cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacologic ER Stress Induces Non-alcoholic Steatohepatitis in an Animal Model

Endoplasmic reticulum (ER) stress refers to a condition of accumulation of unfolded or misfolded proteins in the ER lumen, which is known to activate an intracellular stress signaling termed Unfolded Protein Response (UPR). A number of pharmacologic reagents or pathophysiologic stimuli can induce ER stress and activation of the UPR signaling, leading to alteration of cell physiology that is associated with the initiation and progression of a variety of diseases. Non-alcoholic steatohepatitis (NASH), characterized by hepatic steatosis and inflammation, has been considered the precursor or the hepatic manifestation of metabolic disease. In this study, we delineated the toxic effect and molecular basis by which pharmacologic ER stress, induced by a bacterial nucleoside antibiotic tunicamycin (TM), promotes NASH in an animal model. Mice of C57BL/6J strain background were challenged with pharmacologic ER stress by intraperitoneal injection of TM. Upon TM injection, mice exhibited a quick NASH state characterized by hepatic steatosis and inflammation. An increase in hepatic triglycerides (TG) and a decrease in plasma lipids, including plasma TG, plasma cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL), were observed in the TM-treated mice. In response to TM challenge, cleavage of sterol responsive binding protein (SREBP)-1a and SREBP-1c, the key trans-activators for lipid and sterol biosynthesis, was dramatically increased in the liver. Consistent with the hepatic steatosis phenotype, expression of some key regulators and enzymes in de novo lipogenesis and lipid droplet formation was up-regulated, while expression of those involved in lipolysis and fatty acid oxidation was down-regulated in the liver of mice challenged with TM. Moreover, TM treatment significantly increased phosphorylation of NF-κB inhibitors (IκB), leading to the activation of NF-κB-mediated inflammatory pathway in the liver. Our study not only confirmed that pharmacologic ER stress is a strong “hit” that triggers NASH, but also demonstrated crucial molecular links between ER stress, lipid metabolism, and inflammation in the liver in vivo.
Is the climate of the Bering Sea warming and affecting the ecosystem

Observations from the Bering Sea are good indicators of decadal shifts in climate, as the Bering is a transition region between the cold, dry Arctic air mass to the north, and the moist, relatively warm maritime air mass to the south. The Bering Sea is also a transition region between Arctic and sub-Arctic ecosystems; this boundary can be loosely identified with the extent of winter sea-ice cover. Like a similar transition zone in the eastern North Atlantic [Beaugrand et al., 2002], the Bering Sea is experiencing a northward biogeographical shift in response to changing temperature and atmospheric forcing. If this shift continues over the next decade, it will have major impacts on commercial and subsistence harvests as Arctic species are displaced by sub-Arctic species. The stakes are enormous, as this rich and diverse ecosystem currently provides 47% of the U.S. fishery production by weight, and is home to 80% of the U.S. sea bird population, 95% of northern fur seals, and major populations of Steller sea lions, walrus, and whales.
Controlled Assembly of Magnetic Nanoparticles from Magnetotactic Bacteria Using Microelectromagnets Arrays

Controlled assembly of magnetic nanoparticles was demonstrated by manipulating magnetotactic bacteria in a fluid with microelectromagnets. Magnetotactic bacteria synthesize a chain of magnetic nanoparticles inside their bodies. Microelectromagnets, consisting of multiple layers of lithographically patterned conductors, generate versatile magnetic fields on micrometer length scales, allowing sophisticated control of magnetotactic bacteria inside a microfluidic chamber. A single bacterium was stably trapped and its orientation was controlled; multiple groups of bacteria were assembled in a fluid. After positioning the bacteria, their cellular membranes were removed by cell lysis, leaving a chain and a ring of magnetic nanoparticles on a substrate.
Managing Endangered Species Within the Use–Preservation Paradox: The Florida Manatee (Trichechus manatus latirostris) as a Tourism Attraction

A significant challenge to wildlife managers in tourism settings is to provide visitors with opportunities to observe rare and endangered wildlife while simultaneously protecting the target species from deleterious impacts. Nearly 100,000 people annually visit Crystal River, Florida, USA to observe and swim with the Florida manatee, an endangered species. This research aimed to investigate and describe human-manatee interactions in a tourism context, to understand the salient issues related to such interactions as identified by stakeholders, and to recommend a course of action to address multiple interests in the planning and management of human-manatee interactions. Five issues were identified by all stakeholder groups: water quality, harassment, density and crowding, education, and enforcement. Currently, the U.S. Fish and Wildlife Service, which is responsible for manatee management, does not have mechanisms in place to manage the tourism component of the manatee encounter. Although a regulatory approach can be taken, a better approach would be to create an organization of tour operators to establish "best practices" that reflect the goal of the managing agency to enhance manatee protection (and thus ensure their livelihood) and to enhance the visitor experience.
Disparate in vivo and in vitro immunomodulatory activities of rhodamine B.

