Search

The classifying spaces of handlebody groups form a modular operad. Algebras over the handlebody operad yield systems of representations of handlebody groups that are compatible with gluing. We prove that algebras over the modular operad of handlebodies with values in an arbitrary symmetric monoidal bicategory $\mathcal{M}$ (we introduce for these the name ansular functor) are equivalent to self-dual balanced braided algebras in $\mathcal{M}$. After specialization to a linear framework, this proves that consistent systems of handlebody group representations on finite-dimensional vector spaces are equivalent to ribbon Grothendieck-Verdier categories in the sense of Boyarchenko-Drinfeld. Additionally, it produces a concrete formula for the vector space assigned to an arbitrary handlebody in terms of a generalization of Lyubashenko's coend. Our main result can be used to obtain an ansular functor from vertex operator algebras subject to mild finiteness conditions. This includes examples of vertex operator algebras whose representation category has a non-exact monoidal product., 24 pages, 3 figures; v2: minor edits

Additional file 1.

These are notes from an informal mini-course on factorization homology, infinity-categories, and topological field theories. The target audience was imagined to be graduate students who are not homotopy theorists., Preprint of a book of the same title to be published 2021 by SpringerBriefs in Mathematical Physics, reproduced with permission of Springer International Publishing

Finding new hard and tough materials is a complicated process, described in this thesis. The steps taken in this work will be briey summarised in this chapter, after that the conclusions will be discussed and lastly the question why this work is important will be answered and some questions for further research will be posted. In the rst chapter, the question why hard and tough materials are needed and what the main factors in composing hard and tough materials are, were answered. Furthermore methods to calculate these properties from literature were introduced and compiled in an comprehensive overview. With this knowledge, the formulas were taken to the test in chapter two, where the hardness and fracture toughness of transition metal nitrides, carbides, borides and oxides with properties taken from literature were calculated, compared and the dierent methods were evaluated. While all formulas show good results for specic materials, the two (H v and K IC ) best suited for the application in ceramic-like materials were then applied in chapter 3, to calculate hardness and fracture toughness of 4.700 compounds available in the database "Materials Project". Some of the calculated values were compared with data used to evaluate the formulas, general trends were discussed. In chapter four ternary transition metal compounds were investigated, by applying a method, that uses data from the underlying binary compounds (which is readily available), to calculate the hardness of the ternary compound (solid solution strengthening). Finally one of the ternary compounds was synthesised using PVD, and the agreement of experimental to calculated hardness was shown. The question that needs to be answered next is, what can we learn from these ndings. Firstly some general remarks about the methods. As stated before, all formulas have their applications, where they provide excellent results. However for ceramic-like hard materials the formula proposed by Chen et al. and Niu et al. predict hardness and fracture toughness, respectively, with the highest accuracy. showed to be the most useful. Secondly knowledge about bond type can help provide more accurate predictions, by using the most suitable model, however in transition metal compounds this is a complicated undertaking. With these conclusions at hand, what are some questions that could not be answered in this work. The most important one is probably the characterisation of bond types. In this work only intrinsic properties of ideal crystals were discussed, however in reality crystal lattices have defects and extrinsic strengthening mechanisms like the Hell-Petch eect are applied, which are needed to be account for in order to improve the prediction accuracy for real materials.. On a nal note, the importance of high quality experimental data should be mentioned. For future works a database of experimental H and K IC values could make a dierence in the time needed to evaluate methods, but also the quality of the evaluation.

