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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.04.021 Byline: S. Raisin, L. Ruel, N. Ranieri, L. Staccini-Lavenant, P.P. Therond Keywords: Hedgehog; Costal-2 phosphorylation; Drosophila Abstract: Hedgehog (Hh) proteins are secreted molecules that play an essential role in development and tumorigenesis. In Drosophila cultured cells, phosphorylation of the kinesin-like Costal2 (Cos2) protein at Ser572 is triggered by the kinase fused (Fu) upon Hh pathway activation. Here, we validate the first phospho-antibody for one of the Hh pathway components, Cos2, as a universal in situ readout of Hh signal transduction. For the first time, this tool allows the visualisation of a gradient of signalling activity and therefore the range of the activating Hh ligand in different tissues. We also show that, in vivo, Fu kinase is activated by and necessary to transduce all levels of intracellular Hh signalling. Our study fills a gap in the understanding of the Hh pathway by showing that the molecular cascade leading to Cos2 phosphorylation is conserved in all cells activated by Hh. Therefore, we propose that the extracellular Hh information is conveyed to an intracellular signal through graded Fu kinase activity. Author Affiliation: Universite de Nice/Sophia-Antipolis, Institute of Developmental Biology and Cancer, UMR6543-CNRS, UFR Sciences, Parc Valrose, 06108 Nice cedex 02, France Article History: Received 29 January 2010; Revised 21 April 2010; Accepted 22 April 2010

Abstract Efficient distributed computing offers a scalable strategy for solving resource-demanding tasks, such as parallel computation and circuit optimisation. Crucially, the communication overhead introduced by the allotment process should be minimised—a key motivation behind the communication complexity problem (CCP). Quantum resources are well-suited to this task, offering clear strategies that can outperform classical counterparts. Furthermore, the connection between quantum CCPs and non-locality provides an information-theoretic insight into fundamental quantum mechanics. Here we connect quantum CCPs with a generalised non-locality framework—beyond Bell’s paradigmatic theorem—by incorporating the underlying causal structure, which governs the distributed task, into a so-called non-local hidden-variable model. We prove that a new class of communication complexity tasks can be associated with Bell-like inequalities, whose violation is both necessary and sufficient for a quantum gain. We experimentally implement a multipartite CCP akin to the guess-your-neighbour-input scenario, and demonstrate a quantum advantage when multipartite Greenberger-Horne-Zeilinger (GHZ) states are shared among three users.

Antes restrita a uma área de fronteira da Física, a computação quântica é uma das áreas que mais tem crescido atualmente, justamente por suas aplicações tecnológicas em problemas de otimização, aprendizagem de máquina, segurança da informação e simulações. O objetivo deste artigo é introduzir os fundamentos da computação quântica, tendo como foco um algoritmo quântico promissor e sua aplicação a um problema do mercado financeiro. Mais especificamente, discutimos o problema da otimização de portfólio usando o Quantum Approximate Optimization Algorithm (QAOA). Não somente descrevemos os principais conceitos envolvidos, mas também consideramos exemplos simples práticos, envolvendo ativos financeiros disponíveis na bolsa brasileira, com códigos, tanto clássicos quanto quânticos, dísponíveis livremente em um Jupyter Notebook. Também analisamos em detalhes a qualidade das soluções de otimização combinatória de portfólio por meio do QAOA usando o simulador quântico ATOS QLM do SENAI/CIMATEC.

Seen from the modern lens of causal inference, Bell’s theorem is nothing other than the proof that a specific classical causal model cannot explain quantum correlations. It is thus natural to move beyond Bell’s paradigmatic scenario and consider different causal structures. For the specific case of three observable variables, it is known that there are three nontrivial causal networks. Two of those are known to give rise to quantum nonclassicality: the instrumental and the triangle scenarios. Here we analyze the third and remaining one, which we name the Evans scenario, akin to the causal structure underlying the entanglement-swapping experiment. We prove a number of results about this elusive scenario and introduce new and efficient computational tools for its analysis that can also be adapted to deal with more general causal structures. We do not solve its main open problem—whether quantum nonclassical correlations can arise from it—but give a significant step in this direction by proving that postquantum correlations, analogous to the paradigmatic Popescu-Rohrlich box, do violate the constraints imposed by a classical description of the Evans causal structure.

