Early Late Phase Research Articles

Global positioning system spoofing detection based on Support Vector Machines

The civil Global Positioning System (GPS) is vulnerable to spoofing because of its open signal structure. The performance of previous spoofing detection methods is often limited due to spoofing's strong concealment. In this study, a method is proposed to detect spoofing by analysing the features of improved signal quality monitoring (SQM) moving variance (MV), improved SQM moving average (MA), early-late phase, carrier-to-noise ratio–MV and clock offset rate of receiver using Support Vector Machines. Then, the effectiveness of different kernel functions is compared along with other previous methods, revealing that our method outperforms previous methods when coarse Gaussian is used as kernel function. Specifically, the f1 score of the proposed method is improved by 3.22%, 12.85% and 35.72% in comparison with Back Propagation network, Ratio and Delta. The authors hope this work is beneficial for future research and for the implementation of GPS spoofing detection technology and high-performance receiver, which is of great significance to maintain the normal operation of GPS.

AOJS-3 - Practical issues and future perspectives on early phase development in Asia- competition, collaboration and harmonization

In changing of landscape at drug development process, the nature of oncology early phase 1 drug development has changed substantially in recent years, with key changes in multiple areas of trial design, implementation and interpretation. Two of these trends-increased sample size and increased use of expansion cohorts. Changes in phase 1 trials have evolved as the knowledge of molecular biology accumulates and as molecularly targeted and immuno-oncology agents have become more important parts of the oncology therapeutic strategy. In addition to changing nature of recent early phase oncology new drug development, Asia needs to take the initiative in developing drugs to treat cancers prevalent in the region, especially in Asian specific cancers from the initial-early stage of development. The National Cancer Center (NCC) of Japan signed a memorandum of understanding with key oncology phase 1 centers in Asia including China (HKSAR : Hong Kong Special Administrative Region), Korea, Singapore and Taiwan, to form the Asian Oncology Early Phase 1 Consortium (AsiaOne), to drive the momentum towards international collaborative phase 1 clinical trials across Asia, and to realize efficient clinical development of early phase oncology drugs serving the region since September 2017. By promoting multinational collaborative clinical trials across Asia initiated by global pharmaceutical companies utilizing this platform efficiently, multinational investigator-initiated clinical trials coordinated by Asian investigators, collaboration with early-late phase drug development divisions of pharmaceuticals, and already established accelerated review pathways as well as progress and implementation of the ICH E17 guideline for planning and designing multiregional clinical trials including Asian countries, advancing suitable style of drug development including treatments for unmet needs in Asia and genome-driven drug development need to be accelerated.

Detection of Spoofing Attack using Machine Learning based on Multi-Layer Neural Network in Single-Frequency GPS Receivers

The importance of the Global Positioning System (GPS) and related electronic systems continues to increase in a range of environmental, engineering and navigation applications. However, civilian GPS signals are vulnerable to Radio Frequency (RF) interference. Spoofing is an intentional intervention that aims to force a GPS receiver to acquire and track invalid navigation data. Analysis of spoofing and authentic signal patterns represents the differences as phase, energy and imaginary components of the signal. In this paper, early-late phase, delta, and signal level as the three main features are extracted from the correlation output of the tracking loop. Using these features, spoofing detection can be performed by exploiting conventional machine learning algorithms such as K-Nearest Neighbourhood (KNN) and naive Bayesian classifier. A Neural Network (NN) as a learning machine is a modern computational method for collecting the required knowledge and predicting the output values in complicated systems. This paper presents a new approach for GPS spoofing detection based on multi-layer NN whose inputs are indices of features. Simulation results on a software GPS receiver showed adequate detection accuracy was obtained from NN with a short detection time.

GPS 재방송 재밍신호 검출을 위한 통합 의사잡음신호를 사용한 확장된 ELP 기법

GPS 재방송 재밍신호 검출을 위한 통합 의사잡음신호를 사용한 확장된 ELP 기법

Analysis of early late phase in single-and dual-frequency GPS receivers for multipath detection

