Search

An individual's nutritional status has a powerful effect on sexual maturation. Puberty onset is delayed in response to chronic energy insufficiency and is advanced under energy abundance. The consequences of altered pubertal timing for human health are profound. Late puberty increases the chances of cardiometabolic, musculoskeletal and neurocognitive disorders, whereas early puberty is associated with increased risks of adult obesity, type 2 diabetes mellitus, cardiovascular diseases and various cancers, such as breast, endometrial and prostate cancer. Kennedy and Mitra's trailblazing studies, published in 1963 and using experimental models, were the first to demonstrate that nutrition is a key factor in puberty onset. Building on this work, the field has advanced substantially in the past decade, which is largely due to the impressive development of molecular tools for experimentation and population genetics. In this Review, we discuss the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development, with a focus on perspectives and future directions. Key papers on the role of nutrition and metabolic cues in puberty timing were published in 1963, and there have been many advances in this field in the subsequent 60 years. This Review discusses the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development. Key points: In 1963, Kennedy and Mitra published a seminal study in rats demonstrating that body weight is a major determinant of pubertal timing. An increasing incidence of earlier ages at puberty has been documented; early pubertal timing favours the occurrence of type 2 diabetes mellitus, cardiovascular diseases and certain cancers in adulthood. Macronutrients and hormones that modulate growth and/or signal adipose tissue mass serve as metabolic cues conveying the nutritional status and stored energy available for sexual maturation, differentiation and growth. The effect of metabolic cues on puberty is mediated by neural targets upstream of GnRH neurons; considerable progress in defining the neuronal circuitry and glial components has been achieved. A number of molecular pathways and epigenetic mechanisms have been identified as primary components in the modulation of pubertal timing by hormones and nutritional cues. [ABSTRACT FROM AUTHOR]

Reproductive function is critical for species survival; however, it is energetically costly and physically demanding. Reproductive suppression is therefore a physiologically appropriate adaptation to certain ecological, environmental, and/or temporal conditions. This 'allostatic' suppression of fertility enables individuals to accommodate unfavorable reproductive circumstances and safeguard survival. The mechanisms underpinning this reproductive suppression are complex, yet culminate with the reduced secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, which in turn suppresses gonadotropin release from the pituitary, thereby impairing gonadal function. The focus of this review will be on the role of RFamide-related peptide (RFRP) neurons in different examples of allostatic reproductive suppression. RFRP neurons release the RFRP-3 peptide, which negatively regulates GnRH neurons and thus appears to act as a 'brake' on the neuroendocrine reproductive axis. In a multitude of predictable (e.g., pre-puberty, reproductive senescence, and seasonal or lactational reproductive quiescence) and unpredictable (e.g., metabolic, immune and/or psychosocial stress) situations in which GnRH secretion is suppressed, the RFRP neurons have been suggested to act as modulators. This review examines evidence for and against these roles. [ABSTRACT FROM AUTHOR]

The article presents the results of the survey of the law of professional responsibility in Indiana from August 2021 to September 2022. Also cited are the per curiam rulings by the state's Supreme Court imposing sanctions for lawyer misconduct, the need for civility in both trials and disciplinary proceedings, and the application of the Rules of Professional Conduct to common ethical dilemmas.

In Fall 2020, all universities in Alberta went with remote delivery of classes due to COVID-19 restrictions. This provided not only teaching challenges, but also opportunities. Professors at three Canadian universities teaching similar undergraduate courses in international political economy decided to use the challenges/opportunities of COVID-19 restrictions to experiment with a World Trade Organization (WTO) simulation across three campuses through remote delivery. Simulations are frequently used for teaching in political science, but what was unusual was doing it through remote delivery. This paper assesses the effectiveness of the experiment. It traces the origins/evolution of the idea, learning objectives for the students, preparation by the professors to design the WTO simulation, and the experience of the actual simulation. It also addresses the challenges (technological, timing, assignments, grading, student anxiety, etc.). In addition, it identifies the steps that were taken to reduce and mitigate the challenges. It also acknowledges the mistakes that were made by the professors in designing and implementing the assignment. These observations and reflections are informed by the materials that the professors prepared, their thoughts on the experience, and the feedback from participating students (through official student evaluations as well as a special survey instrument). It provides lessons for future online simulations. [ABSTRACT FROM AUTHOR]

Orthopedic sports surgery of the knee and shoulder is generally considered to be safe and effective. Vascular complications can occur during or after arthroscopy of either joint. A thorough understanding of anatomy, particularly when placing portals in non-routine locations, is extremely important. Prompt recognition of any vascular complication is of significant importance. This review will discuss the potential vascular complications for both knee and shoulder sports surgery, review the relevant anatomy, and discuss the treatment and expected outcome of each. [ABSTRACT FROM AUTHOR]

Being truthful with patients is a critical foundation of the doctorpatient relationship and is fundamental to development of trust. A professional commitment to truth telling may sometimes contradict other principles of bioethics, which may challenge decision-making for the doctor and/or the treatment team. Practitioners may fail to address all ethical or legal aspects of a case and therefore make inappropriate decisions. [ABSTRACT FROM AUTHOR]

Asthma and chronic obstructive pulmonary disease (COPD) are amongst the most common chronic diseases worldwide, and are largely preventable by improving the quality of the air we breathe. The most commonly deployed treatment, the metered dose inhaler (MDI), uses hydrofluorocarbon propellants, which are powerful greenhouse gases that contribute disproportionately to the climate crisis. Alternative treatment strategies are required if we are to avoid contributing to the worst effects of climate change. These strategies include promoting non-pharmacological therapies like smoking cessation and pulmonary rehabilitation; empowering patients to gain better disease control through written management plans and encouraging preventer, rather than reliever therapies. Pharmacological strategies include: improving inhaler technique and spacer use; minimising propellant release by using smaller volume MDIs and simpler dosing regimes; dose counters to prevent waste; switching to low global warming potential inhalers; and inhaler recycling. There are also opportunities to improve disease control alongside reduced greenhouse gas emissions, including better matching of patients' devices to inhaler technique rather than defaulting to MDIs, stopping unnecessary inhaled steroids in COPD and maintenance and reliever therapy in asthma. New, lower global warming potential propellants are on the horizon, and their introduction could offer a golden opportunity to enhance MDIs usability and sustainability by making them refillable, integrating whistles to optimise inhalation technique, adding integrated caps, optimising materials for recycling and adding dose counters to all MDIs. [ABSTRACT FROM AUTHOR]

Donald Trump's tenure as President of the United States has been among the most disruptive in American history. In many areas, President Trump has upended convention, undermined norms, and cast aspersions on a host of institutions. Trump's imposition of punitive tariffs on steel and aluminum, along with the threat to withdraw from the NAFTA have been significant threats to the Canadian economy. The President's instincts on trade may be one of the few constants in a worldview on foreign policy that has otherwise lacked consistency. This article argues that Trump's actions on trade have other precedents in American history, many of which have similarly embroiled Canada. [ABSTRACT FROM AUTHOR]

A professional commitment to patient confidentiality may sometimes contradict other principles of bioethics. Decisionmaking for doctors and their team can be challenging amidst such conflicting principles, and despite the practitioner's best intentions, withholding information can result in potential consequences such as harm to others. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Approximately half of the diagnosed individuals also experience the metabolic syndrome. Central and peripheral resistance to the hormones insulin and leptin have been reported to contribute to both metabolic and reproductive dysregulation. In PCOS and preclinical PCOS animal models, circulating insulin and leptin levels are often increased in parallel with the development of hormone resistance; however, it remains uncertain whether these changes contribute to the PCOS state. In this study, we tested whether central actions of protein tyrosine phosphatase 1B (PTP1B) and suppressor of cytokine signaling 3 (SOCS3), negative regulators of insulin and leptin signaling pathways, respectively, play a role in the development of PCOS-like phenotype. A peripubertal dihydrotestosterone (DHT) excess PCOS-like mouse model was used, which exhibits both metabolic and reproductive dysfunction. Mice with knockout of the genes encoding PTP1B and SOCS3 from forebrain neurons were generated, and metabolic and reproductive functions were compared between knockout and control groups. DHT treatment induced mild insulin resistance but not leptin resistance, so the role of SOCS3 could not be tested. As expected, DHT excess abolished estrous cycles and corpora lutea presence and caused increased visceral adiposity and fasting glucose levels. Knockout mice did not show any rescue of reproductive dysfunction but did have reduced adiposity compared to the control DHT mice. These data suggest that negative regulation of central insulin signaling by PTP1B is not responsible for peripubertal DHT excess-induced reproductive impairments but may mediate its increased adiposity effects. [ABSTRACT FROM AUTHOR]

Reproductive function in mammals is energetically costly and therefore tightly regulated by nutritional status. To enable this integration of metabolic and reproductive function, information regarding peripheral nutritional status must be relayed centrally to the gonadotropin-releasing hormone (GNRH) neurons that drive reproductive function. The metabolically relevant hormones leptin, insulin and ghrelin have been identified as key mediators of this 'metabolic control of fertility'. However, the neural circuitry through which they act to exert their control over GNRH drive remains incompletely understood. With the advent of Cre-LoxP technology, it has become possible to perform targeted gene-deletion and gene-rescue experiments and thus test the functional requirement and sufficiency, respectively, of discrete hormone-neuron signaling pathways in the metabolic control of reproductive function. This review discusses the findings from these investigations, and attempts to put them in context with what is known from clinical situations and wild-type animal models. What emerges from this discussion is clear evidence that the integration of nutritional signals on reproduction is complex and highly redundant, and therefore, surprisingly difficult to perturb. Consequently, the deletion of individual hormone-neuron signaling pathways often fails to cause reproductive phenotypes, despite strong evidence that the targeted pathway plays a role under normal physiological conditions. Although transgenic studies rarely reveal a critical role for discrete signaling pathways, they nevertheless prove to be a good strategy for identifying whether a targeted pathway is absolutely required, critically involved, sufficient or dispensable in the metabolic control of fertility. [ABSTRACT FROM AUTHOR]