Abstract At nontoxic concentrations (1–10 μg/ml) rhodamine B (N-[9-(2-carboxyphenyl)-6-(diethylamino)-3 H-xanthen-3-ylidene]-N-ethylethanaminium chloride; D & C Red No. 19; CAS no. 81-88-9), a low-molecular-weight dye, suppressed the primary in vitro plaque-forming-cell response of BDF1 mouse spleen cells both to the thymus-dependent antigen, sheep red blood cells and to the thymus-independent antigen, E. coli 0127:B8 lipopolysaccharide. Suppression was effective when the D & C Red No. 19 was added at any time up to 48 hr of culture. Rhodamine B at concentrations from 1 to 10 μg/ml significantly suppressed mitogen-induced proliferation of both B- and T-lymphocytes in vitro. BDF1 mice exposed to 50 and 100 ppm dye in their drinking water for 14 days prior to splenectomy gave a depressed in vitro plaque-forming-cell response to sheep red blood cells. In contrast, a significant enhancement of antibody response resulted when mice were exposed to the dye and sheep-red-blood-cell antigen was administered in vivo. Mitogen-induced B- and T-lymphocyte proliferation was also enhanced in mice exposed to the dye for 14 days.
Triennial Reproduction Symposium: the obstacle course to successful establishment of pregnancy in domestic livestock species.

The 2012 Triennial Reproduction Symposium (TRS), "Impediments to Fertility in Domestic Animals," was held immediately before the Joint Annual Meeting of the American Society of Animal Science, American Dairy Science Association, Canadian Society of Animal Science, Western Section of the American Society of Animal Science, and the Asociacion Mexicana de Produccion Animal in Phoenix, AZ, in July, 2012. The theme of the symposium highlighted key impediments or opportunities in the process of creating a pregnancy, beginning with male and female gametes and ending with a viable fetus. The 2012 TRS was designed to focus on areas of current and exciting investigation across a variety of species and to include 8 presentations from a mix of established and early-career scientists. The TRS was also the venue for presentation of the 2012 L. E. Casida Award for Graduate Education; the recipient was R. D. Randel (Texas A&M University). The symposium provided an excellent opportunity for reproductive biologists to consider the broad spectrum of factors that limit fertility in domestic species and contemplate the current status of knowledge relative to several of the significant obstacles to pregnancy.
Inverse Temperature Dependence of Chain Transfer Rate Constant for a Chromium Metalloradical in Polymerization of MMA

Mayo plots have been used to determine the rate constant ktr for chain transfer catalysis by (C5Ph5)Cr(CO)3• of the AIBN-initiated polymerization of MMA from 60 to 80 °C. The value of ktr decreases with temperature, implying that abstraction of H• from the chain-carrying radical by (C5Ph5)Cr(CO)3• does not occur in a single step and suggesting the associative formation of a caged radical pair. No CIDNP is observed for the reaction of (C5Ph5)Cr(CO)3H with MMA.
Cyclic Plate Load Testing of Geosynthetic-Reinforced Unbound Aggregate Roads

A laboratory research program designed to investigate geotextile and geogrid reinforcement of the aggregate layer in unbound pavement sections was performed by the U.S. Army Engineer Research and Development Center. The investigation's objective was to evaluate the performance of geosynthetic-reinforced aggregate road sections over a very soft subgrade. Standard construction materials were used to construct six aggregate road sections in a large steel box. Each instrumented road section was subjected to cyclic plate load tests to evaluate the performance of the model pavement sections under simulated truck traffic. The mechanistic response and permanent deformation of each instrumented pavement section were monitored periodically during each test. Analysis of the experiment data indicated that the geosynthetics improved the performance of the reinforced pavement sections compared with the unreinforced section in terms of improved load distribution and reduced permanent deformation or rutting. Additional i...
Occupational stress in accountancy: A review

Historically, the accounting profession has concerned itself with the phenonmenology and prevalence of stress, both job-related and personal, among its members. Studies dating back to the late 1950's have ad dressed the issue of stress as a problem confronting practitioners in all aspects of the profession. The multi-faceted nature of "stress" and the disparate approaches that have been taken to assess its prevalence and intensity have resulted in a body of literature that is presently frag mented and inconclusive. The purpose of this paper is to review the stress literature in accountancy in a manner as to provide a unifying theoretical structure to the diverse constructs and measures reported. In so doing, the nature of the stress phenomenon is explored, noteworthy empirical investigations are reviewed, and directions for future empiri cal inquiries are outlined.
Randomly Ordered Addressable High-Density Optical Sensor Arrays

Array-based sensors provide an architecture for multianalyte sensing. In this paper, we report a new approach for array fabrication. Sensors are made by immobilizing different reactive chemistries on the surfaces of microspheres. Sensor arrays are prepared by randomly distributing a mixture of microsphere sensors on an optical substrate containing thousands of micrometer-scale wells. The sensors occupy a different location from array to array; thus the identity of each sensor is ascertained and registered on the detector using encoding schemes, rather than by a predetermined location in the array. The approach thereby shifts the demand from fabrication to signal processing. The availability of commercial image analysis software makes such a shift both cost-effective and time efficient.
On the transport of the Florida current

