cssi/SciSciGPT-SciSciNet huggingface dataset:
Biopsy of pheochromocytomas and paragangliomas: Potential for disaster

Background Pheochromocytomas and paragangliomas are highly vascular neuroendocrine neoplasms that often secrete catecholamines. Percutaneous biopsy has been associated with life-threatening hemorrhage, hypertensive crisis, capsular disruption with tumor implantation, and death. We sought to determine the outcomes of biopsy in 20 consecutive patients. Methods We reviewed retrospectively the medical records of patients with biopsied pheochromocytomas and paragangliomas referred to our Endocrine Division for subsequent management between 1995 and 2005. Biopsy complications, operative findings, and outcomes were reviewed. Results Twenty patients (14 pheochromocytomas and 6 paragangliomas) were biopsied percutaneously prior to referral. Mean tumor diameter was 6.4 cm (range, 1–15). Pre-biopsy biochemical testing was not performed in 90% of patients, and was negative in the remainder. Fourteen patients (70%) developed a biopsy-related complication, including: increased difficulty of the definitive operation in 7 of 17 (41%) operative cases with 1 patient requiring conversion to an open procedure; severe hypertension (15%); hematoma (30%); incorrect or inadequate biopsy (25%); severe pain (25%); and delay in surgical treatment (15%). Mean follow-up was 58 months, with 4 tumor-related deaths and 2 recurrences. Conclusion Biochemical testing prior to biopsy of adrenal or suspicious retroperitoneal masses is critical to exclude a catecholamine-secreting neoplasm because serious complications and increased operative difficulty can result.
Estimating the microvascular benefits of screening for type 2 diabetes mellitus.

Objective: To define the relative benefits of screening for diabetes and improved treatment programs and ways of improving the efficiency of screening for a population-based cohort derived from the Third National Health and Nutrition Examination Survey (NHANES III). Methods: A Markov decision model is used to estimate microvascular benefits of glucose control for four different screening and treatment scenarios, including either universal screening or improved glucose control of known diabetic subjects, neither, or both. Results: A population cohort of subjects with recent onset of diabetes (<5 years) was derived from NHANES III (of whom close to half were unaware that they had diabetes). In this population-based cohort, the total benefit achievable by universal screening and improved treatment (limiting HbA1c to less than 9%) is a reduction of about 30,000 cases of blindness over the lifetime of the cohort. Screening alone results in 7% of this benefit, and improved treatment alone provides 65%. Screening a targeted group of patients with three or more risk factors for developing diabetes would reduce the number of required fasting glucose measurements needed by 82% and provide 50% of the total benefit of screening the entire population with a fasting glucose measurement. Conclusions: Morbidity from type 2 diabetes can be most effectively reduced by developing ways to modestly improve the glycemic control of known diabetic subjects, particularly those with high A1c's and early onset of disease. Targeting can significantly reduce the number of persons who need to be screened with a fasting blood test while preserving a large component of the benefit of screening.
Interaction-based programming towards translucent clouds: position paper

Today's cloud computing platforms are typically "opaque": Amazon EC2 users only receive virtual units of CPU and memory, and physical details of the platform are hidden. Such opacity prevents programs from online optimizations and deployment adjustment, and is penalizing the very applications cloud computing attempts to attract: high-performance software. On the other extreme, a completely transparent design of clouds would lead to severe security and reliability concerns. In this position paper, we take the middle-of-the-road approach, proposing a language model for well-defined programmable interactions between the cloud platform and the client program. Our proposed ideas draw from the previous work of Classages, where first-class interactions can be dynamically established and terminated for two parties with mutually satisfiable contracts. In this paper, we justify how our design can help cloud programs to fine-tune performance, and how it may impact on other important issues of cloud computing, such as security, scheduling, and pricing.
Computational Diversions: WordWiring, a Network-Themed Party Game

Fans of ‘‘mathematical games’’ (I’m one) often end up with a small library of books on the subject, collectively containing descriptions of a vast trove of games. There are board games, or informal pencil-and-paper games, with applications to (e.g.) graph theory, number theory, combinatorics, logic, and many other branches of mathematics. In fact, the range and variety of mathematical games is so wide—and so rich in content—that one could plausibly base a pretty good introductory mathematics curriculum on these pastimes. Perhaps a few of the more advanced subjects would be underrepresented in this exercise (real analysis? differential geometry?); but a typical library of mathematical games provides, overall, a broad portrait of mathematics in general. Now, coverage of mathematics is one thing; but does our library provide reasonable coverage of what we mean by games? Interestingly, there are certain important types of games that tend to be near-invisible in recreational mathematics. For one thing, almost all the examples in our library are either solitaire games (which by some definitions of the term would hardly qualify as ‘‘games’’ at all), or two-person games. Think of the standards: tic-tac-toe, Nim, Sim, Sprouts, chess, Go, and so forth. Occasionally there are threeor four-person variations of these games, but for the most part we’re talking about n players, where n is a small positive integer. (Perhaps, if we program a computer to play a mathematical game against itself, we could say that n = 0 in that case?) Not all games are like this. After all, baseball is a game, isn’t it? You need to round up 18 people at the very least to play a weekend-afternoon informal game of baseball. Even a pick-up basketball game will usually have at least six players; touch football would require a dozen or so. And how about children’s favorites, such as musical chairs? Starting a game of musical chairs with only two or three kids on hand seems hardly worth the effort. Other children’s classics—Tag, Duck-Duck-Goose, Capture the Flag—are best played with numbers ranging from a half-dozen (at the low end) to twenty or more. For older children and adults, there are games such as charades, or twenty questions, and these are typically played in moderate-sized groups (three would be a bit small for these games). In other
Pulsed laser deposition of metal oxide films

