Counterfactual quantum computation through quantum interrogation

The logic underlying the coherent nature of quantum information processing often deviates from intuitive reasoning, leading to surprising effects. Counterfactual computation constitutes a striking example: the potential outcome of a quantum computation can be inferred, even if the computer is not run. Relying on similar arguments to interaction-free measurements (or quantum interrogation), counterfactual computation is accomplished by putting the computer in a superposition of 'running' and 'not running' states, and then interfering the two histories. Conditional on the as-yet-unknown outcome of the computation, it is sometimes possible to counterfactually infer information about the solution. Here we demonstrate counterfactual computation, implementing Grover's search algorithm with an all-optical approach. It was believed that the overall probability of such counterfactual inference is intrinsically limited, so that it could not perform better on average than random guesses. However, using a novel 'chained' version of the quantum Zeno effect, we show how to boost the counterfactual inference probability to unity, thereby beating the random guessing limit. Our methods are general and apply to any physical system, as illustrated by a discussion of trapped-ion systems. Finally, we briefly show that, in certain circumstances, counterfactual computation can eliminate errors induced by decoherence.     

Co-design Research and Business Development: Case of Scandinavian Airlines (SAS)

This paper is presenting a case study of Scandinavian Airlines Systems (SAS) showing how improvements of service quality aspects with Avatars can be managed with a Co-design research approach. The Co-design practices are carried out in different fields of studies. Some of the key advocates of Co-design originate from business. In this study the four steps of Co-design approach is applied. From the first step of Co-design, through interviews, log analysis and a channel survey, findings show that the failed dialogues with Avatar Eva are mainly concerned with five factors: interactivity; dialogue capability; consistency; knowledge; and synonyms. In the second step, carrying out customer workshops, we suggested ten ideal scenarios for Avatar Eva to perform better. In the third step, SAS decision makers decided to implement the first three scenarios: Eva’s synonyms; knowledge and Eva’s consistency. In the fourth step, another channel survey was carried out as well as a new log analysis to know the impact of the redevelopment above three scenarios. An important result of the study was that the company adopted a continuous use of Co-design as an approach of continuous improvement of the service quality performed by the Avatar Eva. It also opens a new set of questions framing the relation and transformation between Co-design as a research approach for knowledge creation and Co-design as a method for innovation and service quality improvements. The study presents an Extended Co-design Model, which illustrates how the Co-design inspires staff to use it for other functions within and without the SAS.     

Solid-particle erosion behavior of cast alloys used in the mining industry

The erosive-wear response of five commercial ferrous-based cast alloys used for crushing was examined in this study. The micro-structures of the alloys were modified to elucidate the effect of microstructural features on wear. Erosion tests were conducted using alumi-num oxide particles (90–125 μm) at 70 m/s and a normal impact angle (90°). The worn surfaces were characterized by scanning electron mi-croscopy and 3D non-contact laser profilometry. It is found that (i) a pearlitic structure exhibiting a greater plastic deformation than both bainitic and martensitic structures shows the greatest resistance to erosive wear at normal impact and (ii) the fracture characteristics of car-bide and graphite particles plays an important role in determining the erosion wear behavior of the cast alloy matrices.     

Labelling of a pyrazole derivative with 131I and investigation of its radiopharmaceutical potential

We investigated the radiolabeling efficiency, in vitro stability, and biodistribution of radioactive iodine (131I)-labeled 4-benzoyl-1-(4-carboxyphenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (P3CA). A quality-control study of the labeled substance ( 131I-P3CA) was conducted using electrophoresis and radio thin-layer chromatography (RTLC). Biodistribution studies were undertaken in 9 female albino Wistar rats. Rats were killed at various times (15, 60 and 180 min), their organs removed, and percentage of injected dose per gram (ID%/g) values calculated. The labeling yield of P3CA was 97.08%±0.80%. The maximum uptake of 131I-P3CA was seen in the lungs, stomach and spleen at 15 min. The uptake of labeled compound decreased over time in the lungs, whereas that in the stomach decreased. These data suggest that 131I-P3CA had high binding efficiency, high uptake in the lung, and sufficient stability to be used in diagnostic studies.     

mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells—an ectoenzyme that produces the paracrine factor cyclic ADP ribose—mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.     

Exploiting a natural conformational switch to engineer an interleukin-2 'superkine'

