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The mechanism of gender disparity in cutaneous melanoma incidence remains unclear. Steroid hormones including estrogens have long been implicated in the course of melanoma, but the conclusion is controversial. Estrogen receptors (ERs) and insulin-like growth factor 1 receptor (IGF1R) show extensive crosstalk in cancer development, but how the ER/IGF1R network impacts melanoma is currently unclear. Here we studied the melanoma associations of selected SNPs from the ER/IGF1R network. Part of the International Genes, Environment, and Melanoma (GEM) cohort was used as a discovery set, and the Gene Environment Association Studies Initiative (GENEVA) dataset served as a validation set. Based on the associations with other malignant disease conditions, thirteen single nucleotide polymorphism (SNP) variants in ESR1, ESR2, IGF1, and IGF1R were selected for candidate gene association analyses. The rs1520220 in IGF1 and rs2229765 in IGF1R variants were significantly associated with melanoma risk in the GEM dataset after Benjamini-Hochberg multiple comparison correction, although they were not validated in the GENEVA set. The discrepancy may be caused by the multiple melanoma characteristics in the GEM patients. Further analysis of gender disparity was carried out for IGF1 and IGF1R SNPs in the GEM dataset. The GG phenotype in IGF1 rs1520220 (recessive model) presented an increased risk of melanoma (OR = 8.11, 95% CI: 2.20, 52.5, p = 0.006) in men but a significant opposite effect in women (OR = 0.15, 95% CI: 0.018, 0.86, p = 0.045). The AA genotype in IGF1R rs2229765 (recessive model) showed a significant protective effect in men (OR = 0.24, 95% CI: 0.07, 0.64, p = 0.008) and no effect in women. Results from the current study are warranted for further validation.

Neoantigen-specific T cells are increasingly viewed as important immunotherapy effectors, but physically isolating these rare cell populations is challenging. Here, we describe a sensitive method for the enumeration and isolation of neoantigen-specific CD8+ T cells from small samples of patient tumor or blood. The method relies on magnetic nanoparticles that present neoantigen-loaded major histocompatibility complex (MHC) tetramers at high avidity by barcoded DNA linkers. The magnetic particles provide a convenient handle to isolate the desired cell populations, and the barcoded DNA enables multiplexed analysis. The method exhibits superior recovery of antigen-specific T cell populations relative to literature approaches. We applied the method to profile neoantigen-specific T cell populations in the tumor and blood of patients with metastatic melanoma over the course of anti-PD1 checkpoint inhibitor therapy. We show that the method has value for monitoring clinical responses to cancer immunotherapy and might help guide the development of personalized mutational neoantigen-specific T cell therapies and cancer vaccines.

The different ways, by which MiRingBack (MRB) service, which enables the subscriber to provide customized ring-back tone to a calling party, can seamlessly adapt to changing network paradigms and provide multimedia content such as text, image, audio, or video, are addressed. The evolution of MRB service to Multimedia MiRingback (MmRB) service using the packet service capabilities of the network is described and the call flow for MmRB is detailed.

The enforcement of end-to-end quality of service (QoS) for Internet Protocol (IP) Multimedia Subsystem (IMS), which uses Session Initiation Protocol (SIP)-based sessions in CDMA2000* networks is discussed. It is seen that the IMS elements work together, which assist QoS negotiation on the control plane and traffic enforcement on the bearer plane.

A logical hypercube structure is used to obtain scalability and fault-tolerance in distributed systems.

A closed-loop (demand-driven) approach toward video-on-demand services, called multicast cache (Mcache), is discussed in this paper. Servers use multicast to reduce their bandwidth usage by allowing multiple requests to be served with a single data stream. However, this requires clients to delay receiving the movie until the multicast starts. Using regional cache servers deployed over many strategic locations, Mcache can remove the initial playout delays of clients in multicast-based video streaming. While requests are hatched together for a multicast, clients can receive the prefix of a requested movie clip from caches located in their own regions. The multicast containing the later portion of the movie can wait until the prefix is played out. While this use of regional caches has been proposed previously, the novelty of our scheme lies in that the requests coming after the multicast starts can still be hatched together to be served by multicast patches without any playout delays. The use of patches was proposed before, but they are used either with unicast or with playout delays. Mcache effectively hires the idea of a multicast patch with caches to provide a truly adaptive video-on-demand service whose bandwidth usage is up to par with the best known open-loop schemes under high request rates while using only minimal bandwidth under low request rates. In addition, efficient use of multicast and caches removes the need for a priori knowledge of client disk storage requirements which some of the existing schemes assume. This makes Mcache ideal for the current heterogeneous Internet environments where those parameters are hard to predict. We further propose the Segmented Mcache (SMcache) scheme which is a generalized and improved version of Mcache where the clip is partitioned into several segments in order to preserve the advantages of the original Mcache scheme with nearly the same server bandwidth requirement as the open loop schemes under high request rates.