Einstein-Podolsky-Rosen experiment with two Bose-Einstein condensates

In 1935, Einstein, Podolsky, and Rosen (EPR) conceived a Gedankenexperiment in which two particles are entangled through interactions, spatially separated, and measured. Under the classical assumption of local realism, they showed that the measurement correlations predicted by quantum mechanics for this scenario lead to a violation of the Heisenberg uncertainty principle. This contradiction, later denominated EPR paradox, revealed that the completeness of quantum mechanics is not compatible with the local realist description of nature that characterises classical physics. Although the EPR paradox has been observed between systems consisting of few particles, this has not yet been achieved between larger systems: The entanglement of macroscopic objects has already been demonstrated, but the measured correlations were not strong enough to demonstrate the EPR paradox. However, the presence of entanglement of the EPR type in many-particle systems has been shown by measuring correlations within single systems. In this thesis I describe an EPR experiment with two spatially separated massive many-particle systems: In close analogy to the original Gedankenexperiment, we entangle about 1400 atoms in a two-component Rubidium-87 Bose-Einstein condensate (BEC) via tunable collisional interactions and coherently split them into two separate condensates. Our splitting technique preserves the overlap and coherence between the components in each of the split BECs, allowing us to individually manipulate them. The entanglement inherited from the initial system results in measurement correlations between the two BECs that are strong enough to show the EPR paradox. Our work shows that the conflict between quantum mechanics and local realism does not disappear when the size of the involved systems is increased to ${\sim 10^3}$ atoms. In addition to this, EPR entanglement - in conjunction with the spatial separation and individual addressability of the two systems demonstrated in our experiment - is a valuable resource for quantum metrology and quantum information processing with many-particle systems

Einstein-Podolsky-Rosen experiment with two Bose-Einstein condensates

In 1935, Einstein, Podolsky and Rosen (EPR) conceived a Gedankenexperiment which became a cornerstone of quantum technology and still challenges our understanding of reality and locality today. While the experiment has been realized with small quantum systems, a demonstration of the EPR paradox with spatially separated, massive many-particle systems has so far remained elusive. We observe the EPR paradox in an experiment with two spatially separated Bose-Einstein condensates containing about 700 Rubidium atoms each. EPR entanglement in conjunction with individual manipulation of the two condensates on the quantum level, as demonstrated here, constitutes an important resource for quantum metrology and information processing with many-particle systems. Our results show that the conflict between quantum mechanics and local realism does not disappear as the system size is increased to over a thousand massive particles.Comment: 9 pages, 5 figure

Fundamental limit of phase coherence in two-component Bose-Einstein condensates

We experimentally and theoretically study phase coherence in two-component Bose-Einstein condensates of $^{87}{\rm Rb}$ atoms on an atom chip. Using Ramsey interferometry we measure the temporal decay of coherence between the $|F=1,m_{F}=-1\rangle$ and $|F=2,m_{F}=+1\rangle$ hyperfine ground states. We observe that the coherence is limited by random collisional phase shifts due to the stochastic nature of atom loss. The mechanism is confirmed quantitatively by a quantum trajectory method based on a master equation which takes into account collisional interactions, atom number fluctuations, and losses in the system. This decoherence process can be slowed down by reducing the density of the condensate. Our findings are relevant for experiments on quantum metrology and many-particle entanglement with Bose-Einstein condensates and the development of chip-based atomic clocks

Protective effects of Vitamin D3 on fimbrial cells exposed to catalytic iron damage

