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Objective: To assess long-term safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Patients completing FTY720 Research Evaluating Effects of Daily Oral Therapy in MS (FREEDOMS) were eligible for this dose-blinded, parallel-group extension study, continuing fingolimod 0.5 mg/day or 1.25 mg/day, or switching from placebo to either dose, randomized 1:1. Efficacy variables included annualized relapse rate (ARR), brain volume loss (BVL), and confirmed disability progression (CDP). Between-group analyses were conducted in the intent-to-treat (ITT) population from FREEDOMS baseline to end of study. Within-group analyses compared years 0–2 (FREEDOMS) and years 2–4 (extension) in the extension ITT population. Results: Of 1,272 patients (FREEDOMS ITT population), 1,033 were eligible, and 920 enrolled in the extension study (continuous-fingolimod: 0.5 mg [n = 331], 1.25 mg [n = 289]; placebo–fingolimod: 0.5 mg [n = 155], 1.25 mg [n = 145]); 916 formed the extension ITT population (n = 330; n = 287; n = 154; n = 145) and 773 (84%) completed. In the continuous-fingolimod groups, ARR was lower (p < 0.0001), BVL was reduced (p < 0.05), and proportionately more patients were free from 3-month CDP (p < 0.05) than in a group comprising all placebo–fingolimod patients. Within each placebo–fingolimod group, ARR was lower (p < 0.001, both) and BVL was reduced after switching (p < 0.01, placebo–fingolimod 0.5 mg). Rates and types of adverse events were similar across groups; no new safety issues were reported. Conclusion: Efficacy benefits of fingolimod during FREEDOMS were sustained during the extension; ARR and BVL were reduced after switching. Classification of evidence: This study provides Class IV evidence that long-term fingolimod treatment is well-tolerated and reduces relapse rates, disability progression, and MRI effects in patients with RRMS.

Cortical ICAM-1 expression is increased in AD. Cryopreserved cortex and cerebellum of AD or NCI patients were cut at 20 μm. After PFA fixation sections were washed with PBS and stained against (a) ICAM-I or (b) VCAM-1 and CD31 as a vascular marker and imaged using an inverted fluorescent microscope. Arrow demonstrates colocalization of ICAM-1 and CD31. Bar represents 50 μm (PDF 62676 kb)

HDL treatment does not alter LRP1 or RAGE protein levels in hCMEC/D3. (a-c) hCMEC/D3 were treated with HDL (0–400 μg/mL) for 5 h before lysing in RIPA. (a) LRP1 and (b) RAGE protein levels were quantified by immunoblotting (c). Graphs represent means ± SD relative to vehicle treated cells in 3 trials (PDF 1114 kb)

Aβ induced dose dependent PBMC adhesion and HDL attenuate dose dependent Aβ-induced PBMC adhesion to hCMEC/D3. In all conditions, hCMEC/D3 were stimulated with 0–1 μM Aβ40 (light grey) or Aβ42 (dark grey) monomers for 3 h. Fluorescently labelled PBMC were allowed to adhere to (a) Aβ40- or (b) Aβ42- stimulated cells for 3 additional hours. Cells were washed, fixed, and imaged to count adhered PBMC. hCMEC/D3 were primed with increasing doses (25–400 μg/mL) of HDL for 2 h and stimulated with 0.1 μM (c) Aβ40 (light grey) or (d) Aβ42 (dark grey) for 3 h. Fluorescently labelled PBMC were allowed to adhere to stimulated cells for 3 h followed by washing, fixation, imaging, and counting. Graphs represent mean ± SD of adhered PBMC relative to vehicle control from at least 3 independent trials where * p

Aβ does not activate phosphorylation of multifunctional serine/threonine protein kinases. hCMEC/D3 were stimulated with 0.1 mM of monomeric Aβ or 1 ng/mL of TNF-αfor 15 min before lysing cells in RIPA containing phosphostop. Phosphorylation of (a-b) p65, (c) STAT3, (d) Akt, (e) SAPK/JNK and (f) p42/44 MAPK were analysed by immunoblotting and compared to respective total p65, STAT3, Akt, SAPK/JNK and p42/44 MAPK respectively. (b) Nuclear translocation of p65 was analysed by immunofluorescence 15 min after Aβ stimulation. Graphs represent means ± SD relative to vehicle treated cells in 4 trials. *p

