Activation of the hypoxia-inducible factor pathway protects against acute ischemic stroke by reprogramming central carbon metabolism.

Cell metabolism reprogramming to sustain energy production, while reducing oxygen and energy consuming processes is crucially important for the adaptation to hypoxia/ischemia. Adaptive metabolic rewiring is controlled by hypoxia-inducible factors (HIFs). Accumulating experimental evidence indicates that timely activation of HIF in brain-resident cells improves the outcome from acute ischemic stroke.

Influence of Vanadium Micro-Alloying on the Microstructure of Structural High Strength Steels Welded Joints.

The inter-critically reheated grain coarsened heat affected zone (IC GC HAZ) has been reported as one of the most brittle section of high-strength low-alloy (HSLA) steels welds. The presence of micro-alloying elements in HSLA steels induces the formation of microstructural constituents, capable to improve the mechanical performance of welded joints. Following double welding thermal cycle, with second peak temperature in the range between Ac1 and Ac3, the IC GC HAZ undergoes a strong loss of toughness and fatigue resistance, mainly caused by the formation of residual austenite (RA).

Activated glia cells cause bioenergetic impairment of neurons that can be rescued by knock-down of the mitochondrial calcium uniporter.

Neuroinflammation is a hallmark of various neurological disorders including autoimmune-, neurodegenerative and neuropsychiatric diseases. In neuroinflammation, activated microglia and astrocytes release soluble mediators such as cytokines, glutamate, and reactive oxygen species that negatively affect neuronal function and viability, and thus contribute to neurodegeneration during disease progression. Therefore, the development of neuroprotective strategies might be important in addition to treating inflammation in these diseases.

The antibacterial activity of p-tert-butylcalix[6]arene and its effect on a membrane model: molecular dynamics and Langmuir film studies.

The antibacterial activity of a calixarene derivative, p-tert-butylcalix[6]arene (Calix6), was assessed and was shown not to inhibit the growth of E. coli, S. aureus and B.

The proteasome biogenesis regulator Rpn4 cooperates with the unfolded protein response to promote ER stress resistance.

Misfolded proteins in the endoplasmic reticulum (ER) activate the unfolded protein response (UPR), which enhances protein folding to restore homeostasis. Additional pathways respond to ER stress, but how they help counteract protein misfolding is incompletely understood. Here, we develop a titratable system for the induction of ER stress in yeast to enable a genetic screen for factors that augment stress resistance independently of the UPR.

Structural organization and phase behaviour of meta-substituted dioctadecylaminobenzoquinones at the air/water interface.

The structural organization and phase behaviour of an amphiphilic zwitterionic quinonemonoimine at the air/water interface are presented. Brewster angle microscopy reveals multiple co-existing phases are observed over the entire isotherm while grazing incidence X-ray diffraction (GIXD) shows that these comprise both tilted, untilted and multilayer structures with crystalline headgroups. Despite the heterogeneity, the phase transitions are highly reversible over multiple cycles.

SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress.

When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activities during stress.

Model Lung Surfactant Films: Why Composition Matters.

Lung surfactant replacement therapies, Survanta and Infasurf, and two lipid-only systems both containing saturated and unsaturated phospholipids and one containing additional palmitic acid were used to study the impact of buffered saline on the surface activity, morphology, rheology, and structure of Langmuir monolayer model membranes. Isotherms and Brewster angle microscopy show that buffered saline subphases induce a film expansion, except when the cationic protein, SP-B, is present in sufficient quantities to already screen electrostatic repulsion, thus limiting the effect of changing pH and adding counterions. Grazing incidence X-ray diffraction results indicate an expansion not only of the liquid expanded phase but also an expansion of the lattice of the condensed phase.

Surface Behavior of Boronic Acid-Terminated Silicones.

Silicone polymers, with their high flexibility, lie in a monolayer at the air-water interface as they are compressed until a critical pressure is reached, at which point multilayers are formed. Surface pressure measurements demonstrate that, in contrast, silicones that are end-modified with polar groups take up lower surface areas under compression because the polar groups submerge into the water phase. Boronic acids have the ability to undergo coordination with Lewis bases.

Membrane selectivity and biophysical studies of the antimicrobial peptide GL13K.

GL13K is a short (13 amino acid) antimicrobial peptide derived from the parotid secretory protein. GL13K has been found to exhibit anti-inflammatory and antibacterial activities in physiological salt conditions. We investigated the mechanism of interaction of GL13K, with model membranes comprising 1, 2-dioleoylphosphatidylcholine (DOPC) and 1, 2-dioleoylphosphatidylglycerol (DOPG) using various biophysical and imaging techniques.

New thiol-responsive mono-cleavable block copolymer micelles labeled with single disulfides.

Thiol-responsive symmetric triblock copolymers having single disulfide linkages in the middle blocks (called mono-cleavable block copolymers, ss-ABP(2)) were synthesized by atom transfer radical polymerization in the presence of a disulfide-labeled difunctional Br-initiator. These brush-like triblock copolymers consist of a hydrophobic polyacrylate block having pendent oligo(propylene oxide) and a hydrophilic polymethacrylate block having pendent oligo(ethylene oxide). Gel permeation chromatography and (1)H NMR results confirmed the synthesis of well-defined mono-cleavable block copolymers and revealed that polymerizations were well controlled.

