cssi/SciSciGPT-SciSciNet huggingface dataset:
Long-term outcome of (neo)adjuvant zoledronic acid therapy in locally advanced breast cancer.

The role of zoledronic acid (ZOL), a bone-targeted bisphosphonate, in the treatment of patients with breast cancer remains an active area of study. Here, we report the long-term outcomes of a randomized placebo-controlled phase II clinical trial in which ZOL treatment was added to neoadjuvant chemotherapy in women with locally advanced breast cancer. 120 women with clinical stage II–III (≥ T2 and/or ≥ N1) newly diagnosed breast cancer were randomized to receive either 4 mg intravenous ZOL every 3 weeks for 1 year (17 total doses) beginning with the first dose of neoadjuvant chemotherapy, or chemotherapy alone. Clinical endpoints included time to recurrence (TTR), time to bone recurrence (TTBR), time to non-bone recurrence (TTNBR), breast cancer survival (BCS) and overall survival (OS). With a median follow-up interval of 14.4 years, there were no significant differences in any of the clinical endpoints studied between the control and ZOL groups in the overall study population. However, ER+/HER2− patients younger than age 45 who were treated with ZOL had significantly worse TTR and TTNBR with a trend towards worse TTBR, BCS and OS (TTR: P = 0.024, HR 6.05 [1.26–29.1]; TTNBR: P = 0.026, HR 6.94 [1.26–38.1]; TTBR: P = 0.054, HR 6.01 [0.97–37.1]; BCS: P = 0.138, HR 4.43 [0.62–31.7]; OS: P = 0.138, HR 4.43 [0.62–31.7]). These differences were not seen in older ER+/HER2− patients or triple-negative patients of any age. Addition of ZOL to neoadjuvant therapy did not significantly affect clinical outcomes in the overall study population but was associated with increased extra-skeletal recurrence and a trend towards worse survival in ER+/HER2− patients younger than age 45. These findings suggest caution when using zoledronic acid in young, premenopausal women with locally advanced breast cancer and warrant further investigation. Clinical Trial Registration Number NCT00242203, Date of Registration: 10/17/2005
Thermodynamics of ion binding and occupancy in potassium channels

Potassium channels modulate various cellular functions through efficient and selective conduction of K+ ions. The mechanism of ion conduction in potassium channels has recently emerged as a topic of debate. Crystal structures of potassium channels show four K+ ions bound to adjacent binding sites in the selectivity filter, while chemical intuition and molecular modeling suggest that the direct ion contacts are unstable. Molecular dynamics (MD) simulations have been instrumental in the study of conduction and gating mechanisms of ion channels. Based on MD simulations, two hypotheses have been proposed, in which the four-ion configuration is an artifact due to either averaged structures or low temperature in crystallographic experiments. The two hypotheses have been supported or challenged by different experiments. Here, MD simulations with polarizable force fields validated by ab initio calculations were used to investigate the ion binding thermodynamics. Contrary to previous beliefs, the four-ion configuration was predicted to be thermodynamically stable after accounting for the complex electrostatic interactions and dielectric screening. Polarization plays a critical role in the thermodynamic stabilities. As a result, the ion conduction likely operates through a simple single-vacancy and water-free mechanism. The simulations explained crystal structures, ion binding experiments and recent controversial mutagenesis experiments. This work provides a clear view of the mechanism underlying the efficient ion conduction and demonstrates the importance of polarization in ion channel simulations.
Covariate balancing functional propensity score for functional treatments in cross-sectional observational studies

Abstract Functional data analysis, which handles data arising from curves, surfaces, volumes, manifolds and beyond in a variety of scientific fields, is a rapidly developing area in modern statistics and data science in the recent decades. The effect of a functional variable on an outcome is an essential theme in functional data analysis, but a majority of related studies are restricted to correlational effects rather than causal effects. As the first attempt in the literature, the causal effect is studied for a functional variable as a treatment in cross-sectional observational studies. Despite the lack of a probability density function for the functional treatment, the propensity score is properly defined in terms of its top functional principal component scores which can represent the functional treatment approximately. Two covariate balancing methods are proposed to estimate the propensity score, which minimize the correlation between the treatment and covariates. The appealing performance of the proposed method in both covariate balance and causal effect estimation is demonstrated by a simulation study. The proposed method is applied to study the causal effect of body shape on human visceral adipose tissue.
Discovering Influence of Yelp Reviews Using Hawkes Point Processes

With the development of technology, social media and online forums are becoming popular platforms for people to share opinions and information. A major question is how much influence these have on other users’ behavior. In this paper, we focused on Yelp, an online platform for customers to share information of their visiting experiences on restaurants, to explore the possible relationships between past reviews and future reviews of a restaurant through multiple aspects such as star-ratings, user features and sentiment features. By using the lasso regression model with review features processed through Hawkes Process Model and B-Spline basis functions as the modeling of restaurant basic performance, average star-ratings, low star-ratings and sentiment features of past reviews have been found to have significant influence on future reviews. Due to the limited dataset, we performed simulation on restaurants’ reviews using Multinomial Logistic Regression and re-built the model. A verification process has been performed eventually using Logistical Regression. The simulation and the verification results have been found to support the prior findings which indicate that influence between past and future reviews does exist, and can be revealed on multiple aspects.
A new method for testing the performance of UHF sensors

