74 research outputs found
Tuning the Mechanical Properties of Multiarm RAFT-Based Block Copolyelectrolyte Hydrogels via Ionic Cross-Linking for 3D Cell Cultures
Hydrogels that serve as native extracellular matrix (ECM) mimics are typically naturally derived hydrogels that are physically cross-linked via ionic interactions. This means rapid gelation of synthetic polymers, which give control over the chemical and physical cues in hydrogel formation. Herein, we combine the best of both systems by developing a synthetic hydrogel with ionic cross-linking of block copolyelectrolytes to rapidly create hydrogels. Reversible addition-fragmentation chain-transfer (RAFT) polymerization was used to synthesize oppositely charged polyelectrolyte molecules and, in turn, modulate the mechanical property of stiffness. The mechanical stiffness of a range of 900-3500 Pa was tuned by varying the number of charged ionic groups, the length of the polymer arms, and the polymer concentration. We demonstrate the synthetic polyelectrolyte hydrogel as an ECM mimic for three-dimensional (3D) in vitro cell models using MCF-7 breast cancer cells
Biologic Phenotyping of the Human Small Airway Epithelial Response to Cigarette Smoking
BACKGROUND: The first changes associated with smoking are in the small airway epithelium (SAE). Given that smoking alters SAE gene expression, but only a fraction of smokers develop chronic obstructive pulmonary disease (COPD), we hypothesized that assessment of SAE genome-wide gene expression would permit biologic phenotyping of the smoking response, and that a subset of healthy smokers would have a "COPD-like" SAE transcriptome. METHODOLOGY/PRINCIPAL FINDINGS: SAE (10th-12th generation) was obtained via bronchoscopy of healthy nonsmokers, healthy smokers and COPD smokers and microarray analysis was used to identify differentially expressed genes. Individual responsiveness to smoking was quantified with an index representing the % of smoking-responsive genes abnormally expressed (I(SAE)), with healthy smokers grouped into "high" and "low" responders based on the proportion of smoking-responsive genes up- or down-regulated in each smoker. Smokers demonstrated significant variability in SAE transcriptome with I(SAE) ranging from 2.9 to 51.5%. While the SAE transcriptome of "low" responder healthy smokers differed from both "high" responders and smokers with COPD, the transcriptome of the "high" responder healthy smokers was indistinguishable from COPD smokers. CONCLUSION/SIGNIFICANCE: The SAE transcriptome can be used to classify clinically healthy smokers into subgroups with lesser and greater responses to cigarette smoking, even though these subgroups are indistinguishable by clinical criteria. This identifies a group of smokers with a "COPD-like" SAE transcriptome
Cigarette smoking, nicotine dependence and anxiety disorders : a systematic review of population-based, epidemiological studies
Background Multiple studies have demonstrated that rates of smoking and nicotine dependence are increased in individuals with anxiety disorders. However, significant variability exists in the epidemiological literature exploring this relationship, including study design (cross-sectional versus prospective), the population assessed (random sample versus clinical population) and diagnostic instrument utilized.Methods We undertook a systematic review of population-based observational studies that utilized recognized structured clinical diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD)) for anxiety disorder diagnosis to investigate the relationship between cigarette smoking, nicotine dependence and anxiety disorders.Results In total, 47 studies met the predefined inclusion criteria, with 12 studies providing prospective information and 5 studies providing quasiprospective information. The available evidence suggests that some baseline anxiety disorders are a risk factor for initiation of smoking and nicotine dependence, although the evidence is heterogeneous and many studies did not control for the effect of comorbid substance use disorders. The identified evidence however appeared to more consistently support cigarette smoking and nicotine dependence as being a risk factor for development of some anxiety disorders (for example, panic disorder, generalized anxiety disorder), although these findings were not replicated in all studies. A number of inconsistencies in the literature were identified.Conclusions Although many studies have demonstrated increased rates of smoking and nicotine dependence in individuals with anxiety disorders, there is a limited and heterogeneous literature that has prospectively examined this relationship in population studies using validated diagnostic criteria. The most consistent evidence supports smoking and nicotine dependence as increasing the risk of panic disorder and generalized anxiety disorder. The literature assessing anxiety disorders increasing smoking and nicotine dependence is inconsistent. Potential issues with the current literature are discussed and directions for future research are suggested
The Great American Crime Decline : Possible Explanations
This chapter examines the most important features of the crime decline in the United States during the 1990s-2010s but also takes a broader look at the violence declines of the last three centuries. The author argues that violent and property crime trends might have diverged in the 1990s, with property crimes increasingly happening in the online sphere and thus traditional property crime statistics not being reflective of the full picture. An important distinction is made between âcontact crimesâ and crimes that do not require a victim and offender to be present in the same physical space. Contrary to the uncertainties engendered by property crime, the declines in violent (âcontactâ) crime are rather general, and have been happening not only across all demographic and geographic categories within the United States but also throughout the developed world. An analysis of research literature on crime trends has identified twenty-four different explanations for the crime drop. Each one of them is briefly outlined and examined in terms of conceptual clarity and empirical support. Nine crime decline explanations are highlighted as the most promising ones. The majority of these promising explanations, being relative newcomers in the crime trends literature, have not been subjected to sufficient empirical scrutiny yet, and thus require further research. One potentially fruitful avenue for future studies is to examine the association of the most promising crime decline explanations with improvements in self-control
Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered
Fluorescent amino acids as versatile building blocks for chemical biology
Fluorophores have transformed the way we study biological systems, enabling non-invasive studies in cells and intact organisms, which increase our understanding of complex processes at the molecular level. Fluorescent amino acids have become an essential chemical tool because they can be used to construct fluorescent macromolecules, such as peptides and proteins, without disrupting their native biomolecular properties. Fluorescent and fluorogenic amino acids with unique photophysical properties have been designed for tracking proteinâprotein interactions in situ or imaging nanoscopic events in real time with high spatial resolution. In this Review, we discuss advances in the design and synthesis of fluorescent amino acids and how they have contributed to the field of chemical biology in the past 10 years. Important areas of research that we review include novel methodologies to synthesize building blocks with tunable spectral properties, their integration into peptide and protein scaffolds using site-specific genetic encoding and bioorthogonal approaches, and their application to design novel artificial proteins, as well as to investigate biological processes in cells by means of optical imaging. [Figure not available: see fulltext.]
