cssi/SciSciGPT-SciSciNet huggingface dataset:
Pediatric Preclinical Testing Program (PPTP) evaluation of the multi-targeted kinase inhibitor Sunitinib

527 Background: Sunitinib is an orally available, multi-targeted tyrosine kinase inhibitor with selectivity for PDGF receptors, VEGF receptors, FLT3, and KIT. Sunitinib inhibits the growth of a wide range of established adult tumor xenografts in a dose-dependent manner and is licensed for the treatment of renal cell carcinoma and GIST. Methods: The PPTP includes an in vitro panel (n=27) as well as panels of xenografts (n=61) representing most of the common types of childhood solid tumors and childhood ALL. Sunitinib in vitro testing used media containing 20% FCS and evaluated concentrations from 0.1 nM to 1 micromolar. Testing against the in vivo tumor panels used a dose of 53.5 mg/kg PO X 28 days. Three measures of antitumor activity were used: 1) response criteria modeled after the clinical setting [e.g., partial response (PR), complete response (CR), etc.]; 2) treated to control (T/C) tumor volume at day 21; and 3) a time to event (4X increase in tumor volume) measure based on the median EFS of treated and control lines (intermediate activity required EFS T/C > 2, and high activity additionally required a net reduction in median tumor volume at the end of the experiment). Results: Kasumi-1 (gain-of-function KITAsn822Lys mutation) was the only cell line to show an in vitro response to sunitinib and had an EC50 of 71nM, a concentration well within the range achievable in humans. Sunitinib induced significant differences in EFS distribution in 19 of 35 (54%) of the solid tumor xenografts analyzed, and in 1 of 8 (13%) of the ALL xenografts analyzed. Using the PPTP time to event measure of efficacy, sunitinib had intermediate (13) and high (1) levels of activity against 14 of 34 evaluable solid tumor xenografts. One of 3 rhabdoid tumor xenografts exhibited high activity for the time to event measure, while another exhibited intermediate activity. Intermediate activity was also observed in 4 of 6 rhabdomyosarcoma, 4 of 5 Ewing tumor, 1 of 3 Wilms tumor, and 1 of 3 osteosarcoma. Following cessation of treatment for the 14 solid tumor xenografts that had not had tumor events by Day 28, tumor growth rate increased to that observed for the comparable control groups. The only objective response to sunitinib in the solid tumor panels was a CR in a rhabdoid tumor xenograft. For the ALL panel, sunitinib produced a partial response in 1 of 8 lines. Conclusions: Sunitinib demonstrated broad activity against the PPTP’s solid tumor panel, but only limited activity against the ALL panel. Antitumor activity was manifested primarily as tumor growth delay, consistent with an anti-angiogenic effect for sunitinib against many of the pediatric preclinical models evaluated. A pediatric phase 1 trial of sunitinib has been initiated. (Supported by NCI NO1CM42216)
Mischief in “La Cenizosa”: An Unpublished Creole Fable by Judith Ortiz Cofer

Judith Ortiz Cofer promoted the Puerto Rican Creole culture by means of emblematic characters, mostly women, who were protagonists of her extensive literary work. Ortiz Cofer left an unpublished cr...
Immunogenetic influence of Igh-1 phenotype on experimental herpes simplex virus type-1 corneal infection.

Patterns of herpes simplex virus type-1 (HSV-1) infection were studied in BALB/c congenic, Igh-1 disparate murine strains to establish the influence of Igh-1 phenotype on the development of keratopathy, trigeminal ganglionic latency and keratocyte permissivity. Eighty-two percent of C.AL-20 (Igh-l d ) mice, 40% of BALB/cByJ (Igh-l a ) mice and 12% of the C.B-17 (Igh-l b ) mice developed herpes simplex keratitis (HSK) following corneal challenge with 2.5 X 10 4 PFU HSV-1 strain KOS. While disease frequency was directly proportional to HSV-1 challenge dose, relative resistance and susceptibility patterns in the congenic mice were constant and highly significant. Fl progeny from C.AL-20 X C.B-17 matings demonstrated the HSK pattern of the C.B-17 parent suggesting that Igh-1 linked resistance to HSK is dominantly inherited. Equivalent trigeminal ganglionic latency was established following ocular HSV-1 inoculation in the three congenic Igh-1 disparate murine strains. Cultured keratocytes from the three Igh-1 disparate murine strains demonstrated equivalent in vitro permissivity to HSV-1 replication. These data illustrate a strong correlation between Igh-1 phenotype and the development of a HSK in congenic mice. The susceptibility/resistance to HSK in these mice is unrelated to trigeminal ganglionic latency or keratocyte permissivity. Invest Ophthalmol Vis Sci 29:749-754, 1988
Investigator Assessment of the Utility of the TruGraf Molecular Diagnostic Test in Clinical Practice.