Pulsed laser deposition (PLD), which provides very unique features compared to the conventional physical vapor deposition technique such as sputtering, is one of the most powerful techniques to deposit conductive oxide thin films. Over the past several years, we have optimized the processing conditions to deposit high quality conductive RuO2 and SrRuO3 thin films by PLD. We show that the substrate temperature during the deposition process plays an important role in determining the structural and electrical properties of these films. Epitaxial RuO2 and SrRuO3 thin films with a room-temperature resistivity of 35 (mu) (Omega) -cm and 280 (mu) (omega) -cm, respectively, have been successfully deposited by PLD.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Unsuccessful treatment of phenylketonuria with tyrosine.

ON E of the earliest questions in the treatment of phenylketonuria was whether the severe mental retardation characteristic of this disorder was caused by phenylalanine accumulation or by tyrosine deficiency. Although early therapy with a diet low in phenylalanine and supplemented with tyrosine is effective in preventing mental retardation in PKU, 1, ~ the role of a tyrosinesupplemented diet alone has not been evaluated. We present the case of a child born in 1967 whose parents elected 1o have him treated with tyrosine supplementation rather than with phenylalanine restriction. CASE REPORT The patient was the product of an uncomplicated term pregnancy, labor, and delivery in a gravida 3, para 2, 25-year-old mother. Birth weight was 4.3 kg an d the Apgar score was 10 at 5 minutes. The neonatal course was uncomplicated. However, plasma phenylatanine concentrations at 3 and 10 days of age were 1,400 and 3,030 ~M, respectively (normal range 26 to 61 /~M). Plasma tyros!no concentration was 70/xM at 10 days of age (normal range 31 to 71 /~M). The child was placed on the standard phenylalanine-restricted diet for two weeks. However, the parents noted the child to be irritable and lethargic and requested that the diet be terminated. They questioned whether another form of therapy might be available, and consented to a trial of tyrosine supplementation alone, c-Tyrosine, as a free base, was given with meals at a dose of 200 mg/day. Plasma tyrosine concentration rose to 214 ~M. Tyrosine supplementation was continued until 4 years of age at doses ranging from 200 to 300 mg/day. During this time plasma phenylalanine concentrations ranged from 1,370 to 3,818 tsM and plasma tyrosine values from 62 to 219/~M. Therapy was discontinued at four years when it became apparent that the child was severely retarded. Developmental milestones were delayed from infancy. Motor skills were always less affected than were language skills. The
Resonance shifting and plane impedance calculations for a rectangular cavity in printed circuit board using closed form solutions

A method for arbitrarily shifting the dominant mode frequency of a rectangular cavity in printed circuit boards (PCBs) is presented. Standard closed-form and analytic solutions are used to determine the frequency, quality factor, and impedance of the cavity. Calculations are compared with 3D full wave finite element method (FEM) solutions. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 51: 452–455, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.24080
Reversibility of the reorganization of retinotectal projection in goldfish.

Abstract The goldfish is able to readjust the retinal projection on the midbrain optic tectum. The rostral half tectum may reacquire an orderly compressed visual projection from the whole retina after either surgical excision of the caudal half or separation of the caudal half from the rostral half of the tectum. The present results show that a normal retinotectal projection may be restored following a previous compression of visual projection, initially induced by surgical insertion of a mechanical barrier between the rostral and the caudal halves of the tectum. Furthermore the restored visual projection from the whole retina onto the whole tectum can then be recompressed by excising the caudal half of the tectum. These results suggest that the reorganization of retinotectal connections in the goldfish is a reversible phenomenon which can be induced and then reinstated in correct retinotopic order.
High-dose chemotherapy and autologous stem cell transplantation for multiple myeloma in HIV-positive patients in the highly active antiretroviral therapy era: the myeloma institute of research and therapy experience.

