Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of selection on genes involved in regulatory network: a modelling study

Complex phenotypes are often controlled by many interacting genes. One question emerging from such organization is how selection, acting at the phenotypic level, shapes the evolution of genes involved in regulatory networks controlling the phenotypes. We studied this issue through a matrix model of such networks. In a population submitted to selection, we simulated the evolution of a quantitative trait controlled by a set of loci that regulate each other through positive or negative interactions. Investigating several levels of selection intensity on the trait, we studied the evolution of regulation intensity between the genes and the evolution of the genetic diversity of those genes as an indirect measure of the strength of selection acting on them. We show that an increasing intensity of selection on the phenotype leads to an increased level of regulation between the loci. Moreover, we found that the genes responding more strongly to selection within the network were those evolving towards stronger regulatory action on the other genes and/or those that are the less regulated by the other genes. This observation is strongest for an intermediate level of selection. This may explain why several experimental studies have shown evidence of selection on regulatory genes inside gene networks.
Measurements of 3 He spin-exchange rates

He. In the course of these measurements we developed and tested a new method for Rb densitymeasurements under high power pumping conditions, and a new variant of Rb EPR polarimetry, both of whichare described here.DOI: 10.1103/PhysRevA.66. 032703 PACS number~s! : 34.30. 1h, 32.80. Bx, 33.25. 1kI. INTRODUCTION
Illustration of a Common Framework for Relating Multiple Typing Methods by Application to Macrolide-Resistant Streptococcus pyogenes

ABSTRACT The studies that correlate the results obtained by different typing methodologies rely solely on qualitative comparisons of the groups defined by each methodology. We propose a framework of measures for the quantitative assessment of correspondences between different typing methods as a first step to the global mapping of type equivalences. A collection of 325 macrolide-resistant Streptococcus pyogenes isolates associated with pharyngitis cases in Portugal was used to benchmark the proposed measures. All isolates were characterized by macrolide resistance phenotyping, T serotyping, emm sequence typing, and pulsed-field gel electrophoresis (PFGE), using SmaI or Cfr9I and SfiI. A subset of 41 isolates, representing each PFGE cluster, was also characterized by multilocus sequence typing (MLST). The application of Adjusted Rand and Wallace indices allowed the evaluation of the strength and the directionality of the correspondences between the various typing methods and showed that if PFGE or MLST data are available one can confidently predict the emm type (Wallace coefficients of 0.952 for both methods). In contrast, emm typing was a poor predictor of PFGE cluster or MLST sequence type (Wallace coefficients of 0.803 and 0.655, respectively). This was confirmed by the analysis of the larger data set available from http://spyogenes.mlst. net and underscores the necessity of performing PFGE or MLST to unambiguously define clones in S. pyogenes.
Introducing lasso peptides as molecular scaffolds for drug design: engineering of an integrin antagonist.

Thumbnail image of graphical abstract Tightening the noose: Lasso peptides are a class of stable bacterial peptides with unique characteristics that encourage their application in drug design. Epitope grafting of the integrin binding motif RGD onto the lasso structure of microcin J25 converts the knotted peptide into a nanomolar integrin antagonist (see picture). Engineered lasso peptides can therefore be used for pharmacophore presentation.
Establishing a Case‐Finding and Referral System for At‐Risk Older Individuals in the Emergency Department Setting: The SIGNET Model

Older emergency department (ED) patients have complex medical, social, and physical problems. We established a program at four ED sites to improve case finding of at‐risk older adults and provide comprehensive assessment in the ED setting with formal linkage to community agencies. The objectives of the program are to (1) improve case finding of at‐risk older ED patients, (2) improve care planning and referral for those returning home, and (3) create a coordinated network of existing medical and community services. The four sites are a 1,000‐bed teaching center, a 700‐bed county teaching hospital, a 400‐bed community hospital, and a health maintenance organization (HMO) ED site. Ten community agencies also participated in the study: four agencies associated with the hospital/HMO sites, two nonprofit private agencies, and four public agencies. Case finding is done using a simple screening assessment completed by the primary or triage nurse. A geriatric clinical nurse specialist (GCNS) further assesses those considered at risk. Patients with unmet medical, social, or health needs are referred to their primary physicians or to outpatient geriatric evaluation and management centers and to community agencies. After 18 months, the program has been successfully implemented at all four sites. Primary nurses screened over 70% (n = 28,437) of all older ED patients, GCNSs conducted 3,757 comprehensive assessments, participating agency referrals increased sixfold, and few patients refused the GCNS assessment or subsequent referral services. Thus, case finding and community linkage programs for at‐risk older adults are feasible in the ED setting.
Relationship between adipose tissue lipolytic activity and skeletal muscle insulin resistance in nondiabetic women.

