Temporal dissipative solitons in the Morris-Lecar model with time-delayed feedback.

We study the dynamics and bifurcations of temporal dissipative solitons in an excitable system under time-delayed feedback. As a prototypical model displaying different types of excitability, we use the Morris-Lecar model. In the limit of large delay, soliton like solutions of delay-differential equations can be treated as homoclinic solutions of an equation with an advanced argument. Based on this, we use concepts of classical homoclinic bifurcation theory to study different types of pulse solutions and to explain their dependence on the system parameters. In particular, we show how a homoclinic orbit flip of a single-pulse soliton leads to the destabilization of equidistant multi-pulse solutions and to the emergence of stable pulse packages. It turns out that this transition is induced by a heteroclinic orbit flip in the system without feedback, which is related to the excitability properties of the Morris-Lecar model.

DFTB+, a software package for efficient approximate density functional theory based atomistic simulations.

DFTB+ is a versatile community developed open source software package offering fast and efficient methods for carrying out atomistic quantum mechanical simulations. By implementing various methods approximating density functional theory (DFT), such as the density functional based tight binding (DFTB) and the extended tight binding method, it enables simulations of large systems and long timescales with reasonable accuracy while being considerably faster for typical simulations than the respective ab initio methods. Based on the DFTB framework, it additionally offers approximated versions of various DFT extensions including hybrid functionals, time dependent formalism for treating excited systems, electron transport using non-equilibrium Green's functions, and many more. DFTB+ can be used as a user-friendly standalone application in addition to being embedded into other software packages as a library or acting as a calculation-server accessed by socket communication. We give an overview of the recently developed capabilities of the DFTB+ code, demonstrating with a few use case examples, discuss the strengths and weaknesses of the various features, and also discuss on-going developments and possible future perspectives.

Bias-induced conformational switching of supramolecular networks of trimesic acid at the solid-liquid interface.

Using the tip of a scanning tunneling microscope, an electric field-induced reversible phase transition between two planar porous structures ("chickenwire" and "flower") of trimesic acid was accomplished at the nonanoic acid/highly oriented pyrolytic graphite interface. The chickenwire structure was exclusively observed for negative sample bias, while for positive sample bias only the more densely packed flower structure was found. We suggest that the slightly negatively charged carboxyl groups of the trimesic acid molecule are the determining factor for this observation: their adsorption behavior varies with the sample bias and is thus responsible for the switching behavior.

From hydrogen bonding to metal coordination and back: Porphyrin-based networks on Ag(111).

The self-assembly of a metal-free porphyrin bearing two pyridyl coordinating sites and two pentyl chains at trans meso positions was investigated under ultrahigh vacuum on a Ag(111) surface by scanning tunneling microscopy (STM). The STM measurements revealed a well-ordered close-packed structure with a rhombic unit cell for coverages ≤1 monolayer with their molecular plane parallel to the surface. The growth direction of the molecular islands is aligned along the step edges, which are restructured due to molecule-substrate interactions. The shorter unit cell vector of the molecular superstructure follows the〈1-10〉direction of the Ag(111) substrate. Hydrogen bonds between pyridyl and pyrrole groups of neighboring molecules as well as weak van der Waals forces between the pentyl chains stabilize the superstructure. Deposition of cobalt atoms onto the close-packed structure at room temperature leads to the formation of a hexagonal porous network stabilized by metal-ligand bonding between the pyridyl ligands and the cobalt atoms. Thermal annealing of the Co-coordination network at temperatures >450 K results in the transformation of the hexagonal network into a second close-packed structure. Changes in the molecule-substrate interactions due to metalation of the porphyrin core with Co as well as intermolecular interactions can explain the observed structural transformations.

LOINC in prehospital emergency medicine in Germany - experience of the `DIRK´-project.

