cssi/SciSciGPT-SciSciNet huggingface dataset:
Rounding precedes rupture and breakdown of vacuolar membranes minutes before malaria parasite egress from erythrocytes

Because Plasmodium falciparum replicates inside of a parasitophorous vacuole (PV) within a human erythrocyte, parasite egress requires the rupture of two limiting membranes. Parasite Ca2+ , kinases, and proteases contribute to efficient egress; their coordination in space and time is not known. Here, the kinetics of parasite egress were linked to specific steps with specific compartment markers, using live-cell microscopy of parasites expressing PV-targeted fluorescent proteins, and specific egress inhibitors. Several minutes before egress, under control of parasite [Ca2+ ]i , the PV began rounding. Then after ~1.5 min, under control of PfPKG and SUB1, there was abrupt rupture of the PV membrane and release of vacuolar contents. Over the next ~6 min, there was progressive vacuolar membrane deterioration simultaneous with erythrocyte membrane distortion, lasting until the final minute of the egress programme when newly formed parasites mobilised and erythrocyte membranes permeabilised and then ruptured-a dramatic finale to the parasite cycle of replication.
38: An essential role for Interferon-β in the induction of interferon-stimulated gene expression by lipopolysaccharide in macrophages

TLR agonists such as lipopolysaccharide (LPS) and poly(I:C) induce expression of type I interferons such as IFN-alpha and IFN-beta by macrophages. To examine the role of IFN- β in the induction of IFN-stimulated genes (ISGs) by LPS, we compared the ability of LPS to induce ISGF3 activity and ISG expression in bone marrow-derived macrophages from wild-type (WT) and IFN- β gene knockout (Ifnb1−/−) mice. We found that LPS treatment activated ISGF3 and induced expression of ISGs such as Oas1, Mx1, Ddx58 (RIG-I) and Ifih1 (MDA5) in WT macrophages, but not in macrophages derived from Ifnb1−/− mice or IFN-a/ β receptor gene knockout (Ifnar1−/−) mice. The inability of LPS to induce activation of ISGF3 and ISG expression in Ifnb1−/− macrophages correlated with the failure of LPS to induce activation of STAT1 and STAT2 in these cells. Consistent with these findings, LPS treatment also failed to induce ISG expression in bone marrow-derived macrophages from Stat2 knockout mice. Although activation of ISGF3 and induction of ISG expression by LPS was abrogated in Ifnb1−/− and Ifnar1−/− macrophages, activation of NF-kB and induction of NF-kB responsive genes such as Tnf (TNF-a) and Il1b (IL-1 β ) were not affected by deletion of either the IFN- β or IFN-aR1 genes. These findings demonstrate that induction of ISGF3 activity and ISG expression by LPS is critically dependent on intermediate production of IFN- β and autocrine signaling through type I IFN receptors.
Evaluation of the roles of the conserved residues of aldehyde dehydrogenase

Aspect of the mechanism of action of mammalian liver aldehyde dehydrogenase have b studied since the first mammalian liver enzyme was purified in our laboratory. The initial studies suggested that the enzyme functioned with covalent catalysis and that a cysteine might be the nucleophile (Feldman and Weiner, 1972). It was later shown by chemical modifications that cysteine 302 was at the active site and it most likely functioned as the nucleophile (Hempel and Pietruszko, 1981). Later, it was shown that glutamate 268 appeared also to be involved in the catalytic process (Abriola et al., 1990). Once a number of sequences of diverse ALDHs were aligned it was found that all possessed cystei302 and most contained the glutamate residue (Vasiliou et al., 1995). The few that did not possess a glutamate were enzymes that did not produce a free acid as the final product
Automated Critique of Early Programming Antipatterns

The introductory programming lab, with small cycles of teaching, coding, testing, and critique from instructors, is an extraordinarily productive learning experience for novice programmers. We wish to extend the availability of such critique through automation, capturing the essence of interaction between student and instructor as closely as possible. Integrated Development Environments and Automated Grading Systems provide constant feedback through static analysis and unit testing. But we also wish to tailor automated feedback to acknowledge commonly recurring issues with novice programmers, in keeping with the practice of a human instructor. We argue that the kinds of mistakes that novice programmers make, and the way they are reported to the novices, deserve special care. In this paper we provide examples of early programming antipatterns that have arisen from our teaching experience, and describe different ways of identifying and dealing with them automatically through our tool WebTA. Novice students may produce code that is close to a correct solution but contains syntactic errors; WebTA attempts to salvage the promising portions of the student's submission and suggest repairs that are more meaningful than typical compiler error messages. Alternatively, a student misunderstanding may result in well-formed code that passes unit tests yet contains clear design flaws; through additional analysis, WebTA can identify and flag them. Finally, certain types of antipattern can be anticipated and flagged by the instructor, based on the context of the course and the programming exercise; WebTA allows for customizable critique triggers and messages.
A Quantum State Metanalysis of the Dynamic Inconsistency Effect

