julilili42/papers huggingface dataset:
Enabling cell–cell communication via nanopore formation: structure, function and localization of the unique cell wall amidase AmiC2 of Nostoc punctiforme
2016-02-01

To orchestrate a complex life style in changing environments, the filamentous cyanobacterium Nostoc punctiforme facilitates communication between neighboring cells through septal junction complexes. This is achieved by nanopores that perforate the peptidoglycan ( PGN ) layer and traverse the cell septa. The N ‐acetylmuramoyl‐ l ‐alanine amidase AmiC2 (Npun_F1846; EC 3.5.1.28 ) in N . punctiforme generates arrays of such nanopores in the septal PGN , in contrast to homologous amidases that mediate daughter cell separation after cell division in unicellular bacteria. Nanopore formation is therefore a novel property of AmiC homologs. Immunofluorescence shows that native AmiC2 localizes to the maturing septum. The high‐resolution crystal structure (1.12 Å) of its catalytic domain (AmiC2‐cat) differs significantly from known structures of cell splitting and PGN recycling amidases. A wide and shallow binding cavity allows easy access of the substrate to the active site, which harbors an essential zinc ion. AmiC2‐cat exhibits strong hydrolytic activity in vitro . A single point mutation of a conserved glutamate near the zinc ion results in total loss of activity, whereas zinc removal leads to instability of AmiC2‐cat. An inhibitory α‐helix, as found in the Escherichia coli AmiC E. coli structure, is absent. Taken together, our data provide insight into the cell‐biological, biochemical and structural properties of an unusual cell wall lytic enzyme that generates nanopores for cell–cell communication in multicellular cyanobacteria. The novel structural features of the catalytic domain and the unique biological function of AmiC2 hint at mechanisms of action and regulation that are distinct from other amidases. Database The AmiC2‐cat structure has been deposited in the Protein Data Bank under accession number 5EMI .
Cooling history of the St. Elias syntaxis, southeast Alaska, revealed by geochronology and thermochronology of cobble-sized glacial detritus
2016-02-01

We investigate the spatiotemporal evolution of exhumation in the ice-covered St. Elias syntaxis area, southeast Alaska, using multiple thermochronometers and geochronometers from cobble-sized glacial detritus. Multiple thermochronometers reveal the cooling histories from 500 to 60°C of 27 glacially transported cobbles from the two largest catchments of the syntaxis. Cobble lithologies and 21 zircon U-Pb ages (~277–31 Ma) were examined to determine sample provenance. Furthermore, eight amphibole and seven biotite 40Ar/39Ar ages (~276–16 Ma and ~50–42 Ma, respectively), four zircon and six apatite (U-Th)/He ages (~35–4.8 Ma and ~4.2–0.6 Ma, respectively), and four apatite fission track ages (~17–1.6 Ma) were used to reconstruct the individual cobble cooling histories. An additional four bedrock samples from the Fairweather Range yielded three biotite 40Ar/39Ar ages between ~42 and 5 Ma. A compilation of published bedrock and new cobble cooling histories from the St. Elias Mountains and Fairweather Range reveals the regional Cenozoic cooling and exhumation history, emphasizing the position of the St. Elias syntaxis as a transitional zone between transpression and subduction settings. The new cobble and bedrock data indicate an onset of rapid exhumation at ~5 Ma that was limited in duration (2–3 Myr) and amount (~10 km) in the syntaxial region. This study also demonstrates the usefulness of cobbles for revealing thermal histories of otherwise inaccessible regions as cobble analysis combines advantages of bedrock and detrital thermochronology.
Clinical efficacy and safety of T-DM1 for patients with HER2-positive breast cancer
2016-02-01