Abstract Background TruGraf v1 is a well-validated DNA microarray-based test that analyzes blood gene expression profiles as an indicator of immune status in kidney transplant recipients with stable renal function. Methods In this study, investigators assessed clinical utility of the TruGraf test in patient management. In a retrospective study, simultaneous blood tests and clinical assessments were performed in 192 patients at 7 transplant centers, and in a prospective observational study they were performed in 45 subjects at 5 transplant centers. Results When queried regarding whether or not the TruGraf test result impacted their decision regarding patient management, in 168 of 192 (87.5%) cases the investigator responded affirmatively. The prospective study indicated that TruGraf results supported physicians' decisions on patient management 87% (39/45) of the time, and in 93% of cases physicians indicated that they would use serial TruGraf testing in future patient management. A total of 21 of 39 (54%) reported results confirmed their decision that no intervention was needed, and 17 of 39 (44%) reported that results specifically informed them that a decision not to perform a surveillance biopsy was correct. Conclusions TruGraf is the first and only noninvasive test to be evaluated for clinical utility in determining rejection status of patients with stable renal function and shows promise of providing support for clinical decisions to avoid unnecessary surveillance biopsies with a high degree of confidence. TruGraf is an invaluable addition to the transplant physician's tool kit for managing patient health by avoiding painful and invasive biopsies, reducing health care costs, and enabling frequent assessment of patients with stable renal function to confirm immune quiescence.
Amidyl Radical Directed Remote Allylation of Unactivated sp 3 C−H Bonds by Organic Photoredox Catalysis

The development of visible-light-mediated allylation of unactivated sp3 C-H bonds is reported. The remote allylation was directed by the amidyl radical, which was generated by photocatalytic fragmentation of a pre-functionalized amide precursor. Both aromatic and aliphatic amide derivatives could successfully deliver the remote C-H allylation products in good yields. A variety of electron deficient allyl sulfone systems could be used as δ-carbon radical acceptor.
Mechanical characterization of bone quality in distal femur fractures using pre-operative computed tomography scans.

BACKGROUND Mechanical testing of implant constructs designed to treat distal femur fractures has been hampered by a lack of clinical data on the biomechanical properties of the distal femur in patients who sustain these fractures. Therefore, the purpose of this study was to use quantitative computed tomography (qCT) to investigate the mechanical characteristics of fractured distal femurs to inform the selection of synthetic materials for biomechanical testing. METHODS Distal femur fractures treated at a Level I trauma center were retrospectively reviewed and 43 cases with preoperative CT scans were identified for analysis. Scans were segmented and each bone fragment was reconstructed as a 3D model. The Young's modulus of the distal femur was determined from voxel-based radiodensity. FINDINGS Median patient age was 72 years (IQR = 57-81), with 26% males and 74% females. Young's modulus in the distal femur was negatively correlated with patient age (R2 = 0.50, p < 0.001). The distribution of patient-specific modulus values was also compared with the compressive modulus ranges for graded polyurethane foams according to ASTM F1839. Bone quality ranged from Grade 25 in younger individuals to Grade 5 in older individuals. CONCLUSION No single grade of synthetic polyurethane foam can be selected to model all clinically important scenarios for biomechanical testing of distal femur fracture fixation devices. Rather, this data can be used to select an appropriate material for a given clinical scenario. A Grade 25 foam is appropriate for implant longevity, whereas for implant stability, Grades 5-15 are more appropriate.
The Mapping Class Group in Statistical Mechanics: A Concise Review

The group of mapping classes,i.e. the group ℳ g = π0 Diff (+)(Σg) of path components of isotopy classes of orientation preserving diffeomorphisms of surfaces Σ g ofgenus g, has recently entered the collection of mathematical tools relevant to physics, appearing first in the statistical mechanics of the 3-dimensional Ising Model [1], then in String Theory [2].
Rethinking U.S. enterprise zones: The role of research design in program evaluation:

This paper offers an up-to-date review of Enterprise Zone programs across states in the U.S. An Enterprise Zone program often focuses on target locations, populations, and/or industries. Enterprise...
E 6 model with composite muon and τ families

We present a unified model based on the exceptional group ${\mathrm{E}}_{6}$ in which the electron family ($e$,${\ensuremath{\nu}}_{e}$,$u$, and ${d}^{\ensuremath{'}}$, where the prime denotes a Cabibbo-rotated state) is elementary, and the $\ensuremath{\mu}$ and $\ensuremath{\tau}$ families are composites. The model has a rich particle spectrum starting not far above the $\ensuremath{\tau}$ family and a range of mass scales above the weak-boson masses. Group-theoretical features of the symmetry breaking are discussed in some detail in a language having many other applications.
Remote Wireless Sensor Network Range Extension Using UAVs with Thread Protocol

Native Internet Protocol based Wireless Sensor Network is considered as one of the most pragmatic solutions in market to address interoperability challenges and is gaining more attention in research. However, challenges like reliability, security of data, power consumption, range and maintenance still remain a matter of concern. This paper aims at addressing these challenges using a Low-Powered IPv6 based wireless protocol, Thread and its incorporation into Unmanned Aerial Vehicles (UAVs) to improve interoperability from remote locations with poor internet connectivity. Besides including other features, incorporation of Thread in UAVs has significant advantages in terms of power consumption over other wireless protocols such as Wireless Fidelity (Wi-Fi) and Bluetooth.
Adaptive Array Processing Architecture