The ultra-high frequency(UHF) method is an effective partial discharge detection method, which is widely used for online monitoring of electrical equipment and on-site live detection. At present, effective height is an effective parameter to characterize the performance of sensors, which can reflect the sensitivity of UHF sensors to different frequency spectra in signals. However, there is a problem that the effective height cannot reflect the response degree of the sensor to the pulse signal in the time domain. This parameter only pays attention to the amplitude-frequency characteristics but ignores the phase-frequency characteristics. In order to make up for the lack of performance parameters of existing sensors, this paper proposes a new performance test system to reflect the performance of UHF sensors. Firstly, S parameters are used to get the 2 characteristics of the sensor’s effective height, and then 3 parameters of the analytical impulse response function are retrieved as sensor performance indicators. Experimental results show that this method can effectively reflect the performance of UHF sensors.
Chapter 11 Total syntheses of natural products using the combine C-H activation/cope rearrangement as the key step

Summary In summary, we have demonstrated that the combined C–H activation/Cope rearrangement protocol is an exceptional method for the construction of the three stereogenic centers common to the numerous diterpenes isolated from Pseudopterogorgia elisabethae . The synthetic potential of this chemistry was demonstrated by means of efficient enan-tioselective syntheses of (+)-erogorgiaene ( 2 ), (–)-colombiasin A ( 3 ), (–)-elisapterosin B ( 4 ), the assigned structure of (+)-elisabethadione ( 5 ), the p -benzoquinone natural product ( 6 ), (+)- O -methyl-elisabethadione ( 72 ), (+)- O -methyl- nor -elisabethadione ( 73 ), and the oxidized form of elisabethamine ( 76 ). These studies also demonstrate the value of total synthesis to confirm the assigned structures of natural products.
Fluoride salts as phase change materials for thermal energy storage in the temperature range 1000-1400 K

Eutectic compositions and congruently melting intermediate compounds in binary and ternary fluoride salt systems were characterized for potential use as latent heat of fusion phase change materials to store thermal energy in the temperature range 1000-1400 K. The melting points and eutectic compositions for many systems with published phase diagrams were experimentally verified and new eutectic compositions having melting points between 1000 and 1400 K were identified. Heats of fusion of several binary and ternary eutectics and congruently melting compounds were experimentally measured by differential scanning calorimetry. For a few systems in which heats of mixing in the melts have been measured, heats of fusion of the eutectics were calculated from thermodynamic considerations and good agreement was obtained between the measured and calculated values. Several combinations of salts with high heats of fusion per unit mass (greater than 0.7 kJ/g) have been identified for possible use as phase change materials in advanced solar dynamic space power applications.
Oversampled capacitance-to-voltage converter IC with application to SiC MEMS resonator

This paper reports the first electronic circuit used to measure MEMS resonator motion in the time domain. The measurement of shuttle position is made using a capacitance-to-voltage converter IC that has been developed by combining correlated double sampling with delta modulation in a fully differential circuit topology. This oversampling circuit may be adjusted to trade bandwidth (sample rate) for resolution, while reference level may be adjusted to set the desired sensitivity to accommodate a large range of capacitive sensor interface applications. For example, test results demonstrate a resolution of 170 aF for a signal bandwidth of 3 kHz, a 68-dB dynamic range, and nonlinearity less than 0.16%.
Immunohistochemical analysis of magnocellular elements in rat hypothalamus: Distribution and numbers of cells containing neurophysin, oxytocin, and vasopressin

A cell-by-cell analysis of the magnocellular elements in hypothalami of fifty Long-Evans (normal) and Brattleboro (diabetes insipidus) rats was done using the unlabeled antibody enzyme technique (PAP) with primary antisera directed against oxytocin (OXY), vasopressin (ADH), and the neurophysins. The magnocellular neurons of the hypothalamus were found in the supraoptic (SON), paraventricular (PVN), and anterior commissural (ACN) nuclei, a number of accessory nuclei, and as individual cells in the anterior hypothalamic area. SON was divided by the optic tract into the principal part and retrochiasmatic SON. In retrochiasmatic SON a majority of the cells contained vasopressin. Within the principal part of SON oxytocin-producing cells tended to be found rostrally and dorsally, while the vasopressin cells were more common caudally and ventrally. PVN was divided into three subnuclei, the medial, lateral, and posterior subnuclei, on the basis of cellular morphology and peptide content. The magnocellular cells of the medial and lateral PVN were closely packed together and nearly round, while those of posterior PVN were more separated and fusiform in shape with their long axis running in a medio-lateral direction. Medial PVN consisted primarily of oxytocin-producing cells, while lateral PVN was formed by a core of vasopressin-producing cells with a rim of oxytocin cells. Posterior PVN contained largely oxytocin-producing cells. Both ADH and OXY cells were found in the accessory nuclei. In the Long-Evans rat the SON had, on the average, 1443 OXY and 3236 ADH cells; the PVN had 1174 OXY and 976 ADH cells; and the accessory magnocellular groups in the hypothalamus (including the ACN) had 1286 OXY and 552 ADH cells. The Brattleboro strain animal had similar numbers of cells in these nuclei. (The cells which contain ADH in normal animals were identified in the Brattleboro rat as large, neurophysin-negative cells.) Thus, a large fraction of the magnocellular oxytocin- and vasopressin-producing cells in the rat were located outside of the PVN and SON. One accessory cell group in particular, ACN, had 616 OXY cells, or about 50% as many as PVN. In each nucleus the sum of the numbers of OXY and ADH cells was approximately the number of neurophysin cells.
Evaluating the scalability of multilayer MoS 2 transistors