Abstract Much of the research into multipath detectionand mitigation has not considered the carrier phase delaybetween the line of sight (LOS) and reflected signals. Anew variable referred to as early late phase (ELP) hasrecently been proposed to exploit this phase difference. Ithas been found that in a receiver tracking the L1 GPSsignal, the probability of detecting multipath is lower whenthe carrier phase difference between the LOS and areflected signal is an integer multiple of p. Since thepseudorange error caused by the multipath’s presence is thehighest in this case, we propose to exploit the coexistenceof another GPS civilian signal, the L2C. We present ananalysis of ELP for the L1 and L2C signals, and a com-bination of both, for detecting multipath. The multipathdetection performance has been compared using probabil-ities of false alarm and detection. An ideal algorithmshould have lower probability of false alarm and higherprobability of detection. However, it has been found thatusing dual-frequency ELP increases both probabilities.Thus, receiver operator characteristics (ROC) curves, andthe area under the ROC curves, have been used for effec-tive comparison. It has been found that the L2C signalindividually gives worse performance than L1 because ofits weaker signal strength. However, the combination of L1and L2C gives the best overall performance, and thus it canbe claimed that ELP using dual-frequency receivers is amore effective approach for detecting multipath.Keywords Multipath GPS L2C ELP Dual-frequency receiverIntroductionThe last decade or so has seen an increase in applicationsof GPS in urban and indoor applications, which hasencouraged extensive research activity in the field ofmultipath detection and mitigation. Algorithms widelycited are narrow correlators (Dierendonck et al. 1992),double-difference residuals (DDR) (Townsend and Fenton1994), the vision correlator (Fenton and Jones 2005) andthe multipath estimating delay locked loop (MEDLL)(Townsend et al. 2000). Since a reflected signal reachesthe receiver by a relatively longer path, it is delayed intime and also has a carrier phase difference with respectto the line of sight (LOS) signal (Hatch et al. 2007;Mubarak and Dempster 2008). The above algorithms (andmany others) only use the magnitude of the correlatoroutputs and hence do not exploit this phase difference. Anew parameter, called the ‘‘early late phase (ELP)’’, hasrecently been proposed for multipath detection and esti-mation (Mubarak and Dempster 2007). ELP is the phasedifference between the early and late correlator outputs,where the phase of a correlator output is equal to theinverse tangent of the Q-channel output divided by theI-channel output. It is higher in the presence of multipathand has been shown to be a useful discriminator to detectthe presence of multipath (Mubarak 2008).This paper first provides a brief description of ELP,followed by its analysis in the presence of multipath for theL1 and L2C signals, and the combination of both. Multi-path detection performance is then compared using prob-abilities of false alarm and detection. ROC curves and the

6 Year Experience of Treatment by Imatinib in CML CP Patientsin 6 Million Population Region of Russia(Saint-Petersburg and Leningrad region)with Impact On Time and Kind of Pretreatment.

Abstract 4278Imatinib(IM) has become the “gold standard” for the treatment of CML CP. In clinical trials the majority of pts obtain complete hematologic (CHR) and complete cytogenetic (CCyR) responses. The aim of the study was to evaluate the results of treatment by IM in CML CP pts in general practice (outside clinical trials). Patients and methodsThere are 335 pts with CML in databases in Saint-Petersburg and Leningrad region. Most of them (283/335-84,5%) are ever treated with IM. Disease phases at the time of the start of IM therapy by ELN (from 268/283 evaluable pts) and MDACC (from 256/283 evaluable pts) criteria were: CP – 232 and 215, AP – 28 and 33, BP - 8 and 8 respectively. All 232 pts in CML CP (by ELN criteria) treated since 2001 by IM were included in the study. Before IM 91/232(39%), 114/232(49%) and 17/232 (7,3%) pts were pretreated by hydroxyurea, interferon-alfa with or without hydroxyurea and busulfan. 12/335(4%) pts were undergone alloSCT(6 alive, 6 dead due to progression or TRM)There were 134/232(58%) pts in early (duration before Im ≤ 12 mos) and 98/232(42%) pts in late CP (> 12 mos). In early and late CP, there were 49/123 and 50/89, 40/123 and 23/89, 34/123 and 16/89 evaluable pts with low, intermediate and high Socal score respectively. The predominance of low Sokal score in late CP pts could to be related to survival benefit before imatinib.. The median time before Im for the whole group, for early and late CP pts were 7,4 mos(from 7 days to 132 mons), 1,8 mons (form 7 days to 12 mons) and 39 mons (from 12,1 mos to 132 mos) respectively. Median time of Im therapy was 33 mos (1 - 75 mos) in whole group, 24mons (1 - 73mos) in early and 34mos(2 - 75mos) in late CP pts respectivel ResultsEstimated overall survival by 6 years was 94,2% in whole group, 97% and 87% in early and late CP pts resp. Only 14/228(6,1%) of evaluable patients died due to CML: 4/130(3%) in early and 10/98(10,2%) in late CP group. 4 pts, resistant to IM, were transplanted: 1 in early CP and 3 in BP. Deathes were due to TRM or disease progression.CHR was achieved by 3 mons in most cases: 82/110(74,5%) and 36/64(56%) pt, in early and late CP, resp. Patients (39 in hole group, 12 in early and 27 in late CP) with CHR before IM were excluded from these analyses.The probability of CCyR by 6 years was 98% in early CP and 82% in late CP (p=0.002). The rate of CCyR was 75% 80/107) vs 31% (14/75) in patients with or without CHR by 3 mons (p=0.00). The same differences were found in early and late CP. CCyR in patients with CHR before IM was the same as in patients with newly obtained CHR by 3 mons on IM.Thereafter we have divided group of pts with late CP according to its duration before IM (very early -<6mons, early late - 6-60 mons and very late ≥60 mons) and compared CCyR in early CP with different subgroups of late CP.Achievement of CCyR was higher in pts in very early(69.1%) and early –late(68.2%) than in very late group(34.6%)(p=0.09) Further subdivisions of the period of 6-60 mos did not reveal any differences. Moreover, when we deleted the patients pretreated with busulfan, the differences were found only between early and early-late phases. We have separately analyzed very late group, it appeared that pretreatment with busulfan severely decreases CCyR (22% vs 81% in with (12 pts) or without (7 pts) busulfan pretreatment, p=0,002. Probably, patients in very late CP is a specific group of patients with preformed very good prognosis.Clonal evolution before treatment (8 pts in early CP and 7 in late CP) did not influence CCyR achievement.The probability of progression to AP/BP was slightly higher in late (6%) than in early CP (3%) (p=0.05). The appearance of clonal evolution was higher in late than in early CP (p=0,0002). Progression to AP/BP was 1% vs 11% in pts with or without CHR by 3 mos resp. (p=0.003). ConclusionsImatinib is efficacious drug in general hematological practice with very high probability of overall survival, CCyR and low risk of progression to AP/BP. CHR is an early and very important predictor for further successful treatment. Achievement of CCyR strongly depends on CHR by 3 mons. Patients with CHR before imatinib have similar CCyR in patients with CHR by 3 mons on imatinib. Pretreatment period predispose patients to clonal evolution on imatinib treatment. Busulfan pretreatment severely decreases probability of CCyR. Disclosures:No relevant conflicts of interest to declare.

