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Zusammenfassung: Der demographische Wandel unserer Gesellschaft mit zunehmend älteren Patienten und deren steigender Komorbidität führt dazu, dass die operative Behandlung des invasiven Harnblasenkarzinoms älterer Patienten zunehmend an Bedeutung gewinnt. Angesichts dieser Entwicklung sollten der Stellenwert und die Indikation konservativer bzw. wenig invasiver Therapieansätze immer wieder neu hinterfragt werden. Die radikale Zystektomie unter kurativer Zielsetzung ist weiterhin Goldstandard der Behandlung des invasiven High-grade-Karzinoms. Jedoch ist nicht jeder Patient hierfür geeignet oder er steht einer solchen Operation ablehnend gegenüber. Aus diesem Grund sollten dieser Gruppe von Patienten alternative Therapieansätze, ob in kurativer oder palliativer Zielsetzung, einschließlich Organ- und Funktionserhalt der Harnblase, angeboten werden können. Hierbei kommen die transurethrale Blasentumorresektion (TUR-B), die offene Blasenteilresektion, die Chemotherapie (intravesikal – systemisch), die lokale Bestrahlung und minimal-invasive interventionelle Therapien allein oder in Kombination in Frage. Ziel ist es, aufgrund einer geringeren physischen und psychischen Belastung v. a. eine schnelle Rekonvaleszenz der Patienten zu erreichen und die Lebensqualität zu erhalten. Aus onkologischer Sicht müssen diese Therapieansätze jedoch kritisch betrachtet werden, da sie vielleicht nur zu einem vorübergehenden Stillstand der Erkrankung oder zur Beseitigung von Symptomen führen. Dennoch zeigen die Langzeitergebnisse, dass einem Teil der Patienten mit einem High-grade-Karzinom der Harnblase bei richtiger Indikation eine Kuration als Ziel einer multimodalen Therapie mit Blasenerhalt in Aussicht gestellt werden kann.

While various marine predators form associations, the most commonly studied are those between subsurface predators and seabirds, with gulls, shearwaters or terns frequently co-occurring with dolphins, billfish or tuna. However, the mechanisms underlying these associations remain poorly understood. Three hypotheses have been proposed to explain the prevalence of these associations: (1) subsurface predators herd prey to the surface and make prey accessible to birds, (2) subsurface predators damage prey close to the surface and thereby provide food scraps to birds, and (3) attacks of underwater predators lower the cohesion of prey groups and thereby their collective defences making the prey easier to be captured by birds. Using drone footage, we investigated the interaction between Indo-Pacific sailfish (Istiophorus platypterus) and terns (Onychoprionsp.) preying on schooling fish off the eastern coast of the Malaysian peninsula. Through spatio-temporal analysis of the hunting behaviour of the two predatory species and direct measures of prey cohesion we showed that terns attacked when school cohesion was low, and that this decrease in cohesion was frequently caused by sailfish attacks. Therefore, we propose that sailfish created a by-product benefit for the bird species, lending support to the hypothesis that lowering cohesion can facilitate associations between subsurface predators and seabirds.

Frameshift mutations in the DMDgene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMDreading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD(DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51–52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.