Bo Ma,1 Qianqian Ma,2 Hongqiang Wang,3 Guolei Zhang,1 Huiying Zhang,1 Xiaohong Wang1 1Affiliated Central Hospital of Huzhou Teachers College, Huzhou, Zhejiang, People&amp;amp;rsquo;s Republic of China; 2University Hospital of Tuebingen, Tuebingen, Germany; 3Department of Oncology, Hospital of Zhoushan, Zhoushan, Zhejiang, People&amp;amp;rsquo;s Republic of China Purpose: The aim of this study was to evaluate the therapeutic efficacy and safety of trastuzumab emtansine (T-DM1) for the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer.&amp;amp;nbsp; Methods: We performed a systemic review and meta-analysis of the relevant published clinical studies. A computerized search was performed for controlled clinical trials of T-DM1 in targeted treatment. Overall survival, progression-free survival, objective response rate, symptom progression free, and adverse events (AEs) were evaluated.&amp;amp;nbsp; Results: Eight eligible trials with a total of 2,016 patients with breast cancer were included in the present meta-analysis. The treatment of patients with breast cancer with T-DM1 was associated with significantly increased overall and progression-free survival when compared with controls (P&amp;amp;lt;0.0001). An analysis of the objective response rate and symptom progression free also demonstrated favorable results for T-DM1 treatment (P&amp;amp;le;0.0001). There was no significant difference between the T-DM1 and control groups with respect to nonhematologic or hematologic AEs (P=0.99 and P=0.30, respectively).&amp;amp;nbsp; Conclusion: Overall, T-DM1 is efficacious in the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer and low rates of AEs compared with controls. Keywords: breast cancer, meta-analysis, HER2, T-DM1, efficacy
Iron deficiency anemia in cyclic GMP kinase knockout mice
2016-02-01

Mice with a global inactivation of the cyclic GMP kinase I (cGKI) gene (cGKI−/−) and mice that express cGKIα or cGKIβ in all smooth muscles on a cGKI−/− background1 (cGKI RM mice) have a bleeding duodenal ulcer2 and anemia of unknown cause.3,4 Immunocytochemistry of bone marrow indicated that macrophages but not erythroblasts express cGKI.1 In contrast, it was found that erythroblasts and erythrocytes purified by immunomagnetic selection using labeled anti-Ter119 MicroBeads followed by magnetic cell sorting are cGKI positive.3 cGKI deleted erythrocytes showed a marked increase in annex-in V binding, indicating phosphatidylserine (PS) exposure at the outer membrane leaflet, a hallmark of suicidal erythrocyte death or eryptosis.5 Eryptosis caused faster erythrocyte clearance in vivo. Therefore, it was suggested that the observed anemia was induced by the rapid erythrocyte clearance in the spleen.3
How to Best Name a Place? Facilitation and Inhibition of Route Learning Due to Descriptive and Arbitrary Location Labels
2016-02-01

Establishing verbal memory traces for non-verbal stimuli was reported to facilitate or inhibit memory for the non-verbal stimuli. We show that these effects are also observed in a domain not indicated before-wayfinding. Fifty-three participants followed a guided route in a virtual environment. They were asked to remember half of the intersections by relying on the visual impression only. At the other 50% of the intersections, participants additionally heard a place name, which they were asked to memorize. For testing, participants were teleported to the intersections and were asked to indicate the subsequent direction of the learned route. In Experiment 1, intersections' names were arbitrary (i.e., not related to the visual impression). Here, participants performed more accurately at unnamed intersections. In Experiment 2, intersections' names were descriptive and participants' route memory was more accurate at named intersections. Results have implications for naming places in a city and for wayfinding aids.
Linebased end-to-display encryption for secure documents
2016-02-01

To protect data against theft from Trojan horses, some of the common approaches like End-to-End Encryption fail to counter such malicious attempts as they do not account for vulnerabilities of the user's endpoint. Any data which is decrypted on the endpoint, can become visible to attackers. A technique that can prevent this dataloss is by employing encryption in the pixel-domain and using additional hardware to decrypt the graphics-stream. This is done by End-to-Display Encryption, which decrypts the data between the endpoint and the display, ensuring that the data-at-rest is always encrypted. In this paper, we present a linebased encryption method for a more user-friendly and improved End-to-Display Encryption design, which can be used to effectively counter corporate espionage by providing secure access to confidential documents.
New Results on the Minimum Amount of Useful Space
2016-02-01