The approach of Quantum State analysis for experimental data is presented and used for a metanalysis of the dynamic inconsistency effect experiment of ref.i¾?[ 1 ]. The results of this experiment have already been demonstrated to be in the field of quantum cognition by ref.i¾?[ 2 ]. Here the quantitative collective state of the participants is retrieved at each stage and a value-level diagram is presented. This has led to additional insights about the dynamic inconsistency effect, as well as suggestions and a way to compare with future research. Through the Quantum State analysis, we have been able to construct a quantitative wavefunction from psychological experiment data.
Reducing perioperative blood loss with antifibrinolytics and antifibrinolytic-like agents for patients undergoing total hip and total knee arthroplasty

Total hip and knee arthroplasties may be associated with a significant amount of perioperative blood loss. The severity of blood loss may be great enough to require the use of blood transfusions to treat perioperative anemia. Various methods of blood preservation have been studied. The use of antifibrinolytics and antifibrinolytic-like agents to reduce perioperative bleeding has been researched in orthopaedics and other surgical subspecialties. This review aims to evaluate the current evidence supporting the use of tranexamic acid, aminocaproic acid, fibrin tissue adhesive, and aprotinin in the reduction of perioperative blood loss in total hip and knee arthroplasties.
Joint Problem-Solving in Fluid Health Care Teams

In health care, teams working on process innovation often consist of people from different organizational groups who fluidly shift on and off the team. This research employs multiple methods to dis...
Las raíces biológicas de los conflictos humanos

Les arrels biologiques dels conflictes humans venen de lluny en la seva evolucio i son, per tant, profundes. Per sort, algunes de les nostres tendencies humanes mes destructives poden ser mitigades o eliminades mitjancant l’evolucio cultural. Pero ates que la cultura es per a la biologia el mateix que el programari es per al maquinari, cal entendre correctament la naturalesa biologica dels conflictes per a poder proporcionar solucions, a mes de bastir unes cultures de pau duradores. Aquest article se centra en les arrels biologiques dels conflictes humans. Una continuacio seva giraria al voltant de la resolucio de conflictes mitjancant l’evolucio cultural.
Initiating a Dialogue About Gun Violence: Shifting the Focus

Our society is violent, and people who commit “violent acts” are oppressed human beings who are reacting to their reality and their context. An emerging public health theme is to frame gun violence...
Solid-State Automotive Lighting: Implications for Sustainability and Safety

Solid-state technologies using light-emitting diodes are increasing in acceptance for use in automotive lighting. For signalling systems they have already achieved widespread use; for forward lighting systems they have been introduced and there are substantial ongoing efforts to introduce them for illumination. In the present paper, a brief overview of solid-state lighting technology for automotive applications is given. This overview first focuses on the implications of solid-state lighting for energy utilization and environmental impacts compared to incumbent lighting technologies. Secondly, the unique photometric, colorimetric and temporal characteristics of solid-state lighting systems are described with emphasis on the safety-related implications for driver vision and visual comfort.
Evaluation of the exposure prediction component of Control of Substances Hazardous to Health Essentials

The exposure prediction component of the Control of Substances Hazardous to Health (COSHH) Essentials model (paper version) was evaluated using field measurements from National Institute of Occupat...
Exploiting Metal–Ligand Cooperativity to Sequester, Activate, and Reduce Atmospheric Carbon Dioxide with a Neutral Zinc Complex

As atmospheric levels of carbon dioxide (CO2) continue to increase, there is an immediate need to balance the carbon cycle. Current approaches require multiple processes to fix CO2 from the atmosphere or flue gas and then reduce it to value-added products. The zinc(II) catalyst Zn(DMTH) (DMTH = diacetyl-2-(4-methyl-3-thiosemicarbazonate)-3-(2-pyridinehydrazonato)) reduces CO2 from air to formate with a faradaic efficiency of 15.1% based on total charge. The catalyst utilizes metal-ligand cooperativity and redox-active ligands to fix, activate, and reduce CO2. This approach provides a new strategy that incorporates sustainable earth-abundant metals that are oxygen and water tolerant.
TRPV4 antagonists ameliorate ventriculomegaly in a rat model of hydrocephalus

Hydrocephalus is a serious condition that impacts patients of all ages. The standards of care are surgical options to divert, or inhibit production of, cerebrospinal fluid; to date, there are no effective pharmaceutical treatments, to our knowledge. The causes vary widely, but one commonality of this condition is aberrations in salt and fluid balance. We have used a genetic model of hydrocephalus to show that ventriculomegaly can be alleviated by inhibition of the transient receptor potential vanilloid 4, a channel that is activated by changes in osmotic balance, temperature, pressure and inflammatory mediators. The TRPV4 antagonists do not appear to have adverse effects on the overall health of the WT or hydrocephalic animals.
Oncogenic Activation of AKT by MAPK6

Mitogen-activated protein kinase 6 (MAPK6) is an atypical MAPK closely related to MAPK4. We recently reported that MAPK4 can promote cancer by activating the Protein Kinase B (PKB/AKT) pathway of cell growth and survival. Here we report that MAPK6 overexpression also activates AKT to induce oncogenic outcomes, including transforming "normal" human epithelial cells into anchorage-independent growth and enhancing cancer cell growth. Knockdown of MAPK6 inhibited cancer cell growth and xenograft growth, supporting the tumor-promoting activities of endogenous MAPK6. Unlike MAPK4, which binds AKT through its kinase domain and phosphorylates AKT at T308, MAPK6 interacts with AKT through its C34 region and the unique C-terminal tail and phosphorylates AKT at S473 independent of mTORC2, the major AKT S473 kinase. MAPK6 overexpression is associated with decreased overall survival and the survival of lung adenocarcinoma, mesothelioma, uveal melanoma, and breast cancer patients. We conclude that MAPK6 can promote cancer by activating AKT and that targeting MAPK6 may be effective in human cancers.
Eli Lilly v. Teva: Generic Companies Infringe under Akamai IV in Case of Divided Infringement