Array antennas are becoming ubiquitous in many commercial and military systems. This allows for electronic steering of the antenna in one or more directions simultaneously. However, by combining the individual array element signals at the array, these systems fail to take full advantage of the array capabilities. The newest array antennas are capable of supporting I/Q digital inputs and outputs for each element. This creates new processing challenges, and the need for a new architecture to enable capabilities such as very fast adaptation rates with very high independent beam counts.
Paper 4 – Experimental control of chaos

Publisher Summary It was demonstrated that one can convert the motion of a chaotic dynamical system to periodic motion by controlling the system about one of the many unstable periodic orbits embedded in the chaotic attractor, through only small time dependent perturbations in an accessible system parameter. They demonstrated their method numerically by controlling the Henon map. Far from being a numerical curiosity that requires experimentally unattainable precision, it was believed that this method can be widely implemented in a variety of systems including chemical, biological, optical, electronic, and mechanical systems. The method is based on the observation that unstable periodic orbits are dense in a typical chaotic attractor. Their method assumes only the following four points. First, the dynamics of the system can be represented as arising from an n-dimensional non-linear map. Second, there is a specific periodic orbit of the map which lies in the attractor and around which one wishes to stabilize the dynamics, and so on. To control the chaos, one attempts to confine the iterates of the map to a small neighborhood of the desired orbit.
104 Intended and unintended consequences of a state policy to combat opioid over-prescribing among patients receiving high dose long term opioid therapy

Statement of Purpose In May 2016, the North Carolina Medical Board (NCMB) launched the safe opioid prescribing initiative (SOPI) to limit overprescribing of opioids by investigating high volume prescribers and prescribers who have had two or more patient deaths due to opioid overdose. In this study we examined the immediate and sustained effects of NCMB’s SOPI on tapering and discontinuation of opioids among patients receiving high doses (>90 MME) of long-term (>90 days) opioid therapy (LTOT). Methods We conducted an interrupted time series study to examine change in temporal trends of opioid discontinuation and appropriate and inappropriate tapering among high dose LTOT patients in NC, following the NCMB’s implementation of SOPI in May 2016. We used de-identified data from January 2010 through March 2017 from the NC Controlled Substances Reporting System (CSRS). Results During the study period 205,255 people received high dose LTOT in NC. Compared to ∼0.01% monthly decline in discontinuation and tapering pre-SOPI, immediately after the implementation of SOPI, the rate of abrupt discontinuation, inappropriate tapering, and appropriate tapering of opioids among high dose LTOT patients increased by 1% (95% CI: -0.22, 2.23), 2.2% (95% CI: 0.91, 3.47) and 1.3% (95% CI: 0.96, 1.57), respectively. Those receiving opioids from one prescriber were more frequently discontinued, while multiple prescriber patients were more frequently inappropriately tapered post-SOPI. Conclusions The increase in appropriate tapering can be considered a success of SOPI, but, the simultaneous increase in discontinuations and inappropriate tapering may be cause for some concern as these results represent a chilling effect on opioid prescribing that may adversely affect those receiving high dose LTOT. Significance to Injury and Violence Prevention Science Well-intentioned policies such as the SOPI may have harmful effects when not well communicated and combined with education of prescribers to prevent potential unintended consequences.
RIVALRY AMONGST TOP-FIVE MAJOR AIRLINES IN THE U.S. MARKET

Understanding the economic characteristics of the U.S. airline industry, assessing the degree of competition/rivalry among the competing airline businesses in the U.S. airline industry, and (3) making recommendations to the airlines and to the consumers of air transportation are the primary objectives of this research study. The authors analyze the rivalry among major U.S. airlines operating in the domestic market using datasets extracted from Bureau of Transportation Statistics for operations during a 12-month period ending in May 2019. Amongst the 17 major U.S. airlines, whose annual operational revenue is over $1 billion, a set of top-five airlines has been identified using the percentage of their marketshare. The research findings indicate that these five major airlines have an intense rivalry in the U.S. domestic market in terms of number of markets served, number of departures made, number of passengers transported, amount of cargo carried, load factor, revenue and cost of operations, profit and loss, and net income earned. Hence, these airlines put pressure on one another and limit each other’s profit potential.
Distinguishing Characteristics and Disparities in Child Protective Services-Investigated Maltreatment by Fathers.