We present several new results on minimal space requirements to recognize a nonregular language: (i) realtime nondeterministic Turing machines can recognize a nonregular unary language within weak log log n space, (ii) log log n is a tight space lower bound for accepting general nonregular languages on weak realtime pushdown automata, (iii) there exist unary nonregular languages accepted by realtime alternating one-counter automata within weak log n space, (iv) there exist nonregular languages accepted by two-way deterministic pushdown automata within strong log log n space, and, (v) there exist unary nonregular languages accepted by two-way one-counter automata using quantum and classical states with middle log n space and bounded error.
Strong functional connectivity of parvalbumin-expressing cortical interneurons
2016-02-01

The morphological and electrophysiological properties of parvalbumin-expressing inhibitory interneurons (PV+ neurons) suggest their role as synchronizers and normalizers of the local cortical microcircuit. PV+ cells are thought to average the local activity and dynamically regulate its overall level. In apparent agreement with this model, previous studies have shown stable patterns of correlations of the spiking activity of the PV+ neurons among themselves and with the local excitatory cells. However, we have previously shown that, in sufficiently dense recordings, estimates of the partial pairwise correlations of the spiking activity can yield a more insightful picture of interactions in the circuit, or its functional connectivity. Using high-speed 3D two-photon imaging of calcium signals and genetically encoded fluorescent markers of PV+ neurons, we recorded the activity of the majority of neurons in 200 um x 200 um x 100 um volumes in layers 2/3 and 4 of mouse visual cortex during visual stimulation. If PV+ neurons simply pooled the activity of the local circuit, their activity would be predicted from the local circuit and the partial correlations among the PV+ neurons would all but vanish. Surprisingly, we found that the partial pairwise correlations among the PV+ cells were exceptionally high. In fact, the partial pairwise correlations enhanced the differentiation of PV+ neurons from other cell types. The average partial pairwise correlation between PV+/PV+ pairs was 4.9 times higher than between PV-/PV- pairs whereas the average noise correlations differed by the factor of 1.5. This effect was insensitive to the choice of the temporal scales of correlation analysis. Although other explanations cannot yet be excluded, the present finding may suggest that the correlations among the PV+ neurons are shaped predominantly by structured input from outside the local circuit such as, for example, by input from layer 5.
Reheating breakfast
2016-02-01

Computer-based assessments are popular means to measure individual differences, including age differences, in cognitive ability, but are rarely tested for the extent to which they correspond to more realistic behavior. In the present study, we explored the extent to which performance on an existing computer-based task of multitasking ('cooking breakfast') may be generalizable by comparing it with a newly developed version of the same task that required interaction with physical objects. Twenty younger and 29 older adults performed both the computer-based multitasking task and its laboratory-based equivalent. In each task, two measures determined prospective memory and one measure ascertained speed of completion. The Prospective-Retrospective Memory Questionnaire determined self-reported memory failures. In both age groups, correlations between the computer-based and the laboratory version of the task were largely restricted to a single measure of prospective memory. Whereas performance on the laboratory task correlated with self-reported memory failures across the entire sample, there was no such relationship for the computer-based task. Finally, age group by task interactions suggested that younger and older adults were differentially affected by laboratory versus computer-based assessment. Our study illustrates the need for future evaluations of computer-based psychometric instruments on younger and older samples prior to their application. We compared younger and older adults on computer-vs. non-computer-based multitasking.We found that correlations between the two tasks were limited.Older people experienced disadvantages through the use of the computer-based task.Evaluations of age effects on computer-based assessments are warranted.
Treatment of pancreatic ductal adenocarcinoma (PDAC) by argyrin F (AF) + gemcitabine (G).
2016-02-01