BACKGROUND: Treatment of patients picked up by emergency services can be improved by data transfer ahead of arrival. Care given to emergency patients can be assessed and improved through data analysis. Both goals require electronic data transfer from the emergency medical services (EMS) to the hospital information system. Therefore a generic semantic standard is needed. OBJECTIVES: Objective of this paper is to test the suitability of the international nomenclature Logical Observation Identifiers Names and Codes (LOINC) to encode the core data-sets for rescue service protocols (MIND 2 and MIND 3). Encoding diagnosis and medication categories using ICD-10 and ATC were also assessed. METHODS: Protocols were broken down into concepts, assigned to categories, translated and manually mapped to LOINC codes. Each protocol was independently encoded by two healthcare professionals and in case of discrepancies a third expert was consulted to reach a consensus. RESULTS: Currently 39% of parameters could be mapped to LOINC. Additional use of other coding systems such as International Statistical Classification of Diseases and Related Health Problems (ICD-10) for diagnoses and Anatomical Therapeutic Chemical Classification System (ATC) for medications increases the rate of 'mappable' parameters to 56%. CONCLUSIONS: Although the coverage is low, mapping has shown that LOINC is suitable to encode concepts of the rescue services. In order to create a generic semantic model to be applied in the field our next step is to request new LOINC codes for the missing concepts.

[Duodenal diverticulum--a therapeutic challenge]. / Blutendes Duodenaldivertikel - eine therapeutische Herausforderung.

We report the case of an 81-year-old women with a duodenal diverticular bleeding in the second portion of the duodenum. Various therapies are used to halt haemorrhaging in this tissue, including surgical or endoscopic intervention and transarterial embolisation. The lesion was identified and treated endoscopically with hypertonic saline solution and epinephrine. Because of a fistula and a continual bleeding we use a hemoclip two days later. The bleeding was completely controlled. However, a small mucosal defect was noted at the site where the hemoclip was applied, and an operation was necessary. Finally we discuss the therapy optoins based on a review of the literature.

[Does the algetic supinator syndrome exist?]. / Gibt es ein algetisches Supinatorsyndrom?

The supinator (tunnel) syndrome is a rare chronic compression syndrome of the posterior interosseous nerve. The tennis elbow or the lateral epicondylitis and the algetic supinator syndrome represent painful entities of the lateral epicondyle and inserting tendons which do not have anything to do with a compression syndrome of the radial nerve. Decompression of the interosseous posterior nerve therefore has to be abandoned in the therapy for lateral elbow pain.

Ab initio phase diagram of oxygen adsorption on W(110).

The phase diagram of oxygen adsorption on the W(110) surface is derived without any empirical parameters by a combination of density functional theory (DFT) calculations, the cluster expansion (CE) technique and Monte Carlo (MC) applications. Coverages up to 1 monolayer are considered corresponding to the range of oxygen concentrations, 0≤x(O)≤1. DFT results for single-site adsorption and in particular for full coverage reveal that adsorption at threefold hollow (H3) sites is by far the most stable one. Therefore, the CE is done for an atomic layer with the two H3 sublattices of the W(110) surface. Based on 60 DFT calculations with fully relaxed atomic geometries of lateral unit cells containing 12 atoms, and a ground state search for 80 394 structures, four ground state structures are found with the lateral unit cells (2 × 5) for x(O) = 0.20, (2 × 2) (a) for x(O) = 0.25, (2 × 1) for x(O) = 0.50 and (2 × 2) (b) for x(O) = 0.75. In agreement with experiments the most stable structures are (2 × 1) and (2 × 2) (b), which correspond to higher coverages. The thermodynamical stability of the two ground states at lower coverages is very weak. Detailed analysis of the relaxation of the (2 × 1) structure reveals sizeable lateral stresses acting on the surface tungsten atoms. On the basis of the effective cluster interactions MC simulations are performed in order to derive the critical temperatures by which the phase diagram is finally constructed.

Effect of reduced levels of the LDL receptor of Ehrlich ascites tumor cells on cholesterol uptake and cell proliferation: a coculture study with baby hamster kidney cells.

We have introduced a heterologous coculture model between Ehrlich ascites tumor (EAT) and baby hamster kidney cells (PtK2), and we have studied the influence of PtK2 cells and their newly synthesized cholesterol on uptake and tumor cell proliferation. PtK2 cells produce about five times more cholesterol as compared to EAT cells, and they support tumor cell growth in coculture experiments. This growth stimulation is reduced by 80% when EAT cells are cultured in PtK2 cell-derived medium in the presence of a monoclonal anti-low-density lipoprotein receptor (anti-LDL(r)) antibody. Freshly synthesized cholesterol by PtK2 cells is taken up by EAT cells in a time-dependent manner amounting to a threefold increase after 24 h. Alternatively, cholesterol transfer to EAT cells is decreased between 28% and 35%, when PtK2 cell cholesterol synthesis is inhibited in the presence of mevinolin, the specific inhibitor of the hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Furthermore, lower levels of EAT cell LDL receptor induced by antisense technology reduces cholesterol uptake and cell proliferation. These data demonstrate a metabolic interaction between normal and tumor cells mediated via the exchange of cholesterol, an important membrane constituent.

Dynamic regimes of buoyancy-affected two-phase flow in unconsolidated porous media.

The invasion and subsequent flow of a nonwetting fluid (NWF) in a three-dimensional, unconsolidated porous medium saturated with a wetting fluid of higher density and viscosity have been studied experimentally using a light-transmission technique. Distinct dynamic regimes have been found for different relative magnitudes of viscous, capillary, and gravity forces. It is shown that the ratio of viscous and hydrostatic pressure gradients can be used as a relevant dimensionless number K for the characterization of the different flow regimes. For low values of K, the invasion is characterized by the migration and fragmentation of isolated clusters of the NWF resulting from the prevalence of gravity and capillary forces. At high values of K, the dominance of viscous and gravity forces leads to an anisotropic fingerlike invasion. When the invasion stops after the breakthrough of the NWF at the open upper boundary, the invasion structure retracts under the influence of gravity and transforms into stable vertical channels. It is shown that the stability of these channels is the result of a balance between hydrostatic and viscous pressure gradients.

Phenylbutyrate inhibits growth of cervical carcinoma cells independent of HPV type and copy number.

PURPOSE: Inhibitors of histone deacetylase, such as sodium butyrate, block proliferation of cervical carcinoma cells by inhibiting the G1 to S transition of the cell cycle. The derivative phenylbutyrate (PB), characterized by its higher pharmacological half-life, and its metabolite phenylacetate (PA) were tested for their growth-inhibitory function on cervical cancer cells differing in their HPV type, copy number, and integration sites. METHODS AND RESULTS: Using flow cytometric and Western blot analyses, we show that a 24-h incubation period with PB, but not with PA, was already sufficient to cause a dose-dependent growth arrest by increasing the G1 fraction with a concomitant drop in the S-phase. Consistent with the cell cycle block, only PB, but not PA, induced the cyclin-dependent kinase inhibitors p21(CIP1) and p27(KIP1). The inhibitory effect was not the result of a non-specific cytotoxic effect of PB, since cessation of cellular growth was already completely reversible 5 h after drug removal. CONCLUSIONS: Due to its broad growth inhibitory properties on different cervical carcinoma cells in vitro, and its low toxic profile demonstrated in preceding clinical studies, PB may serve as an effective drug in handling pre-cancerous lesions and cervical cancer in patients.

[Entrapment neuropathies - quality requirements for neurological and neurophysiological diagnosis]. / Nerven-Engpass-Syndrome - Qualitätsanforderungen an die neurologische und neurophysiologische Diagnostik.

In some entrapment neuropathies, the diagnosis is easily established on clinical grounds. The best example is the carpal tunnel syndrome, the most frequently diagnosed entrapment neuropathy. Other entrapment neuropathies are not clear-cut: There is doubt that the syndrome exists at all or its limits are poorly defined, or the frequency is rather variable from one medical center to another. In this situation, a clarification of the diagnostic criteria may be necessary, especially with regard to the most common and the most disputed nerve entrapments.

Central hyperacusis with phonophobia in multiple sclerosis.