Novel observation techniques (e.g., smart tracers) for characterizing coupled hydrological and biogeochemical processes are improving understanding of stream network transport and transformation dynamics. In turn, these observations are thought to enable increasingly sophisticated representations within transient storage models (TSMs). However, TSM parameter estimation is prone to issues with insensitivity and equifinality, which grow as parameters are added to model formulations. Currently, it is unclear whether (or not) observations from different tracers may lead to greater process inference and reduced parameter uncertainty in the context of TSM. Herein, we aim to unravel the role of in‐stream processes alongside metabolically active (MATS) and inactive storage zones (MITS) using variable TSM formulations. Models with one (1SZ) and two storage zones (2SZ) and with and without reactivity were applied to simulate conservative and smart tracer observations obtained experimentally for two reaches with differing morphologies. As we show, smart tracers are unsurprisingly superior to conservative tracers when it comes to partitioning MITS and MATS. However, when transient storage is lumped within a 1SZ formulation, little improvement in parameter uncertainty is gained by using a smart tracer, suggesting the addition of observations should scale with model complexity. Importantly, our work identifies several inconsistencies and open questions related to reconciling time scales of tracer observation with conceptual processes (parameters) estimated within TSM. Approaching TSM with multiple models and tracer observations may be key to gaining improved insight into transient storage simulation as well as advancing feedback loops between models and observations within hydrologic science. Solute experiments and transport models, called commonly tracer experiments, are used to understand the relative importance of different stream processes, especially those that influence water, solutes, and nutrients as they move through a stream network. Within these tracer experiments, there are processes that exchange mass beyond the main stream channel to other parts of the river valley bottom environment. Sometimes, there are single or multiple types of tracers used and modeled to try to understand this exchange. There are also multiple models with different equations and structures to simulate these tracers. This study shows that what you can learn about these stream processes depends on experiment choices and which model you use. Hence, refining future multiple tracer experiments and models is needed to determine how we best obtain consistent measurements of key stream processes. TSM interpretation improved with analysis of multiple tracers but results in increased parameter uncertainty for a more complex modelNonconservative tracers enabled interpretation of parameters that were highly uncertain when estimated by conservative tracers aloneAchieving reliable parameter estimates depends on choice of tracers and model framework and should be coupled with uncertainty assessment

Soil‐surface temperature acts as a master variable driving nonlinear terrestrial ecohydrological, biogeochemical, and micrometeorological processes, inducing short‐lived or spatially isolated extremes across heterogeneous landscape surfaces. However, subcanopy soil‐surface temperatures have been, to date, characterized through isolated, spatially discrete measurements. Using spatially complex forested northern peatlands as an exemplar ecosystem, we explore the high‐resolution spatiotemporal thermal behavior of this critical interface and its response to disturbances by using Fiber‐Optic Distributed Temperature Sensing. Soil‐surface thermal patterning was identified from 1.9 million temperature measurements under undisturbed, trees removedand vascular subcanopy removedconditions. Removing layers of the structurally diverse vegetation canopy not only increased mean temperatures but it shifted the spatial and temporal distribution, range, and longevity of thermal hot spots and hot moments. We argue that linking hot spots and/or hot moments with spatially variable ecosystem processes and feedbacks is key for predicting ecosystem function and resilience. Peatlands cover 3% of the Earth's surface but hold more carbon than the world's forests. Surface temperatures are a key control over many important peatland processes such as carbon storage and release. While peatland function and their response to disturbances has traditionally been examined as uniform, spatially isolated systems, peatland processes occur in a spatially complex and interconnected manner. New technology enables us to explore these fine‐scale behaviors, examining near‐surface temperatures spatially across a peatland. Temperatures were measured high spatial and temporal resolution in an undisturbed ecosystem, and subsequently repeated after the trees canopy was removed, and after the shrubs and grasses were cut and removed. We effectively removed layers of the ecosystem, reducing the complexity of the system. Results showed that average temperatures increased with removal of vegetation layers as expected. However, importantly, this temperature increase was uneven across the peatland surface and did not reflect predisturbance temperature patterns. We relate this system response to ecosystem layers and system complexity. As more layers are removed (e.g., shrub layer, and tree layer), the intensity of thermal hot spots increases. This has important implications for understanding ecosystem resilience and for predicting carbon storage ability of soils. Temporal shifts in environmental stressors cause spatially explicit system feedbacks that define ecosystem resilience to changeLayers of peatland ecosystem complexity reduce thermal hot spot intensityNovel application of Fiber‐Optic Distributed Temperature Sensing gives soil‐surface temperatures at unprecedented spatiotemporal resolution

