Miracle-dz/UniFAR-FTUs huggingface dataset:
Assembly of Theiler's virus recombinants used in mapping determinants of neurovirulence

A major determinant of neurovirulence for the GDVII strain of Theiler's virus, a murine picornavirus, was mapped to the P1 capsid protein region. Chimeric viruses were constructed by using sequences from the 5' noncoding and P1 regions of the virulent GDVII strain to replace equivalent regions of the less virulent BeAn strain. Neurovirulence in mice progressively increased as larger regions of BeAn capsid protein-encoding sequences were replaced. The in vitro growth characteristics of the chimeras showed that some chimeras were growth delayed in BHK-21 cells even though the viral constructs exhibited larger plaque sizes, were less temperature sensitive, and were more thermally stable than BeAn. Examination of assembly intermediates revealed an altered pentamer conformation and delayed empty capsid formation for the growth-compromised viruses. For these constructs, their chimeric nature inadvertently resulted in virion assembly defects that complicated finer-scale mapping of the determinants of virulence within the capsid region. These results demonstrate the importance of determining in vitro growth characteristics of chimeras to correctly decipher the significance of their phenotypes. VP1 does not contain a complete determinate for virulence because a chimera with VP1-encoding sequences from GDVII in an otherwise BeAn virus has an attenuated phenotype but is not growth compromised in vitro. The source of sequences, BeAn or GDVII, in the 5' noncoding region had only slight effects on the virulence of recombinant constructs.
Vom Meister zum Magister, von der Erzieherin zur Diplomandin: berufliche Weiterbildung als Schlüssel zum Hochschulstudium in Niedersachsen

Bildung hat Konjunktur! Angesichts dramatischer Entwicklungen auf dem Arbeitsmarkt bzw. im Beschaftigungssystem werden qualifizierte Bildungs- und Ausbildungsabschlusse immer wichtiger, um struktureller oder technologischer Arbeitslosigkeit und Perspektivlosigkeit entgegenzuwirken. Die wachsende Nachfrage nach qualifizierten Bildungsabschlussen und die Forderung nach lebenslangen Bildungsbemuhungen konnen aber nicht allein durch schulische Bildungseinrichtungen befriedigt werden. Diese mussen vielmehr durch Angebote erganzt werden, durch die junge Erwachsene eine realistische Chance erhalten, nach der Regelschulzeit weiterfuhrende Bildungs- und Ausbildungsabschlusse zu erwerben. Dazu zahlen z.B. in Niedersachsen die Zulassungsprufung in das Hochschulstudium und der prufungsfreie Hochschulzugang fur qualifizierte Berufstatige ohne Abitur. In diesem Buch sind die Ergebnisse einer empirischen Untersuchung uber die Studiensituation von Studierenden veroffentlicht, die ihre Studienberechtigung uber einen herausgehobenen beruflichen Weiterbildungsabschluss ohne Abitur fur die niedersachsischen wissenschaftlichen Hochschulen erhalten haben.
Gastric Cancer Patients with High PLK1 Expression and DNA Aneuploidy Correlate with Poor Prognosis

Gastric cancer is the fourth most common cancer worldwide. Although it is important to identify patients at high risk for a poor outcome, factors correlating with prognosis in gastric cancer are largely unknown. Here, we focus on the correlations among expression of Polo-like kinase 1 (PLK1), DNA ploidy, and clinical outcome in gastric cancer patients. Gastric cancer specimens were analyzed from 207 consecutive patients. Patients were classified into two groups according to tumor PLK1 expression and DNA content, and an analysis of their clinical outcomes was carried out. Prognoses of patients with PLK1-high tumors were worse than those of patients with PLK1-low tumors, but the differences were not statistically significant. In cell lines, overexpression of PLK1 induced centrosome amplification and multipolar spindles, potentially leading to DNA aneuploidy. Indeed, high expression of PLK1 was also associated with DNA aneuploidy in clinical gastric cancer specimens. Patients with both high PLK1 expression and DNA aneuploidy had poor recurrence-free survival, whereas PLK1 expression and DNA ploidy status alone were not significantly associated with outcome. Here, we provide clinical evidence that high expression of PLK1 could have detrimental effects in tumors with DNA aneuploidy, which may increase the risk of recurrence in gastric cancer patients.
Complete Genome Analysis of a Novel Intertypic Recombinant Human Adenovirus Causing Epidemic Keratoconjunctivitis in Japan

