julilili42/papers huggingface dataset:
When do folds unfold during progressive shear?
2013-03-19

Folded layers in rocks can be stretched again, potentially unfolding the folds back to straight layers. Little is known, however, about how to recognize partly or even entirely unfolded layers. When folded layers can unfold, what determines their mechanical behavior, and how can we recognize them in the field? In order to address these questions, we present a series of numerical simulations of the stretching of previously folded single layers and multilayers in simple shear. Layers do not completely unfold when they undergo softening before or during the stretching process, or when adjacent competent layers prevent them from unfolding. Intrafolial folds and cusp-like folds adjacent to straight layers as well as variations in fold amplitudes and limb lengths of irregular folds are indicative of stretching of a fold train.
Macaque Monkeys Perceive the Flash Lag Illusion
2013-03-19

Transmission of neural signals in the brain takes time due to the slow biological mechanisms that mediate it. During such delays, the position of moving objects can change substantially. The brain could use statistical regularities in the natural world to compensate neural delays and represent moving stimuli closer to real time. This possibility has been explored in the context of the flash lag illusion, where a briefly flashed stimulus in alignment with a moving one appears to lag behind the moving stimulus. Despite numerous psychophysical studies, the neural mechanisms underlying the flash lag illusion remain poorly understood, partly because it has never been studied electrophysiologically in behaving animals. Macaques are a prime model for such studies, but it is unknown if they perceive the illusion. By training monkeys to report their percepts unbiased by reward, we show that they indeed perceive the illusion qualitatively similar to humans. Importantly, the magnitude of the illusion is smaller in monkeys than in humans, but it increases linearly with the speed of the moving stimulus in both species. These results provide further evidence for the similarity of sensory information processing in macaques and humans and pave the way for detailed neurophysiological investigations of the flash lag illusion in behaving macaques.
Postmicrosaccadic Enhancement of Slow Eye Movements
2013-03-20

Active sensation poses unique challenges to sensory systems because moving the sensor necessarily alters the input sensory stream. Sensory input quality is additionally compromised if the sensor moves rapidly, as during rapid eye movements, making the period immediately after the movement critical for recovering reliable sensation. Here, we studied this immediate postmovement interval for the case of microsaccades during fixation, which rapidly jitter the “sensor” exactly when it is being voluntarily stabilized to maintain clear vision. We characterized retinal-image slip in monkeys immediately after microsaccades by analyzing postmovement ocular drifts. We observed enhanced ocular drifts by up to ∼28% relative to premicrosaccade levels, and for up to ∼50 ms after movement end. Moreover, we used a technique to trigger full-field image motion contingent on real-time microsaccade detection, and we used the initial ocular following response to this motion as a proxy for changes in early visual motion processing caused by microsaccades. When the full-field image motion started during microsaccades, ocular following was strongly suppressed, consistent with detrimental retinal effects of the movements. However, when the motion started after microsaccades, there was up to ∼73% increase in ocular following speed, suggesting an enhanced motion sensitivity. These results suggest that the interface between even the smallest possible saccades and “fixation” includes a period of faster than usual image slip, as well as an enhanced responsiveness to image motion, and that both of these phenomena need to be considered when interpreting the pervasive neural and perceptual modulations frequently observed around the time of microsaccades.
Working memory‐related brain activity is associated with outcome of lifestyle intervention
2013-03-20

Objective Lifestyle interventions including reduction of caloric intake are still the most pursued option to treat obesity. However, their outcome in terms of weight loss strongly differs between participants. In our study, we hypothesized that initial differences in brain activation in a food specific memory task are associated with weight change during a lifestyle intervention. Design and Methods Magnetic brain activity was recorded during a one‐back visual memory task with food and nonfood pictures in 33 overweight and obese subjects before they underwent a lifestyle intervention. The intervention lasted 6 months and aimed for a reduction in daily caloric intake by 400 kcal. Body mass index (BMI) was determined before and after the intervention. Results Differences between outer tertiles representing people who increased their BMI by 1.4% ± 1.1% (non‐responders) and who reduced their BMI by −6.9% ± 2.6% (responders) are reported. Neuronal activity was related to BMI change in sensor and source space. Non‐responders showed higher activation in right inferior frontal and left occipital visual areas, whereas responders showed increased activation in right temporal areas including hippocampus and fusiform gyrus. Conclusions Differences in the cerebral response during a food specific memory task indicate an altered cognitive control over food intake. These differences might determine the ability to eat less and successfully lose weight.
A natural tapasin isoform lacking exon 3 modifies peptide loading complex function
2013-03-20