Introduction Non-Hodgkin lymphoma is the most common hematopoietic malignancy associated with acquired immune deficiency syndrome (AIDS). However multiple myeloma has also been reported a number f times in patients with human immunodeficiency virus (HIV) since 983 when the first case of a plasmacytoma was reported in a person with IV infection. Before the advent of highly active antiretroviral therapy (HAART) in 1996, the management of HIV-related hematopoietic malignancies was very difficult. High-dose chemotherapy and autologous stem cell transplantation (ASCT), which was standard therapy for he-
Augmentation of Bone Repair by Inductively Coupled Electromagnetic Fields

Pulsing electromagnetic fields of low frequency and strength have been inductively coupled across skin, directly to bone, to enhance the repair of canine osteotomies. The induced voltage field in bone appears to increase the organization and strength of the repair process at 28 days after "fracture."
Retention and Reform: An Evaluation of Peer-Led Team Learning

This study describes an evaluation of the Peer-Led Team Learning (PLTL) reform model in first-semester general chemistry. PLTL was implemented in place of one-third of the available lecture time, maintaining the same amount of structured class time under the reform. The evaluation demonstrates that classes implementing the PLTL reform at the setting featured a statistically significant improvement of 15% in the pass rate for the classes, compared to conventional, lecture-only classes at the same setting. Additionally, the PLTL classes maintained a comparable score on a comprehensive American Chemical Society final exam to that of the conventional classes. Combined, these findings suggest that the improvement in pass rates occurs while maintaining the same level of rigor in the PLTL classes. Examining student groups shows that students in underrepresented minority groups demonstrated the largest improvement in pass rates with the PLTL reform.
Quantitative proteomics of nutrient limitation in the hydrogenotrophic methanogen Methanococcus maripaludis

Background: Methanogenic Archaea play key metabolic roles in anaerobic ecosystems, where they use H2 and other substrates to produce methane. Methanococcus maripaludis is a model for studies of the global response to nutrient limitations. Results: We used high-coverage quantitative proteomics to determine the response of M. maripaludis to growth-limiting levels of H2, nitrogen, and phosphate. Six to ten percent of the proteome changed significantly with each nutrient limitation. H2 limitation increased the abundance of a wide variety of proteins involved in methanogenesis. However, one protein involved in methanogenesis decreased: a low-affinity [Fe] hydrogenase, which may dominate over a higheraffinity mechanism when H2 is abundant. Nitrogen limitation increased known nitrogen assimilation proteins. In addition, the increased abundance of molybdate transport proteins suggested they function for nitrogen fixation. An apparent regulon governed by the euryarchaeal nitrogen regulator NrpR is discussed. Phosphate limitation increased the abundance of three different sets of proteins, suggesting that all three function in phosphate transport. Conclusion: The global proteomic response of M. maripaludis to each nutrient limitation suggests a wider response than previously appreciated. The results give new insight into the function of several proteins, as well as providing information that should contribute to the formulation of a regulatory network model.
Pharmacokinetic evaluation of darbepoetin alfa for the treatment of pediatric patients with chemotherapy-induced anemia.

Background Cancer patients undergoing chemotherapy often develop anemia, which can increase the risk for transfusions and fatigue. The recombinant erythropoiesis-stimulating agent darbepoetin alfa can effectively treat chemotherapy-induced anemia (CIA) in adults, but limited data are available regarding its use in pediatric cancer patients. The goals of this phase 1, open-label, uncontrolled study were to assess the pharmacokinetic profile and safety of darbepoetin alfa in pediatric patients with CIA. Procedure Pediatric patients with nonmyeloid malignancies and CIA received up to six doses of darbepoetin alfa 2.25 mcg/kg subcutaneously. After the first dose, the pharmacokinetic properties of darbepoetin alfa were assessed during a 14-day sampling period. All subsequent doses were given weekly with predose blood samples collected before study drug administration. Results After a single dose of darbepoetin alfa, the mean (SD) peak serum concentration was 10.5 (3) ng/ml, and the median time to peak concentration was 71.4 hr. Darbepoetin alfa exhibited a mean (SD) terminal half-life of 49.4 (32) hr. Upon repeated weekly administration, no evidence of darbepoetin alfa accumulation was observed though there was high intra- and inter-individual variability. In addition, darbepoetin alfa was well tolerated; some study patients experienced increases in hemoglobin. Conclusions The pharmacokinetic profile of darbepoetin alfa indicated that it was slowly absorbed and exhibited a long terminal half-life in these pediatric study patients with CIA. Pediatr Blood Cancer 2007;49:687–693. © 2006 Wiley-Liss, Inc.
Latent species C adenoviruses in human tonsil tissues.

