Martin Luther University of Halle-Wittenberg

About: Martin Luther University of Halle-Wittenberg is a education organization based out in Halle, Germany. It is known for research contribution in the topics: Population & Liquid crystal. The organization has 20232 authors who have published 38773 publications receiving 965004 citations. The organization is also known as: MLU & University of Wittenberg.

DENCLUE 2.0: fast clustering based on kernel density estimation

Abstract: The Denclue algorithm employs a cluster model based on kernel density estimation A cluster is defined by a local maximum of the estimated density function Data points are assigned to clusters by hill climbing, ie points going to the same local maximum are put into the same cluster A disadvantage of Denclue 10 is, that the used hill climbing may make unnecessary small steps in the beginning and never converges exactly to the maximum, it just comes close We introduce a new hill climbing procedure for Gaussian kernels, which adjusts the step size automatically at no extra costs We prove that the procedure converges exactly towards a local maximum by reducing it to a special case of the expectation maximization algorithm We show experimentally that the new procedure needs much less iterations and can be accelerated by sampling based methods with sacrificing only a small amount of accuracy

Nanophase separation and hindered glass transition in side-chain polymers

Abstract: Nanophase separation on length scales of 1–5 nanometres has been reported previously for small-molecule liquids1, metallic glasses and also for several semicrystalline, liquid-crystalline2,3 and amorphous4 polymers. Here we show that nanophase separation of incompatible main and side-chain parts is a general phenomenon in amorphous side-chain polymers with long alkyl groups. We conclude from X-ray scattering and relaxation spectroscopy data for higher poly(n-alkyl acrylates) (PnAA) and poly(n-alkyl methacrylates) (PnAMA) that alkyl groups of different monomeric units aggregate in the melt and form self-assembled alkyl nanodomains with a typical size of 0.5–2 nm. A comparison with data for other polymer series having alkyl groups reveals that important structural and dynamic aspects are main-chain independent. A polyethylene-like glass transition within the alkyl nanodomains is observed and discussed in the context of a hindered glass transition in self-assembled confinements. This is an interesting link between central questions in glass-transition research and structural aspects in nanophase-separated materials.

Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial.

Abstract: Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid α-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers’ maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers’ test, the CK levels and the 6-min walk test (341 ± 149.49 m, median 342.25 m at baseline; 393 ± 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.

A novel Alzheimer disease locus located near the gene encoding tau protein

Abstract: APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.