We study experimentally the far-from-equilibrium dynamics in ferromagnetic Heisenberg quantum magnets realized with ultracold atoms in an optical lattice. After controlled imprinting of a spin spiral ...pattern with an adjustable wave vector, we measure the decay of the initial spin correlations through single-site resolved detection. On the experimentally accessible time scale of several exchange times, we find a profound dependence of the decay rate on the wave vector. In one-dimensional systems, we observe diffusionlike spin transport with a dimensionless diffusion coefficient of 0.22(1). We show how this behavior emerges from the microscopic properties of the closed quantum system. In contrast to the one-dimensional case, our transport measurements for two-dimensional Heisenberg systems indicate anomalous superdiffusion.
The ability to control and tune interactions in ultracold atomic gases has paved the way for the realization of new phases of matter. So far, experiments have achieved a high degree of control over ...short-range interactions, but the realization of long-range interactions has become a central focus of research because it would open up a new realm of many-body physics. Rydberg atoms are highly suited to this goal because the van der Waals forces between them are many orders of magnitude larger than those between ground-state atoms. Consequently, mere laser excitation of ultracold gases can cause strongly correlated many-body states to emerge directly when atoms are transferred to Rydberg states. A key example is a quantum crystal composed of coherent superpositions of different, spatially ordered configurations of collective excitations. Here we use high-resolution, in situ Rydberg atom imaging to measure directly strong correlations in a laser-excited, two-dimensional atomic Mott insulator. The observations reveal the emergence of spatially ordered excitation patterns with random orientation, but well-defined geometry, in the high-density components of the prepared many-body state. Together with a time-resolved analysis, this supports the description of the system in terms of a correlated quantum state of collective excitations delocalized throughout the gas. Our experiment demonstrates the potential of Rydberg gases to realize exotic phases of matter, thereby laying the basis for quantum simulations of quantum magnets with long-range interactions.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We demonstrate single-site-resolved fluorescence imaging of ultracold 87Rb atoms in a triangular optical lattice by employing Raman sideband cooling. Combining a Raman transition at the D1 line and a ...photon scattering through an optical pumping of the D2 line, we obtain images with low background noise. The Bayesian optimisation of 11 experimental parameters for fluorescence imaging with Raman sideband cooling enables us to achieve single-atom detection with a high fidelity of (96.3 ± 1.3)%. Single-atom and single-site resolved detection in a triangular optical lattice paves the way for the direct observation of spin correlations or entanglement in geometrically frustrated systems.
Entanglement is an essential property of quantum many-body systems. However, its local detection is challenging and was so far limited to spin degrees of freedom in ion chains. Here we measure ...entanglement between the spins of atoms located on two lattice sites in a one-dimensional Bose-Hubbard chain which features both local spin- and particle-number fluctuations. Starting with an initially localized spin impurity, we observe an outwards propagating entanglement wave and show quantitatively how entanglement in the spin sector rapidly decreases with increasing particle-number fluctuations in the chain.
The prognosis of the liver transplant patients was frequently deteriorated by ischemia and reperfusion injury (IRI) in the liver. Infiltration of inflammatory cells is reported to play critical roles ...in the pathogenesis of hepatic IRI. Although T lymphocytes, neutrophils and monocytes infiltrated into the liver underwent IRI, we found that neutrophil depletion significantly attenuated the injury and serum liver enzyme levels in a murine model. Interestingly, the expression of CD321/JAM-A/F11R, one of essential molecules for transmigration of circulating leukocytes into inflammatory tissues, was significantly augmented on hepatic sinusoid endothelium at 1 h after ischemia and maintained until 45 min after reperfusion. The intraportal administration of anti-CD321 monoclonal antibody (90G4) significantly inhibited the leukocytes infiltration after reperfusion and diminished the damage responses by hepatic IRI (serum liver enzymes, inflammatory cytokines and hepatocyte cell death). Taken together, presented results demonstrated that blockade of CD321 by 90G4 antibody significantly attenuated hepatic IRI accompanied with substantial inhibition of leukocytes infiltration, particularly inhibition of neutrophil infiltration in the early phase of reperfusion. Thus, our work offers a potent therapeutic target, CD321, for preventing liver IRI.
Development of monoclonal antibody is critical for targeted drug delivery because its characteristics determine improved therapeutic efficacy and reduced side-effect. Antibody therapeutics target ...surface molecules; hence, internalization is desired for drug delivery. As an antibody-drug conjugate, a critical parameter is drug-to-antibody ratio wherein the quantity of drugs attached to the antibody influences the antibody structure, stability, and efficacy. Here, we established a cell-based immunotoxin screening system to facilitate the isolation of functional antibodies with internalization capacities, and discovered an anti-human CD71 monoclonal antibody. To overcome the limitation of drug-to-antibody ratio, we employed the encapsulation capacity of liposome, and developed anti-CD71 antibody-conjugated liposome that demonstrated antigen-antibody dependent cellular uptake when its synthesis was optimized. Furthermore, anti-CD71 antibody-conjugated liposome encapsulating doxorubicin demonstrated antigen-antibody dependent cytotoxicity. In summary, this study demonstrates the powerful pipeline to discover novel functional antibodies, and the optimal method to synthesize immunoliposomes. This versatile technology offers a rapid and direct approach to generate antibodies suitable for drug delivery modalities.
