The spatial patterns of plaques and tangles in Alzheimer's disease do not support the 'cascade hypothesis'

In Alzheimer's disease (AD), the 'Cascade hypothesis' proposes that the formation of paired helical filaments (PHF) may be casually linked to the deposition of beta/A4 protein. Hence, there should be a close spatial relationship between senile plaques and cellular neurofibrillary tangles in a local region of the brain. In tissue from 6 AD patients, plaques and tangles occurred in clusters and individual clusters were often regularly spaced along the cortical strip. However, the clusters of plaques and tangles were in phase in only 4/32 cortical tissues examined. Hence, the data were not consistent with the 'Cascade hypothesis' that beta/A4 and PHF are directly linked in AD.

Q-switched induced gain switching of a twotransition cascade laser

A gain-switched laser transition, of a two-laser-transition cascade laser, that is driven by the adjacent laser transition which is Q-switched is demonstrated using a Ho3+ -doped fluoride fiber laser. Q-switching the 5|6 ? 5|7 transition at 3.002 µm produces stable gain-switched pulses from the 5|7 ? 5|8 transition at 2.074 µm; however, Q-switching the 5|7 ? 5|8 transition produced multiple gain switched pulses from the 5|6 ? 5|7 transition. The gain-switched pulses were measured to be of a similar duration to the Q-switched pulses suggesting that much shorter pulses of closer duration could be generated at pump power higher levels.

Dual wavelength Q-switched cascade laser

A diode-cladding-pumped dual wavelength Q-switched Ho3+ -doped fluoride cascade fiber laser operating in the mid-infrared is demonstrated. Stable pulse trains from the 5|6 -> 5|7 and 5|7 -> 5|8 laser transitions were produced, and the µs-level time delay between the pulses from each transition was dependent on the pump power. At maximum pump power and at an acousto-optic modulator repetition rate of 25 kHz, the 5|8 -> 5|7 transition pulse operated at 3.005 µm, a pulse energy of 29 µJ, and a pulse width of 380 ns; the 5|7 -> 5|8 transition pulse correspondingly produced 7 µJ pulse energy and 260 ns pulse width at 2.074 µm. To the best of our knowledge, this is the first demonstration of a Q-switched fiber laser operating beyond 3 µm.

Tuned cascade laser

Tuning of a diode-cladding-pumped cascade Ho3+ -doped fluoride fiber laser is demonstrated using a single plane ruled diffraction grating. At the maximum available pump power, a tuning range 2955-3021 nm, an output power of >500 mW, and a bandwidth of <1nm was achieved for tuning across the 5|6 -> 5|7 transition. In a separate experiment, the  5|7 -> 5|8 laser transition was tuned from 2064 to 2082 nm (with a bandwidth of <0.5 nm) which simultaneously shortened the average emission wavelen 5|6 -> 5|7 length of the free-running  laser transition of the cascade from 2.959 to 2.954 µm. This demonstration represents the first fiber laser that can tune beyond 3 µm.

3190-3275 nm tuneable, room temperature, external cavity InAs/AlSb Quantum Cascade Laser

We demonstrated a room temperature, tuneable, external cavity Quantum Cascade Laser for the use in compact spectroscopic gas sensing system. Wavelength tuning of 85 nm between 3190 nm and 3275 nm was achieved at room temperature.

InAs/AlSb widely tunable external cavity quantum cascade laser around 3.2 μm

Room temperature, tunable, external-cavity short-wavelength InAs/AlSb quantum cascade laser (QCL) is reported. Wavelength tuning of 85 nm for the spectral range between 3190 nm and 3275 nm has been achieved by rotating the diffraction grating forming the external cavity. To suppress lasing inside the QCL cavity, its ridge was tilted by 7° at the external cavity end. The optimal tilting angle of the laser ridge was chosen by careful consideration of the return losses of the TM-polarized waveguide mode from the diffraction grating in a quasi-Littrow configuration and the Fabry-Pérot feedback from the tilted laser facet. No antireflection coating was used. © 2013 American Institute of Physics.

A critical analysis of the 'amyloid cascade hypothesis'

The 'amyloid cascade hypothesis' (ACH) is the most influential model of the pathogenesis of Alzheimer's disease (AD). The hypothesis proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD, leading to the formation of extracellular senile plaques (SP), tau-immunoreactive neurofibrillary tangles (NFT), neuronal loss, and ultimately, clinical dementia. Ever since the formulation of the ACH, however, there have been questions regarding whether it completely describes AD pathogenesis. This review critically examines various aspects of the ACH including its origin and development, the role of amyloid precursor protein (APP), whether SP and NFT are related to the development of clinical dementia, whether Aβ and tau are 'reactive' proteins, and whether there is a pathogenic relationship between SP and NFT. The results of transgenic experiments and treatments for AD designed on the basis of the ACH are also reviewed. It was concluded: (1) Aβ and tau could be the products rather than the cause of neuro-degeneration in AD, (2) it is doubtful whether there is a direct causal link between Aβ and tau, and (3) SP and NFT may not be directly related to the development of dementia, (4) transgenic models involving APP alone do not completely replicate AD pathology, and (5) treatments based on the ACH have been unsuccessful. Hence, a modification of the ACH is proposed which may provide a more complete explanation of the pathogenesis of AD.