310 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of &lt; 5%. Early diagnosis is rare and treatment options are often limited. Recent studies have reported that the proteasome inhibitor Argyrin A, a cyclic peptide derived from the myxobacterium Archangium gephyra, shows antitumoral activities. The aim of the present study is to explore the anti-tumor activity of this analogue Argyrin F (AF) + Gemcitabine (G) in PDAC carcinogenesis. Methods: We analyzed the effect of AF on proliferation and epithelial plasticity of different human pancreatic cancer cell lines by using MTT-, wound healing-, invasion-, colony formation-, apoptosis- and senescence assay, as well as cell cycle analysis and Western Blot. In vivo, we assessed the effects of AF and combinational (AF + G) therapy in a genetically engineered mouse model (Pdx1- Cre; LSL-KrasG12D; p53 lox/+ ) of PDAC. Results: AF inhibited pancreatic cancer cell proliferation, migration, invasion and colony formation compared to their respective untreated controls (DMSO). We also found that AF impairs epithelial-mesenchymal-transition (EMT) and induces considerable apoptosis and senescence in a dose-and time-dependent manner. AF application resulted in cell cycle G1/S phase transition. Most importantly, double treatment by AF + G showed prolonged survival and caused significant tumor reduction. Expression of Ki67 (anti-proliferative marker) and CD34 (tumor angiogenesis marker) was reduced both after AF and AF + G treatment of PDAC tumors in mice. Conclusions: Our work demonstrates that treatment with AF can successfully inhibit the growth of PDAC cells and combinational treatment with AF + G might be also a new and promising combinational therapy for human PDAC treatment.
Notch and wnt-beta catenin pathways as targets of γ-secretase inhibitor IX (GSI) mediated therapy in CD44+ gastric cancer (GC) cells.
2016-02-01

99 Background: GC is the second most common cause of cancer related death worldwide. New palliative therapeutic approaches to treat GC are of urgent need. Targeting cancer stem cells (CSC) could be an effective approach to treat GC. Recent studies have indicated that Notch signaling and wnt-beta-catenin pathways are crucial for CSC development. In this study, we mainly focused on inactivation of both Notch and wnt-beta-catenin pathways in CSC CD44+ GC cells using GSI. Methods: For our experiments we have used the GC cell line MKN45, as it showed expression of both targets (CD44,Hes1). For in vitro experiments proliferation, wound healing, invasion and tumorsphere assays were performed to analyze the migration, invasive and tumorigenic potential of CD44+ sorted GC initiating cells after GSI treatment. Western blot analyses of downstream signaling targets of Notch and wnt-beta catenin were tested after GSI treatment. SiRNA experiments for Notch1 and CD44 were also performed in order to confirm the Notch and wnt-beta-catenin pathway crosstalk. For in vivo analysis sorted CD44+ cells were subcutaneously injected into NMRI-nu/numice and were treated with vehicle or GSI. Results: CD44+ sorted MKN45 cells showed high expression of Hes1 as compared to the CD44- cell population. GSI treatment showed effective inhibition of cell proliferation, migration, invasion and tumor sphere formation of CD44+ cells. Interestingly, amongst all Notch receptors, Notch1 was found to be important in mediating the crosstalk between Notch and wnt-beta-catenin signaling cascades in CD44+ GC cells. Moreover, upon silencing of both CD44 and Notch1 by SiRNA showed effective inhibition of downstream targets and reconfirmed the proposed hypothesis of CD44 mediated Notch and wnt/beta-catenin crosstalk in GC cells. Conclusions: Our study highlights the crosstalk between Notch and wnt-beta-catenin in GC CD44+ cells. GSI could be an alternative drug to treat human GC as it effectively targets the CD44+ GC cells thus, completely reducing all the chances of relapse and metastasis associated with GC. Therefore, GSI therapy can open up new avenues for GC treatment with improved / better clinical outcome.
Correlation of locoregional treatment failures with radiotherapy target volumes after radiochemotherapy for esophageal cancer.
2016-02-01

