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Abstract Background Notch signaling drives many aspects of neoplastic phenotype. Here, we report that the Integrator complex (INT) is a new component of the Notch transcriptional supercomplex. Together with Notch Activation Complex Kinase (NACK), INT activates Notch1 target genes by driving RNA polymerase II (RNAPII)-dependent transcription, leading to tumorigenesis. Methods Size exclusion chromatography and CBF-1/RBPJ/Suppressor of Hairless/Lag-1 (CSL)-DNA affinity fast protein liquid chromatography (FPLC) was used to purify Notch/CSL-dependent complexes for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Chromatin immunoprecipitation (ChIP) and quantitative polymerase chain reaction (qPCR) were performed to investigate transcriptional regulation of Notch target genes. Transfection of Notch Ternary Complex components into HEK293T cells was used as a recapitulation assay to study Notch-mediated transcriptional mechanisms. Gene knockdown was achieved via RNA interference and the effects of protein depletion on esophageal adenocarcinoma (EAC) proliferation were determined via a colony formation assay and murine xenografts. Western blotting was used to examine expression of INT subunits in EAC cells and evaluate apoptotic proteins upon INT subunit 11 knockdown (INTS11 KD). Gene KD effects were further explored via flow cytometry. Results We identified the INT complex as part of the Notch transcriptional supercomplex. INT, together with NACK, activates Notch-mediated transcription. While NACK is required for the recruitment of RNAPII to a Notch-dependent promoter, the INT complex is essential for RNAPII phosphorylated at serine 5 (RNAPII-S5P), leading to transcriptional activation. Furthermore, INT subunits are overexpressed in EAC cells and INTS11 KD results in G2/M cell cycle arrest, apoptosis, and cell growth arrest in EAC. Conclusions This study identifies the INT complex as a novel co-factor in Notch-mediated transcription that together with NACK activates Notch target genes and leads to cancer cell proliferation. Video abstract

In next-generation wireless communication systems, non-orthogonal multiple access (NOMA) has been recognized as essential technology for improving the spectrum efficiency. NOMA allows multiple users transmit data using the same resource block simultaneously with proper user pairing. Most of the pairing schemes, however, require prior information, such as location information of the users, leading to difficulties in realizing prompt user pairing. To realize real-time operations without prior information in NOMA, a bandit algorithm using chaotically oscillating time series, which we refer to as the laser chaos decision-maker, was demonstrated. However, this scheme did not consider the detailed communication processes, e.g., modulation, error correction code, etc. In this study, in order to adapt the laser chaos decision-maker to real communication systems, we propose a user pairing scheme based on acknowledgment (ACK) and negative acknowledgment (NACK) information considering detailed communication channels. Furthermore, based on the insights gained by the analysis of parameter dependencies, we introduce an adaptive pairing method to minimize the bit error rate of the NOMA system under study. The numerical results show that the proposed method achieves superior performances than the traditional using pairing schemes, i.e., Conventional-NOMA pairing scheme (C-NOMA) and Unified Channel Gain Difference pairing scheme (UCGD-NOMA), and ϵ -greedy-based user pairing scheme. As the cell radius of the NOMA system gets smaller, the superior on the BER of our proposed scheme gets bigger. Specifically, our proposed scheme can decrease the BER from 10 − 1 to 10 − 5 compared to the conventional schemes when the cell radius is 400 m. [ABSTRACT FROM AUTHOR]

Background: Notch signaling drives many aspects of neoplastic phenotype. Here, we report that the Integrator complex (INT) is a new component of the Notch transcriptional supercomplex. Together with Notch Activation Complex Kinase (NACK), INT activates Notch1 target genes by driving RNA polymerase II (RNAPII)-dependent transcription, leading to tumorigenesis. Methods: Size exclusion chromatography and CBF-1/RBPJ/Suppressor of Hairless/Lag-1 (CSL)-DNA affinity fast protein liquid chromatography (FPLC) was used to purify Notch/CSL-dependent complexes for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Chromatin immunoprecipitation (ChIP) and quantitative polymerase chain reaction (qPCR) were performed to investigate transcriptional regulation of Notch target genes. Transfection of Notch Ternary Complex components into HEK293T cells was used as a recapitulation assay to study Notch-mediated transcriptional mechanisms. Gene knockdown was achieved via RNA interference and the effects of protein depletion on esophageal adenocarcinoma (EAC) proliferation were determined via a colony formation assay and murine xenografts. Western blotting was used to examine expression of INT subunits in EAC cells and evaluate apoptotic proteins upon INT subunit 11 knockdown (INTS11 KD). Gene KD effects were further explored via flow cytometry. Results: We identified the INT complex as part of the Notch transcriptional supercomplex. INT, together with NACK, activates Notch-mediated transcription. While NACK is required for the recruitment of RNAPII to a Notch-dependent promoter, the INT complex is essential for RNAPII phosphorylated at serine 5 (RNAPII-S5P), leading to transcriptional activation. Furthermore, INT subunits are overexpressed in EAC cells and INTS11 KD results in G2/M cell cycle arrest, apoptosis, and cell growth arrest in EAC. Conclusions: This study identifies the INT complex as a novel co-factor in Notch-mediated transcription that together with NACK activates Notch target genes and leads to cancer cell proliferation. DmMSvvPJYVoBWTrbTitSG7 Video abstract [ABSTRACT FROM AUTHOR]