Measurement of the CKM angle using with decays
A model-dependent amplitude analysis of the decay is performed using proton-proton collision data
corresponding to an integrated luminosity of 3.0fb, recorded at
and by the LHCb experiment. The CP violation observables
and , sensitive to the CKM angle , are measured to
be \begin{eqnarray*} x_- &=& -0.15 \pm 0.14 \pm 0.03 \pm 0.01, y_- &=& 0.25 \pm
0.15 \pm 0.06 \pm 0.01, x_+ &=& 0.05 \pm 0.24 \pm 0.04 \pm 0.01, y_+ &=&
-0.65^{+0.24}_{-0.23} \pm 0.08 \pm 0.01, \end{eqnarray*} where the first
uncertainties are statistical, the second systematic and the third arise from
the uncertainty on the amplitude model. These
are the most precise measurements of these observables. They correspond to
and , where is
the magnitude of the ratio of the suppressed and favoured decay amplitudes, in a mass region of around the
mass and for an absolute value of the cosine of the decay
angle larger than .Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-007.htm
First experimental study of photon polarization in radiative B-s(0) decays
The polarization of photons produced in radiative B0s decays is studied for the first time. The data are recorded by the LHCb experiment in pp collisions corresponding to an integrated luminosity of 3ââfbâ1 at center-of-mass energies of 7 and 8 TeV. A time-dependent analysis of the B0sâÏÎł decay rate is conducted to determine the parameter AÎ, which is related to the ratio of right- over left-handed photon polarization amplitudes in bâsÎł transitions. A value of AÎ=â0.98+0.46â0.52+0.23â0.20 is measured. This result is consistent with the standard model prediction within 2 standard deviations
Search for dark photons produced in 13 TeV collisions
Searches are performed for both promptlike and long-lived dark photons,
A
0
, produced in proton-proton
collisions at a center-of-mass energy of 13 TeV, using
A
0
â
Ό
ĂŸ
Ό
â
decays and a data sample corresponding
to an integrated luminosity of
1
.
6
fb
â
1
collected with the LHCb detector. The promptlike
A
0
search covers
the mass range from near the dimuon threshold up to 70 GeV, while the long-lived
A
0
search is restricted to
the low-mass region
214
<m
Ă°
A
0
Ă
<
350
MeV. No evidence for a signal is found, and 90% confidence
level exclusion limits are placed on the
Îł
â
A
0
kinetic-mixing strength. The constraints placed on promptlike
dark photons are the most stringent to date for the mass range
10
.
6
<m
Ă°
A
0
Ă
<
70
GeV, and are
comparable to the best existing limits for
m
Ă°
A
0
Ă
<
0
.
5
GeV. The search for long-lived dark photons is the
first to achieve sensitivity using a displaced-vertex signature
Measurement of the electron reconstruction efficiency at LHCb
The single electron track-reconstruction efficiency is calibrated using a sample corresponding to 1.3 fbâ1 of pp collision data recorded with the LHCb detector in 2017. This measurement exploits B+â J/Ï(e+eâ)K+ decays, where one of the electrons is fully reconstructed and paired with the kaon, while the other electron is reconstructed using only the information of the vertex detector. Despite this partial reconstruction, kinematic and geometric constraints allow the B meson mass to be reconstructed and the signal to be well separated from backgrounds. This in turn allows the electron reconstruction efficiency to be measured by matching the partial track segment found in the vertex detector to tracks found by LHCb's regular reconstruction algorithms. The agreement between data and simulation is evaluated, and corrections are derived for simulated electrons in bins of kinematics. These correction factors allow LHCb to measure branching fractions involving single electrons with a systematic uncertainty below 1%
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