A New Keynesian Model with Endogenous Frictions

We develop a New Keynesian model that incorporates rigidities in the ability of households and firms to adjust their utility-efficient / profit-efficient resource allocation in response to shocks. These rigidities reflect the fact that households and firms enter into commitments for several periods of time regarding the allocation of resources limiting their ability to flexibly respond to unforeseen shocks. We show that these rigidities can adversely impact the productivity of firms and households' utility and result in the appearance of higher statistical moments in the demand and supply curves which are not exogenously constant but system-endogenous. As a result, we will derive the appearance of an inflation bias which exists even in the case of an efficient natural output and which cannot be removed by a rule-based monetary policy. Further, we show that monetary policy faces an additional trade-off in managing the friction losses due to inflation uncertainty and output uncertainty.

Piecewise oblique boundary treatment for the elastic-plastic wave equation on a cartesian grid

Numerical schemes for hyperbolic conservation laws in 2-D on a Cartesian grid usually have the advantage of being easy to implement and showing good computational performances, without allowing the simulation of "real-world” problems on arbitrarily shaped domains. In this paper a numerical treatment of boundary conditions for the elastic-plastic wave equation is developed, which allows the simulation of problems on an arbitrarily shaped physical domain surrounded by a piece-wise smooth boundary curve, but using a PDE solver on a rectangular Cartesian grid with the afore-mentioned advantage

A new perspective on the significance of the Ranotsara shear zone in Madagascar

The Ranotsara shear zone in Madagascar has been considered in previous studies to be a >350-km-long, intracrustal strike-slip shear zone of Precambrian/Cambrian age. Because of its oblique strike to the east and west coast of Madagascar, the Ranotsara shear zone has been correlated with shear zones in southern India and eastern Africa in Gondwana reconstructions. Our assessment using remote sensing data and field-based investigations, however, reveals that what previously has been interpreted as the Ranotsara shear zone is in fact a composite structure with a ductile deflection zone confined to its central segment and prominent NW-SE trending brittle faulting along most of its length. We therefore prefer the more neutral term "Ranotsara Zone”. Lithologies, tectonic foliations, and axial trace trajectories of major folds can be followed from south to north across most of the Ranotsara Zone and show only a marked deflection along its central segment. The ductile deflection zone is interpreted as a result of E-W indentation of the Antananarivo Block into the less rigid, predominantly metasedimentary rocks of the Southwestern Madagascar Block during a late phase of the Neoproterozoic/Cambrian East African Orogeny (c. 550-520Ma). The Ranotsara Zone shows significant NW-SE striking brittle faulting that reactivates part of the NW-SE striking ductile structures in the flexure zone, but also extends along strike toward the NW and toward the SE. Brittle reactivation of ductile structures along the central segment of the Ranotsara Zone, confirmed by apatite-fission track results, may have led to the formation of a shallow Neogene basin underlying the Ranotsara plain. The present-day drainage pattern suggests on-going normal fault activity along the central segment. The Ranotsara Zone is not a megascale intracrustal strike-slip shear zone that crosscuts the entire basement of southern Madagascar. It can therefore not be used as a piercing point in Gondwana reconstruction