As telecommunication systems evolve towards new-generation architectures, likewise, new protocols are created in order to improve efficiency. One of these protocols is Transmission Control Protocol (TCP), which controls the transmission bit rate in function of network congestion. Nevertheless, in wireless communications, there appear problems such as noise and interference, for which TCP was not designed. Based on these problems, there exist some methods trying to mitigate congestion, such as explicit loss notifications and the use of end-to-end codification. The aim of this work was to propose a wireless TCP protocol improvement, considering a negative acknowledgment (NACK), which allows to differentiate between losses due to congestion and losses due to wireless channel issues. NACK employs a small protocol packet and produces improvement in the quality of service metrics. The experiments were carried out in in-door and out-door environments, over an online video game scenario, and over a long-distance wireless link between two islands. The average results show a 25-percent delay improvement and a 5-percent jitter improvement when compared to the original TCP Reno protocol, while for throughput a 90-percent improvement was achieved for distances between 100 and 414 m.

This work evaluates the performance of TCP Protocol new algorithm on a wide-area wireless link in order to optimize it and compare the results. To this purpose, is proposed an optimization and QoS solution in order to improve the TCP new algorithm performance. Also a WWAN point to point link was designed and implemented and the optimization solution was configured on it using dedicated hardware. Finally, performance tests using injection of TCP traffic were performed using a real operation environment. Using the obtained results we concluded that the proposed optimization solution improves the performance parameters of the WWAN link using the new algortihm. [ABSTRACT FROM PUBLISHER]

Mobile ad-hoc network is an interesting network, which is classified as an autonomous system. These types of networks are constructed based on low capacity wireless links, without having a centralized infrastructure system. Lack of central monitoring system makes it so vulnerable to an insider attack. These attacks consist of two main categories; false data and false route attack. An efficient intrusion detection system (IDS) should have a good understanding about the categories. It can be defined by comparison between (true positive network throughput/false throughput) and the packet delivery ratio. This paper, DNACK is proposed based on Digital Signature and standard method of Negative Acknowledgment, which is a new method of false data detection in case of en-route filtering IDS. DNACK members can detect both kinds of insider attacks, a false data (false data injected and false modified messages) and false route attacks (packet dropping and flooding attack), regards to DNACK characteristic. The false data will be detected based on source digital signature by upcoming member and the routing attacks, will be monitored by the last member. The network efficiency shall be guaranteed by using of DNACK because of the high percentage of Packet delivery and the minimum of false throughput. [ABSTRACT FROM AUTHOR]

Other than hardware optimization, the communication protocols for heterogeneous Wireless Sensor Network (WSN) are currently playing an important role for achieving the longevity of the network. Among other layers of heterogeneous WSN communication protocol stack, researchers are putting efforts in developing transport layer protocols in order to avoid congestion in WSN and provide data or application level reliability support thereby ensuring the QoS objectives of the heterogeneous WSN application. In this paper we have envisaged a light weight transport protocol design, End-to-End Reliable and Congestion Aware Transport Layer Protocol (ERCTP), which achieves high data reliability by the introduction of distributed memory concept within network and minimum packet drop due to congestion by the effective implementation of congestion detection and rate adjustment scheme that uses stochastic control framework. The proposed scheme is evaluated extensively against the TCP-Westwood+ (TCPWW+), TCP-Westwood (TCP-WW), TCPNewReno(TCP-NR), and TCPReno(TCP-R). The ERCTP has been tested for 24 mote topology and results reveal that the ERCTP effectively controls congestion and exhibits highest good throughput of 0.2941 Mbps, ≤100 msec average End-to-End (E-2-E) data packet latency for heterogeneous packet information, > 99% data packet reliability and overall energy efficient behavior (lowest per packet communication cost) in comparison to TCP-WW+, TCP-WW, TCP-NR and TCP-R. [ABSTRACT FROM AUTHOR]