In this paper, we outline the current state of the art and trends for future development in millimeter-wave (mmw) amplifiers based on gallium nitride (GaN) semiconductors. To that end, we give an overview of recent technological results of currently operational GaN foundries and classify them with respect to their maximum frequency of operation and the current-gain cutoff frequency. Furthermore, focusing on frequencies above 80 GHz, we develop a comprehensive survey of GaN high-power amplifiers (HPAs) and provide a comparison to competing technologies such as indium phosphide (InP) and silicon germanium (SiGe). We also introduce a newly developed 6-stage GaN amplifier that is targeted towards the upper D-band. It provides an output power of up to 22.0 dBm, which sets a new record for GaN HPAs in this band. From our survey, we find that while GaN exhibits an impressive power density, its gain and efficiency characteristics particularly beyond 120 GHz still warrant improvement. Therefore, we describe several areas of future improvement such as the gate module scaling, mitigation of trapping phenomena and recent trends in processing of ohmic contacts and alternative epitaxial stacks. With these further developments, more widespread adoption of GaN-based technologies at even higher frequencies seems feasible in the coming years.

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients’ and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2days 2, 16, 30), procarbazine (60 mg/m2days 2–11) and lomustine (110 mg/m2, day 2)—R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.

Distributed Temperature Sensing (DTS) technology enables downhole temperature monitoring to study hydrogeological processes at unprecedentedly high frequency and spatial resolution. DTS has been widely applied in passive mode in site investigations of groundwater flow, in-well flow, and subsurface thermal property estimation. However, recent years have seen the further development of the use of DTS in an active mode (A-DTS) for which heat sources are deployed. A suite of recent studies using A-DTS downhole in hydrogeological investigations illustrate the wide range of different approaches and creativity in designing methodologies. The purpose of this review is to outline and discuss the various applications and limitations of DTS in downhole investigations for hydrogeological conditions and aquifer geological properties. To this end, we first review examples where passive DTS has been used to study hydrogeology via downhole applications. Secondly, we discuss and categorize current A-DTS borehole methods into three types. These are thermal advection tests, hybrid cable flow logging, and heat pulse tests. We explore the various options with regards to cable installation, heating approach, duration, and spatial extent in order to improve their applicability in a range of settings. These determine the extent to which each method is sensitive to thermal properties, vertical in-well flow, or natural gradient flow. Our review confirms that the application of DTS has significant advantages over discrete point temperature measurements, particularly in deep wells, and highlights the potential for further method developments in conjunction with other emerging hydrogeophysical tools. Distributed Temperature Sensing in subsurface applications allows the monitoring subsurface hydrology in unprecedented spatiotemporal detailThe specific limitations of DTS measurements need to be taken into account in the design of field installationsThe application of DTS in subsurface hydrology is still under development

Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin’s lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63–1.20)) for men and 1.06 (95% CI 0.69–1.55) for women. SIRs were between 0.49 (95% CI 0.13–1.34) for colorectal cancer in men and 4.29 (95% CI 1.09–11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.

DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

P38α/β has been described as a tumor-suppressor controlling cell cycle checkpoints and senescence in epithelial malignancies. However, p38α/β also regulates other cellular processes. Here, we describe a role of p38α/β as a regulator of acute lymphoblastic leukemia (ALL) proliferation and survival in experimental ALL models. We also report first evidence that p38α/β phosphorylation is associated with the occurrence of relapses in TEL-AML1-positive leukemia. First, in vitroexperiments show that p38α/β signaling is induced in a cyclical manner upon initiation of proliferation and remains activated during log-phase of cell growth. Next, we provide evidence that growth-permissive signals in the bone marrow activate p38α/β in a novel avian ALL model, in which therapeutic targeting can be tested. We further demonstrate that p38α/β inhibition by small molecules can suppress leukemic expansion and prolong survival of mice bearing ALL cell lines and primary cells. Knockdown of p38α strongly delays leukemogenesis in mice xenografted with cell lines. Finally, we show that in xenografted TEL-AML1 patients, ex vivop38α/β phosphorylation is associated with an inferior long-term relapse-free survival. We propose p38α/β as a mediator of proliferation and survival in ALL and show first preclinical evidence for p38α/β inhibition as an adjunct approach to conventional therapies.

