Browsing by Author "Schmidt, P."

General pulse sequence elements that achieve sensitivity-enhanced coherence transfer from a heteronucleus to protons of arbitrary multiplicity are introduced. The building blocks are derived from the sensitivity-enhancement scheme introduced by Cavanagh et al. ((1991) J Magn. Reson., 91, 429-436), which was used in conjunction with gradient coherence selection by Kay et al. ((1992) J. Am. Chem. Soc., 114, 10663-10665), as well as from a multiple-pulse sequence effecting a heteronuclear planar coupling Hamiltonian. The building blocks are incorporated into heteronuclear correlation experiments, in conjunction with coherence selection by the formation of a heteronuclear gradient echo. This allows for efficient water suppression without the need for water presaturation. The methods are demonstrated in HSQC-type experiments on a sample of a decapeptide in H2O. The novel pulse sequence elements can be incorporated into multidimensional experiments.

Lysosomal cysteine proteinases of the papain family are involved in lysosomal bulk proteolysis, major histocompatibility complex class II mediated antigen presentation, prohormone processing, and extracellular matrix remodeling. Cathepsin L (CTSL) is a ubiquitously expressed major representative of the papain-like family of cysteine proteinases. To investigate CTSL in vivo functions, the gene was inactivated by gene targeting in embryonic stem cells. CTSL-deficient mice develop periodic hair loss and epidermal hyperplasia, acanthosis, and hyperkeratosis. The hair loss is due to alterations of hair follicle morphogenesis and cycling, dilatation of hair follicle canals, and disturbed club hair formation. Hyperproliferation of hair follicle epithelial cells and basal epidermal keratinocytes-both of ectodermal origin-are the primary characteristics underlying the mutant phenotype. Pathological inflammatory responses have been excluded as a putative cause of the skin and hair disorder. The phenotype of CTSL-deficient mice is reminiscent of the spontaneous mouse mutant furless (fs). Analyses of the cfsl gene of fs mice revealed a G149R mutation inactivating the proteinase activity. CTSL is the first lysosomal proteinase shown to be essential for epidermal homeostasis id regular hair follicle morphogenesis and cycling.

After the successful commissioning of the radioactive beam experiment at ISOLDE (REX-ISOLDE) - an accelerator for exotic nuclei produced by ISOLDE - in 2002 and the promotion to a CERN user facility in 2003, first physics experiments using these beams were performed. Initial experiments focused on the region of deformation in the vicinity of the neutron-rich Na and Mg isotopes. Preliminary results on the neutron-rich Na and Mg isotopes show the high potential and physics opportunities offered by the exotic isotope accelerator REX in conjunction with the modern Germanium gamma spectrometer MINIBALL.

In parlamentarischen Demokratien sind Wahlen für die Bürger die zentrale Möglichkeit, sich an politischen Entscheidungsprozessen zu beteiligen. Gleichzeitig legitimieren allein Wahlen die politische Macht von Regierung und Politikern. Betrachtet man die Wahlbeteiligung bei Bundestagswahlen, so stieg die Beteiligung von 78,5% bei der ersten Bundestagswahl 1949 rasch auf Werte zwischen 86,0% (1953) und 91,1% (1972) an. Ab Mitte der achtziger Jahren ging die Wahlbeteiligung allerdings deutlich zurück. Bei der Bundestagswahl 1987 betrug die Wahlbeteiligung nur 82,3%, bei der Bundestagswahl 1990 in den alten Ländern 78,6% und in den neuen Ländern 74,5% (Ritter und Niehuss 1991: 100–104). In den letzten Jahren ist auf der Bundesebene wieder ein leichter Anstieg der Wahlbeteiligung zu beobachten. Mit Werten von 79,1% bei der Bundestagswahl 1994 und 82,2% bei der Bundestagswahl 1998 liegt sie allerdings immer noch weit unter dem früheren Niveau. Ein Rückgang der Wahlbeteiligung ist auch auf der Ebene der Landes- und Kommunalparlamente zu verzeichnen, die von vornherein geringere Beteiligungsraten aufwiesen.

Objectives: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. Methods: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). Results: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be >= 2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. Conclusions: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report. (C) 2013 Elsevier B.V. All rights reserved.

We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient γ spectrometer MINIBALL. Using Mg-30 ions accelerated to an energy of 2.25 MeV/u together with a thin Ni-nat target, Coulomb excitation of the first excited 2(+) states of the projectile and target nuclei well below the Coulomb barrier was observed. From the measured relative deexcitation γ-ray yields the B(E2;0(gs)(+)→ 2(1)(+)) value of Mg-30 was determined to be 241(31)e(2) fm(4). Our result is lower than values obtained at projectile fragmentation facilities using the intermediate-energy Coulomb excitation method, and confirms the theoretical conjecture that the neutron-rich magnesium isotope Mg-30 resides outside the "island of inversion."