As telecommunication systems evolve towards new-generation architectures, likewise, new protocols are created in order to improve efficiency. One of these protocols is Transmission Control Protocol (TCP), which controls the transmission bit rate in function of network congestion. Nevertheless, in wireless communications, there appear problems such as noise and interference, for which TCP was not designed. Based on these problems, there exist some methods trying to mitigate congestion, such as explicit loss notifications and the use of end-to-end codification. The aim of this work was to propose a wireless TCP protocol improvement, considering a negative acknowledgment (NACK), which allows to differentiate between losses due to congestion and losses due to wireless channel issues. NACK employs a small protocol packet and produces improvement in the quality of service metrics. The experiments were carried out in in-door and out-door environments, over an online video game scenario, and over a long-distance wireless link between two islands. The average results show a 25-percent delay improvement and a 5-percent jitter improvement when compared to the original TCP Reno protocol, while for throughput a 90-percent improvement was achieved for distances between 100 and 414 m. [ABSTRACT FROM AUTHOR]

This letter considers an Internet streaming protocol (SP) for the transport of real time continuous data stream. SP makes use of measured network delay to optimally set retransmission time-outs and scale reliability. The sender streams out packets in a periodic manner, and a NACK is issued by the receiver if it does not receive an expected packet by a certain time. Although it may appear at first glance that the sender's and receiver's clocks must be synchronized, we prove that that the SP would work even if the clocks were not synchronized, a situation not uncommon in the Internet [ABSTRACT FROM PUBLISHER]

Abstract: Today a country''s economic viability and its citizens’ job mobility require that its workforce have a strong micro- and nanotechnology education providing a skill set covering synthesis, fabrication, and characterization. An international model is offered for creating such a skilled workforce which is based on a resource sharing approach between research universities and technical colleges. For the good of a country and its citizens, workers must have the educational background that allows them to move from job to job as sectors wax and wane. This broad twenty-first century education that is proposed provides the infrastructure that is needed to accomplish this and to thereby give a country the intellectual capital to be a competitive force on the rapidly changing world manufacturing scene. [Copyright &y& Elsevier]

Sugen kinases (SgK)269 (also known as PEAK1), and SgK223, an orthologue of rat pragmin and mouse NACK, are human pseudokinases that are implicated in the progression of several cancers. Both are scaffolding proteins that recruit distinct repertoires of signalling proteins and regulate a variety of biological endpoints including cell migration and invasion. To date, SgK269 and SgK223 have been largely studied as separate signalling entities. However, recent work has demonstrated that SgK269 and SgK223 undergo homo- and heterotypic association that determines signal output and biological response. Further characterization of the mechanism of action of these two pseudokinases will provide novel insights into how they promote cancer progression and may reveal novel therapeutic strategies. Here we review their structure, mechanism and function and roles they play in cancer pathogenesis.

Wireless multicasting (also called common information broadcasting) is a technique where a common information message is transmitted to multiple users. This is typically accomplished by having the basestation broadcast out a signal representing this message. In this paper, we consider a multicasting scheme where the basestation transmits the multicasting signal without any a-priori knowledge of the users' channel state information. In this set-up, a hybrid automatic repeat request (ARQ) control is employed to improve the reliability of multicasting communication. In most hybrid ARQ set-ups, each user is usually allocated a dedicated feedback channel to tell the basestation if the previously transmitted signal was correctly decoded. However, dedicated feedback channels waste significant uplink resources, especially when the number of users is large. To mitigate this problem, we consider a negative acknowledgement (NACK) based hybrid ARQ control where the failed users are allowed to transmit the NACK signal (which is assumed to be the same for all users) through a common channel while the other users remain silent. We consider the effect of feedback error and multicasting signal decoding error on our hybrid ARQ system performance as the number of users grows large. Specifically, it is shown that the throughput performance of the proposed hybrid ARQ scheme using repetition retransmission is not severely degraded relative to the throughput performance of the noiseless feedback case. In addition, we show that the performance improvement obtained by replacing repetition encoding with incremental redundancy becomes insignificant for the large number of users asymptote. On the other hand, it is shown that the improvement provided by incremental redundancy is significant when some of the users are allowed to fail to decode the message. [ABSTRACT FROM AUTHOR]