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The availability of positional information is of great importance in many commercial, public safety, and military applications. The coming years will see the emergence of locationaware networks with sub-meter accuracy, relying on accurate range measurements provided by wide bandwidth transmissions. In this two-part paper, we determine the fundamental limits of localization accuracy of wideband wireless networks in harsh multipath environments. We first develop a general framework to characterize the localization accuracy of a given node here and then extend our analysis to cooperative location-aware networks in Part II.In this paper, we characterize localization accuracy in terms of a performance measure called the squared position error bound (SPEB), and introduce the notion of equivalent Fisher information to derive the SPEB in a succinct expression. This methodology provides insights into the essence of the localization problem by unifying localization information from individual anchors and information from a priori knowledge of the agent's position in a canonical form. Our analysis begins with the received waveforms themselves rather than utilizing only the signal metrics extracted from these waveforms, such as time-of-arrival and received signal strength. Hence, our framework exploits all the information inherent in the received waveforms, and the resulting SPEB serves as a fundamental limit of localization accuracy. Index Terms-Cramér-Rao bound (CRB), equivalent Fisher information (EFI), information inequality, localization, ranging information (RI), squared position error bound (SPEB).Using the equation of Shur's complement [66], we have J −1 e (p) = J −1 +

The forkhead family protein FOXP3 acts as a repressor of transcription and is both an essential and sufficient regulator of the development and function of regulatory T cells. The molecular mechanism by which FOXP3-mediated transcriptional repression occurs remains unclear. Here, we report that transcriptional repression by FOXP3 involves a histone acetyltransferase-deacetylase complex that includes histone acetyltransferase TIP60 (Tat-interactive protein, 60 kDa) and class II histone deacetylases HDAC7 and HDAC9. The N-terminal 106 -190 aa of FOXP3 are required for TIP60 -FOXP3, HDAC7-FOXP3 association, as well as for the transcriptional repression of FOXP3 via its forkhead domain. FOXP3 can be acetylated in primary human regulatory T cells, and TIP60 promotes FOXP3 acetylation in vivo. Overexpression of TIP60 but not its histone acetyltransferase-deficient mutant promotes, whereas knockdown of endogenous TIP60 relieved, FOXP3-mediated transcriptional repression. A minimum FOXP3 ensemble containing native TIP60 and HDAC7 is necessary for IL-2 production regulation in T cells. Moreover, FOXP3 association with HDAC9 is antagonized by T cell stimulation and can be restored by the protein deacetylation inhibitor trichostatin A, indicating a complex dynamic aspect of T suppressor cell regulation. These findings identify a previously uncharacterized complex-based mechanism by which FOXP3 actively mediates transcriptional repression.A central theme that has emerged over the last 25 years is that a process of self-regulation of the immune response occurs to limit self-reactivity. Biochemical details of how the immune system distinguishes and regulates self and non-self remain to be fully documented (1). A recently characterized CD4 ϩ CD25 ϩ regulatory T cell subset expresses the Foxp3 transcription factor. As a transcriptional repressor of cytokine gene expression (2), Foxp3 was subsequently identified as an essential and sufficient regulator of natural regulatory T cell development and function (3-5).Mammalian transcriptional repressors can execute their function by either passive or active mechanisms (6, 7). FOXP3 may, for example, function as a passive transcriptional repressor in the case of its association with 9). In this study, we explore the role of FOXP3 as an active transcriptional repressor by revealing the dynamic FOXP3 ensemble formation with a specific histone acetyltransferase (HAT) and certain class II histone deacetylases (HDACs) in expanded human CD4 ϩ CD25 ϩ regulatory T cells (10, 11).Histone acetylation and histone deacetylation affect chromatin remodeling during T cell development and differentiation (12, 13). HAT and HDAC abnormalities have been associated with leukemia (14, 15), diabetes (16) and other diseases of the immune system (17-19). The linkage of HAT and HDAC as components of a single complex permits dynamic responsiveness to extracellular stimulation (18,20). The HAT TIP60 (Tat-interactive protein, 60 kDa), originally isolated as an HIV-1 TAT-interactive protein (21), functions as eith...

Network localization and navigation give rise to a new paradigm for communications and contextual data collection, enabling a variety of new applications that rely on position information of mobile nodes (agents). The performance of such networks can be significantly improved via the use of cooperation. Therefore, a deep understanding of information exchange and cooperation in the network is crucial for the design of location-aware networks. This article presents an exploration of cooperative network localization and navigation from a theoretical foundation to applications, covering technologies and spatiotemporal cooperative algorithms