The role of the Ranotsara Zone in southern Madagascar for Gondwana correlations

The Precambrian basement of southern Madagascar was reworked at high-grade metamorphic conditions during the East African Orogen (EAO of Stern, 1994) that formed during assembly of Gondwana in late Neoproterozoic/early Paleozoic times. At the end of the EAO, Madagascar is generally thought to be sandwiched between southern India and eastern Africa. Constraints on its paleoposition are often inferred from similarities in structural features on now dispersed continental fragments, in particular high-strain zones. Major zones with (sub)vertical foliation planes can be traced over hundreds of kilometres in southern Madagascar and have been interpreted as major vertical ductile shear zones (e.g. Windley et al. 1994; Martelat, 1998). The NW–SE trending Ranotsara Zone (dashed rectangle in Fig. 1) is regarded as an intracrustal mega strike-slip shear zone with a sinistral sense of shear that formed at the end of the Proterozoic (e.g. Nicollet, 1990; de Wit et al., 2001). A large number of studies have used the Ranotsara Zone to propose Gondwana reconstructions. The Ranotsara Zone has been correlated with various ductile shear zones in southern India, e.g. with the Bhavani Shear Zone or the Moyar Shear Zone (Katz & Premoli, 1979), the Palghat-Cauvery Shear Zone (de Wit et al., 1995), the Karur-Kamban- Painavum-Trichur Shear Zone (de Wit et al., 2001; Ghosh et al. 2004) or with the Achankovil Shear Zone (Windley et al., 1994; Martelat, 1998). Within Madagascar, the Ranotsara Zone has been correlated along strike with the more N–S trending Bongolava Zone in central-western Madagascar (Hottin 1976), and the Bongolava- Ranotsara Zone has been further traced into the Surma Shear Zone (Windley et al. 1994) and its along-strike continuation, the Aswa Shear Zone in eastern Africa (Müller 2000). Chetty (2003) suggested that the Ranotsara Zone is not only a mega shear zone, but also a terrane boundary separating a region with Archean crust to the north from a region with Neoproterozoic crust to the south. Our remote sensing and field studies of southern Madagascar indicate that the Ranotsara Zone is neither a major terrane boundary nor an intracrustal mega strike-slip shear zone and therefore can not be used as a ‘piercing point’ in Gondwana reconstructions...conferenc

Wrapping the alpha-crystallin domain fold in a chaperone assembly

Small heat shock proteins (sHsps) are oligomers that perform a protective function by binding denatured proteins. Although ubiquitous, they are of variable sequence except for a C-terminal similar to 90-residue "alpha-crystallin domain". Unlike larger stress response chaperones, sHsps are ATP-independent and generally form polydisperse assemblies. One proposed mechanism of action involves these assemblies breaking into smaller subunits in response to stress, before binding unfolding substrate and reforming into larger complexes. Two previously solved non-metazoan sHsp multimers are built from dimers formed by domain swapping between the alpha-crystallin domains,. adding to evidence that the smaller subunits are dimers. Here, the 2.5 angstrom resolution structure of an sHsp from the parasitic flatworm Taenia saginata Tsp36, the first metazoan crystal structure, shows a new mode of dimerization involving N-terminal regions, which differs from that seen for non-metazoan sHsps. Sequence differences in the a-crystallin domains between metazoans and nonmetazoans are critical to the different mechanism of dimerization, suggesting that some structural features seen for Tsp36 may be generalized to other metazoan sHsps. The structure also indicates scope for flexible assembly of subunits, supporting the proposed process of oligomer breakdown, substrate binding and reassembly as the chaperone mechanism. It further shows how sHsps can bind coil and secondary structural elements by wrapping them around the alpha-crystallin domain. The structure also illustrates possible roles for conserved residues associated with disease, and suggests a mechanism for the sHsp-related pathogenicity of some flatworm infections. Tsp36, like other flatworm sHsps, possesses two divergent sHsp repeats per monomer. Together with the two previously solved structures, a total of four alpha-crystallin domain structures are now available, giving a better definition of domain boundaries for sHsps

A novel, highly sensitive and specific biomarker for Niemann-Pick type C1 disease

Background Lysosomal storage disorders (LSDs), are a heterogeneous group of rare disorders caused by defects in genes encoding for proteins involved in the lysosomal degradation of macromolecules. They occur at a frequency of about 1 in 5,000 live births, though recent neonatal screening suggests a higher incidence. New treatment options for LSDs demand a rapid, early diagnosis of LSDs if maximal clinical benefit is to be achieved. Methods Here, we describe a novel, highly specific and sensitive biomarker for Niemann-Pick Type C disease type 1 (NPC1), lyso-sphingomyelin-509. We cross-validate this biomarker with cholestane-3β,5α,6β-triol and relative lysosomal volume. The primary cohort for establishment of the biomarker contained 135 NPC1 patients, 66 NPC1 carriers, 241 patients with other LSDs and 46 healthy controls. Results With a sensitivity of 100.0% and specificity of 91.0% a cut-off of 1.4 ng/ml was established. Comparison with cholestane-3β,5α,6β-triol and relative acidic compartment volume measurements were carried out with a subset of 125 subjects. Both cholestane-3β,5α,6β-triol and lyso-Sphingomyelin-509 were sufficient in establishing the diagnosis of NPC1 and correlated with disease severity. Conclusion In summary, we have established a new biomarker for the diagnosis of NPC1, and further studies will be conducted to assess correlation to disease progress and monitoring treatment

