cssi/SciSciGPT-SciSciNet huggingface dataset:
Autophagy controls the kinetics and extent of mitochondrial apoptosis by regulating PUMA levels

Macroautophagy is thought to protect against apoptosis; however, underlying mechanisms are poorly understood. We examined how autophagy affects canonical death receptor-induced mitochondrial outer membrane permeabilization (MOMP) and apoptosis. MOMP occurs at variable times in a population of cells, and this is delayed by autophagy. Additionally, autophagy leads to inefficient MOMP, after which some cells die through a slower process than typical apoptosis and, surprisingly, can recover and divide afterward. These effects are associated with p62/SQSTM1-dependent selective autophagy causing PUMA levels to be kept low through an indirect mechanism whereby autophagy affects constitutive levels of PUMA mRNA. PUMA depletion is sufficient to prevent the sensitization to apoptosis that occurs when autophagy is blocked. Autophagy can therefore control apoptosis via a key regulator that makes MOMP faster and more efficient, thus ensuring rapid completion of apoptosis. This identifies a molecular mechanism whereby cell-fate decisions can be determined by autophagy.
Progressive, idiosyncratic changes in wood hardness during decay: Implications for dead wood inventory and cycling

Abstract Coarse woody debris (CWD) plays important roles in forests including carbon storage. Calculating the size of this carbon pool from survey data entails estimating the volume and density of dead wood. Density is highly correlated with other mechanical parameters in intact wood, explaining how penetrometers, which measure a mechanical parameter related to hardness, have proven useful for estimating dead wood density. However, the relationship between wood density and hardness varies with three key factors that vary in CWD: moisture content, tree species and degree of decay. We estimated how these factors influence penetrometer measurements across conditions ranging from lab standards to field conditions during a CWD survey. When measuring experimentally decayed wood under standard conditions, penetrometer distance was highly correlated with sample density and the effects of moisture content and interspecific variation were similar to those expected from analyses of intact wood. However, when we relaxed experimental controls and included samples that had decayed for different lengths of time, these relationships shifted such that penetrometer measurements no longer correlated with intact wood hardness and tended to increase relative to density and moisture content. The decoupling of mechanical properties in decaying wood is consistent with case hardening, which developed differently in different species and contributed to high variability in penetrometer measurements during the CWD survey. These results demonstrate temporal changes in decaying wood mechanical properties that have implications for surveying CWD and understanding carbon dynamics in temperate hardwood forests.
DifA, a Methyl-Accepting Chemoreceptor Protein-Like Sensory Protein, Uses a Novel Signaling Mechanism to Regulate Exopolysaccharide Production in Myxococcus xanthus

DifA is a methyl-accepting chemotaxis protein (MCP)-like sensory transducer that regulates exopolysaccharide (EPS) production in Myxococcus xanthus. Here mutational analysis and molecular biology were used to probe the signaling mechanisms of DifA in EPS regulation. We first identified the start codon of DifA experimentally; this identification extended the N terminus of DifA for 45 amino acids (aa) from the previous bioinformatics prediction. This extension helped to address the outstanding question of how DifA receives input signals from type 4 pili without a prominent periplasmic domain. The results suggest that DifA uses its N-terminus extension to sense an upstream signal in EPS regulation. We suggest that the perception of the input signal by DifA is mediated by protein-protein interactions with upstream components. Subsequent signal transmission likely involves transmembrane signaling instead of direct intramolecular interactions between the input and the output modules in the cytoplasm. The basic functional unit of DifA for signal transduction is likely dimeric as mutational alteration of the predicted dimeric interface of DifA significantly affected EPS production. Deletions of 14-aa segments in the C terminus suggest that the newly defined flexible bundle subdomain in MCPs is likely critical for DifA function because shortening of this bundle can lead to constitutively active mutations.
Effect of modifying quantum dot surface charge on airway epithelial cell uptake in vitro

The respiratory system is one of the portals of entry into the body, and hence inhalation of engineered nanomaterials is an important route of exposure. The broad range of physicochemical properties that influence biological responses necessitate the systematic study to contribute to understanding occupational exposure. Here, we report on the influence of nanoparticle charge and dose on human airway epithelial cells, and show that this platform can be used to evaluate consequences of exposure to engineered nanomaterials.
Tracing the Arc: The Shifting Conceptualizations of Educational “Disadvantage” and “Diversity” at the University of Wisconsin-Madison

This article calls attention to the shifting conceptualizations of belonging and inclusion at universities in the U.S. through shifting framings of “educational disadvantage” and “diversity”. Historically these concepts have been used in various and shifting ways to think about the “Other” and to determine the lines of inclusion and exclusion to access to higher education spaces. This article uses a leading public university, the University of Wisconsin-Madison, as a historical case study to examine the ways the university has responded to those who have historically been excluded from public higher education spaces and the ways inclusion has been expanded and redefined through struggle. This case study is an invitation to carefully consider the current discourses and policy debates about university “diversity” efforts and the inclusion of “disadvantaged” students. We raise questions about what inclusion means.
Severe Complications of Inflammatory Bowel Disease