The notorious quantum measurement problem brings out the difficulty to reconcile two quantum postulates: the unitary evolution of closed quantum systems and the wave-function collapse after a measurement. This problematics is particularly highlighted in the Wigner's friend thought experiment, where the mismatch between unitary evolution and measurement collapse leads to conflicting quantum descriptions for different observers. A recent no-go theorem has established that the (quantum) statistics arising from an extended Wigner's friend scenario is incompatible when one try to hold together three innocuous assumptions, namely no-superdeterminism, parameter independence and absoluteness of observed events. Building on this extended scenario, we introduce two novel measures of non-absoluteness of events. The first is based on the EPR2 decomposition, and the second involves the relaxation of the absoluteness hypothesis assumed in the aforementioned no-go theorem. To prove that quantum correlations can be maximally non-absolute according to both quantifiers, we show that chained Bell inequalities (and relaxations thereof) are also valid constraints for Wigner's experiment.

Preparing and measuring physical systems are the operational building blocks of any physical experiment, and to describe them is the first purpose of any physical theory. Remarkably, even when only uncharacterized preparation and measurement devices are present, it is sometimes possible to distinguish between the behaviors of quantum and classical systems from only observational data. Certifying the physical origin of measurement statistics in the prepare and measure scenario is of primal importance for developing quantum networks, distributing quantum keys, and certifying randomness, to mention a few applications, but, surprisingly, no general methods to do so are known. We progress on this problem by crafting a general, sufficient condition to certify that a given set of preparations can only generate classical statistics, for any number of generalized measurements. As an application, we employ the method to demonstrate nonclassicality activation in the prepare and measure scenario, also considering its application in random access codes. Following that, we adapt our method to certify, again through a sufficient condition, whether a given set of measurements can never give rise to nonclassical behaviors, irrespective of what preparations they may act upon. This, in turn, allows us to find a large set of incompatible measurements that cannot be used to demonstrate nonclassicality, thus showing incompatibility is not sufficient for nonclassicality in the prepare and measure scenario.

Quantum communication networks involving the preparation, sharing, and measurement of quantum states are ubiquitous in quantum information. Of particular relevance within this context is to understand under which conditions a given quantum resource can give rise to correlations incompatible with a classical explanation. Here we consider the so-called prepare-and-measure scenario, in which a quantum or classical message with bounded dimension is transmitted between two parties. In this scenario we derive criteria witnessing whether a set of quantum states can lead or not to nonclassical correlations. Based on that, we show that quantum resources that can only give rise to classical correlations in the simplest prepare-and-measure scenario can have their nonclassicality witnessed if we increase the number of preparations or measurements.

The present study evaluates the efficacy and clinical outcomes of crestal sinus lift techniques used to elevate the sinus floor simultaneously with bone grafting and implant placement as a possible and reproducible alternative to lateral sinus lift. Patients underwent different crestal sinus elevation techniques. The heterologous biomaterial was used as graft material, and multiple implants were placed simultaneously after sinus augmentation. Radiographic and clinical examinations were performed during follow-up. All procedures were successfully performed without any apparent perforation of the Schneider membrane. The sinus floor was augmented with an average height of 5 mm (range: 2.8-7.4 mm). The implants healed smoothly with healing screws. Peri-implant marginal bone was stable with a mean follow-up of 50 months (range: 33-71 mo). No complications were observed during the follow-up. Based on the limited data collected in this study, the new crestal sinus elevation approach can effectively raise the sinus floor and reduce the incidence of postoperative complications. Other cases with long-term follow-up are needed to confirm and improve this crestal sinus lift technique., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Objectives: Recent research suggests that increased cerebral oxygen use during surgical intervention for neonates with congenital heart disease may play a role in the development of postoperative white matter injury. The objective of this study is to determine whether increased cerebral electrical activity correlates with greater decrease of cerebral oxygen saturation during deep hypothermic circulatory arrest., Methods: Neonates with critical congenital heart disease requiring surgical intervention during the first week of life were studied. All subjects had continuous neuromonitoring with electroencephalography and an optical probe (to quantify cerebral oxygen saturation) during cardiac surgical repair that involved the use of cardiopulmonary bypass and deep hypothermic circulatory arrest. A simple linear regression was used to investigate the association between electroencephalography metrics before the deep hypothermic circulatory arrest period and the change in cerebral oxygen saturation during the deep hypothermic circulatory arrest period., Results: Sixteen neonates had both neuromonitoring modalities attached during surgical repair. Cerebral oxygen saturation data from 5 subjects were excluded due to poor data quality, yielding a total sample of 11 neonates. A simple linear regression model found that the presence of electroencephalography activity at the end of cooling is positively associated with the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest ( P  < .05)., Conclusions: Electroencephalography characteristics within 5 minutes before the initiation of deep hypothermic circulatory arrest may be useful in predicting the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest. Electroencephalography may be an important tool for guiding cooling and the initiation of circulatory arrest to potentially decrease the prevalence of new white matter injury in neonates with critical congenital heart disease., (© 2023 The Author(s).)