A segmentation method to obtain a complete geometry model of the hearing organ.

We present a method for obtaining a complete geometry model of the fluid chambers of cochlea (scalae) from tomography images. An accurate segmentation of cochlea is problematic due to the low contrast of the inner membranes of scalae. Our method of 3D segmentation is based on dynamic resampling of an original image stack to achieve a perpendicular cross-section of the scalae on all sections.

Compliance profiles derived from a three-dimensional finite-element model of the basilar membrane.

A finite-element analysis is used to explore the impact of elastic material properties, boundary conditions, and geometry, including coiling, on the spatial characteristics of the compliance of the unloaded basilar membrane (BM). It is assumed that the arcuate zone is isotropic and the pectinate zone orthotropic, and that the radial component of the effective Young's modulus in the pectinate zone decreases exponentially with distance from base to apex. The results concur with tonotopic characteristics of compliance and neural data.

Space-filling trialkoxysilane: synthesis and self-assembly into low-density monolayers.

A novel space-filling trialkoxysilane derivative was synthesized using a two-step strategy from commercially available starting materials to produce the precursor for the formation of low-density self-assembled monolayers. Self-assembled monolayers of the synthesized compound were prepared on three different substrates (Si/SiO(2), glass and ITO) and were characterized using contact angle, ellipsometry and sum-frequency generation spectroscopy. Removal of the space-filling protecting group, (2-chlorophenyl)diphenyl methanol, yields a carboxy-terminated surface.

Perfluorophenyl azide immobilization chemistry for single molecule force spectroscopy of the concanavalin A/mannose interaction.

The versatility of perfluorophenyl azide (PFPA) derivatives makes them useful for attaching a wide variety of biomolecules and polymers to surfaces. Herein, a single molecule force spectroscopy (SMFS) study of the concanavalin A/mannose interaction was carried out using PFPA immobilization chemistry. SMFS of the concanavalin A/mannose interaction yielded an average unbinding force of 70-80 pN for loading rates between 8000 and 40,000 pN/s for mannose surfaces on aminated glass, and an unbinding force of 57 ± 20 pN at 6960 pN/s for mannose surfaces on gold-coated glass.

The creation of geometric three-dimensional models of the inner ear based on micro computer tomography data.

The modeling of the mechanical process of hearing requires an accurate geometrical model of the inner ear (cochlea). The purpose of this study was the creation of a 3-D model of the fluid chambers of Guinea pig cochlea, which could serve as a basis for further mechanical modeling. Micro computer tomography used in this study is a noninvasive method to visualize bony structures.

Kinetic analysis of the ozone processing of an unsaturated organic monolayer as a model of an aerosol surface.

It has been suggested that an organic aerosol containing unsaturated organic compounds at the surface would likely be processed by atmospheric ozone. The ozonolysis of oleic acid gives rise to the formation of products having shorter chain lengths than the starting molecule, and are consequently more water soluble than oleic acid. Hence, the exposure of a monolayer of oleic acid to ozone should lead to a decrease in surface activity at the air-water interface.

Lumbar zygapophysial (facet) joint radiofrequency denervation success as a function of pain relief during diagnostic medial branch blocks: a multicenter analysis.

Background Context: The publication of several recent studies showing minimal benefit for radiofrequency (RF) lumbar zygapophysial (l-z) joint denervation have led many investigators to reevaluate selection criteria. One controversial explanation for these findings is that the most commonly used cutoff value for selecting patients for l-z (facet) joint RF denervation, greater than 50% pain relief after diagnostic blocks, is too low and hence responsible for the high failure rate.

Purpose: To compare l-z joint RF denervation success rates between the conventional greater than or equal to 50% pain relief threshold and the more stringently proposed greater than or equal to 80% cutoff for diagnostic medial branch blocks (MBB).

Real-time monitoring of the ozonolysis of unsaturated organic monolayers.

The reaction of ozone with unsaturated organic molecules at the air-water interface of a pendant drop was followed by axisymmetric drop shape analysis (ADSA).

The effects of racemic D,L-methadone and L-methadone in substituted patients--a randomized controlled study.

Aims: To test the hypothesis that switching from L-methadone to D,L-methadone is associated with more frequent withdrawal symptoms and side-effects than switching from D,L-methadone to L-methadone.

Design: Stratified, randomized 2 x 2 crossover study design over a time-period of 8 weeks. At study entry, every second patient was switched from the pre-study substance to the other medication, after 4 weeks all patients were subject to a (re-)switch.

Monolayer behavior of 1,2-dipalmitoylgalloylglycerol, a synthetic lipid with strong cohesive properties.

Monolayers of 1,2-dipalmitoylgalloylglycerol (DPGG) were investigated at the air-water interface. The monolayers exhibit high rigidity which leads to the formation of surface tension gradients in the film. Transfer to solid substrate yields homogeneous Langmuir-Blodgett films with low surface roughness.