The U.S. Supreme Court’s 2014 decision in Limelight Networks v. Akamai Technologies decision (Akamai III), in conjunction with the Federal Circuit’s stance on divided infringement claims, effectively undermined the value of method claims, particularly in the realm of pharmaceuticals, diagnostics, and other biotechnology related innovation, by limiting the ability of patentees to establish liability in cases where steps of the claimed method are performed by multiple parties. On remand, the en banc Federal Circuit in Akamai Technologies v. Limelight Networks (Akamai IV) sought to address the problem by expanding the definition of direct infringement under 271(a) to encompass more scenarios in which method steps performed by multiple actors can be attributed to a single entity. In January 2017, the Federal Circuit issued a decision in Eli Lilly & Co. v. Teva Parenteral Medicines (Eli Lilly) wherein the court applied Akamai IV to uphold a district court’s determination that sale of a generic version of pemetrexed would induce infringement of method of treatment claims even though two of the recited steps are performed by a physician while the third step is performed by the patient. Although Eli Lilly is an encouraging decision for pharmaceutical and biotechnology firms, that the decision hinged on the specific facts of the case, including the language of the patent claims and the instructions on FDA-mandated labeling for the proposed generic versions of pemetrexed. In this Report, I review the Federal Circuit’s decision in Eli Lilly, pointing out factors that seemed relevant to the court’s finding of infringement. I also discuss potential alternate scenarios involving divided infringement where it is still unclear whether the Federal Circuit would find liability. Finally, I discuss two alternative theories of liability that were put forward by Eli Lilly but which the court declined to address as moot.
Comprehensive Quality Investigations of Wire-feed Additive Manufacturing based on Machine Learning of Experimental Data

Wire-feed Laser-based Additive Manufacturing has gained attention for years with its promises of high-level automation, reducing materials waste, overall costs, and large-scale volume production. However, comprehensive quality quantification and control are difficult to implement due to the limitation of dimensionality and cost of experimental data that traditional trial and error methods and computational methods can handle. To enable quality control of desired part geometry and microstructural properties of the part, this study proposes a comprehensive quality investigation framework based on learning from experimental data. Specifically, experimental data across various process variables and output properties in terms of bead overall quality, geometry (i.g. bead height, fusion zone depth, etc.), and microstructural properties are collected. The predictive process-property relations are then modeled with data-driven ML classification and regression models. The multiple properties of the printed bead are predicted on processing space based on a 3-dimensional contour map. The insights and impacts of process variables on bead morphology, geometric and microstructural properties are comprehensively investigated. The processing parameters leaned by the models can rapidly designing materials with desired functional properties.
Advancing chronobiology across the spectrum

The many scientists and clinicians involved in research or manipulation of biological rhythms in humans and other living beings will likely be interested in the changes in Chronobiology Internation...
Investigating Head-On Crash Severity Involving Commercial Motor Vehicles in Kentucky:

This study examines various features affecting the severity associated with commercial motor vehicle (CMV, i.e., large truck and bus) head-on collisions on Kentucky highways. Recent five-year (2015...
Cessation of smoke exposure improves pediatric CF outcomes: Longitudinal analysis of CF Foundation Patient Registry data.

Abstract Background Tobacco smoke exposure is a major risk factor for the health of children and adolescents with CF. In this study, we assess whether cessation of smoke exposure is associated with improved outcomes in this population. Methods We used annualized and encounter-based data from the U.S. CF Foundation Patient Registry (2006-2018) on all individuals born 1998-2010. The analytical sample included those who ever reported second-hand smoke exposure (daily or weekly), ever lived with a smoker, or ever reported smoking themselves. We used non-linear mixed models for pulmonary exacerbations and linear mixed models for ppFEV1 and BMI as a function of ceased exposure. Results The sample included 3,633 individuals contributing 19,629 person-years. Cessation of smoke exposure reduced the odds of a pulmonary exacerbation in 12 months by 17% (OR 0.83, p Conclusion Eliminating smoke exposure may reduce pulmonary exacerbations and improve respiratory and nutritional outcomes in children and adolescents with CF. Both smoking cessation and exposure prevention should be prioritized in pediatric CF care.
Hydride- and halide-substituted Au9(PH3)83+ nanoclusters: similar absorption spectra disguise distinct geometries and electronic structures.