Although species C human adenoviruses establish persistent infections, the molecular details of this lifestyle remain poorly understood. We previously reported that adenovirus DNA is found in human mucosal T lymphocytes in a noninfectious form (C. T. Garnett, D. Erdman, W. Xu, and L. R. Gooding, J. Virol. 76:10608-10616, 2002). In this study, human tonsil and adenoid tissues were analyzed to determine the dynamics of infection, the rate of clearance of viral DNA, and the possibility of reactivation of virus from these tissues. The presence of viral DNA peaked at 4 years of age and declined thereafter. The average number of viral genomes declined with the age of the donor. The frequency of virus-bearing cells ranged from 3 × 10−7 to 3.4 × 10−4, while the amount of viral DNA per cell varied less, with an average of 280 copies per cell. All species C serotypes were represented in these tissues, although adenovirus type 6 was notably rare. Infectious virus was detected infrequently (13 of 94 of donors tested), even among donors with the highest levels of adenoviral DNA. Adenovirus transcripts were rarely detected in uncultured lymphocytes (2 of 12 donors) but appeared following stimulation and culture (11 of 13 donors). Viral DNA replication could be stimulated in most donor samples by lymphocyte stimulation in culture. New infectious virus was detected in 13 of 15 donors following in vitro stimulation. These data suggest that species C adenoviruses can establish latent infections in mucosal lymphocytes and that stimulation of these cells can cause viral reactivation resulting in RNA transcription, DNA replication, and infectious virus production.
Effects of intracellular zinc depletion on metallothionein and ZIP2 transporter expression and apoptosis

Zinc is critical for the functional and structural integrity of cells. We have used the monocytic cell line THP-1 as a model in which to study both the responsiveness of metallothionein and ZIP2 transporter expression to zinc depletion induced by the intracellular zinc chelator TPEN (N,N,N*,N*-tetrakis(2-pyridylmethyl) ethylenedia- mine) and the extent of concomitant apoptosis. Metallothionein expression increased proportion- ately with the addition of zinc to the medium and decreased with TPEN treatment. When treated with TPEN, both THP-1 cells and human periph- eral blood mononuclear cells exhibited marked de- creases in cellular zinc concentrations and in- creases in ZIP2 mRNA expression. These results suggest that cells attempt to homeostatically adjust to zinc depletion. When THP-1 cells were treated with >5 mM TPEN, cell viability decreased, and cells entered the early stages of apoptosis. These data show that metallothionein and ZIP2 expres- sion are inversely related during zinc depletion and that apoptosis is concurrent with these changes. J. Leukoc. Biol. 70: 559-566; 2001.
Utilizing BIM for Real-Time Visualization and Indoor Localization of Resources

Building Information Modeling (BIM) has been found to be one of the most promising advancement in the Architecture, Engineering, Construction, and Operations and Management (AECOM) industry. BIM integrates the geometric and parametric properties of the 3D model of a facility with all the information and properties of building features and components. However, finding the current location of a specific component or navigation through an unfamiliar facility can be difficult and time consuming. Visualizing the location in real-time can provide the ability to reduce the time for manual searching and locating. This paper demonstrates how the BIM model can be utilized for real-time visualization and localization when integrated with sensing technologies. Real-time visualization and localization requires context-aware information (e.g. space, location, time) in order to function properly. Therefore, the BIM model can provide the spatial relationships while the location sensing technology can provide location and time information. Current indoor localization techniques utilize probabilistic algorithms to estimate landmarks or components, which often require great computational power. Since the model contains the exact locations of components, utilizing BIM provides the advantage of not needing to estimate the true location of the landmarks, drastically reducing the complexity and computing time of the algorithm. PROBLEM DESCRIPTION In an industry where time is crucial for remaining on schedule and lowering facility management costs, manual inspection remains especially inefficient and costly. Current methods of planning and executing facility management are based on personal knowledge and experience (Akcamete et al. 2010). Additionally, current manual efforts and paper-based quality inspections involve labor-intensive methods and are shown to be unreliable, ineffective, and time consuming (Wang 2008). Additionally, building systems are becoming increasingly complex, causing challenges for the management and operation of the facility (Kean 2011). The process of manual inspection proves to be time consuming as it relies distinctly on a worker
Applications of metamaterials to realize efficient electrically small antennas

Metamaterials are engineered media whose electromagnetic responses are different from those of their constituent components. They are often generated by incorporating in a periodic manner various types of artificially fabricated, extrinsic, low dimensional inhomogeneities in some background substrate. Double negative (DNG) metamaterials have both the permittivity and permeability negative. There have been a variety of antenna applications conceived and realized with various types of metamaterials. In this paper, we have investigated the possibility of matching an electrically small electric dipole to free space by surrounding it with a DNG shell. HFSS simulations confirm the resonant power gain predicted analytically and have given us insight into how a realistic electrically small efficient antenna (EESA) could be achieved.
Soccer Hooliganism in Black Africa

Some incidents occurring in Black Africa during soccer matches are reported. Theories regarding causation are presented, as well as tendered suggestions for the lessening of violence and disorder for this phenomenon.
Vibration Characteristics of Mistuned Shrouded Blade Assemblies