ABSTRACT For 4 months from September 2008, 102 conjunctival swab specimens were collected for surveillance purposes from patients across Japan suspected of having epidemic keratoconjunctivitis (EKC). Human adenovirus (HAdV) DNA was detected in 61 samples by PCR, though the HAdV type for 6 of the PCR-positive samples could not be determined by phylogenetic analysis using a partial hexon gene sequence. Moreover, for 2 months from January 2009, HAdV strains with identical sequences were isolated from five conjunctival swab samples obtained from EKC patients in five different regions of Japan. For the analyses of the 11 samples mentioned above, we determined the nucleotide sequences of the entire penton base, hexon, and fiber genes and early 3 (E3) region, which are variable regions among HAdV types, and compared them to those of other HAdV species D strains. The nucleotide sequences of loops 1 and 2 in the hexons of all 11 samples showed high degrees of identity with those of the HAdV type 15 (HAdV-15) and HAdV-29 prototype strains. However, the fiber gene and E3 region sequences showed high degrees of identity with those of HAdV-9, and the penton base gene sequence showed a high degree of identity with the penton base gene sequences of HAdV-9 and -26. Moreover, the complete genome sequence of the 2307-S strain, which was isolated by viral culture from 1 of the 11 samples, was determined. The 2307-S strain was a recombinant HAdV between HAdV-9, -15, -26, -29, and/or another HAdV type; however, the recombination sites in the genome were not obvious. We propose that this virus is a novel intertypic recombinant, HAdV-15/29/H9, and may be an etiological agent of EKC.
Three-dimensional digital subtraction angiographic evaluation of aneurysm remnants after clip placement.

OBJECTIVE The aneurysm remnants rate was evaluated via three-dimensional digital subtraction angiography (3D-DSA) in the postoperative evaluation of clipped aneurysms. METHODS Data on surgically clipped aneurysms of anterior circulation obtained via postoperative 3D-DSA from February 2007 to March 2009 were gathered. The results of the postoperative 3D-DSA and of two-dimensional digital subtraction angiography (2D-DSA) for the detection of aneurysm remnants were compared, and an investigation was performed as to why 2D-DSA had missed some aneurysm remnants that were detected in the 3D-DSA. Various surgical factors that revealed aneurysm remnants in the 3D-DSA were also evaluated. RESULTS A total of 39 neck remnants of 202 clipped aneurysms (19.3%) were confirmed in 3D-DSA, and these were classified according to Sindou's classification of aneurysm remnants. Patients with only a neck remnant found in the 3D-DSA represented 17.3% (35/202 aneurysms) of the whole series, and those with a residuum of neck plus sac found in the 3D-DSA represented 1.9% (4/202 aneurysms). The causes of aneurysm remnants were no full visualization (14/39, 35.9%), parent and perforator artery protection (10/39, 25.6%), clip design problems (8/39, 20.5%), and broad-necked aneurysm (7/39, 17.9%). CONCLUSION Patients with </= 2 mm aneurysm remnants showed an increased risk of undetectable aneurysm remnants in the 2D-DSA. The most frequent location of the missed aneurysm in 2D-DSA was the anterior communicating artery. 3D-DSA showed more aneurysm remnants than what is indicated in the existing literature, the 2D-DSA.
Characterization of drCol 15a1b: A Novel Component of the Stem Cell Niche in the Zebrafish Retina

