cssi/SciSciGPT-SciSciNet huggingface dataset:
Amorphous Drug-Polymer Salt with High Stability under Tropical Conditions and Fast Dissolution: The Challenging Case of Lumefantrine-PAA.

Abstract Lumefantrine (LMF), a high-mobility and easy-to-crystallize WHO drug for treating malaria, can form an amorphous salt with poly(acrylic acid) (PAA) that is remarkably stable against crystallization at high humidity and temperature and has fast dissolution rate. The amorphous salt up to 75% drug loading was synthesized under a mild slurry condition easily implemented in basic facilities for global health. Salt formation was confirmed by IR spectroscopy and the much elevated glass transition temperature. At 50% drug loading, the amorphous salt resists crystallization for at least 18 months under the highly stressful condition of 40 °C and 75% RH. In contrast, the dispersion containing neutral LMF in PVP fully crystallized in 4 d and the dispersion in HPMCAS, a weak polyelectrolyte of lower charge density than PAA, crystallized by 50% in 7 d. The amorphous salt at 50% drug loading showed much faster dissolution than crystalline LMF: In SGF, the area under the curve (AUC) was 30 times larger within the gastric emptying time (4 h); in FaSSIF, the enhancement was even larger – by 200 times. Nanodroplets were detected during the dissolution in SGF, possibly accounting for the apparent enhancement of dissolution rate. The LMF-PAA example as a challenging case, along with the previously reported clofazimine-PAA, demonstrates the general utility of amorphous drug–polymer salts to achieve high stability under tropical conditions and enhanced dissolution and bioavailability.
Mechanism-based inactivation of human CYP3A4 by a piperazine-containing compound (615.5)

Human cytochrome P450 enzymes (CYPs) are monooxygenases that are responsible for metabolism of a variety of small compounds including many pharmaceutical drugs. The main drug metabolizing CYP is CYP3A4 that metabolizes around half of drugs. Some drugs are known to inhibit CYP3A4, lowering the ability of CYP3A4 to metabolize other compounds leading to adverse events. 1-[(2-Ethyl-4-methyl-1H-imidazol-5-yl)-methyl]-4-[4-trifluoromethyl-2pyrinyl]piperazine (EMTPP), while not a pharmaceutical drug, contains a piperazine group and substituted imidazole ring frequently found in pharmaceutical compounds. EMTPP is also similar in structure to SCH66712 and both EMTPP and SCH 66712 have previously been described as inactivators of CYP2D6 [Hutzler, Steenwyk, Smith, Walker, Wienkers (2004) Chem Res Toxicol 17, 174-184; Nagy, Mocny, Diffenderfer, Hsi, Butler, Arthur, Fletke, Palamanda, Nomeir, Furge (2011) Drug Metab Dispos 39, 974-983]. Our group has also recently shown SCH66712 to be a potent inactivator CYP3A4 and h...
Combining unification algorithms for confined regular equational theories

This paper presents a method for combining equational unification algorithms to handle terms containing "mixed" sets of function symbols. For example, given one algorithm for unifying associative-commutative operators, and another for unifying commutative operators, our algorithm provides a method for unifying terms containing both kinds of operators. We restrict our attention to a class of equational theories which we call confined regular theories. The algorithms is proven to terminate with a complete and correct set of E-unifiers. An implementation has been done as part of a larger system for reasoning about equational theories.
High-performance low-leakage enhancement-mode high-K dielectric GaN MOSHEMTs for energy-efficient, compact voltage regulators and RF power amplifiers for low-power mobile SoCs

We have fabricated L G =90nm high-K dielectric enhancement-mode (e-mode) GaN MOS-HEMT which shows low I OFF =70nA/µm (V D =3.5V, V G =0V), low R ON =490Ω-µm, high I D,max =1.4mA/µm, and excellent power-added efficiency (PAE) of 80% at RF output power density (RF Pout) of 0.55W/mm (V D =3.5V, f=2.0GHz). These results represent (i) >3.6X lower RON at equivalent breakdown voltage (BV D ) than industry-standard Si voltage regulator (VR) transistors, and (ii) >10% better PAE at matched RF Pout or >50% higher RF Pout at matched PAE than industry-standard GaAs RF power amplifier (PA) transistors, all at mobile SoC-compatible voltages. These results make GaN MOS-HEMTs attractive for realizing energy-efficient, compact voltage regulators and RF power amplifiers for mobile SoC. This work shows, for the first time, that the application space of GaN electronics can be expanded beyond the existing high-voltage power and RF electronics (e.g. automobile, power conversion, base-station, radar) to include low-power mobile SoCs.
A homolog of Drosophila Notch expressed during mammalian development

