Exploring Cognitive States: Methods for Detecting Physiological Temporal Fingerprints

Cognitive state detection and its relationship to observable physiologically telemetry has been utilized for many human-machine and human-cybernetic applications. This paper aims at understanding and addressing if there are unique psychophysiological patterns over time, a physiological temporal fingerprint, that is associated with specific cognitive states. This preliminary work involves commercial airline pilots completing experimental benchmark task inductions of three cognitive states: 1) Channelized Attention (CA); 2) High Workload (HW); and 3) Low Workload (LW). We approach this objective by modeling these "fingerprints" through the use of Hidden Markov Models and Entropy analysis to evaluate if the transitions over time are complex or rhythmic/predictable by nature. Our results indicate that cognitive states do have unique complexity of physiological sequences that are statistically different from other cognitive states. More specifically, CA has a significantly higher temporal psychophysiological complexity than HW and LW in EEG and ECG telemetry signals. With regards to respiration telemetry, CA has a lower temporal psychophysiological complexity than HW and LW. Through our preliminary work, addressing this unique underpinning can inform whether these underlying dynamics can be utilized to understand how humans transition between cognitive states and for improved detection of cognitive states

Phase I dose-escalation and pharmacokinetic study of dasatinib in patients with advanced solid tumors

PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicity (DLT), and recommended phase II dose of dasatinib in metastatic solid tumors refractory to standard therapies or for which no effective standard therapy exists. <br></br> EXPERIMENTAL DESIGN: In this phase I, open-label, dose-escalation study, patients received 35 to 160 mg of dasatinib twice daily in 28-day cycles either every 12 hours for 5 consecutive days followed by 2 nontreatment days every week (5D2) or as continuous, twice-daily (CDD) dosing. <br></br> RESULTS: Sixty-seven patients were treated (5D2, n = 33; CDD, n = 34). The maximum tolerated doses were 120 mg twice daily 5D2 and 70 mg twice daily CDD. DLTs with 160 mg 5D2 were recurrent grade 2 rash, grade 3 lethargy, and one patient with both grade 3 prolonged bleeding time and grade 3 hypocalcemia; DLTs with 120 mg twice daily CDD were grade 3 nausea, grade 3 fatigue, and one patient with both grade 3 rash and grade 2 proteinuria. The most frequent treatment-related toxicities across all doses were nausea, fatigue, lethargy, anorexia, proteinuria, and diarrhea, with infrequent hematologic toxicities. Pharmacokinetic data indicated rapid absorption, dose proportionality, and lack of drug accumulation. Although no objective tumor responses were seen, durable stable disease was observed in 16% of patients.<br></br> CONCLUSION: Dasatinib was well tolerated in this population, with a safety profile similar to that observed previously in leukemia patients, although with much less hematologic toxicity. Limited, although encouraging, preliminary evidence of clinical activity was observed. Doses of 120 mg twice daily (5D2) or 70 mg twice daily (CDD) are recommended for further studies in patients with solid tumors.<br></br&gt

Pressure dependent electronic properties of MgO polymorphs: A first-principles study of Compton profiles and autocorrelation functions

The first-principles periodic linear combination of atomic orbitals method within the framework of density functional theory implemented in the CRYSTAL06 code has been applied to explore effect of pressure on the Compton profiles and autocorrelation functions of MgO. Calculations are performed for the B1, B2, B3, B4, B8_1 and h-MgO polymorphs of MgO to compute lattice constants and bulk moduli. The isothermal enthalpy calculations predict that B4 to B8_1, h-MgO to B8_1, B3 to B2, B4 to B2 and h-MgO to B2 transitions take place at 2, 9, 37, 42 and 64 GPa respectively. The high pressure transitions B8_1 to B2 and B1 to B2 are found to occur at 340 and 410 GPa respectively. The pressure dependent changes are observed largely in the valence electrons Compton profiles whereas core profiles are almost independent of the pressure in all MgO polymorphs. Increase in pressure results in broadening of the valence Compton profiles. The principal maxima in the second derivative of Compton profiles shifts towards high momentum side in all structures. Reorganization of momentum density in the B1 to B2 structural phase transition is seen in the first and second derivatives before and after the transition pressure. Features of the autocorrelation functions shift towards lower r side with increment in pressure.Comment: 19 pages, 8 figures, accepted for publication in Journal of Materials Scienc

