Theory of coherent two-dimensional vibrational spectroscopy

Two-dimensional (2D) vibrational spectroscopy has emerged as one of the most important experimental techniques useful to study the molecular structure and dynamics in condensed phases. Theory and computation have also played essential and integral roles in its development through the nonlinear optical response theory and computational methods such as molecular dynamics (MD) simulations and electronic structure calculations. In this article, we present the fundamental theory of coherent 2D vibrational spectroscopy and describe computational approaches to simulate the 2D vibrational spectra. The classical approximation to the quantum mechanical nonlinear response function is invoked from the outset. It is shown that the third-order response function can be evaluated in that classical limit by using equilibrium or non-equilibrium MD simulation trajectories. Another simulation method is based on the assumptions that the molecular vibrations can still be described quantum mechanically and that the relevant molecular response functions are evaluated by the numerical integration of the Schrodinger equation. A few application examples are presented to help the researchers in this and related areas to understand the fundamental principles and to use these methods for their studies with 2D vibrational spectroscopic techniques. In summary, this exposition provides an overview of current theoretical efforts to understand the 2D vibrational spectra and an outlook for future developments. c.Published under license by AIP Publishing

On the triple origin of blue stragglers

Blue straggler stars (BSSs) are stars observed to be hotter and bluer than other stars with the same luminosity in their environment. As such they appear to be much younger than the rest of the stellar population. Two main channels have been suggested to produce such stars: (1) collisions between stars in clusters or (2) mass transfer between, or merger of, the components of primordial short-period binaries. Here we suggest a third scenario, in which the progenitor of BSSs are formed in primordial (or dynamically formed) hierarchical triple stars. In such configurations the dynamical evolution of the triples through the Kozai mechanism and tidal friction can induce the formation of very close inner binaries. Angular momentum loss in a magnetized wind or stellar evolution could then lead to the merger of these binaries (or to mass transfer between them) and produce BSSs in binary (or triple) systems. We study this mechanism and its implications and show that it could naturally explain many of the characteristics of the BSS population in clusters, most notably the large binary fraction of long period BSS binaries; their unique period-eccentricity distribution (with typical periods > 700 days); and the typical location of these BSSs in the color-magnitude diagram, far from the cluster turn-off point of their host clusters. We suggest that this scenario has a major (possibly dominant) role in the formation of BSSs in open clusters and give specific predictions for the the BSSs population formed in this manner. We also note that triple systems may be the progenitors of the brightest planetary nebulae in old elliptical galaxies, which possibly evolved from BSSs.Comment: 10 pages, 6 figures. Minor additions; ApJ, in pres

Tariff-Mediated Network Effects versus Strategic Discounting: Evidence from German Mobile Telecommunications

Mobile telecommunication operators routinely charge subscribers lower prices for calls on their own network than for calls to other networks (on-net discounts). Studies on tariff-mediated network effects suggest this is due to large operators using on-net discounts to damage smaller rivals. Alternatively, research on strategic discounting suggests small operators use on-net discounts to advertise with low on-net prices. We test the relative strength of these effects using data on tariff setting in German mobile telecommunications between 2001 and 2009. We find that large operators are more likely to offer tariffs with on-net discounts but there is no consistently significant difference in the magnitude of discounts. Our results suggest that tariff-mediated network effects are the main cause of on-net discounts

Cell based therapy for the management of chronic pain

The management of chronic pain, particularly neuropathic pain, still has significant unmet needs. In addition to inadequate symptomatic relief, there are concerns about adverse effects and addiction associated with treatments. The transplantation of cells that secrete neuroactive substances with analgesic properties into the central nervous system has only become of practical interest in more recent years, but provides a novel strategy to challenge current approaches in treating chronic pain. This review covers pre-clinical and clinical studies from both allogeneic and xenogeneic sources for management of chronic refractory pain

An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

Solitary Small Bowel Metastasis from Breast Cancer

The common sites of metastasis of breast cancer are bone, lung, and liver, but gastrointestinal metastasis from breast cancer is rare. We experienced a case of solitary ileal metastasis from breast cancer. A 45-years-old woman presented with melena for several weeks. She showed no other abdominal symptoms. Colonoscopy findings showed an ulcerative mucosal lesion in the terminal ileum, and biopsy was performed. Pathologic examination revealed metastatic carcinoma, originated from breast. The tumor cells were positive for estrogen receptor and negative for Cdx-2. She had had a previous medical history of bilateral breast cancer and undergone breast conserving surgery with sentinel lymph node biopsy for both breasts. The torso positron emission tomography scan at 19 months after surgery showed mildly increased uptake in the terminal ileum which was considered as inflammation. Finally, she was diagnosed with solitary ileal metastasis from breast cancer at 22 months after surgery

Letter to the Editor: Detection of EML4-ALK and Other ALK Fusion Genes in Lung Cancer: A Lesson from the Leukemia Fusion Gene Analysis and Future Application

We read with interest the article “EML4-ALK Fusion Gene in Korean Non-Small Cell Lung Cancer ” in a recent issue of the Journal of Korean Medical Science by Jin et al. (1). In this study, EML4-ALK fusion gene was detected in 10 of 167 non-small cell lung cancer (NSCLC) patients by using reverse transcriptase-polymerase chain reaction (RT-PCR) as a basic screening technique instead of fluorescence in situ hybridization (FISH) method. The frequency of EML4-ALK fusion gene in this study (6.0%) was not largely different from a previous study that used the FISH method on Korean NSCLC patients (4.2%) (2), while it did not diverge from the results in previous studies on a general NSCLC patient population that yielded 3%-7 % ratios as well. Based on the experience of detecting leukemia fusion genes with several new molecular methods during the diagnosis of leukemia (3-6), we would like to mention the pros and cons of such methods i

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

Middleborns disadvantaged? testing birth-order effects on fitness in pre-industrial finns

Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle-and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first-or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition