2,004 research outputs found
Conflict over resources generates conflict over mate choice: Reply to Smaldino and Newson
This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/doi:10.1016/j.evolhumbehav.2013.12.004Evolutionary computer simulations are an important part of the theoretical biologist's toolkit (Peck, 2004;
DeAngelis & Mooij, 2005; Kokko, 2007), offering insights into a range of fundamental evolutionary
processes, not least sexual selection (e.g. van Doorn & Weissing 2004, 2006; Fawcett et al., 2007, 2011;
van Doorn et al., 2009; reviewed in Kuijper et al., 2012). Like all theoretical tools, they must be used with
care (Hamblin, 2012). Smaldino & Newson (2013, henceforth S&N) have challenged our recent work on
parent–offspring conflict over mate choice (Van den Berg et al., 2013), arguing that our simulations rely
on unrealistic assumptions and that our conclusions are not supported. But all four points of criticism they
present are misguided. (1) The accusation that the handicap principle cannot work in our model is wrong;
Fig. 1a in Van den Berg et al. (2013) clearly demonstrates that a costly preference for a signal of male
quality does evolve. (2) The assertion that mutation bias drove male quality close to zero in our model is
wrong; in fact, male quality reached very high, stable levels in our simulations. (3) The assertion that
overcompensation was responsible for our results is wrong; parent and offspring preferences also diverge
in the absence of overcompensation. (4) The alternative explanation offered for our results is wrong,
because it predicts the opposite pattern to that we actually observed in our simulations. Below we address
each of these misunderstandings and consider two alternative hypotheses suggested by S&
Charge superconductivity from pair density wave order in certain high temperature superconductors
A number of spectacular experimental anomalies\cite{li-2007,fujita-2005} have
recently been discovered in certain cuprates, notably {\LBCO} and {\LNSCO},
which exhibit unidirectional spin and charge order (known as ``stripe order'').
We have recently proposed to interpret these observations as evidence for a
novel ``striped superconducting'' state, in which the superconducting order
parameter is modulated in space, such that its average is precisely zero. Here,
we show that thermal melting of the striped superconducting state can lead to a
number of unusual phases, of which the most novel is a charge
superconducting state, with a corresponding fractional flux quantum .
These are never-before observed states of matter, and ones, moreover, that
cannot arise from the conventional Bardeen-Cooper-Schrieffer (BCS) mechanism.
Thus, direct confirmation of their existence, even in a small subset of the
cuprates, could have much broader implications for our understanding of high
temperature superconductivity. We propose experiments to observe fractional
flux quantization, which thereby could confirm the existence of these states.Comment: 5 pages, 2 figures; new version in Nature Physics format with a
discussion of the effective Josephson coupling J2 and minor changes. Mildly
edited abstract. v3: corrected versio
Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds
Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n =15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occured. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases. The immunohistochemical detection of actin-positive cells, therefore, demonstrates whether an unknown skin wound is aged approximately 5 days or more. Even though a time-dependent decrease of myofibroblasts in human granulation tissue after 31 days in human wounds seems probable, the extended presence (up to about 2 months) of these cells allows no further exact age determination of older wounds
Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate
\ua9 2022, The Author(s). Glycogen synthase (GYS1) is the central enzyme in muscle glycogen biosynthesis. GYS1 activity is inhibited by phosphorylation of its amino (N) and carboxyl (C) termini, which is relieved by allosteric activation of glucose-6-phosphate (Glc6P). We present cryo-EM structures at 3.0–4.0 \uc5 resolution of phosphorylated human GYS1, in complex with a minimal interacting region of glycogenin, in the inhibited, activated and catalytically competent states. Phosphorylations of specific terminal residues are sensed by different arginine clusters, locking the GYS1 tetramer in an inhibited state via intersubunit interactions. The Glc6P activator promotes conformational change by disrupting these interactions and increases the flexibility of GYS1, such that it is poised to adopt a catalytically competent state when the sugar donor UDP-glucose (UDP-glc) binds. We also identify an inhibited-like conformation that has not transitioned into the activated state, in which the locking interaction of phosphorylation with the arginine cluster impedes subsequent conformational changes due to Glc6P binding. Our results address longstanding questions regarding the mechanism of human GYS1 regulation
Simulation-based analysis of micro-robots swimming at the center and near the wall of circular mini-channels
Swimming micro robots have great potential in biomedical applications such as targeted drug delivery, medical diagnosis, and destroying blood clots in arteries. Inspired by swimming micro organisms, micro robots can move in biofluids with helical tails attached to their bodies. In order to design and navigate micro robots, hydrodynamic characteristics of the flow field must be understood well. This work presents computational fluid dynamics (CFD) modeling and analysis of the flow due to the motion of micro robots that consist of magnetic heads and helical tails inside fluid-filled channels akin to bodily conduits; special emphasis is on the effects of the radial position of the robot. Time-averaged velocities, forces, torques, and efficiency of the micro robots placed in the channels are analyzed as functions of rotation frequency, helical pitch (wavelength) and helical radius (amplitude) of the tail. Results indicate that robots move faster and more efficiently near the wall than at the center of the channel. Forces acting on micro robots are asymmetrical due to the chirality of the robot’s tail and its motion. Moreover, robots placed near the wall have a different flow pattern around the head when compared to in-center and unbounded swimmers. According to simulation results, time-averaged for-ward velocity of the robot agrees well with the experimental values measured previously for a robot with almost the same dimensions
Discontinuation of a randomised controlled trial in general practice due to unsuccessful patient recruitment.