Rivers transport contaminant microorganisms (including fecal indicator bacteria and human pathogens) long distances downstream of diffuse and point sources, posing a human health risk. We present a mobile‐immobile model that incorporates transport as well as immobilization and remobilization of contaminant microbes and other fine particles during baseflow and stormflow. During baseflow conditions, hyporheic exchange flow causes particles to accumulate in streambed sediments. Remobilization of stored particles from streambed sediments occurs slowly during baseflow via hyporheic exchange flow, while remobilization is vastly increased during stormflow. Model predictions are compared to observations over a range of artificial and natural flood events in the dairy contaminated Topehaehae Stream, New Zealand. The model outputs closely matched timing and magnitude of E. coliand turbidity observations through multiple high‐flow events. By accounting for both state‐of‐flow and hyporheic exchange processes, the model provides a valuable framework for predicting particle and contaminant microbe behavior in streams. Contaminant microorganisms, including the bacterial indicator E. coli, and various disease‐causing bacteria, viruses, and pathogens, are highly episodic in rivers—with typically low‐contaminant microorganism concentrations during low flows that are 100− fold or more increased during storms. At low flow, microbes and other fine particles tend to accumulate steadily in near‐surface streambed sediments (the “hyporheic zone”), but these stores are remobilized by accelerating currents as flow increases. We developed a numerical model framework to represent exchanges of particles and microbes between water and the streambed sediments under variable states of flow—including the deeper streambed as well as the hyporheic zone. Our model was able to capture microbial behavior measured over both a natural storm event and a series of three artificial floods (without any wash‐in from land) in the dairy‐contaminated Topehaehae Stream, New Zealand. Our modeling approach provides a useful framework for predicting microbial behavior and associated hazards within rivers and downstream waters. Remobilization of microbes is dependent on both their antecedent accumulation in streambed sediments and the magnitude of stream flowStorm events mobilize microbes from streambed stores that are replenished during the falling limb of the storm hydrograph and baseflowOur particle tracking mobile‐immobile model captures exchanges between the surface water, the hyporheic zone and deeper streambed Remobilization of microbes is dependent on both their antecedent accumulation in streambed sediments and the magnitude of stream flow Storm events mobilize microbes from streambed stores that are replenished during the falling limb of the storm hydrograph and baseflow Our particle tracking mobile‐immobile model captures exchanges between the surface water, the hyporheic zone and deeper streambed

This planning study was performed to compare stereotactic linac based radiosurgery of Arteriovenous Malformations (AVM) with current Helical Tomotherapy (HT) and future HT techniques. For 10 patients with AVM, dose distributions and treatment times of “regular” HT delivery (Reg 2.5/1/0.6 cm field width), Running-Start-Stop Treatment (RSS 5/2.5 cm), Axial Mode (Axial 5 cm) and Dynamic Jaw/Dynamic Couch delivery with a maximum field width of 5 cm (DJDC 5) were analysed and compared to linac-based stereotactic radiosurgery. Axial produced the fastest treatment (Axial 4:47 min vs. Linac 32:42 min) at the cost of large brain exposure (V10%289 ml). Except for Reg 0.6, all other HT techniques achieved significantly shorter treatment times than linac-based treatment (e.g.Reg 1, 19:42 min, DJDC 6:30 min). However, high-dose brain exposure (V60%) was higher in all HT plans (e.g.Reg 0.6, 10 ml, Linac 9 ml), and only Reg 0.6 showed better low-dose exposure (V10%of 167 ml vs. 199 ml, not significant). Neither current nor future HT modes in their current version outperformed linac-based stereotactic radiosurgery. However, AVM with special geometry might still benefit from HT.

