cssi/SciSciGPT-SciSciNet huggingface dataset:
PROTEIN-PROTEIN INTERACTIONS IN SARCOPLASMIC RETICULUM: FUNCTIONAL SIGNIFICANCE

ABSTRACT Interactions between lipoprotein complexes are common in biological membranes and presumably contribute to a wide range of cooperative phenomena expressed in excitability, receptor functions, transport processes and enzymatic activity. Recent evidence obtained by rapid kinetic, electron microscope, ultracentrifuge, and fluorescence energy transfer techniques suggests that the Ca-transport ATPase of sarcoplasmic reticulum is also a self-associating system in which oligomers (presumably tetramers) of the enzyme are present in equilibrium with monomers and dimers. Incorporation of purified Ca transport ATPase into phospholipid vesicles increases the passive Ca 2+ permeability of the membrane, by several orders of magnitude and it was suggested that the ATPase tetramers may represent ion channels. So far there is no clear evidence that the equilibrium is indeed influenced by the membrane potential and the contribution of other proteins to the formation of ion channels is not entirely excluded. The properties of interacting systems are sharply dependent on concentration. It may be of significance that the concentration of Ca transport ATPase in sarcoplasmic reticulum membranes isolated from muscles of widely different functional characteristics is similar and close to physical saturation. The interesting exception is during early embryonic development when the concentration of Ca transport ATPase in the membrane is 10-30 times less than in adult animals. The increase in enzyme concentration during development is accompanied by abrupt appearance of contractile activity. Intracellular free [Ca 2+ ] is probably an important regulator of the concentration of Ca transport ATPase during development and in adult animals.
Bypass-Transition Research: Issues and Philosophy

The genesis of wall turbulence in open-flow systems generally starts with slightly perturbed quasi-two-dimensional, quasi-steady laminar wall layers, quasi-homogeneous in the streamwise x- and spanwise z-directions. A primary instability brings about a quasi-periodic vorticity structure in one spatial direction. At least one secondary instability of the (near) saturated primary vortical structures must then take place to prepare the stage for the unsteady , x- and z-nonhomogeneous vorticity structures observed in wall turbulence.
Inguinodynia: Nonoperative Management

Chronic postherniorrhaphy pain is a significant burden on society, and prevention by meticulous hernia repair is essential to reduce this burden. Preoperative identification of patients who are likely to suffer from chronic pain is possible by identifying risk factors. A detailed history and targeted physical examination is required to identify the cause of pain, and diagnostic tests like CT scan or MRI can help rule out treatable causes of pain. Once the diagnosis of chronic postherniorrhaphy pain has been made, a multimodal, multidisciplinary approach to treatment is necessary. Referral to a dedicated pain management facility may be warranted. Identification and treatment of comorbidities is important in the management of all types of chronic pain. Patients should be pharmacologically optimized with antidepressants, antiepileptics, NSAIDs, and topical medications. Patients who have pain in classical nerve distributions should undergo diagnostic and potentially therapeutic nerve blocks. Neuroablation and neuromodulation are promising techniques that may help avoid repeat surgery.
A Combinatorial Testing Framework for Intuitionistic Propositional Theorem Provers

Proving a theorem in intuitionistic propositional logic, with implication as its single connective, is known as one of the simplest to state PSPACE-complete problem. At the same time, via the Curry-Howard isomorphism, it is instrumental to find lambda terms that may inhabit a given type.
Long-Range Chromatin Interactions in the Kidney.

Genome-wide association studies (GWAS) have emerged as one of the most powerful tools to define DNA sequence variants associated with common diseases or phenotypes. Massive phenotyping efforts coupled with inexpensive genotyping arrays have resulted in GWAS data on millions of individuals and an
Living Laparoscopic Donor Nephrectomy

Given the nearly 60,000 patients waiting for renal transplantation, living donor nephrectomy has become a significant source of kidney donation supplementing the shortage of available cadaveric kidneys in the United States. The first laparoscopic living donor nephrectomy (LLDN) was performed by Ratner 10 yr ago with the aim of reducing the morbidity associated with the open procedure. Since that time, more than 200 institutions worldwide have gained expertise in performing LLDN. In 2004, it was estimated that more than 10,000 kidneys had been retrieved with laparoscopic assistance.
Early differential elevation and persistence of phosphorylated cAMP-response element binding protein (p-CREB) in the central nervous system of hens treated with diisopropyl phosphorofluoridate, an OPIDN-causing compound.