Outbreaks of forest pests increase with climate change, and thereby may affect microbial communities and ecosystem functioning. We investigated the structure of phyllosphere and soil microbial communities during defoliation by the nun moth (Lymantria monacha L.) (80% defoliation) and the pine tree lappet (Dendrolimus pini L.) (50% defoliation) in Scots pine forests (Pinus sylvestris L.) in Germany. Ribosomal RNA genes of fungi and bacteria were amplified by polymerase chain reaction (PCR), separated by denaturing gradient gel electrophoresis (DGGE), and subsequently sequenced for taxonomic assignments. Defoliation by both pests changed the structure of the dominant fungal (but not bacterial) taxa of the phyllosphere and the soil. The highly abundant ectomycorrhizal fungal taxon (Russula sp.) in soils declined, which may be attributed to insufficient carbohydrate supply by the host trees and increased root mortality. In contrast, potentially pathogenic fungal taxa in the phyllosphere increased during pest outbreaks. Our results suggest that defoliation of pines by insect pest, change the structure of fungal communities, and thereby indirectly may be contributing to aggravation of tree health.

Die selektive katalytische Reduktion (SCR) von Stickoxiden mit Ammoniak als Reduktionsmittel ist derzeit das vielversprechendste Verfahren, um zuk��nftige Emissionsanforderungen einhalten zu k��nnen. Aufgrund des Gef��hrdungspotenzials kann Ammoniak jedoch nicht direkt im Fahrzeug mitgef��hrt werden, sondern es wird eine Ammoniak-Vorl��ufersubstanz in Form einer Harnstoff-Wasser-L��sung (HWL) in das hei��e Abgas eingespritzt, die dann weiter zu Ammoniak reagiert. Diese Aufbereitung von Ammoniak vor dem Eintritt in den SCR-Katalysator ist ein wirkungsgradbestimmender Bestandteil in der gesamten SCR-Prozesskette. Gegenstand dieser Arbeit ist zum einen die Untersuchung und Beschreibung der Wechselwirkungen, wie sie zwischen den Tropfen des Reduktionsmittels und dem Abgas auftreten, und zum anderen Interaktionen zwischen Tropfen des Reduktionsmittels und hei��en Oberfl��chen, auf denen sie auftreffen. Zur Beschreibung der Tropfenbewegung wurde ein Modell erstellt, das entgegen einigen bisherigen Arbeiten den HWL-Tropfen nicht als massekonstant annimmt. In das vorliegende Modell wurde ein Verdunstungsmodell und ein reaktionskinetischer Ansatz f��r die Harnstoffzersetzung implementiert, sodass zu jedem Zeitpunkt die exakte Position im Str��mungsfeld, die Geschwindigkeit, die Masse, die Zusammensetzung und die Temperatur des Tropfens bestimmt werden kann. Diese Parameter sind f��r den nachfolgenden Reduktionsmittel/Wand-Kontakt von gro��er Bedeutung, und mit ihrer Hilfe konnte das Verhalten von HWL-Tropfen w��hrend des Wandkontaktes beschrieben werden. Im Besonderen wurde die Benetzung der Rohrwand mit HWL untersucht, da diese Wechselwirkung eine erfolgversprechende M��glichkeit einer effizienten Ammoniakaufbereitung vor dem Katalysator bietet. Zu diesem Zweck wurde unter anderem auch die Zusammensetzung des entstandenen Wandfilms bestimmt. In einer abschlie��end durchgef��hrten Potenzialanalyse wurde aus einer Vielzahl von Variationsparametern eine Variante ausgearbeitet, die zu einem maximalen Wandkontakt f��hrt und somit die Bedingungen f��r eine effektive Ammoniakaufbereitung aus dem Wandfilm heraus schafft., The selective catalytic reduction (SCR) of nitrogenous oxides is the most promising technique to meet prospective emission regulations. Due to its toxic potential the reducing agent ammonia cannot be stored in a car but it can be carried in form of a urea-water-solution which is injected into the hot exhaust gas and reacts to ammonia. This generation of ammonia before the catalytic converter is responsible for the efficiency of the complete SCR-process-chain. This thesis deals on one hand with the analysis and description of interactions between droplets of the urea-water-solution and the exhaust gas and on the other hand with interactions between droplets and hot surfaces in the moment of contact. For description of the droplets trajectories a numeric model was developed, which considers on the contrary to previous surveys the loss of the droplets mass due to evaporation of water and thermal decomposition of urea. The model for the droplets motion was extended by a evaporation model for binary fluids and on a kinetic ap-proach to describe the thermal decomposition. This model is able to determine the exact position of the flying droplet, the droplets velocity, the composition and its cur-rent temperature. These parameters are substantial for the next consideration of the interactions between droplets and hot surfaces. Especially the wall-wetting and the creation of a wall-film were investigated, because these effects offer opportunities to increase the ammonia generation before the catalytic converter. For this purpose a sample of liquid wall-film was taken and been analyzed to its composition. The final step was a potential analysis with the developed model to improve the ammonia generation by varying numerous measures. A set up could be stated to maximize the droplet-wall-contact which allows new strategies for the ammonia generation.

