Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. ...Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell instructive properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. In addition, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.
•Nonadhesive alginate hydrogels support growth of human intestinal organoids (HIOs)•Alginate-grown HIO epithelium resembles Matrigel-grown HIO epithelium in vitro•Transplanted alginate-grown HIOs engraft and mature in vivo•Alginate and Matrigel-grown HIOs exhibit molecular similarity in vitro and in vivo
Spence and colleagues identify alginate as a nonadhesive growth matrix to support human intestinal organoid culture. Their results demonstrate that alginate-grown HIOs are virtually indistinguishable from traditional Matrigel-grown HIOs both in vitro and in vivo. This work increases the translational potential of HIOs by eliminating reliance on cell-derived matrices and reducing cost.
BK virus nephritis: Risk factors, timing, and outcome in renal transplant recipients.
BK virus nephritis (BKVN) has emerged as an important cause of renal transplant failure. Quantified analysis of ...its timing and clinical course is generally lacking. We have thus quantified the timing, risk factors, evolution of renal function, and transplant graft outcome in renal transplant recipients with BKVN from our center.
A total of 41 cases of BKVN were diagnosed in 1001 renal and renal/pancreas transplant recipients. There were 2 groups: group I (N = 16), with diagnosis based on renal biopsy alone from January 1996 to August 2001, and group II (N = 25), with diagnosis based on quantitative blood BKV-PCR and biopsy from September 2001 to December 2003. The demographics, the clinical course, immunosuppressive therapy, renal function, and graft outcome were quantified. Donor, recipient, and transplant risk variables were studied using a univariate analysis. Actuarial graft survival was calculated. An immunosuppressive scale created to evaluate the degree of immunosuppression in these patients and its reduction after the diagnosis of BKVN.
The median time from transplant to BKVN diagnosis was 318 days (range 48-1356). The actuarial graft survival in patients with BKVN at 6 months, 1, 3, and 5 years was 97%, 90%, 58%, and 47%. The corresponding values for those without BKVN were 94%, 92%, 83%, and 76%, respectively, P < 0.001. Graft loss occurred in 46% of patients. The rate of decline of renal function in group II (N = 25) patients in the 4 months preceding BKVN was rapid (4.8 mL/min/month) and this declined to 0.7 mL/min/month at 3 months' post-BKVN diagnosis, P = 0.004. In those who recovered, the time to stabilization of renal function was a median of 112 days. The immunosuppressive scale score was 7 units at the time of diagnosis of BKVN and decreased to 3.5 units at 3 months' post-BKVN. Reduction in the dose of calcineurin inhibitors but not the overall reduction in dose of immunosuppression correlated with recovery of renal function in these patients.
BKVN is a relatively late complication of renal transplantation. Despite reduction in immunosuppression, graft loss occurred in 46% of patients. There was a steep decline in renal function in months preceding the diagnosis of BKVN, and reduction in calcineurin inhibitor dose, but not overall immunosuppression, correlated with stabilization of renal function.
This study describes the advantages of nano-hydroxyapatite (n-HAp), a cost effective sorbent for fluoride removal. n-HAp possesses a maximum defluoridation capacity DC of 1845
mg
F
−/kg which is ...comparable with that of activated alumina, a defluoridation agent commonly used in the indigenous defluoridation technology. A new mechanism of fluoride removal by n-HAp was proposed in which it is established that this material removes fluoride by both ion-exchange and adsorption process. The n-HAp and fluoride-sorbed n-HAp were characterized using XRD, FTIR and TEM studies. The fluoride sorption was reasonably explained with Langmuir, Freundlich and Redlich–Peterson isotherms. Thermodynamic parameters such as Δ
G°, Δ
H°, Δ
S° and
E
a were calculated in order to understand the nature of sorption process. The sorption process was found to be controlled by pseudo-second-order and pore diffusion models. Field studies were carried out with the fluoride containing water sample collected from a nearby fluoride endemic area in order to test the suitability of n-HAp material as a defluoridating agent at field condition.
Antigen presenting cells (APCs) in the thymus play an essential role in the establishment of central tolerance, i.e. the generation of a repertoire of functional and self-tolerant T cells to prevent ...autoimmunity. In this study, we have compared the transcriptomes of four primary APCs from human thymus (mTECs, CD19+ B cells, CD141+ and CD123+ DCs). We investigated a set of genes including the HLA genes, genes encoding transcriptional regulators and finally, tissue-enriched genes, i.e, genes with a five-fold higher expression in a particular human tissue. We show that thymic CD141+ DCs express the highest levels of all classical HLA genes and 67% (14/21) of the HLA class I and II pathway genes investigated in this study. CD141+ DCs also expressed the highest levels of the transcriptional regulator DEAF1, whereas AIRE and FEZF2 expression were mainly found in primary human mTECs. We found expression of "tissue enriched genes" from the Human Protein Atlas (HPA) in all four APC types, but the mTECs were clearly dominating in the number of uniquely expressed tissue enriched genes (20% in mTECs, 7% in CD19+ B cells, 4% in CD123+ DCs and 2% in CD141+ DCs). The tissue enriched genes also overlapped with reported human autoantigens. This is, to our knowledge, the first study that performs RNA sequencing of mTECs, CD19+ B cells, CD141+ and CD123+ DCs isolated from the same individuals and provides insight into the transcriptomes of these human thymic APCs.
