Oogenesis and spermatogenesis [animals Kunz, W. (Duesseldorf Univ. (Germany, F.R.). Inst. fuer Allgemeine Biologie); Schaefer, U
Bausteine der modernen Physiologie (Germany, F.R.),
1978
4
Book
This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available ...evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti‐inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long‐term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long‐term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti‐inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.
Exploiting parallelism to accelerate a computation typically involves dividing it into many small tasks that can be assigned to different processing elements. An efficient execution schedule for ...these tasks can be difficult or impossible to determine in advance, however, if there is uncertainty as to when each task's input data will be available. Ideally, each task would run in direct response to the arrival of its input data, thus allowing the computation to proceed in a fine-grained event-driven manner. Realizing this ideal is difficult in practice, and typically requires sacrificing flexibility for performance.
In Anton 2, a massively parallel special-purpose supercomputer for molecular dynamics simulations, we addressed this challenge by including a hardware block, called the dispatch unit, that provides flexible and efficient support for fine-grained event-driven computation. Its novel features include a many-to-many mapping from input data to a set of synchronization counters, and the ability to prioritize tasks based on their type. To solve the additional problem of using a fixed set of synchronization counters to track input data for a potentially large number of tasks, we created a software library that allows programmers to treat Anton 2 as an idealized machine with infinitely many synchronization counters. The dispatch unit, together with this library, made it possible to simplify our molecular dynamics software by expressing it as a collection of independent tasks, and the resulting fine-grained execution schedule improved overall performance by up to 16% relative to a coarse-grained schedule for precisely the same computation.
The regulation of physiological gut functions such as peristalsis or secretion of digestive enzymes by the central nervous system via the Nervus vagus is well known. Recent investigations highlight ...that pathological conditions of neurological or psychiatric disorders might directly interfere with the autonomous neuronal network of the gut - the enteric nervous system, or even derive from there. By using a murine Alzheimer's disease model, we investigated a potential influence of disease-associated changes on gastrointestinal properties. 5xFAD mice at three different ages were compared to wild type littermates in regard to metabolic parameters and enzymes of the gut by fluorimetric enzyme assay and western blotting. Overexpression of human amyloid-β protein precursor (AβPP) within the gut was assessed by qPCR and IHC; fecal microbiome analysis was conducted by 16SrRNA quantitation of selected phyla and species. While general composition of fecal samples, locomotion, and food consumption of male 5xFAD animals were not changed, we observed a reduced body weight occurring at early pathological stages. Human AβPP was not only expressed within the brain of these mice but also in gut tissue. Analysis of fecal proteins revealed a reduced trypsin amount in the 5xFAD model mice as compared to the wild type. In addition, we observed changes in fecal microbiota composition along with age. We therefore suggest that the presence of the mutated transgenes (AβPP and PS1), which are per se the basis for the genetic form of Alzheimer's disease in humans, directly interferes with gut function as shown here for the disease model mice.
This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available ...evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease‐modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen‐specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress‐induced exacerbations. Therapeutic patient education (‘Eczema school’) is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.
This review highlights the role of three key immune pathways in the pathophysiology of major retinal degenerative diseases including diabetic retinopathy, age‐related macular degeneration, and rare ...retinal dystrophies. We first discuss the mechanisms how loss of retinal homeostasis evokes an unbalanced retinal immune reaction involving responses of local microglia and recruited macrophages, activity of the alternative complement system, and inflammasome assembly in the retinal pigment epithelium. Presenting these key mechanisms as complementary targets, we specifically emphasize the concept of immunomodulation as potential treatment strategy to prevent or delay vision loss. Promising molecules are ligands for phagocyte receptors, specific inhibitors of complement activation products, and inflammasome inhibitors. We comprehensively summarize the scientific evidence for this strategy from preclinical animal models, human ocular tissue analyses, and clinical trials evolving in the last few years.
Akhtar‐Schäfer, Langmann and colleagues present here a comprehensive review of a range of mechanisms involved in common retinal degenerative disorders, providing hints into therapeutic approaches through targeting the immune system.
The number of rRNA cistrons is measured by filter saturation hybridization in different stocks of D. hydei, where the wild-type X chromosome has one nucleolus organizer (NO) and wild-type Y has two ...separated NO's. XX/Y females having no X chromosomal NO show an rDNA content exceeding that of a Y chromosome. An even greater increase in the rRNA cistron number is measured in two translocation stocks where the XX is combined with one half of a Y and, therefore, each stock contains only one of the two Y chromosomal NO's. But when the same Y fragments are brought together with a wild-type X chromosome they lose about one-half of their rRNA cistrons within one generation. Males with two complementary Y fragments but having no X chromosomal NO show a considerably higher rDNA content than the XX/Y females, although both are equal in respect of their NO number. Consideration is given to related phenomena in Drosophila melanogaster.
The ATLAS experiment is located at the European Center for Nuclear Research (CERN) in Switzerland. It is designed to observe collisions at the Large Hadron Collider (LHC): the world's largest and ...highest-energy particle accelerator. Event triggering and Data Acquisition is one of the extraordinary challenges faced by the detectors at the high luminosity LHC collider upgrade. During 2011, the LHC reached instantaneous luminosities of 4 × 10 33 cm -1 s -1 and produced events with up to 24 interactions per colliding proton bunch. This places stringent operational and physical requirements on the ATLAS Trigger in order to reduce the nominal 40MHz collision rate to a manageable event storage rate up to 400Hz and, at the same time, select those events considered interesting. The Level-1 Trigger is the first rate-reducing step in the ATLAS Trigger, with an output rate of 75kHz and decision latency of less than 2.5μs. It is primarily composed of the Calorimeter Trigger, Muon Trigger, the Central Trigger Processor (CTP) and by 2014 a complete new electronics module: the Topological Processor (TP). The TP will make it possible, for the first time, to concentrate detailed information from sub-detectors in a single Level-1 module. This allows the determination of angles between jets and/or leptons, or even more complex observables such as muon isolation or invariant mass. This requires to receive on a single module a total bandwidth of about 1Tb/s and process the data within less than 100 ns. In order to accept this new information from the TP, the CTP will be upgraded to process double the number of trigger inputs and logical combinations of these trigger inputs. These upgrades also address the growing needs of the complete Level-1 trigger system as LHC luminosity increases. During the LHC shutdown in 2013, the TP and the upgraded CTP will be installed. We present the justification for such an upgrade, the proposed upgrade to the CTP, and tests on the TP demonstrator and prototype, emphasizing the characterization of the high speed links and tests of the topological algorithm's latency and logic utilization.
The existing evidence for treatment of atopic eczema (atopic dermatitis, AE) is evaluated using the national standard Appraisal of Guidelines Research and Evaluation. The consensus process consisted ...of a nominal group process and a DELPHI procedure. Management of AE must consider the individual symptomatic variability of the disease. Basic therapy is focused on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti‐inflammatory treatment based on topical glucocorticosteroids and topical calcineurin inhibitors (TCI) is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the TCI tacrolimus and pimecrolimus are preferred in certain locations. Systemic immune‐suppressive treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial treatment. Adjuvant therapy includes UV irradiation preferably with UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen‐specific immunotherapy to aeroallergens may be useful in selected cases. Stress‐induced exacerbations may make psychosomatic counselling recommendable. ‘Eczema school’ educational programs have been proven to be helpful. Pruritus is targeted with the majority of the recommended therapies, but some patients need additional antipruritic therapies.
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