Th17, Th22, and Myeloid-Derived Suppressor Cell Population Dynamics and Response to IL-6 in 4T1 Mammary Carcinoma

Immunotherapies relying on type 1 immunity have shown robust clinical responses in some cancers yet remain relatively ineffective in solid breast tumors. Polarization toward type 2 immunity and expansion of myeloid-derived suppressor cells (MDSC) confer resistance to therapy, though it remains unclear whether polarization toward type 3 immunity occurs or has a similar effect. Therefore, we investigated the involvement of type 3 T_h17 and T_h22 cells and their association with expanding MDSC populations in the 4T1 mouse mammary carcinoma model. T_h17 and T_h22 were detected in the earliest measurable mass at d 14 and remained present until the final sampling on d 28. In peripheral organs, T_h17 populations were significantly higher than the non-tumor bearing control and peaked early at d 7, before a palpable tumor had formed. Peripheral T_h22 proportions were also significantly increased, though at later times when tumors were established. To further address the mechanism underlying type 3 immune cell and MDSC recruitment, we used CRISPR-Cas9 to knock out 4T1 tumor production of interleukin-6 (4T1-IL-6-KO), which functions in myelopoiesis, MDSC recruitment, and T_h maturation. While 4T1-IL-6-KO tumor growth was similar to the control, the reduced IL-6 significantly expanded the total CD4⁺ T_h population and T_h17 in tumors, while T_h22 and MDSC were reduced in all tissues; this suggests that clinical IL-6 depletion combined with immunotherapy could improve outcomes. In sum, 4T1 mammary carcinomas secrete IL-6 and other factors, to polarize and reshape T_h populations and expand distinct T_h17 and T_h22 populations, which may facilitate tumor growth and confer immunotherapy resistance.     

An alternative formulation of the geometric stiffness matrix for plate elements

A simplified formulation of the geometric stiffness matrix for plate elements is presented. In this formulation the transverse displacement is defined along the element boundary but not for the element interior as with the usual formulation. As such the formulation is particularly suitable for use with hybrid stress or discrete Kirchhoff methods which are also based on boundary approximation of the transverse displacement.

The simplicity, computational economy and accuracy obtained with the formulation compare favorably with the usual order formulation.     

Selecting and conserving lands for biodiversity: The role of remote sensing

A major focus of conservation is on protecting areas to ensure the persistence of biological diversity. Because such areas may be large, not easily accessible, subject to change, and sensitive to the surrounding landscape, remote sensing can be a valuable tool in establishing and managing protected areas. We describe three case studies to illustrate how remote sensing can contribute to setting priorities for conservation actions, monitoring the status of conservation targets, and evaluating the effectiveness of conservation strategies. In the Connecticut River watershed, remote sensing has been used to assess flood regimes and identify key areas of floodplain forests and their context for conservation planning. At Eglin Air Force Base in Florida, remote sensing has provided information to assess the effectiveness of management strategies to restore fire to the longleaf pine sandhills ecosystem, control invasive species, and prioritize annual prescribed burns. In eastern US forests, remote sensing is being used to evaluate the ecological condition and changes at properties where direct access would be difficult.As the resolution and capacities of remote-sensing technology continue to develop, however, several issues are becoming increasingly important. It is essential that the spatial and temporal resolution of remote-sensing data be matched to the relevant scales of biodiversity, major threats, and management actions. Data layers must be compatible, both in scale and in measurement properties, and key patterns must be distinguished from irrelevant detail, especially at the finer scales of application in local management. Combining remote sensing with ground surveys can expand the array of information used in management and contribute to the ecological interpretation of remote-sensing data. Because conservation funds are always limited, remote sensing also must be cost effective. This requires balancing the wealth of detail afforded by ever-finer resolution of remote-sensing data with what is actually needed to implement sound conservation and management. Remote sensing is a valuable tool, but it is not a panacea for all of the challenges of conservation monitoring and management.     

Cluster randomized trials with treatment noncompliance.

