1,974 research outputs found
A piece of the puzzle: analyses of recent strandings and historical records reveal new genetic and ecological insights on New Zealand sperm whales
Cetacean strandings provide important opportunities to extend current knowledge on species or populations, particularly for species that are notoriously difficult to study, such as sperm whales Physeter macrocephalus (parÄoa). Between 25 May and 9 June 2018, 13 male sperm whales stranded in Taranaki, New Zealand (NZ), with an additional male stranding 1 mo later in Clifford Bay, Marlborough. We profiled these 14 males for mitochondrial DNA (mtDNA) and carbon and nitrogen stable isotopes to examine their similarity to sperm whales from other geographic areas. Analyses of mtDNA revealed 7 haplotypes, including 1 not previously described (âNewâ), and an additional haplotype (âMâ) new to NZ that had been previously reported in sperm whales of the Pacific region. Analysis of rare haplotypes found in NZ males suggested genetic links within NZ and the Southwest Pacific. Differences in stable isotope ratios indicated that, despite the close temporal proximity of these stranding events, individuals originated from at least 2 separate groups, with the whale stranded in Clifford Bay identified as being a regular visitor to KaikĹura, South Island. The analysis of stranding records in NZ dating back to 1873 indicated an increase in recorded single strandings since 1970, and a peak in single strandings in the austral summer months, but no seasonality for mass strandings. Sex predicted latitudinal location for single strandings, with 95.1% of female strandings occurring north of 42° S, fitting the general global distribution of female sperm whales limited to lower latitudes. This study provides the first temporal and spatial assessment of sperm whale strandings in NZ and highlights the need for future research on movements and genetic exchange between NZ sperm whales and sperm whales in the wider Pacific region.Publishe
Mitochondrial DNA changes in pedunculopontine cholinergic neurons in Parkinsonâs disease
In Parkinsonâs disease (PD), mitochondrial dysfunction associates with nigral dopaminergic neuronal loss. Cholinergic neuronal loss co-occurs, particularly within a brainstem structure, the pedunculopontine nucleus (PPN). We isolated single cholinergic neurons from post-mortem PPNs of aged controls and PD patients. Mitochondrial DNA (mtDNA) copy number and mtDNA deletions were increased significantly in PD patients compared to controls. Furthermore, compared to controls the PD patients had significantly more PPN cholinergic neurons containing mtDNA deletion levels exceeding 60%, a level associated with deleterious effects on oxidative phosphorylation. The current results differ from studies reporting mtDNA depletion in nigral dopaminergic neurons of PD patients
Wave fronts and cascades of soliton interactions in the periodic two dimensional Volterra system
In the paper we develop the dressing method for the solution of the two-dimensional periodic Volterra system with a period N. We derive soliton solutions of arbitrary rank k and give a full classification of rank 1 solutions. We have found a new class of exact solutions corresponding to wave fronts which represent smooth interfaces between two nonlinear periodic waves or a periodic wave and a trivial (zero) solution. The wave fronts are non-stationary and they propagate with a constant average velocity. The system also has soliton solutions similar to breathers, which resembles soliton webs in the KP theory. We associate the classification of soliton solutions with the Schubert decomposition of the Grassmannians View the MathML source and View the MathML source
U.S. stock market interaction network as learned by the Boltzmann Machine
We study historical dynamics of joint equilibrium distribution of stock
returns in the U.S. stock market using the Boltzmann distribution model being
parametrized by external fields and pairwise couplings. Within Boltzmann
learning framework for statistical inference, we analyze historical behavior of
the parameters inferred using exact and approximate learning algorithms. Since
the model and inference methods require use of binary variables, effect of this
mapping of continuous returns to the discrete domain is studied. The presented
analysis shows that binarization preserves market correlation structure.
Properties of distributions of external fields and couplings as well as
industry sector clustering structure are studied for different historical dates
and moving window sizes. We found that a heavy positive tail in the
distribution of couplings is responsible for the sparse market clustering
structure. We also show that discrepancies between the model parameters might
be used as a precursor of financial instabilities.Comment: 15 pages, 17 figures, 1 tabl
From Chalcogen Bonding to SâĎ Interactions in Hybrid Perovskite Photovoltaics
The stability of hybrid organicâinorganic halide perovskite semiconductors remains a significant obstacle to their application in photovoltaics. To this end, the use of lowâdimensional (LD) perovskites, which incorporate hydrophobic organic moieties, provides an effective strategy to improve their stability, yet often at the expense of their performance. To address this limitation, supramolecular engineering of noncovalent interactions between organic and inorganic components has shown potential by relying on hydrogen bonding and conventional van der Waals interactions. Here, the capacity to access novel LD perovskite structures that uniquely assemble through unorthodox Sâmediated interactions is explored by incorporating benzothiadiazoleâbased moieties. The formation of Sâmediated LD structures is demonstrated, including oneâdimensional (1D) and layered twoâdimensional (2D) perovskite phases assembled via chalcogen bonding and SâĎ interactions, through a combination of techniques, such as single crystal and thin film Xâray diffraction, as well as solidâstate NMR spectroscopy, complemented by molecular dynamics simulations, density functional theory calculations, and optoelectronic characterization, revealing superior conductivities of Sâmediated LD perovskites. The resulting materials are applied in nâiâp and pâiân perovskite solar cells, demonstrating enhancements in performance and operational stability that reveal a versatile supramolecular strategy in photovoltaics
Patientsâ perceptions and experiences of living with a surgical wound healing by secondary intention : a qualitative study
