Phase retrieval via regularization in self-diffraction based spectral interferometry

A novel variant of spectral phase interferometry for direct electric-field reconstruction (SPIDER) is introduced and experimentally demonstrated. Other than most previously demonstrated variants of SPIDER, our method is based on a third-order nonlinear optical effect, namely self-diffraction, rather than the second-order effect of sum-frequency generation. On one hand, self-diffraction (SD) substantially simplifies phase-matching capabilities for multi-octave spectra that cannot be hosted by second-order processes, given manufacturing limitations of crystal lengths in the few-micrometer range. On the other hand, however, SD SPIDER imposes an additional constraint as it effectively measures the spectral phase of a self-convolved spectrum rather than immediately measuring the fundamental phase. Reconstruction of the latter from the measured phase and the spectral amplitude of the fundamental turns out to be an ill-posed problem, which we address by a regularization approach. We discuss the numerical implementation in detail and apply it to measured data from a Ti:sapphire amplifier system. Our experimental demonstration used 40-fs pulses and a 500 $\mu$m thick BaF${}_2$ crystal to show that the SD SPIDER signal is sufficiently strong to be separable from stray light. Extrapolating these measurements to the thinnest conceivable nonlinear media, we predict that bandwidths well above two optical octaves can be measured by a suitably adapted SD SPIDER apparatus, enabling the direct characterization of pulses down to single-femtosecond pulse durations. Such characteristics appear out of range for any currently established pulse measurement technique

Light-cone distribution amplitudes of octet baryons from lattice QCD

We present lattice QCD results for the wave function normalization constants and the first moments of the distribution amplitudes for the lowest-lying baryon octet. The analysis is based on a large number of $N_f=2+1$ ensembles comprising multiple trajectories in the quark mass plane including physical pion (and kaon) masses, large volumes, and, most importantly, five different lattice spacings down to $a=0.039\,\mathrm{fm}$. This allows us to perform a controlled extrapolation to the continuum and infinite volume limits by a simultaneous fit to all available data. We demonstrate that the formerly observed violation of flavor symmetry breaking constraints can, indeed, be attributed to discretization effects that vanish in the continuum limit

Determination of pyridoxal-5′-phosphate (PLP)-bonding sites in proteins: a peptide mass fingerprinting approach based on diagnostic tandem mass spectral features of PLP-modified peptides

Peptides modified by pyridoxal-5′-phosphate (PLP), linked to a lysine residue via reductive amination, exhibit distinct spectral characteristics in the collision-induced dissociation (CID) tandem mass (MS/MS) spectra that are described here. The MS/MS spectra typically display two dominant peaks whose m/z values correspond to neutral losses of [H 3 PO 4 ] (−98 Da) and the PLP moiety as [C 8 H 10 NO 5 P] (−231 Da) from the precursor peptide ion, respectively. Few other peaks are observed. Recognition of this distinct fragmentation behavior is imperative since determining sequences and sites of modifications relies on the formation of amide backbone cleavage products for subsequent interpretation via proteome database searching. Additionally, PLP-modified peptides exhibit suppressed precursor ionization efficiency which diminishes their detection in complex mixtures. Presented here is a protocol which describes an enrichment strategy for PLP-modified peptides combined with neutral loss screening and peptide mass fingerprinting to map the PLP-bonding site in a known PLP-dependent protein. This approach represents an efficient alternative to site-directed mutagenesis which has been the traditional method used for PLP-bonding site localization in proteins. Copyright © 2009 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64342/1/4270_ftp.pd

MHC Class I+/II− Dendritic Cells Induce Hapten-Specific Immune Responses In Vitro and In Vivo

Activation requirements and biologic properties of hapten-specific, major histocompatibility complex class I-restricted CD8+ T lymphocytes are not fully understood. To address this issue, a novel CD45+/major histocompatibility complex class I+(H-2k)/II−/CD80+ dendritic cell line, termed 80/1, which is capable of stimulating naïve, allogeneic CD8+ but not CD4+ T cells in vitro, was derivatized with trinitrobenzenesulfonic acid and co-cultured for 4 d with syngeneic, naïve CD8+ T cells. Results obtained showed that trinitrophenyl-derivatized, but not underivatized 80/1 dendritic cells, can induce vigorous proliferation of CD8+ T cells. T-cell blasts generated in this fashion were able to lyse syngeneic, trinitrophenyl-derivatized targets but failed to lyse underivatized or trinitrophenyl-derivatized syngeneic, major histocompatibility complex class I− mutant cells or allogeneic targets. The ability of 80/1 dendritic cells to prime naïve, syngeneic T cells in vivo was tested in a contact hypersensitivity model. C3H/HeN mice were injected subcutaneously with identical numbers of (i) trinitro-phenyl-derivatized 80/1 dendritic cells; (ii) trinitro-phenyl-derivatized 80/1 dendritic cells fragmented by freeze-thawing cycles; (iii) trinitrophenyl-derivatized fibrosarcoma L929; and (iv) trinitrophenyl-derivatized lymphoma R1.1 cells. Whereas live trinitrophenyl-derivatized 80/1 dendritic cells were able to sensitize for contact hypersensitivity, killed hapten-derivatized 80/1 dendritic cells or control cells failed to do so. Thus, we conclude that 80/1 dedritic cells, when compared with major histocompatibility complex class I+ non-dendritic cells, can effectively prime naive, syngeneic CD8+ T cells for hapten-specific responses, probably due to their better costimulatory and migratory properties