Toxins, while harmful and potentially lethal, have been engineered to develop potent therapeutics including cytotoxins and immunotoxins (ITs), which are modalities with highly selective targeting ...capabilities. Currently, three cytotoxins and IT are FDA-approved for treatment of multiple forms of hematological cancer, and additional ITs are tested in the clinical trials or at the preclinical level. For next generation of ITs, as well as antibody-mediated drug delivery systems, specific targeting by monoclonal antibodies is critical to enhance efficacies and reduce side effects, and this methodological field remains open to discover potent therapeutic monoclonal antibodies. Here, we describe our application of engineered toxin termed a cell-based IT screening system. This unique screening strategy offers the following advantages: (1) identification of monoclonal antibodies that recognize cell-surface molecules, (2) selection of the antibodies that are internalized into the cells, (3) selection of the antibodies that induce cytotoxicity since they are linked with toxins, and (4) determination of state-specific activities of the antibodies by differential screening under multiple experimental conditions. Since the functional monoclonal antibodies with internalization capacities have been identified successfully, we have pursued their subsequent modifications beyond antibody drug conjugates, resulting in development of immunoliposomes. Collectively, this screening system by using engineered toxin is a versatile platform, which enables straight-forward and rapid selection for discovery of novel functional antibodies.
Malignant melanoma is one of the untreatable cancers in which conventional therapeutic strategies, including chemotherapy, are hardly effective. Therefore, identification of novel therapeutic targets ...involved in melanoma progression is urgently needed for developing effective therapeutic methods. Overexpression of interleukin-13 receptor α2 (IL13Rα2) is observed in several cancer types including glioma and pancreatic cancer. Although IL13Rα2 is implicated in the progression of various types of cancer, its expression and roles in the malignant melanoma have not yet been elucidated. In the present study, we showed that IL13Rα2 was expressed in approximately 7.5% melanoma patients. While IL13Rα2 expression in human melanoma cells decreased their proliferation in vitro, it promoted in vivo tumour growth and angiogenesis in melanoma xenograft mouse model. We also found that the expression of amphiregulin, a member of the epidermal growth factor (EGF) family, was correlated with IL13Rα2 expression in cultured melanoma cells, xenograft tumour tissues and melanoma clinical samples. Furthermore, expression of amphiregulin promoted tumour growth, implicating causal relationship between the expression of IL13Rα2 and amphiregulin. These results suggest that IL13Rα2 enhances tumorigenicity by inducing angiogenesis in malignant melanoma, and serves as a potential therapeutic target of malignant melanoma.
The peritoneal cavity (PerC) is a unique compartment within which a variety of immune cells reside, and from which macrophages (MØ) are commonly drawn for functional studies. Here we define two MØ ...subsets that coexist in PerC in adult mice. One, provisionally called the large peritoneal MØ (LPM), contains approximately 90% of the PerC MØ in unstimulated animals but disappears rapidly from PerC following lipopolysaccharide (LPS) or thioglycolate stimulation. These cells express high levels of the canonical MØ surface markers, CD11b and F4/80. The second subset, referred to as small peritoneal MØ (SPM), expresses substantially lower levels of CD11b and F4/80 but expresses high levels of MHC-II, which is not expressed on LPM. SPM, which predominates in PerC after LPS or thioglycolate stimulation, does not derive from LPM. Instead, it derives from blood monocytes that rapidly enter the PerC after stimulation and differentiate to mature SPM within 2 to 4 d. Both subsets show clear phagocytic activity and both produce nitric oxide (NO) in response to LPS stimulation in vivo. However, their responses to LPS show key differences: in vitro, LPS stimulates LPM, but not SPM, to produce NO; in vivo, LPS stimulates both subsets to produce NO, albeit with different response patterns. These findings extend current models of MØ heterogeneity and shed new light on PerC MØ diversity, development, and function. Thus, they introduce a new context for interpreting (and reinterpreting) data from ex vivo studies with PerC MØ.
Increasing evidence shows that metabolic abnormalities in body fluids are distinguishing features of the pathophysiology of Parkinson's disease. However, a non-invasive approach has not been ...established in the earliest or pre-symptomatic phases. Here, we report comprehensive double-cohort analyses of the metabolome using capillary electrophoresis/liquid chromatography mass-spectrometry. The plasma analyses identified 18 Parkinson's disease-specific metabolites and revealed decreased levels of seven long-chain acylcarnitines in two Parkinson's disease cohorts (n = 109, 145) compared with controls (n = 32, 45), respectively. Furthermore, statistically significant decreases in five long-chain acylcarnitines were detected in Hoehn and Yahr stage I. Likewise, decreased levels of acylcarnitine(16:0), a decreased ratio of acylcarnitine(16:0) to fatty acid(16:0), and an increased index of carnitine palmitoyltransferase 1 were identified in Hoehn and Yahr stage I of both cohorts, suggesting of initial β-oxidation suppression. Receiver operating characteristic curves produced using 12-14 long-chain acylcarnitines provided a large area of under the curve, high specificity and moderate sensitivity for diagnosing Parkinson's disease. Our data demonstrate that a primary decrement of mitochondrial β-oxidation and that 12-14 long-chain acylcarnitines decreases would be promising diagnostic biomarkers for Parkinson's disease.
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