Triphen­yl(prop-2-yn-1-yl)silane

In the title compound, C21H18Si, the coordination geometry around the Si atom is a slightly distorted tetra­hedron with C—Si—C angles in the range 106.05 (11) to 110.58 (10) ° and Si–C bond lengths in the range 1.855 (2) to 1.883 (3) Å. The alkyne C—C bond length is 1.167 (4) Å. The dihedral angles between the three phenyl rings are 63.89 (7), 86.38 (7) and 70.51 (8)°. In the crystal, mol­ecules inter­act only by van der Waals forces

Linking galaxy structural properties and star formation activity to black hole activity with IllustrisTNG

We study the connection between active galactic nuclei (AGN) and their host galaxies through cosmic time in the large-scale cosmological IllustrisTNG simulations. We first compare BH properties, i.e. the hard X-ray BH luminosity function, AGN galaxy occupation fraction, and distribution of Eddington ratios, to available observational constraints. The simulations produce a population of BHs in good agreement with observations, but we note an excess of faint AGN in hard X-ray (L_x ~ 10^{43-44} erg/s), and a lower number of bright AGN (L_x>10^{44} erg/s), a conclusion that varies quantitatively but not qualitatively with BH luminosity estimation method. The lower Eddington ratios of the 10^{9} Msun BHs compared to observations suggest that AGN feedback may be too efficient in this regime. We study galaxy star formation activity and structural properties, and design sample-dependent criteria to identify different galaxy types (star-forming/quiescent, extended/compact) that we apply both to the simulations and observations from the candels fields. We analyze how the simulated and observed galaxies populate the specific star formation rate - stellar mass surface density diagram. A large fraction of the z=0 M_{star}>10^{11} Msun quiescent galaxies first experienced a compaction phase (i.e. reduction of galaxy size) while still forming stars, and then a quenching event. We measure the dependence of AGN fraction on galaxies' locations in this diagram. After correcting the simulations with a redshift and AGN luminosity-dependent model for AGN obscuration, we find good qualitative and quantitative agreement with observations. The AGN fraction is the highest among compact star-forming galaxies (16-20% at z~1.5-2), and the lowest among compact quiescent galaxies (6-10% at z~1.5-2).Comment: 35 pages, 22 figures, accepted for publication in MNRA

Application of the Ultra-Poverty Graduation Model in understanding community health volunteers’ preferences for socio-economic empowerment strategies to enhance retention: a qualitative study in Kilifi, Kenya

Background: A significant shortage of healthcare workforce exists globally. To achieve Universal Healthcare cover- age, governments need to enhance their community-based health programmes. Community health volunteers (CHVs) are essential personnel in achieving this objective. However, their ability to earn a livelihood is compromised by the voluntary nature of their work; hence, the high attrition rates from community-based health programmes. There is an urgent need to support CHVs become economically self-reliant. We report here on the application of the Ultra-Poverty Graduation (UPG) Model to map CHVs’ preferences for socio-economic empowerment strategies that could enhance their retention in a rural area in Kenya. Methods: This study adopted an exploratory qualitative approach. Using a semi-structured questionnaire, we conducted 10 Focus Group Discussions with the CHVs and 10 Key Informant Interviews with County and Sub-county Ministry of Health and Ministry of Agriculture officials including multi-lateral stakeholders’ representatives from two sub-counties in the area. Data were audio-recorded and transcribed verbatim and transcripts analysed in NVivo. Researcher triangulation supported the first round of analysis. Findings were mapped and interpreted using a theory- driven analysis based on the six-step Ultra-Poverty Graduation Model. Results: We mapped the UPG Model’s six steps onto the results of our analyses as follows: (1) initial asset transfer of in-kind goods like poultry or livestock, mentioned by the CHVs as a necessary step; (2) weekly stipends with consump- tion support to stabilise consumption; (3) hands-on training on how to care for assets, start and run a business based on the assets transferred; (4) training on and facilitation for savings and financial support to build assets and instil financial discipline; (5) healthcare provision and access and finally (6) social integration. These strategies were pro- posed by the CHVs to enhance economic empowerment and aligned with the UPG Model. Conclusion: These results provide a user-defined approach to identify and assess strategic needs of and approaches to CHVs’ socio-economic empowerment using the UPG model. This model was useful in mapping the findings of our qualitative study and in enhancing our understanding on how these needs can be addressed in order to economically empower CHVs and enhance their retention in our setting

