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More on how and why: response to commentaries

We are grateful to the commentators for taking the time to respond to our article. Too many interesting and important points have been raised for us to tackle them all in this response, and so in the below we have sought to draw out the major themes. These include problems with both the term ‘ultimate causation’ and the proximate-ultimate causation dichotomy more generally, clarification of the me

Evolution of complex symbiotic relationships in a morphologically derived family of lichen-forming fungi.

We studied the evolutionary history of the Parmeliaceae (Lecanoromycetes, Ascomycota), one of the largest families of lichen-forming fungi with complex and variable morphologies, also including several lichenicolous fungi. We assembled a six-locus data set including nuclear, mitochondrial and low-copy protein-coding genes from 293 operational taxonomic units (OTUs). The lichenicolous lifestyle ori

Exact and approximation algorithms for geometric and capacitated set cover problems

First, we study geometric variants of the standard set cover motivated by assignment of directional antenna and shipping with deadlines, providing the first known polynomial-time exact solutions. Next, we consider the following general (non-necessarily geometric) capacitated set cover problem. There is given a set of elements with real weights and a family of sets of the elements. One can use a s

Proteolytic degradation of neuropeptide Y (NPY) from head to toe: Identification of novel NPY-cleaving peptidases and potential drug interactions in CNS and Periphery.

The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor-selectivity by dipeptidyl-peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selecti

Localised boundary air layer and clothing evaporative resistances for individual body segments.

Evaporative resistance is an important parameter to characterise clothing thermal comfort. However, previous work has focused mainly on either total static or dynamic evaporative resistance. There is a lack of investigation of localised clothing evaporative resistance. The objective of this study was to study localised evaporative resistance using sweating thermal manikins. The individual and inte

Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature.

Pancreatic cancer (PC) has a poor prognosis, with a 5-year survival of 3-4%. This is mainly due to late diagnosis because of diffuse symptoms, where 80-85% of the patients are inoperable. Consequently, early diagnosis would be of significant benefit, resulting in a potential 5-year survival of 30-40%. However, new technologies must be carefully evaluated concerning effectiveness and healthcare cos

Identification of B-cell lymphoma subsets by plasma protein profiling using recombinant antibody microarrays.

B-cell lymphoma (BCL) heterogeneity represents a key issue, often making the classification and clinical management of these patients challenging. In this pilot study, we outlined the first resolved view of BCL disease heterogeneity on the protein level by deciphering disease-associated plasma biomarkers, specific for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma

Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension

Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up val

Habitat and Habitus: Boxed-in versus Box-Breaking Research

This paper argues that scholarly work is increasingly situated in narrowly circumscribed areas of study, which are encouraging specialization, incremental adding-to-the-literature contributions and a blinkered mindset. Researchers invest considerable time and energy in these specialized areas in order to maximize their productivity and career prospects. We refer to this way of doing research and s

Global Upper Ordovician correlation by means of delta C-13 chemostratigraphy: implications of the discovery of the Guttenberg delta C-13 excursion (GICE) in Malaysia

Apart from a single study of the early Katian delta C-13 chemostratigraphy in two regions in China, no investigations of the Sandbian and Katian chemostratigraphy have been published from anywhere in Asia. A recent study of the conodont biostratigraphy of the classical Ordovician succession on Langkawi Islands, peninsular Malaysia, showed the presence there of strata coeval with those having the G

Trends in the first decade of 21st century healthcare utilisation in a rheumatoid arthritis cohort compared with the general population.

PURPOSE: To study 21st century trends in healthcare utilisation by patients with rheumatoid arthritis (RA) compared with the general population. METHODS: Observational cohort study. Using Swedish healthcare register data, we identified 3977 Region Skåne residents (mean age in 2001, 62.7 years; 73% women) presenting with RA (International Classification of Diseases-10 codes M05 or M06) in 1998-2001

Suberythemal Sun Exposures at Swedish Schools Depend on Sky Views of the Outdoor Environments - Possible Implications for Pupils' Health.

More scheduled outdoor stay is increasingly advocated for school children. This study measured 2(nd) , 5(th) and 8(th) graders' erythemal UV-exposure in September, March and May at four Swedish schools. We related those exposures, as fractions of total available ambient radiation, to the schools outdoor environments differing in amount of shade, vegetation, and peripheral city-scape quantified as

Prymnesium parvum invasion success into coastal bays of the Gulf of Mexico: Galveston Bay case study

The toxic haptophyte Prymnesium parvum regularly forms fish-killing blooms in inland brackish water bodies in the south-central USA. Along the Texas coast smaller blooms have occurred in isolated areas. There appears to be an increasing risk that harmful P. parvum blooms will propagate into open coastal waters with implementation of future water plans. These plans will include increased interbasin

Nonlinear compartmental model of F-18-choline

Introduction: This work develops a compartmental model of F-18-choline in order to evaluate its biokinetics and so to describe the temporal variation of the radiopharmaceuticals' uptake in and clearance from organs and tissues. Methods: Ten patients were considered in this study. A commercially available tool for compartmental analysis (SAAM II) was used to model the values of activity concentrati

Relocating the owl of wisdom : Encyclopaedias in a life-historical perspective

Artikeln undersöker människors förhållningssätt till uppslagsverk och encyklopedier i ett livshistoriskt perspektiv under en period när encyklopedier har genomgått dramatiska förändringar. En frågelista som skickats till fasta så kallade meddelare knutna till Folklivsarkivet i Lund har använts som metod. Svaren har analyserats med hjälp av posthumanistisk teori. Analysen visar de sätt som tryckta Encyclopaedias are artefacts that both define and are defined by the culture in which they are produced and used. Encyclopaedias mirror the time of their creation, at the same time as understanding and use of encyclopaedias is tied to both time and space. From the 19th century until the present day encyclopaedias have changed from exclusive and costly Collections of books kept mainly in libraries

Biochemical characterisation and novel classification of monofunctional S-adenosylmethionine decarboxylase of Plasmodium falciparum

Plasmodium falciparum like other organisms is dependent on polyamines for proliferation. Polyamine biosynthesis in these parasites is regulated by a unique bifunctional S-adenosylmethionine decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC). Only limited biochemical and structural information is available on the bifunctional enzyme due to the low levels and impurity of an instable recombinantl

Cancer risk in patients with type 2 diabetes mellitus and their relatives.

Epidemiological studies indicate that risks of certain cancers are increased in individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be representative of the entire population of T2DM patients as most of them are treated in primary health cares. To examine the subsequent cancer risk in individuals with T2DM from hospitals and primary health cares, and in their siblings and s

A Central Role for GRB10 in Regulation of Islet Function in Man.

Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion