cssi/SciSciGPT-SciSciNet huggingface dataset:
Cigarette Smoke Exposure Inhibits Bacterial Killing via TFEB-Mediated Autophagy Impairment and Resulting Phagocytosis Defect

Introduction Cigarette smoke (CS) exposure is the leading risk factor for COPD-emphysema pathogenesis. A common characteristic of COPD is impaired phagocytosis that causes frequent exacerbations in patients leading to increased morbidity. However, the underlying mechanism is unclear. Hence, we investigated if CS exposure causes autophagy impairment as a mechanism for diminished bacterial clearance via phagocytosis by utilizing murine macrophages (RAW264.7 cells) and Pseudomonas aeruginosa (PA01-GFP) as an experimental model. Methods Briefly, RAW cells were treated with cigarette smoke extract (CSE), chloroquine (autophagy inhibitor), TFEB-shRNA, CFTR(inh)-172, and/or fisetin prior to bacterial infection for functional analysis. Results Bacterial clearance of PA01-GFP was significantly impaired while its survival was promoted by CSE (p < 0.01), autophagy inhibition (p < 0.05; p < 0.01), TFEB knockdown (p < 0.01; p < 0.001), and inhibition of CFTR function (p < 0.001; p < 0.01) in comparison to the control group(s) that was significantly recovered by autophagy-inducing antioxidant drug, fisetin, treatment (p < 0.05; p < 0.01; and p < 0.001). Moreover, investigations into other pharmacological properties of fisetin show that it has significant mucolytic and bactericidal activities (p < 0.01; p < 0.001), which warrants further investigation. Conclusions Our data suggests that CS-mediated autophagy impairment as a critical mechanism involved in the resulting phagocytic defect, as well as the therapeutic potential of autophagy-inducing drugs in restoring is CS-impaired phagocytosis.
Activity Theory As a Lens for Characterizing the Participatory Unit

Since the cognitive revolution of the sixties, representation has served as the central concept of cognitive theory and representational theories of mind have provided the establishment view in cognitive science (Fodor, 1980; Gardner, 1985; Vera & Simon, 1993). Central to this line of thinking is the belief that knowledge exists solely in the head, and instruction involves finding the most efficient means for facilitating the “acquisition” of this knowledge (Gagne, Briggs, & Wager, 1993). Over the last two decades, however, numerous educational psychologists and instructional designers have begun abandoning cognitive theories that emphasize individual thinkers and their isolated minds. Instead, these researchers have adopted theories that emphasize the social and contextualized nature of cognition and meaning (Brown, Collins, & Duguid, 1989; Greeno, 1989, 1997; Hollan, Hutchins, & Kirsch, 2000; Lave & Wenger, 1991; Resnick, 1987; Salomon, 1993). Central to these reconceptualizations is an emphasis on contextualized activity and ongoing participation as the core units of analysis (Barab & Kirshner, 2001; Barab & Plucker, 2002; Brown & Duguid, 1991; Cook & Yanow, 1993;
Den-site selection of eastern spotted skunks in the southern Appalachian Mountains

The eastern spotted skunk (Spilogale putorius) is a small, nocturnal omnivore that was once common throughout the eastern United States, but has declined over the last 75 years. We examined den-site selection of eastern spotted skunks in the southern Appalachian Mountains of Alabama from December 2014 to February 2016. We compared the local habitat characteristics of 97 den sites from 8 individual skunks with paired random sites. Dens were most frequently located in burrows, but were also found under uprooted trees, between rocks, in tree stumps, and in tree cavities. Skunks never communally denned and individuals frequently reused the same den. Den sites were located in densely forested areas with greater woody understory cover, midstory cover, and snag density and less overstory density than nearby random sites. Dense understory and midstory around skunk den sites likely provided protective cover from predators, particularly owls. Snags may provide additional cover for spotted skunks while offering possible denning or foraging habitat. Habitat management for eastern spotted skunks in the southern Appalachian Mountains should include retention and promotion of dense understory and midstory cover.
Musical Tasks and Energetic Arousal.

Background Music is widely recognized as a motivating stimulus. Investigators have examined the use of music to improve a variety of motivation-related outcomes; however, these studies have focused primarily on passive music listening rather than active participation in musical activities. Objective To examine the influence of participation in musical tasks and unique participant characteristics on energetic arousal. Methods We used a one-way Welch's ANOVA to examine the influence of musical participation (i.e., a non-musical control and four different musical task conditions) upon energetic arousal. In addition, ancillary analyses of participant characteristics including personality, age, gender, sleep, musical training, caffeine, nicotine, and alcohol revealed their possible influence upon pretest and posttest energetic arousal scores. Results Musical participation yielded a significant relationship with energetic arousal, F(4, 55.62) = 44.38, p = .000, estimated ω2 = 0.60. Games-Howell post hoc pairwise comparisons revealed statistically significant differences between five conditions. Descriptive statistics revealed expected differences between introverts' and extraverts' energetic arousal scores at the pretest, F(1, 115) = 6.80, p = .010, partial η2= .06; however, mean differences failed to reach significance at the posttest following musical task participation. No other measured participant characteristics yielded meaningful results. Conclusions Passive tasks (i.e., listening to a story or song) were related to decreased energetic arousal, while active musical tasks (i.e., singing, rhythm tapping, and keyboard playing) were related to increased energetic arousal. Musical task participation appeared to have a differential effect for individuals with certain personality traits (i.e., extroverts and introverts).
Pattern separation and completion of distinct axonal inputs transmitted via micro-tunnels between co-cultured hippocampal dentate, CA3, CA1 and entorhinal cortex networks.

Objective Functions ascribed to the hippocampal sub-regions for encoding episodic memories include the separation of activity patterns propagated from the entorhinal cortex (EC) into the dentate gyrus (DG) and pattern completion in CA3 region. Since a direct assessment of these functions is lacking at the level of specific axonal inputs, our goal is to directly measure the separation and completion of distinct axonal inputs in engineered pairs of hippocampal sub-regional circuits. Approach We co-cultured EC-DG, DG-CA3, CA3-CA1 or CA1-EC neurons in a two-chamber PDMS device over a micro-electrode array (MEA60), inter-connected via distinct axons that grow through the micro-tunnels between the compartments. Taking advantage of the axonal accessibility, we quantified pattern separation and completion of the evoked activity transmitted through the tunnels from source into target well. Since pattern separation can be inferred when inputs are more correlated than outputs, we first compared the correlations among axonal inputs with those of target somata outputs. We then compared, in an analog approach, the distributions of correlation distances between rate patterns of the axonal inputs inside the tunnels with those of the somata outputs evoked in the target well. Finally, in a digital approach, we measured the spatial population distances between binary patterns of the same axonal inputs and somata outputs. Main results We found the strongest separation of the propagated axonal inputs when EC was axonally connected to DG, with a decline in separation to CA3 and to CA1 for both rate and digital approaches. Furthermore, the digital approach showed stronger pattern completion in CA3, then CA1 and EC. Significance To the best of our knowledge, these are the first direct measures of pattern separation and completion for axonal transmission to the somata target outputs at the rate and digital population levels in each of four stages of the EC-DG-CA3-CA1 circuit.
Seed dispersal mutualism and the population density of Asarum canadense, an ant-dispersed plant

The dispersal of seeds from Asarum canadense by ants was studied to quantify variation in mutualistic benefits and to test the hypothesis that this mutualism has effects on population density. Six populations of A. canadense were monitored in SE West Virginia, in the Monongahela National Forest. The rate of seed removal, dispersal distance, microhabitats of dispersed seeds and disperser species were determined in each study site. I measured ovule production and factors causing loss of ovules and the seeds resulting from them through the stage of dispersed seeds. The proportion of seeds removed from the area under the parent plant was the best indicator of dispersal benefits. Few components of dispersal varied among the six sites, but significant variation was observed for capsule formation, ovule development, and pre-dispersal seed predation. Key factor analysis showed pre-dispersal seed predation to be the major factor influencing spatial variation in seed production. Seedling density in 1984 was directly related to seed production in 1983. No population feedback for mutualism was detected.
The Affordable Care Act and Medical Loss Ratios: Federal and State Methodologies

This Policy Brief focuses on the medical loss ratio (“MLR” or “loss ratio”) provision in the Patient Protection and Affordable Care Act (“ACA,” or “Affordable Care Act”). As part of sweeping health care reform in 2010, Congress established MLR requirements for health insurance issuers offering coverage in the group and individual health insurance markets, including grandfathered but not self-insured plans, hoping to increase the value consumers receive for their premiums and to improve transparency. Medical loss ratio refers to a measure of the percentage of premium dollars that a health insurance company spends on health care as distinguished from administrative expenses and profit, including advertising, marketing, overhead, salaries, and bonuses. Prior to the ACA, some states but not the Federal government regulated loss ratios. The new Federal MLR law, which went into effect on January 1, 2011, for the first time established a national MLR standard, which varies from existing state MLR requirements in important ways. This Policy Brief analyzes the new Federal MLR requirements and how they intersect with and affect New Jersey law and its insurance markets. After providing background on medical loss ratios and highlighting the major similarities and differences between the existing Federal and New Jersey MLR regulatory schemes, this Brief examines several requirements and policy options that New Jersey must consider as it implements the Federal requirements. This Brief also includes appendices that provide more extensive details regarding the components of the Federal MLR requirements, New Jersey’s MLR legal structure, and research regarding experiences with loss ratios nationally and in New Jersey, pre- and post-the ACA.
8 – DESIGNING FOR EXPERTISE

Publisher Summary The people who will engage in the application of the new products are in many instances more than users; they are practitioners of trained skills. They are professionals who contribute their knowledge to the application of the new products and systems as they utilize these to accomplish their goals. Expertise is rooted in a particularly deep-level understanding of a domain of practice. This understanding utilizes explanations and reasoning strategies that are extracted from a conceptual model of the domain, constructed and continuously consulted, tested, and updated by the domain expert in the course of practicing in the domain by engaging in activities in order to achieve goals. The conceptual model takes the form of an abstract representation. Understanding how practitioners make decisions and formulate plans for action is a prerequisite for designing systems that facilitate domain expertise in context. This chapter discusses designing for expertise. It illustrates that expertise is comprised of many factors and relies on the training and experience of practitioners in their domain. Expertise represents a convergence of knowledge, skills, and experience that results in competence—the ability to make appropriate decisions and assessments with regard to the situations at hand. Research on expertise is concerned with issues that arise in the course of work with representations in real settings—where people trained to different levels of proficiency work at tasks to different levels of skill. It focuses on factors that determine the knowledge and performance of experts—in roles as operators of artifacts and systems, and as stakeholders that face the complexities posed by novel technology.
Viscoelastic Relaxation in B2O3

The relative ease with which its viscosity can be measured over a wide range of temperature (260–1600°C) has made B2O3 one of the materials most often used to test viscosity theories. It exhibits two Arrhenius regions: a high temperature region between 800–1400°C and a low temperature one, 260–350°C. In a previous publication1 we have shown that none of the theoretical models for viscosity thus far proposed account for this behavior; not only are they inadequate in an exact quantitative sense, but they also fail to explain the general trends. This inadequacy is quite a general one, having been noted in many types of liquids including silicates, molten salts, aqueous solutions and organic liquids. Recognizing the difficulties that other investigators had encountered, our approach to trying to understand viscous flow was to ask a set of fundamental questions followed by an intensive experimental investigation. In this way we hoped that the data would naturally guide the theoretical development.
The Errors in Reporting Medicare Coverage: A Comparison of Survey Data and Administrative Records.

Objectives: We examine survey reporting of Medicare coverage of the older population by evaluating discordance between survey responses and administrative records. Method: We link data from the 201...
Digit Delight: Problem-solving Activities Using 0 through 9

Number puzzles of all kinds offer intriguing challenges to elementary and junior high school students. As the title suggests, this article presents several problem-solving activities involving only the digits 0 through 9. For classroom use, sets often ceramic tiles (each 1-inch square) can be inexpensively made using marking pens, or plastic sets called "Try-A-Tiles" can be purchased. Each set can be stored in a small plastic bag for student use. Students will find the directions easy to follow. The teacher's guidance is helpful to direct students' interaction about their strategies and later to discuss maximum and minimum solutions. Problems can be shown on an overhead projector, as bulletin-board puzzles, or on individual sheets in learning centers. The problems take two forms: those in which tiles are used only in the problem itself, not in the answer; and those in which tiles are used for the problem and the answer. An example of each is illustrated in figure 1 . Additionally, other well-known puzzles are solvable using some or all of the ten digits. Two such puzzles are shown in figure 2 (magic squares and magic triangles). Previous issues of the Arithmetic Teacher (October 1976; March 1977; October 1978) and the Mathematics Teacher (October 1974; May 1983) have published discussions of these puzzles. Most puzzles, including those sug-
Surfing the right ventricular pressure waveform: methods to assess global, systolic and diastolic RV function from a clinical right heart catheterization

Right ventricular (RV) function strongly associates with mortality in patients with pulmonary arterial hypertension (PAH). Current methods to determine RV function require temporal measurements of ...
The History of Noonan Syndrome

Early in her career, Jacqueline Noonan, a pediatric cardiologist, recognized that a number of children with valvular pulmonary stenosis had similar facial features. Dr. Noonan reported the clinical characteristics of this condition including short stature, hypertelorism, ptosis, mild mental retardation, undescended testes, and skeletal malformations. Further characterization of Noonan Syndrome led to the development of clinical criteria for the diagnosis of the condition. Identification of the first genetic cause of Noonan Syndrome, mutation of ptpn11 was reported in 2001. Multiple subsequent genes have been identified as causes of Noonan Syndrome and the related Rasopathies.
Entropy production and entropy extraction rates for a Brownian particle that walks in underdamped medium.

The expressions for entropy production, free energy, and entropy extraction rates are derived for a Brownian particle that walks in an underdamped medium. Our analysis indicates that as long as the system is driven out of equilibrium, it constantly produces entropy at the same time it extracts entropy out of the system. At steady state, the rate of entropy production ${\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{e}}_{p}$ balances the rate of entropy extraction ${\stackrel{\ifmmode \dot{}\else \.{}\fi{}}{h}}_{d}$. At equilibrium both entropy production and extraction rates become zero. The entropy production and entropy extraction rates are also sensitive to time. As time progresses, both entropy production and extraction rates increase in time and saturate to constant values. Moreover, employing microscopic stochastic approach, several thermodynamic relations for different model systems are explored analytically and via numerical simulations by considering a Brownian particle that moves in overdamped medium. Our analysis indicates that the results obtained for underdamped cases quantitatively agree with overdamped cases at steady state. The fluctuation theorem is also discussed.
A daily study of stressors, continuously measured glucose, and diabetes symptoms in latinos with type 2 diabetes.

This study examined whether daily stressors and continuously monitored glucose levels and glucose variability predict daily diabetes symptoms. Fifty Latinos with type 2 diabetes were randomized to either diabetes education (DE-only; N = 23) or DE plus stress management and relaxation training (DE + SMR; N = 32). After treatment, for 7 days they wore ‘blinded’ continuous glucose monitors and reported common stressors and diabetes symptoms twice daily. Between individuals, participants with more numerous overall stressors and more time in hyperglycemia reported higher symptoms. Within individuals, symptoms were higher during intervals of greater than usual stressors. Yet, diabetes symptoms did not covary with changes in glucose levels or glucose variability. The within-person stressor-symptom association was stronger among older individuals and non-significant for participants in DE + SMR condition. Diabetes symptoms were associated with recent stressor exposure, but not recent glucose level or changes in glucose. ClinicalTrials.gov Identifier (No. NCT01578096).
CDllb+ targeted depletion of macrophages negatively affects bone fracture healing

Abstract Inflammation is important part of the fracture repair process which requires osteogenic cells to interact with innate immune cells such as macrophages. All murine macrophages express the F4/80 cell surface marker but they may be further subdivided into two main phenotypes: M1 (proinflammatory) or M2 (anti-inflammatory) based on surface marker expression and function. Macrophages polarize between these two main classes in response to inflammation while differentially regulating the healing process. Studies have shown that F4/80+ cell ablation impairs fracture healing, however, the distinct phenotypes participate in the early healing process is unclear. We hypothesized that the M1 subtype is essential for the early steps of fracture healing and their depletion would impair fracture repair. To test this hypothesis, M1 (F4/80+/MHCII+/CD86+/CDllb+) macrophages were depleted using a saporin conjugated Mac-1 antibody (Mac1SAP) in vitro using primary macrophages and in vivo using a mouse femur fracture model. Primary macrophages isolated from mice femoral bone marrow were either left undifferentiated (+PBS), differentiated into M1 macrophages (+LPS), or differentiated to M2 macrophages (+IL-4), and then treated with either vehicle or 10 pM Mac1SAP. Samples were collected at day 2 and 5 post Mac1SAP treatment. Macrophage subtypes were identified by flow cytometry and cytokine secretion profiles were quantified using xMAP. For the in vivo model, mice were treated with Mac1SAP 24 h prior to fracture. Femur bone marrow samples were collected and analyzed by flow cytometry, xMAP, immunohistochemistry, MicroCT, and histology. The results demonstrated that Mac1SAP significantly potently depleted M1 macrophages both in vivo and in vitro. Mac1SAP treatment altered expression of 75% of cytokines in vitro and 30% of cytokines in vivo including IL-6, TNF-a, and IP-10. In both the in vitro and in vivo models, the M1 subtypes correlated highly with cytokines G-CSF, IL-1α, IL-6, IL-10, LIX, KC, MCP-1, IP-10, MIP1α, MIP1β, RANTES, IL-9, IL-2 and TNFα. M1 depletion was also found to reduced callus properties at day 14 via microCT analysis. Overall, the data suggests that depletion of M1 macrophages by Mac1SAP treatment alters the cytokine expression profiles during early bone repair which ultimately impairs bone healing.
Ten Tips to Create a Legal Writing Course That Prepares Students for The Real World (preprint)

In the past year, COVID-19 has transformed how legal education – and legal writing – is delivered to students. Online instruction replaced in-person instruction, professors and students were forced to adapt quickly to an alternative learning format, and grading policies were adjusted to account for the unique hardships that online learning engendered for many law students. And all of this occurred while administrators, faculty, and students were living in fear of a virus that has killed more than 570,000 citizens in the United States. Notwithstanding, the challenges involved in transitioning to online learning – along with the challenges of transitioning to in-person instruction post-COVID – need not compromise the transformative and practical instruction that legal writing courses can effectuate, regardless of whether through online or in-person instruction. Indeed, several universal principles or designs can ensure that students learn real-world writing and critical thinking skills in online and in-person contexts. Those principles are below and can be useful to both new and experienced legal writing faculty to ensure that legal writing courses provide students with the competencies to succeed in law school and the legal profession.
Time Is Money: Real Effects of Relationship Lending: Evidence from Community Bank Lending in the Paycheck Protection Program.

We provide evidence that the focus of community banks on relationship lending to small businesses combined with their relatively simple organizational structure allowed them to respond faster to Paycheck Protection Program (PPP) loan requests than larger banks. Moreover, we find that community banks lent more per dollar of assets than larger banks. We also find more PPP lending per small business in areas in which community banks have higher pre-pandemic market shares. Finally, using community bank pre-pandemic share of deposits/assets as an instrument for the intensity of PPP lending, we find a negative and significant relationship between county level bankruptcy filings and PPP lending per small business. Overall, our findings suggest that community banks remain an important conduit for small business credit particularly during crises when a rapid response is required.
Perspective on new evidence showing injury under-reporting among precarious workers

Surveillance data are essential to identify and target prevention for all public health activity, including occupational safety and health. Accurate and timely surveillance data are needed to identify new hazards, monitor prevention activity, plan interventions and to evaluate the efficacy of these interventions. All occupational health specialists need to understand the limitations of the surveillance data available to them in order to make the best use of the data in their work. The inadequacies of the surveillance system for nonfatal work-related injuries and illnesses in the USA have been well documented.1 On the other hand, some European countries with their national compensation programmes (eg, the Nordic countries) and labour force surveys (eg, UK) have been looked to as models to follow to improve non-fatal work-related injury and illness surveillance.1 The paper by Kreshpaj et al in this current issue2 and the previous recent publication from the same authors3 show the Swedish system has deficiencies in providing accurate surveillance data that, not surprisingly, are even greater in precarious workers without job security. The Swedish studies used capture–recapture methodology to look at overlap between two databases: Information System on Occupational Injuries (ISA), that has data on work-related injuries and illnesses reported by employers; and data from the AFA, a mutual insurance company, which mainly insures employees covered by collective …
High T/sub c/ superconductor-sapphire microwave resonator with extremely high Q-values up to 90 K

Several high-temperature-superconductor-sapphire TE/sub 011/ mode resonators were designed, fabricated, and tested. At 5.552 GHz, Q/sub 0/ reached 2*10/sup 6/ at 90 K, 3*10/sup 6/ at 80 K, and 1.4*10/sup 7/ at 4.2 K with circulating power up to 500 kW. Formulas for calculating the resonant frequency and Q-value were derived. These theoretical results showed good agreement with the experimental measurements. Applications such as frequency-stabilized oscillators and filters, and the characterizations of high-temperature superconductor films are discussed. >
Affirmative Target Identification: Operationalizing the Principle of Distinction for U.S. Warfighters

The law of armed conflict (LOAC) principle of distinction has long been recognized as the bedrock of the LOAC’s humanitarian protections, and as such States seek to promulgate rules of engagement and other directives that would give force and effect to this principle. In the post-9/11 era, the U.S. has required its forces to obtain “positive identification” of targets prior to attack, defined as “a reasonable certainty” that the proposed target is a lawful one. This article argues that this is a misleading and incomplete formulation of the LOAC principle of distinction, and after an extensive “deconstruction” of the principle of distinction, proposes an alternative that is drawn directly from international jurisprudence and State practice.
Structure and function of Fc receptors for IgE on lymphocytes, monocytes, and macrophages.

Publisher Summary This chapter establishes that the Fc fragment of immunoglobulins E (IgE) binds with high affinity to specific cell surface receptors (FcɛR) on basophils and mast cells and that cross-linking of FcɛR by antigen–IgE antibody complexes, aggregated IgE or anti-IgE receptor antibodies induces histamine release from these cells. Immunologists were somewhat surprised when it was found that radiolabeled aggregated IgE binds to human lymphocytes and an IgE-dependent killing of schistosomules by rat macrophages (MФ) was described, two observations that suggested the presence of FcɛR on lymphocytes and MФ. Several other researches on the interaction of IgE with lymphocytes and MФ established that these cells carry specific IgE Fc receptors, albeit of a different nature than those on basophils and mast cells. By employing methods involving multiple IgE–FcɛR interactions, such as rosette formation with IgE-coated erythrocytes, cells expressing low-affinity FcɛR can be detected relatively easily. The binding properties of radiolabeled IgE to FcɛR+ human cultured lymphoblastoid cells mouse lymphocytes, cultured human U937 MФ and The binding properties of radiolabeled IgE to FcɛR+ human cultured lymphoblastoid cells, mouse lymphocytes , cultured human U937 MФ have been reported.
Structured versus Semistructured versus Unstructured Interviews

The clinical diagnostic interview is used in the mental health field to help clinicians assign reliable and valid psychiatric diagnoses. This diagnostic process has significant applications in both clinical and research settings. Clinical interviews vary with respect to how much structure they have, ranging from completely unstructured to completely structured. This entry reviews three types of clinical diagnostic interview (unstructured, semistructured, and fully structured interviews) and discusses the strengths and weaknesses of each. The entry also includes a brief review of popular semistructured and structured diagnostic interviews for clinical and personality disorders. Keywords: mental health; practice in clinical psychology; abnormal; assessment; diagnosis; interviewing; personality disorders
Delving Into Teachers’ Development Through Portfolio Reflections: Case Studies of Three Teachers

As part of longitudinal research on the role and scope of portfolios in teacher education programs, this study employs a case study approach to systematically examine the portfolio contents and reflections of three teachers enrolled in an advanced professional development master’s degree program in education; the three teachers were purposely selected as representative of the teachers in our program. Specifically, we examined the written reflections submitted in their program portfolios and transcripts from their exit presentations to identify connections to program learning outcomes and to gain insight into the scope and nature of the change of the teachers during the program. We sought to identify influences that program experiences had on their growth and their teaching practice. We contend that by thorough and systematic examination of portfolio contents, and in particular teachers’ reflections included in the portfolios, programs can gain insights into teachers’ learning, practices, and critical reflection which, in turn, may be used to inform program decisions.
Melatonin Receptors in Central Nervous System

The functional role of melatonin receptors in the mammalian central nervous system and their therapeutic potential is discussed. Melatonin, dubbed the “hormone of darkness,” is produced primarily in the pineal gland and retina following circadian rhythms with high levels of night. The chapter describes the structure, molecular pharmacology, signaling, and function of the MT1 and MT2 mammalian melatonin receptors. This is followed by discussion of recent advances in the regulation of melatonin receptor sensitivity and its role in circadian rhythm modulation by the circadian timing system. Recent advances in the discovery and development of therapeutic agents targeting melatonin receptors for the treatment of insomnia, circadian rhythm dysfunctions, and depression are also highlighted. Keywords: MT1 and MT2 melatonin receptors; luzindole; 4P-PDOT; suprachiasmatic nucleus; circadian rhythms; sleep; depression
Peritoneal Dialysis Underutilization: The Impact of an Interventional Nephrology Peritoneal Dialysis Access Program

Peritoneal dialysis (PD) is an underutilized form of renal replacement therapy. Recent data have emphasized that only 12% of end-stage renal disease (ESRD) patients are initiated on this form of therapy in the United States. Patients requiring PD have most often been referred to general surgeons for catheter placement. This has incurred additional delays in starting treatment and loss of decision-making control by the referring nephrologist. To address this issue, we developed and incorporated our own PD access placement program into the preexisting chronic kidney disease (CKD) education program. To date, 46 patients have undergone 71 procedures. These included 51 (72%) PD catheter insertions, 14 (20%) removals, and 6 (8%) repositioning procedures for poor drainage. PD catheter insertion was performed peritoneoscopically under local anesthesia and a Fogarty catheter was used to reposition a migrated catheter. All of the procedures were performed by nephrologists in a dedicated interventional nephrology (IN) laboratory. All six repositioning procedures failed to restore optimal drainage. Five of these patients had the catheter removed and a new catheter placed during the same procedure. Of these five patients, one had recurrence of poor drainage and opted for hemodialysis (HD). The sixth patient declined reinsertion and chose HD. Of the remaining seven removal procedures, three were due to fungal peritonitis, one due to bowel perforation, one due to severe depression, one due to transplant, and one catheter was removed at the request of the primary physician in a terminally ill patient. Eight of the 51 catheter insertions were during the initial admission of a catastrophic dialysis start. Two of these patients started acute PD and avoided catheter placement for HD. Thirty-seven of 46 patients have a functional PD catheter with a follow-up of 8.6 +/- 0.8 (mean +/- SE) months. During an 18-month period our PD population has increased from 43 to 80 patients. We conclude that a dedicated PD access placement program coupled with a CKD education program can have a dramatic impact on patient choice and PD growth.
Inelastic Electron Scattering Spectroscopy

Publisher Summary Spectroscopy, in one form or another, plays a key role in the evolution of modern physics-optical spectroscopy and atomic physics being the canonical example. One studies the energy dependence of the emission or absorption of some kind of particle or field by a selected sample material. This energy dependence reveals dynamical information about the sample. The most successful kinds of spectroscopy are those in which the particle and sample interact only weakly, because then the dynamical information is characteristic of the unperturbed sample. The chapter provides a comparison between four spectroscopies of solids revealing the range of energies and wave vectors accessible to each. The diagonal line represents optical absorption. It is impossible to independently vary the energy and momentum of a photon, as Maxwell's equations fix one once the other is known. Therefore, any excitation in a solid that is created by absorption of a photon must lie on the line shown. A beam of particles is incident on the sample and scatters through some angle, losing certain energy. If multiple scattering is not a problem, then the energy lost and momentum transferred in the sample are ascribed to the creation of a single excitation. By varying the scattering angle and the energy loss, an entire region in energy-momentum space is studied.
Analysis of Data Relevant to Establishing Outer Limits of a Continental Shelf under Law of the Sea Article 76

Coastal states may extend the limits of their juridically defined continental shelf beyond 200 nautical miles from their baselines under the provisions set forth in Article 76 of the United Nations Convention on the Law of the Sea (UNCLOS). In a preparatory desktop study, the University of New Hampshire’s Center for Coastal and Ocean Mapping/Joint Hydrographic Center analysed existing U.S. bathymetric and geophysical data holdings, identified data adequacy, and survey requirements to prepare a U.S. claim beyond the Exclusive Economical Zone (EEZ). In this paper we describe the methodology for our desktop study with particular emphasis on how we assembled and evaluated the existing data around the shelf areas of the United States, and estimated where additional surveys may be required.
Reviewing and interpreting the effects of brief alcohol interventions: comment on a Cochrane review about motivational interviewing for young adults.

