Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney

Over 100,000 individuals in the United States currently await kidney transplantation, while 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney’s architecture and function, and permit perfusion, filtration, secretion, absorption, and drainage of urine. We decellularized rat, porcine, and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells, then perfused these cell-seeded constructs in a whole organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused via their intrinsic vascular bed. When transplanted in orthotopic position in rat, the grafts were perfused by the recipient’s circulation, and produced urine via the ureteral conduit in vivo

Use of GoFundMe® to crowdfund complementary and alternative medicine treatments for cancer.

PurposeComplementary and alternative medicine (CAM) use is common amongst cancer patients. However, there is growing concern about its safety and efficacy. Online crowdfunding campaigns represent a unique avenue to understand the cancer patient's perspective for using CAM or declining conventional cancer therapy (CCT).MethodsFive hundred GoFundMe campaigns from 2012 to 2019 detailing financial need for cancer treatment were randomly selected and reviewed for endorsement of CAM use, reasons for using CAM, and reasons for declining CCT. Descriptive statistics were used to compare patient and campaign characteristics between 250 CAM users and 250 non-CAM users.ResultsCompared to non-CAM users, CAM users were more likely to be female (70% vs. 54%, p < 0.01), to report more stage IV cancer (54% vs. 12%, p < 0.01), and to have a history of delayed, missed, or misdiagnosis (10% vs. 4%, p < 0.01). Reasons for using CAM include endorsing curative/therapeutic effects 212 (85%), pain/stress reduction 137 (55%), and dissatisfaction with current or past medical treatment options 105 (42%). 87 (35%) CAM users that declined CCT reported that they wanted to try to fight off cancer using CAM first 57 (61%), that CCT was too "toxic" to the body 39 (42%), and cancer was already too advanced, so that CCT would be futile or too aggressive 25 (27%).ConclusionCancer patients on GoFundMe using CAM highly value quality of life, comfort, and autonomy. Physicians should educate themselves on CAM to set realistic expectations and provide comprehensive counseling of the risks and benefits of CAM usage to patients who choose to use CAM to either augment or completely replace CCT

A shared neural ensemble links distinct contextual memories encoded close in time.

Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information

Modeling winter circulation under landfast ice : the interaction of winds with landfast ice

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 117 (2012): C04006, doi:10.1029/2011JC007649.Idealized models and a simple vertically averaged vorticity equation illustrate the effects of an upwelling favorable wind and a spatially variable landfast ice cover on the circulation beneath landfast ice. For the case of no along-shore variations in ice, upwelling favorable winds seaward of the ice edge result in vortex squashing beneath the landfast ice leading to (1) large decreases in coastal and ice edge sea levels, (2) cross-shore sea level slopes and weak (<~.05 m s−1) under-ice currents flowing upwind, (3) strong downwind ice edge jets, and (4) offshore transport in the under-ice and bottom boundary layers of the landfast ice zone. The upwind under-ice current accelerates quickly within 2–4 days and then slows as cross-shore transport gradually decreases the cross-shore sea level slope. Near the ice edge, bottom boundary layer convergence produces ice edge upwelling. Cross-ice edge exchanges occur in the surface and above the bottom boundary layer and reduce the under-ice shelf volume by 15% in 10 days. Under-ice along-shore pressure gradients established by along- and cross-shore variations in ice width and/or under-ice friction alter this basic circulation pattern. For a landfast ice zone of finite width and length, upwelling-favorable winds blowing seaward of and transverse to the ice boundaries induce downwind flow beneath the ice and generate vorticity waves that propagate along-shore in the Kelvin wave direction. Our results imply that landfast ice dynamics, not included explicitly herein, can effectively convert the long-wavelength forcing of the wind into shorter-scale ocean motions beneath the landfast ice.J.K. was supported by the Prince William Sound Oil Spill Recovery Institute (OSRI), Alaska Sea Grant in cooperation with the Center for Global Change and the UAF Graduate School. Additional support was provided to J.K. and T.W. by the U.S. BOEMRE through the University of Alaska Coastal Marine Institute (Contract 1435-01-02-CA-85294) and by the Office of Naval Research through the National Oceanographic Partnership Program (grant N00014-07-1- 1040).2012-10-0

High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children.