Nav1.5 regulates breast tumor growth and metastatic dissemination in vivo

Voltage-gated Na(+) channels (VGSCs) mediate action potential firing and regulate adhesion and migration in excitable cells. VGSCs are also expressed in cancer cells. In metastatic breast cancer (BCa) cells, the Na(v)1.5 α subunit potentiates migration and invasion. In addition, the VGSC-inhibiting antiepileptic drug phenytoin inhibits tumor growth and metastasis. However, the functional activity of Na(v)1.5 and its specific contribution to tumor progression in vivo has not been delineated. Here, we found that Na(v)1.5 is up-regulated at the protein level in BCa compared with matched normal breast tissue. Na(+) current, reversibly blocked by tetrodotoxin, was retained in cancer cells in tumor tissue slices, thus directly confirming functional VGSC activity in vivo. Stable down-regulation of Na(v)1.5 expression significantly reduced tumor growth, local invasion into surrounding tissue, and metastasis to liver, lungs and spleen in an orthotopic BCa model. Na(v)1.5 down-regulation had no effect on cell proliferation or angiogenesis within the in tumors, but increased apoptosis. In vitro, Na(v)1.5 down-regulation altered cell morphology and reduced CD44 expression, suggesting that VGSC activity may regulate cellular invasion via the CD44-src-cortactin signaling axis. We conclude that Na(v)1.5 is functionally active in cancer cells in breast tumors, enhancing growth and metastatic dissemination. These findings support the notion that compounds targeting Na(v)1.5 may be useful for reducing metastasis

The Effects of Square-Stepping Exercise on Risk of Falling and Balance in Senior Adults

As people age, their body systems gradually deteriorate. Muscle function and the vestibular system slowly deteriorate leading to lower body instability. Older adults who struggle with dizziness and imbalance are more prone to falling. Dizziness and imbalance cause falls, and falls are the leading cause of hospitalization and accidental death in older adults (Shinichi & Tatsuya, 2015). It is possible to prevent and reduce the risk of falls through balance training. It is crucial that older adults take the steps needed to improve their balance and therefore reduce their risk of falling. PURPOSE: To evaluate the effect of a 10-week Square-Stepping Exercise (SSE) program in older adults using the Biodex balance system. METHODS: Eleven adults over the age of 60 and involved in the Senior Jacket program at Cedarville University participated in this 10-week study (0 males, 11 females; mean age=76). Measurements taken prior to and after the intervention include Activities-specific Balance Confidence (ABC) Scale, Timed-Up-And-Go Test, 30-Second Chair Stand Test, Limits of Stability Test, and Fall Risk Test. A Repeated Measures ANOVA was used to determine changes in initial and final balance testing scores. RESULTS: The study revealed that significant differences were found for the functional fitness tests. SPSS indicated a significant difference in improvement from pretest to posttest for the Timed-Up-and-Go Test (P = .003) as well as the 30-Second Chair Stand Test (P = .043). For the Limits of Stability test, there was no significant change from pretest to posttest for the overall (P =0.162) or any of the 8 directions. The Fall Risk Test score also showed no significant change (P =0.831). The ABC Scale test did not show significant improvement either (P = 0.995). CONCLUSION: Overall, the results showed that the participants significantly benefited from the training program in areas of functional fitness. Unfortunately, there was no significant improvement with the Biodex balance system’s Fall Risk Test or Limits of Stability Test. Results may be due to the participants already having good balance as they were well below the normative data for risk of falling. It could also be because the training was not specific enough for improvements in the Fall Risk and Limits of Stability tests

The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis.

Background Voltage-gated Na+ channels (VGSCs) are heteromeric protein complexes containing pore-forming ? subunits and smaller, non-pore-forming ? subunits. VGSCs are classically expressed in electrically excitable cells, e.g. neurons. VGSCs are also expressed in tumour cells, including breast cancer (BCa) cells, where they enhance cellular migration and invasion. However, despite extensive work defining in detail the molecular mechanisms underlying the expression of VGSCs and their pro-invasive role in cancer cells, there has been a notable lack of clinically relevant in vivo data exploring their value as potential therapeutic targets. Findings We have previously reported that the VGSC-blocking antiepileptic drug phenytoin inhibits the migration and invasion of metastatic MDA-MB-231 cells in vitro. The purpose of the present study was to establish whether VGSCs might be viable therapeutic targets by testing the effect of phenytoin on tumour growth and metastasis in vivo. We found that expression of Nav1.5, previously detected in MDA-MB-231 cells in vitro, was retained on cells in orthotopic xenografts. Treatment with phenytoin, at a dose equivalent to that used to treat epilepsy (60 mg/kg; daily), significantly reduced tumour growth, without affecting animal weight. Phenytoin also reduced cancer cell proliferation in vivo and invasion into surrounding mammary tissue. Finally, phenytoin significantly reduced metastasis to the liver, lungs and spleen. Conclusions This is the first study showing that phenytoin reduces breast tumour growth and metastasis in vivo. We propose that pharmacologically targeting VGSCs, by repurposing antiepileptic or antiarrhythmic drugs, should be further studied as a potentially novel anti-cancer therapy