Adhesion molecules are enhanced by TNF-α but not Aβ.(a-c) hCMEC/D3 were primed with 100 μg/mL HDL for 2 h followed by stimulation with 1 ng/mL TNF-α for 3 h. Cell lysates were prepared in RIPA and protein levels of (a) ICAM-1 and (b) VCAM-1 were measured by denaturing immunoblotting (c). (d-g) hCMEC/D3 were stimulated with monomeric (d,f) Aβ40 or (e,g) Aβ42 at the indicated concentrations and (d,e) ICAM-1 and (f,g) VCAM-1 mRNA levels were measured by real-time PCR. (h-j) Following Aβ stimulation, cell surface proteins were biotinylated and isolated by immunoprecipitation. Protein levels of cell surface and total (h) ICAM-1 and (i) VCAM-1 were measured by denaturing immunoblotting (j). (k-m) hCMEC/D3 were pre-treated with 100 μg/mL of HDL for 2 h followed by stimulation with Aβ. After 3 h total and cell surface ICAM-1 expression were measured as above. Graphs represent means ± SD from at least 3 independent trials. ***p

HDL suppression of Aβ-induced inflammation is independent of eNOS and S1P in HUVEC. (a) L-NAME and (e) VPC23019 potency was tested by measuring intracellular NO production in HUVEC after incubating with 100 μg/mL HDL and 1 μM DAF-2 for 6 h. Fluorescence was measured at 485 nm. (b-d, f-h) In all conditions, HUVEC or hCMEC/D3 were stimulated with 0.1 μM monomeric Aβ40 or Aβ42 or 1 ng/mL of TNF-α for 3 h prior to measuring PBMC adherence. HUVEC were pre-treated for 1 h with (b-d) the eNOS inhibitor L-NAME or (f-h) the S1P1 and S1P3 inhibitor VPC23019 followed by 100 μg/mL HDL for 2 h. (i) hCMEC/D3 were pre-treated with 100 μg/mL of HDL for 2 h before simulating with Aβ40 or Aβ42. Total cellular expression of Annexin-1 (Anx1) was analysed by immunoblotting and compared to GAPDH. Graphs represent means ± SD from at least 3 independent trials. * p

Lesion count observed on brain magnetic resonance imaging scan is a common end point in phase 2 clinical trials evaluating therapeutic treatment in relapsing remitting multiple sclerosis (MS). This paper compares the performances of Poisson, zero-inflated poisson (ZIP), negative binomial (NB), and zero-inflated NB (ZINB) mixed-effects regression models in fitting lesion count data in a clinical trial evaluating the efficacy and safety of fingolimod in comparison with placebo, in MS. The NB and ZINB models prove to be superior to the Poisson and ZIP models. We discuss the advantages and limitations of zero-inflated models in the context of MS treatment. Copyright © 2012 John Wiley & Sons, Ltd.

The role of genotypic analysis in disease diagnostics and drug response assessment is continually expanding. New genomic discoveries combined with new, novel technologies may provide a greater range of testing capabilities in the near future. We describe the application of nanotechnology, in which DNA microarrays have been placed in a microchannel environment that can be read and analyzed in an optical (CD/DVD) disc drive system. The potential exists to combine molecular and immunological applications together into a rapid, low-cost, high-capacity screening platform. The relevance of this technology is discussed in respect to infectious agent detection, pharmacogenomics, neurogenomics and genetic variations associated with neurologic diseases.

The phosphonate ester group, typified by P(O)(OPh)2, is an effective π-electron acceptor group in donor-acceptor substituted benzenoid compounds for nonlinear optics, and has the added attractions of being easily functionalised for further fabrication into cross-linked films, and imparting transparency to simple derivatives.