BACKGROUND: Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. METHODS: We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. RESULTS: Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. CONCLUSIONS: Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period

Privacy Risks of Securing Machine Learning Models against Adversarial Examples

The arms race between attacks and defenses for machine learning models has come to a forefront in recent years, in both the security community and the privacy community. However, one big limitation of previous research is that the security domain and the privacy domain have typically been considered separately. It is thus unclear whether the defense methods in one domain will have any unexpected impact on the other domain. In this paper, we take a step towards resolving this limitation by combining the two domains. In particular, we measure the success of membership inference attacks against six state-of-the-art defense methods that mitigate the risk of adversarial examples (i.e., evasion attacks). Membership inference attacks determine whether or not an individual data record has been part of a model's training set. The accuracy of such attacks reflects the information leakage of training algorithms about individual members of the training set. Adversarial defense methods against adversarial examples influence the model's decision boundaries such that model predictions remain unchanged for a small area around each input. However, this objective is optimized on training data. Thus, individual data records in the training set have a significant influence on robust models. This makes the models more vulnerable to inference attacks. To perform the membership inference attacks, we leverage the existing inference methods that exploit model predictions. We also propose two new inference methods that exploit structural properties of robust models on adversarially perturbed data. Our experimental evaluation demonstrates that compared with the natural training (undefended) approach, adversarial defense methods can indeed increase the target model's risk against membership inference attacks.Comment: ACM CCS 2019, code is available at https://github.com/inspire-group/privacy-vs-robustnes

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: measuring structure growth using passive galaxies

We explore the benefits of using a passively evolving population of galaxies to measure the evolution of the rate of structure growth between z=0.25 and z=0.65 by combining data from the SDSS-I/II and SDSS-III surveys. The large-scale linear bias of a population of dynamically passive galaxies, which we select from both surveys, is easily modeled. Knowing the bias evolution breaks degeneracies inherent to other methodologies, and decreases the uncertainty in measurements of the rate of structure growth and the normalization of the galaxy power-spectrum by up to a factor of two. If we translate our measurements into a constraint on sigma_8(z=0) assuming a concordance cosmological model and General Relativity (GR), we find that using a bias model improves our uncertainty by a factor of nearly 1.5. Our results are consistent with a flat Lambda Cold Dark Matter model and with GR.Comment: Accepted for publication in MNRAS (clarifications added, results and conclusions unchanged

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: measurements of the growth of structure and expansion rate at z=0.57 from anisotropic clustering

We analyze the anisotropic clustering of massive galaxies from the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey (BOSS) Data Release 9 (DR9) sample, which consists of 264,283 galaxies in the redshift range 0.43 < z < 0.7 spanning 3,275 square degrees. Both peculiar velocities and errors in the assumed redshift-distance relation ("Alcock-Paczynski effect") generate correlations between clustering amplitude and orientation with respect to the line-of-sight. Together with the sharp baryon acoustic oscillation (BAO) standard ruler, our measurements of the broadband shape of the monopole and quadrupole correlation functions simultaneously constrain the comoving angular diameter distance (2190 +/- 61 Mpc) to z=0.57, the Hubble expansion rate at z=0.57 (92.4 +/- 4.5 km/s/Mpc), and the growth rate of structure at that same redshift (d sigma8/d ln a = 0.43 +/- 0.069). Our analysis provides the best current direct determination of both DA and H in galaxy clustering data using this technique. If we further assume a LCDM expansion history, our growth constraint tightens to d sigma8/d ln a = 0.415 +/- 0.034. In combination with the cosmic microwave background, our measurements of DA, H, and growth all separately require dark energy at z > 0.57, and when combined imply \Omega_{\Lambda} = 0.74 +/- 0.016, independent of the Universe's evolution at z<0.57. In our companion paper (Samushia et al. prep), we explore further cosmological implications of these observations.Comment: 19 pages, 11 figures, submitted to MNRAS, comments welcom

History of malaria treatment as a predictor of subsequent subclinical parasitaemia: A cross-sectional survey and malaria case records from three villages in Pailin, western Cambodia

Background: Treatment of the sub-clinical reservoir of malaria, which may maintain transmission, could be an important component of elimination strategies. The reliable detection of asymptomatic infections with low levels of parasitaemia requires high-volume quantitative polymerase chain reaction (uPCR), which is impractical to conduct on a large scale. It is unknown to what extent sub-clinical parasitaemias originate from recent or older clinical episodes. This study explored the association between clinical history of malaria and subsequent sub-clinical parasitaemia. Methods: In June 2013 a cross-sectional survey was conducted in three villages in Pailin, western Cambodia. Demographic and epidemiological data and blood samples were collected. Blood was tested for malaria by high-volume qP

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al