In this article we investigate the ultimate scaling potential of multilayer MoS2 field effect transistors (FETs) with channel lengths ranging from 1μm down to 50nm using a 20nm thick SiO2 back gate and scandium as the source/drain metal contacts. We also report, for the first time, the in-plane dielectric constant for multilayer MoS2 as extracted from our experiments, which plays an important role in determining the scaling limit of any channel material. Our results indicate that multilayer MoS2 FETs are resilient to short channel effects down to 50nm channel length and therefore allow for aggressive channel length scaling likely beyond the 10nm technology node.
Characterization of chronically implanted ventricular endocardial pacing leads

Abstract The expected implant lifetime of pacemaker generators has been extended with the introduction of lithium power sources. Consequently, the pacing lead may become the component that determines the total implant lifetime of the pacemaker. This fact emphasizes the necessity for accurate assessment of the integrity of a chronically implanted lead. In this study, chronic threshold and impedance data from 61 patients having the same type of ventricular endocardial lead for up to 10 years were retrospectively analyzed. The mean acute current threshold was 0.81 ± 0.33 mA. The chronic current threshold had a range of between 1 and 5 mA, which was approximately two to five times greater than the acute implant value. Chronic voltage threshold and impedance were 0.7 to 4 V and 335 to 775 Ω, respectively. The findings of this study provide general guidelines for chronic lead parameters and illustrate some of the difficulties encountered in gathering and interpreting long-term lead data.
Shoulder dystocia: An analysis of risks and obstetric maneuvers

Objective: The purpose of this study was to determine whether there is a risk profile for predicting or preventing shoulder dystocia and whether any of the obstetric maneuvers to disimpact a shoulder reduce the likelihood of permanent injury. Study Design: A retrospective analysis of 14.297 parturients with 12,532 vaginal deliveries and 1765 cesarean sections (12.4%) from January 1986 through June 1990 was performed. A total of 204 maternal and infant charts, related to shoulder dystocia or neonatal injury, were reviewed in depth for age, parity, episiotomy, type of delivery, hemorrhage, maternal obesity, diabetes, weight gain, fetal weight, sex, and Apgar scores. In addition, the type of maneuver or combination thereof used to relieve the dystocia, type of injury to the infant, and follow-up of the injury were reviewed. Results: The 185 coded episodes of shoulder dystocia represent 1.4% of all vaginal deliveries (12,532). There were 42 injuries recorded: 14 fractured clavicles and 28 brachial plexus injuries. An additional 19 patients, not coded for shoulder dystocia, sustained 14 fractured clavicles and five brachial plexus injuries. All but one of the brachial plexus injuries resolved by 6 months. The occurrence of shoulder dystocia increased in direct relationship to the birth weight and becomes significant in newborns over 4000 gm ( p p Conclusions: This study clearly indicates that most of the traditional risk factors for shoulder dystocia have no predictive value, shoulder dystocia itself is an unpredictable event, and infants at risk for permanent injury are virtually impossible to predict. In addition, no delivery method in shoulder dystocia was superior to another with respect to injury. Thus no protocol should serve to substitute for clinical judgment.
Differential Effect of Several Inducers on Hepatic and Mammary Benzo (A) Pyrene Metabolism in Rat and Hamster

ABSTRACTRat and hamster mammary gland, in comparison with the liver, were examined for their in vitro ability to metabolize polycyclic aromatic hydrocarbons, and for the effects of pretreatment with various mixed function oxidase inducers on this metabolism. Hamster mammary microsomal benzo(a)pyrene (BP) hydroxylase activity was 4-fold greater than that in the rat, and this activity was induced 3 - to 5 - fold in the hamster, and 7- to 13 - fold in the rat, by pretreatment with 7, 12-dimethylbenz(a)anthracene, β-naphtho flavone, Aroclor 1254 or 3 - methylcholanthrene. Hamster hepatic microsomal BP-hydroxylase activity was 80-fold greater than in the rat. Whereas pretreatment with these enzyme inducers enhanced rat hepatic activity by 20- to 30-fold, little effect of “inducers” was observed on the hamster hepatic enzyme, even when the formation of the various BP metabolites was determined by high pressure liquid chromatography.
The impaction of spherical particles on cylindrical collectors

Abstract The impaction coefficient of spherical particles moving in an air stream normal to an infinitely long cylindrical collector is analyzed. Experimental results where the radius of the particles is in the same order of magnitude as the radius of the cylindrical collector are compared with the already documented cases of particles much smaller than the collector. A comparison is made of a proposed expression for the impaction coefficient with already documented models as well as with available experimental data. The impaction coefficient is given in terms of the flow Reynolds number and the ratio of particle to collector radii alone.
RelA Inhibits Bacillus subtilis Motility and Chaining