Patients who have inflammatory bowel disease occasionally develop severe complications or emergency situations that require expert and expedited medical care, including toxic colitis, fistulas, abdominal abscesses, malignancy, primary sclerosing cholangitis, and pouchitis. Morbidity and mortality rates of Crohn's disease and ulcerative colitis are increased over the expected rates in the unaffected population. Knowledge of the presenting features, natural history, and treatment of these complications should to lead to early and effective therapy and better outcomes.
Induction accelerator test module for HIF

An induction linac test module suitable for investigating the drive requirements and the longitudinal coupling impedance of a high-power ion induction linac has been constructed by the heavy ion fusion (HIF) group at LBL (Lawrence Berkeley Laboratory). The induction linac heavy ion driver for inertial confinement fusion (ICF) as presently envisioned uses multiple parallel beams which are transported in separate focusing channels but accelerated together in the induction modules. The resulting induction modules consequently have large beam apertures-1-2 m in diameter-and correspondingly large outside diameters. The module geometry is related to a low-frequency gap capacity and high-frequency structural resonances, which are affected by the magnetic core loading and the module pulser impedance. A description of the test module and preliminary results are presented. >
Transmural intestinal penetration of polyester fibers as an uncommon cause of peritoneal adhesions in a dog.

11 However, foreign material can be a problem in veterinary and human medicine, particularly if ingested. The ability of anchored linear threads. to cause mesenteric intestinal perforation is legendary, 4 and intra-abdominal gauze sponges, although fre- quently retained asymptomatically for long intervals follow- ing surgery, may cause intestinal perforation from the serosal surface or mediate the formation of abdominal pseudotu- mors, termed textilomas. 5,14 The long-term retention of sponges or sutures has been associated with development of neoplasia later in life. 10
Gas storage in porous metal–organic frameworks for clean energy applications

Depletion of fossil oil deposits and the escalating threat of global warming have put clean energy research, which includes the search for clean energy carriers such as hydrogen and methane as well as the reduction of carbon dioxide emissions, on the urgent agenda. A significant technical challenge has been recognized as the development of a viable method to efficiently trap hydrogen, methane and carbon dioxide gas molecules in a confined space for various applications. This issue can be addressed by employing highly porous materials as storage media, and porous metal–organic frameworks (MOFs) which have exceptionally high surface areas as well as chemically-tunable structures are playing an unusual role in this respect. In this feature article we provide an overview of the current status of clean energy applications of porous MOFs, including hydrogen storage, methane storage and carbon dioxide capture.
The interaction of radiation with charged particles

The equation-of-motion technique is used to obtain dispersion relations describing the propagation of radiation in an electron gas. Dispersion relations are obtained for the case of no external field and for the case of a uniform magnetic field.
Differential development of tolerance to the effects of d-amphetamine and fenfluramine on food intake in baboons.

Food intake of six adult male baboons (Papio cynocephalus anubis) was monitored during daily 22-hr experimental sessions. Food was available under a chain schedule with two components. After completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the second "consumption component," during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. Complete dose-response functions for amphetamine and fenfluramine were determined before, during and after a period of repeated administration of each drug. On the first day of repeated administration both drugs decreased intake during both the first 8 hr and the entire session to 65% of baseline. Total intake returned to 93% of baseline during repeated amphetamine, but only to 76% of baseline during repeated fenfluramine. There was no recovery of intake, however, during the first 8 hr of the session. Baboons given repeated amphetamine were tolerant to the food intake decreasing effects of acute amphetamine, but not acute fenfluramine. Baboons given repeated fenfluramine did not develop tolerance to the effects of fenfluramine or amphetamine on food intake. The absence of cross-tolerance or increased sensitivity between amphetamine and fenfluramine suggests that although both serotonergic and dopaminergic systems are involved in feeding, they can influence food intake independently.
Relational empathy and holistic care in persons with spinal cord injuries

Objective: Describe perceptions of persons with SCI on their receipt of holistic care and relational empathy during health care encounters.Design: Mailed survey.Participants/Setting: Individuals with SCI who received care from the largest suppliers of SCI care and rehabilitation (Veterans Health Administration and SCI Model Systems).Outcome Measures: Using a survey and administrative databases, we collected demographic and injury characteristics, health status, health conditions, and the main outcome: Consultation and Relational Empathy (CARE) measure.Results: The sample included 450 individuals with SCI (124 Veterans and 326 civilians). Response rate was 39% (450/1160). Analyses were conducted on patients with complete data (n = 389). Veterans and civilians with SCI differed across many demographic characteristics, age at injury, and etiology, but mean CARE scores were equivalent. Fewer than half of the full SCI cohort had CARE scores above the normative value of 43. Having a recent pressure ulcer showed...
Characterization of transverse isotropy in compressed tissue mimicking phantoms

