Miracle-dz/UniFAR-FTUs huggingface dataset:
T Cells Bearing a Chimeric Antigen Receptor against Prostate-Specific Membrane Antigen Mediate Vascular Disruption and Result in Tumor Regression

Santoro and colleagues show that CAR T cells directed against the tumor vascular antigen, prostate-specific membrane antigen, directly killed and eliminated tumor endothelial cells in murine cancer models, providing a rationale for using CAR T cells for tumor vascular disruption. Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of protumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here, we describe the ability of chimeric antigen receptor (CAR)–bearing T cells to recognize human prostate–specific membrane antigen (hPSMA) on endothelial targets in vitro as well as in vivo. CAR T cells were generated using the anti-PSMA scFv, J591, and the intracellular signaling domains: CD3ζ, CD28, and/or CD137/4-1BB. We found that all anti-hPSMA CAR T cells recognized and eliminated PSMA+ endothelial targets in vitro, regardless of the signaling domain. T cells bearing the third-generation anti-hPSMA CAR, P28BBζ, were able to recognize and kill primary human endothelial cells isolated from gynecologic cancers. In addition, the P28BBζ CAR T cells mediated regression of hPSMA-expressing vascular neoplasms in mice. Finally, in murine models of ovarian cancers populated by murine vessels expressing hPSMA, the P28BBζ CAR T cells were able to ablate PSMA+ vessels, cause secondary depletion of tumor cells, and reduce tumor burden. Taken together, these results provide a strong rationale for the use of CAR T cells as agents of tumor vascular disruption, specifically those targeting PSMA. Cancer Immunol Res; 3(1); 68–84. ©2014 AACR.
Liquidity Variation and the Cross-Section of Stock Returns

Stock liquidity varies substantially over time. A significant decrease in liquidity is often followed by a sizable rebound, and vice versa. The month-to-month liquidity change predicts the cross-sectional stock returns in the following month. Caeteris paribus, a liquidity decrease predicts a low return and a liquidity increase predicts a high return. The results are not explained by other cross-sectional return determinants including the liquidity level. The results are consistent with the mean-reverting nature of liquidity and its variation being priced. A liquidity reduction predicts an expected liquidity increase and thus a lower expected return, and vice versa. Our research suggests liquidity variation as an important factor of asset pricing. Its effect is independent from the widely documented liquidity level effect. JEL Classification: G12
The Use of Fictional Stories in Science Exhibits: The Emperor Who Only Believed His Own Eyes

The authors explore how fictional narratives (stories) can be used as a learning tool in the context of informal science environments and specifically science centers. They base their argument on an analysis of the theoretical, structural and epistemological properties of stories and how those can serve to establish a story as a cognitive tool. They offer an example of an application of these properties to a story-based learning design called “The Emperor who only Believed his own Eyes” in the context of a large, public science center, and specifically an exhibition about “senses”. This paper focuses on the idea of a “hack,” a museum sanctioned strategy for exploring the potential and implications of narrative-based design as a way to reinterpret science exhibits in a way that can engage young users in content exploration and offer recommendations for future research
In vitro biomechanical comparison of cervical disk arthroplasty, ventral slot procedure, and smooth pins with polymethylmethacrylate fixation at treated and adjacent canine cervical motion units.

