Efficient all-electron hybrid density functionals for atomistic simulations beyond 10 000 atoms.

Hybrid density functional approximations (DFAs) offer compelling accuracy for ab initio electronic-structure simulations of molecules, nanosystems, and bulk materials, addressing some deficiencies of computationally cheaper, frequently used semilocal DFAs. However, the computational bottleneck of hybrid DFAs is the evaluation of the non-local exact exchange contribution, which is the limiting factor for the application of the method for large-scale simulations. In this work, we present a drastically optimized resolution-of-identity-based real-space implementation of the exact exchange evaluation for both non-periodic and periodic boundary conditions in the all-electron code FHI-aims, targeting high-performance central processing unit (CPU) compute clusters.

[Outcome of selective mating in the Entlebucher Mountain Dog for reduction of ureteral ectopia].

The Entlebucher Mountain Dog is predisposed to ureteral ectopia and associated diseases of the urinary tract as well as the kidneys, which can have severe to lethal consequences. Due to the clustered occurrence of clinical signs in 11 % of Entlebucher Mountain dogs in the absence of a genetic test for ureteral ectopia, screening was introduced in 2008 to allow phenotype-based breeding selection. The ureteral orifices of the dogs are visualized by ultrasound and existing urinary retention or urinary incontinence is documented.

NECI: N-Electron Configuration Interaction with an emphasis on state-of-the-art stochastic methods.

We present NECI, a state-of-the-art implementation of the Full Configuration Interaction Quantum Monte Carlo (FCIQMC) algorithm, a method based on a stochastic application of the Hamiltonian matrix on a sparse sampling of the wave function. The program utilizes a very powerful parallelization and scales efficiently to more than 24 000 central processing unit cores. In this paper, we describe the core functionalities of NECI and its recent developments.

Acute Stress-Induced Coagulation Activation in Patients With Remitted Major Depression Versus Healthy Controls and the Role of Stress-Specific Coping.

Background: Depressed patients have an increased risk of myocardial infarction, for which acute stress is a frequent trigger. Prothrombotic changes could be one involved mechanism that can be modulated by psychological coping.

Purpose: We examined the effects of remitted major depression and situation-specific coping strategies on stress-induced coagulation activation.

Evidence for an enhanced procoagulant state in remitted major depression.

Objectives: Hypercoagulability is one mechanism to explain the increased risk of incident atherothrombotic disease in patients with major depressive disorder (MDD). We examined whether patients with remitted MDD show an enhanced procoagulant state.

Methods: 63 individuals (median age 35 years, 59% women), 40 with a DSM-IV diagnosis of remitted MDD, made by a clinical interview, and 23 healthy controls provided blood samples for the measurement of fibrinogen, D-dimer, von Willebrand factor, and plasminogen activator inhibitor-1.

Half-life extension using serum albumin-binding DARPin® domains.

A long systemic half-life is key for therapeutic proteins. To that end we have generated serum albumin-binding designed ankyrin repeat domains. These domains bind serum albumin of different species with nanomolar affinities, and have significantly improved pharmacokinetic properties both in mouse and cynomolgus monkey compared to non-serum albumin-binding DARPin® domains.

Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases.

For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the hand/foot with fibrotic nodules and fascial cords, which determine debilitating contractures and deformities of fingers/toes, while keloids are exuberant scar formations following burn damage, surgery, and trauma. Although RT has become an established and effective option in the management of these diseases, experimental studies to illustrate cellular composites and factors involved remain to be elucidated.

Long-Term Tissue Culture of Adult Brain and Spleen Slices on Nanostructured Scaffolds.

Long-term tissue culture of adult mammalian organs is a highly promising approach to bridge the gap between single cell cultures and animal experiments, and bears the potential to reduce in vivo studies. Novel biomimetic materials open up new possibilities to maintain the complex tissue structure in vitro; however, survival times of adult tissues ex vivo are still limited to a few days with established state-of-the-art techniques. Here, it is demonstrated that TiO nanotube scaffolds with specific tissue-tailored characteristics can serve as superior substrates for long-term adult brain and spleen tissue culture.

Tumor tissue slice cultures as a platform for analyzing tissue-penetration and biological activities of nanoparticles.

The success of therapeutic nanoparticles depends, among others, on their ability to penetrate a tissue for actually reaching the target cells, and their efficient cellular uptake in the context of intact tissue and stroma. Various nanoparticle modifications have been implemented for altering physicochemical and biological properties. Their analysis, however, so far mainly relies on cell culture experiments which only poorly reflect the in vivo situation, or is based on in vivo experiments that are often complicated by whole-body pharmacokinetics and are rather tedious especially when analyzing larger nanoparticle sets.

Dose-dependent short- and long-term effects of ionizing irradiation on neural stem cells in murine hippocampal tissue cultures: neuroprotective potential of resveratrol.

