cssi/SciSciGPT-SciSciNet huggingface dataset:
Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment for those with rheumatoid disorders. Absorption of NSAIDs does not appear to differ between elderly and young persons. Most NSAIDs are weak acids that avidly bind to plasma proteins, especially albumin; elderly persons often have reductions in albumin concentrations that result in altered kinetic disposition of these drugs. Although the pharmacologic activity resides in the unbound moiety, heretofore most studies report only total NS AID concentrations. Recent knowledge indicates that the S-enantiomer of aryl-propionic acid derivatives is solely active, thereby requiring its assessment; for some, inversion of the R- to S-configuration occurs in vivo. Also it is now apparent that acylglucuronides may accumulate in patients with reduced renal function and may then revert to active drug. Our knowledge of the pharmacokinetics and pharmacodynamics of NSAIDs is still evolving. As such, clinical studies are necessary to design appropriate dosage guidelines that permit safe and effective NS AID treatment of elderly patients.
The Ghost of a Vanished Vortex Ring

Onsager’s suggestion that a roton is a vortex ring of molecular size is discussed, and a review of experimental evidence together with theories based on this idea are presented.
Futures of Hope The Importance of Positive Futures Images at the Community College Level

The writer takes the position that futures studies should lead the way in teaching image literacy and shares experiences and examples from her work teaching futures studies at the undergraduate lev...
Survey of Pesticide Residues and Their Metabolites in Humans

Publisher Summary The chapter focuses on the surveys conducted on pesticide residues and their metabolites in humans. A number of surveys of pesticide residues in humans provide a major element in pesticide policy decision-making. These residues are demonstrative of the extent of the environmental distribution of the particular pesticide, and when coupled with laboratory animal data showing adverse biological effects, signal a potential public health hazard. One major survey that examines humans for pesticide residues and associated chemicals is the National Human Monitoring Program for Pesticides, which is operated by the US Environmental Protection Agency. The program aims to determine, on a national scale, the incidence and level of exposure to pesticides experienced by the general population and to identify trends in these factors when they occur.
Physiological Evaluation and Quantification of Physician’s Cognitive Workload During Interaction with Computer Based Clinical System

Tracking cognitive workload (CWL) of physicians interacting with health information technology (HIT) might be useful in order to identify high-risk tasks, and to flag situations when performance might be expected to decline. Eight physician radiation oncologists (3-faculty, 5-residents) pupillary responses were monitored during treatment-planning tasks. The average change in task evoked pupillary response (TEPR) from pre-set baseline was calculated and the percent of time that the TEPR dilated by ≥0.45 mm (from historical studies) was taken as a measure of CWL where performance degradation could be expected. Physician performance was assessed subjectively (willingness-to-approve the treatment-plan) and objectively (number and severity of errors). There was an association between CWL and subjective performance (p 0.05) as assessed using logistic regression analysis. Future research is needed to further advance available methods to quantify the relationship between CWL and performance during physicians-HIT interactions.
Security Challenges in CPS and IoT: From End-Node to the System

The rising of cyber-physical systems (CPS) and Internet of Things (IoT) has significantly increase the industrial productivities and customer convenience. However, the widely distributed CPS and IoT systems also breeds new challenges among which security is a major concern. In order to help build secure and resilient CPS/IoT systems, systematic analyses are performed on CPS and IoT from individual smart devices which serve as the end nodes to the entire system. The analysis results will help identify the vulnerabilities of CPS/IoT systems and/or provide guidance on how to build security into these systems. Security mitigation methods will also be discussed which can help balance security with other criteria such as safety and performance.
A case-control comparison of direct healthcare-provider medical costs of chronic idiopathic constipation and irritable bowel syndrome with constipation in a community-based cohort.

AbstractObjective: Patients with constipation account for 3.1 million US physician visits a year, but care costs for patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) compared to the general public have received little study. The study aim was to describe healthcare utilization and compare medical costs for patients with IBS-C or CIC vs matched controls from a community-based sample.Methods: A nested case-control sample (IBS-C and CIC cases) and matched controls (1:2) for each case group were selected from Olmsted County, MN, individuals responding to a community-based survey of gastrointestinal symptoms (2008) who received healthcare from a participating Rochester Epidemiology Project (REP) provider. Using REP healthcare utilization data, unadjusted and adjusted standardized costs were compared for the 2- and 10-year periods prior to the survey for 115 IBS-C patients and 230 controls and 365 CIC patients and 730 controls. Two time periods were chose...
Effects of climate on competitive dynamics in mixed conifer forests of the Sierra Nevada