Diisopropyl phosphorofluoridate (DFP) produces organophosphorus-ester-induced delayed neurotoxicity in sensitive species. We studied the effect of single dose of DFP on the expression of phosphorylated cAMP-response element binding protein (p-CREB), which is a well known transcription factor involved in several pathways mediating different types of external stimuli. The hens were perfused with neutral buffered formalin at different time points, i.e., 0.5, 1.0, and 2.0 hrs, as well as 1, 2, 5, and 20 days after dosing. The central nervous system regions of the whole brain were dissected and 7-micron sections were stained for either p-CREB immunopositivity or with hematoxylin and eosin. Results indicated an early differential increase of p-CREB immunopositivity in susceptible regions such as cerebellum, brainstem, and midbrain within 2 hrs. These induced levels persisted upto 5 days in these tissues, although the time course of p-CREB immunopositivity was distinctly different for each region. In the cerebellum induction of p-CREB was seen in the granular layer where both the granulocytes and the glial cells showed induction. Increased immunopositivity for p-CREB in the Purkinje cells and in some basket cells of the molecular layer was noticed over time, but the induction was not as great as in the granular layer. Of all the tissues cerebellum showed the strongest intensity of immunopositivity of the cells as well as the highest (absolute) number of pCREB-positive cells. The brainstem showed a similar fluctuating pattern like the cerebellum with the highest percentage increase of the immunoreactive cells at 5 days preceded by the lowest dip in immunopositivity at 2 days. In the midbrain, there was a time-dependent increase in the immunopositivity from 0.5 hr onwards until reaching control levels at 20 days. Immunopositivity was also noted in portions of the spina medularis and spina oblongata. The cerebrum (non-susceptible tissue) of DFP-treated hens did not show much deviation from the controls. The endothelial cells of the susceptible regions showed induction at early time points, in contrast to the absence of induction in cerebrum. Spatial and temporal differences in the immunopositivity pattern indicate probable involvement of CREB-independent pathways also. Overall, the complex induction pattern of p-CREB, along with our earlier observations of the early induction of c-fos, c-jun and Protein Kinase A (PKA) as well as the induction of Calcium2+/Calmodulin dependent Protein Kinase II (CaM kinase II) at later periods, strongly suggest an activator role of CREB mediated pathways that may lead to the clinical development of delayed neurotoxicity.
Galois Theory of Equations

In this chapter we shall consider the classical application of Galois theory: Galois’ criterion for solvability by radicals of a polynomial equation f(x) = 0. To say that an equation is solvable by radicals means roughly that its roots can be obtained from the coefficients by rational operations and root extractions. A criterion for this was given by Galois after Abel and Ruffini had proved that the general equation of the fifth degree is not solvable by radicals. Galois was led to the development of his theory in order to give the criterion for solvability by radicals. Besides the fundamental group-field correspondence which we gave in the last chapter and whose scope goes far beyond the theory of equations, some results of a more special nature are needed. These concern cyclotomic fields, that is, fields of the roots of 1, and “pure” extensions P = Φ(θ), θ n = α. in Φ. The study of these fields is interesting also beyond the theory of equations and we shall undertake a detailed study of such fields in the next chapter. In the present one we confine ourselves to the minimum which is needed for the theory of equations.
Response of composite engineering structures to combined fire and mechanical loading and fatigue durability

Abstract The adoption of composites has been driven in recent years by various performance advantages traditionally constructed from metals, concrete, and timber strictures. However, shortcomings exist for composites in our ability to predict their performance with a level of confidence suitable for regular deployment. Certification and standardization bodies must rely on predictive methods to advancing the use of composites in various applications in the absence of years of demonstrated confidence in performance and cost. Thus, the need remains to improve our fundamental understanding of composite material performance. In this chapter, we focus on the fundamentals of structural fire response for composite materials in ship applications and mechanics of composite fatigue performance in marine and wind energy. We review the state of our understanding of our ability to predict composite material system structural fire and fatigue performance under spectrum loading and comment on future directions for research.
Exceptional surfaces in PT-symmetric non-Hermitian photonic systems

Exceptional points in non-Hermitian systems have recently been shown to possess nontrivial topological properties and to give rise to many exotic physical phenomena. However, most studies thus far have focused on isolated exceptional points or one-dimensional lines of exceptional points. Here, we substantially expand the space of exceptional systems by designing two-dimensional surfaces of exceptional points, and find that symmetries are a key element to protect such exceptional surfaces. We construct them using symmetry-preserving non-Hermitian deformations of topological nodal lines, and analyze the associated symmetry, topology, and physical consequences. As a potential realization, we simulate a parity-time-symmetric 3D photonic crystal and indeed find the emergence of exceptional surfaces. Our work paves the way for future explorations of systems of exceptional points in higher dimensions, and applications in emission control and sensing.
Statistical Properties and Airspace Capacity for Unmanned Aerial Vehicle Networks Subject to Sense-and-Avoid Safety Protocols

Random mobility models (RMMs) capture the random mobility patterns of mobile agents, and have been widely used as the modeling framework for the evaluation and design of mobile networks. All existing RMMs in the literature assume independent movements of mobile agents, which does not hold for unmanned aircraft systems (UASs). In particular, UASs must maintain a safe separation distance to avoid collision. In this paper, we propose a new modeling framework of random mobility models equipped with physical sense-and-avoid protocols to capture the flexible, variable, and uncertain movement patterns of UASs subject to separation safety constraints. For the random direction (RD) RMM equipped with a commonly used sense-and-avoid (S&A) protocol, named sense-and-stop (S&S), we provide its statistical properties including stationary location distribution and stationary inter-vehicle distance distribution, using the Markov analysis. This study provides knowledge on the impact of S&A protocols to critical UAS networking statistics. In addition, we define collision probabilities and airspace capacity concepts for UASs based on the inter-vehicle distance distribution, and derive their closed-form expressions. This analytical framework mathematically bridges local autonomy with global airspace capacity, and allows the impact analysis of local autonomy configurations for effective UAS airspace capacity management.
Umbilical amnion and amniotic membrane transplantation for infectious scleritis and scleral melt: A case series.