Development of a duodenal gallstone ileus with gastric outlet obstruction (Bouveret syndrome) four months after successful treatment of symptomatic gallstone disease with cholecystitis and cholangitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cases of gallstone ileus account for 1% to 4% of all instances of mechanical bowel obstruction. The majority of obstructing gallstones are located in the terminal ileum. Less than 10% of impacted gallstones are located in the duodenum. A gastric outlet obstruction secondary to a gallstone ileus is known as Bouveret syndrome. Gallstones usually enter the bowel through a biliary enteral fistula. Little is known about the formation of such fistulae in the course of gallstone disease.</p> <p>Case presentation</p> <p>We report the case of a 72-year-old Caucasian woman born in Germany with a gastric outlet obstruction due to a gallstone ileus (Bouveret syndrome), with a large gallstone impacted in the third part of the duodenum. Diagnostic investigations of our patient included plain abdominal films, gastroscopy and abdominal computed tomography, which showed a biliary enteric fistula between the gallbladder and the duodenal bulb. Our patient was successfully treated by laparotomy, duodenotomy, extraction of the stone, cholecystectomy, and resection of the fistula in a one-stage surgical approach. Histopathological examination showed chronic and acute cholecystitis, with perforated ulceration of the duodenal wall and acute purulent inflammation of the surrounding fatty tissue. Four months prior to developing a gallstone ileus our patient had been hospitalized for cholecystitis, a large gallstone in the gallbladder, cholangitis and a small obstructing gallstone in the common biliary duct. She had been treated with endoscopic retrograde cholangiopancreatography, endoscopic biliary sphincterotomy, balloon extraction of the common biliary duct gallstone, and intravenous antibiotics. At the time of her first presentation, abdominal ultrasound and endoscopic examination (including esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography) had not shown any evidence of a biliary enteral fistula. In the four months preceding the gallstone ileus our patient had been asymptomatic.</p> <p>Conclusion</p> <p>In patients known to have gallstone disease presenting with symptoms of ileus, the differential diagnosis of a gallstone ileus should be considered even in the absence of preceding symptoms related to the gallbladder disease. Gallstones large enough to cause intestinal obstruction usually enter the bowel by a biliary enteral fistula. During the formation of such a fistula, patients can be asymptomatic.</p

Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer's disease tau

BackgroundAugmenting the brain clearance of toxic oligomers with small molecule modulators constitutes a promising therapeutic concept against tau deposition. However, there has been no test of this concept in animal models of Alzheimer's disease (AD) with initiation at a late disease stage. Thus, we aimed to investigate the effects of interventional late-stage Anle138b treatment, which previously indicated great potential to inhibit oligomer accumulation by binding of pathological aggregates, on the metabolic decline in transgenic mice with established tauopathy in a longitudinal F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) study.MethodsTwelve transgenic mice expressing all six human tau isoforms (hTau) and ten controls were imaged by FDG-PET at baseline (14.5months), followed by randomization into Anle138b treatment and vehicle groups for 3months. FDG-PET was repeated after treatment for 3months, and brains were analyzed by tau immunohistochemistry. Longitudinal changes of glucose metabolism were compared between study groups, and the end point tau load was correlated with individual FDG-PET findings.ResultsTau pathology was significantly ameliorated by late-stage Anle138b treatment when compared to vehicle (frontal cortex -53%, p<0.001;hippocampus -59%, p<0.005). FDG-PET revealed a reversal of metabolic decline during Anle138b treatment, whereas the vehicle group showed ongoing deterioration. End point glucose metabolism in the brain of hTau mice had a strong correlation with tau deposition measured by immunohistochemistry (R=0.92, p<0.001).ConclusionLate-stage oligomer modulation effectively ameliorated tau pathology in hTau mice and rescued metabolic function. Molecular imaging by FDG-PET can serve for monitoring effects of Anle138b treatment

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