Ligands dramatically affect the electronic structure of gold nanoclusters (NCs) and provide a useful handle to tune the properties required for nanomaterials that have high performance for important functions like catalysis. Recently, questions have arisen about the nature of the interactions of hydride and halide ligands with Au NCs: hydride and halide ligands have similar effects on the absorption spectra of Au9 NCs, which suggested that the interactions of the two classes of ligands with the Au core may be similar. Here, we elucidate the interactions of halide and hydride ligands with phosphine-protected gold clusters via theoretical investigations. The computed absorption spectra using time-dependent density functional theory are in reasonable agreement with the experimental spectra, confirming that the computational methods are capturing the ligand–metal interactions accurately. Despite the similarities in the absorption spectra, the hydride and halide ligands have distinct geometric and electronic effects. The hydride ligand behaves as a metal dopant and contributes its two electrons to the number of superatomic electrons, while the halides act as electron-withdrawing ligands and do not change the number of superatomic electrons. Clarifying the binding modes of these ligands will aid in future efforts to use ligand derivatization as a powerful tool to rationally design Au NCs for use in functional materials.
Decentralized Cooperative Reinforcement Learning with Hierarchical Information Structure.

Multi-agent reinforcement learning (MARL) problems are challenging due to information asymmetry. To overcome this challenge, existing methods often require high level of coordination or communication between the agents. We consider two-agent multi-armed bandits (MABs) and Markov decision processes (MDPs) with a hierarchical information structure arising in applications, which we exploit to propose simpler and more efficient algorithms that require no coordination or communication. In the structure, in each step the ``leader" chooses her action first, and then the ``follower" decides his action after observing the leader's action. The two agents observe the same reward (and the same state transition in the MDP setting) that depends on their joint action. For the bandit setting, we propose a hierarchical bandit algorithm that achieves a near-optimal gap-independent regret of $\widetilde{\mathcal{O}}(\sqrt{ABT})$ and a near-optimal gap-dependent regret of $\mathcal{O}(\log(T))$, where $A$ and $B$ are the numbers of actions of the leader and the follower, respectively, and $T$ is the number of steps. We further extend to the case of multiple followers and the case with a deep hierarchy, where we both obtain near-optimal regret bounds. For the MDP setting, we obtain $\widetilde{\mathcal{O}}(\sqrt{H^7S^2ABT})$ regret, where $H$ is the number of steps per episode, $S$ is the number of states, $T$ is the number of episodes. This matches the existing lower bound in terms of $A, B$, and $T$.
Grape physiology, composition and sensory characteristics in a selective harvest winegrape vineyard

Selective harvest of highest quality wine grapes is often based on field sensory evaluation. Physiological and chemical data were collected over two growing seasons in a premium-production Napa Valley estate vineyard selectively harvested based on subjective taste evaluation. Areas with perceived higher quality were characterized by vines with: (1) lower pre-dawn (ψPD) and midday (yMD) leaf water potential; (2) smaller berries; (3) lower pruning weights; and (4) higher °Brix. Sensory analysis indicated grapes from vines with lowest yMD at veraison (≤- 1.5 MPa) had significantly sweeter, softer pulp, no vegetal character, and browner, crunchier seeds. Results suggested no continuous relationship between water stress and sensory characteristics, but an inflection point related to early season ψPD.
Cyclic Di-GMP Signaling in Vibrio cholerae

The physiological role of cyclic di-GMP (c-di-GMP) in Vibrio cholerae has emerged from the analysis of phenotypes of mutants unable to produce GGDEF/EAL/HD-GYP proteins as well as from phenotypes of strains overproducing GGDEF/EAL/HD-GYP proteins. In V. cholerae, c-di-GMP is involved in the regulation of multiple cellular processes including biofilm formation, motility, and virulence. This chapter first introduces the processes regulated by c-di-GMP signaling, discusses what is currently known about the involvement of specific GGDEF/EAL/HD-GYP proteins in these processes, and then summarizes our current understanding of regulation of GGDEF/EAL/HD-GYP genes. In V. cholerae, similar to other organisms, c-di-GMP controls a motile-to-sessile lifestyle switch and negatively regulates motility. The importance of c-di-GMP in V. cholerae biology has been conclusively shown in studies involving VieA (VC1652). The VieA response regulator harbors an EAL domain and has phosphodiesterase (PDE) activity. A set of GGDEF/EAL/HD-GYP proteins produce a phenotype only when they are overproduced. Studies in other organisms have indicated that c-di- GMP can regulate motility at least at three different levels: transcriptional, posttranscriptional, and functional. cdgF overexpression also affected biofilm formation. Cells with increased c-di-GMP levels exhibited enhanced vps, vpsT, and vpsR expression and, consequently, formed thicker and more developed biofilms than those with wild-type levels of c-di-GMP. The role of Plz proteins in intestinal colonization was analyzed using an infant mouse colonization assay. Strains harboring a plzB deletion or a mutated version of the PilZ domain exhibited a decrease in colonization.
On a Simple Depth-First Search Strategy for Exploring Unknown Graphs

We preset a siple epth-first search strategy for exploring (constructing) an unknown strongly connected graph G with m edges and n vertices by traversing at most min (mn,dn2 + m) edges. Here, d is the minimum number of edges needed to add to G to make it Eulerian. This parameter d is known as the deficiency of a graph and was introduced by Kutten [Kut88]. It was conjectured that graphs with high deficiency. Deng and Papadimitriou [DP90] provided evidence that the conjecture may be true by exhibiting a family of graphs where the robot can be forced to traverse Ω (d2m) edges in the worst case. Since then, there has been some interest in determining whether a graph with deficiency d can be explored by traversing O(poly(d)m) edges. Our algorithm achieves such bound when the graph is dense, say m = Ω(n2).
l-glutamine stimulates jejunal sodium and chloride absorption in pig rotavirus enteritis