Abstract

Understanding of the relationship between stress and magnetic properties in nanostructures is of both fundamental and practical interest. In the present paper, we illustrate this statement with some recent research results. First, we will see how the magnetoelastic interaction in Dy films controls the magnetic structure at the nanoscale due to the presence of the structural defects and their associated strain fields. Then, it will be shown how the magnetoelastic contribution can dominate the total anisotropy in epitaxial (100) oriented Cu/Ni/Cu nanowires, where the film patterning process performed to produce the nanowires induces strain changes large enough to favor a net in-plane anisotropy transverse to the lines.

Eine über den gesamten Lebenszyklus wahrgenommene Produktverantwortung schützt unsere natürlichen Ressourcen und stellt am Ende des Lebensweges die Nutzung der in Altprodukten enthaltenen Wertstoffe sicher. Die chemische Industrie nimmt hierbei eine besondere Funktion ein, da sie Ausgangspunkt für eine Vielzahl von Produkten ist. Im abfallrechtlichen Sinne zielt die Produktverantwortung auf die Schonung natürlicher Ressourcen durch Vermeidung und Verwertung sowie durch umweltverträgliche Beseitigung von Abfällen. Die ganzheitliche Lebenswegbetrachtung des Produktes „Auto” „von der Wiege bis zur Bahre” unterstreicht die Notwendigkeit der Wahrnehmung einer innovativen und nachhaltigkeitsbewussten Produktverantwortung.

Mutations in GNEencoding UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) cause hereditary inclusion body myopathy (HIBM). To define the role of GNEmutations in HIBM pathogenesis, GNE protein expression was analyzed. GNE protein is expressed at equal levels in HIBM patients and normal control subjects. Immunofluorescence detection of GNE did not reveal any mislocalization of GNE in skeletal muscle. We conclude that impaired GNE function, not lack of expression, may be the key pathogenic factor in HIBM. For diagnostic purposes, direct genetic analysis of the GNEgene in patients with IBM will remain the mainstay and is not aided by immunohistochemistry or immunoblotting using antibodies against the GNE protein.

Congenital myasthenic syndromes (CMS) with underlying RAPSNmutations turned out to be of high clinical relevance due to their worldwide frequency. To date, all reported patients with CMS with sequence variations in the translated region of RAPSNcarry the mutation N88K on at least one allele. The authors report two patients lacking the common N88K allele but harboring differing novel mutations of the RAPSNgene on both alleles: one patient is homozygous for a missense mutation (R164C); the second patient is compound heterozygous for a splice (IVS1-15C>A) and another missense mutation (L283P).

The leaky dielectric model (LDM) was extended to large droplet distortions in dc electric fields. The resulting extended LDM (ELDM) reduces to the LDM for small droplet aspect ratios and to the pure dielectric model when the ratio of droplet and matrix conductivities equals the inverse ratio of their permittivities. The ELDM distinguishes between two types of phenomena possible at high electric fields:  continuous deformation and hysteresis. For droplets deforming parallel to the electric field, the relationship that distinguishes between the two phenomena is a function of the droplet and matrix conductivities and viscosities but not of their permittivities. For droplets deforming perpendicular to the electric field, the relationship is a function of the droplet permittivities and conductivities but depends only slightly on the ratio of their viscosities. Some of the predictions of the LDM and the ELDM were compared with our own data and with data from the literature. For the systems that deformed parallel to the field direction, the ELDM not only predicted the data qualitatively but also predicted the data quantitatively when the experimental errors in its input parameters were taken into account, whereas the older LDM did not even predict the qualitative trend of the data. For the systems that deformed perpendicular to the field direction, however, the ELDM predicted the observed the aspect ratios in only one out of the four systems examined. In the other three systems, the LDM appeared to give reasonable predictions when either the ratio of the matrix/droplet viscosities was relatively small or the value of total charge relaxation time was relatively large. Thus, the applicability of the ELDM, as presently formulated, appears to be limited in the case of deformations perpendicular to the electric field.

