Abstract
Human rights have become a dominant paradigm in police reform projects worldwide, championed by policymakers, legislators and campaigners alike. Such projects are often premised on, and ...evaluated according to, a conception of human rights as an autonomous, coherent and legitimate body of norms. It is a paradigm made real through formal training, procedures and oversight. This paper invites a different reading of human rights. Drawing on extensive interviews with junior officers, it reveals how human rights come to be emergent from, and embedded within, the minutia of their working lives. The presence and meaning of human rights are sustained through a series of ‘sensemaking’ narratives arising from the rich intermingling of legal and organizational representations of rights and officers’ own experiences. Subtle variations, inconsistencies and contradictions in officers’ sensemaking are revealed across a four-fold typology which disrupts the stability and coherency of the human rights paradigm, but also generalizations made about police culture.
Crystalline porous materials have a variety of uses, such as for catalysis and separations. Identifying suitable materials for a given application can, in principle, be done by screening material ...databases. Such a screening requires automated high-throughput analysis tools that calculate topological and geometrical parameters describing pores. These descriptors can be used to compare, select, group, and classify materials. Here, we present a descriptor that captures shape and geometry characteristics of pores. Together with proposed similarity measures, it can be used to perform diversity selection on a set of porous materials. Our representations are histogram encodings of the probe-accessible fragment of the Voronoi network representing the void space of a material. We discuss and demonstrate the application of our approach on the International Zeolite Association (IZA) database of zeolite frameworks and the Deem database of hypothetical zeolites, as well as zeolitic imidazolate frameworks constructed from IZA zeolite structures. The diverse structures retrieved by our method are complementary to those expected by emphasizing diversity in existing one-dimensional descriptors, e.g., surface area, and similar to those obtainable by a (subjective) manual selection based on materials’ visual representations. Our technique allows for reduction of large sets of structures and thus enables the material researcher to focus efforts on maximally dissimilar structures.
Here we tell the story of ivermectin, describing its anthelmintic and insecticidal actions and recent studies that have sought to reposition ivermectin for the treatment of other diseases that are ...not caused by helminth and insect parasites. The standard theory of its anthelmintic and insecticidal mode of action is that it is a selective positive allosteric modulator of glutamate-gated chloride channels found in nematodes and insects. At higher concentrations, ivermectin also acts as an allosteric modulator of ion channels found in host central nervous systems. In addition, in tissue culture, at concentrations higher than anthelmintic concentrations, ivermectin shows antiviral, antimalarial, antimetabolic, and anticancer effects. Caution is required before extrapolating from these preliminary repositioning experiments to clinical use, particularly for Covid-19 treatment, because of the high concentrations of ivermectin used in tissue-culture experiments.
Ivermectin and analogs are remarkable broad-spectrum anthelmintics and insecticides, but resistance is now a real concern. Resistance mechanisms have been proposed but they do not appear to account for the resistance seen in parasitic nematodes.Ivermectin is very effective for controlling microfilaria at low doses but it has limited effects on adult filaria for unclear reasons.Ivermectin is a positive allosteric modulator of glutamate-gated chloride channels found in both nematodes and insects, and it binds to the channels in their lipid phase.Ivermectin and analogs also modulate other ion channels and have effects on the mammalian host brain when the blood–brain barrier is impaired.Preliminary repositioning studies of ivermectin show antiviral, antimalarial, antimetabolic, and anticancer effects at concentrations higher than anthelmintic concentrations in tissue culture.
Circulating adipokines and C‐reactive protein (CRP) have been linked to breast cancer risk in observational epidemiological studies. The causal nature of these associations is unclear because of the ...susceptibility of conventional observational designs to residual confounding, reverse causation and other forms of bias. Mendelian randomisation (MR) uses genetic variants as proxies for risk factors to strengthen causal inference in observational settings. We performed a MR analysis to evaluate the causal relevance of six previously reported circulating adipokines adiponectin, hepatocyte growth factor (HGF), interleukin‐6, leptin receptor, plasminogen activator inhibitor‐1 and resistin and CRP in risk of overall and oestrogen receptor‐stratified breast cancer in up to 122,977 cases and 105,974 controls of European ancestry. Genetic instruments were constructed from single‐nucleotide polymorphisms robustly (p < 5 × 10−8) associated with risk factors in genome‐wide association studies. Colocalisation was performed as a sensitivity analysis to examine whether findings reflected shared causal variants or genomic confounding. In MR analyses, there was evidence for an association of HGF with oestrogen receptor‐negative cancer (odds ratio per standard deviation increase: 1.17, 95% confidence interval: 1.01–1.35; p = 0.035) but little evidence for associations of other adipokines or CRP with overall or oestrogen receptor‐stratified breast cancer. Colocalisation analysis suggested that the association of HGF with oestrogen receptor‐negative breast cancer was unlikely to reflect a causal association. Collectively, these findings do not support an important aetiological role of various adipokines or CRP in overall or oestrogen receptor‐specific breast cancer risk.
What's new?
Adipokines and C‐reactive protein have been linked to breast cancer risk in observational studies. But while these molecular mediators potentially connect excess adiposity with breast cancer, whether the associations are causal in nature is uncertain. Here, a Mendelian randomization approach was employed to estimate the causal effect of six circulating adipokines and C‐reactive protein on breast cancer risk. Overall, among 122,977 cases and 105,974 controls, analyses provided little evidence supporting a causal role for these molecular markers in breast cancer etiology. The findings warrant investigation of other mediators that could explain apparent links between adiposity and increased breast cancer risk.