To assure efficient MHC class I (MHC‐I) peptide loading, the peptide loading complex (PLC) recruits the peptide‐receptive form of MHC‐I, and in this process, tapasin (tpn) connects MHC‐I with the peptide transporter TAP and forms a stable disulfide bond with ERp57. Here, we describe an alternatively spliced tpn transcript lacking exon 3, observed in cells infected with human cytomegalovirus. Recognition of exon 3 was regulated via G‐runs, suggesting that members of the hnRNP (heterogeneous nuclear ribonucleoprotein)‐family regulate expression of the ΔExon3 variant of tpn. Exon 3 includes Cys‐95, which is responsible for the disulfide bond formation with ERp57 and, consequently, interaction of the ΔExon3 variant with ERp57 was strongly impaired. Although the ΔExon3 variant specifically stabilized TAP expression but not MHC‐I in tpn‐deficient cells, in tpn‐proficient cells, the ΔExon3 tpn reduced cell surface expression of the tpn‐dependent HLA‐B*44:02 allele; the stability of the tpn‐independent HLA‐B*44:05 was not affected. Most importantly, detailed analysis of the PLC revealed a simultaneous binding of the ΔExon3 variant and tpn to TAP, suggesting modification of PLC functions. Indeed, an altered MHC‐I ligandome was observed in HeLa cells overexpressing the ΔExon3 variant, highlighting the potential of the alternatively spliced tpn variant to impact CD8 + T‐cell responses.
IRAK4 turns IL‐10+ phospho‐FOXO+ monocytes into pro‐inflammatory cells by suppression of protein kinase B
2013-03-20

IRAK4, a serine/threonine kinase is a central adaptor protein in TLR signaling. To better understand the clinical significance of IRAK4 deficiency we examined the impact of IRAK4 on bacterial recognition in human monocytes. We show that IRAK4 knockdown modulates monocyte‐derived cytokine secretion in response to Staphylococcus aureus and Streptococcus pneumoniae , resulting in decreased IL‐12 and elevated IL‐10 production, a finding also reproducible with ligands for TLR2 and TLR4. In contrast, silencing of MyD88 leads to a complete loss of cytokine secretion, indicating that IRAK4 acts as a differential regulator of bacteria/TLR‐induced cytokine secretion downstream of MyD88. Further analysis revealed that this modulatory function results from IRAK4‐mediated suppression of protein kinase B (PKB/Akt). Release of suppression upon IRAK4 silencing (but not MyD88 knockdown) increases phosphorylation of PKB/Akt, counteracts NF‐κB activation and finally results in a monocyte phenotype with tolerogenic features, thus unleashing Akt‐ and mTOR‐dependent release of IL‐10, along with concomitant phosphorylation of FOXO transcription factors. In line with these observations IRAK4‐deficient monocytes failed to induce allogeneic CD8 + and CD4 + T‐cell responses, an effect reverted by neutralization of IL‐10. Taken together, our data highlight an unexpected role of IRAK4, Akt, and mTOR in the regulation of tolerance in human monocytes.
Mutation detection in cholestatic patients using microarray resequencing of ATP8B1 and ABCB11
2013-03-20