Introduction: Conditionally immortalised human neural progenitor cells (hNPCs) represent a robust source of native neural cells to investigate physiological mechanisms in both health and disease. However, in order to recognise the utility of such cells, it is critical to determine whether they retain characteristics of their tissue of origin and generate appropriate neural cell types upon differentiation. To this end, we have characterised the conditionally immortalised, cortically-derived, human NPC line, CTX0E16, investigating the molecular and cellular phenotype of differentiated neurons to determine whether they possess characteristics of cortical glutamatergic neurons. Methods: Differentiated CTX0E16 cells were characterised by assessing expression of several neural fates markers, and examination of developing neuronal morphology. Expression of neurotransmitter receptors, signalling proteins and related proteins were assessed by q- and RT-PCR and complemented by Ca2+ imaging, electrophysiology and assessment of ERK signalling in response to neurotransmitter ligand application. Finally, differentiated neurons were assessed for their ability to form putative synapses and to respond to activity-dependent stimulation. Results: Differentiation of CTX0E16 hNPCs predominately resulted in the generation of neurons expressing markers of cortical and glutamatergic (excitatory) fate, and with a typical polarized neuronal morphology. Gene expression analysis confirmed an upregulation in the expression of cortical, glutamatergic and signalling proteins following differentiation. CTX0E16 neurons demonstrated Ca2+ and ERK1/2 responses following exogenous neurotransmitter application, and after 6 weeks displayed spontaneous Ca2+ transients and electrophysiological properties consistent with that of immature neurons. Differentiated CTX0E16 neurons also expressed a range of pre- and post-synaptic proteins that co-localized along distal dendrites, and moreover, displayed structural plasticity in response to modulation of neuronal activity. Conclusions: Taken together, these findings demonstrate that the CTX0E16 hNPC line is a robust source of cortical neurons, which display functional properties consistent with a glutamatergic phenotype. Thus CTX0E16 neurons can be used to study cortical cell function, and furthermore, as these neurons express a range of disease-associated genes, they represent an ideal platform with which to investigate neurodevelopmental mechanisms in native human cells in health and disease. [ABSTRACT FROM AUTHOR]

Our main result is a local limit law tor the empirical spectral distribution of the anticommutator of independent Wigner matrices, modeled on the local semicircle law. Our approach is to adapt some techniques from recent papers of Erdös-Yau-Yin. We also use an algebraic description of the law of the anlicommutator of free semicircular variables due to Nica-Speicher, the lineatization trick due to Haagerup-Schultz-Thorbjørnsen in a self-adjointness-preserving variant and the Schwinger-Dyson equation. A by-product ot our work is a relatively simple deterministic version of the local semicircle law. [ABSTRACT FROM AUTHOR]

Introduction: Conditionally immortalised human neural progenitor cells (hNPCs) represent a robust source of native neural cells to investigate physiological mechanisms in both health and disease. However, in order to recognise the utility of such cells, it is critical to determine whether they retain characteristics of their tissue of origin and generate appropriate neural cell types upon differentiation. To this end, we have characterised the conditionally immortalised, cortically-derived, human NPC line, CTX0E16, investigating the molecular and cellular phenotype of differentiated neurons to determine whether they possess characteristics of cortical glutamatergic neurons. Methods: Differentiated CTX0E16 cells were characterised by assessing expression of several neural fates markers, and examination of developing neuronal morphology. Expression of neurotransmitter receptors, signalling proteins and related proteins were assessed by q- and RT-PCR and complemented by Ca2+ imaging, electrophysiology and assessment of ERK signalling in response to neurotransmitter ligand application. Finally, differentiated neurons were assessed for their ability to form putative synapses and to respond to activity-dependent stimulation. Results: Differentiation of CTX0E16 hNPCs predominately resulted in the generation of neurons expressing markers of cortical and glutamatergic (excitatory) fate, and with a typical polarized neuronal morphology. Gene expression analysis confirmed an upregulation in the expression of cortical, glutamatergic and signalling proteins following differentiation. CTX0E16 neurons demonstrated Ca2+ and ERK1/2 responses following exogenous neurotransmitter application, and after 6 weeks displayed spontaneous Ca2+ transients and electrophysiological properties consistent with that of immature neurons. Differentiated CTX0E16 neurons also expressed a range of pre- and post-synaptic proteins that co-localized along distal dendrites, and moreover, displayed structural plasticity in response to modulation of neuronal activity. Conclusions: Taken together, these findings demonstrate that the CTX0E16 hNPC line is a robust source of cortical neurons, which display functional properties consistent with a glutamatergic phenotype. Thus CTX0E16 neurons can be used to study cortical cell function, and furthermore, as these neurons express a range of disease-associated genes, they represent an ideal platform with which to investigate neurodevelopmental mechanisms in native human cells in health and disease. [ABSTRACT FROM AUTHOR]

The article discusses problems with using European or Western notions of culture and civilization when they are applied to the historical actions and histories of non-Western or premodern groups of people. Topics include criticisms of historicism and postcolonialism, the ontology used in the field of history, and anthropocentrism.

Abstract: A fundamental result of free probability theory due to Voiculescu and subsequently refined by many authors states that conjugation by independent Haar-distributed random unitary matrices delivers asymptotic freeness. In this paper we exhibit many other systems of random unitary matrices that, when used for conjugation, lead to freeness. We do so by first proving a general result asserting “asymptotic liberation” under quite mild conditions, and then we explain how to specialize these general results in a striking way by exploiting Hadamard matrices. In particular, we recover and generalize results of the second-named author and of Tulino, Caire, Shamai and Verdú. [Copyright &y& Elsevier]

This paper traces the recent evolution of North American economic and security relations within the context of broader debates in international political economy (IPE) concerning globalization and its effects on the state in the international system. Borrowing from David Lake's discussion of hierarchical sovereignty, this paper argues that efforts to meld security to economics in an integrated North American market devoid of institutions have made sovereignty more hierarchical. It presents an approach to looking at North American integration, which can assist in understanding recent developments that are suggestive of new areas of research and policy development for both practitioners and theoreticians. [ABSTRACT FROM PUBLISHER]

This paper argues that since the completion of the NAFTA in the early 1990s, there has been too much focus on what governments in Ottawa, Washington, and Mexico City have or have not been doing to deepen North American integration. The NAFTA was an anomaly that obscures the larger history of incrementalism that has shaped North America's political economy. A focus on large, government-led integration projects like the NAFTA as a model for North American integration distracts from an examination of the many connections and processes taking place across borders every day. Security has become fully entrenched as a driving paradigm of North American relations. However, much of the activity in this domain and others is taking place at the bureaucratic, sub-state, and non-state levels rather than via active direction from national leadership. As scholars and analysts of North America, we would do well to move away from the NAFTA as a model for negotiating North America's future. [ABSTRACT FROM AUTHOR]

Fast track procedures have been key institutional mechanisms for U.S. trade policy making for nearly three decades. In April 2008, the U.S. House of Representatives made a small change to rules for considering the U.S.-Colombia Free Trade Agreement that significantly undermined fast track. However, these actions are really the culmination of the erosion of the utility of fast track in managing U.S. trade policy in the context of the challenges brought by increased openness in the global economy. Those challenges were laid bare with the first major bilateral agreement considered under fast track rules, the Canada-U.S. Free Trade Agreement in the late 1980s. [ABSTRACT FROM AUTHOR]

There is emerging evidence that there are genetic modifiers of iron indices for HFE gene mutation carriers at risk of hereditary hemochromatosis. A random sample, stratified by HFE genotype, of 863 from a cohort of 31 192 people of northern European descent provided blood samples for genotyping of 476 single nucleotide polymorphisms (SNPs) in 44 genes involved in iron metabolism. Single SNP association testing, using linear regression models adjusted for sex, menopause and HFE genotype, was conducted for four continuously distributed outcomes: serum ferritin (log transformed), transferrin saturation, serum transferrin, and serum iron. The SNP rs884409 in CYBRD1 is a novel modifier specific to HFE C282Y homozygotes. Median unadjusted serum ferritin concentration decreased from 1194 μg/l ( N = 27) to 387 μg/l ( N = 16) for male C282Y homozygotes and from 357 μg/l ( N = 42) to 69 μg/l ( N = 12) for females, comparing those with no copies to those with one copy of rs884409. Functional testing of this CYBRD1 promoter polymorphism using a heterologous expression assay resulted in a 30% decrease in basal promoter activity relative to the common genotype ( P = 0·004). This putative genetic modifier of iron overload expression accounts for 11% (95% CI 0·4%, 22·6%) of the variance in serum ferritin levels of C282Y homozygotes. [ABSTRACT FROM AUTHOR]

We provide a period interpretation for multizeta values (in the function field context) in terms of explicit iterated extensions of tensor powers of Carlitz motives (mixed Carlitz–Tate t-motives). We give examples of combinatorially involved relations that these multizeta values satisfy. [ABSTRACT FROM PUBLISHER]

The article studies the Indiana Law of Professional Responsibility appealed by the Indiana Trial Lawyers Association (ITLA) in 2006 to the Indiana Supreme Court for reconsideration. It notes the decisions of the Supreme Court on several cases involving regulated attorney's fees, judicial misconduct, criminal conduct of lawyers, improper trial strategies used by lawyers and neglect of judiciary on a case.

The article presents scientific experiment which examines an inexpensive device for capillary electrophoresis with fluorescence detection. Capillary electrophoresis has emerged as an alternative to high-performance liquid chromatography. The device was constructed from a student microscope, photomultiplier tube (PMT), PMT base socket, housing, a blue light-emitting diode used to excite fluorescence, a dichroic and long-pass filter, a direct current converter and associated power supplies. The instrument provides sufficient sensitivity to determine the mass of riboflavin present in a nutritional supplement tablet.

Abstract: A method for measuring the concentrations of the five regulated haloacetic acids (HAA5) in drinking water is reported. This method uses ion chromatography to separate HAA5 species, followed by post-column reaction with nicotinamide and detection of the fluorescent products. The result of method detection limit, accuracy, precision, linearity and interference studies are reported. The on-line monitoring method is compared directly to USEPA 552.3 in Memphis drinking water. Though not meant to replace the USEPA 552.3 for compliance monitoring, the proposed method does offer attractive alternatives considering the ease of automation and application of on-line monitoring directly from drinking water distribution systems. [Copyright &y& Elsevier]

The so-called new institutional economics (NIE) has generated important insights in a range of fields including transactions cost economics, property rights law, and economic development. However, the majority of the literature in this field has focused on microeconomic institutions and their impact on economic decision making. Very little of it has attempted to apply the lessons of NIE to broader macroeconomic contexts or to international relations generally. The purpose of this article is to try and apply some of the insights of the NIE to recent events in North American economic integration, and suggest how the NIE could be employed to better understand the impact institutional changes to security since September 11, 2001 are having on economic decision-makers and patterns of North American integration. [ABSTRACT FROM AUTHOR]

A law of large numbers and a central limit theorem are derived for linear statistics of random symmetric matrices whose on-or-above diagonal entries are independent, but neither necessarily identically distributed, nor necessarily all of the same variance. The derivation is based on systematic combinatorial enumeration, study of generating functions, and concentration inequalities of the Poincaré type. Special cases treated, with an explicit evaluation of limiting variances, are generalized Wigner and Wishart matrices. [ABSTRACT FROM AUTHOR]