Abstract This paper contains results from the first series of transport measurements made with free instrument techniques. The series consists of the equivalent of 50–60 transects across four sections of the current made over a period of about 3 years. Based on averages of our data, and a comparison of these averages with previous data, we submit 32 ± 3 × 10 6 m 3 /sec as the steady-state volume transport of the Florida Current. Monthly or bi-monthly averages lie within this bound and are reproducible. The total fluctuation bound is ± 12 × 10 6 m 3 /sec. We estimate tidal amptitudes of 3·5 ± 1 × 10 6 m 3 /sec for each of M 2 , K 2 , O 1 and 1·5 ±1 × 10 6 m 3 /sec for S 2 , in excellent agreement with past analysis of potential measurements across the Key West-Havana cable. However, in contrast with some previous investigations, in particular with the past analysis of cable data, there is no evidence in our data for total transport fluctuations at non-tidal periods of amplitudes larger than 10% of the mean.
Poder, resistencia y dominación en las Américas esclavistas: apostillas a Michel Foucault (paradojas y aporías)

This article explores one of the most incidental, and thus least studied, equivocations in Michel Foucault’s work: his understan¬ding of slavery in relation to his conceptualizations of power, domination, resistance and freedom. The article also considers the heuristic value of these equivocations for thinking about the regimes of the large slave plantations of the Americas. Does slavery describe a relation of power or a state of domination? What distinct analytical and ethical implications would this distinction have upon examining the problem of freedom under subjugation? Through a careful exegesis of two late instances in the work of the French thinker, “Subject and power” (1982) and “The ethics of care of the self as a practice of freedom” (1984), this article
RESULTS OF RADICAL TREATMENT FOR INTRAORAL CANCER.

Abstract The records of 150 patients treated with combined operations for intraoral cancers were reviewed with emphasis on correlation between prognosis and age, presence or absence of histologically positive nodes, grade of neoplasm, and previous treatment. The three year survival rate was 48 per cent and the five year survival rate was 40 per cent. Of those patients succumbing with uncontrolled local disease, 89 per cent died in less than three years after operation. The close agreement of the three year and five year survival rates, together with the high percentage of deaths from the disease within three years, suggests that three year survival rates are as reliable as five year survival rates in this disease. Survival rates were significantly less than the over-all average for patients in the following categories: patients less than fifty years of age, patients having histologically proved metastatic involvement of lymph nodes, patients having higher grade tumors, and patients who had had previous roentgen therapy to the primary lesion. Mortality and morbidity were not excessive and deformity was surprisingly minimal. If, in the future, the surgeon can proceed with radical surgery at an earlier stage in the disease, even more promising survival rates may be attained.
In situ growth and properties of epitaxial TlBa/sub 2/CaCu/sub 2/O/sub 7/ and TlBa/sub 2/(Ca/sub 1-x/Y/sub x/)Cu/sub 2/O/sub 7/ thin films

Epitaxial TlBa/sub 2/CaCu/sub 2/O/sub 7/ thin films have been grown on single-crystal LaAlO/sub 3/, NdGaO/sub 3/, and CeO/sub 2/ buffered sapphire substrates by in situ off-axis magnetron sputtering in the presence of Tl/sub 2/O vapor. Phase formation in this system has been investigated for substrate temperatures from 490 degrees C to 600 degrees C and deposition pressures from 50 mTorr to 300 mTorr. The effect of Tl/sub 2/O evaporation rate has also been studied. X-ray diffraction shows that films deposited under optimum conditions are highly epitaxial with the c-axis perpendicular to the substrate surface and
Percutaneous lidocaine administration via a new iontophoresis system in children: tolerability and absence of systemic bioavailability.

Objective Rapid achievement of dermal anesthesia in pediatric practice without discomfort is both desirable and difficult. The Northstar Iontophoretic Drug Delivery System (IDDS) is designed to achieve this objective in 10 minutes using a current of 1.78 mA, compared with the 40 to 60 minutes required for traditional percutaneous methods (eg, eutectic mixture of local anesthetics or EMLA cream). For evaluating the tolerance of this IDDS in pediatrics, 12 healthy children (5-15 years, 4 girls and 8 boys, 10 white, weight 19-79 kg) were evaluated. Methods An open-label trial with random applications of IDDS containing lidocaine (100 mg of 10%) and epinephrine (1.05 mg of 1:10,000) to 3 of the 4 possible sites (back, chest, dorsum of hand, and antecubital fossa) was conducted. Three successive applications (time = 0, 3 hours and 3.5 hours) were performed in each subject, with repeated blood sampling (n = 12 over 10 hours) for assessment of plasma lidocaine concentrations. Skin evaluation (by Draize scoring) at both anode and cathode sites was performed at 10 and 24 hours. Results Few of the subjects (0%-28%) experienced any dermal abnormalities at 10 hours. These findings were maintained at the 24-hour follow-up evaluation with the vast majority of subjects (92%-100%) having no evidence of erythema or edema irrespective of application site. Erythema associated with the anode seemed to be more prominent when the study device was applied to either the chest or the back as compared with the antecubital fossa or dorsum of the hand. No subjects complained of pain/discomfort associated with IDDS delivery. Plasma lidocaine levels in all subjects were below 10 ng/mL at all time points. Conclusions The IDDS seems not to deliver a significant, systemic dose of lidocaine and to be well tolerated and potentially suitable for clinical use in pediatric subjects.
In-vitro effects of cefodizime of leucocyte functions and colony formation from granulocyte-monocyte progenitors

