Fatal anaphylactic sting reaction in a patient with mastocytosis

We report on a 33-year-old female patient with indolent systemic mastocytosis and urticaria pigmentosa who died of an anaphylactic reaction after a yellow jacket sting. As she had no history of previous anaphylactic sting reaction, there was no testing performed in order to detect hymenoptera venom sensitization. But even if a sensitization had been diagnosed, no venom immunotherapy (VIT) would have been recommended. It is almost certain that VIT would have saved her life and it is most likely that VIT is indicated in some patients with mastocytosis with no history of anaphylactic sting reaction. However, no criteria have been established in order to allow a selection of mastocytosis patients eligible for such a `prophylactic' VIT. Copyright (C) 2008 S. Karger AG, Basel

Writing self-assembled monolayers with Cs: Optimization of atomic nanolithography imaging using self-assembled monolayers on gold substrates

We report the results of a study into the factors controlling the quality of nanolithographic imaging. Self-assembled monolayer (SAM) coverage, subsequent postetch pattern definition, and minimum feature size all depend on the quality of the Au substrate used in material mask atomic nanolithographic experiments. We find that sputtered Au substrates yield much smoother surfaces and a higher density of {111}-oriented grains than evaporated Au surfaces. Phase imaging with an atomic force microscope shows that the quality and percentage coverage of SAM adsorption are much greater for sputtered Au surfaces. Exposure of the self-assembled monolayer to an optically cooled atomic Cs beam traversing a two-dimensional array of submicron material masks mounted a few microns above the self-assembled monolayer surface allowed determination of the minimum average Cs dose (2 Cs atoms per self-assembled monolayer molecule) to write the monolayer. Suitable wet etching, with etch rates of 2.2 nm min-1, results in optimized pattern definition. Utilizing these optimizations, material mask features as small as 230 nm in diameter with a fractional depth gradient of 0.820 nm were realized

CSF SerpinA1 in Creutzfeldt\u2013Jakob disease and frontotemporal lobar degeneration

Objective: SerpinA1 (alpha-1 antitrypsin) is an acute inflammatory protein, which seems to play a role in neurodegeneration and neuroinflammation. In Alzheimer\u2019s disease and synucleinopathies, SerpinA1 is overexpressed in the brain and the cerebrospinal fluid (CSF) showing abnormal patterns of its charge isoforms. To date, no comprehensive studies explored SerpinA1 CSF isoforms in Creutzfeldt\u2013Jakob disease (CJD) and frontotemporal lobar degeneration (FTLD). Methods: Using a capillary isoelectric focusing immunoassay, we analyzed CSF SerpinA1 isoforms in control cases (n = 31) and patients with a definite or probable diagnosis of CJD (n=77) or FTLD (n = 30), belonging to several disease subtypes. Results: The overall SerpinA1 signal was significantly higher than in controls in CJD subtypes linked to abnormal prion protein (PrPSc) type 1, such as sporadic CJD (sCJD) MM(V)1, and in FTLD-TDP. Moreover, CJD linked to PrPSc type 1 and FTLD-TAU groups showed a significant relative increase of acidic and basic isoforms in comparison with controls, thereby forming two distinct SerpinA1 isoform profiles. Interpretation: CJD linked to PrPSc type 1 and FTLD show a differential upregulation and post-translational modifications of CSF SerpinA1. Further studies are needed to clarify whether these findings may reflect a common, albeit disease-specific, pathogenetic mechanism related to neurodegeneration

Advancing atomic nanolithography: cold atomic Cs beam exposure of alkanethiol self-assembled monolayers

We report the results of a study into the quality of functionalized surfaces for nanolithographic imaging. Self-assembled monolayer (SAM) coverage, subsequent post-etch pattern definition and minimum feature size all depend on the quality of the Au substrate used in atomic nanolithographic experiments. We find sputtered Au substrates yield much smoother surfaces and a higher density of {111} oriented grains than evaporated Au surfaces. A detailed study of the self-assembly mechanism using molecular resolution AFM and STM has shown that the monolayer is composed of domains with sizes typically of 5-25 nm, and multiple molecular domains can exist within one Au grain. Exposure of the SAM to an optically-cooled atomic Cs beam traversing a two-dimensional array of submicron material masks ans also standing wave optical masks allowed determination of the minimum average Cs dose (2 Cs atoms per SAM molecule) and the realization of < 50 nm structures. The SAM monolayer contains many non-uniformities such as pin-holes, domain boundaries and monoatomic depressions which are present in the Au surface prior to SAM adsorption. These imperfections limit the use of alkanethiols as a resist in atomic nanolithography experiments. These studies have allowed us to realize an Atom Pencil suitable for deposition of precision quantities of material at the microand nanoscale to an active surface

Onset of dissipation in ballistic atomic wires

Electronic transport at finite voltages in free-standing gold atomic chains of up to 7 atoms in length is studied at low temperatures using a scanning tunneling microscope (STM). The conductance vs voltage curves show that transport in these single-mode ballistic atomic wires is non-dissipative up to a finite voltage threshold of the order of several mV. The onset of dissipation and resistance within the wire corresponds to the excitation of the atomic vibrations by the electrons traversing the wire and is very sensitive to strain.Comment: Revtex4, 4 pages, 3 fig