Kaolinite clay obtained from the mines was processed and studied for its fluoride sorption capacity. The surface area of the clay mineral was increased from 15.11
m
2/g (raw) to 32.43
m
2/g ...(activated) by mechanochemical activation. Batch adsorption studies were conducted to optimize various equilibrating conditions like the effect of contact time, dosage, pH for both raw and micronized kaolinites (RK and MK). The effect of other interfering anions on the defluoridation capacity (DC) of the sorbents was studied. Sorption of fluoride by the sorbents was observed over a wide pH range of 3–11. The studies revealed there is an enhanced fluoride sorption on MK. FTIR and XRD were used for the characterization of the sorbent. The surface morphology of the clay material was observed using SEM. The adsorption of fluoride was studied at three different temperatures, viz., 303, 313 and 323
K. The sorption data obtained at optimized conditions were subjected to Freundlich and Langmuir isotherms. Sorption intensity (1/
n) (0.770–0.810) has been evaluated using Freundlich isotherm, whereas the values of sorption capacity
Q
0 (0.609, 0.714 and 0.782
mg/g) and binding energy
b (0.158, 0.145 and 0.133
L/mg) at three different temperatures have been estimated using Langmuir isotherm. Adsorption process was found to be controlled by both Freundlich and Langmuir isotherms. Thermodynamic studies revealed that the sorption of fluoride on MK is endothermic and a spontaneous process. The kinetic studies indicate that the sorption of fluoride on MK follows pseudo-first-order and intraparticle diffusion models.
Soon after it was discovered that intense laser pulses of nanosecond duration from a ruby laser could anneal the lattice of silicon, it was established that this so-called pulsed laser annealing is a ...thermal process. Although the radiation energy is transferred to the electrons, the electrons transfer their energy to the lattice on the timescale of the excitation. The electrons and the lattice remain in equilibrium and the laser simply 'heats' the solid to the melting temperature within the duration of the laser pulse. For ultrashort laser pulses in the femtosecond regime, however, thermal processes (which take several picoseconds) and equilibrium thermodynamics cannot account for the experimental data. On excitation with femtosecond laser pulses, the electrons and the lattice are driven far out of equilibrium and disordering of the lattice can occur because the interatomic forces are modified due to the excitation of a large (10% or more) fraction of the valence electrons to the conduction band. This review focuses on the nature of the non-thermal transitions in semiconductors under femtosecond laser excitation.
Resilient Asymptotic Consensus in Robust Networks LeBlanc, H. J.; Haotian Zhang; Koutsoukos, X. ...
IEEE journal on selected areas in communications,
04/2013, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Odprti dostop
This paper addresses the problem of resilient in-network consensus in the presence of misbehaving nodes. Secure and fault-tolerant consensus algorithms typically assume knowledge of nonlocal ...information; however, this assumption is not suitable for large-scale dynamic networks. To remedy this, we focus on local strategies that provide resilience to faults and compromised nodes. We design a consensus protocol based on local information that is resilient to worst-case security breaches, assuming the compromised nodes have full knowledge of the network and the intentions of the other nodes. We provide necessary and sufficient conditions for the normal nodes to reach asymptotic consensus despite the influence of the misbehaving nodes under different threat assumptions. We show that traditional metrics such as connectivity are not adequate to characterize the behavior of such algorithms, and develop a novel graph-theoretic property referred to as network robustness. Network robustness formalizes the notion of redundancy of direct information exchange between subsets of nodes in the network, and is a fundamental property for analyzing the behavior of certain distributed algorithms that use only local information.
Given a network of interconnected nodes, each with its own value (such as a measurement, position, vote, or other data), we develop a distributed strategy that enables some or all of the nodes to ...calculate any arbitrary function of the node values, despite the actions of malicious nodes in the network. Our scheme assumes a broadcast model of communication (where all nodes transmit the same value to all of their neighbors) and utilizes a linear iteration where, at each time-step, each node updates its value to be a weighted average of its own previous value and those of its neighbors. We consider a node to be malicious or faulty if, instead of following the predefined linear strategy, it updates its value arbitrarily at each time-step (perhaps conspiring with other malicious nodes in the process). We show that the topology of the network completely characterizes the resilience of linear iterative strategies to this kind of malicious behavior. First, when the network contains 2 f or fewer vertex-disjoint paths from some node xj to another node xi , we provide an explicit strategy for f malicious nodes to follow in order to prevent node xi from receiving any information about xj 's value. Next, if node xi has at least 2 f +1 vertex-disjoint paths from every other (non-neighboring) node, we show that xi is guaranteed to be able to calculate any arbitrary function of all node values when the number of malicious nodes is f or less. Furthermore, we show that this function can be calculated after running the linear iteration for a finite number of time-steps (upper bounded by the number of nodes in the network) with almost any set of weights (i.e., for all weights except for a set of measure zero).
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