OBJECTIVE To compare the biomechanical properties of cervical arthroplasty to a ventral slot procedure and pin-polymethylmethacrylate (pin-PMMA) fixation. SAMPLE POPULATION Fresh cadaveric cervical (C2-T1) spines from 6 large dogs. METHODS Four spinal conditions were studied in each spinal specimen: intact, disk arthroplasty, ventral slot, and fixation with smooth pin-PMMA at C5-C6 intervertebral space. Axial compression, torsion, flexion-extension, and lateral bending moments were sequentially tested on each specimen for the 4 spinal conditions. Data from the C3-C4, C4-C5, C5-C6, and C6-C7 vertebral motion units (VMUs) were compared among treatments. RESULTS In axial compression and torsion, the ventral slot procedure allowed significantly less motion than intact, pin-PMMA, and arthroplasty groups at C5-C6. In lateral bending and flexion-extension, pin-PMMA had the least motion of C5-C6, followed by the arthroplasty group, intact spine, and ventral slot, all of which were significantly different from each other. Overall, the artificial disk was better able to mimic the behavior of the intact specimens compared with the ventral slot and pin-PMMA, producing similar displacements in axial compression and rotation in torsion, but more limited motion than intact in flexion-extension and in lateral bending. CONCLUSION Cervical spine specimens with an implanted prosthesis have biomechanical behaviors more similar to an intact spine compared with spinal specimens with ventral slot and pin-PMMA procedures. Cervical arthroplasty may then preserve some of the motion in the affected area after neural decompression while providing distraction. CLINICAL RELEVANCE Cervical arthroplasty should be further investigated in vivo to determine if it is a viable alternative to the ventral slot or pin-PMMA procedures for surgical treatment of cervical diseases in dogs and in particular for treatment of disk-associated caudal cervical spondylomyelopathy.
Sexual desire in a nationally representative Danish population.

INTRODUCTION There are only a few studies on the frequency of sexual desire in the general population, whereas studies investigating the frequency of disordered sexual desire are more common. AIM The aim of this study was to describe the frequency of sexual desire in a representative sample of the adult Danish population and to analyze the relationships between a number of relevant variables and sexual desire. METHODS The study population (N = 10,458, response rate 84.8%) answered a questionnaire with questions on sexual matters. The representativity of the population was examined. The frequency of self-reported sexual desire and decrease in sexual desire over a 5-year period was calculated for the two genders across age cohorts. Multiple logistic regression analysis was used to analyze the relationship between potential determinants and sexual desire. MAIN OUTCOME MEASURES The frequency of self-reported sexual desire and decrease in sexual desire was examined. Factors of importance for sexual desire were tested using two outcome measures: (i) often having sexual desire; and (ii) seldom having sexual desire. RESULTS A significant association between gender and sexual desire was found in all age groups, as men had a significantly higher level of sexual desire than women. In both genders, the frequency of sexual desire was significantly reduced with increasing age. Among the 45- to 66-year-olds, 57% of the men and 47% of the women reported no change in the level of sexual desire over the past 5 years. In general terms, factors related to seldom having sexual desire were age and social, psychological, and physical distress in both genders. CONCLUSION This study shows that overall, men have a higher level of sexual desire than women; sexual desire decreases with increasing age; and social, psychological, or physical distress are associated with low level of sexual desire in both genders.
Bayesian Community Detection

Many networks of scientific interest naturally decompose into clusters or communities with comparatively fewer external than internal links; however, current Bayesian models of network communities do not exert this intuitive notion of communities. We formulate a nonparametric Bayesian model for community detection consistent with an intuitive definition of communities and present a Markov chain Monte Carlo procedure for inferring the community structure. A Matlab toolbox with the proposed inference procedure is available for download. On synthetic and real networks, our model detects communities consistent with ground truth, and on real networks, it outperforms existing approaches in predicting missing links. This suggests that community structure is an important structural property of networks that should be explicitly modeled.
Development and Characterization of a Novel Mouse Line Humanized for the Intestinal Peptide Transporter PEPT1

