Impurity and spin effects on the magneto-spectroscopy of a THz-modulated nanostructure

We present a grid-free DFT model appropriate to explore the time evolution of electronic states in a semiconductor nanostructure. The model can be used to investigate both the linear and the nonlinear response of the system to an external short-time perturbation in the THz regime. We use the model to study the effects of impurities on the magneto-spectroscopy of a two-dimensional electron gas in a nanostructure excited by an intense THz radiation. We do observe a reduction in the binding energy of the impurity with increasing excitation strength, and at a finite magnetic field we find a slow onset of collective spin-oscillations that can be made to vanish with a stronger excitation.Comment: LaTeX,10 pages with 11 embedded postscript figure

Probabilistic approaches for modeling text structure and their application to text-to-text generation

Since the early days of generation research, it has been acknowledged that modeling the global structure of a document is crucial for producing coherent, readable output. However, traditional knowledge-intensive approaches have been of limited utility in addressing this problem since they cannot be effectively scaled to operate in domain-independent, large-scale applications. Due to this difficulty, existing text-to-text generation systems rarely rely on such structural information when producing an output text. Consequently, texts generated by these methods do not match the quality of those written by humans – they are often fraught with severe coherence violations and disfluencies. In this chapter, I will present probabilistic models of document structure that can be effectively learned from raw document collections. This feature distinguishes these new models from traditional knowledge intensive approaches used in symbolic concept-to-text generation. Our results demonstrate that these probabilistic models can be directly applied to content organization, and suggest that these models can prove useful in an even broader range of text-to-text applications than we have considered here.National Science Foundation (U.S.) (CAREER grant IIS- 0448168)Microsoft Research. New Faculty Fellowshi

Proteogenomic integration reveals therapeutic targets in breast cancer xenografts

Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast cancer patient-derived xenograft (PDX) models. Integrated proteogenomic analysis shows positive correlation between expression measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal protein markers. Proteogenomic analysis also validates a number of predicted genomic targets in multiple receptor tyrosine kinases. However, several protein/phosphoprotein events such as overexpression of AKT proteins and ARAF, BRAF, HSP90AB1 phosphosites are not readily explainable by genomic analysis, suggesting that druggable translational and/or post-translational regulatory events may be uniquely diagnosed by MS. Drug treatment experiments targeting HER2 and components of the PI3K pathway supported proteogenomic response predictions in seven xenograft models. Our study demonstrates that MS-based proteomics can identify therapeutic targets and highlights the potential of PDX drug response evaluation to annotate MS-based pathway activities

Proteogenomic landscape of breast cancer tumorigenesis and targeted therapy

The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy

Synthesis and characterization of highly crystalline conjugated polyparaphenylene and polythiophene conductive polymer thin-films

Molecular, crystalline and morphological characteristics of polyparaphenylene (PPP) and polythiophene (PTh) conjugated polymers are reported here. Thin films of PPP and PTh exhibit molecular- and crystalline-anisotropic structures, obtained intrinsically by a single-step approach of electrochemical method. The unique advantage of controlled electrochemical polymerization/crystallization is highlighted by ex-situ high-temperature X-ray diffraction, morphology, luminescence, and ex-situ electrochemical X-ray diffraction data. Structural analysis in terms of degree of crystalline order (Xcr) as the crystalline-gauging parameter and X-ray diffraction profile data as molecular order probe have been reported. The electrochemical thickness effect, high degree of crystalline order (Xcr=99%), and thin film and molecular anisotropy are highlighted in terms of supramolecular order of the highly conjugated polymer molecule

Ex-situ high temperature X-ray diffraction studies on partially crystalline conjugated polymers

Molecular and crystalline structural aspects of partially crystalline conjugated polymers have been reported for polyanilines (PANis) and polythiophene (Pth). Improvement in crystalline order has been observed in chemically synthesized polymers by high-temperature annealing. This paper mainly concerns structural analysis in terms of degree of crystalline order (Xcr) as the crystalline-gauging parameter, and X-ray diffraction profile data as molecular order probe. A large extent of enhancement of crystalline domains up to 25% through recrystallization and crystallite growth has been obtained by high-temperature annealing of EB-and ES-PANis and Pth-dissociated hexithiophene materials (of intrinsic Xcr=20 to 50%). The mechanism of enhancement of crystalline order is given in terms of polymer molecular phenomen