Abstract: Let X be a nonsingular projective curve of genus one defined over an algebraically closed field of characteristic 0. Let D be a divisor of X of degree and let O be a (closed) point of X. As is well known, there exists a unique morphism such that if and only if the divisor is principal. Our main result is a simple explicit description of the map in terms of Wronskians and certain Wronskian-like determinants lacunary in the sense that derivatives of some orders are skipped. Further, for we interpret our main result as a syzygy from classical invariant theory, thus reconciling our work with a circle of ideas treated in two papers by Weil and a recent paper by An, Kim, Marshall, Marshall, McCallum and Perlis. [Copyright &y& Elsevier]

According to classical and postclassical sources, the early Greek "turannoi" were, by definition,. illegitimate rulers who overturned existing political arrangements and installed rogue monarchic regimes in their place. And on this one fundamental point at least, modern observers of archaic "turannides" seem to have little quarrel with their ancient informants. To this day, it remains axiomatic that Cypselus, Peisistratus, and the rest were autocrats who gained power by usurpation. Whatever their individual accomplishments, they were still, in a word, "tyrants." Relying mostly on evidence from the contemporary literary and material records, the paper questions this time-honored commonplace. Prior to the late sixth century, I contend, there was in fact no absolute distinction between "turannoi" and orthodox leaders in Greek poleis. The former aimed to dominate established oligarchies, not to subvert them. A "turannis" was not yet a species of political regime, illegitimate or otherwise. Rather, it was mainstream oligarchic leadership in its most amplified form, conventional de facto authority writ large. [ABSTRACT FROM AUTHOR]

The article presents information on apriori estimate for arbitrary solutions to the linearized Ricci flow on compact 3-manifolds which may be useful in its study. An important component of Hamilton's program for the Ricci flow on compact 3-manifolds is the classification of singularities which form under the flow for certain initial metrics. Ricci flow uses several techniques, including Harnack inequalities of Li-Yau-Hamilton type, the strong maximum principle for systems, dimension reduction, and the study of the geometry at infinity of noncompact stationary solutions.

The expansion in Schur functions of the product ∏i is well known. It is more or less equivalent to Weyl''s identity for root-systems of type Dn. In this paper we obtain the expansion in Schur functions of the product ∏i0aℓxixj(xiℓ-xjℓ)/(xi-xj)), thus generalizing Weyl''s identity. We obtain this result by systematic calculation in fermionic Fock space. But familiarity with the latter is not a prerequisite for reading this paper. We develop from scratch the modest amount of theory that we need in elementary and purely algebraic fashion, taking pains to integrate the theory with classical symmetric function theory. The tools developed in this paper ought to have many further applications, e.g., to random matrix theory and to computational abelian function theory. [Copyright &y& Elsevier]

The notion of determinant groupoid is a natural outgrowth of the theory of the Sato Grassmannian and thus well-known in mathematical physics. We briefly sketch here a version of the theory of determinant groupoids over an artinian local ring, taking pains to put the theory in a simple concrete form suited to number-theoretical applications. We then use the theory to give a simple proof of a reciprocity law for the Contou-Carrère symbol. Finally, we explain how from the latter to recover various classical explicit reciprocity laws on nonsingular complete curves over an algebraically closed field, namely sum-of-residues-equals-zero, Weil reciprocity, and an explicit reciprocity law due to Witt. Needless to say, we have been much influenced by the work of Tate on sum-of-residues-equals-zero and the work of Arbarello-De Concini-Kac on Weil reciprocity. We also build in an essential way on a previous work of the second-named author. [ABSTRACT FROM AUTHOR]

Faults in complex tectonic environments interact in various ways, including triggered rupture of one fault by another, that may increase seismic hazard in the surrounding region. We model static and dynamic fault interactions between the strike-slip and thrust fault systems in southern California. We find that rupture of the Sierra Madre-Cucamonga thrust fault system is unlikely to trigger rupture of the San Andreas or San Jacinto strike-slip faults. However, a large northern San Jacinto fault earthquake could trigger a cascading rupture of the Sierra Madre-Cucamonga system, potentially causing a moment magnitude 7.5 to 7.8 earthquake on the edge of the Los Angeles metropolitan region. [ABSTRACT FROM AUTHOR]

The abeliant is a polynomial rule which to each n×n by n+2 array with entries in a commutative ring with unit associates an n×n matrix with entries in the same ring. The theory of abeliants, first introduced in an earlier paper of the author, is simplified and extended here. Now let J be the Jacobian of a nonsingular projective algebraic curve defined over an algebraically closed field. With the aid of the theory of abeliants we obtain explicit defining equations for J and its group law. [Copyright &y& Elsevier]

Presents a study which described a modeling analysis of the geochemical evolution of a contaminated sandy aquifer at a uranium mill tailings site in the western United States. Site characteristics; Field sampling and analytical data; Speciation and solubility modeling.

The article discusses a study on an explicit algebraic representation of the Abel map as defined in Theorem 2.5.1. It provides a brief review of the elements of the theory of algebraic functions of one variable dealing with algebraic curves. It notes that a simple and explicit collection of equations are used as a nonsingular projective curve of genus g and an effective divisor G of positive even degree not less than 4g.