No abstracts.

The electromechanical behavior of two cross-linked strong acid hydrogels&sbd;(1) 50% sulfonated poly(styrene-b-ethylene-co-butylene-b-styrene) (S-SEBS) and (2) 69% sulfonated polystyrene (S-PS)&sbd;were studied in 0.005−0.1 M solutions of Na2SO4, Cs2SO4, (CH3)4NHSO4, and (C4H9)4NHSO4 (TBA) in a 1.6 V/cm dc electric field. Both gels bent toward the cathode when they were preequilibrated in the corresponding salt solutions. The bending angle increased linearly with time at the start and then more slowly toward a steady-state bending angle, θss. The time needed to reach θss depended on the mobility of the cations, the electric field, and the thickness of each gel, but not on the salt concentration. Both θss and the initial speed of bending reached a maximum at the same intermediate salt concentration, C*, that changed little with type of salt or gel. θss decreased while the initial bending speed increased with the mobility of the cation. When the S-PS gel was preequilibrated in distilled water before the bending measurements, the gel first bent toward the anode before reversing toward the cathode in 0.065−0.08 M TBA solutions. The S-PS gel did this in none of the other salt solutions, and the S-SEBS did not reverse its bending behavior at all. The reasons for some of these results are discussed.

A novel type of electromechanical actuator that utilizes the speed of electrorheological fluids (ERFs) coupled with the elastic response of polymeric gels has been investigated. ERF's were made using polyaniline (PANI) particles suspended in a trimethyl-terminated poly(dimethylsiloxane) (3MPDMS) fluid. These ERF's were then cured into matrices of both ordered and randomly cross-linked PDMS networks (XPDMS). Electric fields were applied to these systems using flexible electrodes. Both electrode displacement and compression modulus of the composite gels were measured as a function of cross-link density of the gels, viscosity, and electrical properties of the 3MPDMS fluid, conductivity and dielectric constant of both the pure PANI and the gel matrix, weight percent PANI in the ERF, volume percent ERF in the final gel composite, and applied electric field strength. The dc electric field required to move the electrodes toward each other by a fixed distance depended more on the type and amount of cross-linking in the XPDMS matrix, the viscosity of the ERF phase, and whether the ERF particles were prealigned in the XPDMS network than it did on the compression modulus of the systems. In addition, the results indicated that the motion generated by this actuator also depends on the amount of force exerted on the electrodes by the polarized ERF particles in the gels.

The protein product of the Toll-like receptor (TLR) 4 gene has been implicated in the signal transduction events induced by lipopolysaccharide (LPS). In mice, destructive mutations of Tlr4 impede the normal response to LPS and cause a high susceptibility to Gram-negative infection. Expression of TLR4 mRNA in humans is restricted to a small number of cell types, including LPS-responsive myeloid cells, B-cells, and endothelial cells. To investigate the molecular basis for TLR4 expression in cells of myeloid origin, we cloned the human TLR4 gene and analyzed its putative 5'-proximal promoter. In transient transfections a region of only 75 base pairs upstream of the major transcription initiation site was sufficient to induce maximal luciferase activity in THP-1 cells. The sequence of this region is similar in human and mouse TLR4 genes and lacks a TATA box, typical Sp1-sites or CCAAT box sequences. Instead, it contains consensus-binding sites for Ets family transcription factors, octamer-binding factors, and a composite interferon response factor/Ets motif. The activity of the promoter in macrophages was strictly dependent on the integrity of both half sites of the composite interferon response factor/Ets motif, which was constitutively bound by the myeloid and B-cell-specific transcription factor PU.1 and interferon consensus sequence-binding protein. These results indicate that the two tissue-restricted transcription factors PU.1 and interferon consensus sequence-binding protein participate in the basal regulation of human TLR4 in myeloid cells. Cloning of the human TLR4 gene provides a basis for further investigation of the possible impact of genetic variations on the susceptibility to infection and sepsis.