Nucleoside diphosphate kinase--a component of the [Na+1]- and [Cl-]-sensitive phosphorylation cascade in human and murine airway epithelium

We have shown that proteins within apically enriched fractions of human nasal respiratory epithelium vary their phosphohistidine content with ambient [Cl-] and other anion concentrations. This membrane-delimited phosphorylation cascade includes a multifunctional protein histidine kinase - nucleoside diphosphate kinase (NDPK). NDPK is itself a cascade component in both human and ovine airway, the self-phosphorylation of which is inhibited selectively by [Na+] in the presence of ATP (but not GTP). These findings led us to propose the existence of a dual anion-/cation-controlled phosphorylation-based "sensor" bound to the apical membrane. The present study showed that this cascade uses ATP to phosphorylate a group of proteins above 45 kDa (p45-group, identities unknown). Additionally, the Cl- dependence of ATP (but not GTP) phosphorylation is conditional on phosphatase activity and that interactions exist between the ATP- and GTP-phosphorylated components of the cascade under Cl--free conditions. As a prelude to studies in cystic fibrosis (CF) mice, we showed in the present study that NDPK is present and functionally active in normal murine airway. Since NDPK is essential for UTP synthesis and regulates fetal gut development, G proteins, K+channels, neutrophil-mediated inflammation and pancreatic secretion, the presence of ion-regulated NDPK protein in mouse airway epithelium might aid understanding of the pathogenesis of CF.

Speculating About Mountains

∗Partially supported by Grant MM 409/94 of the Mininstry of Education, Science and Technology, Bulgaria. ∗∗Partially supported by Grants MM 521/95, MM 442/94 of the Mininstry of Education, Science and Technology, Bulgaria.

The Cascade Orthogonal Neural Network

In the paper new non-conventional growing neural network is proposed. It coincides with the Cascade- Correlation Learning Architecture structurally, but uses ortho-neurons as basic structure units, which can be adjusted using linear tuning procedures. As compared with conventional approximating neural networks proposed approach allows significantly to reduce time required for weight coefficients adjustment and the training dataset size.

The Cascade Neo-Fuzzy Architecture and its Online Learning Algorithm

In the paper learning algorithm for adjusting weight coefficients of the Cascade Neo-Fuzzy Neural Network (CNFNN) in sequential mode is introduced. Concerned architecture has the similar structure with the Cascade-Correlation Learning Architecture proposed by S.E. Fahlman and C. Lebiere, but differs from it in type of artificial neurons. CNFNN consists of neo-fuzzy neurons, which can be adjusted using high-speed linear learning procedures. Proposed CNFNN is characterized by high learning rate, low size of learning sample and its operations can be described by fuzzy linguistic “if-then” rules providing “transparency” of received results, as compared with conventional neural networks. Using of online learning algorithm allows to process input data sequentially in real time mode.

The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility

The interplay between long-term potentiation and long-term depression (LTD) is thought to be involved in learning and memory formation. One form of LTD expressed in the hippocampus is initiated by the activation of the group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to be critical for acquisition of new memories and for reversal learning, processes that are thought to be crucial for cognitive flexibility. Here we provide evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal spine morphology, synaptic transmission and plasticity. Furthermore, mGluR-LTD is impaired in the hippocampus of MK2/3 double knockout (DKO) mice, an observation that is mirrored by deficits in endocytosis of GluA1 subunits. Consistent with compromised mGluR-LTD, MK2/3 DKO mice have distinctive deficits in hippocampal-dependent spatial reversal learning. These novel findings demonstrate that the MK2/3 cascade plays a strategic role in controlling synaptic plasticity and cognition. © 2014 Macmillan Publishers Limited. All rights reserved.

Making mole-hills out of mountains:Peer Mentoring in Engineering education - A case-study

Based on the emergent findings of a pilot study which examined the issues around introducing Peer Mentoring into an Engineering School, this paper, which is very much a 'work in progress', describes and discusses results from the first year of what will be a three year exploratory study. Focusing on three distinctive concepts integral to the student experience, Relationships, Variety and Synergy, the study follows an Action Research Design in that it aims to find a realistic and workable solution to issues of attrition within the Engineering School in which the Project and Study are set. Starting with the research question "Does Peer Mentoring improve engineering students' transition into university?"', the Pilot Project and Study will run for three years, each year building on the lessons of the previous year.

Kelvin-wave cascade in the vortex filament model

The small-scale energy-transfer mechanism in zero-temperature superfluid turbulence of helium-4 is still a widely debated topic. Currently, the main hypothesis is that weakly nonlinear interacting Kelvin waves (KWs) transfer energy to sufficiently small scales such that energy is dissipated as heat via phonon excitations. Theoretically, there are at least two proposed theories for Kelvin-wave interactions. We perform the most comprehensive numerical simulation of weakly nonlinear interacting KWs to date and show, using a specially designed numerical algorithm incorporating the full Biot-Savart equation, that our results are consistent with the nonlocal six-wave KW interactions as proposed by L'vov and Nazarenko.

Oribatid assemblies of tropical high mountains on some points of the “Gondwana-Bridge” – a case study

This work is the first part of a series of studies, which introduces the methodological possibilities of coenological and zoogeographical indication and – following the climate, vegetation and elevation zones – the pattern-describing analysis of the main Oribatid sinusia of the world explored till our days.This current work is a case-study, which displays the comparison of 9 examination sites from 3 different geographical locations. On each location, three vegetation types have been examined: a plain rain-forest, a mossforest and a mountainous paramo. Analyses are based on the hitherto non-published genus-level database and coenological tables of the deceased János Balogh professor. Occurrence of 18 genera is going to be published as new data for the given zoogeographical region.