Second harmonic generation (SHG) was observed from Z-type Langmuir-Blodgett multilayers of 4-[4-(N-n-dodecyl-N-methylamino)phenylazo]-3-nitrobenzoic acid (DPNA) on irradiation at 1.06 ?m (Nd3+:YAG laser). Even a single LB layer gave a SH signal significantly above background; further layers increased the intensity although the increase did not obey the expected square law. As the incidence angle was varied, all the signals showed a pattern of fringes due to dispersion of the glass substrate. The ?(2) of film deposited in the presence of Cd2+ ions was calculated to be (2.5???0.5)???10-20 C3 J-2, a value significantly higher than the best known crystalline materials and comparable with other LB materials.

Logical methods for preparing small metal clusters with heteronuclear metal-metal bonds can be devised by appreciating the isolobal relationships that exist between certain metal ligand combinations and organic fragments. Thus the group W(CO) 2 (r|-C 5 H 5 ) has frontier orbitals of similar pattern to those of CH, while those of Rh(CO) (r|-C 5 Me 5 ) and CH 2 are also similar. This paper shows how such ideas have been employed to generate compounds with bonds between rhodium and other metals.

Details are given of a new organic electro‐optic crystal, 3‐(1,1‐dicyanoethenyl)‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazole, having a reduced half‐wave voltage of 370 V (approximately 8 times lower than lithium niobate). The molecular design, synthesis, and molecular characterization of this compound are outlined and a description is given of growth of 1‐cm dimension crystals. These crystals have been characterized in terms of their structure, linear optical properties (refractive index, orientation of optical axes, absorption spectra), and also of their linear electro‐optic (Pockels) effect. The compound crystallizes in the noncentrosymmetric space group Cc, with the molecules showing a high degree of parallelism. This structure is discussed in terms of the applicability of the crystals to different nonlinear optical effects. Calculated molecular hyperpolarizabilities are used, in conjunction with the determined crystal structure, to estimate the coefficients of the crystalline χ(2) tensor, which is dominated by t...

Second harmonic generation experiments are performed in alternate multilayers of two non-linear molecules, the hydrophobic chain being grafted onto the acceptor group of the first species A and onto the donor group of the second species B. Two families of non-linear molecules are studied: p-aminobenzoic acid derivatives and diazostilbene derivatives. High χ(2) values (around 5×10-10SI) and β values (around 10-37 SI) are obtained for the diazostilbenes. The variation in the second harmonic intensity with respect to the number N of active layers is interpreted in terms of the disorder appearing in the upper monolayer of the Langmuir-Blodgett film.

THE customer-accounting division might well be regarded as the heart of any water utility. On its efficient operation depends the flow of that life-giving substance, commonly called "cash," that is so essential to a successful business. It is particularly important for the small water system, where the gross revenue received in a year is probably less than that of the corner grocery store. In adopting commercial records for a small water system serving up to 10,000 people or 2,500 customersthe first consideration should be simplicity, because the office personnel will probably consist of one girl, who must be office manager, cashier, bookkeeper, and file clerk, to name only a few of the many jobs that she will be asked to do. On the other hand, the records must be inclusive enough to meet the requirements of regulatory boards, tax bureaus, stockholders, or other interested parties. This discussion will be limited to four basic types of records that are necessary for a successful system of customer accounting: [1] the service record, [2] the meter book or flat-rate fixture survey book, [3] the customer's bill and ledger card, and 1 4] the route control ledger.

The vast majority of the natural dyes used prior to the nineteenth century have been replaced by synthetic dyes discovered since then. The early advances made in organic chemistry were largely responsible for this remarkable revolution and for many years organic chemistry and dyestuffs chemistry were inextricably linked. However, as more areas of organic chemistry were investigated, e.g. the chemistry of natural products, so the development of organic chemistry depended to a decreasing extent upon dyestuffs research. This trend has more recently been reversed. Interest is once again focused upon dyes for, with their essentially planar it systems, they represent an interesting challenge to the application of the Molecular Orbital theories developed during the present century (see Appendix I).

In Chapters 3–5 we have discussed the physico-chemical properties of the more important classes of dyes. We shall now describe how dyes are applied to substrates, mainly fibres, and discuss the fastness properties of the dyed fabric to various agents such as water (laundering) and light. To do this we need to have some idea of both the physical and chemical structure of the substrates to which the dyes are applied for, as will become apparent later, the same dye can exhibit widely differing fastness properties on different fibres.