Rotavirus enteritis is the leading cause of diarrhea in infants worldwide. A research priority of the World Health Organization is to develop oral rehydration solutions containing amino acids or other additives that will stimulate intestinal absorption more efficiently than the current glucose-based oral rehydration solutions. Glutamine is the principal metabolic fuel of the small bowel and a putative stimulator of mucosal repair. This report describes the transport response to mucosal L-glutamine following intestinal injury caused by porcine rotavirus. Peak symptoms and mucosal damage were observed 2-7 days after oral rotavirus inoculation. In vitro transport studies of the maximally injured region, the midjejunum (80% reduction in lactase), surprisingly, showed transport responses to L-glutamine (30 mmol/L) and L-alanine (30 mmol/L) that were similar qualitatively and quantitatively to those observed in control tissue. Subsequent application of mucosal D-glucose (30 mmol/L) caused additional stimulation of electrogenic Na+ transport, but the response to glucose was blunted (P less than 0.05) in the infected tissues. Glutamine and alanine enhanced Na+ absorption to a similar degree (2-2.5 muEq.cm-2.h-1), but glutamine stimulated equal amounts of electrogenic and electroneutral NaCl absorption, whereas alanine had no significant effect on net Cl- flux. Glutamine is a potentially useful substrate for investigation in oral rehydration solutions for infant diarrhea.
Our antitrust laws are anticompetitive: An examination of price and quota enforcement

Abstract This article summarizes the author's views of antitrust laws, in theory and in practice, primarily on economic grounds. Such laws, he believes, are worth-while only if they either increase total income and/or distribute income in a more desirable way. They have, however, proved to be inappropriate for contemporary American society; neither objective has been accomplished by their enforcement. Several cases of the most popular types of antitrust action, those dealing with price fixing and market quotas, are examined; the author concludes that the result has not been socially beneficial, and that industry would be more competitive and come closer to meeting economically related social objectives if there were no antitrust laws at all.
The relationship of health, loneliness, housing, and communities for aging adults

Home accessibility and community livability are essential ingredients in healthy aging and have a substantial impact on the safety and well-being of older adults. Increases in the aging population, coupled with the desire to age in place, requires additional research to understand what is needed to keep elders healthy, safe, and independent for as long as possible. The current study examined the relationships among home accessibility, community livability, loneliness, and health (e.g. self-rated health, physical activities, and prescription medications) to better understand the implications for those adults who age in place. Descriptive statistics and bivariate correlation analysis were used to explore basic relationships among the variables for a subsample of 1,134 individuals (55.4% male, 44.6% female) aged 65 and older from the 2005 Iowa Family Survey. The survey was mailed to 6,400 Iowa households; the Dillman (2000) method was used to construct and retrieve questionnaires. In all, 3,998 surveys were returned for a 65% response rate. Nearly 75% of respondents lived in rural areas with populations less than 50,000. Additionally, multiple regression and logistic regression analyses were used to predict relationships among health, loneliness, housing, and community variables. Older adults were found to have better levels of health when communities were larger, included more livability features, when they were more satisfied with them, and when they felt they could age in place. Respondents rated their health worse, however, when accessibility features were present in the home and when they were lonelier. The research highlights the importance of creating and/or maintaining a barrier-free environment and livable community for aging adults.
Determination of pesticide residues by neutron-activation analysis

Although activation analysis was first employed during the 1930’s, it remained as a seldom-used technique until the advent of the nuclear reactor — with its attendant high neutron fluxes. It became considerably better known during the 1950’s, when the activation analysis service of the Oak Ridge National Laboratory made the technique available, at least indirectly, to any interested persons. More recently, the development of lower-cost, high-performance research reactors, low-cost neutron generators (deuteron accelerators), and versatile multichannel pulse-height analyzers has brought the technique directly into many laboratories. Neutron-activation analysis has now been applied in a great many different fields of science and industry, for example, the petroleum, chemical, and plastics industries, metallurgy, biology and medicine, criminalistics, and, most recently, pesticide residue studies.
Evaluating strategy with internal and environmental effects. A response elasticities approach

Abstract When assessing strategy effectiveness, managers are challenged to identify and evaluate two major types of effects-internal firm strategy effects and external environmental effects. A study of the U.S. non-rubber footwear market is presented that illustrates how these effects impact firm profit performance. Seven firm-specific equations are specified in multiplicative model form and estimated simultaneously with econometric methods. The resulting coefficients can be directly compared being measured as constant response elasticities. Using these coefficients, strategies for both the firm and its competitors are inferred and evaluated for their effectiveness. J busn res 1994. 31.213–224
Adaptive Optics Imaging of Retinal Photoreceptors Overlying Lesions in White Dot Syndrome and its Functional Correlation