Abstract Purpose To report the outcomes of two cases of infectious scleritis with severe scleral thinning managed using combined mechanical debridement, cryopreserved umbilical amnion (UA) and amniotic membrane (AM) grafts, and antimicrobial therapy. Observations Two patients presented with severe infectious scleritis with progressive scleral melts secondary to Pseudomonas aeruginosa subsequent to pterygium surgery and intravitreal injection, respectively. Surgical debridement was followed by UA grafting, AM transplantation, and antimicrobial therapy. Epithelialization and vascularization were seen within 1–4 weeks post-operatively. At last follow up of 5–6 months, the structural integrity of the sclera remained preserved with no infection recurrence, graft necrosis, or wound dehiscence. Conclusions and importance This case series highlights the utilization of UA grafting along with AM transplantation and topical and systemic antibiotics to preserve the globe in cases of severe infectious scleritis.
The Erosion of Common Law Privacy and Defamation: Reconsidering the Law's Balancing of Speech, Privacy, and Reputation

Privacy and reputation have come under siege because of new technologies, the general communications practices of society, and the changing journalism environment. At the same time, the common law's ability to provide an effective remedy for privacy and reputation harms has diminished. A major reason for this shortcoming is that the common law does not give enough weight to privacy and reputation when balanced against speech interests. Even in common law torts -- where the constitutional protections of speech may not apply -- free speech is seen as a vital foundation in the structure of democratic society. This Article argues that privacy and reputation are also vital foundations. What common law courts almost always fail to recognize are the broader social underpinnings of privacy and reputation, and how a healthy democratic society depends on a vibrant respect for individual privacy and reputation. Therefore, as this Article argues, courts should reconsider the common law's overweighing of speech in both privacy and defamation torts, because privacy and reputation (like speech) serve vital social roles and important individual interests.
The Solanum lycocarpum butter

The wolf apple is otherwise known as fruit of wolf. It is grown in small brushes or small branched tree. It is perennial. It belongs to the family of tomato, but it is wild species. Now-a-days most of the people are suffer by diabetes, heart problem, hypertension, hypercholestrolemia, blood pressure,obesity due to high cholesterol in our body.The overall raised cholesterol is estimated to cause 2.6 million death and 29.7 million people cannot lead their normal life.Not only it control cholesterol but also it contains many medicine benefits,like resist slash and burn.The main advantage it is grown in dry and arid conditions.So it is grown where the cultivation is less due to irrigation.
Too much of a good thing: Excess exercise can harm mitochondria.

Health benefits of aerobic exercise are indisputable and are closely related to the maintenance of mitochondrial energy homeostasis and insulin sensitivity. Flockhart et al. (2021) demonstrate, however, that a high volume of high-intensity aerobic exercise adversely affects mitochondrial function and may cause impaired glucose tolerance.
Using Manpower Policies to Transform the Force and Society: The Case of the Pakistan Army

Military manpower policies have an impact beyond the garrison. Policymakers have long held that military service can darn social fabrics that have been rent by ethnic, communal, class, and other cleavages, while scholars debate whether and how this occurs. Because military participation has implications for citizenship, marginalized groups have campaigned to be allowed to participate in the military, and leveraged their service to achieve greater enfranchisement. Military service affects the society as a whole in other ways as well: for example, leaders with military experience are less likely than others to prefer military force when other options are available. This paper examines the Pakistan Army, which, with its domination of the state, feared Islamist tendencies, and incessant belligerence toward India, seems to differ markedly from other militaries. But, using army recruitment and household survey data, it shows that even the Pakistan Army has used personnel policies to reshape its force, despite t...
Acute urinary retention in pediatric cerebral palsy: Is there an optimal management strategy?