The nucleotide second messengers pppGpp and ppGpp [(p)ppGpp] are responsible for the global downregulation of transcription, translation, DNA replication, and growth rate that occurs during the stringent response. More recent studies suggest that (p)ppGpp is also an important effector in many nonstringent processes, including virulence, persister cell formation, and biofilm production. In Bacillus subtilis, (p)ppGpp production is primarily determined by the net activity of RelA, a bifunctional (p)ppGpp synthetase/hydrolase, and two monofunctional (p)ppGpp synthetases, YwaC and YjbM. We observe that in B. subtilis, a relA mutant grows exclusively as unchained, motile cells, phenotypes regulated by the alternative sigma factor SigD. Our data indicate that the relA mutant is trapped in a SigD "on" state during exponential growth, implicating RelA and (p)ppGpp levels in the regulation of cell chaining and motility in B. subtilis. Our results also suggest that minor variations in basal (p)ppGpp levels can significantly skew developmental decision-making outcomes.
Effects of pH on cholinergic vascular receptors of rainbow trout, Salmo gairdneri

Abstract 1. 1. Contractile responses of helically-cut strips of bulbus arteriosus were obtained after increasing the pH to 7·20 or decreasing the pH to 5·80 and compared to control responses obtained at pH 6·46. 2. 2. Responses to acetylcholine were slightly augmented at pH 7·20 and were depressed at pH 5·80. 3. 3. Atropine and methyl atropine shifted acetylcholine dose-response curves to the right to a greater degree at pH 5·80 than at pH 7·20. 4. 4. Pilocarpine was less effective as an agonist at pH 5·80 than at 7·20. 5. 5. Responses to potassium chloride were increased at pH 7·20 and were reduced at pH 5·80. 6. 6. Since responses were augmented at pH 7·20 and depressed at pH 5·80 in each of the approaches, it is concluded that the effects of pH on the responses to cholinergic and anticholinergic drugs in this study were largely non-specific.
kCAT Inactivation of mushroom polyphenol oxidase

Abstract Mushroom polyphenol oxidase is rapidly inactivated during turnover of substrate to product ( k cat inactivation). As shown by use of [U- 14 C]-phenol as substrate, there is a marked nonspecific covalent binding of product to polyphenol oxidase (85 mol 14 C-labeled product per mol of polyphenol oxidase subunits). In the presence of sufficient ascorbic acid to keep the product o -benzoquinone reduced to dihydroxyphenol, only 0.04 mol of 14 C-labeled product per mol of polyphenol oxidase subunits was covalently bound. Therefore, k cat inactivation of mushroom polyphenol oxidase probably involves a free radical mechanism, rather than covalent binding of product at the active site proposed as one mechanism by Wood and Ingraham [5].
Structuring Typewriting Production Skill

(1975). Structuring Typewriting Production Skill. The Journal of Business Education: Vol. 51, No. 1, pp. 23-24.
Do emotions have distinct vocal profiles? A study of idiographic patterns of expression

Research on vocal expressions of emotion indicates that persons can identify emotions from voice with relatively high accuracy rates. In addition, fairly consistent vocal profiles for specific emotions have been identified. However, important methodological issues remain to be addressed. In this paper, we address the issue of whether there are individual differences in the manner in which particular emotions may be expressed vocally and whether trained speakers’ portrayals of emotion are in some sense superior to untrained speakers’ portrayals. Consistent support was found for differences across speakers in the manner in which they expressed the same emotions. No accompanying relationship was found between differences in expression and accuracy of identification of those expressions. Little evidence for the superiority of trained speakers was found. Implications of these findings for future studies of vocal expressions of emotion, as well as our understanding of emotions in general, are discussed.
Differential progression of motor impairment in levodopa-treated Parkinson's disease.

OBJECTIVE To monitor comparative progression of clinical impairment over 4 years in patients with Parkinson's disease (PD) who present on levodopa at two different levels of Hoehn and Yahr (HY) stages, II and III. BACKGROUND The rate of clinical impairment progression in patients with PD being treated with levodopa has not been studied in detail using current, standardized assessment tools. Sample size estimates for all levodopa adjunctive treatment studies and proper definition of study groups require a solid estimate of longitudinal motor impairment progression. DESIGN/METHODS From our computer database, we identified two groups of patients with PD being treated with levodopa based on their initial HY stage at presentation to our center (II or III). Fifty randomly selected subjects in each stage were monitored in the ON state with annual Unified Parkinson's Disease Rating Scale (UPDRS) motor scores, dyskinesia ratings, and antiparkinsonian medication doses using a repeated measures analysis of variance. RESULTS The stage II and stage III subjects had similar disease duration. In stage II subjects, parkinsonian impairment was maintained without progression over 4 years, but in association with significantly higher dyskinesia scores and dopaminergic medication doses. In stage III subjects, UPDRS motor scores deteriorated despite more medication and increased dyskinesias. Of the established six factors comprising the UPDRS motor scale, bradykinesia accounted for the increased impairment. Initial UPDRS motor score and disease duration did not influence progression of motor impairment. CONCLUSION In subjects with similar disease duration, progression of PD motor impairment differs significantly between stage II and stage III subjects over 4 years. Whereas in stage II subjects, parkinsonian impairment can be stabilized at the expense of increased dyskinesia and dopaminergic drugs, once subjects reach stage III, motor impairment progresses. Power estimates and sample size calculations for these groups of patients should be calculated separately.
Laparoscopy and major retroperitoneal vascular injuries (MRVI)