There is a clear need to develop novel tools to help improve our understanding of stem cell biology, and potentially also the utility of stem cells in regenerative medicine. We report the cloning, functional, and bioinformatic characterization of a novel stem cell marker in the zebrafish retina, drCol 15a1b. The expression pattern of drCol 15a1b is restricted to stem cell niches located in the central nervous system, whereas other collagen XVs are associated with muscle and endothelial tissues. Knocking down drCol 15a1b expression causes smaller eyes, ear defects, and brain edema. Microscopic analysis reveals enhanced proliferation in the morphant eye, with many mitotic nuclei located in the central retina, together with a delayed differentiation of the mature retinal cell types. Besides, several markers known to be expressed in the ciliary marginal zone display broader expression areas in morpholino‐injected embryos, suggesting an anomalous diffusion of signaling effectors from the sonic hedgehog and notch pathways. These results indicate that drCol 15a1b is a novel stem cell marker in the central nervous system that has a key role in homing stem cells into specialized niches in the adult organism. Moreover, mutations in the hCol 18a1 gene are responsible for the Knobloch syndrome, which affects brain and retinal structures, suggesting that drCol 15a1b may function similarly to mammalian Col 18a1. Thus, our results shed new light on the signaling pathways that underlie the maintenance of stem cells in the adult organism while helping us to understand the role of extracellular matrix proteins in modulating the signals that determine stem cell differentiation, cell cycle exit and apoptosis. STEM CELLS 2010;28:1399–1411
Effects of Fat Supplementation on Postprandial GIP, GLP-1, Ghrelin and IGFBP-1 Levels: A Pilot Study on Adolescents with Type 1 Diabetes

Aims: To compare the responses of GIP, GLP-1, ghrelin and IGFBP-1 between meals with different fat and energy content in adolescents with type 1 diabetes (T1DM) and to relate them to gastric emptying and glycaemia. Methods: On different days and in a random order, 7 adolescents with T1DM ingested a high- and low-fat meal (fat content: 38 and 2 g, energy content: 640 and 320 kcal, respectively). At normoglycaemia, the same prandial insulin dose was given at both meals and to all subjects. Postprandial blood samples were taken repeatedly over 4 hours. Gastric emptying was estimated by the paracetamol absorption method. Results: The area under the curve (AUC) for GIP0–240 min and for GLP-10–120 min was larger, but smaller for relative ghrelin0–240 min, after the high-fat meal (p = 0.002, 0.030 and 0.043, respectively). IGFBP-1 decreased significantly, but not differently, after the meals. Larger GLP-1 secretion correlated with slower gastric emptying (p = 0.029) and higher fasting ghrelin levels correlated with lower postprandial glycaemia (p = 0.007). Conclusion: In adolescents with T1DM, the postprandial responses of GIP, GLP-1 and ghrelin, but not that of IGFBP-1, depend more on meal size than on insulin.
How the connectivity structure of neuronal networks influences responses to oscillatory stimuli

Propagation of oscillatory signals through the cortex and coherence is shaped by the connectivity structure of neuronal circuits. This study systematically investigates the network and stimulus properties that shape network responses. The results show how input to a cortical column model of the primary visual cortex excites dynamical modes determined by the laminar pattern. Stimulating the inhibitory neurons in the upper layer reproduces experimentally observed resonances at gamma frequency whose origin can be traced back to two anatomical sub-circuits. We develop this result systematically: Initially, we highlight the effect of stimulus amplitude and filter properties of the neurons on their response to oscillatory stimuli. Subsequently, we analyze the amplification of oscillatory stimuli by the effective network structure. We demonstrate that the amplification of stimuli, as well as their visibility in different populations, can be explained by specific network patterns. Inspired by experimental results we ask whether the anatomical origin of oscillations can be inferred by applying oscillatory stimuli. We find that different network motifs can generate similar responses to oscillatory input, showing that resonances in the network response cannot, straightforwardly, be assigned to the motifs they emerge from. Applying the analysis to a spiking model of a cortical column, we characterize how the dynamic mode structure, which is induced by the laminar connectivity, processes external input. In particular, we show that a stimulus applied to specific populations typically elicits responses of several interacting modes. The resulting network response is therefore composed of a multitude of contributions and can therefore neither be assigned to a single mode nor do the observed resonances necessarily coincide with the intrinsic resonances of the circuit.
Marine bacterial organisation around point-like sources of amino acids.