Purpose To quantify retinal photoreceptor density using adaptive optics (AO) imaging and correlate it with retinal tomography, fundus autofluorescence, and retinal sensitivity overlying lesions in various white dot syndromes (WDS). Design Prospective cross-sectional study. Methods setting: Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA. study population: Thirty-five lesions of WDS from 12 patients (19 eyes; mean age: 54.4 ± 15.8 years; 9 female) were analyzed. intervention: Macular lesions (≤3 regions of interest/eye), at 2 fixed eccentric loci, were imaged using AO, spectral-domain optical coherence tomography, and fundus autofluorescence. In this study, lesions were defined as active if there was presence of hyperautofluorescence within the lesions. Photoreceptor density was calculated after manual correction and adjustment for axial length. Retinal sensitivity was assessed using microperimetry and correlated with photoreceptor density using Spearman rank correlation test. outcome measures: Mean retinal sensitivity and photoreceptor density at the WDS lesions. Results Mean photoreceptor density was 7331 ± 4628 cones/mm 2 overlying 16 active lesions and 6546 ± 3775 cones/mm 2 overlying 19 inactive lesions ( P = .896). Mean retinal sensitivity (9.37 ± 5.34 dB) showed modest correlation with photoreceptor density (ρ = 0.42, P = .03). Retinal sensitivity over lesions with intact inner segment-outer segment (IS-OS) junction was 13.35 ± 3.75 dB and 6.33 ± 4.31 dB over lesions with disrupted IS-OS junction ( P = .005). Conclusions AO imaging may allow high-resolution analysis of photoreceptor loss among lesions in WDS. Such microstructural changes may correlate with functional loss.
Global warming due to increasing absorbed solar radiation

[1] Global climate models used in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) are examined for the top-of-atmosphere radiation changes as carbon dioxide and other greenhouse gases build up from 1950 to 2100. There is an increase in net radiation absorbed, but not in ways commonly assumed. While there is a large increase in the greenhouse effect from increasing greenhouse gases and water vapor (as a feedback), this is offset to a large degree by a decreasing greenhouse effect from reducing cloud cover and increasing radiative emissions from higher temperatures. Instead the main warming from an energy budget standpoint comes from increases in absorbed solar radiation that stem directly from the decreasing cloud amounts. These findings underscore the need to ascertain the credibility of the model changes, especially insofar as changes in clouds are concerned.
Reflexive Ethnography: A Guide to Researching Selves and Others

Reflexive Ethnography:. Guide to Researching Selves and Others. Charlotte Aull Davies. New York: Routledge, 1999.257 pp.
Mechanisms underlying aberrant expression of miR-29c in uterine leiomyoma.

Objective To determine the expression of miR-29c and its target genes in leiomyoma and the role of NF-κB, specific protein 1 (SP1), and DNA methylation in its regulation. Design Experimental study. Setting Academic research laboratory. Patient(s) Women undergoing hysterectomy for leiomyoma. Intervention(s) Over- and underexpression of miR-29c; blockade of transcription factors. Main Outcome Measure(s) MiR-29c and its target gene levels in leiomyoma and the effects of blockade of transcription factors on miR-29c expression. Result(s) Leiomyoma as compared with myometrium expressed significantly lower levels of miR-29c, with an inverse relationship with expression of its targets, COL3A1 and DNMT3A. Gain of function of miR-29c inhibited the expression of COL3A1 and DNMT3A at protein and mRNA levels, secreted COL3A1, and rate of cell proliferation. Loss of function of miR-29c had the opposite effect. E 2 , P, and their combination inhibited miR-29c in leiomyoma smooth muscle cells (LSMC). Phosphorylated NF-κB (p65) and SP1 protein expression were significantly increased in leiomyoma. SiRNA knockdown of SP1 and DNMT3A or their specific inhibitors significantly increased the expression of miR-29c, accompanied by the inhibition of cellular and secreted COL3A1 in siRNA-treated cells. Knockdown of p65 also induced miR-29c expression but had no effect on COL3A1 expression. Conclusion(s) MiR-29c expression is suppressed in leiomyoma, resulting in an increase in expression of its targets COL3A1 and DNMT3A. The suppression of miR-29c in LSMC is primarily mediated by SP1, NF-κB signaling, and epigenetic modification. Collectively, these results indicate a significant role for miR-29c in leiomyoma pathogenesis.
FORSE-1: a positionally regulated epitope in the developing rat central nervous system

We designed a protocol to identify cell surface molecules expressed in restricted spatial patterns in the developing central nervous system (CNS) that might be regulated by regionally restricted transcription factors. The immunogen was a membrane fraction from NT2/D1 embryocarcinoma cells that were induced to differentiate into neurons and upregulate Hox gene expression in response to retinoic acid. One monoclonal antibody (mAb), FORSE-1, specifically labels the rostral rat CNS from the earliest stages. Staining is observed in the rostral but not caudal neural folds of the embryo prior to neural tube closure. Staining is enriched in the forebrain as compared to the rest of the CNS, until E18. Between E11.5 and E13.5, only certain areas of the telencephalon and diencephalon are labeled. Later, up to E17.5, FORSE-1 labeling is specifically restricted to the telencephalon, where a correlation with mitotic activity is apparent: the ventricular zone labels with FORSE-1, while the cortical plate is negative. The staining of the neuroepithelium is intensified by acetone fixation, which also reveals, between E11.5 and E13.5, a dorsoventrally restricted, FORSE-1- positive region of the spinal cord. After E18, the entire CNS is labeled, through adulthood. The mAb labels the surfaces of dissociated, living cells. Other, non-CNS areas of FORSE-1 labeling are nasal and otic placodes, nasal epithelium, nasal glands, and early (E9.5–10.5) endoderm. mAb FORSE-1 recognizes an epitope present on both a high- molecular-weight (> 200 kDa) proteoglycan from embryonic and early postnatal brain, and on a 80 kDa doublet that is restricted to the CNS in the adult. These findings suggest the FORSE-1 antigen as a candidate cell surface molecule for mediating regional specification from the earliest stages of CNS development.
IL-15 mimics T cell receptor crosslinking in the induction of cellular proliferation, gene expression, and cytotoxicity in CD8+ memory T cells.