CONTEXT Increased adipose tissue lipolytic activity is considered an important factor in the pathogenesis of skeletal muscle insulin resistance associated with obesity. OBJECTIVE The objective of the study was to evaluate the relationship between the rate of release of free fatty acids (FFA) into plasma and skeletal muscle insulin sensitivity in human subjects. METHODS We determined the palmitate rate of appearance (Ra) per kilogram fat-free mass (an index of FFA availability to lean tissues) during basal conditions and during insulin infusion (to simulate postprandial insulin concentrations) and skeletal muscle insulin sensitivity, defined as the percent increase in the glucose rate of disappearance, in 110 nondiabetic women (body mass index 20.6-46.4 kg/m(2)) by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer methods. RESULTS Basal (r(s) = -0.379, P < 0.001) and insulin-suppressed (r(s) = -0.631, P < 0.001) palmitate Ra correlated negatively with skeletal muscle insulin sensitivity. However, the strength of the correlation was greater for palmitate Ra during insulin infusion than palmitate Ra during basal conditions (P = 0.0007) when lipolytic rates and FFA availability were reduced to less than 20% of basal values. The relative suppression of palmitate Ra correlated directly with the relative stimulation of glucose rate of disappearance during insulin infusion (r(s) = 0.530, P < 0.001). CONCLUSION These data suggest that the correlation between FFA kinetics and muscle glucose metabolism is due to multiorgan insulin resistance rather than a direct effect of FFA itself on skeletal muscle insulin action and challenge the view that increased adipose tissue lipolytic rate is an important cause of insulin resistance.
Determination of the minimal clinically important difference in rheumatoid arthritis joint damage of the Sharp/van der Heijde and Larsen/Scott scoring methods by clinical experts and comparison with the smallest detectable difference.

OBJECTIVE To assess the minimal clinically important difference (MCID) in joint damage on hand and foot radiographs of patients with early rheumatoid arthritis (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to study how the smallest detectable difference (SDD) relates to the MCID for each method. METHODS The judgments of an international panel of experts on the clinical relevance of progression of joint damage as seen on sets of radiographs obtained at 1-year intervals in 4 clinical settings (early versus late RA and mild versus high disease activity) were used as the external criterion, which was compared with the progression scores as determined by the 2 scoring methods. Progression scores with the highest combined sensitivity and specificity for detecting clinically relevant progression represented the MCID. Subsequently, the sensitivity and specificity of the scoring methods were determined when using the SDD as the threshold for relevant progression, and these were compared with the sensitivity and specificity of the MCID. RESULTS The panel judged changes in joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method as minimal clinically important, resulting in satisfactory sensitivity (mean 79%) and specificity (mean 84%) for detecting clinically important progression in the 4 clinical settings when using the SDD as the threshold value. The MCID (mean 2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the sensitivity for detecting clinically important progression by applying the SDD as threshold was consequently low (mean 51%), accompanied by high specificity (mean 99%). CONCLUSION This study suggests that the SDD of the Sharp/van der Heijde method can be used as the MCID, i.e., as the threshold level for individual response criteria. The SDD of the Larsen/Scott method, however, turned out to be too insensitive to use as the threshold for individual clinically relevant change.
The Right Picture Is Worth a Thousand Numbers: Data Displays in Anesthesia

Objective: To review the literature on data displays in anesthesia identifying issues and developing design recommendations. Background: Unexpected incidents are common in critical care medicine. Adverse outcomes are frequently the catastrophic endpoints of an “evolving” chain of subtle incidents. One strategy to reduce the likelihood of an adverse patient outcome during anesthesia is to improve the anesthesiologist's ability to detect, diagnose, and treat critical incidents. Method: A literature review and analysis of data displays. Results: Current numerical and waveform displays do not support anesthesiologists optimally. An alternative is graphical displays that functionally integrate variables into objects. In a well-designed graphic object, deviations from normal are shown by distortions in the object's symmetry. The emerging patterns that result from distorted symmetry facilitate the correct diagnosis. When treatment is effective, an object's shape is restored to normal. Graphical displays can be an effective tool in supporting anesthesiologists' situation awareness. Conclusion: Problems related to graphical displays have delayed their use in anesthesia, including the lack of conclusive clinical evidence of their value. However, currently more evidence is accumulating that graphical displays have the potential to improve clinical performance. The successful development of these graphical displays takes into account task requirements, a user's perceptual processes, and task-specific cognition. Application: This paper provides suggestions for the development of more effective displays in anesthesiology. Graphical displays can increase the anesthesiologist's situation awareness and improve clinical performance. Clinical use of these displays has the potential to significantly improve patient safety.
The influence of anesthetic technique on perioperative complications after carotid endarterectomy.

