Amyotrophic Lateral Sclerosis, the Primary Motor Neuron Disease

Amyotrophic lateral sclerosis is a degenerative neurological disease that damages nerve cells in the brain, in particular the neurons that are involved in voluntary muscle movements. Internationally the disorder is also known as Charcot’s disease and motor neuron disease. In the United States, amyotrophic lateral sclerosis is often referred to as Lou Gehrig’s disease, motor neuron disease, and more colloquially ALS. Amyotrophic Lateral Sclerosis is the most prominent of the five motor neuron diseases, distinguishing itself from the others through degeneration of both upper motor neurons (UMN) and lower motor neurons (LMN) respectively. The “Father of neurology” Jean-Marie Charcot founded the disease in 1869 after thorough work and observation in his laboratory. Unfortunately ALS is a rapidly progressive disease in which all voluntary muscle control is eventually lost, with general life expectancy of three to five years after being diagnosed

Novel Advances in Alzheimer\u27s Disease

Alzheimer’s disease, the most common form of dementia in adults, is a progressive degenerative neurological disease that affects memory, cognition, and behavior. Dr. Alois Alzheimer discovered and diagnosed the irreversible disease in 1906 after documenting the famous case of Auguste Deter.1 Since the discovery of the disease, numerous advances have made it possible to not only better understand the causal factors, but also to improve the medical diagnosis and preventative measures that healthcare providers can implement. For the first time since 1984, the National Institute on Aging (NIAA) and the Alzheimer’s Association (AA) proposed and published new diagnostic guideline revisions for Alzheimer’s disease. 3 The complexity of Alzheimer’s makes it difficult to focus on one specific therapeutic target; instead this revision’s aim is to divide the disease into three phases. Furthermore, the NIAA-AA research has documented two types of biomarkers, which can help assist healthcare providers by providing measurable biological changes in patients with Alzheimer’s that can be used to predict cognitive impairment. This research article aims to present the main pathophysiological mechanisms in Alzheimer’s disease, the new diagnostic guideline revisions, and the growing evidence of biochemistry that may cause changes in patients years or even decades before there are manifested clinical symptoms. The momentum is growing with each new research advancement, and the goal to live in a time era with reduced cases of dementia is on the horizon

Novel Advances in Alzheimer\u27s Disease

Alzheimer’s disease, the most common form of dementia in adults, is a progressive degenerative neurological disease that affects memory, cognition, and behavior. Dr. Alois Alzheimer discovered and diagnosed the irreversible disease in 1906 after documenting the famous case of Auguste Deter.1 Since the discovery of the disease, numerous advances have made it possible to not only better understand the causal factors, but also to improve the medical diagnosis and preventative measures that healthcare providers can implement. For the first time since 1984, the National Institute on Aging (NIAA) and the Alzheimer’s Association (AA) proposed and published new diagnostic guideline revisions for Alzheimer’s disease. 3 The complexity of Alzheimer’s makes it difficult to focus on one specific therapeutic target; instead this revision’s aim is to divide the disease into three phases. Furthermore, the NIAA-AA research has documented two types of biomarkers, which can help assist healthcare providers by providing measurable biological changes in patients with Alzheimer’s that can be used to predict cognitive impairment. This research article aims to present the main pathophysiological mechanisms in Alzheimer’s disease, the new diagnostic guideline revisions, and the growing evidence of biochemistry that may cause changes in patients years or even decades before there are manifested clinical symptoms. The momentum is growing with each new research advancement, and the goal to live in a time era with reduced cases of dementia is on the horizon

Simultaneous Kummer congruences and E∞\mathbb{E}_\infty-orientations of KO and tmf

Building on results of M. Ando, M.J. Hopkins and C. Rezk, we show the existence of uncountably many $\mathbb{E}_\infty$-String orientations of real K-theory KO and of topological modular forms tmf, generalizing the $\hat{A}$- (resp. the Witten) genus. Furthermore, the obstruction to lifting an $\mathbb{E}_\infty$-String orientations from KO to tmf is identified with a classical Iwasawa-theoretic condition. The common key to all these results is a precise understanding of the classical Kummer congruences, imposed for all primes simultaneously. This result is of independent arithmetic interest.Comment: final versio

The curvHDR Method for Gating Flow Cytometry Samples

Motivation: High-throughput flow cytometry experiments produce hundreds of large multivariate samples of cellular characteristics. These samples require specialized processing to obtain clinically meaningful measurements. A major component of this processing is a form of cell subsetting known as gating. Manual gating is time-consuming and subjective. Good automatic and semi-automatic gating algorithms are very beneficial to high-throughput flow cytometry. Results: We develop a statistical procedure, named curvHDR, for automatic and semi-automatic gating. The method combines the notions of significant high negative curvature regions and highest density regions and has the ability to adapt well to human-perceived gates. The underlying principles apply to dimension of arbitrary size, although we focus on dimensions up to three. Accompanying software, compatible with contemporary flow cytometry informatics, is developed. Availability: Software for Bioconductor within R is available

Highly polarized alkenes as organocatalysts for the polymerization of lactones and trimethylene carbonate

In this work, the activity of N-heterocyclic olefins (NHOs), a newly emerging class of organopolymerization catalyst, is investigated to affect the metal-free polymerization of lactones and trimethylene carbonate (TMC). A decisive structure−activity relationship is revealed. While catalysts of the simplest type bearing an exocyclic CH2 moiety polymerize L-lactide (L-LA) and δ-valerolactone (δ-VL) in a non-living and non-quantitative manner, the introduction of methyl substituents on the exocyclic carbon radically changes this behavior. 2-Isopropylidene-1,3,4,5-tetramethylimidazoline is found to be highly active for a range of monomers such as L-LA, δ-VL, ε-caprolactone (ε-CL), and TMC, with quantitative conversion occurring within seconds with catalyst loadings of just 0.2 mol %. The high activity of this NHO further enables the ring-opening polymerization (ROP) of the macrolactone ω-pentadecalactone (PDL). However, this broad applicability is offset by a lack of control over the polymerizations, including side reactions as a consequence of its strong basicity. To overcome this, a saturated, imidazolinium-derived analogue was synthesized and subsequently demonstrated to possess a harnessed reactivity which enables it to polymerize both L-LA and TMC in a controlled manner (ĐM < 1.2). NMR spectroscopic and MALDI-ToF MS experiments highlight the differences in polymerization pathways for 2-methylene-1,3,4,5-tetramethylimidazoline, in which the exocyclic carbon is not substituted, in contrast to 2-isopropylidene-1,3,4,5-tetramethylimidazoline, with the former operating via its nucleophilicity and the latter acting as a base with enolizable δ-VL