Excess levels of circulating androgens during prenatal or peripubertal development are an important cause of polycystic ovary syndrome (PCOS), with the brain being a key target. Approximately half of the women diagnosed with PCOS also experience metabolic syndrome; common features including obesity, insulin resistance and hyperinsulinemia. Although a large amount of clinical and preclinical evidence has confirmed this relationship between androgens and the reproductive and metabolic features of PCOS, the mechanisms by which androgens cause this dysregulation are unknown. Neuron‐specific androgen receptor knockout alleviates some PCOS‐like features in a peripubertal dihydrotestosterone (DHT) mouse model, but the specific neuronal populations mediating these effects are undefined. A candidate population is the agouti‐related peptide (AgRP)‐expressing neurons, which are important for both reproductive and metabolic function. We used a well‐characterised peripubertal androgenized mouse model and Cre‐loxP transgenics to investigate whether deleting androgen receptors specifically from AgRP neurons can alleviate the induced reproductive and metabolic dysregulation. Androgen receptors were co‐expressed in 66% of AgRP neurons in control mice, but only in <2% of AgRP neurons in knockout mice. The number of AgRP neurons was not altered by the treatments. Only 20% of androgen receptor knockout mice showed rescue of DHT‐induced androgen‐induced anovulation and acyclicity. Furthermore, androgen receptor knockout did not rescue metabolic dysfunction (body weight, adiposity or glucose and insulin tolerance). While we cannot rule out developmental compensation in our model, these results suggest peripubertal androgen excess does not markedly influence Agrp expression and does not dysregulate reproductive and metabolic function through direct actions of androgens onto AgRP neurons. [ABSTRACT FROM AUTHOR]

Infertility associated with insulin resistance is characterised by abnormal hormone secretion by the hypothalamus, pituitary gland and gonads. These endocrine tissues can maintain insulin sensitivity even when tissues such as the muscle and liver become insulin‐resistant, resulting in excessive insulin stimulation as hyperinsulinaemia develops. Experiments conducted to determine the role of neuronal insulin signalling in fertility were unable to recapitulate early findings of hypogonadotrophic hypogonadism in mice lacking insulin receptors throughout the brain. Rather, it was eventually shown that astrocytes critically mediate the effects of insulin on puberty timing and adult reproductive function. However, specific roles for neurones and gonadotrophs have been revealed under conditions of hyperinsulinaemia and by ablation of insulin and leptin receptors. The collective picture is one of multiple insulin‐responsive inputs to gonadotrophin releasing hormone neurones, with astrocytes being the most important player. [ABSTRACT FROM AUTHOR]

Lawrie and Margaret had five children, and he is survived by Elizabeth - herself a distinguished hepatologist, Mark, Martine and Christa. GLO:EUW/01nov22:jgh16031-gra-0001.jpg PHOTO (COLOR): . gl More than "Mr. Iron", Lawrie Powell was a Foundation Stone of Asia-Pacific Gastroenterology and Liver disease. Remembering Lawrie Powell 1934-2022. [Extracted from the article]

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in themost common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. To investigate their properties, we isolated glia and neurons from Cln3-deficient mice and studied their basic biology in culture. Upon stimulation, both Cln3-deficient astrocytes and microglia also showed an attenuated ability to transform morphologically, and an altered protein secretion profile. These defects were more pronounced in astrocytes, including the reduced secretion of a range of neuroprotective factors, mitogens, chemokines and cytokines, in addition to impaired calcium signalling and glutamate clearance. Cln3-deficient neurons also displayed an abnormal organization of their neurites. Most importantly, using a co-culture system, Cln3-deficient astrocytes and microglia had a negative impact on the survival and morphology of both Cln3-deficient and wildtype neurons, but these effects were largely reversed by growing mutant neurons with healthy glia. These data provide evidence that CLN3 disease astrocytes are functionally compromised. Together with microglia, they may play an active role in neuron loss in this disorder and can be considered as potential targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Focuses on the conceptual and administrative issues in the creation of a shared serials publication pattern database. Components of the model for a shared database; Changes in the focus of academic libraries; Actions and strategies for serials libraries.

The Navy has a need for monitoring conditions and gathering information in marine environments. Sensors can monitor and report environmental parameters and potential activities such as animal movements, ships, or personnel. However, there has to be a means to power these sensors. One promising enabling technology that has been shown to provide long-term power production in underwater environments is the benthic microbial fuel cells (BMFC). BMFCs are devices that generate energy by coupling bioanodes and biocathodes through an external energy harvester. Recent studies have demonstrated success for usage of BMFCs in powering small instruments and other devices on the seafloor over limited periods of time. In this effort, a seven-stranded BMFC linear array of 30 m was designed to power a seafloor magnetometer to detect passing ship movements through Pearl Harbor, Hawaii. The BMFC system was connected to a flyback energy harvesting circuit that charged the battery powering the magnetometer. The deployment was demonstrated the BMFC supplied power to the battery for approximately 38 days. This is the first large-scale demonstration system for usage of the SeptiStrand BMFC technology to power a relevant sensor. [ABSTRACT FROM AUTHOR]