Tissues such as skeletal muscle and kidneys have well-defined structure that affects the measurements of mechanical properties. As an approach to characterize the material properties of these tissues, different groups have assumed that they are transversely isotropic (TI) and measure the shear wave velocity as it varies with angle with respect to the structural architecture of the organ. To refine measurements in these organs, it is desirable to have tissue mimicking phantoms that exhibit similar anisotropic characteristics. Some approaches involve embedding fibers into a material matrix. However, if a homogeneous solid is under compression due to a static stress, an acoustoelastic effect can manifest which makes the measured wave velocities change with the compression stress. We propose to exploit this characteristic to demonstrate that stressed tissue mimicking phantoms can be characterized as a TI material. We tested four gelatin phantoms made with different concentrations of gelatin. Stress was applied by the weight of a water container centered on top of a plate on top of the phantom. A linear array transducer and a V-1 Verasonics system (Verasonics, Inc., Redmond, WA) were used to induce and measure shear waves in the phantoms. The shear wave motion was measured using a compound plane wave imaging technique and applying autocorrelation to the received in-phase/quadrature data. The shear wave velocity, c, was estimated using a Radon transform method. The transducer was mounted on a rotating stage so measurements were made every 10° over a range of 0–360°, where the stress is applied along 0–180° direction. The shear moduli were estimated. A TI model was fit to the data and the fractional anisotropy was evaluated. This approach can be used to explore many configurations of transverse isotropy with the same phantom, simply by applying stress to the tissue mimicking phantom.
Effect of trypsin and chymotrypsin on the granuloma pouch.

SummaryTrypsin and chymotrypsin, given parenterally through various injection routes, did not alter the growth of granulation tissue forming in response to a chronic sterile inflammation in the rat.
Ecology of Hunterellus hookeri (Hymenoptera: Encyrtidae) and Evaluation of Its Impact on Ixodes scapularis (Acari: Ixodidae) on Nonamesset Island in Massachusetts

The impact of Hunterellus hookeri Howard on Ixodes scapularis Say was examined in 1990–1992 at a site in coastal Massachusetts where the parasitoid was released in 1926. Rates of nymphal parasitism were estimated from regression as 25, 21, and 26% for the 3 yr of observation. Analysis of the rates of decline in percentage parasitism values from samples of field-collected nymphs that were dissected immediately compared with subsamples held in the laboratory for 0–4 mo suggests that parasitized nymphs experience enhanced mortality (before parasitoid emergence) compared with unparasitized nymphs. Voltinism and host preferences of H. hookeri also were examined. Analysis of developmental times and seasonality of hosts suggests that >1 generation per year of H. hookeri is unlikely in southeastern Massachusetts. Significantly more I. scapularis nymphs than larvae became parasitized when these stages were exposed together to H. hookeri while feeding on a laboratory mouse. H. hookeri also parasitized 9% of fed, detached I. scapularis larvae that were exposed in a petri dish. Parasitism rates of fed I. scapularis larvae collected from Peromyscus leucopus (Rafinesque) in the field and larvae exposed to H. hookeri while feeding on P. leucopus in a laboratory arena were low (1% and 6%, respectively). These rates are too low to account for the level of parasitism seen in the field in unfed, questing nymphs (21–26%). This finding implies that while some parasitism may occur on mice under field conditions, larger mammals or detached larval ticks must be the principal site where H. hookeri encounters and oviposits in ticks. Further field studies of parasitism of larval ticks on larger mammals would be needed to clarify this issue.
Effect of sweetpotato latex on sweetpotato weevil (Coleoptera: Curculionidae) feeding and oviposition

Latex in some laticiferous plants acts as a natural defense system against certain herbivores. The potential of latex produced by the sweet potato as a defense mechanism against the sweet potato weevil, Cylas formicarius (F.) was investigated. Genetic and environmental differences were found in latex production in a broad cross section of sweet potato germ plasm (96 lines). Most lines produced 2.6-10 mg fresh weight x vine -1 of latex when the 2nd inter node from the apex was severed. Some lines, however, produced more, the highest being 48.3 mg X vine-1. Young vine material produced more latex and had less weevil feeding damage than older more mature portions of the vine. Application of latex to the surface of root cores reduced feeding and oviposition. Addition of latex to a semi-artificial media also significantly reduced the number of feeding punctures. Leaf feeding location (veins) and direction (basipetal), however, were not indicative of a major deterrent role for latex against the sweet potato weevil.
Multiple Fano Resonances in Plasmonic Metamaterials Composed of Al/Al2O3 Nanomatryushka Structures