<ns4:p><ns4:bold>Background</ns4:bold><ns4:bold>: </ns4:bold>Neonatal cholestasis is a common presentation of childhood liver diseases and can be a feature of various conditions including disorders of bile acid biogenesis and transport, various inborn errors of metabolism and perinatal infections. Some inherited metabolic diseases can be easily screened using biochemical assays, however many can only be accurately diagnosed by DNA sequencing. Fluorescent capillary Sanger sequencing (FS) is the gold standard method used by clinical laboratories for genetic diagnosis of many inherited conditions; however, it does have limitations. Recently microarray resequencing (MR) has been introduced into research and clinical practice as an alternative method for genetic diagnosis of heterogeneous conditions. In this report we compared the accuracy of mutation detection for MR with FS in a group of patients with ‘low-normal’ gamma glutamyl transpeptidase (gGT) cholestasis without known molecular diagnoses.</ns4:p><ns4:p><ns4:bold>Methods</ns4:bold><ns4:bold>:</ns4:bold> 29 patient DNA samples were tested for mutations in the <ns4:italic>ATP8B1</ns4:italic> and <ns4:italic>ABCB11</ns4:italic> genes using both FS and MR. Other known causes of “low gGT cholestasis” such as ARC syndrome and bile acid biosynthesis disorders were excluded.</ns4:p><ns4:p><ns4:bold>Results</ns4:bold><ns4:bold>:</ns4:bold> Mutations were identified in 13/29 samples. In 3/29 samples FS and MR gave discordant results: MR had a false positive rate of 3.4% and a false negative rate of 7%.</ns4:p><ns4:p><ns4:bold>Conclusions</ns4:bold><ns4:bold>:</ns4:bold> The major advantage of MR over FS is that multiple genes can be screened in one experiment, allowing rapid and cost-effective diagnoses. However, we have demonstrated that MR technology is limited in sensitivity. We therefore recommend that MR be used as an initial evaluation, with FS deployed when genetic and clinical or histopathological findings are discordant.</ns4:p>
Iodine in Modern Oxidation Catalysis
2013-03-21

This review discusses the origins of iodine-mediated oxidation catalysis and gives a comprehensive overview on this young field of research. The focus is set on oxidative C–X bond-forming reactions starting from two unfunctionalized C–H and X–H bonds. In addition, iodine-mediated oxidative domino reactions will be discussed. 1 Introduction 2 Why Iodine? 3 C–N Bond Formations 3.1 Aziridinations 3.2 Oxidative Aminations of Heteroarenes 3.3 Oxidative Aminations of sp<sup>3</sup> C–H Bonds 3.4 Oxidative Amidations and Esterifications 4 C–O and C–S Bond Formations 5 C–C Bond Formations 6 Simple Oxidations of Functional Groups 7 Oxidative Domino Reactions 8 Conclusion
SNARE complexes of different composition jointly mediate membrane fusion inArabidopsiscytokinesis
2013-03-21

Membrane fusion is mediated by soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane fusion is required for separating daughter cells in eukaryotic cytokinesis, the SNARE complexes involved are not known. In plants, membrane vesicles targeted to the cell division plane fuse with one another to form the partitioning membrane, progressing from the center to the periphery of the cell. In Arabidopsis, the cytokinesis-specific Qa-SNARE KNOLLE interacts with two other Q-SNAREs, SNAP33 and novel plant-specific SNARE 11 (NPSN11), whose roles in cytokinesis are not clear. Here we show by coimmunoprecipitation that KNOLLE forms two SNARE complexes that differ in composition. One complex is modeled on the trimeric plasma membrane type of SNARE complex and includes, in addition to KNOLLE, the promiscuous Qb,c-SNARE SNAP33 and the R-SNARE vesicle-associated membrane protein (VAMP) 721,722, also involved in innate immunity. In contrast, the other KNOLLE-containing complex is tetrameric and includes Qb-SNARE NPSN11, Qc-SNARE SYP71, and VAMP721,722. Elimination of only one or the other type of KNOLLE complex by mutation, including the double mutant npsn11 syp71, causes a mild or no cytokinesis defect. In contrast, the two double mutants snap33 npsn11 and snap33 syp71 eliminate both types of KNOLLE complexes and display knolle-like cytokinesis defects. Thus the two distinct types of KNOLLE complexes appear to jointly mediate membrane fusion in Arabidopsis cytokinesis.
Circulating Lysophosphatidylcholines Are Markers of a Metabolically Benign Nonalcoholic Fatty Liver
2013-03-21