The effect of dietary nitrate on salivary, plasma, and urinary nitrate metabolism in humans

Dietary nitrate is metabolized to nitrite by bacterial flora on the posterior surface of the tongue leading to increased salivary nitrite concentrations. In the acidic environment of the stomach, nitrite forms nitrous acid, a potent nitrating/nitrosating agent. The aim of this study was to examine the pharmacokinetics of dietary nitrate in relation to the formation of salivary, plasma, and urinary nitrite and nitrate in healthy subjects. A secondary aim was to determine whether dietary nitrate increases the formation of protein-bound 3-nitrotyrosine in plasma, and if dietary nitrate improves platelet function. The pharmacokinetic profile of urinary nitrate excretion indicates total clearance of consumed nitrate in a 24 h period. While urinary, salivary, and plasma nitrate concentrations increased between 4- and 7-fold, a significant increase in nitrite was only detected in saliva (7-fold). High dietary nitrate consumption does not cause a significant acute change in plasma concentrations of 3-nitrotyrosine or in platelet function

The effect of dietary nitrate on salivary, plasma, and urinary nitrate metabolism in humans

Dietary nitrate is metabolized to nitrite by bacterial flora on the posterior surface of the tongue leading to increased salivary nitrite concentrations. In the acidic environment of the stomach, nitrite forms nitrous acid, a potent nitrating/nitrosating agent. The aim of this study was to examine the pharmacokinetics of dietary nitrate in relation to the formation of salivary, plasma, and urinary nitrite and nitrate in healthy subjects. A secondary aim was to determine whether dietary nitrate increases the formation of protein-bound 3-nitrotyrosine in plasma, and if dietary nitrate improves platelet function. The pharmacokinetic profile of urinary nitrate excretion indicates total clearance of consumed nitrate in a 24 h period. While urinary, salivary, and plasma nitrate concentrations increased between 4- and 7-fold, a significant increase in nitrite was only detected in saliva (7-fold). High dietary nitrate consumption does not cause a significant acute change in plasma concentrations of 3-nitrotyrosine or in platelet function

Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition

Ubiquitination plays a key role in protein degradation and signal transduction. Ubiquitin is a small protein modifier that is adducted to lysine residues by the combined function of E1, E2, and E3 enzymes and is removed by deubiquitinating enzymes. Characterization of ubiquitination sites is important for understanding the role of this modification in cellular processes and disease. However, until recently, large-scale characterization of endogenous ubiquitination sites has been hampered by the lack of efficient enrichment techniques. The introduction of antibodies that specifically recognize peptides with lysine residues that harbor a di-glycine remnant (K-{epsilon}-GG) following tryptic digestion has dramatically improved the ability to enrich and identify ubiquitination sites from cellular lysates. We used this enrichment technique to study the effects of proteasome inhibition by MG-132 and deubiquitinase inhibition by PR-619 on ubiquitination sites in human Jurkat cells by quantitative high performance mass spectrometry. Minimal fractionation of digested lysates prior to immunoaffinity enrichment increased the yield of K-ε-GG peptides three- to fourfold resulting in detection of up to ~3300 distinct K-GG peptides in SILAC triple encoded experiments starting from 5 mg of protein per label state. In total, we identify 5533 distinct K-{epsilon}-GG peptides of which 4907 were quantified in this study, demonstrating that the strategy presented is a practical approach to perturbational studies in cell systems. We found that proteasome inhibition by MG-132 and deubiquitinase inhibition by P-619 induces significant changes to the ubiquitin landscape, but that not all ubiquitination sites regulated by MG-132 and PR-619 are likely substrates for the ubiquitin-proteasome system. Additionally, we find that the proteasome and deubiquitinase inhibitors studied induced only minor changes in protein expression levels regardless of the extent of regulation induced at the ubiquitin site level. We attribute this finding to the low stoichiometry of the majority ubiquitination sites identified in this study