Trees in more competitive environments appear to respond to climate differently than trees in less competitive environments. In turn, climate patterns may affect inter- or intra-specific competition, favoring certain individuals over others. Using dendrochronological methods, we sampled cores from dominant pine trees and their nearby competitors in 40 stands in the northern Sierra Nevada. Our dendroclimatological analyses showed complex responses to climate for the dominant pine and their competitors. Pinus lambertiana Dougl. and Pinus ponderosa Dougl. Ex P. & C. Laws benefited from cooler temperatures in the past May; all species benefited from warmer winter temperatures; Calocedrus decurrens (Torr.) Florin benefited from cooler temperatures in the past summer, while Abies concolor (Gord. & Glend.) Lindl.) and the two pine species benefited from cooler temperatures in the present summer. All species showed consistently positive effects from increased precipitation and increased moisture availability. A competition ratio calculated as the ratio between the dominant tree’s radial increments to the competitor’s indicated that climate could influence competition through one of two mechanisms. One, negative responses to climate conditions that were negative for one species but neutral for another tended to drive the competition ratios. Two, conditions that were negative for both competing trees tended to hurt competitors more than dominant trees, while conditions that were generally positive tended to help competitors more than dominant trees. These results suggest that the dominant pine trees may be more resilient to climate stress than competitors. Reducing competition via management such as thinning may increase climatic resilience for all species and possibly have positive competitive results for competitors. Increasing temperatures will tend to harm Sierra Nevada conifers in the summer and spring, but may show some benefit over the winter as long as precipitation is not reduced.
Optical coherence tomography (OCT) guided smart laser knife for cancer surgery (Conference Presentation)

Neurological cancer surgeries require specialized tools that enhance imaging for precise cutting and removal of tissue without damaging adjacent neurological structures. The novel combination of high-resolution fast optical coherence tomography (OCT) alongside short pulsed nanosecond thulium (Tm) lasers offers stark advantages utilizing the superior beam quality, high volumetric tissue removal rates of thulium lasers with minimal residual thermal footprint in the tissue and avoiding damage to delicate sub-surface structures (e.g., nerves and microvessels); which has not been showcased before. A bench-top system is constructed, using a 15W 1940nm nanosecond pulsed Tm fiber laser (500uJ pulse energy, 100ns pulse duration, 30kHz repetition rate) for removing tissue and a swept source laser (1310±70nm, 100kHz sweep rate) is utilized for OCT imaging, forming a combined Tm/OCT system – a smart laser knife. The OCT image-guidance informs the Tm laser for cutting/removal of targeted tissue structures. Tissue phantoms were constructed to demonstrate surgical incision with blood vessel avoidance on the surface where 2mm wide 600um deep cuts are executed around the vessel using OCT to guide the procedure. Cutting up to delicate subsurface blood vessels (2mm deep) is demonstrated while avoiding damage to their walls. A tissue removal rate of 5mm^3/sec is obtained from the bench-top system. We constructed a blow-off model to characterize Tm cut depths taking into account the absorption coefficients and beam delivery systems to compute Arrhenius damage integrals. The model is used to compare predicted tissue removal rate and residual thermal injury with experimental values in response to Tm laser-tissue modification.
Probabilistic assessment of aquatic species risk from thermoelectric power plant effluent: Incorporating biology into the energy-water nexus

Abstract As global populations grow, demand for generation of affordable and efficient electricity will likely increase, requiring tradeoffs between power generation and ecosystems sustainability, including water quality and species habitat. Once-through thermoelectric power plants, representing 30% of the electricity generation in the United States, withdraw and discharge large quantities of water for cooling purposes. This process can cause thermal pollution in waterways, adversely affecting aquatic communities. Incorporating biology into the energy-water nexus can aid decision-makers in identifying tradeoffs and more effectively assessing and managing aquatic ecosystems. To quantify thermal pollution and the risk posed to aquatic species, we created an adaptable, novel methodology that utilizes plume mixing and probability distribution analyses on temperature and flow data for both a power plant’s discharge and the adjoining river. To assess risk, we developed a probability risk space that quantifies the probability of exceeding a given temperature. The Shawnee Fossil Plant on the Ohio River was selected to demonstrate the methodology, and three fish species with associated upper thermal avoidance limits were selected for comparison. Our results highlight that both the lateral and longitudinal location from the point of effluent mixing within the river affects the probability of thermal risk to aquatic species. A high degree of risk within a plume can reduce to a smaller total risk within the context of a large river cross-section. Our results emphasize the need for individualized risk assessment for Clean Water Act §316(a) requirements for power plant effluent temperature limits and National Pollutant Discharge Elimination System permits. These findings are applicable in policy-making, environmental mitigation, and power plant operations management.
Needle localization of small pulmonary nodules: Lessons learned