Background Cochrane recently published a systematic review on motivational interviewing (MI) for alcohol misuse in young adults. The review authors concluded that ‘there are no substantive, meaningful benefits of MI interventions for the prevention of alcohol misuse’ (p. 2), as effect sizes were ‘small and unlikely to be of any meaningful benefit in practice’ (p. 27). As most of these interventions were quite brief, we wish to open a dialogue about interpreting effect sizes in this review and of (brief) alcohol interventions more generally. Analysis We analyze four methodological aspects of the review that likely influenced the author's conclusions about intervention effects: (1) risk of bias assessments, (2) search strategies, (3) assessing the quality of the body of evidence and (4) definitions of sustainability and clinical significance. Conclusions We interpret the effect sizes found in this review to indicate modest yet beneficial and potentially meaningful effects of these interventions, given their brevity and low cost. This interpretation is consistent with other reviews on brief, MI-based interventions and brief interventions more generally. We therefore encourage the field to re-open dialogue about the clinical importance of the effects of MI on alcohol misuse by young adults. Rather than dismissing interventions with small effects, we believe a more fruitful way forward for the field would be to catalogue effect sizes for various alcohol interventions. Such a catalogue would help stakeholders themselves to choose which interventions meet their minimum desired impact, and thus may be suitable given their targeted populations, setting and resources.
Observation of positively charged state generation near the Si/SiO2 interface during Fowler–Nordheim tunneling

In previous work, we have established that thin oxide (40–50 A) MOS structures exhibit, prior to large levels of Fowler–Nordheim injection, the ideal tunneling behavior of a uniform trapezoidal barrier with thick oxide properties. With increasing levels of electron injection towards the Si/SiO2 interface (up to 6×1018 e/cm2), a build‐up of excess current results. This behavior is shown to be due to the generation of positive states in the SiO2 about 14 A from the Si/SiO2 interface, giving excellent agreement with our analysis of charge‐assisted tunneling. The approach is seen to offer a sensitive probe of the oxide interfacial region, capable of locating and detecting as few as 1010 cm−2 positive states. Comparisons are made among three oxidation processes, revealing wet oxides to be more susceptible than dry oxides to the state generation process. The results are consistent with the mechanism of breaking strained Si–O–Si bonds near the interface, observed in x‐ray photoelectron spectroscopy experiments.
A van Kampen theorem

Abstract This paper contains a generalization of the Seifert-van Kampen Theorem to the case in which not all of the elements in the cover contain the basepoint. In particular, a condition on the cover is given which permits the definition of a fundamental group functor from the cover into the category of groups. The colimit of this functor is the fundamental group of X . The techniques used in this paper are similar to those used in [1], where the case of covers in which the intersection of three elements is void was considered.
Improving Local Manufacturing Employment Forecasts Using Cointegration Analysis

Procedures for tracking and forecasting economic conditions in regional economies have evolved significantly over the last 30 years. Much of this evolution has followed developments in macroeconomics, where techniques for tracking/forecasting key economic variables have tended to originate. This technique adoption and adaptation process continues today, as developments in the technique adoption and adaptation process continues today, as developments in the modeling of cointegrated macroeconomic time series have begun to appear in the regional modeling and forecasting literature. This paper presents an effort at modeling a segment of a regional economy using the cointegration testing procedures suggested by Johansen and Jusilius (1990) to develop a forecasting model for manufacturing employment in Milwaukee, WI. The paper demonstrates how Vector Error Correction (VEC) modeling can lead to gains in the accuracy of local manufacturing employment forecasts relative to more traditional VAR models in either levels or first-differenced form. In the process, it demonstrates procedures for developing a relatively simple VEC model that reveals something about the structure of the local manufacturing sector, including possible linkages to the national economy. This information can assist local policy makers in anticipating and adapting to business cycle-related fluctuations in this critical sector of the local economy.
Plutonism, oblique subduction, and continental growth: An example from the Mesozoic of California

Major episodes of Mesozoic plutonism in California correlate with periods of oblique subduction and trench-parallel transport of western California along intrabatholithic faults. Major episodes of plutonism occurred in the Late Jurassic, during left-oblique convergence, and in the mid-Cretaceous, during right-oblique convergence. In contrast, a conspicuous lull in plutonism (but continuation of volcanism) in the earliest Cretaceous coincides with a time when the North America-Farallon convergence vector, although large in magnitude, was oriented perpendicular to the trench. This correlation suggests that plutonism is facilitated by strike-slip faulting within the batholithic belt; one explanation, which helps to solve the plutonic room problem, is that plutons are passively emplaced at releasing bends in the strike-slip faults, and volume is conserved by thrusting at the trench. If this correlation is generally applicable, then it implies that mid-crustal plutonism is limited beneath areas in which the convergence vector is subperpendicular to the trench. Continental growth in such areas may occur dominantly by volcanism.
Biochemical mechanisms of resistance to tiazofurin.