PURPOSE This study evaluated the influence of anesthetic techniques on perioperative complications after carotid endarterectomy. METHODS Perioperative complications, the use of a carotid artery shunt, the duration of the operative procedure and postoperative hospital course were retrospectively compared in 584 consecutive patients undergoing 679 carotid endarterectomies with use of either general anesthesia (n = 361) or cervical block regional anesthesia (n = 318). There was no significant difference in the preoperative medical characteristics between the two anesthetic groups. Symptomatic carotid artery disease was the indication for surgery in 247 (68.4%) patients receiving general anesthetics, whereas 180 (56.6%) patients treated with a cervical block anesthetic had a symptomatic carotid artery stenosis (p = 0.02). RESULTS The perioperative stroke rate and stroke-death rate for the entire series was 2.4% and 3.2%, respectively, and was not significantly different between the anesthetic groups or between patients with symptomatic or asymptomatic disease. A carotid artery shunt was used in 61 (19.2%) patients receiving a cervical block anesthetic and 152 (42.1%) patients treated with a general anesthetic (p < 0.0001). Use of cervical block anesthesia was associated with a significantly shorter operative time, fewer perioperative cardiopulmonary complications, and a shorter postoperative hospitalization when compared with general anesthesia. Multivariate risk factor analysis indicated that age greater than 75 years, operative time greater than 3 hours, and the use of a carotid artery shunt were all independent risk factors for perioperative cardiopulmonary complications. When a carotid artery shunt was not analyzed as a multivariate risk factor, then general anesthesia became a significant risk factor for perioperative cardiopulmonary complications (risk ratio 2.08; p = 0.04). CONCLUSIONS We conclude that cervical block anesthesia is safer and results in a more efficient use of hospital resources than general anesthesia in the treatment of patients undergoing carotid endarterectomy.
Clustered cortical organization and the enhanced probability of intra-areal functional integration

Similarly responsive neurons organize into submillimeter-sized clusters (domains) across many neocortical areas, notably in Areas V1 and V2 of primate visual cortex. While this clustered organization may arise from wiring minimization or from self-organizing development, it could potentially support important neural computation benefits. Here, we suggest that domain organization offers an efficient computational mechanism for intra-areal functional integration in certain cortical areas and hypothesize that domain proximity could support a higher-than-expected spatial correlation of their respective terminals yielding higher probabilities of integration of differing domain preferences. To investigate this hypothesis we devised a spatial model inspired by known parameters of V2 functional organization, where neighboring domains prefer either colored or oriented stimuli. Preference-selective joint probabilities were calculated for model terminal co-occurrence with configurations encompassing diverse domain proximity, shape, and projection. Compared to random distributions, paired neighboring domains (<=1200 µm apart) yielded significantly enhanced coincidence of terminals converging from each domain. Using this reference data, a second larger-scale model indicated that V2 domain organization may accommodate relatively complete sets of intra-areal color/orientation integrations. Together, these data indicate that domain organization could support significant and efficient intra-areal integration of different preferences and suggest further experiments investigating prevalence and mechanisms of domain-mediated intra-areal integration.
Novel agents and targets in managing patients with metastatic prostate cancer.

BACKGROUND Docetaxel has recently been found to improve survival in patients with metastatic androgen-independent prostate cancer (AIPC). Chemotherapy as a first-line option leaves room for improvement, while second-line options are multiple and somewhat controversial. METHODS Clinically relevant articles focusing on chemotherapy drugs for metastatic prostate cancer and their mechanism of action and efficacy were reviewed from January 2004 through April 2006. RESULTS Docetaxel is the standard of care for AIPC. However, for doublets with docetaxel or second-line chemotherapy, multiple studies have shown interesting and promising results with calcitriol, thalidomide, bevacizumab, satraplatin, vaccines, ixabepilone, and atrasentan. CONCLUSIONS Docetaxel should be considered for first-line treatment of metastatic AIPC. Due to its progression-free survival of only 6 months, more effective drugs and drug combinations need to be developed to treat patients with AIPC. Combination treatments with docetaxel and other new agents are promising, but adequately powered phase III trials need to be conducted with survival as the principal endpoint for these promising drug combinations.
Grain-Size Specific Characterisation and Resource Potentials of Municipal Solid Waste Incineration (MSWI) Bottom Ash: A German Case Study

Municipal solid waste incineration (MSWI) is a major element of modern waste management and produces annually around 5.7 million tonnes of bottom ash (BA) in Germany. In order to save natural resources and protect the environment, utilisable materials need to be recovered from BA. It was the aim of the present study to determine metal and mineral resource potentials of MSWI BA based on a characterisation study of raw and aged BA of the MSWI plant in Kassel (Germany). The BA investigated consisted of 82.2% mineral materials, 16.3% metals, and 1.5% unburnt organic matter. Overall, 12.1% and 3.6% of the MSWI BA were theoretically recoverable as native ferrous (Fe) and non-ferrous (NFe) metals, respectively. Assuming state-of-the-art recovery technology, 10.7% and 2.0% of the BA were actually extractable as Fe and NFe metals. The processed BA, as a mixture, did not comply with current German limit values for use as a construction material mainly due to excessive soluble salt contents. Coarser grain size fractions were less contaminated, resulting in a utilisable potential of less than 30% of the BA as a construction material. Hence, grain-size specific processing routes need to be developed for MSWI BA to fully exploit its mineral resource potential.
Influence of hydration status on thermoregulation and cycling hill climbing.