Metamaterial structures composed of ordered arrays of metallic nanoparticles (NPs) and nanocavities are able to support strong plasmon and Fano resonances in the optical frequencies, where the appeared Fano dips can be utilized in bio/chemical sensing and spectroscopic purposes with a significant sensitivity. Herein, we utilize two concentric compositional Aluminum (Al) nanoshells (Al/Al 2 O 3 ) to design nanomatryushka (NM) structures in periodic arrays, where each one of Al NPs is covered by a certain thickness of the oxide layer. Depositing studied Al NM arrays on metasurfaces, we determined the optical response of the metamaterial. It is shown that the proposed structure is able to support multiple strong Fano resonances in the visible spectrum. Evaluating the plasmon response of the metamaterial configuration for the presence of various semiconductor metasurfaces (Silicon and GaP), the quality of Fano dips is analyzed for different regimes. In this method, we measured the accuracy and sensitivity of the metamaterial structure by plotting the linear figure of merit (FoM) and quantifying this parameter.
Contamination with bacterial zoonotic pathogen genes in U.S. streams influenced by varying types of animal agriculture

Animal waste, stream water, and streambed sediment from 19 small (<32km(2)) watersheds in 12U.S. states having either no major animal agriculture (control, n=4), or predominantly beef (n=4), dairy (n=3), swine (n=5), or poultry (n=3) were tested for: 1) cholesterol, coprostanol, estrone, and fecal indicator bacteria (FIB) concentrations, and 2) shiga-toxin producing and enterotoxigenic Escherichia coli, Salmonella, Campylobacter, and pathogenic and vancomycin-resistant enterococci by polymerase chain reaction (PCR) on enrichments, and/or direct quantitative PCR. Pathogen genes were most frequently detected in dairy wastes, followed by beef, swine and poultry wastes in that order; there was only one detection of an animal-source-specific pathogen gene (stx1) in any water or sediment sample in any control watershed. Post-rainfall pathogen gene numbers in stream water were significantly correlated with FIB, cholesterol and coprostanol concentrations, and were most highly correlated in dairy watershed samples collected from 3 different states. Although collected across multiple states and ecoregions, animal-waste gene profiles were distinctive via discriminant analysis. Stream water gene profiles could also be discriminated by the watershed animal type. Although pathogen genes were not abundant in stream water or streambed samples, PCR on enrichments indicated that many genes were from viable organisms, including several (shiga-toxin producing or enterotoxigenic E. coli, Salmonella, vancomycin-resistant enterococci) that could potentially affect either human or animal health. Pathogen gene numbers and types in stream water samples were influenced most by animal type, by local factors such as whether animals had stream access, and by the amount of local rainfall, and not by studied watershed soil or physical characteristics. Our results indicated that stream water in small agricultural U.S. watersheds was susceptible to pathogen gene inputs under typical agricultural practices and environmental conditions. Pathogen gene profiles may offer the potential to address both source of, and risks associated with, fecal pollution.
On Withdrawal of Provision for Bad Bebts

Enterprises should follow the principle of prudential and withdraw provision for bad debts in accordance with regulations specified by accounting principles. They should reasonably estimate bad debts according to previous experiences, financial position and flow of the debtor as well as other information concerned. They ought to confirm present balance of provision for bad debts by different means, and meanwhile, consider present balance and adjust the original balance to present one.
Understanding the Complex Universe and Role of Fixed-Income Funds as Investment Vehicles

The bond market has come a long way since 1970, when prices were fairly stable and the types of bonds were quite limited. So dull was the bond market prior to 1970, that many investors still remember when they were told that bond exposure should be proportional to one’s age. If you were lucky enough to have lived to the ripe age of 80, then, according to this old adage, you should have 80% of your investments in bonds. Likewise, this rule of thumb limits your exposure to bonds to 20% if you are only 20 years of age.
Iterative design of feedback and feedforward controller with input saturation constraint for building temperature control

In this paper, an iterative design of feedforward and feedback controller is proposed for a building temperature regulation application. An iterative learning control (ILC) strategy is utilized to eliminate the influence of repetitive disturbance and an iteratively tuned feedback controller is applied to reduce the influence of non-repetitive disturbance components. With constraints from input saturation, the controller design is formulated into a constrained optimization problem. To reduce the complexity of the problem, an alternating procedure is proposed to solve the optimization problem, separating the original problem into two parts, namely, constrained ILC problem and iterative feedback tuning problem. The proposed algorithm is demonstrated by simulations on a four-room testbed system.
The Influence of Weight Status Duration on Weight Perception Accuracy.

Purpose To examine the association between weight status duration and weight perception accuracy. Design Retrospective study. Setting National Health and Nutrition Examination Survey 2003 to 2006. Sample A total of 4029 adults aged 20 years or older. Measures To assess weight status duration, participants' past (10 years ago) and present body mass indexes were used to create 4 groups: normal weight in the past and present (group 1), normal weight in the past but overweight/obese in the present (group 2), overweight/obese in the present but not in the past (group 3), and overweight/obese in the past and present (group 4). We classified individuals as having an accurate/inaccurate weight perception based on present body mass index and whether they considered themselves as overweight, underweight, or about the right weight. Analysis Logistic regression. Results Our findings suggest that participants who were overweight/obese in the past, present, or during both time periods had increased odds of possessing an inaccurate weight perception. Furthermore, being normal weight in the past but obese in the present increased the odds of having an inaccurate weight perception nearly 10-fold and almost 5-fold for those obese in both the past and present. Conclusion Studies such as this can aid clinicians in identifying individuals who may have increased odds of inaccurately identifying their weight status, thereby providing additional opportunities to facilitate weight loss.
Phytochrome in etiolated annual rye. IV. Physical and chemical characterization of phytochrome.