166 Background: Radiotherapy is a mainstay in curative treatment concepts of esophageal cancer. Despite extensive treatment fields locoregional recurrences are frequent. We therefore aimed to evaluate the exact patterns of locoregional recurrence and correlate these recurrences with radiotherapy target volumes. Methods: Diagnostic PET-CT or CT imaging studies showing locoregional recurrences after preoperative or definitive radiochemotherapy for squamous or adenocarcinoma of the esophagus were matched with CT scans used for treatment planning. Distance of the recurrence from the Clinical Target Volume (CTV), Planning Target Volume (PTV) and the dose at the failure site were the determined. Target volume definition was in line with international standards. Results: We identified 104 patients treated with either definitive (n = 81) or preoperative radiochemotherapy (n = 23). After exclusion of patients with a history of second malignancies we found 25 locoregional recurrences in 20 patients. Median time to locoregional failure was 8 months (range 2-26 months). Six of 25 recurrences (24%) were located intraluminal in the initial Gross Tumor Volume (GTV), three of 25 (12%) were in-field nodal failures and five (20%) more than 1 cm distant from the PTV. Nine (36%) locoregional recurrences occurred within 1 cm of the cranial or distal end of the CTV, between the CTV and PTV or out-of-field adjacent to the PTV. Two patients developed anastomotic recurrence after surgery. Conclusions: Matching of diagnostic CTs showing local recurrences with radiotherapy planning CT data set allows the correlations of local recurrences with target volumes. Despite extensive safety margins, field margin recurrences remain a considerable problem in the treatment of esophageal cancer. The use of advanced radiotherapy techniques might facilitate larger treatment volumes without increasing toxicity.
Foreign Direct Investment as a Signal
2016-02-01

This paper models competition among multinational firms in an environment &#13;\\nof firm heterogeneity, incomplete cost information and strategic interaction. In &#13;\\nthis context, &#13;\\nFDI serves as a signal of productivity: when firms sort into exporters and &#13;\\nmultinationals, they also show whether they have low or high productivity. &#13;\\nWe show that the signaling effect of FDI increases the FDI incentive as firms &#13;\\nwould like to avoid sending a low productivity signal.
Abstract 164: Specific Point-of-Care Testing of Coagulation in Patients Treated With Non-Vitamin K Antagonist Oral Anticoagulants Part I (SPOCT-NOAC I)
2016-02-01

Introduction: Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF) and venous thrombosis. Ischemic stroke rate in NOAC-treated AF-patients is 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT. Hypothesis: Ecarin clotting time (ECT)- and anti-Xa activity-POCT accurately predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban. Methods: 80 patients receiving first NOAC-dose and 80 already on NOAC-treatment will be enrolled (N=40 for each NOAC). Subjects receiving other anticoagulants will be excluded. 6 blood samples will be collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations will be measured by mass spectrometry. Results (preliminary): Until now 138 blood samples of 23 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-371ng/mL. ECT-POCT ranged from 20-219s. Pearson’s correlation coefficient showed strong correlation for ECT-POCT and dabigatran-concentrations (r=0.94, p&lt;0.001). Dabigatran-concentrations &gt;50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT (&gt;50s) with 100% sensitivity and 82% specificity. Baseline-samples not containing any dabigatran yielded normal ECT-POCT. Conclusions: This is the first study evaluating NOAC-specific POCT. Preliminary results show excellent correlation for ECT-POCT and dabigatran; relevant dabigatran-concentrations were detected in 100%. More pioneering results on NOAC-specific POCT will be presented.
A feedback mechanism converts individual cell features into a supracellular ECM structure in Drosophila trachea
2016-02-02

The extracellular matrix (ECM), a structure contributed to and commonly shared by many cells in an organism, plays an active role during morphogenesis. Here, we used the Drosophila tracheal system to study the complex relationship between the ECM and epithelial cells during development. We show that there is an active feedback mechanism between the apical ECM (aECM) and the apical F-actin in tracheal cells. Furthermore, we reveal that cell-cell junctions are key players in this aECM patterning and organisation and that individual cells contribute autonomously to their aECM. Strikingly, changes in the aECM influence the levels of phosphorylated Src42A (pSrc) at cell junctions. Therefore, we propose that Src42A phosphorylation levels provide a link for the ECM environment to ensure proper cytoskeletal organisation.