Expressed genes in regenerating rat liver after partial hepatectomy

To reveal the liver regeneration (LR) and its control as well as the occurrence of liver disease and to study the gene expression profiles of 551 genes after partial hepatectomy (PH) in regenerating rat livers. Five hundred and fifty-one expressed sequence tags screened by suppression subtractive hybridization were made into an in-house cDNA microarray, and the expressive genes and their expressive profiles in regenerating rat livers were analyzed by microarray and bioinformatics. Three hundred of the analyzed 551 genes were up- or downregulated more than twofolds at one or more time points during LR. Most of the genes were up- or downregulated 2-5 folds, but the highest reached 90 folds of the control. One hundred and thirty-nine of them showed upregulation, 135 displayed downregulation, and up or down expression of 26 genes revealed a dependence on regenerating livers. The genes expressed in 24-h regenerating livers were much more than those in the others. Cluster analysis and generalization analysis showed that there were at least six distinct temporal patterns of gene expression in the regenerating livers, that is, genes were expressed in the immediate early phase, early phase, intermediate phase, early-late phase, late phase, terminal phase. In LR, the number of down-regulated genes was almost similar to that of the upregulated genes; the successively altered genes were more than the rapidly transient genes. The temporal patterns of gene expression were similar 2 and 4 h, 12 and 16 h, 48 and 96 h, 72 and 144 h after PH. Microarray combined with suppressive subtractive hybridization can effectively identify the genes related to LR.

Clock and data recovery IC for 40-Gb/s fiber-optic receiver

The integrated clock and data recovery (CDR) circuit is a key element for broad-band optical communication systems at 40 Gb/s. We report a 40-Gb/s CDR fabricated in indium-phosphide heterojunction bipolar transistor (InP HBT) technology using a robust architecture of a phase-locked loop (PLL) with a digital early-late phase detector. The faster InP HBT technology allows the digital phase detector to operate at the full data rate of 40 Gb/s. This, in turn, reduces the circuit complexity (transistor count) and the voltage-controlled oscillator (VCO) requirements. The IC includes an on-chip LC VCO, on-chip clock dividers to drive an external demultiplexer, and low-frequency PLL control loop and on-chip limiting amplifier buffers for the data and clock I/O. To our knowledge, this is the first demonstration of a mixed-signal IC operating at the clock rate of 40 GHz. We also describe the chip architecture and measurement results.

A plastic packaged 10 Gb/s BiCMOS clock and data recovering 1:4-demultiplexer with external VCO

Architecture and realization of a 10 Gb/s clock and data recovering demultiplexer (CDR-DMUX) test chip fabricated in a 0.7-/spl mu/m single poly, 16-GHz BiCMOS process are described. The first stage of the circuit is a combination of a 1:2 DMUX and a parallel early-late phase detector, both supplied with 5-GHz clocks from an external VCO. The plastic package does not measurably degrade the differential data input reflection. The 2.3/spl times/2.3 mm/sup 2/ chip dissipates 450 mW at -3.6 V.