An investigation of the mode localization phenomenon associated with mistuning is presented for shrouded blade assemblies. The calculations are based on a generic finite element model, which permits modeling of arbitrary mistuning and both slipping and nonslipping shroud interfaces. The results presented indicate that interactions occur between mistuning and slip effects, with maximum mode localization occurring when the shrouds slip freely. Certain modes are found to be very sensitive to shroud slip, and in some cases completely change character when slip occurs. Mode localization is most pronounced in the predominantly bending modes, and varies considerably from mode to mode. As the ratio of interblade coupling strength to mistuning strength is increased, the effect of mistuning is observed to decrease significantly. This result has important implications for the flutter problem, since it suggests that the stabilization effect available from mistuning is significantly less for a shrouded rotor as compared to an unshrouded rotor.
Inverse Consistent Deformable Image Registration

This paper presents a novel variational model for inverse consistent deformable image registration. The proposed model deforms both source and target images simultaneously, and aligns the deformed images in the way that the forward and backward transformations are inverse consistent. To avoid the direct computation of the inverse transformation fields, our model estimates two more vector fields by minimizing their invertibility error using the deformation fields. Moreover, to improve the robustness of the model to the choice of parameters, the dissimilarity measure in the energy functional is derived using the likelihood estimation. The experimental results on clinical data indicate the efficiency of the proposed method with improved robustness, accuracy, and inverse consistency.
Statin Therapy for Low-LDL, High-hsCRP Patients: From JUPITER to CORONA

In the recently completed Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)1 trial, which was conducted with 17 802 primary-prevention patients with LDL cholesterol concentrations <3.37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) concentrations ≥2 mg/L, random allocation to treatment with 20 mg rosuvastatin was associated with a 54% reduction in the incidence of myocardial infarction, a 48% reduction in stroke, a 47% reduction in the need for angioplasty or bypass surgery, a 43% reduction in venous thrombosis, and a 20% reduction in all-cause mortality (1). These effects were consistent in all of the evaluated subgroups, including among women as well as men, among minority populations, at all levels of Framingham risk, and among those with and without metabolic syndrome. Within the JUPITER trial, as had previously been shown in high-risk patients with acute coronary ischemia and among those with stable coronary disease, the clinical benefits of statin therapy compared with placebo were greatest among patients who reduced not only their LDL cholesterol concentration but also their hsCRP value (2). On the basis of these data, an advisory panel to the US Food and Drug Administration recently voted in favor of expanding the labeling for statin therapy to include those with low LDL cholesterol and increased hsCRP. Furthermore, 2009 guidelines from the Canadian Cardiovascular Society—the first national guidelines to appear since publication of the JUPITER trial data—now explicitly endorse hsCRP screening among “intermediate risk” patients, including those with low LDL cholesterol concentrations (3). The concept that low-LDL, high-hsCRP patients are at a higher than anticipated vascular risk and thus good candidates for statin therapy has also recently been confirmed in the multiethnic Atherosclerosis Risk in Communities (ARIC) study, in which patients with low LDL cholesterol values but high hsCRP concentrations had a substantially …
Photonic downconversion and microwave-to-digital subsystems

Frequency downconversion is an essential part of many RF systems and is particularly important in microwave to digital systems. Photonic technology offers numerous potential benefits including very broad bandwidths, low loss signal transport over optical fiber, and various physical advantages related to fiber transport including electromagnetic interference immunity and signal multiplexing. The key to realizing these advantages is the efficient conversion from the electrical-to-optical and optical-to-electrical domain. In this paper, system design issues are discussed to take full advantage of recently available photonic technology including photonic downconversion and downsampling. These concepts are discussed and demonstrated within the context of two promising photonic microwave to digital architectures.
Mental Practice and Motor Learning of a Functional Motor Task in Older Adults: A Pilot Study

The purpose of this study was to examine the influence of mental practice on retention of a newly learned functional motor task in older adults. Nineteen non-demented community-dwelling older adults were randomly assigned to experimental and control groups and received a session of individual instruction in a novel motor task. Subjects were scored on their performance of the motor task on the final practice trial of the training session, and again 48–72 hours later. The experimental group mentally rehearsed the procedure 4 times in the 48 hour interval between training and testing while control subjects did not. Subjects in the experimental group scored significantly higher on the test day than the control subjects (p < 1.0), and difference scores from training to testing dates were significantly different between groups (p < 0.50). These findings suggest that for older adults, mental practice facilitates retention of a newly learned functional motor task.
Childhood Obesity: Adrift in the “Limbic Triangle”

The prevalence and severity of childhood obesity have increased steadily over the past three decades. The human species evolved to rigorously defend its lower limit for weight and adiposity but is tolerant of the upper limit, which, until recent times, was rarely approached. Neuroendocrine mechanisms within the limbic core of the brain prevent starvation (ventromedial hypothalamus), heighten reward (ventral tegmental area and nucleus accumbens), and attenuate stress (amygdala), in order to promote food-seeking and ingestive behavior and to conserve energy output. In a stressful modern environment with ready access to calorie-dense, highly palatable foods and limited venues for activity, normal, reflexive responsiveness to these three drives makes weight gain all but inevitable. The obesity that ensues often engenders insulin resistance, which undermines the ability of normal hunger and satiety signals to accurately modulate energy intake versus expenditure. Obesity interventions that rely on cognitive information alone cannot free children from this "limbic triangle." Integrated multidisciplinary family- and community-based education, effective stress reduction, and a societal commitment to alter the food and built environments are all necessary components to battle the global obesity epidemic.
A TRPA1-dependent mechanism for the pungent sensation of weak acids.