Hearing disorders are a well-described symptom in patients with multiple sclerosis (MS). Unilateral or bilateral hyperacusis or deafness in patients with normal sound audiometry is often attributed to demyelinating lesions in the central auditory pathway. Less known in MS is a central phonophobia, whereby acoustic stimuli provoke unpleasant and painful paresthesia and lead to the corresponding avoidance behaviour. In our comparison collective, patient 1 described acute shooting pain attacks in his right cheek each time set off by the ringing of the telephone. Patient 2 complained of intensified, unbearable noise sensations when hearing nonlanguage acoustic stimuli. Patient 3 noticed hearing unpleasant echoes and disorders of the directional hearing. All patients had a clinical brainstem syndrome. ENT inspection, sound audiometry and stapedius reflex were normal. All three patients had pathologically changed auditory evoked potentials (AEPs) with indications of a brainstem lesion, and in magnetic resonance imaging (MRI) demyelinating lesions in the ipsilateral pons and in the central auditory pathway. The origin we presume in case 1 is an abnormal impulse conduction from the leminiscus lateralis to the central trigeminus pathway and, in the other cases, a disturbance in the central sensory modulation. All patients developed in the further course a clinically definite MS. Having excluded peripheral causes for a hyperacusis, such as, e.g., an idiopathic facial nerve palsy or myasthenia gravis, one should always consider the possibility of MS in a case of central phonophobia. Therapeutic possibilities include the giving of serotonin reuptake inhibitors or acoustic lenses for clearly definable disturbing frequencies.

[Central hyperacusis with phonophobia in multiple sclerosis]. / Zentrale Hyperakusis mit Phonophobie bei Multipler Sklerose.

Auditory disturbances are a well known symptom in patients with multiple sclerosis (MS). Uni- or bilateral hypacusis or deafness in patients with normal auditory testing is considered to be a result of lesions in the central auditory pathway. Only rarely described is a central phonophobia whereby acoustic stimuli induce unpleasant and painful perceptions, with consecutive avoidance of these factors. Our first patient described acute shooting pain in the right cheek, triggered only through the ringing of a telephone. The second patient had uncomfortable perception of nonverbal noise. For example the wrinkling of paper bags was unbearable for him. The third patient had difficulties localizing the source of sound and disturbing echos while listening to speech or music. Clinically, in all patients symptoms of a brainstem syndrome were found, whereas auditory testing including inspection, audiometry, and stapedius reflex was normal. We found pathological acoustic evoked potentials (AEP) in all three patients with a prolonged latency III-V and T2 lesions in the ipsilateral pons and central auditory pathway. In case one, we suppose a lateral spread between the lateral lemniscus and the central trigeminal pathway. In the other cases, a dysfunction of the central sensory modulation which controls the regulation of sensitivity of incoming acoustic stimuli seems to be the cause of hyperacusis. All our patients developed clinically confirmed MS in the further course after suffering from phonophobia as their first symptom.

Biphasic effect of protein kinase C activators on spontaneous and glucocorticoid-induced apoptosis in primary mouse thymocytes.

Spontaneous and glucocorticoid (fluocinolone acetonide, FA)-induced apoptosis of primary mouse thymocytes was inhibited by protein kinase C (PKC) activators such as bryostatin-1 and phorbol ester 12-O-tetradecanoyl-phorbol-13 acetate (TPA) within the first 2-4 h of incubation but was enhanced upon prolonged treatment. Only the anti-apoptotic but not the pro-apoptotic effect of TPA was completely suppressed by the PKC inhibitor Goe 6983 and moderately inhibited by Goe 6976. Immunoblot analysis revealed distinct PKC alpha, beta, delta, eta, theta, mu and zeta signals, a very faint PKCepsilon and no PKCgamma signal. Upon prolonged TPA treatment all PKC isoenzymes became downregulated, albeit at different rates (PKCdelta>alpha>mu>beta,theta>>eta,zeta). No significant generation of caspase-derived catalytic PKC fragments, as found to be produced upon induction of apoptosis and to be pro-apoptotic in other systems, was observed in FA- or TPA-treated thymocytes. It is concluded that the early anti-apoptotic effect of TPA depends on the activation of n-type PKC isoenzymes, whereas stimulation of spontaneous and FA-induced apoptosis by TPA ensues, at least partially, from a downregulation (or inactivation) of anti-apoptotic PKC species, i.e. in primary thymocytes PKC activation is primarily involved in a negative regulation of apoptosis.

A comparison of gamma and neutron irradiation on Raji cells: effects on DNA damage, repair, cell cycle distribution and lethality.

