Rights and Right-Wing Lawyers

Reviewing: Amanda Hollis-Brusky, Ideas with Consequences: The Federalist Society and the Conservative Counterrevolution (Oxford University Press 2015); Jefferson Decker, The Other Rights Revolution: Conservative Lawyers and the Remaking of American Government (Oxford University Press 2016)

The Volatile Composition of the Split Ecliptic comet 73P/Schwassmann-Wachmann 3: A Comparison of Fragments C and B

The composition of fragments C and B of the Jupiter-family comet 73P/Schwassmann-Wachmann 3 (SW3) was investigated in early April of 2006 at IR wavelengths using high-dispersion echelle spectroscopy. Both fragments were depleted in ethane, and C was depleted in most forms of volatile carbon. In particular, fragment C shows a severe depletion of CH_(3)OH but a "normal" abundance of HCN (which has a similar volatility). Thermal processing is a possible explanation, but since fragment B is perhaps sublimating fresher material because of the frequent outbursts and fragmentation, the observed depletions might have cosmogonic implications. The chemistry of the volatile ices in SW3, like in the Oort Cloud comet C/1999 S4 (LINEAR), may be associated with sublimation of icy mantles from precometary grains followed by subsequent gas-phase chemistry and recondensation

A comprehensive study of infrared OH prompt emission in two comets. I. Observations and effective g-factors

We present high-dispersion infrared spectra of hydroxyl (OH) in comets C/2000 WM1 (LINEAR) and C/2004 Q2 (Machholz), acquired with the Near Infrared Echelle Spectrograph at the Keck Observatory atop Mauna Kea, Hawaii. Most of these rovibrational transitions result from photodissociative excitation of H_2O giving rise to OH "prompt" emission. We present calibrated emission efficiencies (equivalent g-factors, measured in OH photons s^(-1) [H_2O molecule]^(-1)) for more than 20 OH lines sampled in these two comets. The OH transitions analyzed cover a broad range of rotational excitation. This infrared database for OH can be used in two principal ways: (1) as an indirect tool for obtaining water production in comets simultaneously with the production of other parent volatiles, even when direct detections of H_2O are not available; and (2) as an observational constraint to models predicting the rotational distribution of rovibrationally excited OH produced by water photolysis

Wow, that portal vein is small: Preventing portal vein thrombosis in liver transplantation for small children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107365/1/lt23865.pd

Comet C/2004 Q2 (MACHHOLZ): Parent Volatiles, a Search for Deuterated Methane, and Constraint on the CH4 Spin Temperature

High-dispersion (l/dl ~ 25,000) infrared spectra of Comet C/2004 Q2 (Machholz) were acquired on Nov. 28-29, 2004, and Jan. 19, 2005 (UT dates) with NIRSPEC at the Keck-2 telescope on Mauna Kea. We detected H2O, CH4, C2H2, C2H6, CO, H2CO, CH3OH, HCN, and NH3 and we conducted a sensitive search for CH3D. We report rotational temperatures, production rates, and mixing ratios (with respect to H2O) at heliocentric distances of 1.49 AU (Nov. 2004) and 1.21 AU (Jan. 2005). We highlight three principal results: (1) The mixing ratios of parent volatiles measured at 1.49 AU and 1.21 AU agree within confidence limits, consistent with homogeneous composition in the mean volatile release from the nucleus of C/2004 Q2. Notably, the relative abundance of C2H6/C2H2 is substantially higher than those measured in other comets, while the mixing ratios C2H6/H2O, CH3OH/H2O, and HCN/H2O are similar to those observed in comets, referred to as "organics-normal". (2) The spin temperature of CH4 is > 35-38 K, an estimate consistent with the more robust spin temperature found for H2O. (3) We obtained a 3s upper limit of CH3D/CH4 < 0.020 (D/H < 0.005). This limit suggests that methane released from the nucleus of C/2004 Q2 is not dominated by a component formed in extremely cold (near 10 K) environments. Formation pathways of both interstellar and nebular origin consistent with the measured D/H in methane are discussed. Evaluating the relative contributions of these pathways requires further modeling of chemistry including both gas-phase and gas-grain processes in the natal interstellar cloud and in the protoplanetary disk.Comment: Accepted by The Astrophysical Journa

Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.