Injury to major retroperitoneal vessels is a potential serious complication of laparoscopy occurring when the Veress needle or trocar is inserted. This report is a review of major retropertioneal vascular injuries (MRVI) occurring during laparoscopy, as these injuries have not been well documented in the literature. A retrospective, observational review of general surgical laparoscopy cases was conducted over a 3.5-year period in three community, university-affiliated hospitals. We identified 4 MRVI in 3591 laparoscopic procedures. These cases were critically analyzed and compared. The incidence of MRVI was ∼0.1%. All cases occurred with the closed (blind) insertion technique of Veress needle and primary trocar insertion technique with disposable “safety” shield trocars. All patients sustaining MRVI had acute hypotension introperatively and significant blood loss necessitating postoperative transfusions. Recognition and rapid conversion to laparotomy are keys to enhancing outcome. There is significant potential for morbidity and mortality with laparoscopic MRVI, although each patient in this series was discharged without obvious short-term problems. The advantages of an open approach for primary trocar insertion are numerous and should alleviate the risk of MRVI associated with general laparoscopic surgery.
Increased urinary cortisol levels during the menopausal transition.

Objective To determine whether cortisol levels change prospectively during the menopausal transition (MT); whether these changes are associated with changes in the hypothalamic-pituitary-ovarian axis (follicle-stimulating hormone [FSH] and estrone glucuronide [E1G]), stressors, or menopause symptoms; and whether women who experienced a rise in cortisol levels during the transition had behavioral practices, stressors, vasomotor symptoms, or mood or sleep disturbances that affected hypothalamic-pituitary-adrenal axis function. Design One hundred sixty-nine women in the middle or late MT or early postmenopause stages provided monthly urine specimens for cortisol, FSH, and E1G, and rated symptoms and stress levels as part of a longitudinal study of the MT. Of these women, 91 completed a transition to the next MT stage: from early to middle (n = 30), middle to late (n = 39), or late to postmenopause (n = 22) and were eligible for inclusion in the analyses. Results Cortisol increased from 7 to 12 months before the late MT stage to 7 to 12 months after onset of the late MT stage. There were no differences before and after the middle MT stage or the final menstrual period. Women with increased cortisol (>10 ng/mg creatinine) during the late MT stage had more severe vasomotor symptoms than those without changes, but did not differ in terms of age, body mass index, levels of FSH or E1G, health practices, exercise, mood, sleep, cognition, or stress levels. Conclusions Cortisol levels rise with age, but have not been linked to stages of the MT. Increased cortisol levels during the late MT stage, when menstrual irregularities are greatest, suggests increases in adrenal androgens and intraabdominal fat with menopause, and may influence risk of cardiovascular disease, vasomotor symptoms, mood, cognition, and bone loss.
Determination of COREXIT components used in the Deepwater Horizon cleanup by liquid chromatography-ion trap mass spectrometry

The oil spill dispersant, COREXIT 9500, used in the BP Deepwater Horizon oil spill, was analyzed by high-performance liquid chromatography-ion trap mass spectrometry with electrospray ionization. Two components present in the mixture, dioctyl sodium sulfonate (DOSS) and dipropylene glycol butyl ether (DGBE), were recovered from spiked ocean water samples. Compounds were isolated from ocean water spiked with COREXIT 9500 by solid phase extraction using C18 cartridges prior to separation with high performance liquid chromatography-ion trap mass spectrometry using an acetonitrile and 0.1% formic acid gradient. Both compounds were identified using a simultaneous extraction procedure. Dioctyl sodium sulfonate is identified by negative electrospray-ion mode, and dipropylene glycol butyl ether by positive electrospray-ion mode. This method identifies trace levels of dispersants used in oil-spill cleanup efforts through the identification of two major components, which could provide validation for the correct identification of a dispersant mixture. This method was validated by recovering COREXIT components from spiked natural ocean water samples collected in the Gulf of Mexico. Oil-impacted ocean water samples were collected in Grand Isle, Louisiana at an oil-impacted beach, but no traces of COREXIT were identified.
Functional Analysis of PA Binding by Influenza A Virus PB1: Effects on Polymerase Activity and Viral Infectivity