The Comet assay (microgel electrophoresis) was used to study DNA damage in Raji cells, a B-lymphoblastoid cell line, after treatment with different doses of neutrons (0.5 to 16 Gy) or gamma rays (1.4 to 44.8 Gy). A better growth recovery was observed in cells after gamma-ray treatments compared with neutron treatments. The relative biological effectiveness (RBE) of neutron in cell killing was determined to be 2.5. Initially, the number of damaged cells per unit dose was approximately the same after neutron and gamma-ray irradiation. One hour after treatment, however, the number of normal cells per unit dose was much lower for neutrons than for gamma rays, suggesting a more efficient initial repair for gamma rays. Twenty-four hours after treatment, the numbers of damaged cells per unit dose of neutrons or gamma rays were again at comparable level. Cell cycle kinetic studies showed a strong G2/M arrest at equivalent unit dose (neutrons up to 8 Gy; gamma rays up to 5.6 Gy), suggesting a period in cell cycle for DNA repair. However, only cells treated with low doses (up to 2 Gy) seemed to be capable of returning into normal cell cycle within 4 days. For the highest dose of neutrons, decline in the number of normal cells seen at already 3 days after treatment was deeper compared with equivalent unit doses of gamma rays. Our present results support different mechanisms of action by these two irradiations and suggest the generation of locally multiply damaged sites (LMDS) for high linear energy transfer (LET) radiation which are known to be repaired at lower efficiency.

Protein-kinase-Cmu expression correlates with enhanced keratinocyte proliferation in normal and neoplastic mouse epidermis and in cell culture.

In order to gain insight into the biological function of a PKC iso-enzyme, the protein kinase Cmu, we analyzed the expression pattern of this protein in mouse epidermis and keratinocytes in culture. Daily analysis of neonatal mouse epidermis immediately after birth showed a time-dependent reduction in the PKCmu content. Expression of the proliferating-cell nuclear antigen (PCNA), indicative of the proliferative state of cells, was reduced synchronously with PKCmu as the hyperplastic state of the neonatal tissue declined. In epidermal mouse keratinocytes, fractionated according to their maturation state, PKCmu expression was restricted to PCNA-positive basal-cell fractions. In primary cultures of those cells, growth arrest and induction of terminal differentiation by Ca2+ resulted in strongly reduced PKCmu expression, concomitantly with the loss of PCNA expression. Treatment of PMK-R1 keratinocytes with 100 nM of the mitogen 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in activation of PKCmu, reflected by translocation from the cytosolic to the particulate fraction and by shifts in electrophoretic mobility. DNA synthesis was significantly inhibited by the PKCmu inhibitor Goedecke 6976, while Goedecke 6983 did not inhibit PKCmu. Carcinomas generated according to the 2-stage carcinogenesis protocol in mouse skin consistently exhibited high levels of PKCmu. These data correlate PKCmu expression with the proliferative state of murine keratinocytes and point to a role of PKCmu in growth stimulation. A correlation between PKCmu expression and enhanced cell proliferation was also observed for NIH3T3 fibroblasts transfected with and overexpressing human PKCmu.

[Thoraco-abdominal manifestation of stage II Lyme neuroborreliosis]. / Die thorakoabdominale Manifestation der Lyme-Neuroborreliose Stadium II.

In the past little attention was paid to the thoracoabdominal manifestation of Lyme radiculoneuritis, because paralysis of the abdominal wall muscles was considered to be a very uncommon clinical manifestation of Lyme neuroborreliosis. In a group of 90 patients suffering from early stage Lyme neuroborreliosis we found abdominal wall weakness in 11 cases. In the majority of patients thoracoabdominal radiculoneuritis was located in the lower thoracic segments (Th 7-12) and involved more than 3 segments (62%) mostly bilaterally (69%). Abdominal wall paralysis was mostly bilateral (91%) and involved always the lower half of the abdominal wall. It was very severe in 18%. Electromyographic studies were done in the paraspinal and abdominal wall muscles showing fibrillation potentials and positive sharp waves in 86% and 50%, respectively. Diagnosis of thoracoabdominal radiculoneuritis in Lyme neuroborreliosis may be difficult and diagnostic errors may occur. Therefore we recommend to look carefully for paralysis of the abdominal wall, which can easily be overlooked on routine neurological examination. In patients from an area with a high incidence of Lyme disease it is recommended to exclude neuroborreliosis even in patients with known diabetes mellitus in order to avoid the misdiagnosis of diabetic thoracoabdominal radiculopathy. This has occured in 2 of our patients.