Infections in immunocompromised patients are often difficult to treat, even with currently available antimicrobial agents. An understanding of the effects of antibiotic therapy on the host's immune response is therefore important when deciding on the clinical management of such patients. Antimicrobial agents which lack immunodepressive effects and/or potentiate the immune response are the goal of current research into the treatment of infections in immunocompromised patients. The effects of cefodizime (1-250 micrograms/mL) in vitro on some functional activities of leucocytes and on colony formation by granulocyte monocyte progenitors were studied to investigate the effects of the antibiotic on the host's immune response. A marked enhancement in the lymphocyte transformation reaction was observed in cells exposed to cefodizime. This effect was dose-dependent. Cefodizime had no significant effect on antibody-dependent cell cytotoxicity or on natural killer cell-mediated cytotoxicity. The chemotactic activity of neutrophils was not influenced by the presence of cefodizime (P > 0.05). The phagocytic activity of neutrophils was significantly increased by cefodizime (P > 0.01). Cefodizime significantly stimulated, in a dose-dependent manner, colony formation by granulocyte-monocyte progenitors (P < 0.01). Results suggest that cefodizime has certain stimulatory effects on immunocompetent cells such as enhancing the transformation reaction of lymphocytes, neutrophil phagocytosis and colony formation by granulocyte-monocyte progenitors. Further studies are required to clarify the mechanisms responsible for these effects.
Electron transport phenomena in two-dimensional thin films of pure bismuth

Abstract The Boltzmann transport equation was set up for the charge carriers (electrons and holes) in ultrathin films of pure bismuth. The motions of the charge carriers were two-dimensional in the film plane. Solutions of the Boltzmann equation were obtained in the presence of an electric field with and without the presence of a magnetic field. The electric conductivity, magnetoresistance and Hall resistance were derived and discussed. The possibility of the occurrence of the integral quantized Hall effect in two such carrier semimetallic films was also discussed.
Adaptation of distortion product otoacoustic emissions predicts susceptibility to acoustic over-exposure in alert rabbits.

A noninvasive test was developed in rabbits based on fast adaptation measures for 2f1-f2 distortion-product otoacoustic emissions (DPOAEs). The goal was to evaluate the effective reflex activation, i.e., “functional strength,” of both the descending medial olivocochlear efferent reflex (MOC-R) and the middle-ear muscle reflex (MEM-R) through sound activation. Classically, it is assumed that both reflexes contribute toward protecting the inner ear from cochlear damage caused by noise exposure. The DP-gram method described here evaluated the MOC-R effect on DPOAE levels over a two-octave (oct) frequency range. To estimate the related activation of the middle-ear muscles (MEMs), the MEM-R was measured by monitoring the level of the f1-primary tone throughout its duration. Following baseline measures, rabbits were subjected to noise over-exposure. A main finding was that the measured adaptive activity was highly variable between rabbits but less so between the ears of the same animal. Also, together, the MOC-R and MEM-R tests showed that, on average, DPOAE adaptation consisted of a combined contribution from both systems. Despite this shared involvement, the amount of DPOAE adaptation measured for a particular animal's ear predicted that ear's subsequent susceptibility to the noise over-exposure for alert but not for deeply anesthetized rabbits.
Effects of shifts in magnitude and delay of reward upon runway performance in the rat

Six independent groups of rats were first trained in a runway to receive either 1 or 12 pellets after a delay of 0, 15, or 30 sec (Phase 1). Subsequently (Phase 2), all Ss received 12 pellets under the same delay interval as in Phase 1. Finally (Phase 3), all Ss were delayed 15 sec before receiving the 12-pellet reward. In Phase 1 performance was a positive function of amount of reward and a negative function of delay of reward. The effects of magnitude and delay of reward were independent of each other. In Phase 2 no elation effects were obtained in the 0-, 15-, or 30-sec delay conditions. A depression, but not an elation, effect was obtained in Phase 3.
The mutational spectrum produced in Drosophila by N-methyl-N′-nitro-N-nitrosoguanidine

Abstract N-Methyl-N′-nitro-N-nitrosuguanidine when injected into young Drosophila males induces a high frequency of deletions of either the y+ or B markers from the y+ sc8.Y.Bs chromosome in meiotic and post-meiotic cells, causes loss of both of these markers or of the entire Y-chromosome in meiotic and post-meiotic cells, but very few in spermtogonial cells. It also causes translocations between major chromosomes in meiotic and post-meiotic cells, but not in spermatogonia. It causes an increase in non-disjunctional females carrying the marked Y-chromosome in all stages of the male-germ line, and is an effective producer of point mutations at the y, dp, pp, and st loci. It appears to cause recombinants between the markers dp and were produced in germ cells in all stages of maturity.
Genesis of rods in teleost fish retina.