OBJECTIVE Nonalcoholic fatty liver (NAFL) is thought to contribute to insulin resistance and its metabolic complications. However, some individuals with NAFL remain insulin sensitive. Mechanisms involved in the susceptibility to develop insulin resistance in humans with NAFL are largely unknown. We investigated circulating markers and mechanisms of a metabolically benign and malignant NAFL by applying a metabolomic approach. RESEARCH DESIGN AND METHODS A total of 265 metabolites were analyzed before and after a 9-month lifestyle intervention in plasma from 20 insulin-sensitive and 20 insulin-resistant subjects with NAFL. The relevant plasma metabolites were then tested for relationships with insulin sensitivity in 17 subjects without NAFL and in plasma from 29 subjects with liver tissue samples. RESULTS The best separation of the insulin-sensitive from the insulin-resistant NAFL group was achieved by a metabolite pattern including the branched-chain amino acids leucine and isoleucine, ornithine, the acylcarnitines C3:0-, C16:0-, and C18:0-carnitine, and lysophosphatidylcholine (lyso-PC) C16:0 (area under the ROC curve, 0.77 [P = 0.00023] at baseline and 0.80 [P = 0.000019] at follow-up). Among the individual metabolites, predominantly higher levels of lyso-PC C16:0, both at baseline (P = 0.0039) and at follow-up (P = 0.001), were found in the insulin-sensitive compared with the insulin-resistant subjects. In the non-NAFL groups, no differences in lyso-PC C16:0 levels were found between the insulin-sensitive and insulin-resistant subjects, and these relationships were replicated in plasma from subjects with liver tissue samples. CONCLUSIONS From a plasma metabolomic pattern, particularly lyso-PCs are able to separate metabolically benign from malignant NAFL in humans and may highlight important pathways in the pathogenesis of fatty liver–induced insulin resistance.
Optical Spectroscopy and XRD Study of Molecular Orientation, Polymorphism, and Phase Transitions in Fluorinated Vanadyl Phthalocyanine Thin Films
2013-03-21

The molecular arrangement and phase transitions in the vanadyl hexadecafluorophthalocyanine (VOPcF16) thin films grown by physical vapor deposition have been studied using in situ X-ray diffraction, atomic force microscopy, and optical spectroscopy techniques (UV, IR, and Raman). The complete transition from the low-temperature linear cofacial structure to the slipped dimeric one occurs in the temperature range 160–220 °C. This conversion was found to be irreversible upon cooling the VOPcF16 film back to 20 °C. The structural transformation leads to decrease of the in-plane conductivity of the film by 2 orders of magnitude. According to the polarized Raman spectroscopy measurements, the mean tilt angles between the VOPcF16 species and the substrate surface were 59 ± 5° and 30 ± 5° in the as-deposited and annealed films, respectively. For the sake of comparison, the structure of the thin films of vanadyl phthalocyanine (VOPc) was also studied. The mean tilt angle between the VOPc species and the substrate surface was found to be 77 ± 5°, in good agreement with existing experimental data (∼70°). All intense bands in the experimental IR and Raman spectra of VOPcF16 and VOPc were assigned using DFT calculations (B3LYP) and the 15N isotopic shifts in the vibrational spectra of VOPc.
Reperfusion of liver graft during transplantation: techniques used in transplant centres within Eurotransplant and meta-analysis of the literature
2013-03-21

It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients' mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs.
Bilateral Laparoscopic Postchemotherapy Retroperitoneal Lymph-Node Dissection in Nonseminomatous Germ Cell Tumors–a Comparison to Template Dissection
2013-03-21

Postchemotherapy L-RPLND remains technically challenging. However, the morbidity of primary bilateral post-chemotherapy L-RPLND is similar to that of template dissection. Additional oncological safety is provided, which is particularly relevant in patients with more extensive retroperitoneal tumor volume.
Recent mass balance of Purogangri ice cap, central Tibetan Plateau, by means of differential X-band SAR interferometry
2013-03-21