Acetic acid produces an irritating sensation that can be attributed to activation of nociceptors within the trigeminal ganglion that innervate the nasal or oral cavities. These sensory neurons sense a diverse array of noxious agents in the environment, allowing animals to actively avoid tissue damage. Although receptor mechanisms have been identified for many noxious chemicals, the mechanisms by which animals detect weak acids, such as acetic acid, are less well understood. Weak acids are only partially dissociated at neutral pH and, as such, some can cross the cell membrane, acidifying the cell cytosol. The nociceptor ion channel TRPA1 is activated by CO2, through gating of the channel by intracellular protons, making it a candidate to more generally mediate sensory responses to weak acids. To test this possibility, we measured responses to weak acids from heterologously expressed TRPA1 channels and trigeminal neurons with patch clamp recording and Ca2+ microfluorometry. Our results show that heterologously expressed TRPA1 currents can be induced by a series of weak organic acids, including acetic, propionic, formic, and lactic acid, but not by strong acids. Notably, the degree of channel activation was predicted by the degree of intracellular acidification produced by each acid, suggesting that intracellular protons are the proximate stimulus that gates the channel. Responses to weak acids produced a Ca2+-independent inactivation that precluded further activation by weak acids or reactive chemicals, whereas preactivation by reactive electrophiles sensitized TRPA1 channels to weak acids. Importantly, responses of trigeminal neurons to weak acids were highly overrepresented in the subpopulation of TRPA1-expressing neurons and were severely reduced in neurons from TRPA1 knockout mice. We conclude that TRPA1 is a general sensor for weak acids that produce intracellular acidification and suggest that it functions within the pain pathway to mediate sensitivity to cellular acidosis.
PIV application in advanced low Reynolds number facility

The advent of micro aerial vehicles (MAV) and advanced flow control methods, using microelectromechanical systems (MEMS) and micro-blowing or suction, has significantly increased the need for a better understanding of very low Reynolds number flows. Aerodynamic testing in this flow regime using conventional facilities, such as wind or water tunnels, is seriously hampered by the necessary small model sizes and low testing speeds, rendering it very difficult to diagnose the flow with adequate spatial resolution and to measure aerodynamic loads with sufficient accuracy. A proof-of-concept pilot of a novel facility specifically intended for low Reynolds number testing has been built and is briefly described. It is based on the use of a high kinematic viscosity test medium, which allows testing superscale models at the correct Reynolds number. The facility is akin to a towing tank, but does not have a free surface with its associated shortcomings. Implementation of the particle image velocimetry (PIV) technique in this type of facility is complicated by the fact that the optics, rather than being stationary as is the case in conventional aerodynamic testing facilities, move in synchronism with the model. Mistracking directly results in velocity-field errors which must be corrected. Methods to do so are described.
Curcumin implants for continuous systemic delivery: safety and biocompatibility.

Curcumin, an anti-oxidant, anti-inflammatory, and anti-neoplastic agent, exhibited limited oral efficacy due to its poor bioavailability. To overcome this limitation, polymeric implants for continuous systemic delivery of curcumin were developed and tested for their safety and biocompatibility. Two 2-cm polycaprolactone implants containing polyethylene glycol and 20% (w/w) curcumin were grafted subcutaneously at the back of the Augustus Copenhagen Irish rats. Rats were euthanized and blood was analyzed for various hematological parameters; biochemical markers of liver/kidney function and local tissues were analyzed for local inflammatory reactions. Curcumin implants exhibited biphasic release kinetics with ∼3.6 + 0.8, 5.8 ± 1.1, 13.1 ± 2.1, 21.8 ± 0.3, 38.1 ± 0.6, and 47.2 ± 1.6 mg cumulative curcumin being released from both the implants after 1, 4, 12, 25, and 90 days. No significant differences in various hematological parameters (like white blood cells, red blood cells, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin), liver enzymes (like aspartate transaminase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, amylase, or lipase), or biochemical parameters of kidney function (like blood urea nitrogen, creatinine, Ca2+, Na+, and Cl− levels) were observed at any of these time points. However, a significant increase in serum phosphorus levels was observed at all the time points in sham implants as well as in curcumin diet and implant groups. Local implantation site showed foreign body granulomatous reaction with influx of histiocytes and occasional multi-nucleated giant cells with sham implants and was minimal around the curcumin implants. These polymeric implants were found to have little or no systemic toxicity with an acute reaction at local site which was reduced significantly by curcumin implants.
The Environmental Protection Agency's Budget from 1970 to 2010: A Lifecycle Analysis