On the Flexibility of Metal–Organic Frameworks Sarkisov, Lev; Martin, Richard L; Haranczyk, Maciej ...
Journal of the American Chemical Society,
02/2014, Letnik:
136, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Occasional, large amplitude flexibility in metal–organic frameworks (MOFs) is one of the most intriguing recent discoveries in chemistry and material science. Yet, there is at present no theoretical ...framework that permits the identification of flexible structures in the rapidly expanding universe of MOFs. Here, we propose a simple method to predict whether a MOF is flexible, based on treating it as a system of rigid elements, connected by hinges. This proposition is correct in application to MOFs based on rigid carboxylate linkers. We validate the method by correctly classifying known experimental MOFs into rigid and flexible groups. Applied to hypothetical MOFs, the method reveals an abundance of flexibility phenomena, and this seems to be at odds with the proportion of flexible structures among experimentally known MOFs. We speculate that the flexibility of a MOF may constitute an intrinsic impediment on its experimental realization. This highlights the importance of systematic prediction of large amplitude flexibility regimes in MOFs.
This book presents applied probability and stochastic processes in an elementary but mathematically precise manner, with numerous examples and exercises to illustrate the range of engineering and ...science applications of the concepts. The book is designed to give the reader an intuitive understanding of probabilistic reasoning, in addition to an understanding of mathematical concepts and principles. The initial chapters present a summary of probability and statistics and then Poisson processes, Markov chains, Markov processes and queuing processes are introduced. Advanced topics include simulation, inventory theory, replacement theory, Markov decision theory, and the use of matrix geometric procedures in the analysis of queues. Included in the second edition are appendices at the end of several chapters giving suggestions for the use of Excel in solving the problems of the chapter. Also new in this edition are an introductory chapter on statistics and a chapter on Poisson processes that includes some techniques used in risk assessment. The old chapter on queues has been expanded and broken into two new chapters: one for simple queuing processes and one for queuing networks. Support is provided through the web site http://apsp.tamu.edu where students will have the answers to odd numbered problems and instructors will have access to full solutions and Excel files for homework. TOC:Basic Probability Review.- Basic of Monte Carlo Simulation.- Basic Statistical Review.- Poisson Processes.- Markov Chains.- Markov Processes.- Queueing Processes.- Queueing Networks.- Event-Driven Simulation and Output Analyses.- Inventory Theory.- Replacement Theory.- Markov Decision Processes.- Advanced Queues.- Matrix Review.- Index.
Porous polymer networks (PPNs) are a class of advanced porous materials that combine the advantages of cheap and stable polymers with the high surface areas and tunable chemistry of metal–organic ...frameworks. They are of particular interest for gas separation or storage applications, for instance, as methane adsorbents for a vehicular natural gas tank or other portable applications. PPNs are self-assembled from distinct building units; here, we utilize commercially available chemical fragments and two experimentally known synthetic routes to design in silico a large database of synthetically realistic PPN materials. All structures from our database of 18,000 materials have been relaxed with semiempirical electronic structure methods and characterized with Grand-canonical Monte Carlo simulations for methane uptake and deliverable (working) capacity. A number of novel structure–property relationships that govern methane storage performance were identified. The relationships are translated into experimental guidelines to realize the ideal PPN structure. We found that cooperative methane–methane attractions were present in all of the best-performing materials, highlighting the importance of guest interaction in the design of optimal materials for methane storage.
Risk factors for pancreatic cancer include a cluster of metabolic conditions such as obesity, hypertension, dyslipidemia, insulin resistance, and type 2 diabetes. Given that these risk factors are ...correlated, separating out causal from confounded effects is challenging. Mendelian randomization (MR), or the use of genetic instrumental variables, may facilitate the identification of the metabolic drivers of pancreatic cancer.
We identified genetic instruments for obesity, body shape, dyslipidemia, insulin resistance, and type 2 diabetes in order to evaluate their causal role in pancreatic cancer etiology. These instruments were analyzed in relation to risk using a likelihood-based MR approach within a series of 7110 pancreatic cancer patients and 7264 control subjects using genome-wide data from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Potential unknown pleiotropic effects were assessed using a weighted median approach and MR-Egger sensitivity analyses.
Results indicated a robust causal association of increasing body mass index (BMI) with pancreatic cancer risk (odds ratio OR = 1.34, 95% confidence interval CI = 1.09 to 1.65, for each standard deviation increase in BMI 4.6 kg/m2). There was also evidence that genetically increased fasting insulin levels were causally associated with an increased risk of pancreatic cancer (OR = 1.66, 95% CI = 1.05 to 2.63, per SD 44.4 pmol/L). Notably, no evidence of a causal relationship was observed for type 2 diabetes, nor for dyslipidemia. Sensitivity analyses did not indicate that pleiotropy was an important source of bias.
Our results suggest a causal role of BMI and fasting insulin in pancreatic cancer etiology.
In the ProtecT trial, over 1600 men with PSA-detected localized prostate cancer were assigned to active monitoring, prostatectomy, or radiotherapy. Although more patients assigned to active ...monitoring had disease progression, overall survival was similar in the three groups.
The management of clinically localized prostate cancer that is detected on the basis of prostate-specific antigen (PSA) levels remains controversial. In the United States alone, an estimated 180,890 cases will be diagnosed in 2016, and 26,120 men will die from the disease.
1
The widespread use of PSA testing has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer, but many men do not benefit from intervention because the disease is either indolent or disseminated at diagnosis. Prostate cancer often progresses slowly, and many men die of competing causes. In addition, interventions for prostate cancer can have . . .
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