Abstract Background Lung nodules that are small and deep within lung parenchyma, and have semisolid characteristics are often challenging to localize with video-assisted thoracoscopic surgery (VATS). We describe our cumulative experience using needle localization of small nodules before surgical resection. We report procedural tips, operative results, and lessons learned over time. Methods A retrospective review of all needle localization cases between July 1, 2006, and December 30, 2016, at a single institution was performed. A total of 253 patients who underwent needle localization of lung nodules ranging from 0.6 to 1.2 cm before operation were enrolled. Nodules were localized by placing two 20-gauge Hawkins III coaxial needles from different trajectories with tips adjacent to the nodule, injection of 0.3 to 0.6 mL of methylene blue, and deployment of 2 hookwires, under computed tomography guidance. Patients then underwent VATS wedge resection for diagnosis, followed by anatomic resection for lung carcinoma. Procedural and perioperative outcomes were assessed. Results Needle localization was successful in 245 patients (96.8%). Failures included both wires falling out of lung parenchyma before operation (5 patients), wire migration (2 patients), and bleeding resulting in hematoma requiring transfusion (1 patient). The most common complication of needle localization was asymptomatic pneumothorax (11/253 total patients; 4.3%) and was higher in patients with bullous emphysema (9/35 patients; 25.7%). Of the 8 individuals who had unsuccessful needle localization, 7 had successful wedge resection in the area of methylene blue injection that included the nodule; 1 required segmentectomy for diagnosis. Completion lobectomy (154 VATS, 2 minithoracotomies) or VATS segmentectomy (18 patients) was performed in 174 individuals with a diagnosis of non–small cell carcinoma or carcinoid. The average length of hospital stay was 1.4 days for wedge resection, 1.9 days for VATS segmentectomy, 3.1 days for VATS lobectomy, and 4.9 days for minithoracotomy. Perioperative survival was 100%. Conclusions Needle localization with hookwire deployment and methylene blue injection is a safe and feasible strategy to localize small, deep lung nodules for wedge resection and diagnosis. Multidisciplinary coordination between the thoracic surgeon and the interventional radiologist is key to the success of this procedure.
Racial Differences in Childhood Obesity: Pathogenesis and Complications

Race and ethnicity are terms used to categorize populations on the basis of shared characteristics. Race is traditionally used to categorize populations on the basis of shared biological characteristics such as skin color, other observable features, and the genetic determinants of such differences (1). Ethnicity is used to categorize individuals on the basis of cultural characteristics such as shared language, ancestry, religious traditions, dietary preferences, and history. Although ethnic groups can share a range of phenotypic characteristics due to shared ancestry, the term is typically used to highlight cultural and social characteristics instead of biological ones (1). Both race and ethnicity are frequently used interchangeably and are constantly evolving concepts, especially in the United States, making the task of comparing groups or following the same group over time quite challenging.
Fingerprint Synthesis: Evaluating Fingerprint Search at Scale

A database of a large number of fingerprint images is highly desired for designing and evaluating large scale fingerprint search algorithms. Compared to collecting a large number of real fingerprints, which is very costly in terms of time, effort and expense, and also involves stringent privacy issues, synthetic fingerprints can be generated at low cost and does not have any privacy issues to deal with. However, it is essential to show that the characteristics and appearance of real and synthetic fingerprint images are sufficiently similar. We propose a Generative Adversarial Network (GAN) to generate 512X512 rolled fingerprint images. Our generative model for rolled fingerprints is highly efficient (12ms/image) with characteristics of synthetic rolled prints close to real rolled images. Experimental results show that our model captures the properties of real rolled fingerprints in terms of (i) fingerprint image quality, (ii) distinctiveness and (iii) minutiae configuration. Our synthetic fingerprint images are more realistic than other approaches.
Time-Domain Dielectric Spectroscopy Using a Miniaturized Contact-Based UWB System

This paper presents a miniaturized contact-based system for dielectric spectroscopy using time-domain (TD) technique in ultrawideband (UWB) frequency range. The system consists of a miniaturized UWB transmitter, a planar sensor having direct contact with a liquid material under test (MUT), and a high-speed oscilloscope receiver. In the transmitter, a baseband (BB) pulse with 3.5-GHz bandwidth is generated from a square-wave input signal by employing a step recovery diode and a short-circuited stub. Then, the BB pulse is upconverted by a UWB mixer with 6.5-GHz local oscillator frequency, creating a 3–10-GHz passband pulse. After being amplified, the passband pulse excites the miniaturized sensor, including two stages of microstrip open-circuited stub between meander inductors. This sensor has a small area, requires only 0.3 $\mu \text{L}$ of liquid MUT for accurate sensing, and responds to both $\epsilon '$ and $\epsilon ''$ properties. The sensor output is captured by the oscilloscope in TD and then converted to frequency domain (FD) by the fast Fourier transform operation. Considering $\epsilon '$ and $\epsilon ''$ of MUT simultaneously affect both phase and magnitude of output signal in FD, the behavior of the system is described by testing 12 reference MUTs. From the behavioral model of the system, three unknown MUTs are characterized with errors less than $0.1|\epsilon ^{*}|$ in both $\epsilon '$ and $\epsilon ''$ from 3.28 to 10 GHz.
Putative tumor suppressor cytoglobin promotes aryl hydrocarbon receptor ligand–mediated triple negative breast cancer cell death