Using three approaches, we attempt to explain changes in the Environmental Protection Agency's operating budget from 1970 to 2010. First, we compare qualitative predictions from two general types of agency lifecycle theories to the actual path of the EPA's budget. Second, we test empirically several hypotheses regarding the effects of political, economic, and other variables on the agency's budget. Third, we conduct detailed historical case studies of selected years. The results offer hints of support for theories predicting incremental change but do not support the hypothesized effects of external factors. We also uncover some historical anomalies that warrant further research.
Effect of lipid composition on buforin II structure and membrane entry

Buforin II is a 21-amino acid polycationic antimicrobial peptide derived from a peptide originally isolated from the stomach tissue of the Asian toad Bufo bufo gargarizans. It is hypothesized to target a wide range of bacteria by translocating into cells without membrane permeabilization and binding to nucleic acids. Previous research found that the structure and membrane interactions of buforin II are related to lipid composition. In this study, we used molecular dynamics (MD) simulations along with lipid vesicle experiments to gain insight into how buforin II interacts differently with phosphatidylcholine (PC), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) lipids. Fluorescent spectroscopic measurements agreed with the previous assertion that buforin II does not interact with pure PC vesicles. Nonetheless, the reduced entry of the peptide into anionic PG membranes versus neutral PC membranes during simulations correlates with the experimentally observed reduction in BF2 translocation through pure PG membranes. Simulations showing membrane entry into PC also provide insight into how buforin II may initially penetrate cell membranes. Our MD simulations also allowed us to consider how neutral PE lipids affect the peptide differently than PC. In particular, the peptide had a more helical secondary structure in simulations with PE lipids. A change in structure was also apparent in circular dichroism measurements. PE also reduced membrane entry in simulations, which correlates with decreased translocation in the presence of PE observed in previous studies. Together, these results provide molecular-level insight into how lipid composition can affect buforin II structure and function and will be useful in efforts to design peptides with desired antimicrobial and cell-penetrating properties.
A discrete truncated Pareto distribution

Abstract We propose a new discrete distribution with finite support, which generalizes truncated Pareto and beta distributions as well as uniform and Benford’s laws. Although our focus is on basic properties and stochastic representations, we also consider parameter estimation and include an illustration from ecology showing potential applications of this new stochastic model.
Transtelephonic versus remote monitoring of cardiovascular implantable electronic devices: is one approach to be preferred?

Intracardiac pacemaker implantation was first described a half century ago; the same authors first reported on transtelephonic monitoring (TTM) of such devices a dozen years later ([1,2][1]). Follow-up of the pacemaker patient was recognized as critical, particularly in view of the uncertain
Signatures and Consequences of the Substrate Corrugation

Information on the amplitudes of the spatially periodic terms in the adatom substrate potential energy is reviewed for a series of adsorbates on graphite. The use of data for the structure and dynamics of the ordered adlayer is discussed. Generalizing interaction models to reflect the anisotropic polarizability of the substrate may account for the results for adsorbed inert gases, but does not appear to be sufficient to treat molecular adsorbates.
Review: James Frazer Stirling: Notes from the Archive by Anthony Vidler

Anthony Vidler . James Frazer Stirling: Notes from the Archive . New Haven and London: Canadian Centre for Architecture and Yale Center for British Art, in association with Yale University Press, 2010, xix + 303 pp., 360 color illus. $70, (cloth) ISBN 9780300167238 First some disclosures: I attended the Liverpool University School of Architecture, starting in 1953, three years after James Stirling graduated from that same institution. When I began teaching at Cambridge in 1962 I inherited from Colin Rowe a tutorial supervisee named Anthony Vidler. On sabbatical leave to Harvard from Cambridge in 1968, I was called in to "pinch-hit" for Stirling at Yale for a semester, much, I'm sure, to the dismay of his students. These connections made reviewing this book a journey of reminiscence. There was the recognizable work of a postwar student of the Liverpool University School of Architecture—typically commonsensical and programmatically thorough, revealing influences from international figures such as Le Corbusier and Marcel Breuer, and at the same time very aware of Liverpool's architectural, maritime, and industrial history, and its orientation westward towards the U.S.A. There was the influence of Colin Rowe, who refused to accept that architecture had separated itself from its past during the rise of modernism. There was the punctilious work of a Cambridge-trained history scholar (Vidler). There were all the names associated with the English architectural debates of the fifties and the sixties: Peter and Alison Smithson, Reyner Banham, Colin St. John …
Action of Tincture of Iodine when Injected into the Pericardial Sac