Fish grow throughout life1 and new neurones are added to the retina as the eyes increase in size2–6. As the retina expands, the density of cells decreases: ganglion cells, cones and cells in the inner nuclear layer are spaced further apart in retinas from larger (older) fish2–5,7–9. In contrast, the density of rods increases during larval development and is then maintained approximately constant as the adult eye grows2–5. Previous developmental studies, in which 3H-thymidine was used to identify proliferating cells, revealed a germinal zone at the margin of the retina. The germinal cells divide to produce new retinal neurones which are added annularly at the perimeter of the growing retina5,6,10. A similar circumferential pattern of growth has been demonstrated in larval amphibians11–15. These studies concluded that the retinal margin is the only site of neurogenesis in post-embryonic retinas. In contrast, our observations suggest that new rods originate from mitotic divisions of precursor cells which are interspersed among the nuclei of mature rods within the retina. The selective addition of rods throughout the retina could explain how the proportion of rods relative to other neurones increases as the retinas of fish grow2–4,7. Preliminary reports of these experiments have appeared elsewhere16,17.
Comparison of aerosol optical thickness measurements by MODIS, AERONET sun photometers, and Forest Service handheld sun photometers in southern Africa during the SAFARI 2000 campaign

The Moderate Resolution Imaging Spectroradiometer (MODIS) instrument on the NASA Terra satellite has been used to monitor aerosol optical thickness (AOT, τ) daily at 10 km×10 km resolution worldwide since August 2000. This information, together with the locations of active fires detected by the MODIS instrument, is essential for understanding the seasonal trends and interannual variability of fires and their impacts on air pollution, atmospheric chemistry, and global climate. We compared aerosol optical thickness derived from MODIS, five automated sun photometers of the Aerosol Robotic Network (AERONET), and 38 Forest Service (FS) handheld sun photometers in western Zambia from 20 August to 20 September 2000. Aerosol optical thicknesses derived from AERONET sun photometers and FS sun photometers were also compared in the same region between mid‐June and late September 2000. Our objectives were to validate the AOT measurements by MODIS and to investigate the factors that affect AOT measurements. We demonst...
Pulmonary hypertension in children following extracorporeal membrane oxygenation therapy and repair of congenital diaphragmatic hernia.

OBJECTIVE: Pulmonary hypertension (PHT) is present in all children at birth, but its degree and rate of resolution in infants diagnosed with congenital diaphragmatic hernia (CDH) requiring extracorporeal membrane oxygenation (ECMO) need to be established. STUDY DESIGN: Twenty-one ECMO/CDH survivors (aged 3.2 ± 1.4 years) were prospectively evaluated by Doppler echocardiography (ECHO) to determine the presence of PHT. Twenty children without structural heart disease were used as controls. Study patients received a physical examination and an electrocardiograph examination, and their charts were reviewed for neonatal course data. Patients found to have PHT by ECHO received a complete history and exercise treadmill/oxygen desaturation study. RESULTS: Eight of the 21 patients (38%) met echocardiographic criteria for PHT. No neonatal course data were found to be predictive of eventual PHT status. There was no correlation between physical examination or electrocardiographic findings and PHT. Complete histories showed five of the eight patients with PHT had some degree of exercise intolerance and seven had wheezing. Two of the seven patients studied on the treadmill desaturated 5% or greater from baseline. CONCLUSION: There is evidence that PHT either persists or recurs in a significant portion of the ECMO/CDH population and may remain symptomatic well beyond the neonatal period.
Scaling properties of perpendicular MTJ with dual-CoFeB/MgO interfaces and step-etch structure

We had built and studied the size scaling effect of perpendicular magnetic tunnel junctions (p-MTJs) with dual MgO/CoFeB interface and step-etch structure. Although the spin-torque-transfer (STT) switching current reduces with MTJ area, the current density increases. Our micromagnetic simulations verify that this is an intrinsic property of STT switching. The switching mode shifts gradually from coherent switching in small junctions to incoherent in large junctions. The energy density of coherent switching is higher and demands higher spin current density. At same current density, smaller size takes longer time to switch. Fortunately, the write efficiency (Δ/Isw) is higher for smaller MTJ.
Remembering the past and imagining the future: common and distinct neural substrates during event construction and elaboration

People can consciously re-experience past events and pre-experience possible future events. This fMRI study examined the neural regions mediating the construction and elaboration of past and future events. Participants were cued with a noun for 20 seconds and instructed to construct a past or future event within a specified time period (week, year, 5–20 years). Once participants had the event in mind, they made a button press and for the remainder of the 20 seconds elaborated on the event. Importantly, all events generated were episodic and did not differ on a number of phenomenological qualities (detail, emotionality, personal significance, field/observer perspective). Conjunction analyses indicated the left hippocampus was commonly engaged by past and future event construction, along with posterior visuospatial regions, but considerable neural differentiation was also observed during the construction phase. Future events recruited regions involved in prospective thinking and generation processes, specifically right frontopolar cortex and left ventrolateral prefrontal cortex, respectively. Furthermore, future event construction uniquely engaged the right hippocampus, possibly as a response to the novelty of these events. In contrast to the construction phase, elaboration was characterized by remarkable overlap in regions comprising the autobiographical memory retrieval network, attributable to the common processes engaged during elaboration, including self-referential processing, contextual and episodic imagery. This striking neural overlap is consistent with findings that amnesic patients exhibit deficits in both past and future thinking, and confirms that the episodic system contributes importantly to imagining the future.
Influenza A Virus M2 Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture

The amantadine-sensitive ion channel activity of influenza A virus M2 protein was discovered through understanding the two steps in the virus life cycle that are inhibited by the antiviral drug amantadine: virus uncoating in endosomes and M2 protein-mediated equilibration of the intralumenal pH of the trans Golgi network. Recently it was reported that influenza virus can undergo multiple cycles of replication without M2 ion channel activity (T. Watanabe, S. Watanabe, H. Ito, H. Kida, and Y. Kawaoka, J. Virol. 75:5656-5662, 2001). An M2 protein containing a deletion in the transmembrane (TM) domain (M2-del(29-31)) has no detectable ion channel activity, yet a mutant virus was obtained containing this deletion. Watanabe and colleagues reported that the M2-del(29-31) virus replicated as efficiently as wild-type (wt) virus. We have investigated the effect of amantadine on the growth of four influenza viruses: A/WSN/33; N31S-M2WSN, a mutant in which an asparagine residue at position 31 in the M2 TM domain was replaced with a serine residue; MUd/WSN, which possesses seven RNA segments from WSN plus the RNA segment 7 derived from A/Udorn/72; and A/Udorn/72. N31S-M2WSN was amantadine sensitive, whereas A/WSN/33 was amantadine resistant, indicating that the M2 residue N31 is the sole determinant of resistance of A/WSN/33 to amantadine. The growth of influenza viruses inhibited by amantadine was compared to the growth of an M2-del(29-31) virus. We found that the M2-del(29-31) virus was debilitated in growth to an extent similar to that of influenza virus grown in the presence of amantadine. Furthermore, in a test of biological fitness, it was found that wt virus almost completely outgrew M2-del(29-31) virus in 4 days after cocultivation of a 100:1 ratio of M2-del(29-31) virus to wt virus, respectively. We conclude that the M2 ion channel protein, which is conserved in all known strains of influenza virus, evolved its function because it contributes to the efficient replication of the virus in a single cycle.
Empirical Determination of Physical Controls on Megafaunal Footprint Formation Through Neoichnological Experiments with Elephants

ABSTRACT We performed a series of neoichnological experiments with elephants to investigate the relationship between the various factors involved in controlling megafaunal footprint formation. Our ultimate goal was to provide a means to calculate original sedimentary properties of fossil-footprint–bearing siliciclastic rocks, especially those containing sauropod dinosaur tracks. Previous semiquantitative and model-based research identified multiple variables that influence footprint creation and preservation, but no rigorous, empirically based models have been constructed. We conducted track-making trials with experimental sediments and one adult female African elephant (Loxodonta africana) and one adult female Asian elephant (Elephas maximus) in a zoo setting. Data collected included track dimensions, sediment particle size distribution, sediment bulk density (ρb), volumetric water content of the sediment (θv), and trackmaker walking velocity (v) and weight. We performed multiple regression analysis with...
Piezo1 links mechanical forces to red blood cell volume

Red blood cells (RBCs) experience significant mechanical forces while recirculating, but the consequences of these forces are not fully understood. Recent work has shown that gain-of-function mutations in mechanically activated Piezo1 cation channels are associated with the dehydrating RBC disease xerocytosis, implicating a role of mechanotransduction in RBC volume regulation. However, the mechanisms by which these mutations result in RBC dehydration are unknown. In this study, we show that RBCs exhibit robust calcium entry in response to mechanical stretch and that this entry is dependent on Piezo1 expression. Furthermore, RBCs from blood-cell-specific Piezo1 conditional knockout mice are overhydrated and exhibit increased fragility both in vitro and in vivo. Finally, we show that Yoda1, a chemical activator of Piezo1, causes calcium influx and subsequent dehydration of RBCs via downstream activation of the KCa3.1 Gardos channel, directly implicating Piezo1 signaling in RBC volume control. Therefore, mechanically activated Piezo1 plays an essential role in RBC volume homeostasis.
A comparison of high- and low-virulence Flavobacterium columnare strains reveals differences in iron acquisition components and responses to iron restriction

Flavobacterium columnare, the causative agent of columnaris disease causes substantial mortality worldwide in numerous freshwater finfish species. Due to its global significance, an improved understanding of the factors that contribute to virulence is urgently needed. In a laboratory challenge, we found that significantly greater mortality was observed in channel catfish Ictalurus punctatus (Rafinesque) challenged with isolate LSU-066-04 (LSU) as compared to fish challenged with isolate LV-359-01 (LV). Strikingly, mortality was 100% in LSU-challenged fish, with all fish dying within the first 24 h after challenge, while mortality in the LV-challenged group was significantly lower with 26.7% of fish dying on days 1-4 post-challenge. There were no differences in initial bacterial adhesion between the isolates at 1-2 h post-challenge; however, by 4 h LSU-challenged fish had a greater bacterial load on the gill. Next, to better understand this variation in virulence, we examined transcriptional and functional attributes related to iron acquisition. The isolates were differentially sensitive to iron restriction both in vitro and in vivo and the basal expression of TonB family member genes and a ferroxidase gene differed significantly. Our findings provide new insight into iron uptake and pathogen virulence, and offer promising new targets for columnaris prevention and treatment.
The Wrickkened Pathways of FGF23, MEPE and PHEX