One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting human GUCY2C-expressing metastases. Human GUCY2C-targeted murine CAR-T cells promoted antigen-dependent T-cell activation quantified by activation marker upregulation, cytokine production, and killing of GUCY2C-expressing, but not GUCY2C-deficient, cancer cells in vitro. GUCY2C CAR-T cells provided long-term protection against lung metastases of murine colorectal cancer cells engineered to express human GUCY2C in a syngeneic mouse model. GUCY2C murine CAR-T cells recognized and killed human colorectal cancer cells endogenously expressing GUCY2C, providing durable survival in a human xenograft model in immunodeficient mice. Thus, we have identified a human GUCY2C-specific CAR-T cell therapy approach that may be developed for the treatment of GUCY2C-expressing metastatic colorectal cancer

Hypertension

Defining hypertension in pregnancy is challenging because blood pressure levels in pregnancy are dynamic, having a circadian rhythm and also changing with advancing gestational age. The accepted definition is a sustained systolic (sBP) of ≥140 mmHg or a sustained diastolic blood pressure (dBP) ≥90 mmHg, by office (or in-hospital) measurement. Measurement of blood pressure in pregnancy should follow standardised methods, as outside pregnancy. Blood pressure measurement may occur in three types of settings, which will dictate in part, which measurement device(s) will be used. The settings are (1) health care facility; and two types of settings outside the facility: (2) ‘ambulatory’ blood pressure measurement (ABPM); and (3) home blood pressure measurement (HBPM). Furthermore, blood pressure can be measured using auscultatory (mercury or aneroid devices) or automated methods. Factors to consider when selecting a blood pressure measurement device include validation, disease specificity, observer error and the need for regular recalibration. The accuracy of a device is repeatedly compared to two calibrated mercury sphygmomanometers (the gold standard), by trained observers, over a range of blood pressures and for women with different hypertensive disorders of pregnancy; only a few devices have been validated among women with pre-eclampsia. This chapter discusses the advantages and/or disadvantages of the various settings and devices. Low- and middle-income countries (LMICs) bear a disproportionate burden of maternal morbidity and mortality from the hypertensive disorders of pregnancy. While regular blood pressure monitoring can cost-effectively reduce this disparity, LMIC-health systems face unique challenges that reduce this capacity. Assessment of service gaps and programmatic responses to ensure access to blood pressure measurement are a priority, supported where appropriate by implementation research.Publisher PD

Tumor radiation therapy creates therapeutic vaccine responses to the colorectal cancer antigen GUCY2C.

PURPOSE: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. METHODS AND MATERIALS: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. RESULTS: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P CONCLUSIONS: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance of modality sequence optimization before the initiation of clinical trials of RT and IT to maximize immune and antitumor responses

A Search for Variation in the H_2O Ortho-Para Ratio and Rotational Temperature in the Inner Coma of Comet C/2004 Q2 (Machholz)

We present spatially resolved measurements of the rotational temperature and ortho-para ratio for H_2O in the inner coma of the Oort Cloud comet C/2004 Q2 (Machholz). Our results are based on direct simultaneous detections of ortho-H_2O and para-H_2O via "hot-band" fluorescence near 2.9 μm. We find a well-defined decline in rotational temperature with increasing nucleocentric distance (up to ~1000 km). The ortho-para ratio remains constant (within stochastic uncertainty) with increasing nucleocentric distance and is close to the statistical equilibrium value of 3.0 (2.86 ± 0.06 [0.17], including, respectively, stochastic [systematic] uncertainty), resulting in spin temperature T_(spin) ≥ 34 K. We compare the present results with those reported for other comets and discuss the difficulties in interpreting spin temperatures deduced from measured ortho-para ratios. Improved understanding of the special conditions that enable nuclear spin conversion would test the extent to which derived spin temperatures reflect the formative history or the processing record of cometary ices

GUCY2C lysosomotropic endocytosis delivers immunotoxin therapy to metastatic colorectal cancer.

The emergence of targeted cancer therapy has been limited by the paucity of determinants which are tumor-specific and generally associated with disease, and have cell dynamics which effectively deploy cytotoxic payloads. Guanylyl cyclase C (GUCY2C) may be ideal for targeting because it is normally expressed only in insulated barrier compartments, including intestine and brain, but over-expressed by systemic metastatic colorectal tumors. Here, we reveal that GUCY2C rapidly internalizes from the cell surface to lysosomes in intestinal and colorectal cancer cells. Endocytosis is independent of ligand binding and receptor activation, and is mediated by clathrin. This mechanism suggests a design for immunotoxins comprising a GUCY2C-directed monoclonal antibody conjugated through a reducible disulfide linkage to ricin A chain, which is activated to a potent cytotoxin in lysosomes. Indeed, this immunotoxin specifically killed GUCY2C-expressing colorectal cancer cells in a lysosomal- and clathrin-dependent fashion. Moreover, this immunotoxin reduced pulmonary tumors \u3e80% (