Influenza A virus expresses three viral polymerase (P) subunits—PB1, PB2, and PA—all of which are essential for RNA and viral replication. The functions of P proteins in transcription and replication have been partially elucidated, yet some of these functions seem to be dependent on the formation of a heterotrimer for optimal viral RNA transcription and replication. Although it is conceivable that heterotrimer subunit interactions may allow a more efficient catalysis, direct evidence of their essentiality for viral replication is lacking. Biochemical studies addressing the molecular anatomy of the P complexes have revealed direct interactions between PB1 and PB2 as well as between PB1 and PA. Previous studies have shown that the N-terminal 48 amino acids of PB1, termed domain α, contain the residues required for binding PA. We report here the refined mapping of the amino acid sequences within this small region of PB1 that are indispensable for binding PA by deletion mutagenesis of PB1 in a two-hybrid assay. Subsequently, we used site-directed mutagenesis to identify the critical amino acid residues of PB1 for interaction with PA in vivo. The first 12 amino acids of PB1 were found to constitute the core of the interaction interface, thus narrowing the previous boundaries of domain α. The role of the minimal PB1 domain α in influenza virus gene expression and genome replication was subsequently analyzed by evaluating the activity of a set of PB1 mutants in a model reporter minigenome system. A strong correlation was observed between a functional PA binding site on PB1 and P activity. Influenza viruses bearing mutant PB1 genes were recovered using a plasmid-based influenza virus reverse genetics system. Interestingly, mutations that rendered PB1 unable to bind PA were either nonviable or severely growth impaired. These data are consistent with an essential role for the N terminus of PB1 in binding PA, P activity, and virus growth.
Managing tsunamis through early warning systems : a multidisciplinary approach

This study attempts to identify the key factors that will make a tsunami warning system most effective, to develop a framework in which results of natural science and engineering research can be effectively integrated into coastal natural hazard planning, and to develop a numerical example that illustrates how benefit-cost analysis may be used to assess early warning systems. Results of the study suggest that while the science of tsunami wave propagation and inundation is relatively advanced, our knowledge on the relationships between tsunami generation and undersea earthquakes, volcanic eruptions, and landslides remains poor, resulting in significant uncertainties in tsunami forecasting. Probabilities of damaging tsunamis for many coastal regions are still unknown, making tsunami risk assessment and management difficult. Thus it is essential to develop new techniques to identify paleo-tsunami events and to compile and develop size and frequency information on historical tsunamis for different locations. An effective tsunami early warning system must include not only the ocean technologies for accurately detecting an emerging tsunami, but also a civil communication system through which the population can be timely warned by the local government and other sources. Since minimizing the evacuation time is a key factor to make a warning system effective, adequate pre-event education and preparation of the population must be a critical component of the system. Results of a numerical example of the South Pacific region suggest that investments in a tsunami warning system in the region may lead to significant economic benefits.
Dynamic Coupling and Control Response Effects on Spacecraft Handling Qualities During Docking

NASA is developing a newgeneration of spacecraft to replace the Space Shuttle and return astronauts to themoon. These spacecraft will have a manual control capability for several mission tasks, and the ease and precision with which pilots can execute these tasks will have an important effect on mission risk and training costs. A simulation evaluated the handling qualities of a generic space vehicle based on dynamics similar to one of these spacecraft, NASA’s Crew Exploration Vehicle, during the last segment of the docking task with a space station. This handling qualities evaluation looked at fourdifferent translational control systems, called response types, thatmappilot inputs to thruster firings in a way that gives predictable and useful vehicle responses. These response types were flownwith three levels of translation-into-rotation dynamic coupling arising from a longitudinal offset between the reaction control system thrusters and the vehicle’s center of mass. The results indicate that greater translation-into-rotation coupling is strongly correlated with degraded handling qualities, but that different response types do not have a major effect on pilot workload, final docking performance, or handling qualities.
Collective propensity of orientation for multielectron ions in collisions.

The orientation parameter, [l angle][ital J][sub [ital y]][r angle]/[ital J]([ital J]+1), of the [sup 2][ital F][sub 7/2] state of Ar[sup +], formed in the two-electron process He[sup +]+Ar[r arrow]He(1[ital s][sup 2])+Ar[sup +](3[ital p][sup 4]4[ital p],[sup 2][ital F][sub 7/2]) has been measured at various scattering angles. The measured value of [l angle][ital J][sub [ital y]][r angle], the component of the total angular momentum perpendicular to the collision plane, is interpreted as resulting from a collective circulation of the inactive 3[ital p][sup 4] core electrons as well as the active 4[ital p] electron. We find that over the range of scattering angles studied, this collective-electron circulation is in the direction of the rotating internuclear axis, the direction given by the propensity rule, suggesting that this rule is more general than heretofore proposed.
Mass shifting roles of negative kernel mass in density estimation

f(x) is a univariate density in C 4 with bounded support. For any n and sufficiently small kernel bandwidths, the symmetric appendage of any negative mass, −U, to any smooth unimodal symmetric kernel of order p=2 shifts expected estimator mass from regions where f″(x)>0 to regions where f″(x)<0. For large n, the mean automatic kernel adaptation induced by −U is analyzed in the simplest MISE reduction scenario: The symmetric appendage of −U to the uniform kernel K(x, X) over MISE-optimal bandwidths reduces MISE by shifting K(x, X) mass asymmetrically across the observation X in the direction of decreasing |f″(x)|.
AP1 Proteins Mediate the cAMP Response of the Dopamine β-Hydroxylase Gene