Conclusions(1) Tincture of iodine injected into the pericardial sac is rapidly absorbed, as indicated by the presence of iodides in the urine. (2) Tincture of iodine injected in the pericardial sac effects a gradual rise in blood pressure with an increase in pulse pressure. There is also a temporary decrease in intestinal activity, which occurs after section of the vagi, and is also obtained by intravenous injection of the iodine. (3) The M.L.D. of tincture of iodine injected intravenously, when given at the rate of 0.1 cc of tincture of iodine per kg of body weight every 5 minutes, is 1 cc per kg of body weight. (4) Ten cc (1 dose), and 16 cc given in divided doses of tincture of iodine in the pericardial sac were not lethal.
Effect of Aspect Ratio on Flat-Plate Membrane Airfoils

The objective of the investigation presented in this paper is to assess the effect of aspect ratio on flat plate membrane wings. A series of membrane and rigid flat test plates with varying aspect ratio (0.9 to 4.3) were tested at low Reynolds numbers (Re < 51,000). Results show that compared to the rigid flat plate, the membrane wing has a higher lift curve slope, stall-region lift and aerodynamic efficiency. These membrane-induced characteristics persist as aspect ratio and Reynolds number are decreased.
Altered lymphocyte reactivity to E. coli in chronic pyelonephritis.

Abstract Based on the concept that the progressive course of chronic pyelonephritis may be related to a form of distorted host immunity, the reactivity of lymphocytes from patients with this disease was tested with the bacterial adherence technique. With this method, circumferential adhesion of bacteria to the lymphocyte surface is considered an antigen-antibody reaction indicating antibody production by this cell. Human lymphocytes, incubated with autologous urinary and heterotypic fecal E. coli , demonstrated absent or markedly diminished bacterial adherence compared with lymphocytes from normal control patients reacted with their own and cross-reacted with heterotypic fecal E. coli in the same assay. When Staphylococci were used as a substitute test antigen, bacterial adherence of patient lymphocytes was normal. Furthermore, in vitro tissue culture stimulation of normal lymphocytes with autologous and heterotypic fecal E. coli resulted in appreciably increased bacterial adherence, although this heightened response could not be achieved with patient lymphocytes and urinary and normal fecal E. coli antigen. However, bacterial adherence of patient lymphocytes was augmented when they were grown in tissue culture in the presence of an extract made from normal lymphocytes previously exposed, in vitro, to heterotypic E. coli and that isolated from patient urine. The hyporeactivity of patient lymphocytes to certain bacteria may, by definition, be considered a form of immune tolerance since it appears to be related to a direct effect of E. coli on immunologically competent cells. This may be attributable, in part, to the continual presence of this organism in the renal parenchyma. The reactivation of the cellular response by normal lymphocyte extract in vitro suggests that, under certain circumstances, this defect may be reversed. It is conceivable that the diminished efficacy of this aspect of the immune defense mechanism may facilitate extension of renal infection in vivo and that a definitive approach to the clinical management of chronic pyelonephritis should be directed toward means which prevent the development of tolerance in this disease.
Neutralizing activity of sera from guinea-pigs inoculated with foot-and-mouth disease virus variants.

Summary The neutralizing activity of sera from guinea-pigs inoculated with small-plaque (SP) and large-plaque (LP) variants of foot-and-mouth disease virus (FMDV) was studied. Virus neutralization tests were performed in suckling mice using the SP and LP variants as well as a low passage virus of the same type and strain. Higher titres were obtained with homologous virus than when a vims of low passage in tissue culture was used. Neutralizing activity was not demonstrable in some guinea-pig sera with a low passage virus, whereas a significant level of neutralizing activity was detected when homologous virus-serum mixtures were tested.
Identification of clinically achievable combination therapies in childhood rhabdomyosarcoma

Systemic therapy has improved rhabdomyosarcoma event-free and overall survival; however, approximately 40 % of patients will have progressive or recurrent disease which is difficult to cure and remains a considerable challenge. Minimal progress has been made in improving outcomes for metastatic or relapsed RMS due to a lack of effective therapeutic agents. Targeted therapies are likely to be incorporated into regimens which rely on conventional cytotoxic chemotherapy. A system to evaluate novel combinations of interest is needed. In this study, we explored 8 agents, 5 that are routinely used or similar to agents used in the clinical management of RMS and 3 biologically targeted agents with novel mechanisms of action, the Wee1 inhibitor AZD1775, the tyrosine kinase inhibitor cabozantinib, and the proteasome inhibitor bortezomib. All were tested individually at clinically achievable concentrations for activity in 4 RMS cell lines and then for potential synergy in two-drug combinations. We found single-agent activity in five of the agents (or their active metabolites) that constitute the standard of care in RMS and for AZD1775 with mean IC50 values of 207 ng/ml, well below clinically achievable levels. In addition, the combination of individual cytotoxic chemotherapeutics currently used for RMS demonstrated largely synergistic activity with higher, but clinically achievable concentrations of AZD1775 in our assays. Prioritization of chemotherapeutics in RMS is possible using an in vitro system that can define novel drug combinations worthy of future investigation. AZD1775 exhibits single-agent activity, as well as synergy with conventional cytotoxic chemotherapy, and is a novel targeted agent that warrants further study in RMS.