Abstract. Due to their remoteness, altitude and harsh climatic conditions, little is known about the glaciological parameters of ice caps on the Tibetan Plateau (TP). This study presents an interferometrical approach aiming at surface elevation changes of Purogangri ice cap, located on the central TP. Purogangri ice cap covers an area of 397 ± 9.7 km2 and is the largest ice cap on the TP. Its behavior is determined by dry and cold continental climate suggesting a polar-type glacier regime. We employed data from the actual TerraSAR-X mission and its add-on for Digital Elevation Measurements (TanDEM-X) and compare it with elevation data from the Shuttle Radar Topography Mission (SRTM). These datasets are ideal for this approach as both datasets feature the same wavelength of 3.1 cm and are available at a fine grid spacing. Similar snow conditions can be assumed since the data were acquired in early February 2000 and late January 2012. The trend in glacier extend was extracted using a time series of Landsat data. Our results show a balanced mass budget for the studied time period which is in agreement with previous studies. Additionally, we detected an exceptional fast advance of one glacier tongue in the eastern part of the ice cap between 1999 and 2011.
Derivation and Expansion Using Only Small Molecules of Human Neural Progenitors for Neurodegenerative Disease Modeling
2013-03-22

Phenotypic drug discovery requires billions of cells for high-throughput screening (HTS) campaigns. Because up to several million different small molecules will be tested in a single HTS campaign, even small variability within the cell populations for screening could easily invalidate an entire campaign. Neurodegenerative assays are particularly challenging because neurons are post-mitotic and cannot be expanded for implementation in HTS. Therefore, HTS for neuroprotective compounds requires a cell type that is robustly expandable and able to differentiate into all of the neuronal subtypes involved in disease pathogenesis. Here, we report the derivation and propagation using only small molecules of human neural progenitor cells (small molecule neural precursor cells; smNPCs). smNPCs are robust, exhibit immortal expansion, and do not require cumbersome manual culture and selection steps. We demonstrate that smNPCs have the potential to clonally and efficiently differentiate into neural tube lineages, including motor neurons (MNs) and midbrain dopaminergic neurons (mDANs) as well as neural crest lineages, including peripheral neurons and mesenchymal cells. These properties are so far only matched by pluripotent stem cells. Finally, to demonstrate the usefulness of smNPCs we show that mDANs differentiated from smNPCs with LRRK2 G2019S are more susceptible to apoptosis in the presence of oxidative stress compared to wild-type. Therefore, smNPCs are a powerful biological tool with properties that are optimal for large-scale disease modeling, phenotypic screening, and studies of early human development.
Correlation of Simultaneously Acquired Diffusion-Weighted Imaging and 2-Deoxy-[18F] fluoro-2-D-glucose Positron Emission Tomography of Pulmonary Lesions in a Dedicated Whole-Body Magnetic Resonance/Positron Emission Tomography System
2013-03-22

Examinations of pulmonary lesions in a simultaneous whole-body MR/PET system provide diagnostic image quality in both modalities. Although DWI and FDG-PET reflect different tissue properties, there may very well be an association between the measures of both methods most probably because of increased cellularity and glucose metabolism of FDG-avid pulmonary lesions. A voxelwise DWI and FDG-PET correlation might provide a more sophisticated spatial characterization of pulmonary lesions.
Non–Mycosis Fungoides Cutaneous T-Cell Lymphomas
2013-03-22

Primary cutaneous T-cell lymphomas (CTCL) excluding mycosis fungoides (MF) were discussed in 2 sessions of the 2011 Society for Hematopathology/ European Association of Haematopathology Workshop, Los Angeles, CA. Session 2 focused on primary cutaneous CD30+ T-cell lymphoproliferative disorders and their differential diagnosis, including systemic CD30+ T-cell lymphoma secondarily infiltrating the skin. Interesting features like special morphologic variants and atypical phenotypes were presented. In addition, the possibility of rare ALK+ primary cutaneous lymphomas was discussed. Session 3 examined other more uncommon non-MF CTCLs, including subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and rare subtypes of primary cutaneous peripheral T-cell lymphoma, not otherwise specified. In addition, systemic T-cell lymphomas involving the skin secondarily, such as angioimmunoblastic T-cell lymphoma, were included in this session. In this report, novel findings, areas of special interest, and diagnostic challenges emerging from the cases submitted to the workshop will be highlighted. The necessity to integrate histologic, immunophenotypical, genetic, and in particular, clinical data to arrive at the correct diagnosis, and subsequently provide adequate treatment, is emphasized.