Prevention of early stage Kras-mutant lung adenocarcinoma via targeted KrasG12D inhibition

https://openworks.mdanderson.org/sumexp22/1118/thumbnail.jp

Contact Discontinuities in Models of Contact Binaries Undergoing Thermal Relaxation Oscillations

In this paper we pursue the suggestion by Shu, Lubow & Anderson (1979) and Wang (1995) that contact discontinuity (DSC) may exist in the secondary in the expansion TRO (thermal relaxation oscillation) state. It is demonstrated that there is a mass exchange instability in some range of mass ratio for the two components. We show that the assumption of {\it constant} volume of the secondary should be relaxed in DSC model. For {\it all} mass ratio the secondary alway satisfies the condition that no mass flow returns to the primary through the inner Lagrangian point. The secondary will expand in order to equilibrate the interaction between the common convective envelope and the secondary. The contact discontinuity in contact binary undergoing thermal relaxation does not violate the second law of thermodynamics. The maintaining condition of contact discontinuity is derived in the time-dependent model. It is desired to improve the TRO model with the advanced contact discontinuity layer in future detailed calculations.Comment: 5 pages in emulateapj, 1 figur

The Effect of Locally Delivered Statins on Treating Periodontal Intrabony Defects: A Systematic Review and Metaâ Analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142319/1/jper0357.pd

Spatially-offset Raman spectroscopy for monitoring mineralization of bone tissue engineering scaffolds: feasibility study based on phantom samples

Using phantom samples, we investigated the feasibility of spatially-offset Raman spectroscopy (SORS) as a tool for monitoring non-invasively the mineralization of bone tissue engineering scaffold in-vivo. The phantom samples consisted of 3D-printed scaffolds of poly-caprolactone (PCL) and hydroxyapatite (HA) blends, with varying concentrations of HA, to mimic the mineralisation process. The scaffolds were covered by a 4 mm layer of skin to simulate the real in-vivo measurement conditions. At a concentration of HA approximately 1/3 that of bone (~0.6 g/cm 3), the characteristic Raman band of HA (960 cm-1) was detectable when the PCL:HA layer was located at 4 mm depth within the scaffold (i.e. 8 mm below the skin surface). For the layers of the PCL:HA immediately under the skin (i.e. top of the scaffold), the detection limit of HA was 0.18 g/cm 3 , which is approximately one order of magnitude lower than that of bone. Similar results were also found for the phantoms simulating uniform and inward gradual mineralisation of the scaffold, indicating the suitability of SORS to detect early stages of mineralisation. Nevertheless, the results also show that the contribution of the materials surrounding the scaffold can be significant and methods for subtraction need to be investigated in the future. In conclusion, these results indicate that spatially-offset Raman spectroscopy is a promising technique for in-vivo longitudinal monitor scaffold mineralization and bone re-growth

The battle over Syria's reconstruction

Reconstruction is becoming the new battleground in the Syrian conflict—its continuation by other means. It is instrumentalized by the regime as a way to reconsolidate its control over the country and by rival regional and international powers to shape the internal balance of power and establish spheres of influence in the country. The paper examines the Asad regime’s practices, including co-optation of militia leaders via reconstruction concessions and use of reconstruction to clear strategic areas of opposition-dominated urban settlements. The paper then surveys how the geopolitical struggle in Syria has produced an asymmetry as regards reconstruction: those powers that lost the geo-political contest on the ground seek to use geo-economic superiority to reverse the geo-political outcome. Then the impact of proxy wars and spheres of influence in the country on the security context for reconstruction is examined. Finally, the reconstruction initiatives of the various external parties are assessed, including Russia, Iran and Turkey as well as the spoiler role by which the US seeks to obstruct reconstruction that would spell victory in Syria for its Russian and Iranian rivals.PostprintPeer reviewe

Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery

Background: In over 20% of breast conserving operations, postoperative pathological assessment of the excised tissue reveals positive margins, requiring additional surgery. Current techniques for intra-operative assessment of tumor margins are insufficient in accuracy or resolution to reliably detect small tumors. There is a distinct need for a fast technique to accurately identify tumors smaller than 1 mm2 in large tissue surfaces within 30 min. Methods: Multi-modal spectral histopathology (MSH), a multimodal imaging technique combining tissue auto-fluorescence and Raman spectroscopy was used to detect microscopic residual tumor at the surface of the excised breast tissue. New algorithms were developed to optimally utilize auto-fluorescence images to guide Raman measurements and achieve the required detection accuracy over large tissue surfaces (up to 4 × 6.5 cm2). Algorithms were trained on 91 breast tissue samples from 65 patients. Results: Independent tests on 121 samples from 107 patients - including 51 fresh, whole excision specimens - detected breast carcinoma on the tissue surface with 95% sensitivity and 82% specificity. One surface of each uncut excision specimen was measured in 12–24 min. The combination of high spatial-resolution auto-fluorescence with specific diagnosis by Raman spectroscopy allows reliable detection even for invasive carcinoma or ductal carcinoma in situ smaller than 1 mm2. Conclusions: This study provides evidence that this multimodal approach could provide an objective tool for intra-operative assessment of breast conserving surgery margins, reducing the risk for unnecessary second operations

Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study

This is the final version. Available on open access from the American Chemical Society via the DOI in this recordThe variable configuration of Raman spectroscopic platforms is one of the major obstacles in establishing Raman spectroscopy as a valuable physicochemical method within real-world scenarios such as clinical diagnostics. For such real world applications like diagnostic classification, the models should ideally be usable to predict data from different setups. Whether it is done by training a rugged model with data from many setups or by a primary-replica strategy where models are developed on a 'primary' setup and the test data are generated on 'replicate' setups, this is only possible if the Raman spectra from different setups are consistent, reproducible, and comparable. However, Raman spectra can be highly sensitive to the measurement conditions, and they change from setup to setup even if the same samples are measured. Although increasingly recognized as an issue, the dependence of the Raman spectra on the instrumental configuration is far from being fully understood and great effort is needed to address the resulting spectral variations and to correct for them. To make the severity of the situation clear, we present a round robin experiment investigating the comparability of 35 Raman spectroscopic devices with different configurations in 15 institutes within seven European countries from the COST (European Cooperation in Science and Technology) action Raman4clinics. The experiment was developed in a fashion that allows various instrumental configurations ranging from highly confocal setups to fibre-optic based systems with different excitation wavelengths. We illustrate the spectral variations caused by the instrumental configurations from the perspectives of peak shifts, intensity variations, peak widths, and noise levels. We conclude this contribution with recommendations that may help to improve the inter-laboratory studies.COST (European Cooperation in Science and Technology)Portuguese Foundation for Science and TechnologyNational Research Fund of Luxembourg (FNR)China Scholarship Council (CSC)BOKU Core Facilities Multiscale ImagingDeutsche Forschungsgemeinschaft (DFG, German Research Foundation

Dry Eye Disease in the Middle East and Northern Africa: A Position Paper on the Current State and Unmet Needs

Sihem Lazreg,1 Mohamed Hosny,2 Muhammad A Ahad,3 Mazen M Sinjab,4 Riadh Messaoud,5 Shady T Awwad,6 Antoine Rousseau7 1Ophthalmology Cabinet, Blida, Algeria; 2Refractive and Cornea Service, Cairo University Hospitals, Cairo, Egypt; 3Department of Ophthalmology, Anterior Segment Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; 4Dr Sulaiman Al Habib Hospital, DHCC, Dubai, United Arab Emirates; 5Department of Ophthalmology, Tahar SFAR University Hospital, Mahdia, Tunisia; 6Department of Ophthalmology, American University of Beirut - Medical Center, Beirut, Lebanon; 7Department of Ophthalmology, Bicêtre Hospital, Paris-Saclay University, Le Kremlin-Bicêtre, FranceCorrespondence: Antoine Rousseau, Pierre Testas Building, Bicêtre Hospital, 78 Rue du Général Leclerc, Le Kremlin-Bicêtre, 94270, France, Tel +33145213690, Email [email protected]: In the Middle East and Northern Africa (MENA), dry eye disease (DED) is often misdiagnosed or overlooked. This review summarizes a series of conversations with ophthalmologists in the region around a variety of climatic, lifestyle, and iatrogenic factors that contribute to specific features of DED in the MENA region. These considerations are further classified by patient lifestyle and surgical choices. All statements are based on discussions and formal voting to achieve consensus over three meetings. Overall, a deeper understanding of the disease characteristics of DED specific to MENA can better guide local eyecare practitioners on appropriate management and follow-up care. Additionally, population-based studies and patient and physician education on ocular surface diseases, together with the use of culturally appropriate and language-specific questionnaires can help ease the public health burden of DED in this region.Keywords: ocular surface, regional clinical practice, epidemiology, treatment, patient outcome

Imidazole-induced contractility of vascular smooth muscle cells in the presence of U-73122, ODQ, indomethacin and 7-nitroindazole

The aim of the study was to assess the impact of modulating factors on vascular smooth muscle cells reactivity. Vascular resistance was induced by the administration of increasing concentrations of imidazole. The experiments were performed on isolated and perfused tail artery of Wistar rats (weight 250 g – 350 g). Rats were been narcotized by urethane (intraperitoneal injection) at a dose of 120 mg/kg, stunned and then sacrificed by cervical dislocation. In the following investigation classical pharmacometric methods were used. Relationships between concentration-response curves (CRCs) for imidazole observed in the presence of ODQ [(1H-(1,2,4)oxadiazolo-[4,3-a]quinoxalin-1-one)], 7-nitroindazole and indomethacin were analyzed. Imidazole-induced contractility of vascular smooth muscle cells was independent from alpha-adrenergic receptors and PLC activity. Reactivity of VSMCsinduced by imidazole, was significantly changed in the presence of ODQ and 7-nitroindazole