitterion (3a), was also prepared and studied by crystallography, but 3 had more desirable physicochemical properties. 3 Is potent in vitro and in vivo and has found widespread use as a tool to modulate NAADP effects in autoimmunity and cardiovascular applications. Taken together, data suggest that the NAADP/Ca2+ signalling mechanism may serve as a potential target for T cell- or cardiomyocyte-related diseases such as multiple sclerosis or arrhythmia. Further modification of these lead compounds may potentially result in drug candidates of clinical use

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