Neurotransmitter biosynthesis is regulated by environmental stimuli, which transmit intracellular signals via second messengers and protein kinase pathways. For the catecholamine biosynthetic enzymes, dopamine β-hydroxylase and tyrosine hydroxylase, regulation of gene expression by cyclic AMP, diacyl glycerol, and Ca2+ leads to increased neurotransmitter biosynthesis. In this report, we demonstrate that the cAMP-mediated regulation of transcription from the dopamine β-hydroxylase promoter is mediated by the AP1 proteins c-Fos, c-Jun, and JunD. Following treatment of cultured cells with cAMP, protein complexes bound to the dopamine β-hydroxylase AP1/cAMP response element element change from consisting of c-Jun and JunD to include c-Fos, c-Jun, and JunD. The homeodomain protein Arix is also a component of this DNA-protein complex, binding to the adjacent homeodomain recognition sites. Transfection of a dominant negative JunD expression plasmid inhibits cAMP-mediated expression of the dopamine β-hydroxylase promoter construct in PC12 and CATH.a cells. In addition to the role of c-Fos in regulating dopamine β-hydroxylase gene expression in response to cAMP, a second pathway, involving Rap1/B-Raf is involved. These experiments illustrate an unusual divergence of cAMP-dependent protein kinase signaling through multiple pathways that then reconverge on a single element in the dopamine β-hydroxylase promoter to elicit activation of gene expression.
The Synthesis, X-ray Crystal Structure, and Molecular Structure of Rhenium Tetra- carbonylbromidetrimethylamineisocyanoborane.

The highly nucleophilic trimethylamineisocyanoborane Me3N+−-BH2−N+⋮-C: interacts with [Re(CO)4Br]2 to give cis and trans coordinated complexes.
Open-State Substructure of Single Chloride Channels from Torpedo Electroplax

Chloride channels from Torpedo californica electroplax were inserted into planar phospholipid membranes, and single-channel currents were studied at high time-resolution. The open channel fluctuates rapidly between three substates, with conductances of 18.5, 9.4 and 0 pS in 150 mM Cl-. Under various ionic conditions the three substates are always equally spaced in conductance; at various voltages leading to different probabilities of observing the three substates, the substate frequencies are always binomially distributed. The conclusion emerges that the conducting of unit of Cl- channel is composed of two identical Cl- diffusion pathways, each with a voltage-dependent gate.
The influence of mixing on rotifer assemblages of Michigan lakes

Seasonal changes in the rotifer assemblages of 42 lakes in northern lower Michigan was closely related to lake mixing characteristics, basin morphometry, and the presence of an oxygenated coldwater refuge. Three major classes of lakes (dimictic, discontinuous polymitic, and continuous polymictic) were evident by their capacity to maintain coldwater species as seasons progressed from winter through fall. The disappearance of coldwater assemblages from dimictic lakes coincided with oxygen depletion in the hypolimnion or with erosion of the hypolimnion through mixing. Coldwater species disappeared from large discontinuous polymictic lakes when deep epilimnetic mixing occured in late summer and fall. Species assemblages of nearly all stratified lakes converged with those of continuous polymictic lakes when the hypolimnetic refuge deteriorated in summer and fall. Local weather conditions, however, between years had a pronounced effect on the persistence of cold water species through the seasons by affecting the temperature and oxygen conditions of the hypolimnion. Large lakes of the region contain many of the coldwater species of the Laurentian Great Lakes but some taxa are conspicuosly absent. Cold stenothermal rotifers persist in the lakes of the region despite adverse environmental conditions. Their life histories and ability to form resting stages permit them to escape periods of oxygen depletion and thermal stress. In contrast, the crustacean glacial marine fauna (i.e. Mysis relicta, Limnocalanus macrurus, and Scenecella calanoides) was absent from all of the study lakes even though many of the present-day basins were once connected to the Laurentian Great Lakes. These species long life cycles, lack of diapausing stages, and limited dispersal may make them vulnerable to local extinction with the deterioration and loss of the coldwater refuge.
Surgical management of adolescent idiopathic scoliosis

Abstract Without a complete understanding of the natural history of adolescent idiopathic scoliosis (AIS), the treating spine surgeon will be unable to effectively appreciate the indications for surgery nor will the long-term management plan be appropriate. Basic evaluation of the patient with AIS should center on a thorough history and physical examination. It is crucial that applicable radiographic imaging is obtained as well, which must be tailored to each individual patient given the findings on history and physical examination. For patients in whom surgical correction is indicated, many factors comprise the ultimate treatment plan. The goals of surgery center on prevention of curve progression, adequate coronal and sagittal realignment, and the preservation of as much motion as possible. Vertebral-level selection, curve-reduction techniques, fixation strategies, postoperative protocols, and potential complications each play a vital role in the successful surgical treatment of AIS. With an in-depth understanding of all of these variables, the spine surgeon can achieve excellent outcomes for his or her AIS patients.
Aspartic protease and caspase 3/7 activation are central for macrophage apoptosis following infection with Escherichia coli