Generation of CD8+ memory T cells requires antigenic stimulation through T cell receptor (TCR); however, maintenance of CD8+ memory T cells seems to be mediated by cytokines, such as IL-15, in a TCR-independent manner. Compared with the TCR-induced activation, less is known about the mechanisms of IL-15 action. We report here a comparative and kinetic analysis of the responses of memory phenotype CD8+ T cells to IL-15 or TCR (anti-CD3) stimulation in vitro. These two stimuli induce highly similar responses in memory phenotype CD8+ T cells as measured by cellular proliferation, gene expression changes, synthesis of effector molecules (IFNγ, tumor necrosis factor β, granzyme B, and perforin), and induction of cytotoxicity. From 189 genes/expressed sequence tags (ESTs) whose expression changed in CD8+ memory T cells after IL-15 and anti-CD3 stimulation identified by cDNA microarray analysis, 77% of the genes/ESTs exhibit a highly similar pattern of expression between IL-15 and anti-CD3-treated cells, and only 16% and 7% of the genes/ESTs are differentially expressed in response to IL-15 and anti-CD3 treatments, respectively. These results show that IL-15 and anti-CD3 stimulation induced remarkably similar gene expression and effector function. Thus, IL-15 acts not only as a crucial growth factor but also as an antigen-independent activator of effector functions for CD8+ memory T cells.
Oxidation of dmso and methanesulfinic acid by the hydroxyl radical

The quantitation of methanesulfinic acid, the reaction product of dimethylsulfoxide oxidation by the hydroxyl radical, has been reported as a useful tool for the detection of this radical. The present report describes two HPLC methods for determination of methanesulfinate. The first is based on the reversed phase separation and detection of the derivative formed between methanesulfinate and the diazonium salt fast garnet GBC. The second is based on anion exchange HPLC using conductivity detection. In incubations containing xanthine plus xanthine oxidase, the formation of the hydroxyl radical was demonstrated by trapping with DMSO and detection of methanesulfinate. Formation of the sulfinate from DMSO did not occur in the presence of catalase or with the omission of xanthine oxidase. In the absence of xanthine oxidase, methanesulfinate added as an internal standard could be completely recovered. In the presence of of xanthine oxidase, however, the recovery of added methanesulfinate was less than 40%. Using the Fenton reaction to generate these radicals, both methanesulfinate and methanesulfonate were formed in the presence DMSO. In incubations with methanesulfinate, hydroxyl radical generation led to stoichiometric loss of methansulfinate and production of methanesulfonate. Methanesulfinate was only slowly oxidized to methanesulfonate in incubations containing hydrogen peroxide in the absence of iron. The data illustrate that the product of DMSO oxidation by the hydroxyl radical, methanesulfinate, is further oxidized by this radical to methanesulfonate. Determination of methanesulfinate formation from DMSO underestimates the production of the hydroxyl radical.
The effect of high temperatures on the mid-to-far-infrared emission and near-infrared reflectance spectra of phyllosilicates and natural zeolites: Implications for martian exploration

Abstract Most phyllosilicates on Mars appear to be associated with ancient terrains. As such, they may have experienced shock heating produced by impacts and could have been significantly altered or melted. We characterized the effects of high temperatures on the mid-to-far-infrared (mid-to-far-IR) emission (100–1400 cm−1; 7.1–100 μm) and near-infrared (NIR) reflectance (1.2–2.5 μm) spectra of phyllosilicates by measuring experimentally calcined (100–900 °C) phyllosilicates and also two zeolites. Correlated differential scanning calorimetry (DSC) measurements were also performed on each sample to provide insight into the thermal activities of the phyllosilicates and natural zeolites. Our results indicate that all phyllosilicates exhibit characteristic degradations in both NIR and mid-to-far-IR spectral properties between 400 and 800 °C, mainly attributable to the dehydroxylation and recrystallization processes as temperature increases. Spectral features of natural zeolites persist to higher temperatures compared to features of phyllosilicates during heating treatments. The thermal behaviors of phyllosilicate infrared (IR) properties are greatly influenced by the compositions of the octahedral cations: (1) changes in both the NIR and mid-to-far-IR spectra of phyllosilicates tend to occur at lower temperatures (300–400 °C) in the Fe3+-rich samples as compared to the Al3+-rich types (400–600 °C); (2) Mg2+-trioctahedral phyllosilicates hectorite, saponite, and sepiolite all display major mid-to-far-IR spectral changes at 700 °C, corresponding to the formation of enstatite; (3) phyllosilicates that have minor replacement of Mg2+ for Al3+ in octahedral positions (e.g. cheto-type montmorillonite and palygorskite) show an absorption band at ∼920 cm−1 that becomes strong at 900 °C. Inconsistency between spectral behaviors in the mid-to-far-IR and NIR regions is also discussed for phyllosilicates. Results from this study have provided suggestive evidence for the scenario that some phyllosilicates could lose all original spectral features in mid-to-far-IR region while maintaining their characteristic hydration bands in NIR region in the same temperature range.
Grain-size effects in ferroelectric switching