Summary Introduction and objective Cerebral palsy (CP) patients commonly have lower urinary tract dysfunction. Urinary retention (UR), which has been associated with dysfunctional voiding in CP can correlate to chronic upper tract dysfunction. We sought to provide insight into the pediatric presentation of acute UR in patients with CP and subsequent outcomes in this at-risk population. Study design All children with perinatally acquired CP presenting to a regional health network were identified from 2009 to 2019. Retrospective analysis of a hospitalized subset concurrently diagnosed with a first episode of acute UR was performed. Factors associated with new-onset UR are described, as well as management. Using follow-up data, we also assessed the risk for recurrent UR and/or abnormal renal imaging after an initial UR presentation. Results 3404 CP patients were analyzed with only 33 fulfilling inclusion criteria. Median age was 10(IQR 7.5–16; range 1–22) years, 87.9% were GMFCS-V. 39.4% had a reported history of decreased urinary frequency. At presentation, median maximal time without void prior to catheterization was 13 h, and catheterized volume was a median 120% expected capacity-for-age. 84.8% of presentations were associated with a known transient/reversible etiology. 51.5% were post-anesthesia at median 3.5 days, 33.3% had associated constipation, 30.3% had received exacerbating medications. 11/33 were taught clean intermittent catheterization (CIC) after the initial presentation (all pro re nata [PRN] except one). At a median follow-up of 37 months: 50% of those without a CIC PRN no void plan had a repeat episode, at a median of 10.8 months later. Of the patients who had follow-up renal imaging at a median 22.0 months after presentation, 45% had abnormalities: 7 with debris or suspected stones and 2 with collecting system dilation. No factors associated with the initial UR presentation were found to be significantly predictive of recurrence or abnormal follow-up imaging. Discussion Patients with CP presenting with acute UR are often those with the most severe limitations and have a history of decreased urinary frequency. They usually have transient or reversible factors associated with UR presentation, however UR recurrence and abnormal imaging in this population subset is common. Conclusions Pediatric patients with CP who present with acute UR usually present in the context of recent anesthesia and in the setting of exacerbating factors. They are at risk for recurrence and may be best managed with caretaker education of CIC PRN no void to address recurrent episodes. Providers should consider surveillance of these patients for the development of abnormal renal imaging. Download : Download high-res image (822KB) Download : Download full-size image Summary figure
A Sketch Based Game Theoretic Approach to Detect Anomalous Dense Sub-Communities in Large Data Streams

Detecting anomalous subgraphs in a dynamic graph in an online or streaming fashion is an important requirement in industrial settings for intrusion detection or denial of service attacks. While only detecting anomalousness in the system by edge frequencies is an optimal approach, many latent information can get unnoticed in the process, since as a characteristic of the network only edge frequencies are considered. We propose a game theoretic approach whereby using the modularity function we try to estimate in a streaming graph \emph{whether addition of a new edge in the current time tick results in a dense subgraph creation, thus indicating possible anomalous score}. Our contributions are as follows: (a) We propose a novel game-theoretic framework for detecting dense subcommunities in an online streaming environment; (b) We detect such subcommunities using constant memory storage. Our results are corroborated with empirical evaluation on real datasets.
A Brief History of Autism

In the 70 years that have elapsed since the first description of infantile autism considerable progress has been made. The official recognition of the condition in 1980 stimulated further research and around the same time the strong neurobiological and genetic aspects of autism began to emerge. Subsequent research has focused on issues of early diagnosis and intervention, understanding the neural mechanisms of autism, and approach to treatment. Unfortunately the research base varies considerably by age group with much research on younger individuals and rather little on adults—particularly older adults. Recent changes in diagnostic practice may complicate the interpretation of past, and future, research.
Fitting semantics for conditional term rewriting

This paper investigates the semantics of conditional term rewriting systems with negation, which may not satisfy desirable properties like termination. It is shown that the approach used by Fitting [5] for Prolog-style logic programs is applicable in this context. A monotone operator is developed, whose fixpoints describe the semantics of conditional rewriting. Several examples illustrate this semantics for non-terminating rewrite systems which could not be easily handled by previous approaches.
An intervention analysis of the war on poverty

Abstract Intervention analysis is used to examine the impact of the War on Poverty on the proportion of income received by families in the lowest quintile of the income distribution in the United States. Evidence presented indicates that the War on Poverty intervention was of the ‘abrupt start, temporary duration’ type and, thus, that the position of the poor was only temporarily affected by the Economic Opportunity Act of 1964 and subsequent programs. Residual analysis suggest an interesting ancillary political economy hypothesis: government programs which are ‘marginally funded’ are more likely to be subject to political fine-tuning before Presidential elections than those that are ‘well advertised’ and ‘fully funded’.
Association of D4-GDI expression with breast cancer progression

D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We havepreviouslyfound thatD4-GDIwasselectivelyexpressedinbreastcancer celllinesover normalmammaryepithelialcells(45). In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n = 165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues ( p< 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease inmetastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis.
Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction

The hammerhead ribozyme is a self-cleaving RNA broadly dispersed across all kingdoms of life. Although it was the first of the small, nucleolytic ribozymes discovered, the mechanism by which it catalyzes its reaction remains elusive. The nucleobase of G12 is well positioned to be a general base, but it is unclear if or how this guanine base becomes activated for proton transfer. Metal ions have been implicated in the chemical mechanism, but no interactions between divalent metal ions and the cleavage site have been observed crystallographically. To better understand how this ribozyme functions, we have solved crystal structures of wild-type and G12A mutant ribozymes. We observe a pH-dependent conformational change centered around G12, consistent with this nucleotide becoming deprotonated. Crystallographic and kinetic analysis of the G12A mutant reveals a Zn(2+) specificity switch suggesting a direct interaction between a divalent metal ion and the purine at position 12. The metal ion specificity switch and the pH-rate profile of the G12A mutant suggest that the minor imino tautomer of A12 serves as the general base in the mutant ribozyme. We propose a model in which the hammerhead ribozyme rearranges prior to the cleavage reaction, positioning two divalent metal ions in the process. The first metal ion, positioned near G12, becomes directly coordinated to the O6 keto oxygen, to lower the pKa of the general base and organize the active site. The second metal ion, positioned near G10.1, bridges the N7 of G10.1 and the scissile phosphate and may participate directly in the cleavage reaction.
Reproductive Technologies for Prenatal Diagnosis

Reproductive genetic technology provides unprecedented opportunities for pregnant women and their families to obtain direct information about the genetic makeup of their developing fetus. Ultrasonography, maternal serum markers, amniocentesis, chorionic villus sampling and percutaneous umbilical blood sampling already offer opportunities for prenatal diagnosis in early pregnancy. New techniques, such as preimplantation, prenatal diagnosis and fetal cell sorting offer opportunities for prenatal diagnosis in even earlier stages of pregnancy.
The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions.

Abstract In recent years, the observation that the response of patients to opioid drugs may be influenced by properties inherent in the pain or pain syndrome, such as its pathophysiology, has evolved into the belief that certain types of pain e.g., neuropathic pains, may be unresponsive to these drugs. This concept has important implications for both clinical practice and basic understanding of opioid mechanisms. We critically evaluate opioid responsiveness, particularly as it relates to neuropathic pain, and propose a clinically relevant definition and a paradigm for its investigation. The paradigm is illustrated by analgesic responses to opioid infusion in 28 patients with neuropathic pains and by a detailed presentation of the pharmacokinetic and pharmacodynamic relationships in one of these patients, whose central pain responded promptly to an infusion of hydromorphone. From this analysis, we hypothesize that (1) opioid responsiveness in man can be defined by the degree of analgesia achieved during dose escalation to either intolerable side effects or the occurrence of ‘complete’ or ‘adequate’ analgesia; (2) opioid responsiveness is a continuum, rather than a quantal phenomenon; (3) opioid responsiveness is determined by a diverse group of patient characteristics and pain-related factors, as well as drug-selective effects; and (4) a neuropathic mechanism may reduce opioid responsiveness, but does not result in an inherent resistance to these drugs. Given the complexity of factors contributing to opioid responsiveness and the observation that outcome cannot be reliably predicted, opioids should not be withheld on the assumption that pain mechanism, or any other factor, precludes a favorable response. Both the clinical use of opioids and paradigms to investigate opioid responsiveness should include dose escalation to maximally tolerated levels and repeated monitoring of analgesia and other effects.
Photoemissive scanning microscopy of doped regions on semiconductor surfaces

Photoelectric emission induced by a focused UV laser beam (λ=257 nm) has been used to probe semiconductor surfaces. It was possible to distinguish between regions of different doping levels on a silicon surface. The spatial resolution was found to be limited only by the laser beam spot size.
"It's Been Real": Forms of Television Representation.

“Realism” as a notion applied to visual media comes to television studies encrusted with ideas from centuries of debate. This essay suggests that “verisimilitude” is a more fruitful term not only because it is less value laden but because, by definition (“real‐seeming”), it implies the notion of “work.” Television verisimilitude, like all forms of television representation, is a product of engagement between program and viewer in the process of text construction. Television offers varying degrees of verisimilitude, from the preferred naturalized codes that parallel television ‘s achieved ontology of “liveness” to the self‐reflexive nature of verite. I argue that much of the reason a series like Hill Street Blues, whose verisimilitude is so obviously constructed, can appear more “real” is because much of its verisimilitude arises paradigmatically. Viewers, involved in the work of text construction, may engage Hill Street Blues' encoding not so much as verite but as something that most of the rest of televi...
The effect of the duration of GnRH-agonist down regulation before ovarian stimulation on the biological and clinical outcome after intracytoplasmic sperm injection

The object of this study was to compare the biological outcome (oocyte maturity, fertilization, cleavage) and the clinical outcome after a 'long' (15-24 days) and a 'long-long' (25-40 days) protocol of GnRH-agonist administration for intracytoplasmic sperm injection. Group A consisted of 51 patients with a 15-24-day down regulation period and Group B consisted of 35 patients with a 25-40-day down regulation period, all of which entered ICSI due to severe male factor infertility. Duration and amount of gonadotropin stimulation, serum E2 on the day of hCG administration, number of oocytes retrieved, oocyte maturity, fertilization rate, cleavage rate and pregnancy outcome were comparable for the two groups of patients. Therefore, a flexible period of pituitary desensitization can be employed, allowing us to simplify planning for patients and for the medical staff without affecting the outcome of the trial.
Binding of aldosterone by mitochondria-rich cells of the toad urinary bladder.