The left frontal cortex supports reserve in aging by enhancing functional network efficiency

Background: Recent evidence from fMRI studies suggests that functional hubs, i.e. highly connected brain regions, are important for mental health. We found recently that global connectivity of a hub in the left frontal cortex (LFC-connectivity) is associated with relatively preserved memory abilities and higher levels of protective factors (education, IQ) in normal aging and Alzheimer’s disease. These results suggest that LFC-connectivity supports reserve capacity alleviating memory decline. An open question is, however, why LFC-connectivity is beneficial and supports memory function in the face of neurodegeneration. We hypothesized that higher LFCconnectivity is associated with enhanced efficiency in connected major networks involved in episodic memory. We further hypothesized that higher LFC-related network efficiency predicts higher memory abilities. Methods: We assessed fMRI during a face-name association learning task in 26 healthy cognitively normal elderly participants. Using beta-series correlation analysis, we computed task-related LFC-connectivity to key memory networks including the default-mode network (DMN) and dorsal attention network (DAN). Network efficiency within the DMN and DAN was estimated by the graph theoretical small-worldness statistic. We applied linear regression analyses in order to test the association between LFC-connectivity to the DMN/DAN and small-worldness of these networks. Mediation analysis was applied to test LFC-connectivity to the DMN and DAN as a mediator of the association between education and higher DMN and DAN smallworldness. Lastly, we tested network small-worldness as a predictor of memory performance. Results: We found that higher LFC-connectivity to the DMN and DAN during successful memory encoding and recognition was associated with higher small-worldness of those networks. Higher task-related LFC-connectivity mediated the association between education and higher small-worldness in the DMN and DAN. Further, higher small-worldness of these networks predicted better performance in the memory task. Conclusions: The current results suggest that higher education-related LFC-connectivity to key memory networks during a memory task is associated with higher network efficiency and thus enhanced reserve of memory abilities in aging

Tract-specific white matter hyperintensities disrupt neural network function in Alzheimer's disease

Introduction: White matter hyperintensities (WMHs) increase the risk of Alzheimer's disease (AD). Whether WMHs are associated with the decline of functional neural networks in AD is debated. Method: Resting-state functional magnetic resonance imaging and WMH were assessed in 78 subjects with increased amyloid levels on AV-45 positron emission tomography (PET) in different clinical stages of AD. We tested the association between WMH volume in major atlas-based fiber tract regions of interest (ROIs) and changes in functional connectivity (FC) between the tracts' projection areas within the default mode network (DMN). Results: WMH volume within the inferior fronto-occipital fasciculus (IFOF) was the highest among all tract ROIs and associated with reduced FC in IFOF-connected DMN areas, independently of global AV-45 PET. Higher AV-45 PET contributed to reduced FC in IFOF-connected, temporal, and parietal DMN areas. Conclusions: High fiber tract WMH burden is associated with reduced FC in connected areas, thus adding to the effects of amyloid pathology on neuronal network function

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Resting-State Connectivity of the Left Frontal Cortex to the Default Mode and Dorsal Attention Network Supports Reserve in Mild Cognitive Impairment

Reserve refers to the phenomenon of relatively preserved cognition in disproportion to the extent of neuropathology, e.g., in Alzheimer’s disease. A putative functional neural substrate underlying reserve is global functional connectivity of the left lateral frontal cortex (LFC, Brodmann Area 6/44). Resting-state fMRI-assessed global LFC-connectivity is associated with protective factors (education) and better maintenance of memory in mild cognitive impairment (MCI). Since the LFC is a hub of the fronto-parietal control network that regulates the activity of other networks, the question arises whether LFC-connectivity to specific networks rather than the whole-brain may underlie reserve. We assessed resting-state fMRI in 24 MCI and 16 healthy controls (HC) and in an independent validation sample (23 MCI/32 HC). Seed-based LFC-connectivity to seven major resting-state networks (i.e., fronto-parietal, limbic, dorsal-attention, somatomotor, default-mode, ventral-attention, visual) was computed, reserve was quantified as residualized memory performance after accounting for age and hippocampal atrophy. In both samples of MCI, LFC-activity was anti-correlated with the default-mode network (DMN), but positively correlated with the dorsal-attention network (DAN). Greater education predicted stronger LFC-DMN-connectivity (anti-correlation) and LFC-DAN-connectivity. Stronger LFC-DMN and LFC-DAN-connectivity each predicted higher reserve, consistently in both MCI samples. No associations were detected for LFC-connectivity to other networks. These novel results extend our previous findings on global functional connectivity of the LFC, showing that LFC-connectivity specifically to the DAN and DMN, two core memory networks, enhances reserve in the memory domain in MCI

Insertion and Substitution Chemistry at the Boron Fourth Position in Charge-Neutral Zwitterionic Tripodal Tris(methimazolyl)borate Ligands

A number of new charge-neutral zwitterionic tris(methimazolyl)borate ligands have been synthesized, either by substitution of the dimethylamine group in the adduct (dimethylamine)tris(methimazolyl)borane (1) or by insertion into its B–N(dimethylamine) bond by an unsaturated Lewis base. Two new anionic ligands, (thiocyanato)tris(methimazolyl)borate and (cyano)tris(methimazolyl)borate, have also been accessed by this method