Reproductive function is tightly regulated by both environmental and physiological factors. The adipose-derived hormone leptin has been identified as one such critical factor that relays information about peripheral energy availability to the centrally-governed HPG axis to ensure there is sufficient energy availability to support the high energy demands of mammalian reproduction. In the absence of adequate central leptin signaling, reproductive function is suppressed. While leptin levels are predominantly regulated by adiposity, circulating leptin levels are also under the modulatory influence of other factors, such as stress system activation, circadian rhythmicity, and immune activation and the inflammatory response. Furthermore, changes in leptin sensitivity can affect the degree to which leptin exerts its influence on the neuroendocrine reproductive axis. This review will discuss the different mechanisms by which leptin serves to integrate and relay information about metabolic, psychological, environmental and immune conditions to the central neuronal network that governs reproductive function. [ABSTRACT FROM AUTHOR]

Agouti‐related peptide (AgRP) neurons are thought to indirectly regulate the activity of hypothalamic gonadotrophin‐releasing hormone neurons which control fertility. AgRP neurons also drive caloric intake and are modulated by metabolically‐relevant hormones, providing a link to the hypothalamic–pituitary‐gonadal axis. In mice expressing Cre‐dependant designer receptors (DREADDs) in AgRP neurons, we activated or silenced these neurons in vivo using the synthetic ligand clozapine‐N‐oxide (CNO) to observe the effect of AgRP neuron activity on timing of puberty. To validate these animals, we chronically treated both stimulatory (hM3Dq) and inhibitory (hM4Di) DREADD × AgRP‐Cre mice with CNO, observing a pronounced increase and decrease of food intake, respectively, consistent with the known orexigenic effects of these neurons. RNAscope was performed to visually confirm the activation of AgRP neurons. Puberty onset was assessed in males and females. There was no effect on preputial separation in males or vaginal opening and first oestrus in females after CNO treatment from day 26 to 30 to chronically modulate AgRP neurons. Next, to determine whether the delay in puberty onset occurring in response to neonatal underfeeding could be overcome by inhibiting AgRP neuronal activity, mice were raised in large (neonatally underfed) or normal litter sizes. The delay in puberty from underfeeding was completely reversed in CNO‐treated AgRP‐hM4Di male mice. These data highlight the inhibitory role of AgRP neurons to delay puberty onset when undernutrition occurs during the neonatal period, at least in male mice. Trail registration number: JNE‐22‐0081‐OA.R2 [ABSTRACT FROM AUTHOR]

Female anti-Müllerian hormone (AMH) overexpressing (Thy1.2-AMHTg/0) mice experience fetal resorption (miscarriage) by mid-gestation. This study examined whether the ovary, uterine implantation sites and hypothalamus are potential sites of AMH action, as AMH type-2 receptor (AMHR2) expression is reported in each tissue. Pregnancy in Thy1.2-AMHTg/0 mice was compared to wild-type (WT) mice via histological examination of implantation sites, hormone assays, embryo culture and embryo transfer. Uterine AMH and AMHR2 expression was examined by RT-qPCR and immunohistochemistry. The first signs of fetal resorption in the Thy1.2-AMHTg/0 dams occurred at embryonic day 9.5 (E9.5) with 100% of fetuses resorbing by E13.5. Cultured embryos from Thy1.2-AMHTg/0 dams had largely normal developmental rates but a small proportion experienced a minor developmental delay relative to embryos from WT dams. However, embryos transferred from WT donor females always failed to survive to term when transferred into Thy1.2-AMHTg/0 dams. Amh and Amhr2 mRNA was detected in the gravid uterus but at very low levels relative to expression in the ovaries. Progesterone and estradiol levels were not significantly different between WT and Thy1.2-AMHTg/0 dams during pregnancy but luteinizing hormone (LH) levels were significantly elevated in Thy1.2-AMHTg/0 dams at E9.5 and E13.5 relative to WT dams. Collectively, these experiments suggest that AMH overexpression does not cause fetal resorption through an effect on oocytes or preimplantation embryo development. The Thy1.2-AMHTg/0 fetal resorption phenotype is nearly identical to that of transgenic LH overexpression models, suggesting that neuroendocrine mechanisms may be involved in the cause of the miscarriage. [ABSTRACT FROM AUTHOR]

Coupling of haloarenes to arenes has been facilitated by a diverse range of organic additives in the presence of KOtBu or NaOtBu since the first report in 2008. Very recently, we showed that the reactivity of some of these additives (e.g., compounds 6 and 7) could be explained by the formation of organic electron donors in situ, but the role of other additives was not addressed. The simplest of these, alcohols, including 1,2-diols, 1,2-diamines, and amino acids are the most intriguing, and we now report experiments that support their roles as precursors of organic electron donors, underlining the importance of this mode of initiation in these coupling reactions. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to report progress concerning the design of a computer-assisted simulation training (CAST) platform for developing decision-making skills in police students. The overarching aim is to outline a theoretical framework for the design of CAST to facilitate police students’ development of search techniques in complex interactions within the built environment, learning to apply and perform the five “quick peek” techniques for information gathering, and subsequent risk evaluation. Design/methodology/approach – The paper draws on Luckin's ecology of resources model of learner context informed with perspectives on reflective thinking from John Dewey and Donald Schön. The paper discusses design issues within the ecology of resources model applied on CAST for complex police situations. Findings – It is suggested that Luckin's framework with its focus on the interaction between different elements and filters in the learner's context together with Schön's perspective on reflection challenge educational designers to look beyond the immediate development of specific tools (such as the CAST in this project) and examine how these tools will be effectively embedded in the overall learning experience. Originality/value – This paper has presented two theoretical perspectives, Luckin's ecology of resources model and Schön's perspective on reflective practice as foundations for the educational design of CAST. Applying Luckin's framework as informed by Schön helps focus attention on issues that are important in the design process in order to facilitate educational transfer. [ABSTRACT FROM AUTHOR]

Study Design. A prospective, randomized study was used to compare 2 anesthesia/analgesia methods for reconstructive spine surgery. Objective. To assess the efficacy and influence of 2 anesthetic methods on clinical outcome and stress response during reconstructive spine surgery. Summary of Background Data. Pain control is an important goal of the postoperative care after spinal surgery. Some prior studies have suggested that epidural anesthesia with or without postoperative epidural analgesia may blunt the surgical stress response after major surgery. This treatment approach has not been fully investigated for patients undergoing major spinal surgery. We hypothesized that the stress response after major spine surgery would be attenuated by continuous epidural anesthesia/analgesia with ropivacaine, fentanyl, and epinephrine. Methods. Eighty-five patients were randomly allocated to 2 groups as follows: group E (n = 45) had epidural anesthesia and endotracheal anesthesia with sevoflurane during surgery and continuous epidural analgesia with ropivacaine, fentanyl, and epinephrine after surgery; group G (n = 40) had general anesthesia with sevoflurane and fentanyl and systemically administered opioids after surgery. Patient pain, nausea, mobility, and satisfaction were measured after surgery along with levels of cortisol, glucose, interleukin (IL)-1β, IL-6, an IL-10 during and after surgery. Results. In group E, there were significantly less pain, less nausea, earlier mobility, and higher satisfaction than those in group G. Group E also experienced significantly less introperative and postoperative blood loss. Group E demonstrated lower levels of glucose, cortisol, IL-1β, IL-6, and IL-10 during the postoperative period. Conclusion. Combined epidural/general anesthesia and postoperative epidural analgesia produced better pain control, less bleeding, and a lower surgical stress response than general anesthesia with postoperative systemically administered narcotic analgesia. This technique deserves further study in the setting of major spinal surgery. [ABSTRACT FROM AUTHOR]

The adipocyte-derived 'satiety promoting' hormone, leptin, has been identified as a key central regulator of body weight and fertility, such that its absence leads to obesity and infertility. Plasma leptin levels reflect body adiposity, and therefore act as an 'adipostat', whereby low leptin levels reflect a state of low body adiposity (under-nutrition/starvation) and elevated leptin levels reflect a state of high body adiposity (over-nutrition/obesity). While genetic leptin deficiency is rare, obesity-related leptin resistance is becoming increasingly common. In the absence of adequate leptin sensitivity, leptin is unable to exert its 'anti-obesity' effects, thereby exacerbating obesity. Furthermore, extreme leptin resistance and consequent low or absent leptin signalling resembles a state of starvation and can thus lead to infertility. However, leptin resistance occurs on a spectrum, and it is possible to be resistant to leptin's metabolic effects while retaining leptin's permissive effects on fertility. This may be because leptin exerts its modulatory effects on energy homeostasis and reproductive function through discrete intracellular signalling pathways, and these pathways are differentially affected by the molecules that promote leptin resistance. This review discusses the potential mechanisms that enable leptin to exert differential control over metabolic and reproductive function in the contexts of healthy leptin signalling and of diet-induced leptin resistance. [ABSTRACT FROM AUTHOR]

Background: Organizations of all types require the use of teams. Poor team member engagement costs billions of US dollars annually. Objective: This study aimed to explain how team building can be accomplished with team video gaming based on a team cohesion model enhanced by team flow theory. Methods: In this controlled experiment, teams were randomly assigned to a team video gaming treatment or a control treatment. Team productivity was measured during both pretreatment and posttreatment team tasks. After the pretest, teams who were involved in the team video gaming treatment competed against other teams by playing the Halo or Rock Band video game for 45 minutes. After the pretest, teams in the control treatment worked alone for 45 minutes. Then, all teams completed the posttest team activity. This same experimental protocol was conducted on 2 different team tasks. Results: For both tasks, teams in the team video gaming treatment increased their productivity significantly more (F1=8.760, P=.004) on the posttest task than teams in the control treatment. Our flow-based theoretical model explained team performance improvement more than twice as well (R²=40.6%) than prior related research (R²=18.5%). Conclusions: The focused immersion caused by team video gaming increased team performance while the enjoyment component of flow decreased team performance on the posttest. Both flow and team cohesion contributed to team performance, with flow contributing more than cohesion. Team video gaming did not increase team cohesion, so team video gaming effects are independent of cohesion. Team video gaming is a valid practical method for developing and improving newly formed teams. [ABSTRACT FROM AUTHOR]

Parasites, as with the vast majority of organisms, are dependent on iron. Pathogens must compete directly with the host for this essential trace metal, which is sequestered within host proteins and inorganic chelates. Not surprisingly, pathogenic prokaryotes and eukaryotic parasites have diverse adaptations to exploit host iron resources. How pathogenic bacteria scavenge host iron is well characterized and is reasonably well known for a few parasitic protozoa, but is poorly understood for metazoan parasites. Strategies of iron acquisition by schistosomes are examined here, with emphasis on possible mechanisms of iron absorption from host serum iron transporters or from digested haem. Elucidation of these metabolic mechanisms could lead to the development of new interventions for the control of schistosomiasis and other helminth diseases. [Copyright &y& Elsevier]