This study examines distinguishing characteristics of father-perpetrated maltreatment and disparities in Child Protective Services (CPS) investigation outcomes based on perpetrator gender and race....
Distress tolerance and subsequent substance use throughout high school

Abstract Objective To examine the association of perceived distress tolerance—one’s ability to endure aversive experiences—with subsequent substance use frequency during adolescence. Methods High school students (N = 3,203) were surveyed semiannually from 2013 to 2017. The Distress Tolerance Scale (DTS) was administered at baseline (9th grade) and self-reported past 30-day number of days used of alcohol, cigarettes, e-cigarettes, cannabis, and opioids (range: 0–30) were assessed at all timepoints. Self-reported baseline ever (vs. never) use of each substance and depressive/anxiety symptom status (clinical and subclinical vs. none) were tested as moderators. Results Among baseline never substance users, a greater baseline mean DTS score was associated with fewer days of alcohol, cigarette, and opioid use in past-30 days over 4 years of follow-up (IRR range = 0.60–0.84); among ever-users, baseline mean DTS was not significantly associated with substance use across follow-up timepoints (p-interaction = 0.03). The association of DTS and frequency of substance use did not differ by baseline mental health status for any substance (all ps > 0.05). Conclusions Greater perceived distress tolerance at the start of high school may be a protective factor against substance use frequency prior to initial use. Interventions that build distress tolerance in early adolescence may be warranted to prevent higher frequency substance use throughout high school.
Nonadiabatic dynamics with spin-flip vs linear-response time-dependent density functional theory: A case study for the protonated Schiff base C5H6NH2+

Nonadiabatic trajectory surface hopping simulations are reported for trans-C5H6NH2+, a model of the rhodopsin chromophore, using the augmented fewest-switches algorithm. Electronic structure calculations were performed using time-dependent density functional theory (TDDFT) in both its conventional linear-response (LR) and its spin-flip (SF) formulations. In the SF-TDDFT case, spin contamination in the low-lying singlet states is removed by projecting out the lowest triplet component during iterative solution of the TDDFT eigenvalue problem. The results show that SF-TDDFT qualitatively describes the photoisomerization of trans-C5H6NH2+, with favorable comparison to previous studies using multireference electronic structure methods. In contrast, conventional LR-TDDFT affords qualitatively different photodynamics due to an incorrect excited-state potential surface near the Franck–Condon region. In addition, the photochemistry (involving pre-twisting of the central double bond) appears to be different for SF- and LR-TDDFT, which may be a consequence of different conical intersection topographies afforded by these two methods. The present results contrast with previous surface-hopping studies suggesting that the LR-TDDFT method’s incorrect topology around S1/S0 conical intersections is immaterial to the photodynamics.
Decoupling the unfairness propagation chain in crowd sensing and learning systems for spatio-temporal urban monitoring

In smart cities, urban monitoring systems rely on advanced mobile sensing and learning technologies to track large-scale urban systems and provide efficient urban services in real time. However, the fidelity and amount of sensors deployed at different geo-communities are closely related to their socioeconomic conditions, demographics, and entrenched geographic patterns, causing inequal sensing opportunities across communities. The biased sensing data contain distorted spatio-temporal patterns of undersensed community, inducing unfairness in subsequent algorithmic prediction and decision-making. This work characterize this unfairness propagation chain of sensing - learning - decision-making process. We introduce the first formal mathematical definitions to quantify and decouple community-level unfairness induced by joint cascading effects of sensing inequality and algorithmic bias. Our real-world experiments with vehicular crowdsensing system in Cangzhou, China verifies that sensing inequality, especially community-level gap of sensor fidelity, result in large fairness gap in spatio-temporal data imputation task. Our preliminary results show that sensing inequality amplifies the algorithmic bias. This work is a critical first step in formally defining and understanding unfairness propagation in intelligent spatio-temporal urban monitoring system.
Complementary suppression of aphids by predators and parasitoids

Abstract Biocontrol practitioners have long debated the relative merits of specialist parasitoids versus generalist predators as biological control agents. Predators and parasitoids exhibit a broad array of ecological differences that might lead them to play different, and perhaps complementary, roles in pest suppression. However, predators often feed on parasitoids with the potential to disrupt biological control. We compared suppression of the woolly apple aphid (Eriosoma lanigerum) when attacked solely by the specialist parasitoid Aphelinus mali, to aphid suppression when the parasitoid was joined by a diverse community of generalist predators (primarily earwigs, syrphids, predatory bugs and spiders). In a series of exclusion-cage experiments conducted on apple trees (Malus domestica) placed in the field, we found that the parasitoid alone significantly slowed aphid population growth. However, consistently flat or declining aphid densities were seen only when the parasitoid was paired with the generalist predator guild. This suggested that predators and parasitoid exerted complementary impacts, with the most effective aphid suppression achieved when the two natural enemy classes were present together. Consistent with this observation, percentage aphid parasitism was not consistently reduced in the presence of predators; this implies relatively weak predator–parasitoid interference. Altogether, our results suggest that the conservation of a diverse community of natural enemies, including both predators and parasitoids, is an effective way to strengthen suppression of this, and perhaps other, aphid species.
Melanin: Structure, Function, and Biosynthesis in Cryptococcus