Abstract To better understand the trigger for and use of motility in marine bacterial chemotaxis, specific (amino acids) chemical stimuli were used to test the effect on bacterial speed and reorientation. An assay system was developed to analyse bacterial behavioural responses to point-like nutrient sources (beads 10-40 mum). The marine bacteria Pseudoalteromonas haloplanktis, Shewanella putrefaciens, Deleya marina, the enteric bacterium Escherichia coli and an enriched assemblage of marine bacteria were used in the assay. E. coli responded to the amino acids (e.g. serine, leucine) in this assay in a manner similar to the classical capillary plating method, and accumulated near the attractants using biased random walks and maximum speeds of less than 30 mum s(-1). The marine bacteria travelled more than 100 mum s(-1) and reversed direction instead of randomly tumbling to reorientate. Marine bacteria also showed different chemotactic responses. The enriched marine community and P. haloplanktis were repelled by serine while leucine was an attractant for all three marine isolates. More importantly marine bacteria formed band specific distances (>20 mum) away from individual beads. The bands were composed of free-swimming bacteria rather than bacteria attached to the beads or chamber surfaces. The bands' formation time (25-180 s) and width (5-20 mum) varied depending on the bacterial strains and attractant. This variation in chemotactic responses by the marine isolates may reflect adaptations to specific ecological niches of bacterioplankton in the ocean. However, band forming ability by marine bacteria has still only been reported in experimental studies, nutrient coupling between nutrient sources and bands of chemotactic marine bacteria have yet to be detected in the natural environment. The fragility of the bands, a clear association between free-swimming bacteria and nutrient, indicates the difficulty and potentially sets limits for finding microzones of bacteria around particles in the open ocean.
Evaluation of Implicit Feedback in Coordinated Multipoint Transmission beyond LTE-Advanced

Coordinated Multipoint (CoMP) was adapted as a key technique to improve the coverage of high data rates and the cell-edge user experience in beyond LTE- Advanced systems. CoMP simultaneously supports multiple Transmission Points (TPs) to serve mobile devices in the high interference areas, which occur between cells. In theory it can provide significant gains in the order of high double-digit percentages for cell-edge user throughput while increasing overall network efficiency. The aim of this paper is to get an insight of the system performance and configuration flexibility of CoMP transmission in beyond LTE-Advanced systems. Different channel state information feedback concepts for CoMP networks have been analyzed theoretically and verified through Monte Carlo simulations. Complexity and implementation issues have been addressed as well. The results have shown that downlink CoMP schemes are very effective in improving the overall system performance. Furthermore, the investigation has shown that different feedback approaches bring different performance gains but also different complexity and implementation challenges. Finally, the most effective feedback approach and system configuration for CoMP scenarios investigated in this study is suggested.
Synchronization of wave-pipelined circuits

We investigate the synchronization schemes of wave-pipelined circuits. Previous analysis of valid clocking in wave-pipelined circuits is discussed and an intentional clock skew is introduced between the input and output registers as a function of the timing parameters of the wave-pipelined circuit, registers, and clock period. It is shown that, a clock skew value can be determined from the circuit information to achieve expected valid clock speed within the range bounded only by the basic timing constraints of wave pipelining. This is illustrated by applying the clock skew models to a 16-bit wave-pipelined adder designed using Wave-pipelined Transmission-Gate Logic (WTGL) technique. The results confirm the timing analysis. General clocking strategies of wave-pipelined systems are also discussed. <<ETX>>
Multiple Mechanisms Downstream of TLR-4 Stimulation Allow Expression of NKG2D Ligands To Facilitate Macrophage/NK Cell Crosstalk