Abstract The purpose of this investigation was to examine factos which regulate the reprogramming of gene expression in tumors responsible for resistance to tiazofurin. To study the resistance phenomenon drug-induced tumor lines were selected and examined for the mechanism of resistance. A comparison of the biochemical expression of resistance to tiazofurin in drug-induced resistant lines of hepatoma 3924A, leukemia L1210 and P388 revealed that the 3 lines expressed similar genetic alterations related to reduced TAD content, decreased NAD pyrophosphorylase activity and increased synthesis of guanylates from salvaging preformed guanine indicating that these 3 factors play an important role in the resistance to tiazofurin. Resistance was stable in the leukemia lines and did not require drug to maintain resistance. Hepatoma 3924A resistant line reverted to sensitive state in the absence of drug selection pressure. NAD pyrophosphorylase activity was substantially deleted in the tiazofurin resistant leukemia lines, but was only signficantly decreased in the hepatoma resistant line, Extensive biochemical alterations including enhanced activity of IMP dehydrogenase, increased inosinate and guanylate pools, and reduced uptake of tiazofurin were ound in the hepatoma line resistant to tiazofurin. To examine the applicability of these results to naturally sensitive and spontaneously resistant tumors, murine tumors were examined. In murine tumors, TAD accumulation, ratios of enzyme activities responsible for the synthesis and degradation of TAD, and the ratios of perturbation of inosinate and guanylate pools following tiazofurin challenge demonstrated significant correlation with the sensitive or resistant nature of the tumors. To extrapolate these observations to human tumor systems, cytotoxicity of tiazofurin and its metabolic effects were compared in 6 human lung cancer cell lines derived from cancer patients with small cell lung cancer (4 lines) and lung adenocarcinoma (2 lines). Cell lines exhibiting greater sensitivity to tiazofurin accumulated significantly larger amounts of TAD and showed signficant reduction of guanylate pools following tiazofurin incubation. The activity of the enzyme responsible for the formation of TAD, NAD prophosphorylase, did not correlate with responsiveness to tiazofurin but the enzyme which hydrolzes TAD, TADase, correlated positively with the status of resistance. These studies demonstrate the adaptability of the factors responsible for the sensitivity of resistance to tiazofurin from experimental animal tumors to human tumor systems, indicating the need to monitor important biochemical parameters such as TAD content and levels of IMP, GTP and dGTP during clinical trials.
Structure and evolution of a family of interspersed repetitive DNA sequences in Caenorhabditis elegans

The structure of three members of a repetitive DNA family from the genome of the nematodeCaenorhabditis elegans has been studied. The three repetitive elements have a similar unitary structure consisting of two 451-bp sequences in inverted orientation separated by 491 bp, 1.5 kb, and 2.5 kb, respectively. The 491-bp sequence separating the inverted 451-bp sequences of the shortest element is found adjacent to one of the repeats in the other two elements as well. The combination of the three sequences we define as the basic repetitive unit. Comparison of the nucleotide sequences of the three elements has allowed the identification of the one most closely resembling the primordial repetitive element. Additionally, a process of co-evolution is evident that results in the introduction of identical sequence changes into both copies of the inverted sequence within a single unit. Possible mechanisms are discussed for the homogenization of these sequences. A direct test of one possible homogenization mechanism, namely homologous recombination between the inverted sequences accompanied by gene conversion, shows that recombination between the inverted repeats does not occur at high frequency.
How important is terminus cliff melt?: a study of the Canada Glacier terminus, Taylor Valley, Antarctica

Abstract The glacier terminus cliffs on Canada Glacier, Taylor Valley, Antarctica represent 2% of the total ablation zone, but account for 15–20% of the overall meltwater runoff from the glacier during the 1995–1996 and 1996–1997 summers. To ascertain what drives this enhanced melt, meteorologic measurements were made on the Canada Glacier terminus cliffs during the summers of 1995–1996 and 1996–1997. The results indicate that, unlike on the glacier surface where sublimation accounted for 40% of the ablation in 1995–1996, on the terminus cliffs ablation is almost entirely due to melt. This melt is driven primarily by shortwave radiation and varies with location on the terminus cliff as a result of varying exposure. Discharge in Andersen Creek, which is fed by Canada Glacier, is correlated with extended periods of above-freezing air temperatures at the terminus cliffs. Since air temperatures in the valley vary as the dry adiabatic lapse rate and the terminus cliffs are significantly lower in altitude than the glacier surface, this implies that terminus melt is important in maintaining streamflow during cool periods, particularly the beginning and end of summer. Terminus cliff melt may, therefore, be instrumental in extending the seasonal streamflow in the dry valleys.
The Spirit in Early Jewish Biblical Interpretation: Examining John R. Levison’s Filled with the Spirit

The following article examines John Levison’s Filled with the Spirit for its overall contribution to pneumatology and in particular its contribution to biblical interpretation. I especially examine his contribution in light of Second Temple Jewish literature and the concept of inspiration and spiritual revelation. Levison’s work has opened up new lines of inquiry from which many new questions have been raised in the area of biblical interpretation and pneumatology.