The immunostimulatory cytokine interleukin-2 (IL-2) is a growth factor for a wide range of leukocytes, including T cells and natural killer (NK) cells. Considerable effort has been invested in using IL-2 as a therapeutic agent for a variety of immune disorders ranging from AIDS to cancer. However, adverse effects have limited its use in the clinic. On activated T cells, IL-2 signals through a quaternary 'high affinity' receptor complex consisting of IL-2, IL-2Rα (termed CD25), IL-2Rβ and IL-2Rγ. Naive T cells express only a low density of IL-2Rβ and IL-2Rγ, and are therefore relatively insensitive to IL-2, but acquire sensitivity after CD25 expression, which captures the cytokine and presents it to IL-2Rβ and IL-2Rγ. Here, using in vitro evolution, we eliminated the functional requirement of IL-2 for CD25 expression by engineering an IL-2 'superkine' (also called super-2) with increased binding affinity for IL-2Rβ. Crystal structures of the IL-2 superkine in free and receptor-bound forms showed that the evolved mutations are principally in the core of the cytokine, and molecular dynamics simulations indicated that the evolved mutations stabilized IL-2, reducing the flexibility of a helix in the IL-2Rβ binding site, into an optimized receptor-binding conformation resembling that when bound to CD25. The evolved mutations in the IL-2 superkine recapitulated the functional role of CD25 by eliciting potent phosphorylation of STAT5 and vigorous proliferation of T cells irrespective of CD25 expression. Compared to IL-2, the IL-2 superkine induced superior expansion of cytotoxic T cells, leading to improved antitumour responses in vivo, and elicited proportionally less expansion of T regulatory cells and reduced pulmonary oedema. Collectively, we show that in vitro evolution has mimicked the functional role of CD25 in enhancing IL-2 potency and regulating target cell specificity, which has implications for immunotherapy.     

The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin

Nephronophthisis, the most common genetic cause of chronic renal failure in children, is a progressive tubulo-interstitial kidney disorder that is inherited as an autosomal recessive trait. The disease is characterized by polyuria, growth retardation and deterioration of renal function during childhood or adolescence. The most prominent histological features are modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Nephronophthisis can also be associated with conditions affecting extrarenal organs, such as retinitis pigmentosa (Senior-L?ken syndrome) and ocular motor apraxia (Cogan syndrome). Three loci are associated with the juvenile, infantile and adolescent forms, on chromosomes 2q13 (NPHP1; refs 5,6), 9q22 (NPHP2; ref. 7) and 3q21 (NPHP3; ref. 8), respectively. NPHP1, the only gene identified so far, encodes nephrocystin, which contains a Src homology 3 (SH3) domain and interacts with intracytoplasmic proteins involved in cell adhesion. Recently, a second locus associated with the juvenile form of the disease, NPHP4, was mapped to chromosome 1p36 (ref. 14). We carried out haplotype analysis of families affected with nephronophthisis that were not linked to the NPHP1, NPHP2 or NPHP3 loci, using markers covering this region. This allowed us to reduce the NPHP4 interval to a one centimorgan interval between D1S2795 and D1S2870, which contains six genes. We identified five different mutations in one of these genes, designated NPHP4, in unrelated individuals with nephronophthisis. The NPHP4 gene encodes a 1,250-amino acid protein of unknown function that we named nephrocystin-4. We demonstrated the interaction of nephrocystin-4 with nephrocystin suggesting that these two proteins participate in a common signaling pathway.     

Ambra1 regulates autophagy and development of the nervous system

Autophagy is a self-degradative process involved both in basal turnover of cellular components and in response to nutrient starvation or organelle damage in a wide range of eukaryotes. During autophagy, portions of the cytoplasm are sequestered by double-membraned vesicles called autophagosomes, and are degraded after fusion with lysosomes for subsequent recycling. In vertebrates, this process acts as a pro-survival or pro-death mechanism in different physiological and pathological conditions, such as neurodegeneration and cancer; however, the roles of autophagy during embryonic development are still largely uncharacterized. Beclin1 (Becn1; coiled-coil, myosin-like BCL2-interacting protein) is a principal regulator in autophagosome formation, and its deficiency results in early embryonic lethality. Here we show that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulates autophagy and has a crucial role in embryogenesis. We found that Ambra1 is a positive regulator of the Becn1-dependent programme of autophagy, as revealed by its overexpression and by RNA interference experiments in vitro. Notably, Ambra1 functional deficiency in mouse embryos leads to severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death. In addition to identifying a new and essential element regulating the autophagy programme, our results provide in vivo evidence supporting the existence of a complex interplay between autophagy, cell growth and cell death required for neural development in mammals.     

Mechanical properties and microstructure of composites produced by recycling metal chips

In this study, the processing and mechanical properties of porous metal matrix composites (MMCs) composed of spheroidal cast iron chips (GGG40) and bronze chips (CuSn10) and formed by hot isostatic pressing were investigated. Bronze chips (CuSn10) were used as a matrix component, and spheroidal cast iron (GGG40) chips were used as a reinforcement component. The MMCs were produced with different CuSn10 contents (90wt%, 80wt%, 70wt%, and 60wt%). The hot isostatic pressing process was performed under three different pressures and temperatures. The produced MMCs were characterized using density tests, Brinell hardness tests, and compression tests. In addition, the consolidation mechanism was investigated by X-ray diffraction (XRD) analysis and scanning electron microscopy. The test results were compared with those for bulk CuSn10 and bulk GGG40. Mechanical tests results revealed that the metallic chips can be recycled by using hot pressing and that the mechanical properties of the produced MMCs were similar to those of bulk CuSn10. XRD and microscopy studies showed that no intermetallic compounds formed between the metallic chips. The results showed that the CuSn10 and GGG40 chips were consolidated by mechanical interlocking.