ALDOSTERONE causes a large increase in the active transport of sodium by the urinary bladder1 of the toad. This response, analogous to the effects of the steroid on the kidney, has been the object of considerable biochemical study2. Aldosterone also enhances the stimulation by neurohypophyseal hormones of sodium and hydro-osmotic flux3,4. Because the response in sodium transport seems quantitatively related to the increment of cyclic AMP generated by vasopressin5, augmentation of the sodium response is presumably related to the larger increment of intracellular nucleotide induced by a given dose of vaso-pressin in steroid-treated bladders6. Using a technique for separating the two major cell types of the bladder mucosal epithelium—the granular (G) and the mitochondria-rich (MR) cells—we found that a response to neurohypophyseal hormones, as reflected by hormone-induced increases in the intracellular cyclic AMP content, is apparently limited to the MR cell7. This apparent synergism of the neurohypophyseal and steroid hormones on transport suggests that their loci of action are in close proximity. We therefore examined the binding of 3H-aldosterone by the two major cell types.
Exercise-induced alterations in pro-inflammatory cytokines and prostaglandin F2α in horses

Abstract Using an established standardized exercise test on a high-speed treadmill, thirteen Thoroughbred racehorses were exercised to fatigue (failure); blood samples were obtained before exercise, at failure, and at 2, 6, 24, 48, and 72 h after exercise. The exercise test induced a systemic inflammatory response characterized by a mild transient endotoxemia, leukocytosis, increased leukocyte expression of mRNA for tumor necrosis factor-α (TNF-α), IL-1β, and IL-6, and increased circulating concentrations of TNF-α and prostaglandin F2α (PGF2α), with the most pronounced changes being evident at failure and 2 h after exercise. Expression of mRNA for IL-6, TNF-α, and IL-1β was increased by 120-fold, three-fold, and four-fold, respectively, when compared to pre-exercise values. Plasma concentrations of 6-keto-PGF1α and PGE2 did not change in response to the exercise test. Collectively, these findings indicate that brief, strenuous exercise induces endotoxemia and a systemic pro-inflammatory response in horses that persists for at least 2 h.
Modeling tritium transport through a deep unsaturated zone in an arid environment

Understanding transport of tritium ( 3 H) in unsaturated zones is critical to evaluating options for waste isolation. Tritium typically is a large component of low-level radioactive waste (LLRW). Studies at the U.S. Geological Survey9s Amargosa Desert Research Site (ADRS) in Nevada investigate 3 H transport from a closed LLRW facility. Two boreholes are 100 and 160 m from the nearest waste trench and extend to the water table at 110 m. Soil-water vapor samples from the deep boreholes show elevated levels of 3 H at all depths. The objectives of this study were to (i) test source thermal and gas-advection mechanisms driving 3 H transport and (ii) evaluate model sensitivity to these mechanisms and to selected physical and hydraulic properties including porosity, tortuosity, and anisotropy. A two-dimensional numerical model incorporated a non-isothermal, heterogeneous domain of the unsaturated zone and instantaneous isotopic equilibrium. The TOUGH2 code was used; however, it required modification to account for temperature dependence of both the Henry9s law equilibrium constant and isotopic fractionation with respect to tritiated water. Increases in source temperature, pressure, and porosity enhanced 3 H migration, but failed to match measured 3 H distributions. All anisotropic simulations with a source pressure component resembled, in shape, the upper portion of the 3 H distribution of the nearest borehole. Isotopic equilibrium limited migration of 3 H, while effects of radioactive decay were negligible. A 500 Pa pressure increase above ambient pressure in conjunction with a high degree of anisotropy (1:100) was necessary for simulated 3 H transport to reach the nearest borehole.
Structure of the LINGO-1–Anti-LINGO-1 Li81 Antibody Complex Provides Insights into the Biology of LINGO-1 and the Mechanism of Action of the Antibody Therapy

Multiple sclerosis (MS) is an autoimmune–inflammatory disease of the central nervous system (CNS) with prominent demyelination and axonal injury. While most MS therapies target the immunologic response, there is a large unmet need for treatments that can promote CNS repair. LINGO-1 (leucine-rich repeat and Ig-containing Nogo receptor interacting protein-1) is a membrane protein selectively expressed in the CNS that suppresses myelination, preventing the repair of damaged axons. We are investigating LINGO-1 antagonist antibodies that lead to remyelination as a new paradigm for treatment of individuals with MS. The anti-LINGO-1 Li81 antibody,BIIB033, is currently in clinical trials and is the first MS treatment targeting CNS repair. Here, to elucidate the mechanism of action of the antibody, we solved the crystal structure of the LINGO-1–Li81 Fab complex and used biochemical and functional studies to investigate structure-function relationships. Li81 binds to the convex surface of the leucine-rich repeat domain of LINGO-1 within repeats 4–8. Fab binding blocks contact points used in the oligomerization of LINGO-1 and produces a stable complex containing two copies each of LINGO-1 and Fab that results from a rearrangement of contacts stabilizing the quaternary structure of LINGO-1. The formation of the LINGO-1–Li81 Fab complex masks functional epitopes within the Ig domain of LINGO-1 that are important for its biologic activity in oligodendrocyte differentiation. These studies provide new insights into the structure and biology of LINGO-1 and how Li81 monoclonal antibody can block its function.
MANDATED EXPERTISE: CONSULTANTS AND LOCAL CAPACITY‐BUILDING

The article looks at the delivery process in capacity-building assistance. Specifically, federal and state mandated requirements that local governments use certain types of professional expertise, ...
The differentiation of emergences into adventitious shoots in peanut, Arachis hypogea (L.)