Cluster randomized trials (CRTs) have been widely used in field experiments treating a cluster of individuals as the unit of randomization. This study focused particularly on situations where CRTs are accompanied by a common complication, namely, treatment noncompliance or, more generally, intervention nonadherence. In CRTs, compliance may be related not only to individual characteristics but also to the environment of clusters individuals belong to. Therefore, analyses ignoring the connection between compliance and clustering may not provide valid results. Although randomized field experiments often suffer from both noncompliance and clustering of the data, these features have been studied as separate rather than concurrent problems. On the basis of Monte Carlo simulations, this study demonstrated how clustering and noncompliance may affect statistical inferences and how these two complications can be accounted for simultaneously. In particular, the effect of the intervention on individuals who not only were assigned to active intervention but also abided by this intervention assignment (complier average causal effect) was the focus. For estimation of intervention effects considering noncompliance and data clustering, an ML-EM estimation method was employed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

ILB®, a Low Molecular Weight Dextran Sulphate,Restores Glutamate Homeostasis,Amino Acid Metabolism and Neurocognitive Functions in a Rat Model of Severe Traumatic Brain Injury

In a previous study, we found that administration of ILB^®, a new low molecular weight dextran sulphate, significantly improved mitochondrial functions and energy metabolism, as well as decreased oxidative/nitrosative stress, of brain tissue of rats exposed to severe traumatic brain injury (sTBI), induced by the closed-head weight-drop model of diffused TBI. Using aliquots of deproteinized brain tissue of the same animals of this former study, we here determined the concentrations of 24 amino acids of control rats, untreated sTBI rats (sacrificed at 2 and 7 days post-injury) and sTBI rats receiving a subcutaneous ILB^® administration (at the dose levels of 1, 5 and 15 mg/kg b.w.) 30 min post-impact (sacrificed at 2 and 7 days post-injury). Additionally, in a different set of experiments, new groups of control rats, untreated sTBI rats and ILB^®-treated rats (administered 30 min after sTBI at the dose levels of 1 or 5 mg/kg b.w.) were studied for their neurocognitive functions (anxiety, locomotor capacities, short- and long-term memory) at 7 days after the induction of sTBI. Compared to untreated sTBI animals, ILB^® significantly decreased whole brain glutamate (normalizing the glutamate/glutamine ratio), glycine, serine and γ-aminobutyric acid. Furthermore, ILB^® administration restored arginine metabolism (preventing nitrosative stress), levels of amino acids involved in methylation reactions (methionine, L-cystathionine, S-adenosylhomocysteine), and N-acetylaspartate homeostasis. The macroscopic evidences of the beneficial effects on brain metabolism induced by ILB^® were the relevant improvement in neurocognitive functions of the group of animals treated with ILB^® 5 mg/kg b.w., compared to the marked cognitive decline measured in untreated sTBI animals. These results demonstrate that ILB^® administration 30 min after sTBI prevents glutamate excitotoxicity and normalizes levels of amino acids involved in crucial brain metabolic functions. The ameliorations of amino acid metabolism, mitochondrial functions and energy metabolism in ILB^®-treated rats exposed to sTBI produced significant improvement in neurocognitive functions, reinforcing the concept that ILB^® is a new effective therapeutic tool for the treatment of sTBI, worth being tested in the clinical setting.     

Photorhabdus luminescens TccC3 Toxin Targets the Dynamic Population of F-Actin and Impairs Cell Cortex Integrity