Carvedilol reduces disease progression in heart failure, but to our knowledge, its effects on hospitalizations and costs have not been evaluated.We examined the effects on hospitalization frequency and costs in the U.S. Carvedilol Heart Failure Trials Program. This program consisted of four concurrent, multicenter, double-blind, placebo-controlled studies involving 1,094 patients with New York Heart Association class II to IV heart failure, which treated patients with placebo or carvedilol for up to 15 months (median, 6.5 months).Detailed resource utilization data were collected for all hospitalizations occurring between randomization and the end of follow-up. In-patient care costs were estimated based on observed levels of resource use.Compared with placebo, carvedilol reduced the risk of hospitalization for any reason by 29% (p = 0.009), cardiovascular hospitalizations by 28% (p = 0.034) and heart failure hospitalizations by 38% (p = 0.041). Carvedilol also decreased the mean number of hospitalizations per patient (for cardiovascular reasons 30% [p = 0.02], for heart failure 53% [p = 0.03]). Among hospitalized patients, carvedilol reduced severity of illness during hospital admission, as reflected by shorter length of stay and less frequent use of intensive care. For heart failure hospital admissions, carvedilol decreased mean length of stay by 37% (p = 0.03) and mean number of intensive care unit/coronary care unit days by 83% (p = 0.001), with similar effects on cardiovascular admissions. As a result, estimated inpatient care costs with carvedilol were 57% lower for cardiovascular admissions (p = 0.016) and 81% lower for heart failure admissions (p = 0.022).Carvedilol added to angiotensin-converting enzyme inhibition reduces hospitalization risk as well as severity of illness and resource utilization during admission in patients with chronic heart failure.

The success of beta-blocking agents in clinical trials of heart failure (HF) has led to a widespread call for their increased use, which assumes these agents will perform as well in the usual care setting. Given the traditional contraindication of the use of beta-blocking agents in HF, and their perception as difficult to use in HF, observing how they perform in the usual care setting could be critical in accelerating their widespread application. Carvedilol is the only beta-blocking agent currently approved in the United States for use in HF.The Coreg (brand of carvedilol; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) Heart Failure Registry (COHERE) is intended to collect data on outcomes and other clinical variables in a typical HF population and to observe experience with carvedilol in the hands of community practitioners. COHERE does not include any specific patient selection or exclusion criteria. The decision to use carvedilol is entirely at the discretion of the participant physician, based on evidence of HF as judged by assessments the practitioner usually uses. All patients will be followed for 1 year, with information on outcomes and other clinical variables collected and analyzed at baseline, the end of titration, and at 6 and 12 months after reaching the maximum tolerated dose. About 600 participant physicians selected to be as representative as possible of the community practice setting will enroll approximately 6,000 patients.COHERE will be the first and largest prospective observational experience with a new treatment, ie, carvedilol, in patients with HF managed in the usual care setting and should provide valuable information about this new treatment in this environment compared with the more rigid clinical trials setting.