Macrophages are vital for host defense against microbial infections. We have previously shown that infection of macrophages with a non- pathogenic strain of Escherichia coli induces apo- ptosis rapidly. Here, we demonstrate that infection of macrophages results in the activation of caspases prior to the induction of the intrinsic apoptosis pathway. Caspases 9 and 3 are activated prior to the release of intermembrane mitochondrial pro- tein cytochrome C into the cytosol in infected mac- rophages. Treatment with an inhibitor to caspase 9 has no effect on the death of macrophages and does not prevent activation of the downstream effector caspase 3/7. In contrast, an inhibitor to caspase 3/7 reduces cell death in E. coli-infected macro- phages. Although caspase 9 is not required, activa- tion of aspartic proteases, of which cathepsin D is one of the central members, is essential for activa- tion of caspase 3/7. Treatment with pepstatin A, an inhibitor of aspartic proteases, markedly dimin- ishes the activation of cathepsin D and caspase 3/7 and reduces death in E. coli-infected macrophages. Collectively, these data suggest that cathepsin D activation of caspase 3/7 may be required for in- ducing one of the death pathways elicited by E. coli. J. Leukoc. Biol. 81: 000-000; 2007.
Ionic-strength dependence of electron-transfer reactions of Keggin heteropolytungstates: Mechanistic probes of O2 activation in water

Abstract Kinetic data needed to use α-AlW 12 O 40 6− (α- 2 1e ) as well-defined probe for investigating electron-transfer processes in water is evaluated using the extended Debye–Huckel equation. First, rate constants, as a function of ionic strength in water, are determined for electron self-exchange reactions between a series of AlW 12 O 40 n − ions (α and β isomers of fully oxidized, one- and two-electron reduced ions). The kinetic data are plotted using the extended Debye–Huckel equation, in which the distance of closest contact is set equal to twice the hydrodynamic radius of a Keggin anion. In all cases, slopes of these plots give charge-product ( z 1 z 2 ) values within error of those anticipated based on the charges of the reacting ions. The aqueous solution chemistry of α-AlW 12 O 40 5− (α- 2 ox ) and α-AlW 12 O 40 6− (α- 2 1e ) is then fully defined, and the reduction potential of the α- 2 ox /α- 2 1e couple is determined. These studies provide the information needed to use α- 2 1e , a powerful reducing agent, to obtain detailed information about the first steps in reduction of O 2 to H 2 O, a process of considerable importance to chemistry and biology.
Distinct effects of two stresses on the behavioral response to apomorphine

Isolation and intermittent oscillation produced distinct effects on the subsequent stereotypic response to apomorphine in rats. These effects also differed from the effects of intermittent apomorphine and chronic haloperidol pre-treatment. Varying the frequency of oscillation stress changed the magnitude but not the type of the effect. Thus, different types of stress may effect the dopaminergic neurochemical system uniquely.
Recurrent Carpal Tunnel Syndrome

Carpal tunnel release is a common procedure with a high rate of alleviating the patient's symptoms. The incidence of recurrent or persistent carpal tunnel syndrome is rare, although likely underestimated. Complaints of worsening numbness, tingling, or weakness should alert the physician to possible nerve injury and need for early exploration. The overall results of revision carpal tunnel procedures are less successful than primary surgery; however, surgery should be performed when indicated, as it may alleviate or improve symptoms.
Optical instabilities in sodium vapor

We present here instabilities observed in the transverse profile of a continuous-wave light beam that crosses a sample of sodium vapor twice by means of a feedback mirror. The wave front and the intensity of the beam are spatially modulated by the intensity-dependent dispersive and absorptive action of the vapor. Experimental evidence indicates that the vapor acts as a phase-conjugate mirror, thus providing an active cavity when it is coupled with the feedback mirror. The instabilities develop as a consequence of sideband generation at the resonant modes of this cavity. The transverse-mode profiles of these sidebands are analyzed experimentally.
Exchange rates and traded goods prices

Abstract This paper presents a partial equilibrium model of the determination of domestic and export prices by a monopolistic competitive firm. The model stresses the role of exchange rate uncertainty and expectations. The most important result of the analysis is that the stochastic properties of deviations from the ‘law of one price’ are crucially affected by the currency of denomination of export prices. Using data on domestic and dollar export prices of Japanese goods, I find that deviations from the ‘law of one price’ are due to exchange rate surprises, but also to price staggering and ex ante price discrimination.
Minimum variance analysis‐based propagation of the solar wind observations: Application to real‐time global magnetohydrodynamic simulations

[1] The performance of the bulk of the current real-time space weather applications is dependent on the accuracy of the driver solar wind data. One of the central aspects associated with the accuracy of the driver data is the determination of the propagation delay time of single-spacecraft solar wind observations from Lagrangian point L1 to the Earth. In this work, the value of the minimum variance analysis-based solar wind propagation technique as applied to real-time global magnetohydrodynamic (MHD) simulations is investigated. Both the method that uses the newly introduced technique for minimizing the effect of the poorly determined phase planes and the minimum variance analysis-based setup by Weimer and King (2008) along with the standard simple convection delay-based (no phase planes used) solar wind propagation technique are applied to global MHD-based modeling of the ground magnetic field and geomagnetically induced current variations. All computations are carried out in a real-time setting. It is shown by means of comparisons to ground-based observations that while the minimum variance analysis-based propagation techniques can be used to optimize the timing associated with the propagated solar wind fluctuations, the improvement is so modest that from the statistical viewpoint, the benefit over using the simpler propagation technique vanishes for the studied storm period when the information is passed through real-time global MHD modeling process.