Terminal maturation of blood monocytes (MO) in vitro and in vivo into macrophages (MAC) occurs as a result of interactions with various cell types. To characterize some of the cell‐cell connections that maybe important for MO differentiation we cocultured human MO with lymphocytes and/or with platelets. We found that intact platelets strongly promoted MO maturation under serum‐free conditions as evident from the expression of differentiation‐dependent antigens and morphology. To further characterize the differentiation‐inducing component(s) we prepared membrane and cytosol fractions of platelets. Both fractions could induce MO maturation, comparable to intact platelets. Further centrifugation of the cytosolic fraction revealed that only the pellet of ultracentrifugation, e.g., membrane fragments, could induce MO differentiation. Digestion with either trypsin or neuraminidase could only partially inhibit this effect. The same was true for heat‐treated fractions, indicating that this platelet‐derived differentiation stimulus is not solely an intact protein. Next we prepared protein and lipid fractions of platelets. Treatment of MO with platelet proteins or platelet lipids clearly showed that only the lipid components were able to induce MO maturation. We propose components present in the lipid fraction of platelet membranes as possible inducers of MO maturation in vitro. J. Leukoc. Biol. 63: 469–476; 1998.

The adhesion of chemically and electrochemically deposited copper films on commercial polyimide foils has been studied using scanning electron microscopy, photoelectron spectroscopy, EDX and IR reflection-absorption spectroscopy. Experiments have been carried out on the bare surface and the deposited layers as well as on surfaces prepared by peeling off the deposits. The results show that, at least for the case considered here, poor adhesion is caused by cohesion failure in the foil itself, and that a thin surface layer of the polyimide foil is important for the interface bond. IR spectroscopy was used to study the molecular nature of this surface layer.

Abstract: The operation of an electrically excited gasdynamic CO laser with closed-cycle gas flow is described. Details of the gasdynamics, the recompression, and the cooling of the flowing gas are given. The electrical discharge produces contaminating gas compounds—in particular CO2—which accumulate in the recirculating gas. The resulting transient behavior of the laser gas composition, the discharge characteristics, and the laser performance are studied and compared with the results obtained with the same CO laser in an open-flow system. It is found that the closed-cycle system may be operated for considerable time if the CO2 contamination is removed from the laser gas.

The behaviour of two different enteric coatings with pHdependent properties has been investigated as a model system for the degradation of polymer coated electrodes using impedance spectroscopy. Since the stability of these polymers depends strongly on pH, it was possible to halt the breakdown at well defined stages, which were investigated systematically. Although both polymers, Eudragit S-100 and a modified maleic anhydride copolymer, have similar chemical structures, they had different breakdown mechanisms. Eudragit S-100 films dissolved, initially forming electrolyte filled pores through which electrolyte penetrated to the gold and spread along the electrode surface. The electrolyte layer between coating and electrode was found to be typically 0.7μm thick for a 30μm thick coating with a porosity of 2×10−4. Layers of the modified maleic anhydride copolymer, unlike the Eudragit S-100, did not dissolve, but swelled in the course of the breakdown. It was shown that only positively charged ions can penetrate this polymer during breakdown. For the redox couple [Ru(NH3)6]2+/[Ru(NH3)6]3+ a mean diffusion coefficient of D=0.7×10−8cm−2s−1in the swollen polymer was determined.

Cadmium and zinc immissions around a zinc coating plant were evaluated by analysis of these elements in grass samples. Applying cluster analysis, we were able to distinguish between two groups of data. Cadmium and zinc concentrations in these groups proved to be significantly different as shown by the Wilcoxon-Mann-Whitney test. Localities with elevated concentrations coincided with prevailing wind directions and were located near the suspected point emission source.