Abstract Isolated phytochrome was demonstrated to be free from all but trace impurities by high speed velocity and equilibrium ultracentrifugation, polyacrylamide electrophoresis, and gel filtration in Sephadex G-200. The results from these techniques and from electron microscopy, amino acid analyses, and tryptic peptide separations were consistent with the native phytochrome molecules existing as 14-S hexamers and 9-S tetramers of 2-S monomer units. The monomer unit appears to be chemically identical, existing as a single polypeptide chain of approx. 42 000 molecular weight. These monomer units appear to be associated through noncovalent type bonds. Fluorescence studies indicated that when the 660 nm-absorbing form of phytochrome was excited at 290 nm, it fluoresced intensely at 340 nm and slightly at 672 nm. When excited at 370 nm, it fluoresced at 672 nm.
Technical Note: Insertion of digital lesions in the projection domain for dual-source, dual-energy CT

Purpose To compare algorithms performing material decomposition and classification in dual-energy CT, it is desirable to know the ground truth of the lesion to be analyzed in real patient data. In this work, we developed and validated a framework to insert digital lesions of arbitrary chemical composition into patient projection data acquired on a dual-source, dual-energy CT system. Methods A model that takes into account beam-hardening effects was developed to predict the CT number of objects with known chemical composition. The model utilizes information about the x-ray energy spectra, the patient/phantom attenuation, and the x-ray detector energy response. The beam-hardening model was validated on samples of iodine (I) and calcium (Ca) for a second-generation dual-source, dual-energy CT scanner for all tube potentials available and a wide range of patient sizes. The seven most prevalent mineral components of renal stones were modeled and digital stones were created with CT numbers computed for each patient/phantom size and x-ray energy spectra using the developed beam-hardening model. Each digital stone was inserted in the dual-energy projection data of a water phantom scanned on a dual-source scanner and reconstructed with the routine algorithms in use in our practice. The geometry of the forward projection for dual-energy data was validated by comparing CT number accuracy and high-contrast resolution of simulated dual-energy CT data of the ACR phantom with experimentally acquired data. Results The beam-hardening model and forward projection method accurately predicted the CT number of I and Ca over a wide range of tube potentials and phantom sizes. The images reconstructed after the insertion of digital kidney stones were consistent with the images reconstructed from the scanner, and the CT number ratios for different kidney stone types were consistent with data in the literature. A sample application of the proposed tool was also demonstrated. Conclusion A framework was developed and validated for the creation of digital objects of known mineral composition, and for inserting the digital objects into projection data from a commercial dual-source, dual-energy CT scanner. Among other applications, it will allow a systematic investigation of the impact of scan and reconstruction parameters on kidney stone dual-energy properties under rigorously controlled conditions.
Health insurance subsidies and the expansion of an implicit marriage penalty: a regional comparison of various means-tested programmes

ABSTRACTAny subsidy provision for healthcare premiums, including those embedded in Affordable Care Act (ACA), has the potential to result in some couples facing an implicit penalty when married relative to unmarried. To illustrate such consequences of means-tested subsidies of health insurance premiums, we construct hypothetical households earning different levels of income who are eligible for current subsidies in the USA. and compare the estimated implicit marriage penalty faced by these households to the one faced by low-income households who are eligible for various means-tested programmes (e.g. TANF, WIC, SNAP) for each of the 48 contiguous states. We find that, like very low-income households, marriage can potentially penalize couples who receive health insurance premium subsidies by decreasing their overall disposable income by as much as 14%. We find that the ACA increases the number of households subject to marriage penalties embedded in means-tested programmes for low-income couples. This distor...
Economic Perspectives on the Restatement of the Law on Liability Insurance Project

This paper provides perspectives on the Restatement of the Law, Liability Insurance (RLLI) project in view of theory and evidence on the economics of liability insurance and the operation and regulation of liability insurance markets. The RLLI project reflects prodigious effort by the Reporters over six years, and many revisions in response to feedback in the drafting process and the project’s evolution from Principles to Restatement. My focus is on the proposed black letter rules regarding insurers’ defense obligations and other issues that would expand policyholder rights compared with existing law in a significant number or even majority of jurisdictions. These proposed rules reflect an emphasis on the potential advantages to insureds facing legal actions of expanding their post-claim rights and protections, with relatively little attention paid to the potential impacts on insurance prices, coverage terms, and demand for coverage ex ante. Such proposals risk significant disruption of current law with uncertain, unintended, and adverse consequences on liability insurance markets in the form of higher prices, less availability of coverage, reductions in policy limits purchased, aggravation of the judgment proof problem, and increased adverse selection and moral hazard.
Missense variants in Lynch Syndrome genes in endometrial cancer patients characterized by The Cancer Genome Atlas (TCGA) project.