The proton-coupled oligopeptide transporter PEPT1 (SLC15A1) is abundantly expressed in the small intestine, but not colon, of mammals and found to mediate the uptake of di/tripeptides and peptide-like drugs from the intestinal lumen. However, species differences have been observed in both the expression (and localization) of PEPT1 and its substrate affinity. With this in mind, the objectives of this study were to develop a humanized PEPT1 mouse model (huPEPT1) and to characterize hPEPT1 expression and functional activity in the intestines. Thus, after generating huPEPT1 mice in animals previously nulled for mouse Pept1, phenotypic, PCR, and immunoblot analyses were performed, along with in situ single-pass intestinal perfusion and in vivo oral pharmacokinetic studies with a model dipeptide, glycylsarcosine (GlySar). Overall, the huPEPT1 mice had normal survival rates, fertility, litter size, gender distribution, and body weight. There was no obvious behavioral or pathological phenotype. The mRNA and protein profiles indicated that huPEPT1 mice had substantial PEPT1 expression in all regions of the small intestine (i.e., duodenum, jejunum, and ileum) along with low but measurable expression in both proximal and distal segments of the colon. In agreement with PEPT1 expression, the in situ permeability of GlySar in huPEPT1 mice was similar to but lower than wildtype animals in small intestine, and greater than wildtype mice in colon. However, a species difference existed in the in situ transport kinetics of jejunal PEPT1, in which the maximal flux and Michaelis constant of GlySar were reduced 7-fold and 2- to 4-fold, respectively, in huPEPT1 compared to wildtype mice. Still, the in vivo function of intestinal PEPT1 appeared fully restored (compared to Pept1 knockout mice) as indicated by the nearly identical pharmacokinetics and plasma concentration–time profiles following a 5.0 nmol/g oral dose of GlySar to huPEPT1 and wildtype mice. This study reports, for the first time, the development and characterization of mice humanized for PEPT1. This novel transgenic huPEPT1 mouse model should prove useful in examining the role, relevance, and regulation of PEPT1 in diet and disease, and in the drug discovery process.
Cortico-striatal circuitry in visual perception.

main effcct of stimulation and the interaction between stimulation type and block of trials was also not significant. neuronal subserving goal-directed functions. impulse activity of the in the basal ganglia-thalamocortical no-go lack of activation in can be explained by the malfunctioning of the basal pathways to dopamine depletion the may not differential other parts of the categorization network, lack early, categorization-related electrophysiological signs.
Ultrasound Assessment of Flow-Mediated Dilation

Developed in 1992, the flow-mediated dilation test is now the most commonly used noninvasive assessment of vascular endothelial function in humans. Since its inception, scientists have refined their understanding of the physiology, analysis, and interpretation of this measurement. Recently, a significant growth of knowledge has added to our understanding and implementation of this clinically relevant research methodology. Therefore, this tutorial provides timely insight into recent advances and practical information related to the ultrasonic assessment of vascular endothelial function in humans.
Preparation and Characterization of Nanocomposite Polymer Membranes Containing Functionalized SnO2 Additives

In the research of new nanocomposite proton-conducting membranes, SnO2 ceramic powders with surface functionalization have been synthesized and adopted as additives in Nafion-based polymer systems. Different synthetic routes have been explored to obtain suitable, nanometer-sized sulphated tin oxide particles. Structural and morphological characteristics, as well as surface and bulk properties of the obtained oxide powders, have been determined by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) and Raman spectroscopies, N2 adsorption, and thermal gravimetric analysis (TGA). In addition, dynamic mechanical analysis (DMA), atomic force microscopy (AFM), thermal investigations, water uptake (WU) measurements, and ionic exchange capacity (IEC) tests have been used as characterization tools for the nanocomposite membranes. The nature of the tin oxide precursor, as well as the synthesis procedure, were found to play an important role in determining the morphology and the particle size distribution of the ceramic powder, this affecting the effective functionalization of the oxides. The incorporation of such particles, having sulphate groups on their surface, altered some peculiar properties of the resulting composite membrane, such as water content, thermo-mechanical, and morphological characteristics.
Do-Not-Resuscitate Orders: From the Ward to the Operating Room; From Procedures to Goals

An anesthesiologist is called to the emergency department to see an 18-year-old man with an acute small bowel obstruction, probably related to adhesions from previous surgeries. He had a lymphoma diagnosed at age 12, with a bone marrow transplant performed at age 13, during his first remission. He relapsed at age 17, and has been in partial remission since that time. He has moderately impaired left ventricular function secondary to adriamycin toxicity; he can climb only one set of stairs before becoming short of breath. The general surgeons recommend an immediate laparotomy to relieve his small bowel obstruction. He has an outpatient Do-Not-Resuscitate (DNR) order instructing paramedics not to resuscitate him in the event of a cardiac arrest. He also had a DNR order written during his last admission to the hospital several months ago. In the preoperative discussion, the anesthesiologist learns that: (1) the patient definitively wants to proceed with surgery, and (2) he wants to maintain his DNR order intraoperatively. During further discussion, the anesthesiologist elucidates some of the patient’s concerns about resuscitation during the perioperative period. The patient’s oncologists have told him that outcomes from CPR for patients with malignant disease are very poor. It unlikely that he would survive CPR, and if he survived he would most likely suffer further impairment to his neurologic and cardiac status that would diminish the quality of his life to an intolerable level. In addition, if he survived CPR he would most likely require an ICU admission and postoperative ventilation. The patient was intubated in the ICU for several weeks for a pneumonia following his bone marrow transplant, and he does not want to experience another prolonged ICU course. He has seen CPR performed on televi-
Mental Mirroring as the Origin of Attributions