Abstract In vitro regeneration of peanut may be useful in gene transfer research to develop transgenic peanut plants. The purpose of this study was to determine the feasibility of developing adventitious shoots from emergences. Three different types of explants, viz: whole embryo, whole leaf and hypocotyl were compared for the regeneration potential of their emergences. Segments of explants, including emergences in various stages of differentiation into adventitious shoots, were studied using brightfield and scanning electron microscopy. Emergences, multicellular structures that resemble multicellular trichomes, were observed at the cotyledonary node, petiole base, and on the rachis of the leaf where folioles are attached. Of these sites, the greatest number of emergences was found at the cotyledonary node. Explants grown on a medium containing 10 mg/l thidiazuron (TDZ) for 3 weeks exhibited progressive morphological changes of emergences when compared to controls. Emergences differentiated into three types of adventitious structures with one type resembling radially concentric shoots. These adventitious shoots had an organized apex region from which flattened leaf-like appendages emerged, a central core of procambium that differentiated into vascular tissue, and stomates borne in the epidermal layer. The greatest extent of shoot differentiation occurred at the cotyledonary node. A total of 11% of these shoots developed roots and grew to maturity in a greenhouse. The ability of emergences to form adventitious shoots has important implications for gene transfer research because of their superficial origin in epidermal and subepidermal tissues that would be directly exposed to particle bombardment.
68. Relationships between global epigenetic modifications and NK cell function in women with breast cancer

A diagnosis of breast cancer results in psychosocial distress measured by increased perceived stress (PSS) and depressive mood (CES-D). This psychosocial distress is accompanied by reduced NK cell activity and elevated proinflammatory cytokine production (i.e., immune dysregulation). The effect of psychosocial distress on immune dysregulation has been attributed to elevations in glucocorticoids, such as cortisol. Glucocorticoids can impact gene transcription and alter epigenetic modifications. The purpose of this study was to identify epigenetic modifications hypothesized to underlie this immune dysregulation during periods of psychosocial distress. Global epigenetic modifications were analyzed in woman diagnosed with breast cancer and a matched cancer free group. Relationships among psychosocial distress and global acetylation of histone 4-lysine −8 (H4-K8-Ac) and global phosphorylation of histone 3-serine 10 (H3-S10-P) were measured in NK cells. A significant negative correlation was measured between PSS and global H4-K8-Ac. In contrast, a positive significant correlation was observed among global H4-K8-Ac with NKCA and intracellular perforin levels. Further analysis found the effect of cortisol on perforin to be significantly mediated by global H4-K8-Ac. Conversely, a strong positive relationship was measured between PSS, H3-S10-P and with intracellular interferon gamma levels These data suggest global H4-H8-Ac and H3-S10-P to be important epigenetic modifications associated with both the immune suppressive and immune enhancing effects demonstrable in women experiencing this naturalistic stressor.
Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-α-positive human cells☆

Abstract Bisphenol-A (BPA) shows proliferative actions in uterus and mammary glands and may influence the development of male and female reproductive tracts in utero or during early postnatal life. Because of its ability to function as an estrogen receptor (ER) agonist, BPA has the potential to disrupt normal endocrine signaling through regulation of ER target genes. Some genes are regulated by both estradiol (E2) and BPA, but those exclusive to either agent have not been described. Using a yeast strain incorporating a vitellogenin A2 ERE- Lac Z reporter gene into the genome, we found that BPA induced expression of the reporter in colonies transformed with the ER α expression plasmid, illustrating BPA-mediated regulation within a chromatin context. Additionally, a reporter gene transiently transfected into the endometrial cancer (Ishikawa) cell line also showed BPA activity, although at 100-fold less potency than E2. To compare global gene expression in response to BPA and E2, we used a variant of the MCF-7 breast cancer cell line stably expressing HA-tagged ER α . Cultures were treated for 3 h with an ethanol vehicle, E2 (10 −8 M), or BPA (10 −6 M), followed by isolation of RNA and microarray analysis with the human U95A probe array (Affymetrix, Santa Clara, CA, USA). More than 300 genes were changed 2-fold or more by either or both agents, with roughly half being up-regulated and half down-regulated. A number of growth- and development-related genes, such as HOXC1 and C6, Wnt5A, Frizzled, TGF β -2, and STAT inhibitor 2, were found to be affected exclusively by BPA. We used quantitative real-time PCR to verify regulation of the HOXC6 gene, which showed decreased expression of approximately 2.5-fold by BPA. These results reveal novel effects by BPA and E2, raising interesting possibilities regarding the role of endocrine disruptors in sexual development.
Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes

The Rad52 protein has critical functions in distinct pathways of the homology-directed DNA repair, one of which is to promote the annealing of complementary strands of DNA. Both yeast and human Rad52 proteins organize into ring-shaped oligomers with the predominant form being a heptamer. Despite the wealth of information obtained in previous investigations, how Rad52 mediates homology search and annealing remains unclear. Here, we developed single-molecule fluorescence resonance energy transfer approaches to probe hRad52-mediated DNA annealing events in real time. We found that annealing proceeds in successive steps involving rearrangements of the ssDNA-hRad52 complex. Moreover, after initial pairing, further search for extended homology occurs without dissociation. This search process is driven by an interaction between 2 overlapping nucleoprotein complexes. In light of these observations we propose a model for hRad52-mediated DNA annealing where ssDNA release and dsDNA zippering are coordinated through successive rearrangement of overlapping nucleoprotein complexes.
Lethal and sublethal effects of chlorantraniliprole on three species of Rhagoletis fruit flies (Diptera: Tephritidae).

BACKGROUND: Chlorantraniliprole formulated as a 350 g kg−1 WG (Altacor 35WG) for management of apple maggot Rhagoletis pomonella (Walsh), blueberry maggot R. mendax Curran and cherry fruit fly R. cingulata (Loew) (Diptera: Tephritidae) was evaluated in laboratory assays and field trials. RESULTS: A tarsal contact toxicity bioassay showed that a surface residue of 500 mg L−1 of chlorantraniliprole caused significantly higher mortality of male and female flies of all species compared with a control. Male apple maggot and blueberry maggot mortality was significantly higher than that for females, but there was similar mortality of male and female cherry fruit flies. An ingestion toxicity bioassay showed that 500 mg L−1 of chlorantraniliprole in diet caused significantly higher mortality of male and female flies of all species than the control, but there were no significant differences among the sexes. Delayed egglaying by females that had ingested chlorantraniliprole was found, but there were no significant sublethal effects on either the number of eggs laid or the egg hatch. Field trials with apple maggot and cherry fruit fly showed that protection of fruit by chlorantraniliprole was comparable with that of standard broad-spectrum insecticides. CONCLUSIONS: The present data indicate that chlorantraniliprole has suppressant activity against Rhagoletis fruit flies, preventing fruit infestation primarily through direct lethal effects. Copyright © 2008 Society of Chemical Industry
Polyaniline nanofiber/vanadium pentoxide sprayed layer-by-layer electrodes for energy storage

Layer-by-layer assembly, as a low-cost process to create high-performance coatings, has been widely studied over the past 20 years. However, conventional layer-by-layer assembly is not well suited to large-area, large-scale and rapid application because of the long time scale required to complete a multilayer coating. Here, we develop a simple, water-based, rapid spray-on method to produce and prepare polyaniline/vanadium pentoxide layer-by-layer thin film cathodes for Li-ion batteries. This method uses spray-assisted LbL assembly, which is suitable to coating over large areas rapidly. The result is a water-processable hybrid cathode with high capacity (up to 232 mA h g−1 at a discharge current of 5 μA cm−2), specific energy (up to 650 mW h g−1 at a discharge current of 0.5 μA cm−2), specific power (up to 3395 mW g−1 at a discharge current of 25 μA cm−2), and good cycle life. The performance is dependent on thickness and discharge rate. Compared to the traditional polyaniline/vanadium pentoxide prepared by dipping at a rate of 0.0373 nm s−1, sprayed electrodes grow at a significantly high rate of 0.42 nm s−1 – 11 times faster. This approach demonstrates the rapid layer-by-layer assembly of Li-ion battery electrodes without sacrificing performance.
Influence of competitors on caching behaviour in the common raven,Corvus corax

Both territorial breeding common ravens and nonbreeding vagrants scatter-hoard carcass meat extensively. We show experimentally with four captive nonbreeders in a large semi-natural enclosure that common ravens alter their caching behaviour in the presence of conspecifics. When four birds were simultaneously given a small amount of food, which any one bird by itself could easily remove in several trips, all four birds decreased the latency to begin caching and increased caching speed. In contrast, when the four birds were given only enough food for a single individual to control, caching was greatly delayed. If, as these results suggest, competition between conspecifics over food sources induces caching behaviour, then individuals should cache close to the food source to reduce travelling time and increase the time available to effectively compete for food in the presence of conspecifics. Here we show, that in the presence of competitors, common ravens instead cached further from the food source, provided they had space into which they could escape from the sight of the competitors. When escape from competitor vigilance was not possible, common ravens delayed caching and/or hid food when the competitor was preoccupied. A second factor that influenced caching behaviour was cache robbing; ravens not only recovered their own caches, but also routinely recovered the caches they saw others make.