PURPOSE Although dehydration can impair endurance performance, a reduced body mass may benefit uphill cycling by increasing the power-to-mass ratio. This study examined the effects of a reduction in body mass attributable to unreplaced sweat losses on simulated cycling hill-climbing performance in the heat. METHODS Eight well-trained male cyclists (mean +/- SD: 28.4 +/- 5.7 yr; 71.0 +/- 5.9 kg; 176.7 +/- 4.7 cm; VO2peak: 66.2 +/- 5.8 mL x kg(-1) x min(-1)) completed a maximal graded cycling test on a stationary ergometer to determine maximal aerobic power (MAP). In a randomized crossover design, cyclists performed a 2-h ride at 53% MAP on a stationary ergometer, immediately followed by a cycling hill-climb time-to-exhaustion trial (88% MAP) on their own bicycle on an inclined treadmill (8%) at approximately 30 degrees C. During the 2-h ride, they consumed either 2.4 L of a 7% carbohydrate (CHO) drink (HIGH) or 0.4 L of water (LOW) with sport gels to match for CHO content. RESULTS After the 2-h ride and before the hill climb, drinking strategies influenced body mass (LOW -2.5 +/- 0.5% vs HIGH 0.3 +/- 0.4%; P < 0.001), HR (LOW 158 +/- 15 vs HIGH 146 +/- 15 bpm; P = 0.03), and rectal temperature (T(re): LOW 38.9 +/- 0.2 vs HIGH 38.3 +/- 0.2 degrees C; P = 0.001). Despite being approximately 1.9 kg lighter, time to exhaustion was significantly reduced by 28.6 +/- 13.8% in the LOW treatment (LOW 13.9 +/- 5.5 vs HIGH 19.5 +/- 6.0 min, P = 0.002), as was the power output for a fixed speed (LOW 308 +/- 28 vs HIGH 313 +/- 28 W, P = 0.003). At exhaustion, T(re) was higher in the LOW treatment (39.5 vs HIGH 39.1 degrees C; P < 0.001), yet peak HR, blood lactate, and glucose were similar. CONCLUSION Exercise-induced dehydration in a warm environment is detrimental to laboratory cycling hill-climbing performance despite reducing the power output required for a given speed.
Wound duration and healing rates: Cause or effect?

Multiple factors affect the likelihood of a wound healing. One of these factors, wound duration, is well known to be related to healing rates, with numerous publications showing that older wounds are less likely to heal. However, disentangling the effect of this factor on wound healing rates is complex. Is this simply an observation of the obvious; wounds of longer duration will by definition be harder to heal? Or does time represent an independent factor, implying that should treatments be given earlier in the disease process, better outcomes may result? This review summarizes the available evidence of the effects of wound duration on healing rates and examines potential biological aberrations identified in chronic wounds, which may be significant in making chronic wounds difficult to heal. Wounds of longer duration are associated with excessive inflammation, fibroblast senescence, and alterations in wound bed flora, which appears to have a temporal relationship. Early and aggressive treatment of ulcers that fail to respond to standard care may well aid in reducing the burden of wounds that become chronic.
Puttin' on the Ritz: Pre-Ipo Enlistment of Prestigious Affiliates as Deadline-Induced Remediation

We describe two theoretical explanations for the amount, pace, and costs of the prestige enhancement a firm engages in during the year before its initial public offering. The “snowball model” captures well-known processes whereby prestige-rich organizations accumulate even more prestige. The “dressing-up model” builds upon deadline-induced remediation, a phenomenon not previously studied in a macro-organizational context. In 242 software IPOs, the snowball model substantially explains final-year prestigious hiring. But there is also strong evidence of a tandem dressing-up process. As the final year counts down, prestige-poor firms aggressively hire prestigious executives and directors and pay higher prices to do so.
PROMETHEAN FIRE: REFLECTIONS ON THE ORIGIN OF MIND.

Written for a lay audience as well as the specialist, this book discusses Lumsden and Wilson's posited evolutionary process of gene-culture coevolution. This process "is a complicated, fascinating interaction in which culture is generated and shaped by biological imperatives while biological traits are simultaneously altered by genetic evolution in response to cultural innovation" (p. 19). The authors' main postulate is that "certain unique and remarkable properties of the human mind result in a tight linkage between genetic evolution and cultural history" (p. 20).