1547 Background: We sought to characterize the missense variants in the Lynch Syndrome genes in patients with endometrial cancer that had normal germline DNA characterized by TCGA. Methods: We obtained institutional IRB approval and approval from the National Center for Biotechnology Information Genotypes and Phenotypes Database (NCBI dbGaP) for data access to TCGA data files. We utilized Variant Call Format (VCF) files to annotate germline single nucleotide variants in exomic regions of the Lynch Syndrome genes (MLH1, MSH2, MSH6, PMS2) among 248 patients with endometrial cancer. We used the MetaLR composite score from Annovar, which combines data from SIFT, PolyPhen2, LRT, MutationTaster, MutationAssessor, FATHMM, GERP++, PhyloP and SiPhy for prediction of variant effects on protein function. Results: A total of 120 different missense variants from 248 patients were found in the Lynch Syndrome genes (8 in MLH1, 26 in MSH2, 41 in MSH6, 45 in PMS2). 82 (68%) of these variants were novel and were not annota...
Dreading Crispr: GMOs, Honest Brokers, And Mertonian Transgressions

Newly arriving biotechnologies are beginning to force us all—scientists, policy makers, and the public—to confront questions of extraordinary difficulty. We will urgently need scientists to act as ...
Physiology and Pharmacology of Peptide, Steroid, and Other Hormones in Cerebrospinal Fluid

The concept of peptide secretion by neurons was first proposed by Scharrer and Scharrer201 in 1940. The identification of the hypothalamic hypophysiotropic hormones, thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), and somatostatin, between 1969 and 1972 and subsequent studies elicidated the neurophysiology of pituitary hormone release and peripheral endorcrine regulation.38 Recently, the isolation of substance P (SP)147 and neurotensin55 from the hypothalamus and the discovery of the endogenous opioid peptides83,84 have resulted from the intensified investigation of central neuroregulation by peptide, steroid, and other hormones. The secretion and function of peptides in the centralnervous tissue (Table 1) have recently been reviewed.38,106,107,124
Carrying Plant Knowledge Forward in the USA

Botany education steadily declines in the USA as universities eliminate traditional botany courses, and plant science is integrated into interdisciplinary studies. Botanical expertise is essential to addressing the current and pending challenges with the environment. Surveys indicate that individuals are not being trained with the skills and knowledge needed to fill jobs in science and resource management. Yet, never before has it been more critical to understand the pivotal role plants play in our own health and well-being. A recent study in the USA has identified critical gaps in botanical capacity and has made recommendations to enhance education and training in the botanical sciences. Educators surveyed indicate a broad spectrum of interests, aptitudes, and obstacles in passing along plant knowledge to the next generation. Increasingly, nontraditional education centers are filling the gap for botanical education. The National Science Foundation (NSF) issued a call for action in higher education to move biology teaching towards reform. A national conversation, fueled by a revolution taking place in the biological sciences, is magnifying the need for change in the way we are preparing students to work and contribute in a rapidly changing scientific and technological society. The emerging field of ethnobiology education is positioned and ready to lead the way for change in the way students learn and gain understanding of the nature of science. We must continue to find effective ways to engage young minds in botanical science to ensure the transfer of critical knowledge and skills needed to meet the challenges ahead.
32. Laparoscopic Inguinal Hernia Repair: Transabdominal Preperitoneal and Totally Extraperitoneal Approaches

Laparoscopic herniorrhaphy is the minimally invasive approach to the preperitoneal space, where all hernias of the myopectineal orifice in the pelvic floor can be identified and repaired. This advantage, coupled with the benefits of decreased postoperative pain and a quicker recovery has made it a valuable skill to be mastered by the general surgeon. It can be an especially useful approach for bilateral and recurrent inguinal hernias, though it is appropriate for selected patients with primary unilateral inguinal hernias as well. Two approaches to laparoscopic herniorrhaphy are used: totally extraperitoneal (TEP) and transabdominal preperitoneal (TAPP). Each has a different approach to the preperitoneal space but with similar repair techniques. Mastery of the preperitoneal anatomy is essential in limiting technical complications. Potential complications associated with laparoscopic inguinal hernia repair include bleeding, vascular and urologic injuries, nerve injury (chronic pain), and recurrence. Mesh size and type are also important factors that affect short- and long-term outcomes. Finally, as with all surgical procedures, there are technical nuances and controversies that can be individualized to the procedure based on clinical data and surgeon preference.
How emotions are made: The secret life of the brain.