There is an extensive body of evidence from several laboratories that establishes a role for melanization in virulence, providing a fascinating example of how a microorganism can utilize a ubiquitous pigment to undermine host defense mechanisms. Melanin-deficient mutant strains generated by UV-irradiation are avirulent in murine models of cryptococcal infection. The majority of Cryptococcus neoformans melanin is produced by Lac1, although a second laccase enzyme, Lac2, adjacent to LAC1 in the genome exists. Various microscopy techniques were used to develop the melanin model, including atomic force and scanning electron microscopy to examine the surface structure of melanin, transmission electron microscopy (TEM) to study cross sections of melanin, and nuclear magnetic resonance (NMR) cryoporometry to investigate the porosity of melanin. In the environment, melanin is thought to protect C. neoformans from various stresses including enzymatic degradation, radiation (UV, solar, gamma), and heavy metals (silver nitrate) while providing thermotolerance and structural integrity to withstand osmotic challenges. Melanin-binding drugs may be useful as therapeutics against C. neoformans infection. In fact, administration of melanin-binding monoclonal antibodies (MAbs) prolongs the survival of mice in a lethal intravenous infection model. In this study, the fungal burdens of collected brains and lungs of infected mice were taken 7 days after infection, and mice administered MAbs to melanin had significantly lower fungal burdens than control mice administered irrelevant immunoglobulin. Early studies that linked melanin to C. neoformans virulence used classical genetic techniques to generate mutants through nonspecific mutagenesis to identify yeast cells deficient in melanin production.
Tax Consequences when Churches Participate in Political Campaigns

The Internal Revenue Code conditions important tax benefits for churches on their not intervening in political campaigns on behalf of particular candidates. Churches that violate this condition are not eligible to receive deductible contributions and may not be tax-exempt. The Internal Revenue Service and many commentators take the position that the ban on partisan political activity should be vigorously enforced against churches and should apply to core religious activities such as sermons. The article demonstrates that this approach needlessly threatens religious liberties, causes undue entanglement of government with religion, and adversely affects political campaigns. There are convincing arguments for treating churches differently from other section 501(c)(3) organizations when interpreting and applying the prohibition against intervening in political campaigns. The article recommends that pastors and other church leaders be able to communicate with members about the merits of political candidates without risking loss of favorable tax status. Such leniency for churches is consistent with the legislative history of the prohibition and would not violate the Establishment Clause of the First Amendment. Furthermore, strict enforcement of the ban against participation in political campaigns by churches risks violating the Free Exercise Clause of the First Amendment and the Religious Freedom Restoration Act of 1993.
The Rights Offer Puzzle: Clues from the 1930s and 1940s

We study the offer choice between rights and firm commitments for a sample of industrial firms issuing equity in the 1930's and 1940's. Unlike existing studies, our sample is drawn from a time period when rights were as common an offer method for industrial firms as were firm commitments. This sample allows us to perform out-of-sample tests of existing theories of offer choice. Our analysis indicates that firms choosing rights were larger, healthier firms with lower leverage and higher cash flow liquidity. Firms electing the firm commitment method experienced significantly negative size-adjusted returns during the 12 months following the offer, consistent with recent evidence for SEO's. In striking contrast, firms issuing equity through rights were not subject to negative post-offer returns, suggesting that firm commitments were timed to exploit overvaluation while rights offers were not. Finally, we investigate a number of long term factors that could have contributed to the decision to migrate from rights issues to firm commitment.
Classification of single-trial neural responses to cutaneous stimulation

Given the response of a population of neurons to a set of stimuli (or events), classification methods have been used to determine which stimulus generated the response on a single-trial basis. Various linear and non-linear methods have been used to solve this classification problem with surprising little performance differences. We therefore developed a PSTH-based classification method with the aim of maximizing computational efficiency rather than classification performance. This method was tested by applying it to populations of neurons simultaneously recorded from the somatosensory cortex of the rat during cutaneous stimulation of the forepaw and the results were compared to linear discriminant analysis (LDA), which has been considered the "standard". This method performs at least as well as LDA and it is particularly efficient for complete cross-validation designs.
Proceedings of the 7th workshop on Foundations of aspect-oriented languages

Aspect-oriented programming is a paradigm in software engineering and programming languages that promises better support for separation of concerns. The seventh Foundations of Aspect-Oriented Languages (FOAL) workshop was held at the Seventh International Conference on Aspect-Oriented Software Development in Brussels Beligum, on April 1, 2008. This workshop was designed to be a forum for research in formal foundations of aspect-oriented programming languages. The call for papers announced the areas of interest for FOAL as including: semantics of aspect-oriented languages, specification and verification for such languages, type systems, static analysis, theory of testing, theory of aspect composition, and theory of aspect translation (compilation) and rewriting. The call for papers welcomed all theoretical and foundational studies of foundations of aspect-oriented languages. The goals of this FOAL workshop were to: • Make progress on the foundations of aspect-oriented programming languages. • Exchange ideas about semantics and formal methods for aspect-oriented programming languages. • Foster interest within the programming language theory and types communities in aspect-oriented programming languages. • Foster interest within the formal methods community in aspect-oriented programming and the problems of reasoning about aspect-oriented programs. The workshop was organized by Curtis Clifton (Rose-Hulman Institute of Technology, USA), Shmuel Katz (Technion---Israel Institute of Technology, Israel), Gary T. Leavens (University of Central Florida, USA), and Mira Mezini (Darmstadt University of Technology, Germany). The program committee was chaired by Curtis Clifton.
A single dose of fentanyl and midazolam prior to Cesarean section have no adverse neontal effects