Due to its essential role in cellular processes, actin is a common target for bacterial toxins. One such toxin, TccC3, is an effector domain of the ABC-toxin produced by entomopathogenic bacteria of Photorhabdus spp. Unlike other actin-targeting toxins, TccC3 uniquely ADP-ribosylates actin at Thr-148, resulting in the formation of actin aggregates and inhibition of phagocytosis. It has been shown that the fully modified F-actin is resistant to depolymerization by cofilin and gelsolin, but their effects on partially modified actin were not explored. We found that only F-actin unprotected by tropomyosin is the physiological TccC3 substrate. Yet, ADP-ribosylated G-actin can be produced upon cofilin-accelerated F-actin depolymerization, which was only mildly inhibited in partially modified actin. The affinity of TccC3-ADP-ribosylated G-actin for profilin and thymosin-β4 was weakened moderately but sufficiently to potentiate spontaneous polymerization in their presence. Interestingly, the Arp2/3-mediated nucleation was also potentiated by T148-ADP-ribosylation. Notably, even partially modified actin showed reduced bundling by plastins and α-actinin. In agreement with the role of these and other tandem calponin-homology domain actin organizers in the assembly of the cortical actin network, TccC3 induced intense membrane blebbing in cultured cells. Overall, our data suggest that TccC3 imposes a complex action on the cytoskeleton by affecting F-actin nucleation, recycling, and interaction with actin-binding proteins involved in the integration of actin filaments with each other and cellular elements.     

对服务中FTTH网络故障诊断的创新解决方案

在无源光网络(PON)上激活服务后,电话、高速互联网和视频信号从中心局(CO)的光线路终端(OLT)发送到用户不同位置的光网络终端(ONT).这种情况下,如果有一个ONT出现故障,并且不能与OLT同步重启,PON的这一支路会进入非激活状态,并将暂停此支路相关用户的服务,这时必须找技术人员来进行故障诊断并重新启动服务.而一旦出现在非激活位置,技术人员必须测量光功率级别,以确定其是否足以使ONT与OLT同步.     

Managing the risk of a COVID-19 outbreak from border arrivals

In an attempt to maintain the elimination of COVID-19 in New Zealand, all international arrivals are required to spend 14 days in government-managed quarantine and to return a negative test result before being released. We model the testing, isolation and transmission of COVID-19 within quarantine facilities to estimate the risk of community outbreaks being seeded at the border. We use a simple branching process model for COVID-19 transmission that includes a time-dependent probability of a false-negative test result. We show that the combination of 14-day quarantine with two tests is highly effective in preventing an infectious case entering the community, provided there is no transmission within quarantine facilities. Shorter quarantine periods, or reliance on testing only with no quarantine, substantially increases the risk of an infectious case being released. We calculate the fraction of cases detected in the second week of their two-week stay and show that this may be a useful indicator of the likelihood of transmission occurring within quarantine facilities. Frontline staff working at the border risk exposure to infected individuals and this has the potential to lead to a community outbreak. We use the model to test surveillance strategies and evaluate the likely size of the outbreak at the time it is first detected. We conclude with some recommendations for managing the risk of potential future outbreaks originating from the border.     

Mosquito sound communication: are male swarms loud enough to attract females?

Given the unsurpassed sound sensitivity of mosquitoes among arthropods and the sound source power required for long-range hearing, we investigated the distance over which female mosquitoes detect species-specific cues in the sound of station-keeping mating swarms. A common misunderstanding, that mosquitoes cannot hear at long range because their hearing organs are ‘particle-velocity’ receptors, has clouded the fact that particle velocity is an intrinsic component of sound whatever the distance to the sound source. We exposed free-flying Anopheles coluzzii females to pre-recorded sounds of male An. coluzzii and An. gambiae s.s. swarms over a range of natural sound levels. Sound levels tested were related to equivalent distances between the female and the swarm for a given number of males, enabling us to infer distances over which females might hear large male swarms. We show that females do not respond to swarm sound up to 48 dB sound pressure level (SPL) and that louder SPLs are not ecologically relevant for a swarm. Considering that swarms are the only mosquito sound source that would be loud enough to be heard at long range, we conclude that inter-mosquito acoustic communication is restricted to close-range pair interactions. We also showed that the sensitivity to sound in free-flying males is much enhanced compared to that of tethered ones.     

II,CORRELATION OF GLAZE THICKNESS WITH AIR PERMEABILITY*

An attempt was made to correlate the thickness of deposition of glazes with the air permeabilities of the bodies. The correlation was satisfactory under certain restricted conditions but not for general cases. An adequate correlation was obtained, independent of the type of body, between thickness of glaze deposition, glaze consistency (coherence value), and water receptivity.