Novel conjugated nonlinear optical polyene molecules, having donor and acceptor substituents and being designed so as to be suitable for Langmuir Blodgett deposition have been synthesised, deposited and characterised. Alternating Y-type multilayer structures have been fabricated, and their nonlinear optical properties have been studied by second harmonic generation experiments. The dependence of the observed second harmonic signal on film thickness and on deposition conditions will be described. The magnitude of the nonlinear optical coefficients obtained from the best films exceeds that of other systems reported in the literature.

Take a look around; colour is everywhere. The clothes we wear, our surroundings, both man-made and natural, abound with colour. Indeed, from prehistoric times, man has been fascinated by colour. From the early cavemen, who adorned their walls with coloured representations of animals, through the Egyptian, Greek and Roman eras, right up to the present time, colour has been a constant companion of mankind.

The Langmuir-Blodgett (L-B) technique is well known as a method of building-up ordered arrays of organic molecules, and especially as a means of imposing a noncentrosymmetric structure from molecules that crystallize in a centrosymmetric space group(1–3). L-B films for use in quadratic nonlinear optics can be ordered in a statistically noncentrosymmetric lattice. The method involves the compression of a mono-layer of the organic molecule, spread on top of a water surface, into a two-dimensional solid, followed by the repeated dipping of the substrate to be coated into and out of the subphase. Monolayers may be deposited onto the substrate both on immersion and withdrawal, resulting in a centrosymmetric arrangement of layers (Y-type deposition), or just on immersion (X-type) or withdrawal (Z-type), in which case a noncentrosymmetric structure should be obtained. However, this kind of samples is not very stable and tends to relax towards disordered structures. An alternative method is the successive deposition of alternate layers ABAB… where A and B are two different molecular species stacked following a Y-type structure, the hydrophobic chain being grafted onto the acceptor group of the first species A and onto the donor group of the second species B (4,5). The quadratic nonlinear response, resulting from the addition of the individual nonlinearities of each moiety, is quite large, with the additional advantage of a high degree of order and a good stability of the multilayers.

Appreciation of the landscape has occurred throughout human history. Only in recent times, however, has the majority of the population, and then only in the richer "developed" countries, had the leisure time to enjoy it. Formerly the landscape was merely the hack-drop to toil except for the few individuals granted, through circumstances, time they could spend "unproductively." By contrast, today we have a situation where landscape has become the land's newest resource, eagerly sought out and argued for by increasing numbers of people. This thesis is an analysis of landscape as a resource. Recognising the comparative new-ness of the field and the consequent proliferation of exploratory studies on its many aspects, the present work does not pretend to extend the field into higher realms of learning: it is an attempt to review and correlate the more relevant areas of significance. Among them are the development of attitudes towards the landscape, the basic visual elements of the landscape and how they are perceived and subsequently modified by preconceptions, and the present-day situation where attempts are being made to accurately describe and quantify the landscape resource and evolve a discipline of visual resource management.

HDL does not signal through miR-223 to reduce Aβ-induced inflammation in hCMEC/D3. (a-c) hCMEC/D3 were pre-treated with 100 μg/mL of HDL as described in Fig. 2 with or without 10 nM of miR-223 mimetic nucleotides or (d-f) in the absence or presence of a specific miR223 inhibitor for 2 h before stimulation with (a,d) Aβ40, (b,e) Aβ42 or (c, f) TNF-α before testing PBMC adherence to ECs. (g) Intracellular levels of mature miR-223 in hCMEC/D3 were quantified by real-time PCR and normalized to U6 after a 5 h treatment with 100 μg/mL of HDL. Graphs represent means ± SD of adhered PBMC relative to vehicle treated cells for at least 5 independent trials. *p