The last 350 years since the publication of the first medical monograph on rickets (old English term wrickken) (Glisson et al., 1651) have seen spectacular advances in our understanding of mineral-homeostasis. Seminal and exciting discoveries have revealed the roles of PTH, vitamin D, and calcitonin in regulating calcium and phosphate, and maintaining healthy teeth and skeleton. However, it is clear that the PTH/Vitamin D axis does not account for the entire picture, and a new bone-renal metabolic milieu has emerged, implicating a novel set of matrix proteins, hormones, and Zn-metallopeptidases. The primary defects in X-linked hypophosphatemic rickets (HYP) and autosomal-dominant hypophosphatemic rickets (ADHR) are now identified as inactivating mutations in a Zn-metalloendopeptidase (PHEX) and activating mutations in fibroblast-growth-factor-23 (FGF23), respectively. In oncogenic hypophosphatemic osteomalacia (OHO), several tumor-expressed proteins (MEPE, FGF23, and FRP-4) have emerged as candidate mediators of the bone-renal pathophysiology. This has stimulated the proposal of a global model that takes into account the remarkable similarities between the inherited diseases (HYP and ADHR) and the tumor-acquired disease OHO. In HYP, loss of PHEX function is proposed to result in an increase in uncleaved full-length FGF23 and/or inappropriate processing of MEPE. In ADHR, a mutation in FGF23 results in resistance to proteolysis by PHEX or other proteases and an increase in half-life of full-length phosphaturic FGF23. In OHO, over-expression of FGF23 and/or MEPE is proposed to result in abnormal renal-phosphate handling and mineralization. Although this model is attractive, many questions remain unanswered, suggesting a more complex picture. The following review will present a global hypothesis that attempts to explain the experimental and clinical observations in HYP, ADHR, and OHO, plus diverse mouse models that include the MEPE null mutant, HYP-PHEX transgenic mouse, and MEPE-PHEX double-null-mutant.
A Longitudinal Study of the Reliability of Acupuncture Deqi Sensations in Knee Osteoarthritis

Deqi is one of the core concepts in acupuncture theory and encompasses a range of sensations. In this study, we used the MGH Acupuncture Sensation Scale (MASS) to measure and assess the reliability of the sensations evoked by acupuncture needle stimulation in a longitudinal clinical trial on knee osteoarthritis (OA) patients. The Knee injury and Osteoarthritis Outcome Score (KOOS) was used as the clinical outcome. Thirty OA patients were randomized into one of three groups (high dose, low dose, and sham acupuncture) for 4 weeks. We found that, compared with sham acupuncture, real acupuncture (combining high and low doses) produced significant improvement in knee pain () and function in sport (). Intraclass correlation analysis showed that patients reliably rated 11 of the 12 acupuncture sensations listed on the MASS and that heaviness was rated most consistently. Overall perceived sensation (MASS Index) (), ratings of soreness (), and aching () differed significantly across acupuncture groups. Compared to sham acupuncture, real acupuncture reliably evoked stronger deqi sensations and led to better clinical outcomes when measured in a chronic pain population. Our findings highlight the MASS as a useful tool for measuring deqi in acupuncture research.
Second Order Isomorphism: A Reinterpretation and Its Implications in Brain and Cognitive Sciences

Shepard and Chipman’s second order isomorphism describes how the brain may represent the relations in the world. However, a common interpretation of the theory can cause difficulties. The problem originates from the static nature of representations. In an alternative interpretation, I propose that we assign an active role to the internal representations and relations. It turns out that a collection of such active units can perform analogical tasks. The new interpretation is supported by the existence of neural circuits that may be implementing such a function. Within this framework, perception, cognition, and motor function can be understood under a unifying principle of analogy.
Adult Norms for the Nine Hole Peg Test of Finger Dexterity

The purposes of this study were to establish standardized procedures for the Nine Hole Peg Test of finger dexterity, to evaluate its reliability and validity, and to establish new clinical norms based on these standardized procedures. For the reliability and validity study, 26 female occupational therapy students were tested Very high interrater reliability (right r = .97, left r = .99) was found Test-retest reliability was reported to be moderate to high (right r = .69, left r = .43) and a significant practice effect was found between the test and retest occasions. Possible variables that may have affected these results are discussed To evaluate concurrent validity, the Nine Hole Peg Test was compared to the Purdue Pegboard. The observed correlations (right r = −.61, left r = −.53) indicated that the tests are similar but not equivalent tests of finger dexterity. For the normative data study, 628 normal subjects from 20 to 94 years were tested Data were stratified by sex and by 12 age groups to allow the...
Changing Norms of Accountability: Opportunities for Democratic Change