Nearly 40 000 women die annually from breast cancer in the United States. Clinically available targeted breast cancer therapy is largely ineffective in triple negative breast cancer (TNBC), characterized by tumors that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2). TNBC is associated with a poor prognosis. Previous reports show that aryl hydrocarbon receptor (AhR) partial agonist 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) selectively inhibits the growth of breast cancer cells, including those of the TNBC subtype. We previously demonstrated that 5F 203 induced the expression of putative tumor suppressor gene cytoglobin (CYGB) in breast cancer cells. In the current study, we determined that 5F 203 induces apoptosis and caspase-3 activation in MDA-MB-468 TNBC cells and in T47D ER+ PR + Her2 - breast cancer cells. We also show that caspases and CYGB promote 5F 203-mediated apoptosis in MDA-MB-468 cells. 5F 203 induced lysosomal membrane permeabilization (LMP) and cathepsin B release in MDA-MB-468 and T47D cells. In addition, silencing CYGB attenuated the ability of 5F 203 to induce caspase-3/-7 activation, proapoptotic gene expression, LMP, and cathepsin B release in MDA-MB-468 cells. Moreover, 5F 203 induced CYGB protein expression, proapoptotic protein expression, and caspase-3 cleavage in MDA-MB-468 cells and in MDA-MB-468 xenograft tumors grown orthotopically in athymic mice. These data provide a basis for the development of AhR ligands with the potential to restore CYGB expression as a novel strategy to treat TNBC.
Activity of iridium pyridine-based nanophotoswitches in retina

Purpose : Nanophotoswitches (NPSs) offer a new tool for optical stimulation of neuronal activity, in vitro and potentially in vivo. Our group previously reported a ruthenium bipyridine-based NPS (Rubpy-C17) that, after injection into the eyes of photoreceptor degenerated blind rats, elicited electrical activity in the contralateral superior colliculus upon light exposure. Compared with the ruthenium complexes, the family of iridium complexes has been more widely used in clinics, owing to its biosafety profile. We have thus synthesized and tested Irbpy-C17, an analog of Rubpy-C17 with the ruthenium core replaced by iridium. Methods : Rubpy molecules can be visualized by their luminescence upon visible wavelength illumination. To examine membrane incorporation, fluorescence imaging of HEK cells was obtained after incubation with Irbpy-C17. Activity of Irbpy-C17 was studied by MEA recording from wholemount retina after intravitreal injection. The test molecules were administered into the vitreous of blind RCS rats at the concentration of 200 µM. Animals were kept in dark after injection until the surgical dissection of retina. Acutely isolated retina was mounted on the MEA with the ganglion cell layer facing down to capture the spiking activity in response to light stimuli. Results : Irbpy-C17 exhibited good membrane incorporation similar to that of Rubpy-C17. Interestingly, despite that Irbpy-C17 elicited minimal light response initially, subsequent application of synaptic blocker cocktail that pharmacologically isolated RGCs substantially enhanced the light activation of RGCs (1.8 ± 0.3 fold increase in spike frequency). In comparison with the 3-hour incubation between injection and dissection, prolonged 24-hour incubation led to a more pronounced 2.5 ± 0.5 fold increase in spike frequency. Conclusions : Our data suggest that Irbpy-C17 may act on multiple components of the retinal neural circuitry that could suppress its direct action on RGCs via synaptic transmission. These molecules intravitreally administered remain stable and active in the ocular environment up to at least one day post injection. These data will prompt us to further study the iridium complexes in parallel with the ruthenium counterparts, particularly for the underlying mechanism of their differential behavior. The NPSs obviates the need for gene manipulation or toxic UV illumination, highlighting its potential in generating high-acuity prosthetic vision in the blind.
Abstract 212: Chronic Systemic Inflammation Accelerates Endothelial Cholesterol Crystal Formation and Lysosomal Dysfunction

Objective: Atherogenesis is an inflammatory process accelerated in psoriasis, a chronic inflammatory skin disease associated with premature cardiovascular diseases (CVD). Cholesterol crystal (CC) f...
Principles for a practical Moon base

Abstract NASA planning for the human space flight frontier is coming into alignment with the goals of other planetary-capable national space agencies and independent commercial actors. US Space Policy Directive 1 made this shift explicit: “the United States will lead the return of humans to the Moon for long-term exploration and utilization”. The stage is now set for public and private American investment in a wide range of lunar activities. Assumptions about Moon base architectures and operations are likely to drive the invention of requirements that will in turn govern development of systems, commercial-services purchase agreements, and priorities for technology investment. Yet some fundamental architecture-shaping lessons already captured in the literature are not clearly being used as drivers, and remain absent from typical treatments of lunar base concepts. A prime example is general failure to recognize that most of the time (i.e., before and between intermittent human occupancy), a Moon base must be robotic: most of the activity, most of the time, must be implemented by robot agents rather than astronauts. This paper reviews key findings of a seminal robotic-base design-operations analysis commissioned by NASA in 1989. It discusses implications of these lessons for today's Moon Village and SPD-1 paradigms: exploration by multiple actors; public-private partnership development and operations; cislunar infrastructure; production-quantity exploitation of volatile resources near the poles to bootstrap further space activities; autonomy capability that was frontier in 1989 but now routine within terrestrial industry. It outlines new work underway to close these gaps; and articulates conclusions that can guide future work.
Frequency of whole-organ in lieu of split-liver transplantation over the last decade: Children experienced increased wait time and death.