BACKGROUND: A randomised controlled trial (RCT) in general practice, recruiting incident patients with (sub)acute sciatica, was discontinued because of insufficient recruitment. AIM: To describe factors that influenced the recruitment process and ultimately led to discontinuation of this trial, and to enable others to learn from this experience. DESIGN & SETTING: A pragmatic RCT was designed to compare two pain medication prescription strategies for treatment of (sub)acute sciatica in general practice. After 1 year of patient recruitment, the trial was prematurely terminated. METHOD: To analyse the underperforming recruitment, patient information systems of 20 general practices were screened twice a month to search for eligible patients and identify reasons for non-eligibility. Secondly, after study termination, an open question was distributed to the participating GPs for their views on the recruitment process. RESULTS: A total of 116 GPs from 37 general practices collaborated in the trial. Only eight of 234 patients were included after 12 months. The 22 GPs who offered their opinion on the main reasons for unsuccessful recruitment considered that these were the low incidence rate and strict eligibility criteria, a strong patient and/or GP preference, and time constraints. CONCLUSION: For this RCT, multiple factors were related to recruitment problems but it remains unknown which determinants prevailed. As the research question is unanswered but remains relevant, it is recommended that GPs' daily practice is taken into account when designing an RCT, a pilot study should be performed for feasibility of recruitment, and GP assistants should be involved at an early stage
Time-Based Partitioning Model for Predicting Neurologically Favorable Outcome among Adults with Witnessed Bystander Out-of-Hospital CPA
Background:Optimal acceptable time intervals from collapse to bystander cardiopulmonary resuscitation (CPR) for neurologically favorable outcome among adults with witnessed out-of-hospital cardiopulmonary arrest (CPA) have been unclear. Our aim was to assess the optimal acceptable thresholds of the time intervals of CPR for neurologically favorable outcome and survival using a recursive partitioning model.Methods and Findings:From January 1, 2005 through December 31, 2009, we conducted a prospective population-based observational study across Japan involving consecutive out-of-hospital CPA patients (N = 69,648) who received a witnessed bystander CPR. Of 69,648 patients, 34,605 were assigned to the derivation data set and 35,043 to the validation data set. Time factors associated with better outcomes: the better outcomes were survival and neurologically favorable outcome at one month, defined as category one (good cerebral performance) or two (moderate cerebral disability) of the cerebral performance categories. Based on the recursive partitioning model from the derivation dataset (n = 34,605) to predict the neurologically favorable outcome at one month, 5 min threshold was the acceptable time interval from collapse to CPR initiation; 11 min from collapse to ambulance arrival; 18 min from collapse to return of spontaneous circulation (ROSC); and 19 min from collapse to hospital arrival. Among the validation dataset (n = 35,043), 209/2,292 (9.1%) in all patients with the acceptable time intervals and 1,388/2,706 (52.1%) in the subgroup with the acceptable time intervals and pre-hospital ROSC showed neurologically favorable outcome.Conclusions:Initiation of CPR should be within 5 min for obtaining neurologically favorable outcome among adults with witnessed out-of-hospital CPA. Patients with the acceptable time intervals of bystander CPR and pre-hospital ROSC within 18 min could have 50% chance of neurologically favorable outcome
Aerodynamics of the Hovering Hummingbird
Despite profound musculoskeletal differences, hummingbirds (Trochilidae) are widely thought to employ aerodynamic mechanisms similar to those used by insects. The kinematic symmetry of the hummingbird upstroke and downstroke has led to the assumption that these halves of the wingbeat cycle contribute equally to weight support during hovering, as exhibited by insects of similar size. This assumption has been applied, either explicitly or implicitly, in widely used aerodynamic models, and in a variety of empirical tests. Here we provide measurements of the wake of hovering rufous hummingbirds (Selasphorus rufus) obtained with digital particle image velocimetry that show force asymmetry: hummingbirds produce 75% of their weight support during the downstroke and only 25% during the upstroke. Some of this asymmetry is probably due to inversion of their cambered wings during upstroke. The wake of hummingbird wings also reveals evidence of leading-edge vortices created during the downstroke, indicating that they may operate at Reynolds numbers sufficiently low to exploit a key mechanism typical of insect hovering. Hummingbird hovering approaches that of insects, yet remains distinct because of effects resulting from an inherently dissimilar—avian—body plan
Central adrenal insufficiency is rare in adults with Prader-Willi syndrome
CONTEXT: Prader-Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. In some countries, it is general practice to prescribe stress-dose hydrocortisone during physical or psychological stress in patients with PWS. Side effects of frequent hydrocortisone use are weight gain, osteoporosis, diabetes mellitus, and hypertension-already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity-or even mortality. OBJECTIVE: To prevent both over- and undertreatment with hydrocortisone, we assessed the prevalence of CAI in a large international cohort of adults with PWS. As the synacthen test shows variable results in PWS, we only use the metyrapone test (MTP) and insulin tolerance test (ITT). DESIGN: Metyrapone test or ITT in adults with PWS (N = 82) and review of medical files for symptoms of hypocortisolism related to surgery (N = 645). SETTING: Outpatient clinic. PATIENTS OR OTHER PARTICIPANTS: Eighty-two adults with genetically confirmed PWS. MAIN OUTCOME MEASURE: For MTP, 11-deoxycortisol > 230 nmol/L was considered sufficient. For ITT, cortisol > 500 nmol/L (Dutch, French, and Swedish patients) or > 450 nmol/L (British patients) was considered sufficient. RESULTS: Central adrenal insufficiency was excluded in 81 of 82 patients. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative hydrocortisone treatment. None of them had displayed any features of hypocortisolism. CONCLUSIONS: Central adrenal insufficiency is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing hydrocortisone stress-doses in adults with PWS
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