: A ‘Radical Simulationist’ account of how folk psychology functions has been developed by Robert Gordon. I argue that Radical Simulationism is false. In its simplest form it is not sufficient to explain our attribution of mental states to subjects whose desires and preferences differ from our own. Modifying the theory to capture these attributions invariably generates innumerable other false attributions. Further, the theory predicts that deficits in mentalizing ought to co-occur with certain deficits in imagining perceptually-based scenarios. I present evidence suggesting that this prediction is false, and outline further possible empirical tests of the theory.
SCN Outputs and the Hypothalamic Balance of Life

The circadian clock in the suprachiasmatic nucleus (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. Still, the major question remains how these individual oscillators are organized into a biological clock producing a coherent output able to time all the different daily changes in behavior and physiology. In the present review, the authors discuss the anatomical connections and neurotransmitters used by the SCN to control the daily rhythms in hormone release. The efferent SCN projections mainly target neurons in the medial hypothalamus surrounding the SCN. The activity of these preautonomic and neuroendocrine target neurons is controlled by differentially timed waves of, among others, vasopressin, GABA, and glutamate release from SCN terminals. Together, the data on the SCN control of neuroendocrine rhythms provide clear evidence not only that the SCN consists of phenotypically (i.e., according to neurotransmitter content) different subpopulations of neurons but also that subpopulations should be distinguished (within phenotypically similar groups of neurons) based on the acrophase of their (electrical) activity. Moreover, the specialization of the SCN may go as far as a single body structure, that is, the SCN seems to contain neurons that specifically target the liver, pineal, and adrenal.
Effects of Ploidy and Recombination on Evolution of Robustness in a Model of the Segment Polarity Network

Many genetic networks are astonishingly robust to quantitative variation, allowing these networks to continue functioning in the face of mutation and environmental perturbation. However, the evolution of such robustness remains poorly understood for real genetic networks. Here we explore whether and how ploidy and recombination affect the evolution of robustness in a detailed computational model of the segment polarity network. We introduce a novel computational method that predicts the quantitative values of biochemical parameters from bit sequences representing genotype, allowing our model to bridge genotype to phenotype. Using this, we simulate 2,000 generations of evolution in a population of individuals under stabilizing and truncation selection, selecting for individuals that could sharpen the initial pattern of engrailed and wingless expression. Robustness was measured by simulating a mutation in the network and measuring the effect on the engrailed and wingless patterns; higher robustness corresponded to insensitivity of this pattern to perturbation. We compared robustness in diploid and haploid populations, with either asexual or sexual reproduction. In all cases, robustness increased, and the greatest increase was in diploid sexual populations; diploidy and sex synergized to evolve greater robustness than either acting alone. Diploidy conferred increased robustness by allowing most deleterious mutations to be rescued by a working allele. Sex (recombination) conferred a robustness advantage through “survival of the compatible”: those alleles that can work with a wide variety of genetically diverse partners persist, and this selects for robust alleles.
Partially Matched Related Donor Transplantation Can Achieve Outcomes Comparable with Unrelated Donor Transplantation for Patients with Hematologic Malignancies