Background: Severe hypertriglyceridemia (HTG) is one cause of acute pancreatitis, yet the level of plasma triglycerides likely to be responsible for inducing pancreatitis has not been clearly defined. Methods and Results: A retrospective cohort study was conducted on patients presenting non-acutely to the Healthy Heart Program Lipid Clinic at St. Paul's Hospital with a TG level > 20 mM (1772 mg/dl) between 1986 and 2007. Ninety-five patients with TG > 20 mM at the time of referral were identified, in who follow up data was available for 84. Fifteen patients (15.8%), with a mean outpatient TG level of 38.1 mM, had a history of acute pancreatitis. Among 91 additional patients with less severe HTG, none had a history of pancreatitis when TG were between 10 and 20 mM. Among patients with TG > 20 mM on presentation, 8 (8.5%), with a mean TG level of 67.8 mM, exhibited eruptive xanthomata. A diet high in carbohydrates and fats (79%) and obesity (47.6%) were the two most frequent secondary causes of HTG at initial visit. By 2009, among patients with follow up data 53% exhibited either pre-diabetes or overt Type 2 diabetes mellitus. Upon referral only 23 patients (24%) were receiving a fibrate as either monotherapy or part of combination lipid-lowering therapy. Following initial assessment by a lipid specialist this rose to 84%, and remained at 67% at the last follow up visit. Conclusions: These results suggest hypertriglyceridemia is unlikely to be the primary cause of acute pancreatitis unless TG levels are > 20 mM, that dysglycemia, a diet high in carbohydrates and fats, and obesity are the main secondary causes of HTG, and that fibrates are frequently overlooked as the drug of first choice for severe HTG.

HDL does not signal through miR-223 to reduce Aβ-induced inflammation in hCMEC/D3. (a-c) hCMEC/D3 were pre-treated with 100 μg/mL of HDL as described in Fig. 2 with or without 10 nM of miR-223 mimetic nucleotides or (d-f) in the absence or presence of a specific miR223 inhibitor for 2 h before stimulation with (a,d) Aβ40, (b,e) Aβ42 or (c, f) TNF-α before testing PBMC adherence to ECs. (g) Intracellular levels of mature miR-223 in hCMEC/D3 were quantified by real-time PCR and normalized to U6 after a 5 h treatment with 100 μg/mL of HDL. Graphs represent means ± SD of adhered PBMC relative to vehicle treated cells for at least 5 independent trials. *p

[Background]: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally., [Methods]: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005., [Findings]: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12∙0 years (IQR 5∙5–27∙0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14∙7 mmol/L (IQR 11∙6–18∙4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3∙93 mmol/L, IQR 2∙6–5∙8) versus non-highincome countries (9∙3 mmol/L, 6∙7–12∙7), with greater use of three or more lipid-lowering therapies (LLT; highincome 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24∙5 years (IQR 17∙0–34∙5) versus 37∙0 years (29∙0–49∙0) in high-income countries (adjusted hazard ratio 1∙64, 95% CI 1∙13–2∙38)., [Interpretation]: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH., Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Society

Chemically or optically powered active matter plays an increasingly important role in materials design, but its computational potential has yet to be explored systematically. The competition between energy consumption and dissipation imposes stringent physical constraints on the information transport in active flow networks, facilitating global optimization strategies that are not well understood. Here, we combine insights from recent microbial experiments with concepts from lattice-field theory and non-equilibrium statistical mechanics to introduce a generic theoretical framework for active matter logic. Highlighting conceptual differences with classical and quantum computation, we demonstrate how the inherent non-locality of incompressible active flow networks can be utilized to construct universal logical operations, Fredkin gates and memory storage in set–reset latches through the synchronized self-organization of many individual network components. Our work lays the conceptual foundation for developing autonomous microfluidic transport devices driven by bacterial fluids, active liquid crystals or chemically engineered motile colloids., Alfred P. Sloan Foundation. Fellowship, Massachusetts Institute of Technology. Department of Mathematics (Edmund F. Kelly Research Award), National Science Foundation (U.S.) (Award CBET-1510768)

Recent experiments show that both natural and artificial microswimmers in narrow channel-like geometries will self-organise to form steady, directed flows. This suggests that networks of flowing active matter could function as novel autonomous microfluidic devices. However, little is known about how information propagates through these far-from-equilibrium systems. Through a mathematical analogy with spin-ice vertex models, we inves tigate here the input-output characteristics of generic incompressible active flow networks (AFNs). Our analysis shows that information transport through an AFN is inherently different from conventional pressure or voltage driven networks. Active flows on hexagonal arrays preserve input information over longer distances than their passive counterparts and are highly sensitive to bulk topological defects, whose presence can be inferred from marginal input-output distributions alone. This sensitivity further allows controlled permutations on parallel inputs, revealing an unexpected link between active matter and group theory that can guide new microfluidic mixing strategies facilitated by active matter and aid the design of generic autonomous information transport networks., National Science Foundation (U.S.) (Grant CBET-1510768)