Background: Surgical procedures involving the aortic arch present unique challenges to maintaining cerebral perfusion, and optimal neuroprotective strategies to prevent neurological injury during such high-risk procedures are not completely understood. The use of antegrade cerebral perfusion (ACP) has gained favor as a neuroprotective strategy over deep hypothermic circulatory arrest (DHCA) due to the ability to selectively perfuse the brain. Despite this theoretical advantage over DHCA, there has not been conclusive evidence that ACP is superior to DHCA. One potential reason for this is the incomplete understanding of ideal ACP flow rates to prevent both ischemia from underflowing and hyperemia and cerebral edema from overflowing. Critically, there are no continuous, noninvasive measurements of cerebral blood flow (CBF) and cerebral oxygenation (StO 2 ) to guide ACP flow rates and help develop standard clinical practices. The purpose of this study is to demonstrate the feasibility of using noninvasive, diffuse optical spectroscopy measurements of CBF and cerebral oxygenation during the conduct of ACP in human neonates undergoing the Norwood procedure., Methods: Four neonates prenatally diagnosed with hypoplastic left heart syndrome (HLHS) or a similar variant underwent the Norwood procedure with continuous intraoperative monitoring of CBF and cerebral oxygen saturation (StO 2 ) using two non-invasive optical techniques, namely diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS). Changes in CBF and StO 2 due to ACP were calculated by comparing these parameters during a stable 5 min period of ACP to the last 5 min of full-body CPB immediately prior to ACP initiation. Flow rates for ACP were left to the discretion of the surgeon and ranged from 30 to 50 ml/kg/min, and all subjects were cooled to 18°C prior to initiation of ACP., Results: During ACP, the continuous optical monitoring demonstrated a median (IQR) percent change in CBF of -43.4% (38.6) and a median (IQR) absolute change in StO 2 of -3.6% (12.3) compared to a baseline period during full-body cardiopulmonary bypass (CPB). The four subjects demonstrated varying responses in StO 2 due to ACP. ACP flow rates of 30 and 40 ml/kg/min ( n  = 3) were associated with decreased CBF during ACP compared to full-body CPB. Conversely, one subject with a higher flow6Di rate of 50 ml/kg/min demonstrated increased CBF and StO 2 during ACP., Conclusions: This feasibility study demonstrates that novel diffuse optical technologies can be utilized for improved neuromonitoring in neonates undergoing cardiac surgery where ACP is utilized. Future studies are needed to correlate these findings with neurological outcomes to inform best practices during ACP in these high-risk neonates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Shaw, Mavroudis, Ko, Jahnavi, Jacobwitz, Ranieri, Forti, Melchior, Baker, Yodh, Licht, Nicolson and Lynch.)

A "toolkit" consisting of a handheld Raman spectrometer equipped with a 1064 nm laser, a portable Fourier transform infrared (FT-IR) spectrometer and a portable direct analysis in real-time mass spectrometer (DART-MS) was employed in a laboratory setting to examine 82 representative products collected during a nationwide mail blitz for the presence of APIs. These results were compared to those obtained using laboratory-based methods; 8 of the products were not found to contain APIs and 74 of the products were found to contain a total of 88 APIs (65 of the 88 APIs were unique). The individual performance of each device and combined performance of the three-device toolkit were evaluated with regard to true positives, true negatives, false positives and false negatives. Using this toolkit, 81 (92.0 %) of the APIs were detected by at least one technique and 47 (64.8 %) of the APIs were detected by at least two techniques. Seven false negatives (8.0 %) were encountered and while the toolkit yielded 12 false positives, no false positives were detected by more than one technique. Overall, this study demonstrated that when the toolkit detects an API using two or more devices, the results are as reliable as those generated by a full-service laboratory., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Published by Elsevier B.V.)

