Rhythmic inhibition allows neural networks to search for maximally consistent states

Gamma-band rhythmic inhibition is a ubiquitous phenomenon in neural circuits yet its computational role still remains elusive. We show that a model of Gamma-band rhythmic inhibition allows networks of coupled cortical circuit motifs to search for network configurations that best reconcile external inputs with an internal consistency model encoded in the network connectivity. We show that Hebbian plasticity allows the networks to learn the consistency model by example. The search dynamics driven by rhythmic inhibition enable the described networks to solve difficult constraint satisfaction problems without making assumptions about the form of stochastic fluctuations in the network. We show that the search dynamics are well approximated by a stochastic sampling process. We use the described networks to reproduce perceptual multi-stability phenomena with switching times that are a good match to experimental data and show that they provide a general neural framework which can be used to model other 'perceptual inference' phenomena

The geology and geochronology of Al Wahbah maar crater, Harrat Kishb, Saudi Arabia

Al Wahbah is a large (∼2.2 km diameter, ∼250 m deep) maar crater in the Harrat Kishb volcanic field in western Saudi Arabia. It cuts Proterozoic basement rocks and two Quaternary basanite lava flows, and is rimmed with an eroded tuff ring of debris from the phreatomagmatic explosion that generated the crater. A scoria cone on the northern wall of the crater was dissected by the explosion and exposes a dolerite plug that was intruded immediately prior to crater formation. The dolerite plug yields a <sup>40</sup>Ar/<sup>39</sup>Ar age of 1.147 ± 0.004 Ma. This is the best possible estimate of the time Al Wahbah crater formed. It is a few tens of thousand years younger than the age of the lower and upper basalt flows, 1.261 ± 0.021 Ma and 1.178 ± 0.007 Ma respectively. A dolerite dyke exposed within the basement in the wall of the crater is dated at 1.886 ± 0.008 Ma. This is the most precise age so far determined for the initiation of basaltic volcanism of Harrat Kishb, and confirms that it is significantly younger than the other post-rift volcanic provinces in the region. This study provides constrains the timing of humid climatic conditions in the region and suggests that the Quaternary basaltic volcanism that stretches the length of the western side of the Arabian peninsula may prove to be useful for establishing palaeoclimatic conditions

Radiopharmaceutical dose distribution in different organs and tissues for Lu-177 with different carrier

177Lu refers to rare earth elements from a group of lanthanides. Relative to its short time span, 177Lu has virtually pervaded all areas of in vivo radionuclide therapy and becomes one of important keys for therapeutic radionuclides of choice for targeted radionuclide therapy. The rising interest in the use of 177Lu in targeted molecular therapies has primarily developed from recent unmatched advances in molecular and cell biology, which include the use of peptides targeted to cell surface receptors, which are overexpressed on the surface of tumour cells. Therefore, the use of 177Lu-labelled radiopharmaceuticals have been the major factors evoking excitement among researchers and capturing the imagination of the clinical community thanks to advances in molecular and cellular biology. In this work, radiopharmaceutical comparison for 177Lu absorbed dose in health human organs and tissues is presented. The comparison between unlabelled 177Lu (ionic form) and labelled with 177Lu-MDP (methylenediphosphonate) and 177Lu-MAb (monoclonal antibodies). The biokinetic model in each case are described and presented. The absorbed dose in health human organs and tissues are simulated with two recommended programs WinAct and IDAC 2.1(Internal Dose Assessment by Computer) software. The distribution of absorbed dose in the main organs nearly the same with different in the value for the ionic form and 177Lu-MDP. The absorption in the case of ionic form is high. The distribution is completely change while 177Lu-MAb is used. The most absorbed dose fraction goes to spleen and liver unlike bone surface absorb nearly 50 % of dose. © 2019 Author(s)

Design, synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI$_{50}$ values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI$_{50}$ value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC$_{50}$ values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC$_{50}$ = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC$_{50}$ values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC$_{50}$ = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score

Novel 1,5-diaryl pyrazole-3-carboxamides as selective COX-2/sEH inhibitors with analgesic, anti-inflammatory, and lower cardiotoxicity effects

Funding Information: The authors extend their appreciation to the Deanship of Scientific Research at Jouf University for funding this work through research grant number (DSR2020-04-421 )Peer reviewedPostprin

Design, synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI50 values ranging from 0.70 mM to 1.20 mM, compared to doxorubicin GI50 value = 1.10 mM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC50 values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC50 = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC50 values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC50 = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Monitoring and Assessing the Coastal Ecosystem at Hurghada, Red Sea Coast, Egypt

In the framework of the investment plan, the government of Egypt introduced an accelerated development of Hurghada in collaboration with the private sector, as   early as 1980's.  The government intended to construct tourist resort communities, which required establishment of infrastructures. The  demand  of  such  facilities, in absence of enforced environmental roles led owners  to implement  processes  of  landfilling  and  dredging  for the purpose of smoothing, paving and widening the beach in order to construct swimming pools, marinas and other recreational facilities. Such activities came on the expense of the marine ecosystem and especially assault on the coral reef communities. For monitoring and assessing such oppressive activities;  MSS,  TM,  ETM+,  and SPOT XS 4 satellite images acquired  during  1972,  1984,  1992,  2004  and 2011. Shoreline change detection from 1972 to 2011 reveals landfilling of some 7.56Km2 and dredging of 2.67km2, with loss of 5.34km2 of the reef tracts. At the same period, the region has witnessed expansions in urban and road network by 16.47km2 and 8.738km2 respectively. The Egyptian government issued the essential laws for regulating and saving the coastal ecosystem, yet mostly violated. Activation of such laws, applying judicial officers, toughening penalties and establishment of coastal building front line (CBFL), and a reef protection line (RPL) are important tasks especially south of Hurghada to the Egyptian-Sudanese borders to preserve the remnants of such unique coastal ecosystem. Keywords: Satellite images, Hurghada, Red Sea, coastal ecosystem, shoreline changes, urban, road network, environment law