Active biological flow networks pervade nature and span a wide range of scales, from arterial blood vessels and bronchial mucus transport in humans to bacterial flow through porous media or plasmodial shuttle streaming in slime molds. Despite their ubiquity, little is known about the self-organization principles that govern flow statistics in such non-equilibrium networks. Here we connect concepts from lattice field theory, graph theory, and transition rate theory to understand how topology controls dynamics in a generic model for actively driven flow on a network. Our combined theoretical and numerical analysis identifies symmetry-based rules that make it possible to classify and predict the selection statistics of complex flow cycles from the network topology. The conceptual framework developed here is applicable to a broad class of non-biological far-from-equilibrium networks, including actively controlled information flows, and establishes a new correspondence between active flow networks and generalized ice-type models., 7 pages, 4 figures; SI text available at article on pnas.org

Coherent, large scale dynamics in many nonequilibrium physical, biological, or information transport networks are driven by small-scale local energy input. Here, we introduce and explore an analytically tractable nonlinear model for compressible active flow networks. In contrast to thermally-driven systems, we find that active friction selects discrete states with a limited number of oscillation modes activated at distinct fixed amplitudes. Using perturbation theory, we systematically predict the stationary states of noisy networks and find good agreement with a Bayesian state estimation based on a hidden Markov model applied to simulated time series data. Our results suggest that the macroscopic response of active network structures, from actomyosin force networks to cytoplasmic flows, can be dominated by a significantly reduced number of modes, in contrast to energy equipartition in thermal equilibrium. The model is also well-suited to study topological sound modes and spectral band gaps in active matter., Comment: new title, several text and figure changes, new results on band gaps added, supplementary information now included

A random search process in a networked environment is governed by the time it takes to visit every node, termed the cover time. Often, a networked process does not proceed in isolation but competes with many instances of itself within the same environment. A key unanswered question is how to optimise this process: how many concurrent searchers can a topology support before the benefits of parallelism are outweighed by competition for space? Here, we introduce the searcher-averaged parallel cover time (APCT) to quantify these economies of scale. We show that the APCT of the networked symmetric exclusion process is optimised at a searcher density that is well predicted by the spectral gap. Furthermore, we find that non-equilibrium processes, realised through the addition of bias, can support significantly increased density optima. Our results suggest novel hybrid strategies of serial and parallel search for efficient information gathering in social interaction and biological transport networks., Comment: 17 pages, 4 figures

Despite their inherent non-equilibrium nature, living systems can self-organize in highly ordered collective states that share striking similarities with the thermodynamic equilibrium phases of conventional condensed matter and fluid systems. Examples range from the liquid-crystal-like arrangements of bacterial colonies, microbial suspensions and tissues to the coherent macro-scale dynamics in schools of fish and flocks of birds. Yet, the generic mathematical principles that govern the emergence of structure in such artificial and biological systems are elusive. It is not clear when, or even whether, well-established theoretical concepts describing universal thermostatistics of equilibrium systems can capture and classify ordered states of living matter. Here, we connect these two previously disparate regimes: Through microfluidic experiments and mathematical modelling, we demonstrate that lattices of hydrodynamically coupled bacterial vortices can spontaneously organize into distinct phases of ferro- and antiferromagnetic order. The preferred phase can be controlled by tuning the vortex coupling through changes of the inter-cavity gap widths. The emergence of opposing order regimes is tightly linked to the existence of geometry-induced edge currents, reminiscent of those in quantum systems. Our experimental observations can be rationalized in terms of a generic lattice field theory, suggesting that bacterial spin networks belong to the same universality class as a wide range of equilibrium systems., Original journal submission; revised version in press at Nature Physics. (19 pages, 8 figures)