The activating receptor NKG2D recognizes proteins that are not normally expressed at the surface of most cells but are expressed during a cellular “stress” response (e.g., upon induction of the DNA damage pathway). This establishes recognition of “induced self” as an important strategy for surveillance of infections or tumor transformation. However, NKG2D ligands can also be induced on human macrophages by TLR stimulation, which has been far less studied. In this paper, we clarify that LPS, which ligates TLR-4, preferentially upregulated MICA and not MICB; CL097, which ligates TLR-7/8, upregulated both MICA and MICB; and polyinosinic-polycytidylic acid, which ligates TLR-3, upregulated neither. To probe how LPS stimulation triggers MICA expression, we determined that the stability of MICA mRNA was much longer than that of MICB mRNA, but neither was changed by LPS stimulation. This finding suggests that increased levels of MICA mRNA following LPS stimulation resulted from increased transcription. However, it was not sufficient for surface protein expression, which was controlled posttranscriptionally via a separate pathway involving the ataxia telangiectasia mutated/ataxia telangiectasia and Rad3 related kinases. Moreover, LPS stimulation decreased expression of microRNAs (miRNA)—miR-17-5, miR-20a, and miR-93—which target MICA, implicating a novel role for miRNAs in NKG2D ligand expression. Thus, TLR stimulation allows expression of NKG2D ligands through multiple pathways, including downmodulation of specific miRNAs.
The Influence of MHC Class II on B Cell Defects Induced by Invariant Chain/CD74 N-Terminal Fragments

The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a−/− B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1. To gain insight into CD74 determinants and the role of MHCII, we compared B cells from CatS−/−, SPPL2a−/−, and SPPL2a-MHCII double-deficient mice. We assessed differentiation of B cells in bone marrow and spleen and analyzed their endosomal morphology, BCR expression, and signal transduction. We demonstrate that MHCII is dispensable for the B cell phenotype of SPPL2a−/− mice, further supporting a CD74-intrinsic effect. Despite significant vacuolization of endosomal compartments similar to SPPL2a−/− B cells, CatS−/− traditional stage 1 B cells show unimpaired degradation of endocytic cargo, have intact BCR signaling, and do not exhibit any relevant defects in maturation. This could indicate that CD74 NTF–induced structural changes of endosomes are not directly involved in these processes. We further found that the block of CD74 degradation in CatS−/− B cells is incomplete, so that NTF levels are significantly lower than in SPPL2a−/− B cells. This suggests a dose dependency and threshold for the CD74 NTF–associated impairment of B cell signaling and maturation. In addition, different functional properties of the longer, MHCII-bound CD74 NTF could contribute to the milder phenotype of CatS−/− B cells.
Guidelines for clinical use of CBCT: a review.

OBJECTIVES To identify guidelines on the clinical use of CBCT in dental and maxillofacial radiology, in particular selection criteria, to consider how they were produced, to appraise their quality objectively and to compare their recommendations. METHODS A literature search using MEDLINE (Ovid(®)) was undertaken prospectively from 1 January 2000 to identify published material classifiable as "guidelines" pertaining to the use of CBCT in dentistry. This was supplemented by searches on websites, an internet search engine, hand searching of theses and by information from personal contacts. Quality assessment of publications was performed using the AGREE II instrument. Publications were examined for areas of agreement and disagreement. RESULTS 26 publications were identified, 11 of which were specifically written to give guidelines on the clinical use of CBCT and contained sections on selection criteria. The remainder were a heterogeneous mixture of publications that included guidelines relating to CBCT. Two had used a formal evidence-based approach for guideline development and two used consensus methods. The quality of publications was frequently low as assessed using AGREE II, with many lacking evidence of adequate methodology. There was broad agreement between publications on clinical use, apart from treatment planning, in implant dentistry. CONCLUSIONS Reporting of guideline development is often poorly presented. Guideline development panels should aim to perform and report their work using the AGREE II instrument as a template to raise standards and avoid the risk of suspicions of bias.