Background: The US FDA recently developed CD3+, a counterfeit detection tool that is based on sample illumination at specific wavelengths of light and visual comparison of suspect sample and packaging materials to an authentic sample. To test performance of the CD3+ in field conditions, a study was conducted in Ghana which compared the CD3+ side-by-side with two existing medicine quality screening technologies-TruScan™ Portable Raman spectrometer and GPHF Minilab(®)., Methods: A total of 84 anti-malarial test samples comprising artemether-lumefantrine tablets and artesunate-amodiaquine tablets were used. The technologies were evaluated for sensitivity in determining counterfeit/substandard (The term counterfeit or falsified is used in this article to refer to medicines that carry a false representation of identity or source or both. The term substandard is used to refer to medicines that do not meet the quality specifications given in the accepted pharmacopeia.) medicines, specificity in determining authentic products, and reliability of the results. Authentic samples obtained from manufacturers were used as reference standards. HPLC analysis data was used as the "gold standard" for decisions regarding a sample being authentic or substandard/counterfeit., Results: CD3+ had a sensitivity of 1.00 in detecting counterfeit/substandard products compared to Minilab (0.79) and TruScan (0.79). CD3+ had a lower specificity (0.53) in determining authentic products compared to the specificities reached by Minilab (0.99) and TruScan (1.00). High sensitivity in this context means that the technology is effective in identifying substandard/counterfeit products whereas the low specificity means that the technique can sometimes mischaracterize good products as substandard/counterfeit. Examination of dosage units only (and not packaging) using CD3+ yielded improved specificity 0.64. When only assessment of sample identification was done, the TruScan provided sensitivity (1.00) and specificity (0.99); and the Minilab provided sensitivity (1.00) and specificity (1.00). All three technologies demonstrated 100 % reliability when used to analyse the same set of samples over 3 days by a single analyst and also when used to determine the same set of samples by three different analysts. Eight of the field samples were confirmed to be counterfeits with no active pharmaceutical ingredient content. All three technologies identified these samples as counterfeits., Conclusions: The study revealed the relative effectiveness of the technologies as quality control tools. Using a combination of CD3+, with either the Minilab or TruScan, to screen for medicine quality will allow for complete examination of both the dosage units and the packaging to decide whether it is authentic or counterfeit.

The availability of falsified antimalarial drugs can be reduced with effective drug regulatory agencies and proper enforcement. Fundamental to these agencies taking action, rapid identification must be made as soon as they appear in the market place. Since falsified antimalarials occur mostly in developing countries, performing drug analysis presents itself with unique challenges. A fundamental factor in choosing a useful technique is affordability and simplicity. Therefore, we suggest a three-tiered drug evaluation strategy for identifying a falsified drug in resource-poor areas. Tier I is a simple comparison of a tablet's weight and dimensions with official specifications. Tier II uses inexpensive photometric devices (laser and fluorescence) to evaluate a tablet. Suspicious samples from Tier I and II assessments are then subjected to a colorimetric assay for active ingredients identification and quantification. In this article, we evaluate a novel colorimetric assay for the simultaneous assessment of both lumefantrine and artemether in co-formulated Coartem™ tablets, and integrate the method with two novel, low-cost, fluorescence and laser photometric devices. Image analysis software is used for the assessments. Although artemether-lumefantrine is used as an example, the strategy may be adapted to other medicines., (© The American Society of Tropical Medicine and Hygiene.)

There is an urgent need for accurate and inexpensive handheld instruments for the evaluation of medicine quality in the field. A blinded evaluation of the diagnostic accuracy of the Counterfeit Detection Device 3 (CD-3), developed by the US Food and Drug Administration Forensic Chemistry Center, was conducted in the Lao People's Democratic Republic. Two hundred three samples of the oral antimalarial artesunate were compared with authentic products using the CD-3 by a trainer and two trainees. The specificity (95% confidence interval [95% CI]), sensitivity (95% CI), positive predictive value (95% CI), and negative predictive value (95% CI) of the CD-3 for detecting counterfeit (falsified) artesunate were 100% (93.8-100%), 98.4% (93.8-99.7%), 100% (96.2-100%), and 97.4% (90.2-99.6%), respectively. Interobserver agreement for 203 samples of artesunate was 100%. The CD-3 holds promise as a relatively inexpensive and easy to use instrument for field evaluation of medicines, potentially empowering drug inspectors, customs agents, and pharmacists., (© The American Society of Tropical Medicine and Hygiene.)

Hedgehog (Hh) signalling is crucial for developmental patterning and tissue homeostasis. In Drosophila, Hh signalling is mediated by a bifunctional transcriptional mediator, called Cubitus interruptus (Ci). Protein Kinase A (PKA)-dependent phosphorylation of the serpentine protein Smoothened (Smo) leads to Ci activation, whereas PKA-dependent phosphorylation of Ci leads to the formation of Ci repressor form. The mechanism that switches PKA from an activator to a repressor is not known. Here we show that Hh signalling activation causes PKA to switch its substrates from Ci to Smo within the Hh signalling complex (HSC). In particular, Hh signalling increases the level of Smo, which then outcompetes Ci for association with PKA and causes a switch in PKA substrate recognition. We propose a new model in which the PKA is constitutively present and active within the HSC, and in which the relative levels of Ci and Smo within the HSC determine differential activation and cellular response to Hh signalling.