Background: Most surgical wounds heal by primary intention, that is to say, the edges of the wound are brought together with sutures, staples, adhesive glue or clips. However, some wounds may be left open to heal (if there is a risk of infection, or if there has been significant tissue loss), and are known as âsurgical wounds healing by secondary intentionâ. They are estimated to comprise approximately 28% of all surgical wounds and are frequently complex to manage. However, they are under researched and little is known of their impact on patientsâ lives. Objectives: To explore patientsâ views and experiences of living with a surgical wound healing by secondary intention. Design: A qualitative, descriptive approach. Settings: Participants were recruited from acute and community nursing services in two locations in the North of England characterised by high levels of deprivation and diverse populations. Participants: Participants were aged 18 years or older and had at least one surgical wound healing by secondary intention, which was slow to heal. Purposeful sampling was used to include patients of different gender, age, wound duration and type of surgery (general, vascular and orthopaedic). Twenty people were interviewed between January and July 2012. 2 Methods: Semi-structured interviews were conducted, guided by use of a topic guide developed with input from patient advisors. Data were thematically analysed using steps integral to the âFrameworkâ approach to analysis, including familiarisation with data; development of a coding scheme; coding, charting and cross comparison of data; interpretation of identified themes. Findings: Alarm, shock and disbelief were frequently expressed initial reactions, particularly to âunexpectedâ surgical wounds healing by secondary intention. Wound associated factors almost universally had a profound negative impact on daily life, physical and psychosocial functioning, and wellbeing. Feelings of frustration, powerlessness and guilt were common and debilitating. Patientsâ hopes for healing were often unrealistic, posing challenges for the clinicians caring for them. Participants expressed dissatisfaction with a perceived lack of continuity and consistency of care in relation to wound management. Conclusions: Surgical wounds healing by secondary intention can have a devastating effect on patients, both physical and psychosocial. Repercussions for patientsâ family members can also be extremely detrimental, including financial pressures. Health care professionals involved in the care of patients with these wounds face multiple, complex challenges, compounded by the limited evidence base regarding cost-effectiveness of different treatment regimens for these types of wounds
From Chalcogen Bonding to SâĎ Interactions in Hybrid Perovskite Photovoltaics
The stability of hybrid organicâinorganic halide perovskite semiconductors remains a significant obstacle to their application in photovoltaics. To this end, the use of lowâdimensional (LD) perovskites, which incorporate hydrophobic organic moieties, provides an effective strategy to improve their stability, yet often at the expense of their performance. To address this limitation, supramolecular engineering of noncovalent interactions between organic and inorganic components has shown potential by relying on hydrogen bonding and conventional van der Waals interactions. Here, the capacity to access novel LD perovskite structures that uniquely assemble through unorthodox Sâmediated interactions is explored by incorporating benzothiadiazoleâbased moieties. The formation of Sâmediated LD structures is demonstrated, including oneâdimensional (1D) and layered twoâdimensional (2D) perovskite phases assembled via chalcogen bonding and SâĎ interactions, through a combination of techniques, such as single crystal and thin film Xâray diffraction, as well as solidâstate NMR spectroscopy, complemented by molecular dynamics simulations, density functional theory calculations, and optoelectronic characterization, revealing superior conductivities of Sâmediated LD perovskites. The resulting materials are applied in nâiâp and pâiân perovskite solar cells, demonstrating enhancements in performance and operational stability that reveal a versatile supramolecular strategy in photovoltaics
Efficacy of a Non-Hypercalcemic Vitamin-D2 Derived Anti-Cancer Agent (MT19c) and Inhibition of Fatty Acid Synthesis in an Ovarian Cancer Xenograft Model
BACKGROUND:Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING:Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3) xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR) antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN) activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K) activity independently of PPAR-gamma protein. SIGNIFICANCE:Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis
Regulating E-Cigarettes: Why Policies Diverge
This paper, part of a festschrift in honor of Professor Malcolm Feeley, explores the landscape of e-cigarette policy globally by looking at three jurisdictions that have taken starkly different approaches to regulating e-cigarettesâthe US, Japan, and China. Each of those countries has a robust tobacco industry, government agencies entrusted with protecting public health, an active and sophisticated scientific and medical community, and a regulatory structure for managing new pharmaceutical, tobacco, and consumer products. All three are signatories of the World Health Organizationâs Framework Convention on Tobacco Control, all are signatories of the Agreement on Trade-Related Aspects of Intellectual Property Rights, and all are members of the World Trade Organization. Which legal, economic, social and political differences between the three countries explain their diverse approaches to regulating e-cigarettes? Why have they embraced such dramatically different postures toward e-cigarettes? In seeking to answer those questions, the paper builds on Feeley\u27s legacy of comparative scholarship, policy analysis, and focus on law in action
Read-across and new approach methodologies applied in a 10-step framework for cosmetics safety assessment â A case study with parabens
Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for the value added by new approach methodologies (NAMs) in read-across (RAX) for use in a next-generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics. In addition to structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data from PBK models, and bioactivity data are used to provide evidence of the chemical and biological similarity of PP and analogues and to establish potency trends for observed effects in vitro. The chemical category under consideration is short (C1âC4) linear chain n-alkyl parabens: methylparaben, ethylparaben, propylparaben and butylparaben. The goal of this case study is to illustrate how a practical framework for RAX can be used to fill a hypothetical data gap for reproductive toxicity of the target chemical PP
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