BACKGROUND: Recently, vitamin D3 (1alpha, 25-dihydroxyvitamin D) has shown its capability to take part in many extraskeletal functions and its serum levels have been related to patient survival rate and malignancy of many types of neoplasms, including ovarian cancers. Catalytic iron is a free circulating form of iron that is able to generate reactive oxygen species and consequently to promote a number of cellular and tissutal dysfunctions including tumorigenesis. In fertile women an important source of catalytic iron is derived from retrograde menstruation. Epithelial secretory cells from fimbriae of fallopian tubes are greatly exposed to catalytic iron derived from menstrual reflux and so represent the site of origin for most serous ovarian cancers. The aim of this study was to assess whether vitamin D3 can play a role in counteracting catalytic iron-induced oxidative stress in cells from fimbriae of fallopian tubes. METHODS: The cells, isolated from women undergoing isteroannessiectomy, were treated with catalytic iron 50-75-100 mM and vitamin D3 at a concentration ranging from 0.01 to 10 nM to study cell viability, radical oxygen species production, p53, pan-Ras, Ki67 and c-Myc protein expressions through Western Blot, and immunocytochemistry or immunofluorescence analysis. RESULTS: The pre-treatment with vitamin D3 1 nM showed its beneficial effects that consists in a significant decrease in ROS production. In addition a novel finding is represented by the demonstration that pre-treatment with vitamin D3 is also able to significantly counteract tumoral biomarkers activation, such as p53, pan-Ras, Ki67 and c-Myc, and consequently the catalytic iron-induced cellular injury. CONCLUSIONS: This study demonstrates for the first time that vitamin D3 plays an important role in preventing catalytic iron-dependent oxidative stress in cultured fimbrial cells. These results support the hypothesis that vitamin D3 could counteract carcinogenic changes induced by catalytic iron

Artificial neural networks allow the use of simultaneous measurements of Alzheimer Disease markers for early detection of the disease

BACKGROUND: Previous studies have shown that in platelets of mild Alzheimer Disease (AD) patients there are alterations of specific APP forms, paralleled by alteration in expression level of both ADAM 10 and BACE when compared to control subjects. Due to the poor linear relation among each key-element of beta-amyloid cascade and the target diagnosis, the use of systems able to afford non linear tasks, like artificial neural networks (ANNs), should allow a better discriminating capacity in comparison with classical statistics. OBJECTIVE: To evaluate the accuracy of ANNs in AD diagnosis. METHODS: 37 mild-AD patients and 25 control subjects were enrolled, and APP, ADM10 and BACE measures were performed. Fifteen different models of feed-forward and complex-recurrent ANNs (provided by Semeion Research Centre), based on different learning laws (back propagation, sine-net, bi-modal) were compared with the linear discriminant analysis (LDA). RESULTS: The best ANN model correctly identified mild AD patients in the 94% of cases and the control subjects in the 92%. The corresponding diagnostic performance obtained with LDA was 90% and 73%. CONCLUSION: This preliminary study suggests that the processing of biochemical tests related to beta-amyloid cascade with ANNs allows a very good discrimination of AD in early stages, higher than that obtainable with classical statistics methods

Time course and mechanisms of motoneuron death in a type II spinal muscular atrophy mouse model

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease leading to motor impairment, muscle atrophy and premature death caused by motoneuron degeneration. It is caused by the deletion/mutation of the telomeric survival motoneuron gene (SMN1), whereas the number of copies of the centromeric gene SMN2, which produces reduced levels of functional protein, is inversely proportional to the severity of disease (from severe to mild). However, the causes of selective motoneuron death still remain elusive. To clarify the time course and the mechanisms of motoneuron (MN) death, we investigated the SMNdelta7 murine model of SMA II (the intermediate SMA form), in which motor dysfunction leads to death at P13. We collected brains and spinal cords from SMA II and wild type embryos/pups at E19, P4, P9 and P13 for neuron counts and immunohistochemistry. Newborns underwent a battery of motor tasks and were assessed daily for body weight and survival. In ChAT-immunoreacted and Nissl-stained spinal sections, stereological counts reported a dramatic reduction in the number of lower (cervical) MNs (almost 40% at P13) in the SMA II mice; in particular MNs innervating proximal muscles seemed the most affected. In addition, we noticed an increased ChAT expression through time, making ChAT-MN count less reliable than Nissl-ones. Moreover, even though most studies mainly report death of lower motoneurons, stereological counts in the motor cortex revealed a specific decrease of layer V cortical pyramidal neurons in SMA II mice compared to WT. Also the corpus callosum thickness appeared halved in the P9 SMA II mice. Finally, immunohistochemistry against cleaved Caspase-3 and LC-3 suggested an involvement of the apoptotic and autophagic modes of cell death, respectively. Therefore, at least in the animal model, SMA affects both upper and lower motoneurons, and SMN1 role in neuronal development and survival should be further investigated. Targeting apoptotic and autophagic pathways can delay the disease progression, as we are currently showing in other studies