Organ shortage is a barrier to liver transplantation (LT). Split LT (SLT) increases organ utilization, saving 2 recipients. A simulation of Organ Procurement and Transplantation Network/United Network for Organ Sharing data (2007-2017) was performed to identify whole-organ LT grafts (WLT) that met the criteria for being splittable to 2 recipients. Waitlist consequences presented. Deceased donor (DD) livers transplanted as whole organs were evaluated for suitability to split. Of these DD organs, we identified the adolescent and adult recipients of WLT who were suitable for SLT. Pediatric candidates suitable to share the SLT were ascertained from DD match-run lists, and 1342 splittable DD organs were identified; 438 WLT recipients met the criteria for accepting a SLT. Review of the 438 DD match-run lists identified 420 children next on the list suitable for SLT. Three hundred thirty-three children (79%) underwent LT, but had longer wait-times compared to 591 actual pediatric SLT recipients (median 147 days vs 44 days, P < 0.001). Thirty-three of 420 children died on waitlist after a mean 206 days (standard deviation 317). Sharing organs suitable for splitting increases the number of LT, saving more lives. With careful patient selection, SLT will not be a disadvantage to the adult recipients. With a children-first allocation scheme, SLT will naturally increase the number of allografts because adult organs are too large for small children.
A social network approach to analyzing body dissatisfaction among sorority members using two network generators

Objective: This article uses social network analysis (SNA) to analyze how various measures of social connectedness relate to body dissatisfaction (BD) in sorority members.Participants: 208 sorority members participated in the study.Methods: Measures of social connectedness (network variables) were created based on two relational networks: persons members felt closest to and persons they spent the most time with. SNA tested whether demographic variables, body mass index (BMI), compulsive exercise, and network variables were related to BD in both networks.Results: Members reported BD was related to less social connectedness in the "close-to" and the "time-spent" networks, although specific network variables varied between the two. Compulsive exercise, BMI, and grade classification were related to BD in both networks.Conclusions: How a sorority member connects to others in her network could impact BD in this population. This study supports efforts facilitating increased social connection within a sorority as a means to decrease BD.
Room-Temperature FTIR Spectra of the Cyclic S4 (H2O)4 Cluster in Crystalline Li2(H2O)4(B12F12): Observation of B and E ν(OH) Bands and Coupling of Strong O-H···O and Weak O-H···F Vibrations.

Room-temperature-attenuated total reflection-Fourier transform infrared (FTIR) spectra of the structurally characterized crystalline lithium salt Li2(H2O)4(B12F12), which contains a cyclic S4 symme...
Soave-Like Transanal Endorectal Pull-Through

This chapter describes the surgical procedure for Soave-like transanal endorectal pull-through. The text includes an introduction that outlines the indications, risks, alternatives, essential steps, needed equipment, and variations in technique for the procedure in question. This is followed by a template operative dictation, which provides the reader with an operative report, such as is found in a patient chart or electronic medical record. A description is provided of the following critical concepts for this procedure: (1) placement of the Lone Star self-retaining retractor proximal to the dentate line, (2) placement of circumferential interrupted silk sutures proximal to the dentate line, (3) performance of a submucosal, then full-thickness dissection of the bowel until the level of the normal, ganglionic bowel is reached, (4) pull-through of colon, (5) placement of a deep layer of suture circumferentially from muscle to colonic serosa, (6) resection of the distal, aganglionic segment of bowel with electrocautery, (7) incising of the muscular cuff posteriorly, and (8) placement of a second layer of sutures from mucosa to mucosa to complete the coloanal anastomosis.
Allosteric coupling between Mn2+and dsDNA controls the catalytic efficiency and fidelity of cGAS

Cyclic-G/AMP (cGAMP) synthase (cGAS) triggers host innate immune responses against cytosolic double-stranded (ds)DNA arising from genotoxic stress and pathogen invasion. The canonical activation mechanism of cGAS entails dsDNA-binding and dimerization. Here, we report an unexpected activation mechanism of cGAS in which Mn2+ activates monomeric cGAS without dsDNA. Importantly, the Mn2+-mediated activation positively couples with dsDNA-dependent activation in a concerted manner. Moreover, the positive coupling between Mn2+ and dsDNA length-dependent activation requires the cognate ATP/GTP substrate pair, while negative-cooperativity suppresses Mn2+ utilization by either ATP or GTP alone. Additionally, while Mn2+ accelerates the overall catalytic activity, dsDNA length-dependent dimerization specifically accelerates the cyclization of cGAMP. Together, we demonstrate how the intrinsic allostery of cGAS efficiently yet precisely tunes its activity.
Negative heritage: the material-cultural politics of the American haunted history tour

This article assesses the defining features and cultural significance of the haunted history tour as it has come to be practiced in American urban spaces. A distinctive cultural form that has risen...
TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss

Early pregnancy loss affects ∼15% of all implantation-confirmed human conceptions. However, evolutionarily conserved molecular mechanisms that regulate self-renewal of trophoblast progenitors and their association with early pregnancy loss are poorly understood. Here, we provide evidence that transcription factor TEAD4 ensures survival of postimplantation mouse and human embryos by controlling self-renewal and stemness of trophoblast progenitors within the placenta primordium. In an early postimplantation mouse embryo, TEAD4 is selectively expressed in trophoblast stem cell–like progenitor cells (TSPCs), and loss of Tead4 in postimplantation mouse TSPCs impairs their self-renewal, leading to embryonic lethality before embryonic day 9.0, a developmental stage equivalent to the first trimester of human gestation. Both TEAD4 and its cofactor, yes-associated protein 1 (YAP1), are specifically expressed in cytotrophoblast (CTB) progenitors of a first-trimester human placenta. We also show that a subset of unexplained recurrent pregnancy losses (idiopathic RPLs) is associated with impaired TEAD4 expression in CTB progenitors. Furthermore, by establishing idiopathic RPL patient-specific human trophoblast stem cells (RPL-TSCs), we show that loss of TEAD4 is associated with defective self-renewal in RPL-TSCs and rescue of TEAD4 expression restores their self-renewal ability. Unbiased genomics studies revealed that TEAD4 directly regulates expression of key cell cycle genes in both mouse and human TSCs and establishes a conserved transcriptional program. Our findings show that TEAD4, an effector of the Hippo signaling pathway, is essential for the establishment of pregnancy in a postimplantation mammalian embryo and indicate that impairment of the Hippo signaling pathway could be a molecular cause for early human pregnancy loss.
Large-scale multiple inference of collective dependence with applications to protein function

Measuring the dependence of k≥3 random variables and drawing inference from such higher-order dependences are scientifically important yet challenging. Motivated here by protein coevolution with multivariate categorical features, we consider an information theoretic measure of higher-order dependence. The proposed collective dependence is a symmetrization of differential interaction information which generalizes the mutual information of a pair of random variables. We show that the collective dependence can be easily estimated and facilitates a test on the dependence of k≥3 random variables. Upon carefully exploring the null space of collective dependence, we devise a Classification-Assisted Large scaLe inference procedure to DEtect significant k-COllective DEpendence among d≥k random variables, with the false discovery rate controlled. Finite sample performance of our method is examined via simulations. We apply this method to the multiple protein sequence alignment data to study the residue or position coevolution for two protein families, the elongation factor P family and the zinc knuckle family. We identify novel functional triplets of amino acid residues, whose contributions to the protein function are further investigated. These confirm that the collective dependence does yield additional information important for understanding the protein coevolution compared to the pairwise measures.
The Linked-Convergent Distinction–Refining the Criterion

Recognizing the probative relevance of one statement to another is a matter of having a Peircean belief-habit conveying one from the former to the latter. These habits may be formulated as inference rules. We may thus understand relevance as a ternary relation holding between statements P and Q (or a set of statements {P1, P2, …, Pn} and Q), and a set of inference rules I. P is relevant to Q with respect to I if and only if P/Q instances some rule in I. A necessary condition for two (or more) premises to be linked in supporting some conclusion is that some two (or more) premise inference rule conveys us from the premises to the conclusion. A further necessary condition is that the premises must share a mediating component, a predicate (or predicate schema) occurring in at least two premises but not in the conclusion. These two conditions are jointly sufficient. This is a syntactic criterion for making the linked-convergent distinction. We criticize a number of tests for making the distinction as involving counterintuitive or anomalous results because they apply semantic considerations to do a syntactic job. We argue that recognizing that premises may function as counter-defeaters indicates that Pinto and Blair’s suggestion that we need to identify complementary arguments besides linked and convergent is unnecessary. We conclude the chapter by addressing critical questions raised by Bassham, Vorobej, Gratton, Fisher, Conway, and Goddu.
The ages of anxiety--differences across the lifespan in the default mode network functional connectivity in generalized anxiety disorder.

Objectives Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders, but its neural basis is relatively understudied. This study aims to characterize the functional connectivity in the default mode network (DMN) in GAD across the lifespan. Design and settings Functional and structural magnetic resonance imaging data were collected with subjects at rest. We analyzed the resting state functional connectivity patterns in the DMN for 27 GAD participants and 39 non-anxious comparison participants. Using a two-way analysis of variance, we explored the interaction between age and GAD status on functional connectivity. In GAD participants, we analyzed the correlation of functional connectivity indices with the duration of illness and worry severity. Results The age-by-anxiety interaction showed a greater anxiety effect on the functional connectivity between the posterior cingulate seed and the medial prefrontal cortex for the older group relative to the younger participants. Longer duration of illness was positively correlated with greater functional connectivity between the posterior cingulate cortex and the insula. Worry severity was inversely correlated with the functional connectivity between the posterior cingulate cortex seed and the medial prefrontal cortex. Conclusion The presence of GAD, longer duration of illness, and more severe worry exacerbate the effects of age on the functional connectivity in the DMN. These results support the need for tailored research and interventions in late-life anxiety. Copyright © 2013 John Wiley & Sons, Ltd.
Anaerobic Growth and Denitrification among Different Serogroups of Soybean Rhizobia