A model of ferroelectric switching that describes crystals composed of a large number of relatively small grains is presented. It is shown that, if the grain boundaries stop or significantly affect domain-wall growth, then the observed switching current transients will deviate from those predicted by the infinite-grain model of Ishibashi and Takagi. The model accounts for constant nucleation rate throughout the switching period and for constant domain-wall velocity. It is shown that at some time dependent only on the size of the grains and the domain-wall velocity, the switching-current transient changes from its small-time infinite-grain behavior to an exponential decay. The results are applied to two-dimensional Ising-model simulations.
Detection and identification of input/output stuck-at and bridging faults in combinational and sequential VLSI networks by universal tests

In this paper we present universal tests for detection or identification of single and multiple stuck-at and bridging faults in combinational and sequential VLSI networks. Denote by P(T, F, m, k, s) the fraction of all devices with m inputs, k outputs and S feedback lines such that all faults from a set F of possible faults are detected (respectively, identified) by test T. We say that T is a universal test detecting (identifying) all faults from F if lim"m" "->" "~P(T, F, m, k, s) = 1. In this paper we consider single and multiple stuck-at and bridging faults at input or output lines. For these faults we construct corresponding universal tests T, estimate probabilities P(T, F, m, k, s) of fault detection or identification and present lower and upper bounds for the minimum number N(m, k, s) of test patterns in universal tests. Asymptotic optimality of the suggested universal tests is proved for the important case of single stuck-at and bridging faults. We also present practical examples of devices and tests which illustrate the usefulness of the estimates of minimum numbers N(m, k, s) of test patterns. For the universal tests T proposed in this paper probabilities P(T, F, m, k, s) of fault detection or identification converge to one very fast. This implies that these universal tests may be quite efficient either as a first step in a testing procedure or in the case when a broad spectrum of complex VLSI devices has to be tested.
Engineering A-kinase anchoring protein (AKAP)-selective regulatory subunits of protein kinase A (PKA) through structure-based phage selection.

PKA is retained within distinct subcellular environments by the association of its regulatory type II (RII) subunits with A-kinase anchoring proteins (AKAPs). Conventional reagents that universally disrupt PKA anchoring are patterned after a conserved AKAP motif. We introduce a phage selection procedure that exploits high-resolution structural information to engineer RII mutants that are selective for a particular AKAP. Selective RII (RSelect) sequences were obtained for eight AKAPs following competitive selection screening. Biochemical and cell-based experiments validated the efficacy of RSelect proteins for AKAP2 and AKAP18. These engineered proteins represent a new class of reagents that can be used to dissect the contributions of different AKAP-targeted pools of PKA. Molecular modeling and high-throughput sequencing analyses revealed the molecular basis of AKAP-selective interactions and shed new light on native RII-AKAP interactions. We propose that this structure-directed evolution strategy might be generally applicable for the investigation of other protein interaction surfaces. Background: PKA is confined to subcellular compartments by A-kinase anchoring proteins (AKAPs). Results: A structure-based phage-directed evolution strategy has yielded modified PKA regulatory type II subunits with AKAP-selective binding properties. Conclusion: Engineered RSelect proteins preferentially target particular AKAP-PKA interfaces Significance: RSelect subunits are tools to distinguish and manipulate subpopulations of anchored PKA.
A Winning Combination: Successful Resource Sharing Benefits All Library Users

Beard, Academic Librarian extraordinaire, explains how West Georgia College affects not only his community with its services to all comers — including youth — but how the bottom line for libraries is impacted throughout the state. Beard's message centers on the key role cooperative collection management can play in combatting the high cost of providing adequate services to today's youth.
Effect of wavelength on in vivo images of the human cone mosaic

In images of the human fundus, the fraction of the total returning light that comes from the choroidal layers behind the retina increases with wavelength [Appl. Opt.28, 1061 (1989); Vision Res.36, 2229 (1996) ]. There is also evidence that light originating behind the receptors is not coupled into the receptor waveguides en route to the pupil [S. A. Burns et al., Noninvasive Assessment of the Visual System, Vol. 11 of 1997 Trends in Optics and Photonics Series, D. Yager, ed. (Optical Society of America, 1997), p. a1; Invest. Ophthalmol. Visual Sci.38, 1657 (1997) ]. These observations imply that the contrast of images of the cone mosaic should be greatly reduced with increasing wavelength. This hypothesis was tested by imaging the light distributions in both the planes of the photoreceptors and the pupil at three wavelengths, 550, 650, and 750 nm, with the Rochester adaptive optics ophthalmoscope. Surprisingly, the contrast of the retinal images varied only slightly with wavelength. Furthermore, the ratio of the receptorally guided component to the total reflected light measured in the pupil plane was found to be similar at each wavelength, suggesting that, throughout this wavelength range, the scattered light from the deeper layers in the retina is guided through the receptors on its return path to the pupil.