Analgesia and sedation, routinely used as adjunct medications for regional anesthesia, are rarely used in the pregnant patient because of concerns about adverse neonatal effects. In an effort to obtain more information about maternal analgesia and sedation we studied neonatal and maternal effects of iv fentanyl and midazolam prior to spinal anesthesia for elective Cesarean section. In this double-blinded, randomized, placebo-controlled trial, 60 healthy women received either a combination of 1 µg·kg-1 fentanyl and 0.02 mg·kg-1 midazolam intravenously or an equal volume of iv saline at the time of their skin preparation for a bupivacaine spinal anesthetic. Sample size was based on a non-parametric power analysis (power > 0.80 and alpha = 0.05) for clinically important differences in Apgar scores. Fetal outcome measures included Apgar scores, continuous pulse oximetry for three hours, and neurobehavioural scores. Maternal outcomes included catecholamine levels, and recall of anesthesia and delivery. There were no between-group differences of neonatal outcome variables (Apgar score, neurobehavioural scores, continuous oxygen saturation). Mothers in both groups showed no difference in their ability to recall the birth of their babies. Maternal analgesia and sedation with fentanyl (1 µg·kg-1) and midazolam (0.02 mg·kg-1) immediately prior to spinal anesthesia is not associated with adverse neonatal effects.
ADME Profiling in Drug Discovery and Development: An Overview

The applications of parallel synthesis and combinatory chemistry to expedite lead finding and lead optimization processes have shifted the chemical libraries toward poorer biopharmaceutical, ADME (absorption, distribution, metabolism, and excretion), and pharmacokinetic (PK) properties. A drug candidate should have desirable biopharmaceutical properties such as good solubility and good permeability, as well as optimal and ADME/PK properties. The early knowledge of liability of biopharmaceutical, ADME/PK, and DDI properties is very valuable in drug candidate selection process. In the last one decade, multiple in silico, in vitro, and in vivo ADME studies have been developed and implemented in the drug discovery and development process to alert chemists and drug metabolism scientists of the potential ADME, PK and DDI issues in the clinic. In this chapter, we attempt to discuss these various ADME profiling approaches in drug discovery and development process and the latest technologies of the selected assays. Keywords: absorption; ADME; in silico; in vitro; in vivo; disposition; mass spectrometry; metabolism; clearance; pharmacokinetics
Azotobacter vinelandii ferredoxin I. Alteration of individual surface charges and the [4FE-4S]2+/+ cluster reduction potential.

The structures of Azotobacter vinelandii ferredoxin I (AvFdI) and Peptococcus aerogenes ferredoxin (PaFd), near their analogous [4e-4S]2+/+ clusters, are highly conserved (Backes, G., Mino, Y., Loehr, T.M., Meyer, T.E., Cusanovich, M.A., Sweeney, W.V., Adman, E.T., and Sanders-Loehr, J. (1991) J. Am. Chem. Soc. 11, 2055-2064). Despite these similarities, the reduction potential (E0') of the AvFdI [4Fe-4S]2+/+ cluster is more than 200 mV more negative than that of PaFd. We have tested the contribution that individual amino acid residues make to the control of E0' by converting residues in AvFdI into the corresponding residue in PaFd. Four mutations involved substitutions of negatively charged surface residues with neutral residues and two involved substitution of buried hydrophobic residues. All AvFdI variants were characterized by x-ray crystallography, absorption, CD, EPR, and 1H NMR spectroscopies and by electrochemical methods. For the F25I mutation, significant structural changes occurred that affected the EPR and 1H NMR spectroscopic properties of AvFdI and had a minor influence on E0'. For all other mutations there were no changes in reduction potential. Thus we conclude, that variations in charged surface residues do not account for the observed differences in E0' between the analogous [4Fe-4S]2+/+ cluster of PaFd and AvFdI. These differences are therefore most likely to be due to differences in solvent accessibility.
An assessment of DSS performance: the impact of utilization and closure

Abstract The information technology described is a U.S. Coast Guard vessel movement reporting system, known as a vessel traffic service. This group decision support system aids vessel operators to navigate a treacherous portion of the Mississippi River from the Gulf of Mexico to Baton Rouge. Voluntary participants provide inputs for a computer simulated tracking of vessels and receive relevant information about marine traffic from the system. Two time series regression models explain changes in system performance as specified by objective, quantitative criterion variables known as critical success factors. One model relates changes in the safety criteria (vessel accidents) with utilization of the vessel traffic service, and the other regression explains changes in system utilization with factors which dictate use. Despite initial criticism that this decision support system was technically flawed because it did not use radar or television to establish the real-time presence and progress of vessel traffic, this research provides evidence that the vessel traffic service has been very effective in reducing vessel accidents on the lower Mississippi River. The findings suggest that not only are utilization levels of these systems important, but also their very presence is crucial for vessels wishing to avail themselves of the service. The presence of the system provided measurable benefits, while the absence of the vessel traffic system precipitated higher accident rates through lower user participation after its eventual reinstatement.
Inhibition of RhoA by p120 catenin

