Feature enhancement of reverberant speech by distribution matching and non-negative matrix factorization

This paper describes a novel two-stage dereverberation feature enhancement method for noise-robust automatic speech recognition. In the first stage, an estimate of the dereverberated speech is generated by matching the distribution of the observed reverberant speech to that of clean speech, in a decorrelated transformation domain that has a long temporal context in order to address the effects of reverberation. The second stage uses this dereverberated signal as an initial estimate within a non-negative matrix factorization framework, which jointly estimates a sparse representation of the clean speech signal and an estimate of the convolutional distortion. The proposed feature enhancement method, when used in conjunction with automatic speech recognizer back-end processing, is shown to improve the recognition performance compared to three other state-of-the-art techniques

Seroepidemiology of Human Polyomaviruses

In addition to the previously characterized viruses BK and JC, three new human polyomaviruses (Pys) have been recently identified: KIV, WUV, and Merkel Cell Py (MCV). Using an ELISA employing recombinant VP1 capsid proteins, we have determined the seroprevalence of KIV, WUV, and MCV, along with BKV and JCV, and the monkey viruses SV40 and LPV. Soluble VP1 proteins were used to assess crossreactivity between viruses. We found the seroprevalence (+/− 1%) in healthy adult blood donors (1501) was SV40 (9%), BKV (82%), JCV (39%), LPV (15%), KIV (55%), WUV (69%), MCV strain 350 (25%), and MCV strain 339 (42%). Competition assays detected no sero-crossreactivity between the VP1 proteins of LPV or MCV or between WUV and KIV. There was considerable sero-crossreactivity between SV40 and BKV, and to a lesser extent, between SV40 and JCV VP1 proteins. After correcting for crossreactivity, the SV40 seroprevalence was ∼2%. The seroprevalence in children under 21 years of age (n = 721) for all Pys was similar to that of the adult population, suggesting that primary exposure to these viruses likely occurs in childhood

Seroprevalence of 34 Human Papillomavirus Types in the German General Population

The natural history of infections with many human papillomavirus (HPV) types is poorly understood. Here, we describe for the first time the age- and sex-dependent antibody prevalence for 29 cutaneous and five mucosal HPV types from 15 species within five phylogenetic genera (alpha, beta, gamma, mu, nu) in a general population. Sera from 1,797 German adults and children (758 males and 1,039 females) between 1 and 82 years (median 37 years) were analysed for antibodies to the major capsid protein L1 by Luminex-based multiplex serology. The first substantial HPV antibody reactions observed already in children and young adults are those to cutaneous types of the genera nu (HPV 41) and mu (HPV 1, 63). The antibody prevalence to mucosal high-risk types, most prominently HPV 16, was elevated after puberty in women but not in men and peaked between 25 and 34 years. Antibodies to beta and gamma papillomaviruses (PV) were rare in children and increased homogeneously with age, with prevalence peaks at 40 and 60 years in women and 50 and 70 years in men. Antibodies to cutaneous alpha PV showed a heterogeneous age distribution. In summary, these data suggest three major seroprevalence patterns for HPV of phylogenetically distinct genera: antibodies to mu and nu skin PV appear early in life, those to mucosal alpha PV in women after puberty, and antibodies to beta as well as to gamma skin PV accumulate later in life

BID-F1 and BID-F2 Domains of Bartonella henselae Effector Protein BepF Trigger Together with BepC the Formation of Invasome Structures

The gram-negative, zoonotic pathogen Bartonella henselae (Bhe) translocates seven distinct Bartonella effector proteins (Beps) via the VirB/VirD4 type IV secretion system (T4SS) into human cells, thereby interfering with host cell signaling [1], [2]. In particular, the effector protein BepG alone or the combination of effector proteins BepC and BepF trigger massive F-actin rearrangements that lead to the establishment of invasome structures eventually resulting in the internalization of entire Bhe aggregates [2], [3]. In this report, we investigate the molecular function of the effector protein BepF in the eukaryotic host cell. We show that the N-terminal [E/T]PLYAT tyrosine phosphorylation motifs of BepF get phosphorylated upon translocation but do not contribute to invasome-mediated Bhe uptake. In contrast, we found that two of the three BID domains of BepF are capable to trigger invasome formation together with BepC, while a mutation of the WxxxE motif of the BID-F1 domain inhibited its ability to contribute to the formation of invasome structures. Next, we show that BepF function during invasome formation can be replaced by the over-expression of constitutive-active Rho GTPases Rac1 or Cdc42. Finally we demonstrate that BID-F1 and BID-F2 domains promote the formation of filopodia-like extensions in NIH 3T3 and HeLa cells as well as membrane protrusions in HeLa cells, suggesting a role for BepF in Rac1 and Cdc42 activation during the process of invasome formation

Synthesis of Indomorphan Pseudo Natural Product Inhibitors of Glucose Transporters GLUT‐1 and ‐3

Bioactive compound design based on natural product (NP) structure may be limited due to partial coverage of NP‐like chemical space and biological target space. These limitations can be overcome by combining NP‐centered strategies with fragment‐based compound design through combination of NP‐derived fragments to structurally unprecedented “pseudo natural products” (pseudo‐NPs). We describe the design, synthesis and biological evaluation of a collection of indomorphan pseudo‐NPs that combine biosynthetically unrelated indole‐ and morphan‐alkaloid fragments. Biological investigation in a cell‐based screen for modulators of glucose uptake identified the indomorphane derivative Glupin as potent inhibitor of glucose uptake. Glupin selectively targets and upregulates both, glucose transporters GLUT‐1 and GLUT‐3. Glupin suppresses glycolysis, reduces the levels of glucose‐derived metabolites and attenuates the growth of various cancer cell lines. Our findings underscore the importance of dual GLUT‐1 and GLUT‐3 inhibition to efficiently suppress tumor cell growth and the cellular rescue mechanism, which counteracts glucose scarcity

Rapid Internalization of the Oncogenic K+ Channel KV10.1

KV10.1 is a mammalian brain voltage-gated potassium channel whose ectopic expression outside of the brain has been proven relevant for tumor biology. Promotion of cancer cell proliferation by KV10.1 depends largely on ion flow, but some oncogenic properties remain in the absence of ion permeation. Additionally, KV10.1 surface populations are small compared to large intracellular pools. Control of protein turnover within cells is key to both cellular plasticity and homeostasis, and therefore we set out to analyze how endocytic trafficking participates in controlling KV10.1 intracellular distribution and life cycle. To follow plasma membrane KV10.1 selectively, we generated a modified channel of displaying an extracellular affinity tag for surface labeling by α-bungarotoxin. This modification only minimally affected KV10.1 electrophysiological properties. Using a combination of microscopy and biochemistry techniques, we show that KV10.1 is constitutively internalized involving at least two distinct pathways of endocytosis and mainly sorted to lysosomes. This occurs at a relatively fast rate. Simultaneously, recycling seems to contribute to maintain basal KV10.1 surface levels. Brief KV10.1 surface half-life and rapid lysosomal targeting is a relevant factor to be taken into account for potential drug delivery and targeting strategies directed against KV10.1 on tumor cells