Demonstration of Shor’s factoring algorithm for N $$=$$ 21 on IBM quantum processors

We report a proof-of-concept demonstration of a quantum order-finding algorithm for factoring the integer 21. Our demonstration involves the use of a compiled version of the quantum phase estimation routine, and builds upon a previous demonstration. We go beyond this work by using a configuration of approximate Toffoli gates with residual phase shifts, which preserves the functional correctness and allows us to achieve a complete factoring of $$N=21$$ N = 21 . We implemented the algorithm on IBM quantum processors using only five qubits and successfully verified the presence of entanglement between the control and work register qubits, which is a necessary condition for the algorithm’s speedup in general. The techniques we employ may be useful in carrying out Shor’s algorithm for larger integers, or other algorithms in systems with a limited number of noisy qubits.

Cyanide as a Primordial Reductant enables a Protometabolic Reductive Glyoxylate Pathway

Investigation of prebiotic chemical pathways leading to protometabolic forerunners of metabolism has been largely based on bio-inspired (iron-mediated) reductive conversion of carbon dioxide and of carboxylic acid substrates.1,2 While attractive from a parsimony point of view, this approach has been challenging with debatable outcomes.3,4 Herein, we show that cyanide reacts with citric acid cycle (TCA) intermediates and derivatives and acts as a primordial reducing agent mediating abiotic reductive transformations. The hydrolysis of the cyanide adducts followed by decarboxylation enables the efficient reductive-decarboxylative transformation of oxaloacetate to malate and fumarate to succinate while pyruvate and α-ketoglutarate are not reduced. In the presence of glyoxylate,5,6 malonate7 and malononitrile,8 alternative pathways emerge, which after decarboxylation produce metabolic intermediates and related compounds also found in meteorites.9 These results, along with the previous demonstration of the metal-free alpha-keto analog of the reverse-TCA cycle,4,6 suggest that (a) alternative paradigms of cyanide-based protometabolic reactions bypassing the abiotic reductive-carboxylation steps can be prebiotically viable, (b) a novel reductive glyoxylate pathway can be a precursor to the r-TCA cycle and (c) the type of sophisticated carboxylation and reduction chemistries which are part of extant metabolic cycles10,11 are an evolutionary invention mediated by complex metalloproteins11.

Validation of the Preoperative Score to Predict Postoperative Mortality (POSPOM) in Germany

Background The Preoperative Score to Predict Postoperative Mortality (POSPOM) based on preoperatively available data was presented by Le Manach et al. in 2016. This prognostic model considers the kind of surgical procedure, patients' age and 15 defined comorbidities to predict the risk of postoperative in-hospital mortality. Objective of the present study was to validate POSPOM for the German healthcare coding system (G-POSPOM). Methods and findings All cases involving anaesthesia performed at the University Hospital Bonn between 2006 and 2017 were analysed retrospectively. Procedures codified according to the French Groupes Homogènes de Malades (GHM) were translated and adapted to the German Operationen- und Prozedurenschlüssel (OPS). Comorbidities were identified by the documented International Statistical Classification of Diseases (ICD-10) coding. POSPOM was calculated for the analysed patient collective using these data according to the method described by Le Manach et al. Performance of thereby adapted POSPOM was tested using c-statistic, Brier score and a calibration plot. Validation was performed using data from 199,780 surgical cases. With a mean age of 56.33 years (SD 18.59) and a proportion of 49.24% females, the overall cohort had a mean POSPOM value of 18.18 (SD 8.11). There were 4,066 in-hospital deaths, corresponding to an in-hospital mortality rate of 2.04% (95% CI 1.97 to 2.09%) in our sample. POSPOM showed a good performance with a c-statistic of 0.771 and a Brier score of 0.021. Conclusions After adapting POSPOM to the German coding system, we were able to validate the score using patient data of a German university hospital. According to previous demonstration for French patient cohorts, we observed a good correlation of POSPOM with in-hospital mortality. Therefore, further adjustments of POSPOM considering also multicentre and transnational validation should be pursued based on this proof of concept.

PAK1 Regulates MEC-17 Acetyltransferase Activity and Microtubule Acetylation during Proplatelet Extension

Mature megakaryocytes extend long processes called proplatelets from which platelets are released in the blood stream. The Rho GTPases Cdc42 and Rac as well as their downstream target, p21-activated kinase 2 (PAK2), have been demonstrated to be important for platelet formation. Here we address the role, during platelet formation, of PAK1, another target of the Rho GTPases. PAK1 decorates the bundled microtubules (MTs) of megakaryocyte proplatelets. Using a validated cell model which recapitulates proplatelet formation, elongation and platelet release, we show that lack of PAK1 activity increases the number of proplatelets but restrains their elongation. Moreover, in the absence of PAK1 activity, cells have hyperacetylated MTs and lose their MT network integrity. Using inhibitors of the tubulin deacetylase HDAC6, we demonstrate that abnormally high levels of MT acetylation are not sufficient to increase the number of proplatelets but cause loss of MT integrity. Taken together with our previous demonstration that MT acetylation is required for proplatelet formation, our data reveal that MT acetylation levels need to be tightly regulated during proplatelet formation. We identify PAK1 as a direct regulator of the MT acetylation levels during this process as we found that PAK1 phosphorylates the MT acetyltransferase MEC-17 and inhibits its activity.

East Village at Knutsford: A Case Study in Sustainable Urbanism

With increasing pressure to ensure that sustainability features in homes are commercially viable, demonstration projects are vital to highlight the real-world challenges and opportunities for innovation. This paper documents the incorporation of sustainability objectives into the “East Village at Knutsford” residential “living laboratory” development, within the Knutsford urban regeneration precinct, approximately 1.5 km east of the Fremantle central business district in Western Australia. The sustainability objectives for the project include being a “Net Zero Energy Development” using 100% renewable energy and maximizing the self-supply of energy, reducing mains water consumption as much as is practical, and using the landscape design to complement these objectives without compromising a best-practice urban greening outcome. The paper documents the design initiatives and strategies that have been included to achieve these objectives in a commercially viable project and the results of modelling where it has been used to test the design against the objectives to ensure their validity. The key features that have been incorporated into the townhouses component of the development are outlined, illustrating integrated design and systems thinking that builds on previous demonstration projects, incorporating solar energy storage and electric vehicle charging plus significant mains water savings by adopting water-sensitive features in the homes and the within the private and public gardens. The expected grid energy and mains water consumption levels in the homes through modelling compared to the metropolitan average is 80% lower. The project is presented as an important step in the application of available technologies and design features to meet stated sustainability objectives, highlighting the benefits of an embedded living laboratory research approach.

Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse

No therapies currently exist for intellectual disability in Down syndrome (DS). In view of its similarities with DS, including learning and memory (L&M) defects, the Ts65Dn mouse model of DS is widely used for the design of therapy. 7,8-dihydroxyflavone (7,8-DHF), a flavonoid that targets the tropomyosin-related kinase B (TrkB) receptor of brain-derived neurotrophic factor (BDNF), exerts positive effects in various brain disease models. Based on previous demonstration that administration of 7,8-DHF in the postnatal period P3-P15 restores hippocampal neurogenesis and spinogenesis, we sought to establish whether these effects translate into behavioral benefits after treatment cessation. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) during postnatal days P3-P15 did not show any L&M improvement at one month after treatment cessation, indicating that the effects of 7,8-DHF on the brain are ephemeral. Based on evidence that chronic treatment with 7,8-DHF in juvenile Ts65Dn mice restores L&M, we sought to establish whether a similar effect is elicited in adulthood. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) for about 40 days starting from 4 months of age did not show any improvement in L&M. The results suggest that timing of therapy with 7,8-DHF is a critical issue for attainment of positive effects on the brain.

The role of matrilineality in shaping patterns of Y chromosome and mtDNA sequence variation in southwestern Angola

Southwestern Angola is a region characterized by contact between indigenous foragers and incoming food-producers, involving genetic and cultural exchanges between peoples speaking Kx’a, Khoe-Kwadi and Bantu languages. Although present-day Bantu-speakers share a patrilocal residence pattern and matrilineal principle of clan and group membership, a highly stratified social setting divides dominant pastoralists from marginalized groups that subsist on alternative strategies and have previously been though to have pre-Bantu origins. Here, we compare new high-resolution sequence data from 2.3 Mb of the non-recombining Y chromosome (NRY) from 170 individuals with previously reported mitochondrial genomes (mtDNA), to investigate the population history of seven representative southwestern Angolan groups (Himba, Kuvale, Kwisi, Kwepe, Twa, Tjimba, !Xun) and to study the causes and consequences of sex-biased processes in their genetic variation. We found no clear link between the formerly Kwadi-speaking Kwepe and pre-Bantu eastern African migrants, and no pre-Bantu NRY lineages among Bantu-speaking groups, except for small amounts of “Khoisan” introgression. We therefore propose that irrespective of their subsistence strategies, all Bantu-speaking groups of the area share a male Bantu origin. Additionally, we show that in Bantu-speaking groups, the levels of among-group and between-group variation are higher for mtDNA than for NRY. These results, together with our previous demonstration that the matriclanic systems of southwestern Angolan Bantu groups are genealogically consistent, suggest that matrilineality strongly enhances both female population sizes and interpopulation mtDNA variation.