A complex pattern of chemokine receptor expression is seen in osteosarcoma

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma is the most frequent bone tumor in childhood and adolescence. Patients with primary metastatic disease have a poor prognosis. It is therefore important to better characterize the biology of this tumor to define new prognostic markers or therapeutic targets for tailored therapy. Chemokines and their receptors have been shown to be involved in the development and progression of malignant tumors. They are thought to be active participants in the biology of osteosarcoma. The function of specific chemokines and their receptors is strongly associated with the biological context and microenvironment of their expression. In this report we characterized the expression of a series of chemokine receptors in the complex environment that defines osteosarcoma.</p> <p>Methods</p> <p>The overall level of chemokine receptor mRNA expression was determined using TaqMan RT-PCR of microdissected archival patient biopsy samples. Expression was then verified at the protein level by immunohistochemistry using a series of receptor specific antibody reagents to elucidate the cellular association of expression.</p> <p>Results</p> <p>Expression at the RNA level was found for most of the tested receptors. CCR1 expression was found on infiltrating mononuclear and polynuclear giant cells in the tumor. Cells associated with the lining of intratumoral vessels were shown to express CCR4. Infiltrating mononuclear cells and tumor cells both showed expression of the receptor CCR5, while CCR7 was predominantly expressed by the mononuclear infiltrate. CCR10 was only very rarely detected in few scattered infiltrating cells.</p> <p>Conclusion</p> <p>Our data elucidate for the first time the cellular context of chemokine receptor expression in osteosarcoma. This is an important issue for better understanding potential chemokine/chemokine receptor function in the complex biologic processes that underlie the development and progression of osteosarcoma. Our data support the suggested involvement of chemokines and their receptors in diverse aspects of the biology of osteosarcoma, but also contradict aspects of previous reports describing the expression of these receptors in this tumor.</p

Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity in vivo and in vitro

Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6) is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble μ receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental tumor, nerve injury or inflammation recovery was not preserved in the maintenance phase and nociceptors exhibited normal mechanical thresholds comparable to untreated mice. Together, the results argue for IL-6 signal transducer gp130 as an essential prerequisite in nociceptors for long-term mechanical hypersensitivity associated with cancer, inflammation and nerve injury

Implementing Neural Network-Based Equalizers in a Coherent Optical Transmission System Using Field-Programmable Gate Arrays

In this work, we demonstrate the offline FPGA realization of both recurrent and feedforward neural network (NN)-based equalizers for nonlinearity compensation in coherent optical transmission systems. First, we present a realization pipeline showing the conversion of the models from Python libraries to the FPGA chip synthesis and implementation. Then, we review the main alternatives for the hardware implementation of nonlinear activation functions. The main results are divided into three parts: a performance comparison, an analysis of how activation functions are implemented, and a report on the complexity of the hardware. The performance in Q-factor is presented for the cases of bidirectional long-short-term memory coupled with convolutional NN (biLSTM + CNN) equalizer, CNN equalizer, and standard 1-StpS digital back-propagation (DBP) for the simulation and experiment propagation of a single channel dual-polarization (SC-DP) 16QAM at 34 GBd along 17x70km of LEAF. The biLSTM+CNN equalizer provides a similar result to DBP and a 1.7 dB Q-factor gain compared with the chromatic dispersion compensation baseline in the experimental dataset. After that, we assess the Q-factor and the impact of hardware utilization when approximating the activation functions of NN using Taylor series, piecewise linear, and look-up table (LUT) approximations. We also show how to mitigate the approximation errors with extra training and provide some insights into possible gradient problems in the LUT approximation. Finally, to evaluate the complexity of hardware implementation to achieve 400G throughput, fixed-point NN-based equalizers with approximated activation functions are developed and implemented in an FPGA.Comment: Invited paper at Journal of Lightwave Technology - IEE