Application of two phosphorus models with different complexities in a mesoscale river catchment

The water balance and phosphorus inputs of surface waters of the Weiße Elster catchment, Germany, have been quantified using the models GROWA/MEPhos and SWAT. A comparison of the model results shows small differences in the mean long-term total runoff for the entire study area. All relevant pathways of phosphorus transport were considered in MEPhos with phosphorus inputs resulting to about 65% from point sources. SWAT focuses on agricultural areas and estimates a phosphorus input of about 60% through erosion. The mean annual phosphorus input from erosion calculated with SWAT is six times higher than the estimation with MEPhos due to the differing model concepts. This shows the uncertainty contributed by the modelling description of phosphorus pathways

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

The effect of contemplation and meditation on ‘great compassion’ on the psychological well-being of adolescents

Abstract: Please refer to full text to view abstrac

CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state

Accurate chromosome segregation requires assembly of the multiprotein kinetochore complex. Prior work has identified more than 100 different kinetochore components in human cells. However, little is known about the regulatory processes that specify their assembly upon mitotic entry and disassembly at mitotic exit. In this paper, we used a live-cell imaging–based assay to quantify kinetochore disassembly kinetics and systematically analyze the role of potential regulatory mechanisms in controlling kinetochore assembly state. We find that kinetochore assembly and disassembly was driven primarily by mitotic phosphorylation downstream of cyclin-dependent kinase (CDK). In addition, we demonstrate that nuclear exclusion of the Ndc80 complex helped restrict kinetochore formation to mitosis. Combining constitutive CDK-dependent phosphorylation of CENP-T and forced nuclear localization of the Ndc80 complex partially prevented kinetochore disassembly at mitotic exit and led to chromosome segregation defects in subsequent divisions. In total, we find that the coordinated temporal regulation of outer kinetochore assembly is essential for accurate cell division.Kinship Foundation. Searle Scholars ProgramLeukemia & Lymphoma Society of AmericaNational Institutes of Health (U.S.) (National Institute of General Medical Sciences (U.S.) Grant GM088313)Leukemia & Lymphoma Society of America (Special Fellows Award

The functions and consequences of force at kinetochores

Chromosome segregation requires the generation of force at the kinetochore—the multiprotein structure that facilitates attachment of chromosomes to spindle microtubules. This force is required both to move chromosomes and to signal the formation of proper bioriented attachments. To understand the role of force in these processes, it is critical to define how force is generated at kinetochores, the contributions of this force to chromosome movement, and how the kinetochore is structured and organized to withstand and respond to force. Classical studies and recent work provide a framework to dissect the mechanisms, functions, and consequences of force at kinetochores.National Institute of General Medical Sciences (U.S.) (Grant GM088313

A two-step mechanism for epigenetic specification of centromere identity and function

The basic determinant of chromosome inheritance, the centromere, is specified in many eukaryotes by an epigenetic mark. Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagate centromere function indefinitely. Initially, centromere position is replicated and maintained by chromatin assembled with the centromere-targeting domain (CATD) of CENP-A substituted into H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing chromatin is shown to require either the amino- or carboxy-terminal tail of CENP-A for recruitment of inner kinetochore proteins, including stabilizing CENP-B binding to human centromeres or direct recruitment of CENP-C, respectively.National Institutes of Health grant: (GM 074150); Ludwig Institute for Cancer Research; European Molecular Biology Organization (EMBO) long-term fellowship

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