Engineered G-protein coupled receptors are powerful tools to investigate biological processes and behaviors

Understanding how discreet tissues and neuronal circuits function in relation to the whole organism to regulate physiological processes and behaviors is a fundamental goal of modern biological science. Powerful and important new tools in this discovery process are modified G-protein coupled receptors (GPCRs) known as 'Receptors Activated Solely by Synthetic Ligands (RASSLs),' and 'Designer Receptors Exclusively Activated by a Designer Drug (DREADDs).' Collectively, these are GPCRs modified either through rational design (RASSLs) or directed molecular evolution (DREADDs), that do not respond to native ligand, but functionally respond only to synthetic ligands. Importantly, the utility of these receptors is not limited to examination of the role of GPCR-coupled effector signal transduction pathways. Due to the near ubiquitous expression of GPCRs throughout an organism, this technology, combined with whole animal transgenics to selectively target expression, has the ability to regulate activity of discreet tissues and neuronal circuits through effector pathway modulation to study function and behavior throughout the organism. Advantages over other systems currently used to modify in vivo function include the ability to rapidly, selectively and reversibly manipulate defined signal transduction pathways both in short term and long term studies, and no need for specialized equipment due to convenient systemic treatment with activating ligand. © 2009 Nichols and Roth

Change in lifestyle behaviors and medication use after a diagnosis of ductal carcinoma in situ

Women with ductal carcinoma in situ (DCIS) of the breast represent a growing cancer survivor population with a diagnosis of uncertain malignant potential. These survivors face an absence of scientific guidelines regarding lifestyle changes that can help to prevent a breast cancer recurrence. In this first report from the Wisconsin In Situ Cohort (WISC) study, we examine how women are currently changing their lifestyle behaviors and medication use following a diagnosis of DCIS. At study entry (1997-2006), 1,959 subjects (78% of eligible) with DCIS were identified from the Wisconsin cancer registry and administered an interview assessing behaviors prior to diagnosis. Follow-up interviews were completed every 2 years after the initial interview, beginning in 2003 and continuing through 2006. After adjusting for age and calendar year, women were 2.2 kg (95% CI 1.4, 3.0) heavier, 35% (95% CI 20, 47) less likely to be a smoker, 19% (95% CI -1, 43) more likely to use non-steroidal anti-inflammatory drugs, and 57% (95% CI 26, 95) more likely to use antidepressants after a DCIS diagnosis compared to 1 year prior to diagnosis. Use of postmenopausal hormones decreased sharply (OR = 0.06; 95% CI 0.04, 0.09) following a DCIS diagnosis. These findings indicate that women make substantial changes in their behaviors after a DCIS diagnosis. This cohort will be further monitored to evaluate the association between these behaviors and health outcomes following DCIS

Logarithmic extensions of minimal models: characters and modular transformations

We study logarithmic conformal field models that extend the (p,q) Virasoro minimal models. For coprime positive integers $p$ and $q$, the model is defined as the kernel of the two minimal-model screening operators. We identify the field content, construct the W-algebra W(p,q) that is the model symmetry (the maximal local algebra in the kernel), describe its irreducible modules, and find their characters. We then derive the SL(2,Z) representation on the space of torus amplitudes and study its properties. From the action of the screenings, we also identify the quantum group that is Kazhdan--Lusztig-dual to the logarithmic model.Comment: 43pp., AMSLaTeX++. V3: Some explanatory comments added, notational inaccuracies corrected, references adde

Extended multiplet structure in Logarithmic Conformal Field Theories

We use the process of quantum hamiltonian reduction of SU(2)_k, at rational level k, to study explicitly the correlators of the h_{1,s} fields in the c_{p,q} models. We find from direct calculation of the correlators that we have the possibility of extra, chiral and non-chiral, multiplet structure in the h_{1,s} operators beyond the `minimal' sector. At the level of the vacuum null vector h_{1,2p-1}=(p-1)(q-1) we find that there can be two extra non-chiral fermionic fields. The extra indicial structure present here permeates throughout the entire theory. In particular we find we have a chiral triplet of fields at h_{1,4p-1}=(2p-1)(2q-1). We conjecture that this triplet algebra may produce a rational extended c_{p,q} model. We also find a doublet of fields at h_{1,3p-1}=(\f{3p}{2}-1)(\f{3q}{2}-1). These are chiral fermionic operators if p and q are not both odd and otherwise parafermionic.Comment: 24 pages LATEX. Minor corrections and extra reference

Extended chiral algebras and the emergence of SU(2) quantum numbers in the Coulomb gas

We study a set of chiral symmetries contained in degenerate operators beyond the `minimal' sector of the c(p,q) models. For the operators h_{(2j+2)q-1,1}=h_{1,(2j+2)p-1} at conformal weight [ (j+1)p-1 ][ (j+1)q -1 ], for every 2j \in N, we find 2j+1 chiral operators which have quantum numbers of a spin j representation of SU(2). We give a free-field construction of these operators which makes this structure explicit and allows their OPEs to be calculated directly without any use of screening charges. The first non-trivial chiral field in this series, at j=1/2, is a fermionic or para-fermionic doublet. The three chiral bosonic fields, at j=1, generate a closed W-algebra and we calculate the vacuum character of these triplet models.Comment: 23 pages Late

The Neveu-Schwarz and Ramond Algebras of Logarithmic Superconformal Field Theory

We describe the general features of the Neveu-Schwarz and Ramond sectors of logarithmic conformal field theories with N=1 supersymmetry. Three particular systems are examined in some detail -- D-brane recoil, a superconformal extension of the c=-2 model, and the supersymmetric SU(2)_2 WZW model.Comment: 65 pages AMSTeX; Typos corrected, references added and update

Diagnosis of biliary tract and ampullary carcinomas

Diagnostic methods for biliary tract carcinoma and the efficacy of these methods are discussed. Neither definite methods for early diagnosis nor specific markers are available in this disease. When this disease is suspected on the basis of clinical symptoms and risk factors, hemato-biochemical examination and abdominal ultrasonography are performed and, where appropriate, enhanced computed tomography (CT) and/or magnetic resonance cholangiopancreatography (MRCP) is carried out. Diagnoses of extrahepatic bile duct cancer and ampullary carcinoma are often made based on the presence of obstructive jaundice. Although rare, abdominal pain and pyrexia, as well as abnormal findings of the hepatobiliary system detected by hemato-biochemical examination, serve as a clue to making a diagnosis of these diseases. On the other hand, the early diagnosis of gallbladder cancer is scarcely possible on the basis of clinical symptoms, so when this cancer is found with the onset of abdominal pain and jaundice, it is already advanced at the time of detection, thus making a cure difficult. When gallbladder cancer is suspected, enhanced CT is carried out. Multidetector computed tomography (MDCT), in particular — one of the methods of enhanced CT — is useful for decision of surgical criteria, because MDCT shows findings such as localization and extension of the tumor, and the presence or absence of remote metastasis. Procedures such as magnetic resonance imaging, endoscopic ultrasonography, bile duct biopsy, and cholangioscopy should be carried out taking into account indications for these procedures in individual patients. However, direct biliary tract imaging is necessary for making a precise diagnosis of the horizontal extension of bile duct cancer

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society