This article considers how civil society can bring about local-level democratic change when national political systems remain authoritarian. Existing literature has tended to focus on democratic characteristics of civil society that reinforce political democratisation. A close reading of the literature on sub-Saharan Africa, along with a Cameroonian case study, illustrates how a civic association can provide opportunities for democratic change by emphasising accountability. This article addresses an important gap in the literature by showing where democratisation opportunities may be limited to the local level but can still improve citizens' quality of life.
Satellite Position and Attitude Estimation Using an Extended Kalman Filter

Free space laser communication is being proposed for a number of satellite-to-satellite and satellite-to-aircraft links. They provide high speed data transfer over the large distances involved between objects. Recently, the question has arisen as to whether these systems can be used for more than just communication. In order for two objects to communicate using lasers, they need some knowledge of the line of sight vector between them. Real time estimation techniques such as the extended Kalman filter can use this information to improve their accuracy. This paper studies a six satellite problem, five of which are in geostationary orbits, with the remaining satellite in a low earth orbit. The geostationary satellites are contained within the equatorial plane, while the orbit of the low earth satellite is not. Line of sight vectors and time of flight measurements are generated at each time step. The time of flight measurements are used to correct clock differences between the satellites and improve range estimates. Radio frequency communication between one geostationary satellite and an earth based tracking station is also included within the simulation. Results demonstrate that both position and attitude can be estimated using only the line of sight measurements. Time of flight measurements are shown to improve accuracy of both the position and attitude state estimates. Robustness to initial condition errors is also demonstrated.
Predicting the responsiveness of soil biodiversity to deforestation: a cross-biome study

The consequences of deforestation for aboveground biodiversity have been a scientific and political concern for decades. In contrast, despite being a dominant component of biodiversity that is essential to the functioning of ecosystems, the responses of belowground biodiversity to forest removal have received less attention. Single-site studies suggest that soil microbes can be highly responsive to forest removal, but responses are highly variable, with negligible effects in some regions. Using high throughput sequencing, we characterize the effects of deforestation on microbial communities across multiple biomes and explore what determines the vulnerability of microbial communities to this vegetative change. We reveal consistent directional trends in the microbial community response, yet the magnitude of this vegetation effect varied between sites, and was explained strongly by soil texture. In sandy sites, the difference in vegetation type caused shifts in a suite of edaphic characteristics, driving substantial differences in microbial community composition. In contrast, fine-textured soil buffered microbes against these effects and there were minimal differences between communities in forest and grassland soil. These microbial community changes were associated with distinct changes in the microbial catabolic profile, placing community changes in an ecosystem functioning context. The universal nature of these patterns allows us to predict where deforestation will have the strongest effects on soil biodiversity, and how these effects could be mitigated.
Successful Pregnancy After Marrow Transplantation for Severe Aplastic Anemia and Immunosuppression With Cyclosporine

ALLOGENEIC marrow transplantation has been used successfully for more than a decade to treat patients with severe aplastic anemia. At present, 70% to 80% of patients become long-term survivors, 1,2 and most of these patients are being followed up in general medical clinics rather than at specialized institutions. Since many patients afflicted by this disease are young, any treatment must take into consideration potential long-term side effects. Although there has been concern that high doses of cyclophosphamide, most widely used to condition patients for transplantation, might affect gonadal and reproductive function, there have been some reports of normal pregnancies and normal offspring in patients after marrow transplantation. 3-5 All these patients had received methotrexate after grafting as prophylaxis for graft- v -host disease. At present, however, many transplant centers are using the new immunosuppressant cyclosporine rather than methotrexate as prophylaxis of graft- v -host disease. 6-8 Experience with this drug
RECIPROCAL PEER MANAGEMENT: IMPROVING STAFF INSTRUCTION IN A VOCATIONAL TRAINING PROGRAM

To test the feasibility and utility of involving peers as sources of feedback, 6 subjects, instructors in a vocational program for adults with mental retardation, participated in a staff training and management program. Subjects' teaching interactions were assessed during baseline, in-service training (on effective teaching), return-to-baseline, peer management, and follow-up phases. Peer management was introduced in multiple baseline fashion across pairs of subjects. Members of each pair were trained to monitor peer teaching, to record and graph data, to provide feedback, and to set goals with the peer. Each pair then performed these procedures on the job for several weeks, during which time 4 of the 6 subjects increased their use of effective teaching methods (over baseline). However, inconsistencies in the magnitude and durability of these increases require that the study be viewed as inconclusive, although it has heuristic value as a promising model for involving co-workers in staff management programs.
Question types in social Q&A sites

Social question and answer (Q&A) Web sites field a remarkable variety of questions: while one user seeks highly technical information, another looks to start a social exchange. Prior work in the field has adopted informal taxonomies of question types as a mechanism for interpreting user behavior and community outcomes. In this work, we contribute a formal taxonomy of question types to deepen our understanding of the nature and intent of questions that are asked online. Our taxonomy is grounded in Aristotelian rhetorical theory, and complemented by contributions of leading twentieth century rhetorical theorists. This taxonomy offers a way to differentiate between similar-sounding questions, while remaining flexible enough to encompass the wide range of questions asked online. To ground the taxonomy in reality, we code questions drawn from three popular social Q&A sites, and report on the distributions of several objective and subjective measures.