We screened soybean rhizobia originating from three germplasm collections for the ability to grow anaerobically in the presence of NO(3) and for differences in final product formation from anaerobic NO(3) metabolism. Denitrification abilities of selected strains as free-living bacteria and as bacteroids were compared. Anaerobic growth in the presence of NO(3) was observed in 270 of 321 strains of soybean rhizobia. All strains belonging to the 135 serogroup did not grow anaerobically in the presence of NO(3). An investigation with several strains indicated that bacteria not growing anaerobically in the presence of NO(3) also did not utilize NO(3) as the sole N source aerobically. An exception was strain USDA 33, which grew on NO(3) but failed to denitrify. Dissimilation of NO(3) by the free-living cultures proceeded without the significant release of intermediate products. Nitrous oxide reductase was inhibited by C(2)H(2), but preceding steps of denitrification were not affected. Final products of denitrification were NO(2), N(2)O, or N(2); serogroups 31, 46, 76, and 94 predominantly liberated NO(2), whereas evolution of N(2) was prevalent in serogroups 110 and 122, and all three were formed as final products by strains belonging to serogroups 6 and 123. Anaerobic metabolism of NO(3) by bacteroid preparations of Bradyrhizobium japonicum proceeded without delay and was evident by NO(2) accumulation irrespective of which final product was formed by the strain as free-living bacteria. Anaerobic C(2)H(2) reduction in the presence of NO(3) was observed in bacteroid preparations capable of NO(3) respiration but was absent in bacteria that were determined to be deficient in dissimilatory nitrate reductase.
Characterization of the resting potential in Chironomus salivary gland cells: evidence for an electrogenic sodium pump.

Abstract The ionic basis of the resting potential (Er) across the plasma membrane of Chironomus thummi salivary gland cells has been investigated. Er was found to vary with developmental stage. The dependence of Er on [K]0 was studied in the presence and absence of external chloride. The results could not be accounted for by the Goldman equation, and they suggested that an electrogenic sodium pump might be present. This was evaluated by repeating the experiments with: (1) external sodium replaced by Tris; (2) addition of 10−5 M ouabain; (3) temperature reduction to 5 °C, and by a combination of these treatments. The results, along with earlier studies by Loewenstein and co-workers, provide strong evidence that 6–10 mV of the resting potential in standard saline is due to a metabolically dependent component. Most, but not all, of the results are consistent with the presence of an electrogenic sodium efflux produced by the Na,K-ATPase. This pump can produce changes in intracellular cation composition consistent with theories of the ionic variation of gene activity. It also explains the depolarization produced by most agents which destroy intercellular electrical communication.
8-channel microdisk CW laser arrays vertically coupled to low-loss common bus waveguides

1.6-nm-spaced, 8-channel microdisk laser arrays are presented, where high-Q disk lasing modes are coupled out through a common bus waveguide. Typical linewidth of 0.25 nm and SMSR of 20 dB are achieved under CW operation.
Learning science by participating in design: a case where multiple design subgoals interfere with systematic progress

Two contrasting teams were analyzed qualitatively in a science unit in which students collaborate in teams to learn science concepts through a design project. The unit was focused on learning concepts of electricity by designing an electronic alarm system. The difference in the success of one of the teams to learn the science content can be attributed to their ability to focus systematic efforts on exploring one lower-level design goal at a time.
Robotic-assisted laparoscopic radical cystectomy in the octogenarian

Background The advanced age and comorbidities often associated with bladder cancer patients creates a difficult scenario regarding further management. Robotic-assisted laparoscopic radical cystectomy (RALRC) has had favorable results as am inimally invasive treatment option. We studied perioperative outcomes of RALRC in octogenarians to discern if there is any added benefi ti n this patient population. Methods One hundred and sixty robotic cystectomies have been performed between October 2003 and June 2010. We identified 24 octogenarians who underwent RALRC and form the cohort of the study. Results Mean patient age was 84.7years and mean BMI was 24kg/m 2 . Most of the patients in the study had serious medical comorbidities, as 82.6% of them had an ASA classification ≥3 and 95.6% had Charlson scores ≥3. There was one open conversion and two patients had positive surgical margins. There were a total of 45 complications in the study, with 14 major complications observed in the 90-day period after surgery. There were five patients who had no complications, and two patients expired as a result of multiple organ failure. At 24months the overall, disease-free and disease-specific survivals were 51.1%, 64.3%, and 79%, respectively. The 90-day mortality rate was 8.7%. Conclusions Octogenarians undergoing RALRC have a significant risk of morbidity and mortality. The relationship between advanced age and oncologic outcomes or complications needs to be discerned further as it relates to the octogenarian. Further study is needed to delineate the safety and efficacy of this approach. Copyright © 2012 John Wiley & Sons, Ltd.
The Fabrication of Facts in Investigation and Adjudication