Carvedilol is a nonselective beta-receptor antagonist with vasodilating properties primarily due to selective alpha-1 antagonism. This 4-treatment, 5-period, double-blind, crossover study evaluated the efficacy and safety of 3 doses of carvedilol (12.5, 25, and 50 mg given twice daily) versus placebo in 122 patients with chronic stable angina. Carvedilol in doses of 25 mg twice daily and 50 mg twice daily was statistically superior to placebo with respect to time to angina (placebo: 316 seconds; 25 mg carvedilol: 337 seconds, p = 0.0039; 50 mg: 345 seconds, p0.0001) and time to 1-mm ST-segment depression (placebo: 301 seconds; 25 mg: 313 seconds; 50 mg: 323 seconds; p0.0001). The percentage of patients reporting any adverse experience was slightly less in those receiving placebo (placebo: 28.4%; 12.5 mg: 33.1%; 25 mg: 34.5%; 50 mg: 31.9%). Carvedilol is effective and safe in treating patients with chronic stable angina.

Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function.One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P.05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004).The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

We tested the hypothesis that carvedilol inhibits clinical progression in patients with mildly symptomatic heart failure due to left ventricular (LV) systolic dysfunction.Patients (n = 366) who had mildly symptomatic heart failure with an LV ejection fraction (LVEF)or = 0.35, had minimal functional impairment (defined as the ability to walk 450 to 550 m on a 6-minute walk test), and were receiving optimal standard therapy, including ACE inhibitors, were randomized double-blind to carvedilol (n = 232) or placebo (n = 134) and followed up for 12 months. The primary end point was clinical progression, defined as death due to heart failure, hospitalization for heart failure, or a sustained increase in heart failure medications. Clinical progression of heart failure occurred in 21% of placebo patients and 11% of carvedilol patients, reflecting a 48% (P = .008) reduction in the primary end point of heart failure progression (relative risk, 0.52; CI, 0.32 to 0.85). This effect of carvedilol was not influenced by sex, age, race, cause of heart failure, or baseline LVEF. Carvedilol also significantly improved several secondary end points, including LVEF, heart failure score, NYHA functional class, and the physician and patient global assessments. Carvedilol reduced all-cause mortality but had no effects on the Minnesota Living With Heart Failure scale, the distance walked in 9 minutes on a self-powered treadmill, or cardiothoracic index. The drug was well tolerated.Carvedilol, when added to standard therapy, including an ACE inhibitor, reduces clinical progression in patients who are only mildly symptomatic with well-compensated heart failure.

Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials.We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fractionor = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P.001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P.001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure.These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.

Go(a) (D(Cor)) is a low-frequency antigen in the Rh system found on red cells lacking part of the D mosaic (category IVa). Anti-Go(a) has not been previously reported to cause hemolytic transfusion reactions. A 27-year-old African American male with sickle-cell disease, maintained on chronic transfusion, was noted to have dark plasma during an erythrocytapheresis, procedure, and the pretransfusion hemoglobin was noted to be 1 g/dl lower than 4 weeks before (with hyperbilirubinemia and a significantly increased LDH). Polyspecific direct antiglobulin test (DAT) was weakly positive (C3-weak, IgG-weak), and indirect antiglobulin tests (IATs) performed on the serum (pre- and posttransfusion reaction) and a red blood cell (RBC) eluate from the postreaction sample were negative. A segment from one of the four implicated units from the prior month's transfusion was strongly reactive at 37 degrees C and using anti-human globulin (AHG) when crossmatched with the postreaction serum and the eluate. The postreaction serum, screened with a panel of red cells positive for low-prevalence antigens, reacted with three Go(a+) cells. The implicated unit was reactive with a previously identified anti-Go(a) serum.