Abstract-The availability of positional information is of great importance in many commercial, governmental, and military applications. Localization is commonly accomplished through the use of radio communication between mobile devices (agents) and fixed infrastructure (anchors). However, precise determination of agent positions is a challenging task, especially in harsh environments due to radio blockage or limited anchor deployment. In these situations, cooperation among agents can significantly improve localization accuracy and reduce localization outage probabilities. A general framework of analyzing the fundamental limits of wideband localization has been developed in Part I of the paper. Here, we build on this framework and establish the fundamental limits of wideband cooperative location-aware networks. Our analysis is based on the waveforms received at the nodes, in conjunction with Fisher information inequality. We provide a geometrical interpretation of equivalent Fisher information for cooperative networks. This approach allows us to succinctly derive fundamental performance limits and their scaling behaviors, and to treat anchors and agents in a unified way from the perspective of localization accuracy. Our results yield important insights into how and when cooperation is beneficial.Index Terms-Cooperative localization, Cramér-Rao bound (CRB), equivalent Fisher information (EFI), information inequality, ranging information (RI), squared position error bound (SPEB).

Assisted living (AL) technologies, enabled by technical advances such as the advent of the Internet-of-Things, are increasingly gaining importance in our ageing society. This article discusses the potential of future high-accuracy localization systems as a key component of AL applications. Accurate location information can be tremendously useful to realize, e.g., behavioral monitoring, fall detection, and real-time assistance. Such services are expected to provide older adults and people with disabilities with more independence and thus to reduce the cost for caretaking.Total cost of ownership and ease of installation are paramount to make sensor systems for AL viable. In case of a radiobased indoor localization system, this implies that a conventional solution is unlikely to gain widespread adoption because of its requirement to install multiple fixed nodes (anchors) in each room. This paper therefore places its focus on (i) discussing radiolocalization methods that reduce the required infrastructure by exploiting information from reflected multipath components and (ii) showing that knowledge about the propagation environment enables localization with high accuracy and robustness. It is demonstrated that new millimeter-wave (mm-wave) technology, under investigation for 5G communications systems, will be able to provide cm-accuracy indoor localization in a robust manner, ideally suited for AL.

Postoperative delirium is associated with increased morbidity, mortality and cost. However, its neuropathogenesis remains largely unknown, partially owing to lack of animal model(s). We therefore set out to employ a battery of behavior tests, including natural and learned behavior, in mice to determine the effects of laparotomy under isoflurane anesthesia (Anesthesia/Surgery) on these behaviors. The mice were tested at 24 hours before and at 6, 9 and 24 hours after the Anesthesia/Surgery. Composite Z scores were calculated. Cyclosporine A, an inhibitor of mitochondria permeability transient pore, was used to determine potential mitochondria-associated mechanisms of these behavioral changes. Anesthesia/Surgery selectively impaired behaviors, including latency to eat food in buried food test, freezing time and time spent in the center in open field test, and entries and duration in the novel arm of Y maze test, with acute onset and various timecourse. The composite Z scores quantitatively demonstrated the Anesthesia/Surgery-induced behavior impairment in mice. Cyclosporine A selectively ameliorated the Anesthesia/Surgery-induced reduction in ATP levels, the increases in latency to eat food, and the decreases in entries in the novel arm. These findings suggest that we could use a battery of behavior tests to establish a mouse model to study postoperative delirium.

BackgroundWhether healthy older people can benefit from cognitive training (CogTr) remains controversial. This study explored the benefits of CogTr in community dwelling, healthy, older adults and compared the effects of single-domain with multi-domain CogTr interventions.MethodsA randomized, controlled, 3-month trial of CogTr with double-blind assessments at baseline and immediate, 6-month and 12-month follow-up after training completion was conducted. A total of 270 healthy Chinese older people, 65 to 75 years old, were recruited from the Ganquan-area community in Shanghai. Participants were randomly assigned to three groups: multi-domain CogTr, single-domain CogTr, and a wait-list control group. Twenty-four sessions of CogTr were administrated to the intervention groups over a three-month period. Six months later, three booster training sessions were offered to 60% of the initial training participants. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Form A), the Color Word Stroop test (CWST), the Visual Reasoning test and the Trail Making test (TMT) were used to assess cognitive function.ResultsMulti-domain CogTr produced statistically significant training effects on RBANS, visual reasoning, and immediate and delayed memory, while single-domain CogTr showed training effects on RBANS, visual reasoning, word interference, and visuospatial/constructional score (all P < 0.05). At the 12-month posttest, the multi-domain CogTr showed training effects on RBANS, delayed memory and visual reasoning, while single-domain CogTr only showed effects on word interference. Booster training resulted in effects on RBANS, visual reasoning, time of trail making test, and visuospatial/constructional index score.ConclusionsCognitive training can improve memory, visual reasoning, visuospatial construction, attention and neuropsychological status in community-living older people and can help maintain their functioning over time. Multi-domain CogTr enhanced memory proficiency, while single-domain CogTr augmented visuospatial/constructional and attention abilities. Multi-domain CogTr had more advantages in training effect maintenance.Clinical Trial RegistrationChinese Clinical Trial Registry. Registration number: ChiCTR-TRC-09000732.