RhoA organizes actin stress fibres and is necessary for cell transformation by oncogenes such as src and ras. Moreover, RhoA is implicated in cadherin clustering during the formation of adherens junctions. The catenin p120 has also been implicated in cadherin clustering through an unknown mechanism. Here we show that p120 selectively inhibits RhoA activity in vitro and in vivo. RhoA inhibition and the interaction of p120 with cadherins are mutually exclusive, suggesting a mechanism for regulating the recruitment and exchange of RhoA at nascent cell-cell contacts. By affecting RhoA activation, p120 could modulate cadherin functions, including suppression of invasion, neurite extension and junction formation.
Lower bound techniques for data structures

We describe new techniques for proving lower bounds on data-structure problems, with the following broad consequences: (1) the first Ω(lg n) lower bound for any dynamic problem, improving on a bound that had been standing since 1989; (2) for static data structures, the first separation between linear and polynomial space. Specifically, for some problems that have constant query time when polynomial space is allowed, we can show Ω(lg n/lg lg n) bounds when the space is O(n · polylog n). Using these techniques, we analyze a variety of central data-structure problems, and obtain improved lower bounds for the following: (1) the partial-sums problem (a fundamental application of augmented binary search trees); (2) the predecessor problem (which is equivalent to IP lookup in Internet routers); (3) dynamic trees and dynamic connectivity; (4) orthogonal range stabbing. (5) orthogonal range counting, and orthogonal range reporting; (6) the partial match problem (searching with wild-cards); (7) (1 + e)-approximate near neighbor on the hypercube; (8) approximate nearest neighbor in the e ∞ to metric. Our new techniques lead to surprisingly non-technical proofs. For several problems, we obtain simpler proofs for bounds that were already known. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)
Domain States Determined by Neutron Refraction and Scattering

This chapter discusses various neutron refraction and scattering techniques, which are used to investigate magnetic domain states in ferromagnets and antiferromagnets. Besides giving a brief introduction into the various possible techniques, there are also examples of the current relevant science issues presented, which lend themselves to neutron measurement investigations. Keywords: neutron scattering; neutron reflectometry; ferromagnets; antiferromagnets; odmains
Highly inclined electrodeposited metal lines using an excimer laser patterning technique

This paper presents a simplified fabrication method to make highly elevated electrical signal lines up to 700 /spl mu/m in height from the substrates. The immediate application is a bioMEMS device that requires high aspect ratio three-dimensional (3D) multi-electrode arrays (MEA) to detect signals from deep within 3D networks of neurons. The demonstrated method generated thick electroplated metal lines on excimer laser patterned parylene molds. The directionality of the laser beam makes it possible to achieve practically straight patterns on the inclined sidewalls in addition to the bottom surface, which are several hundred microns below. 3D multi-electrodes on various elevation surfaces and insulation of parylene coating were efficiently implemented by using the directionality of excimer lasers and the conformal coating of parylene.
Summary of Final Discussion

The last session of the Colloquium was Chaired by Harry Nussbaumer and opened with statements from members of a panel comprised of Livio, Mikolajewska, Luud, Viotti, Magalhaes, Slovak, Kwok and Whitelock. Viotti began by comparing the available data for symbiotics historically and since IAU Colloquium 70 in 1981. He emphasized new UV, X-ray, infrared and radio observations. He also sketched the recent history of wavelength specific publications. Whitelock stated that it now seems clear all D-types probably contain Miras and that S-types do not evolve into D-types. Luud stated that his group intends to continue its near infrared observations with the 2 meter at Tartu, and that it is important to confirm conclusions based on IRAS data. He mentioned that masses for the Miras are needed given the discrepancy between observed and evolutionary masses.
Literature Circles Go to College.

In basic writing classrooms and scholarship, reading too often remains invisible; neither research nor established practice provides tangible activities to support reading and connect it to writing. This article documents a search for structured, scaffolded, low-stakes reading activities, a search that moves off the college campus and into the elementary classroom where reading is more commonly taught. It is in this classroom space that Harvey Daniels’s Literature Circles have evolved, and they offer a model for helping students engage in and experience reading as a process that supports and complements writing. The article posits Literature Circles, a student-centered and collaborative approach to reading used primarily in the lower grades, as a methodology that can offer college-level, basic-writing students an inventory of reading strategies for entering and navigating a text, initiating textual discussions, deepening comprehension of and connection to reading, and expanding the experience of writing.
Effects on Radioimmunoassay of Digoxin of Varying Incubation Periods for Antigen—Antibody Reaction and Varying Periods of Adsorption by Dextran-Coated Charcoal

In radioimmunoassay of digoxin by the dextran-coated charcoal method, duration of the incubation period for the antigen-antibody reaction and time allowed for dextran-coated charcoal to adsorb the free antigen are critical factors. We compared effects of prolonged periods of adsorption on results obtained with five commercial kits. In all cases, the digoxin concentrations increased linearly with adsorption time, but the increase varied among kits. Kallestad and New England Nuclear 3H-kits and the Squibb 125I-kit showed less increase (i.e., gave relatively consistent results after various periods of adsorption); the Schwarz/Mann 125I-kit and Clinical Assays 3H-kit showed greater increases. Precautionary steps are outlined for radioimmunoassays by this technique.
Effect of Concurrent Hormone Therapy on the Positional Stability of Electromagnetic Transponders Implanted in the Prostate