The characterization of three YAC/P1 contigs from adjacent segments of the central region of mouse Chromosome (Chr) 11 is described. These contigs are based upon 63 YACs and 40 P1 recombinants. From these clones, 185 end sequences were obtained, of which 147 sequences could be converted into sequencetagged sites and mapped within the three contigs. Deletions were detected in 16 out of 63 YACs; 19 of 63 YACs were found to be chimeric. No such aberrations were found in P1 recombinants. A total of 22 public and 34 newly developed microsatellite markers were unambiguously localized to and ordered in the contigs. In the cryb1/Nf1 interval of the central contig, several new genes have been identified by exon trapping and precisely localized with respect to known STS markers.

Annealed interfaces between high-density polyethylene (HDPE), low-density polyethylene (LDPE), and polypropylene (PP) and some ethylene-co-vinyl acetate (EVA) and ethylene-co-acrylic acid (EAA) copolymers were examined using optical microscopy, scanning electron microscopy (SEM), and electron microprobe analysis. Transcrystalline zones were observed in a polarizing microscope on the copolymer side of the interfaces between EVA copolymers with ≤18 wt % VA or EAA copolymers with ≤6.5 wt % AA and HDPE or LDPE when the samples were heated above the melting points of both polymers and allowed to cool slowly to room temperature. The crystallization temperatures in the transcrystalline zones were all above those of the bulk copolymers and, in some cases, above the melting points of the bulk copolymers. Electron microprobe data on EVA−HDPE freeze-fractured interfaces showed a percentage of VA less than that in the bulk copolymer in the region corresponding to the transcrystalline zone on the copolymer side of the interface. The data indicated that polyethylene migrated into the transcrystalline zone. This was confirmed by optical microscopy which showed that some PE oligomers with molecular weights up to 507 were completely miscible with EVA samples having VA contents up to 18 wt %. Also, calculations using Flory−Huggins theory indicated that copolymers of low wt % VA or AA should be miscible with low molecular weight PE at elevated temperatures. Optical microscopy of EAA or EVA interfaces with PP showed the formation of influxes of copolymer into the PP side of the interface, resulting in a mechanically interlocked interface.

In an Argon-Magnesium-Plasma and a Xenon-Magnesium-Plasma number densities of the four lowest excited levels in Magnesium II were measured using a special absorption method and the absolute spectral line intensities from an optically non-thin layer. Near-Resonant-Charge-Exchange is demonstrated experimentally between Argon ions and MgII(4s2S) and between Xenon ions and Mgll (3p2Po), respectively

Binding capacities for purified malate dehydrogenase from pig heart and malate dehydrogenase from Escherichia coli were determined for different gel matrices and a Cibacron Blue modified membrane. During batch adsorption the membrane has nearly the same capacity as Blue Sepharose. During filtration the effective capacity of the membrane was increased in contrast to Blue Sepharose. With cell homogenates, when used under cross-flow conditions, the membrane displayed better performance than Blue Sepharose.

SUMMARY.Using a platelet counting technique, spontaneous platelet aggregation (SPA) was determined in citrated whole blood (WB) and platelet-rich plasma (PRP) obtained from 27 patients with insulin-dependent diabetes mellitus and from 32 healthy controls. SPA in WB, but not in PRP, was significantly enhanced in the patients compared with the controls. In the patient group, SPA in WB correlated positively with poor metabolic control as measured by glycosylated haemoglobin (Hb A1). Furthermore, the increased SPA in WB from diabetics was found to be associated with an increased mechanical fragility of red blood cells (RBC) measured as liberation of haemoglobin into the plasma in stirred samples of WB. Pentoxifylline, which is believed to increase the deformability of RBC, reduced the extent of SPA in WB from the patients but was without effect on SPA in PRP from the patients or in WB from the controls.