The atom pencil: serial writing in the sub-micrometre domain

The atom pencil we describe here is a versatile tool that writes arbitrary structures by atomic deposition in a serial lithographic process. This device consists of a transversely laser-cooled and collimated cesium atomic beam that passes through a 4-pole atom-flux concentrator and impinges on to micron- and sub-micron-sized apertures. The aperture translates above a fixed substrate and enables the writing of sharp features with sizes down to 280 nm. We have investigated the writing and clogging properties of an atom pencil tip fabricated from silicon oxide pyramids perforated at the tip apex with a sub-micron aperture

Implementation of a population-based epidemiological rare disease registry: study protocol of the amyotrophic lateral sclerosis (ALS) - registry Swabia

BACKGROUND: The social and medical impact of rare diseases is increasingly recognized. Amyotrophic lateral sclerosis (ALS) is the most prevalent of the motor neuron diseases. It is characterized by rapidly progressive damage to the motor neurons with a survival of 2–5 years for the majority of patients. The objective of this work is to describe the study protocol and the implementation steps of the amyotrophic lateral sclerosis (ALS) registry Swabia, located in the South of Germany. METHODS/DESIGN: The ALS registry Swabia started in October 2010 with both, the retrospective (01.10.2008-30.09.2010) and prospective (from 01.10.2010) collection of ALS cases, in a target population of 8.6 million persons in Southern Germany. In addition, a population based case–control study was implemented based on the registry that also included the collection of various biological materials. Retrospectively, 420 patients (222 men and 198 women) were identified. Prospectively data of ALS patients were collected, of which about 70% agreed to participate in the population-based case–control study. All participants in the case–control study provided also a blood sample. The prospective part of the study is ongoing. DISCUSSION: The ALS registry Swabia has been implemented successfully. In rare diseases such as ALS, the collaboration of registries, the comparison with external samples and biorepositories will facilitate to identify risk factors and to further explore the potential underlying pathophysiological mechanisms

Mechanisms Models and Biomarkers in Amyotrophic Lateral Sclerosis

The last 30 years have seen a major advance in the understanding of the clinical and pathological heterogeneity of amyotrophic lateral sclerosis (ALS), and its overlap with frontotemporal dementia. Multiple, seemingly disparate biochemical pathways converge on a common clinical syndrome characterized by progressive loss of upper and lower motor neurons. Pathogenic themes in ALS include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, altered energy metabolism, and most recently RNA mis-processing. The transgenic rodent, overexpressing mutant superoxide dismutase-1, is now only one of several models of ALS pathogenesis. The nematode, fruit fly and zebrafish all offer fresh insight, and the development of induced pluripotent stem cell-derived motor neurons holds promise for the screening of candidate therapeutics. The lack of useful biomarkers in ALS contributes to diagnostic delay, and the inability to stratify patients by prognosis may be an important factor in the failure of therapeutic trials. Biomarkers sensitive to disease activity might lessen reliance on clinical measures and survival as trial endpoints and reduce study length. Emerging proteomic markers of neuronal loss and glial activity in cerebrospinal fluid, a cortical signature derived from advanced structural and functional MRI, and the development of more sensitive measurements of lower motor neuron physiology are leading a new phase of biomarker-driven therapeutic discovery

Прогнозирование социальной успешности студентов-бойцов стройотрядов с использованием методов Data Mining

Работа посвящена вопросам исследованиям контингента бойцов стройотрядов университета для формирования управленческого резерва с использованием методов Data MiningThe work be devoted to the question of research student who also amember of student brigades for the formation of reserve management with the use of Data Mining technique

TDP-43 loss of function inhibits endosomal trafficking and alters trophic signaling in neurons

Nuclear clearance of TDP-43 into cytoplasmic aggregates is a key driver of neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but the mechanisms are unclear. Here, we show that TDP-43 knockdown specifically reduces the number and motility of RAB11-positive recycling endosomes in dendrites, while TDP-43 overexpression has the opposite effect. This is associated with delayed transferrin recycling in TDP-43-knockdown neurons and decreased 2-transferrin levels in patient CSF. Whole proteome quantification identified the upregulation of the ESCRT component VPS4B upon TDP-43 knockdown in neurons. Luciferase reporter assays and chromatin immunoprecipitation suggest that TDP-43 represses VPS4B transcription. Preventing VPS4B upregulation or expression of its functional antagonist ALIX restores trafficking of recycling endosomes. Proteomic analysis revealed the broad reduction in surface expression of key receptors upon TDP-43 knockdown, including ErbB4, the neuregulin 1 receptor. TDP-43 knockdown delays the surface delivery of ErbB4. ErbB4 overexpression, but not neuregulin 1 stimulation, prevents dendrite loss upon TDP-43 knockdown. Thus, impaired recycling of ErbB4 and other receptors to the cell surface may contribute to TDP-43-induced neurodegeneration by blocking trophic signaling