S100A7, a Novel Alzheimer's Disease Biomarker with Non-Amyloidogenic α-Secretase Activity Acts via Selective Promotion of ADAM-10

Alzheimer's disease (AD) is the most common cause of dementia among older people. At present, there is no cure for the disease and as of now there are no early diagnostic tests for AD. There is an urgency to develop a novel promising biomarker for early diagnosis of AD. Using surface-enhanced laser desorption ionization-mass spectrometry SELDI-(MS) proteomic technology, we identified and purified a novel 11.7-kDa metal- binding protein biomarker whose content is increased in the cerebrospinal fluid (CSF) and in the brain of AD dementia subjects as a function of clinical dementia. Following purification and protein-sequence analysis, we identified and classified this biomarker as S100A7, a protein known to be involved in immune responses. Using an adenoviral-S100A7 expression system, we continued to examine the potential role of S100A7 in AD amyloid neuropathology in in vitro model of AD. We found that the expression of exogenous S100A7 in primary cortico-hippocampal neuron cultures derived from Tg2576 transgenic embryos inhibits the generation of β-amyloid (Aβ)1–42 and Aβ1–40 peptides, coincidental with a selective promotion of “non- amyloidogenic” α-secretase activity via promotion of ADAM (a disintegrin and metalloproteinase)-10. Finally, a selective expression of human S100A7 in the brain of transgenic mice results in significant promotion of α-secretase activity. Our study for the first time suggests that S100A7 may be a novel biomarker of AD dementia and supports the hypothesis that promotion of S100A7 expression in the brain may selectively promote α-secretase activity in the brain of AD precluding the generation of amyloidogenic peptides. If in the future we find that S1000A7 protein content in CSF is sensitive to drug intervention experimentally and eventually in the clinical setting, S100A7 might be developed as novel surrogate index (biomarker) of therapeutic efficacy in the characterization of novel drug agents for the treatment of AD

Ginkgo biloba Extract in Alzheimer’s Disease: From Action Mechanisms to Medical Practice

Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, is one of the most popular herbal supplements. Numerous preclinical studies have shown the neuroprotective effects of EGb761 and support the notion that it may be effective in the treatment and prevention of neurodegenerative disorders such as Alzheimer’s disease (AD). Despite the preclinical promise, the clinical efficacy of this drug remains elusive. In this review, possible mechanisms underlying neuroprotective actions of EGb761 are described in detail, together with a brief discussion of the problem of studying this herb clinically to verify its efficacy in the treatment and prevention of AD. Moreover, various parameters e.g., the dosage and the permeability of the blood brain barrier (BBB), impacting the outcome of the clinical effectiveness of the extract are also discussed. Overall, the findings summarized in this review suggest that, a better understanding of the neuroprotective mechanisms of EGb761 may contribute to better understanding of the effectiveness and complexity of this herb and may also be helpful for design of therapeutic strategies in future clinical practice. Therefore, in future clinical studies, different factors that could interfere with the effect of EGb761 should be considered

Small molecule inhibitors of Aβ-aggregation and neurotoxicity

Alzheimer disease (AD) is characterized pathologically by extracellular amyloid deposits composed of Aβ peptide, neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau, and a deficit of cholinergic neurons in the basal forebrain. Presently, only symptomatic therapies are available for the treatment of AD and these therapies have a limited time frame of utility. Amyloid disorders represent the effects of chronic Aβ production and are not a secondary pathological effect caused by a distant trigger; therefore targeting Aβ is a viable pursuit. In this review, we will discuss the various small molecule anti-aggregation inhibitors that have been reported in the literature, with emphasis on compounds that are presently being investigated in clinical trials

Ginkgo Biloba Extract Ameliorates Oxidative Phosphorylation Performance and Rescues Aβ-Induced Failure

Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD). Recently, we demonstrated that chronic exposure to amyloid-beta (Abeta) in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP) resulted in (i) activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is able to rescue Abeta-induced defects in energy metabolism