Introduction: Radiation therapy plays an essential role in the treatment of brain tumors, but neurocognitive deficits remain a significant risk, especially in pediatric patients. In recent trials, hippocampal sparing techniques are applied to reduce these adverse effects. Here, we investigate dose-dependent effects of ionizing radiation (IR) on juvenile hippocampal neurogenesis.

Optimized polyethylenimine (PEI)-based nanoparticles for siRNA delivery, analyzed in vitro and in an ex vivo tumor tissue slice culture model.

The non-viral delivery of small RNA molecules like siRNAs still poses a major bottleneck for their successful application in vivo. This is particularly true with regard to crossing physiological barriers upon systemic administration. We have previously established polyethylenimine (PEI)-based complexes for therapeutic RNA formulation.

Organotypic slice cultures of human gastric and esophagogastric junction cancer.

Gastric and esophagogastric junction cancers are heterogeneous and aggressive tumors with an unpredictable response to cytotoxic treatment. New methods allowing for the analysis of drug resistance are needed. Here, we describe a novel technique by which human tumor specimens can be cultured ex vivo, preserving parts of the natural cancer microenvironment.

FKBP5 genotype-dependent DNA methylation and mRNA regulation after psychosocial stress in remitted depression and healthy controls.

Background: Polymorphisms in the FK506 binding protein 5 (FKBP5) gene have been shown to influence glucocorticoid receptor sensitivity, stress response regulation, and depression risk in traumatized subjects, with most consistent findings reported for the functional variant rs1360780. In the present study, we investigated whether the FKBP5 polymorphism rs1360780 and lifetime history of major depression are associated with DNA methylation and FKBP5 gene expression after psychosocial stress.

Methods: A total of 116 individuals with a positive (n = 61) and negative (n = 55) lifetime history of major depression participated in the Trier Social Stress Test.

Increased HPA axis response to psychosocial stress in remitted depression: the influence of coping style.

The aim of the study was to examine the modulating effects of coping style on the response to psychosocial stress in remitted major depression (MD) and healthy controls. Thirty-three participants with a lifetime history of MD, who were in remission, and 32 age- and gender-matched healthy controls were recruited from a longitudinal-epidemiological study, in which the presence or absence of mental disorders was prospectively ascertained. Participants (aged 30-41 years) underwent two consecutive Trier Social Stress Tests (TSSTs).

Hypofractionated stereotactic radiotherapy of acoustic neuroma: volume changes and hearing results after 89-month median follow-up.

Purpose: The goal of this work was to evaluate toxicity and local control following hypofractionated stereotactic radiation treatment with special focus on changes in tumor volume and hearing capacity.

Patients And Methods: In all, 29 patients with unilateral acoustic neuroma were treated between 2001 and 2007 within a prospective radiation protocol (7 × 4 Gy ICRU dose). Median tumor volume was 0.

Slice cultures from head and neck squamous cell carcinoma: a novel test system for drug susceptibility and mechanisms of resistance.

Background: Human head and neck squamous cell carcinoma (HNSCC) fundamentally vary in their susceptibility to different cytotoxic drugs and treatment modalities. There is at present no clinically accepted test system to predict the most effective therapy for an individual patient.

Methods: Therefore, we established tumour-derived slice cultures which can be kept in vitro for at least 6 days.

IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: long term results of an ISIORT pooled analysis.

Purpose: Linac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy.

Material And Methods: Until 10/2005, 1109 unselected patients of any risk group have been identified among seven centers using identical methods, sequencing and dosage for intra- and postoperative radiotherapy.

Organotypic slice cultures of human glioblastoma reveal different susceptibilities to treatments.

Background: Glioblastoma multiforme is the most common lethal brain tumor in human adults, with no major therapeutic breakthroughs in recent decades. Research is based mostly on human tumor cell lines deprived of their organotypic environment or inserted into immune-deficient animals required for graft survival. Here, we describe how glioblastoma specimens obtained from surgical biopsy material can be sectioned and transferred into cultures within minutes.

Saturation of gyrokinetic turbulence through damped eigenmodes.

In the context of toroidal gyrokinetic simulations, it is shown that a hierarchy of damped modes is excited in the nonlinear turbulent state. These modes exist at the same spatial scales as the unstable eigenmodes that drive the turbulence. The larger amplitude subdominant modes are weakly damped and exhibit smooth, large-scale structure in velocity space and in the direction parallel to the magnetic field.

Free energy cascade in gyrokinetic turbulence.

In gyrokinetic theory, the quadratic nonlinearity is known to play an important role in the dynamics by redistributing (in a conservative fashion) the free energy between the various active scales. In the present study, the free energy transfer is analyzed for the case of ion temperature gradient driven turbulence. It is shown that it shares many properties with the energy transfer in fluid turbulence.

SecA interacts with ribosomes in order to facilitate posttranslational translocation in bacteria.

In Escherichia coli, translocation of exported proteins across the cytoplasmic membrane is dependent on the motor protein SecA and typically begins only after synthesis of the substrate has already been completed (i.e., posttranslationally).