Bone marrow transplantation (BMT) is now an option for some patients with sickle cell disease (SCD). Many SCD patients are multiply transfused with red blood cells (RBCs), and may be immunized to alloantigens other than erythrocyte antigens. Because platelet refractoriness is a significant complication during BMT, we wished to determine the prevalence of alloimmunization to platelets in transfused SCD patients. Sera collected from 47 transfused and 14 untransfused SCD patients were screened for HLA and platelet-specific antibodies. Transfusion and RBC antibody histories were reviewed. A subset of the patients were rescreened 1 year later. Eighty-five percent of patients with at least 50 RBC transfusions (22 of 26), 48% of patients with less than 50 transfusions (10 of 21), and none of 14 untransfused patients demonstrated platelet alloimmunization (P.05). Platelet alloimmunization was more prevalent than RBC alloimmunization (20% to 30%). Half of the platelet reactivity was chloroquine-elutable. Eighteen of 22 patients (82%) on chronic RBC transfusion remained platelet-alloimmunized 11 to 22 months after initial testing. In summary, 85% of heavily transfused SCD patients are alloimmunized to HLA and/or platelet-specific antigens. These patients may be refractory to platelet transfusion, a condition that would increase their risk during BMT. Leukodepletion in the transfusion support of SCD patients should be considered to prevent platelet alloimmunization.

Carvedilol is a novel multiple-action cardiovascular drug that has recently been introduced to the market for the treatment of mild to moderate hypertension. Clinical studies have demonstrated that once daily therapy with carvedilol is efficacious and has a favourable side-effect profile. Clinical studies are in progress to establish the utility of carvedilol in angina and congestive heart failure. Carvedilol is a beta-adrenoceptor antagonist and a vasodilator, with the vasodilating activity resulting primarily from alpha 1-adrenoceptor blockade and possibly also from calcium channel blockade. The reduction in BP produced by carvedilol results from the vasodilating activity of the drug because peripheral vascular resistance is significantly reduced. The reduction in BP produced by carvedilol is not associated with reflex tachycardia owing to the beta-adrenoceptor blocking activity of the compound. Throughout its antihypertensive dose range, carvedilol has been a renal-sparing antihypertensive agent in animals and also in humans, inasmuch as renal blood flow, glomerular filtration rate and sodium excretion are all maintained. In preclinical experimental models of acute myocardial infarction, carvedilol has produced marked reductions in infarct size in the pig, rat and dog. The cardioprotection observed with carvedilol is greater than that provided by beta-adrenoceptor antagonists alone, suggesting that the additional activities of carvedilol may provide benefit in the setting of myocardial ischaemia.

The search for the ideal antihypertensive drug is ongoing. Since hypertension initially is a relatively symptom-free disease, it is important that any agent developed be not only efficacious but also safe, with minimal side effects. Additionally such a drug should ideally possess both primary and secondary cardiovascular preventive properties. This review discusses the most commonly used antihypertensive drugs in the light of these goals, and highlights the development of multiaction drugs. Carvedilol, which is a nonselective beta-blocking and alpha 1-blocking drug, with additional Ca(2+)-antagonistic properties, is being developed as an antihypertensive, antianginal drug and as an adjunct therapy in congestive heart failure. The development challenges for this single-entity drug are discussed and evidence for its antihypertensive efficacy, as well as its antianginal efficacy, is presented. The cardioprotective potential of carvedilol based on preclinical experiments is addressed. Finally, the regulatory questions regarding the development of a multiaction drug are highlighted.

Consider the prototype ill-posed problem of a first kind integral equation ℛ with discrete noisy data di, = f(xi) + εi, i = 1, …, n. Let u0 be the true solution and unα a regularised solution with regularisation parameter α. Under certain assumptions, it is known that if α → 0 but not too quickly as n → ∞, then unα converges to u0. We examine the dependence of the optimal sequence of α and resulting optimal convergence rate on the smoothness of f or u0, the kernel K, the order of regularisation m and the error norm used. Some important implications are made, including the fact that m must be sufficiently high relative to the smoothness of u0 in order to ensure optimal convergence. An optimal filtering criterion is used to determine the order where is the maximum smoothness of u0. Two practical methods for estimating the optimal α, the unbiased risk estimate and generalised cross validation, are also discussed.