12 patients who had hormone therapy concurrently with radiation were selected in comparison to a control group of 10 patients with no hormone therapy. Inter-transponder distances (ITD) between transponders APX, LmB and RmB as shown in Fig. 1 were measured from CT scans or by the Calypso® System. Changes in ITDs measured at each radiation treatment were used to assess the positional stability of transponders in the prostate. Results
Total ozone trends deduced from Nimbus 7 TOMS data

The Total Ozone Mapping Spectrometer (TOMS) on the Nimbus 7 satellite has been measuring the total column amount of ozone over the globe for more than 11 years. Recent improvements in the data analysis have led to a technique for determining and removing drift in the calibration such that the data at the end of the record are precise to + or - 1.3 percent (2-sigma) relative to the data at the beginning of the record. A statistical model, including terms for seasonal variation, linear trend, quasi-biennial oscillation, solar cycle and second-order autoregressive noise has been fit to the TOMS time series of total ozone data. The linear trend obtained when this statistical model is fit to the TOMS data averaged between 65 N and 65 S latitudes is -0.26 + or - 0.14 percent/year or -3 percent over the 11.6 year time period from November 1978 to May 1990. The trend is near zero (0.0002 + or - 0.2 percent/year) at the equator and increases toward both poles.
Light-scattering study of effect of electrolytes on α- and β-casein solutions

Abstract Solutions of α- and β-casein are aggregated by electrolytes. This contrasts with the behavior of native ovalbumin, serum albumin, and lactoglobulin, but resembles that of the denatured forms of these proteins (the latter two after addition of ethanol). It is concluded that the caseins have the properties of denatured proteins. Determination of their molecular weights is complicated by the aggregation effect, and values in which confidence can be felt probably do not now exist.
On the possibility of a lower-hybrid instability driven by fast ions sputtered from a meteoroid

Abstract Recently, the sputtering of fast meteoroids by impinging atmospheric particles, and the subsequent interaction of the sputtered material with the atmosphere, has been proposed to explain the meteor luminosity observed at high altitudes. In this brief communication, we consider the possibility of a lower hybrid instability driven by the ionized component of the material sputtered from a fast large meteoroid at high altitudes.
Business Driven User Role Assignment: Nimble Adaptation of RBAC to Organizational Changes

The authors propose a business-oriented approach to support accurate and dynamic user-role assignments for the Role Based Access Control RBAC model. Their model, called Business-Driven Role Based Access Control BD-RBAC, is composed of three layers. The first layer extends the RBAC model with the concepts of business roles, system roles, credentials, and users' capabilities. The second layer dynamically assigns users to business and system roles, and filters outdated abnormal user-role assignments. The third layer supports exception handling and partial authorization. The novel aspect of the work is the adaptation of RBAC-based access control systems to changes in organizational needs, while reducing the burden of security administration. To this end, the authors have developed 1 a series of algorithms to compute internal and external user-role assignments based on organizational policies, users' requests and capabilities, 2 and shown that their outputs are permissible, i.e., a legitimate user is authorized to activate the role, complete, i.e., a legitimate user can activate the roles necessary to perform all the requested tasks, and minimal, i.e., a legitimate user does not receive any non-authorized or not-needed privileges.
The accuracy of condom information in three selected abstinence-only education curricula

Based on a review of 3 purposively selected curricula used in federally funded programs, the authors identified the types of scientific errors about condoms present in abstinence-only education. These curricula explicitly and implicitly convey the message that condoms fail to provide protection against HIV and commonly use out-of-date references. In addition, the curricula often misrepresent cited research, such as by reporting only the highest condom failure rates from study findings. The curricula do not explain differences between typical-use and perfect-use contraceptive failure associated with condom use and often incorrectly compare HIV transmission risk with pregnancy risk. Finally, these curricula use faulty reasoning to explain risk and promote misinformation about condoms (such as condom permeability) that has been repudiated by scientific consensus. The information these curricula present about condoms does not represent complete, current, or accurate medical knowledge about the effectiveness of condoms in preventing sexually transmitted infections, including HIV.
Does Design-Build Project Delivery Affect the Future of the Public Engineer?:

More than half the U.S. states have some form of legislated authority to procure transportation projects through design-build project delivery. Some states use the design-build delivery method extensively and some not at all because of perceived implementation barriers. One concern is that the use of design-build could result in major staff cutbacks within public agencies. To evaluate this concern objectively, this study employed a combination of literature review, surveys of state departments of transportation (DOTs), and content analysis of design-build requests for proposals and policy documents. It sought to quantify the impact on the state DOT professional workforce when the state authorizes design-build project delivery. The study reached a number of conclusions, but primarily implementation of design-build had no negative effect on the number of engineering jobs at public agencies that use it. The study also found that implementing design-build did not eliminate the use of the traditional design-bi...