Purpose: The study aimed to compare the outcomes of patients undergoing hematopoietic stem cell transplantation (HSCT) from partially matched related donors (PMRD) and unrelated donors (URD) for hematologic malignancies without the use of in vitro T cell depletion. Experimental Design: HSCT was done on 297 consecutive patients from URDs (n = 78) and PMRDs (n = 219) during the same time period. Incidences of graft-versus-host disease (GVHD), relapse, nonrelapse mortality, overall survival, and leukemia-free survival between the PMRD and URD groups were compared. Results: All patients achieved full engraftment. The cumct65ulative incidences of grades II to IV acute GVHD in the PMRD and URD cohorts were 47% [95% confidence interval (95% CI), 33-62%] versus 31% (CI, 20-42%; P = 0.033), with a relative risk of 1.72 (95% CI, 1.01-2.94; P = 0.046). The incidence of chronic GVHD did not differ significantly between the two cohorts (P = 0.17). The 2-year incidences of nonrelapse mortality and relapse were 20% (CI, 15-26%) versus 18% (CI, 10-27%), with P = 0.98, and 12% (CI, 8-16%) versus 18% (CI, 10-27%), with P = 0.12, for the PMRD versus the URD cohort, respectively. The 4-year overall survival and leukemia-free survival were 74% (CI, 67-80%) versus 74% (CI, 62-85%), with P = 0.98, and 67% (CI, 59-75%) versus 61% (CI, 47-74%), with P = 0.74, respectively. Conclusions: Our comparisons show that every major end point, including relapse, nonrelapse mortality, overall survival, and leukemia-free survival, was comparable between the PMRD and the URD groups.
The efficacy of emamectin benzoate against infestations of sea lice, Lepeophtheirus salmonis, on farmed Atlantic salmon, Salmo salar L., in British Columbia.

Sea lice are a naturally occurring ectoparasite of wild salmon (Nagasawa 2001; Beamish, Neville, Sweeting & Ambers 2005). There is also clear evidence that these parasites are seldom a production or fish health concern on farms in British Columbia (Saksida, Constantine, Karreman & Donald 2007), in direct contrast to most other salmon-producing regions (Heuch, Revie & Gettinby 2003; O Donohoe, Kane, Kelly, Nixon, Power, Naughton & Jackson 2008; Lees, Gettinby & Revie 2008a). Nevertheless, owing to concerns regarding the potential impact of sea lice originating from farmed Atlantic salmon, Salmo salar L. , on wild Pacific salmon species, Oncorhynchus spp. , in BC, their effective control continues to be a subject of considerable interest (Morton, Routledge, Peet & Ladwig 2004; Krkošek, Ford, Morton, Lele, Myers & Lewis 2007). Indeed, it has been suggested that the recent reductions in sea lice infestations on wild salmonids in the Broughton Archipelago (an area of major research focus over the past 5 years) are a consequence of improved lice management actions on salmon farms (Harvey 2009). While a number of management practices, such as single year-class production and between-cycle fallowing, can have a positive effect on lice control within farms, the most direct effects are associated with the use of medicines to control sea lice. This is particularly the case if a goal is to minimize lice numbers at a specific point in the production cycle, for example during the period when wild smolts are most likely to be migrating past farms. In 2003, BC regulatory authorities established requirements that farms maintain lice abundance below a threshold of three motile stage Lepeophtheirus salmonis between March and June (Saksida et al. 2007). In 2004, these same authorities commenced a sea lice surveillance programme where between 25% and 50% of active Atlantic salmon farms were assessed by government biologists for sea lice during each quarter to verify reported levels (Saksida et al. 2007). These regulations have not changed. In BC, the only product that is currently available to treat sea lice on salmon farms is SLICE (Intervet Schering-Plough Animal Health). SLICE is an oral formulation of emamectin benzoate, which is added to fish feed and delivered at a dosage of 0.5 lg kg fish for 7 days. There have been a number of reports indicating reduced efficacy of emamectin benzoate when used on farmed fish in a range of other salmonproducing countries. These include Chile (Bravo, Sevatdal & Horsberg 2008) and Scotland (Lees, Baillie, Gettinby & Revie 2008b), with less welldocumented reports in Ireland (O Donohoe et al. 2008 – non-specific report of reduced sensitivities , Journal of Fish Diseases 2010, 33, 913–917 doi:10.1111/j.1365-2761.2010. 01192.x