Economic Cooperation Between Latvia and China on the Background of Belt and Road Initiative with Focus on Cargo Potential

Latvia is a Belt and Road Initiative country and can contribute to its Eurasian Land Bridge. The existing railway infrastructure can be used for establishing the Eurasian Land Bridge Northern Branch via Latvia, but the problem is a lack of cargo for this route. It can be integrated into the existing Eurasian Land Bridge with specialization to connect China and some European countries—the Scandinavian countries. The aim of the study is to assess the potential volume of Latvian cargo for the Eurasian Land Bridge Northern Branch through Latvia. The methods of the study are statistical analyses and the forecasts of experts. Forecast of experts is an innovative method for investigating this topic. The study contributes to the discussion regarding One Belt One Road and Eurasian Land Bridge. The research shows that it is possible to establish regular container block train between Latvia and China for distribution of Chinese goods in the Scandinavian countries and vice versa because cargo potential for this route is growing, the seaport of Riga in Latvia is the shortest route to the seaport in the European Union and previous demonstration trains were successful.

Transplantation of Cultured Olfactory Bulb Cells Prevents Abnormal Sensory Responses during Recovery from Dorsal Root Avulsion in the Rat

The central branches of the C7 and C8 dorsal roots were avulsed close to their entry point into the spinal cord in adult rats. The forepaw responses to heat and cold stimuli were tested at 1, 2, and 3 weeks after injury. Over this period, the paws were sensitive to both stimuli at 1-2 weeks and returned toward normal at 3 weeks. Immunohistology showed no evidence of axonal regeneration into the spinal cord in a control group of rats with avulsion only, implying that adjacent dorsal roots and their corresponding dermatomes were involved in the recovery. In a further group of rats, a mixture of bulbar olfactory ensheathing cells and olfactory nerve fibroblasts were transplanted into the gap between the avulsed roots and the spinal cord at the time of avulsion. These rats showed no evidence of either loss of sensation or exaggerated responses to stimuli at any of the time points from 1 to 3 weeks. Immunohistology showed that the transplanted cells formed a complete bridge, and the central branches of the dorsal root fibers had regenerated into the dorsal horn of the spinal cord. These regenerating axons, including Tuj1 and CGRP immunoreactive fibers, were ensheathed by the olfactory ensheathing cells. This confirms our previous demonstration of central regeneration by these transplants and suggests that such transplants may provide a useful means to prevent the development of abnormal sensations such as allodynia after spinal root lesions.

Band 3 Phosphorylation Induces Irreversible Alteration of Stored Red Blood Cells

Introduction: Storage of red blood cells (RBCs) for transfusion purposes is accompanied by a number of morphological and biochemical changes (storage lesions) that reduce post-transfusion survival/efficacy and increase risk for adverse reactions in the recipients. The clearance of altered and older RBCs from circulation is triggered by the clustering of Band 3, an aggregate state that is recognized by a low-affinity naturally occurring IgG antibody (Nab). Considering the key role of Band 3 in the maintenance of RBC structure and survival, elucidation of functional and structural modifications of Band 3 during storage should lead to new approaches aiming to improve RBC storage and post-transfusion viability. Results: Immunoblot analysis of RBC membrane proteins using an anti-phosphotyrosine antibody showed a progressive increase in the phosphorylation status of Band 3 during RBC storage (Figure 1). In addition, using the quenching fluorescence of eosin-5-maleimide (EMA), we showed an increase of the mobile fraction of Band 3. These findings are consistent with previous demonstration that tyrosine phosphorylation of Band 3 reduces its affinity for ankyrin, leading to the release of the immobile fraction of Band 3 from the skeleton complex, and enhancement of the lateral mobility of Band 3 into the lipid bilayer. Immunoblot experiments using an antibody that specifically recognizes the clustered form of Band 3 revealed an increase of Band 3 cluster formation from the 28th day of storage. We also showed that the release of microparticles (MPs) that occurs during RBC aging increases from the 28th day of storage (Figure 2). Finally, stopped-flow-based functional studies showed a decrease of the anion exchanger activity of Band 3 from the 28th day of storage. Conclusion: Altogether, our results suggest that the 28th of storage represents a key moment for the molecular processes leading to irreversible lesions of RBCs and allow us to propose a new Band 3 phosphorylation/clustering-based mechanism of RBC aging. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.