Introduction - i: Introduction: The Two Thousand Year Old Assumption Chapter - 1: The Search For Emotion's ''Fingerprints'' Chapter - 2: Emotions Are Constructed Chapter - 3: The Myth of Universal Emotions Chapter - 4: The Origin of Feeling Chapter - 5: Concepts, Goals, and Words Chapter - 6: How the Brain Makes Emotions Chapter - 7: Emotions As A Social Reality Chapter - 8: A New View of Human Nature Chapter - 9: Mastering Your Emotions Chapter - 10: Emotions and Illness Chapter - 11: Emotion and the Law Chapter - 12: Is a Growling Dog Angry? Chapter - 13: From Brain to Mind: The New Frontier Acknowledgements - ii: Acknowledgments Section - iii: Appendix A: Brain Basics Section - iv: Appendix B: Supplement for Chapter 2 Section - v: Appendix C: Supplement for Chapter 3 Section - vi: Appendix D: Evidence for the Concept Cascade Section - vii: Bibliography Section - viii: Notes Section - ix: Illustration Credits Index - x: Index
Virtual meeting ground for colonial (re)Interpretation of the Banda Islands, Indonesia

This paper presents a conceptual project aimed to create a digital archive pertaining to the colonial past of the Banda Islands. This archive not only offers a bottom-up opportunity to gather archival material through crowdsourcing but could also be connected to an interactive virtual map that connects this information real-time. As crowdsourcing would be a main tool, this archive has the potential to function as a platform where both the former colonizer and colonized can reflect on the past, moreover, it will provide scholars a source of information to revisit the history of the Banda Islands.
Phospholipid Synergy in Prothrombinase Activity

Abstract 1175 Most steps in the blood coagulation cascade obligatorily take place on membrane surfaces and are dependent on the exposure of phosphatidylserine (PS). Previous studies from our lab and others have shown that phosphatidylethanolamine (PE) poorly supports clotting reactions by itself, but strongly synergizes with PS to promote several membrane-dependent steps in the blood clotting cascade, although the mechanism for PE-PS synergy has been unclear. We recently put forward a new mechanistic explanation – which we termed the ABC or Anything But Choline hypothesis – for how PS and PE synergize to enhance factor X (fX) activation by the factor VIIa-tissue factor complex (Tavoosi et al., J. Biol. Chem. 286:23247–53, 2011). The membrane contribution to this reaction is dominated by the affinity of fX for the membrane surface; since fX binds to membranes via its gamma-carboxyglutamate-rich (GLA) domain, the ABC hypothesis therefore focuses on the mechanisms by which GLA domains engage the phospholipid bilayer. We identified two main types of GLA domain-phospholipid interactions: a single phospho-L-serine-specific binding site in each GLA domain; and multiple ”phosphate-specific” interactions in which the phosphate groups of non-phosphatidylcholine phospholipids form coordination complexes with the tightly bound calcium ions in GLA domains. In the current study, we test the ABC hypothesis in the context of the prothrombinase complex – i.e., activation of prothrombin by the membrane-bound complex of fXa and factor Va (fVa). Using a variety of approaches including surface plasmon resonance analyses, we measured the contributions of varying phospholipid compositions to the membrane binding affinities of fXa, fVa and prothrombin, as well as to the enzymatic activity of prothrombinase. Our results suggest that phospholipid synergy in prothrombinase activity differs in certain respects from that observed for the factor VIIa-tissue factor complex. Not only did PS synergize with PE for enhancing the activity of prothrombinase, but phosphatidylglycerol (PG) and phosphatidylacid (PA) also synergized with PE, albeit more weakly than with PS (i.e., significantly higher levels of PG or PA in the presence of PE were required to achieve prothrombinase activities comparable to mixtures of PS and PE). In contrast, PE failed to synergize with either PG or PA to support fX activation by the factor VIIa-tissue factor complex. These differences primarily arise from differential membrane binding of the substrates for these two complexes (fX for factor VIIa-tissue factor and prothrombin for prothrombinase). The data suggest that the phospho-L-serine-specific binding site in the GLA domain of prothrombin may not be as stringent as that of fX, as high levels of PG or PA can substitute for PS in membrane binding of prothrombin but not for fX. This study provides further insights into the membrane9s role in regulating blood clotting reactions, specifically the binding interactions between GLA domains and membrane surfaces. Disclosures: No relevant conflicts of interest to declare.
Legal Briefs: Multiple Missteps and System Failures Cause Kernicterus in 2 Infants