This paper explores the logical dynamics of investigation. The discussion emphasizes the irreversibility of investigative action and inaction.
Anion exchange of metal complexes—II the cadmium-thiocyanate system

Abstract The distribution of tracer 115 m Cd between Dowex-1, strong base anion exchanger, and solutions of lithium thiocyanate, sodium thiocyanate, potassium thiocyanate and ammonium thiocyanate have been measured. Mononuclear complexes were verified in potassium thiocyanate up to 10 −5 M in tracer. Distribution isotherms were determined for thiocyanate solutions between ∼10 −2 to ∼6 M. Above 0·2 M increasing adsorbability was in the order: Na + > Li + > K + > NH 4 + with a maximum at ∼1 M in each case. These distributions, when invasion was taken into account, gave corrected distribution curves from which the overall complexity parameters related to the neutral complex were evaluated by curve fitting as: k 2+ = 4·0 × 10 −3 ; k 1+ = 0·22; k 1− = 0·1; k 2− = 3·25. Resin sorption effects a 500-fold stabilization of the neutral species over the aqueous phase.
Evaluating CO2 emissions, cost, and service quality trade-offs in an urban delivery system case study

Growing pressure to limit greenhouse gas emissions is changing the way businesses operate. This paper presents the trade-offs between cost, service quality (represented by time window guarantees), and emissions of an urban pickup and delivery system under these changing pressures. A model, developed by the authors in ArcGIS, is used to evaluate these trade-offs for a specific case study involving a real fleet with specific operational characteristics. The problem is modeled as an emissions minimization vehicle routing problem with time windows. Analyses of different external policies and internal operational changes provide insight into the impact of these changes on cost, service quality, and emissions. Specific consideration of the influence of time windows, customer density, and vehicle choice are included. The results show a stable relationship between monetary cost and kilograms of CO2, with each kilogram of CO2 associated with a $3.50 increase in cost, illustrating the influence of fuel use on both cost and emissions. In addition, customer density and time window length are strongly correlated with monetary cost and kilograms of CO2 per order. The addition of 80 customers or extending the time window 100 minutes would save approximately $3.50 and 1 kilogram of CO2 per order. Lastly, the evaluation of four different fleets illustrates significant environmental and monetary gains can be achieved through the use of hybrid vehicles. The results demonstrate there is not a trade-off between CO2 emissions and cost, but that these two metrics trend together. This suggests the most effective way to encourage fleet operators to limit emissions is to increase the cost of fuel or CO2 production, as this is consistent with current incentives that exist to reduce cost, and therefore emissions.
Cost analysis of relined mercaptan rubber impressions

An investigation was conducted to compare the time and amount of material used in a corrective reline impression procedure and in a complete remake of a new double-mix impression. The reline technique required 22.22 gm less material, and the reline technique was achieved in approximately 7.6 minutes less time than that required for a complete remake. This results in a monetary saving while preserving quality.
Using multiple time-series analysis, of assembly-line production of automobile engines — a case study

Abstract In recent years researchers have dealt with multiple time series problems in practically meaningful ways. In this paper, the assembly-line data of a major producer of automobile engines is analyzed and multivariate models are constructed and estimated to investigate the relationship among weekly engine production, downtime and the man-hours worked. The assembly line is operated on a Just-In-Time basis for normally two shifts per five day week. Such an analysis could help them in developing contingency plans consistent with their obligations to the automobile manufacturer they supplied.
Topography and Dislocations in (112)B HgCdTe/CdTe/Si

Scanning electron microscopy (SEM), atomic force microscopy (AFM), and x-ray diffraction (XRD) measurements all indicate an approximate factor of ten increase in the Everson etch pit density (EPD) over standard Nomarski microscopy Everson EPD determination. A new (112)B CdTe/Si EPD etch has also been demonstrated which reduces the surface roughness of the etched epilayer and makes etch pit density determination less problematic.
How novices formulate models. Part I: qualitative insights and implications for teaching

Teaching novices how to formulate mathematical models for ill-structured problems is a challenging task. Little is known about how novices approach ill-structured problems and how their performance differs from that of experts. We audiotaped 28 MBA students while they worked through four ill-structured modelling problems. The task in each problem was to begin to develop a model that could ultimately be used for forecasting or analysis of alternative courses of action. We analysed transcripts of these think-aloud protocols both quantitatively and qualitatively. We observed five behaviours that are not typical of experts and that limit the effectiveness of our subjects. These include: over-reliance on given numerical data, taking shortcuts to an answer, insufficient use of abstract variables and relationships, ineffective self-regulation, and overuse of brainstorming relative to structured problem solving. We conclude that an effective modelling pedagogy should teach how to: formulate models both in the presence and the absence of data, abstract variables and relationships, employ control strategies for self-regulation, and use structured problem-solving methods.