A Characterization of Scale Invariant Responses in Enzymatic Networks

An ubiquitous property of biological sensory systems is adaptation: a step increase in stimulus triggers an initial change in a biochemical or physiological response, followed by a more gradual relaxation toward a basal, pre-stimulus level. Adaptation helps maintain essential variables within acceptable bounds and allows organisms to readjust themselves to an optimum and non-saturating sensitivity range when faced with a prolonged change in their environment. Recently, it was shown theoretically and experimentally that many adapting systems, both at the organism and single-cell level, enjoy a remarkable additional feature: scale invariance, meaning that the initial, transient behavior remains (approximately) the same even when the background signal level is scaled. In this work, we set out to investigate under what conditions a broadly used model of biochemical enzymatic networks will exhibit scale-invariant behavior. An exhaustive computational study led us to discover a new property of surprising simplicity and generality, uniform linearizations with fast output (ULFO), whose validity we show is both necessary and sufficient for scale invariance of enzymatic networks. Based on this study, we go on to develop a mathematical explanation of how ULFO results in scale invariance. Our work provides a surprisingly consistent, simple, and general framework for understanding this phenomenon, and results in concrete experimental predictions

Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Diversity analysis of Sweet Potato (Ipomoea batatas[L.] Lam) genotypes using morphological, biochemical and molecular markers

276-285Sweet potato [Ipomeabatatas(L.) Lam.]is a nutritious food crop primarily grown by small and marginal farmers. Successful breeding and germplasm conservation programs demands characterization of its germplasm. Here, we tried to determine genetic diversity among 21 sweet potato genotypes using morphological, biochemical and molecular markers. Ten morphological traits were studied and subjected to analysis of variance (ANOVA). Mean square due to germplasm were highly significant as well as wide mean range performance was observed for tuber number per plant, individual tuber weight, tuber fresh yield per plant, tuber dry yield per plant, tuber yield per plot and tuber length. UPGMA (Unweighted Pair Group Method Arithmetic Average) cluster analysis based on morphological traits separated the germplasm into three groups. The genotypes Gautam, Shree Arun, RS-92 and CO-3-4 appeared promising with regard to yield characters. Total phenol was maximum in in V-12 genotype (1.39 mg), while minimum was recorded in Samrat genotype (0.95 mg). The highest total antioxidant was observed in the genotype Samrat (0.30 mg), while minimum was recorded in the genotype Navsari Local (0.16 mg). Molecular diversity analysis was carried out using 25 RAPD (Random Amplified Polymorphic DNA) primers, out of which 13 primers produced 117 reproducible amplicons (106 polymorphic, 7 monomorphic and 4 unique amplicons). UPGMA dendogram based on RAPD data separated the genotypes into two major clusters having the similarity coefficient ranged from 0.56 to 0.76. The results can be used for sweet potato crop improvement through molecular breeding and marker assisted selection of for desired traits in future

POLAROGRAPHIC STUDIES OF As (III) AND Sb(III) WITH SERINE

ABSTRACT The reduction of As(III) and Sb(III) with serine is investigated polarographically in aqueous medium. As(III) and Sb(III) formed 1:1, 1:2 and 1:3 complex species with Serine. The stability constants of As(III) and Sb(III) with serine were evaluated by the method of DeFord and Hume. The reduction of the system in each case is quasireversible and diffusion controlled, involving three electrons. The thermodynamic parameters have been determined. The stability constants of these species at 300K for As(III) with serine are logβ 1 = 2.17, logβ 2 = 4.60, logβ 3 = 6.73 and at 310 K are logβ 1 = 1.87, logβ 2 = 4.00, logβ 3 = 6.55 and thermodynamic parameters free energy (KCal mo