EDITOR’S NOTE The Legal Briefs feature is based on actual malpractice cases with opinions of the plaintiff and defense physician experts interspersed throughout the case. The format of this feature does not provide evidence that supports or refutes each of these opinions. A 3,350-g, 38-week-gestation Asian female infant is delivered via vacuum-assisted delivery. Her Apgar scores were 3 and 8 at 1 and 5 minutes, respectively. Her physical examination findings were normal. A 4% weight loss was found at 25 hours, which was 12 hours before discharge. She was not weighed again. She was exclusively breastfed and discharged at 37 hours. The plaintiff neonatologist pointed out that tracking an infant’s weight provides a useful assessment of adequacy of breast milk intake and that a loss greater than 3% at 24 hours should have prompted an evaluation; the plaintiff discussed that at a minimum, the infant should have had a repeat weight check for accuracy and another weight assessment before discharge, and if equivocal, a weight check the following day. A weight measurement immediately before and after breastfeeding is very useful. The bilirubin level was not evaluated before discharge. The plaintiff neonatologist was critical of this omission, especially because this infant had multiple risk factors including Asian ancestry, vacuum-assisted delivery, perhaps excessive weight loss, early discharge, and exclusive breastfeeding. The mother was instructed to call for a pediatric appointment in 5 days, but when the mother tried to make an appointment, she was told that no appointments were available until the infant was 7 days old. The plaintiff neonatologist was critical of the infant not being assessed sooner because of the various risk factors. When the infant was evaluated by the pediatrician at 7 days, the mother shared with the physician that the infant’s eyes were very yellow. According to the …
Noninvasive Vascular Testing for the Trauma Patient

For decades, the management of traumatic vascular injuries to the extremity has challenged surgeons. However, even during the dark times of conflict in the United States, where surgeon faced an inordinate amount of mangled extremities, surgical technique was advanced and not only benefited military personnel but eventually civilian victims. Parallel to the course of surgery with movement toward minimally invasive techniques, the diagnosis of vascular trauma has progressed from an invasive, often low-yielding surgical exploration to a selective, noninvasive paradigm. Outside of overt signs of vascular injury (e.g., pulsatile bleeding), reliance solely on physical examination lacked the sensitivity to support an adoption of a less invasive diagnostic approach. Ankle-brachial index (ABI) was paramount in guiding clinicians to proper selection of injured patients who benefited from further diagnostic investigations or observation. Color-flow duplex scanning also contributed to a noninvasive diagnostic testing for vascular injuries in the extremity. However, due to variability in results based on technician expertise, off-hour unavailability, and stagnant technological movement the role of color-flow duplex remained limited. Conversely, computed tomography is emerging as the diagnostic modality of choice for vascular trauma. Current multi-detector units allow accurate acquisition of long body segment in minutes. Due to the increasing application of computed tomography (CT) angiography, digital subtraction angiography has been relegated from the “gold standard” diagnostic modality to a treatment modality. This chapter discusses the progression of this overall change in the diagnostic management of patients with traumatic vascular injuries.
On the possibility of direct triplet state excitation of indole

We studied the luminescence properties of indole in poly (vinyl alcohol) (PVA) film. The indole molecules are effectively immobilized in this polymer film and display both fluorescence and phosphorescence emission at room temperature. We noticed that the phosphorescence of indole in PVA film can be effectively excited at a longer wavelength than its typical singlet to triplet population route involving intersystem crossing. The maximum of the phosphorescence excitation is about 410 nm which corresponds to the energy of indole's triplet state. Interestingly, the phosphorescence anisotropy excited with the longer wavelength (405 nm) is positive and reaches a value of about 0.25 in contrast to the phosphorescence anisotropy excited within the indole singlet absorption spectrum (290 nm), which is negative. Very different temperature dependences have been observed for fluorescence and phosphorescence of indole in PVA film. While fluorescence depends minimally, the phosphorescence decreases with temperature dramatically. The fluorescence lifetime was measured to be a single component 4.78 ns while the intensity weighted average phosphorescence lifetime with 290 nm and 405 nm excitations were 6.57 and 5.62 ms, respectively. We believe that the possibility of the excitation of indole phosphorescence in the blue region of visible light and its high anisotropy opens a new avenue for future protein studies.
Long-term Neighborhood Effects on Adolescent Outcomes: Mediated through Adverse Childhood Experiences and Parenting Stress

Past research suggests that neighborhood structural and social environments are important contextual factors associated with children's development; however, investigations of the long-term effects of neighborhood environments in early childhood on subsequent adolescents' social and behavioral outcomes remain limited. Further, it is unclear whether and how the home environment as a mediating mechanism links neighborhood conditions and adolescents' outcomes. Using national surveys from multi-stressed families and census datasets, the present study aims to examine the longitudinal associations between neighborhood concentrated poverty and collective efficacy, mothers' parenting stress, exposure to adverse childhood experiences (ACEs), and later adolescent outcomes. Participants included 4898 children (52% boys) and their mothers (48% black, 25 years of age, on average, 64% living in poverty); children born in unmarried families (75% unmarried) were oversampled. The results suggest that neighborhood collective efficacy is associated directly and indirectly (via parenting stress and ACEs) with adolescents' behavior problems and social skills, and indirectly with their delinquency. Neighborhood concentrated poverty was indirectly related to adolescents' behavior problems, delinquency, and social skills transmitted through collective efficacy and family processes. Both mothers' parenting stress and exposure to ACEs were identified as significant mediators. This study highlights the importance of early intervention for high-risk children, programs to build community resilience and reinforce social support for vulnerable families, and policy efforts to create safe and nurturing relationships and environments.