Drosophila Notch and the related Caenorhabditis elegans proteins lin-12 and glp-1 function as mediators of local cell-cell interactions required for cell-fate decisions during invertebrate development. To investigate the possibility that similar proteins play determinative roles during mammalian development, we isolated cDNA clones encoding rat Notch. The deduced amino acid sequence of this protein contains 36 epidermal growth factor (EGF)-like repeats, and is remarkably similar in both its extracellular and cytoplasmic domains to the sequence of Xenopus Xotch and Drosophila Notch. In the developing central nervous system, in situ hybridisation analyses revealed that Notch transcripts were dramatically restricted to the ventricular proliferative zones of embryonic neuroepithelia. Notch was also strongly expressed during development of non-neural tissues, such as hair follicles and tooth buds, whose correct differentiation requires epithelial-mesenchymal interactions. These data support the hypothesis that Notch plays an essential role in mammalian development and pattern formation that closely parallels its role in the development of invertebrates.
Achieving U.S. Health Information Technology Adoption: The Need For A Third Hand

The U.S. health care information technology (HIT) market is broken; broad-scale adoption of HIT is not occurring despite considerable evidence of its impact on the quality of care and patient safety. Although adoption of HIT will not cure all that ails health care, it is an important step toward transformation of the U.S. health care delivery system. In this commentary I describe several critical issues pertaining to the HIT market failure and several ways in which the federal government may act as a deft and gentle “Third Hand” to assist the Invisible Hand of Adam Smith.
Effects of an office-based carotid ultrasound screening intervention.

Background Carotid ultrasound screening (CUS) has been recommended for cardiovascular disease risk prediction, but its effectiveness in clinical practice is unknown. The purpose of this study was to prospectively determine the effects of office-based CUS on physician decision making and patient health-related behaviors. Methods Physicians from five nonacademic, community practices recruited patients aged ≥40 years with ≥1 cardiovascular disease risk factor. Abnormal results on CUS (AbnlCUS) were defined as carotid intima-media thickness >75th percentile or carotid plaque presence. Subjects completed questionnaires before and immediately after CUS and then 30 days later to determine self-reported behavioral changes. Odds ratios (ORs) for changes in physician management and patient health-related behaviors were determined from multivariate hierarchical logistic regression models. Results There were 355 subjects (mean age, 53.6 ± 7.9 years; mean number of risk factors, 2.3 ± 0.9; 58% women); 266 (74.9%) had AbnlCUS. The presence of AbnlCUS altered physicians' prescription of aspirin ( P P P = .002), regardless of their test results. Subjects with AbnlCUS reported increased cardiovascular disease risk perception (OR, 4.14; P P = .008), make dietary changes (OR, 2.95; P P = .022). After 30 days, 34% increased exercise frequency and 37% reported weight loss, but these changes were not predicted by the CUS results. AbnlCUS modestly predicted reduced dietary sodium (OR, 1.45; P = .002) and increased fiber (OR, 1.55; P = .022) intake. Conclusions Finding abnormal results on CUS had major effects on physician but not patient behaviors.
A solution to a class of agency problems, with application to the question of limited liability

Abstract A complete solution is provided for a class of principal-agent problems where the principal is risk neutral, the agent is risk averse with a piece-wise linear utility function and where the distribution of outcomes is binomial. Incentive schemes with limited and unlimited liability are compared and shown to be efficient in the limit.
Determining Basic Satellite Shape from Photometric Light Curves

based sensors. However, other techniques can be used to characterize and describe these satellites. One method is analyzing the photometric signature from the satellite. In this paper, the results of determining a satellite’s shape independent of its size and material composition using simulated data from a photometric modeling tool are presented. A total of 54 test cases were used in the study: six satellite passes, three regular polyhedron shapes, and three satellite attitudes. For each combination of pass, shape, and attitude, 3600 telescope locations centered on the satellite pass were created, andsimulated photometry signatures of the satellite as observed from each location were generated. Comparing simulated photometry data from four different telescope locations to a phase-anglemagnitude distribution for each satellite shape, it was possible to automatically determine the satellite shape 80% of thetimeforrotatingsatellites.Whenthesatellitehadamorestableattitude,however,itwasonlypossibletocorrectly determine the satellite shape 72% of the time.
Theoretical study of stability and electronic structure of Li(Mg,Zn)N alloys: A candidate for solid state lighting

Using selective chemical mutation, we propose and investigate the electronic structure of an alloy with the potential to fill the green gap left open by existing InGaN based emission devices. The small mismatch between LiMgN and LiZnN, along with electronic band gaps spanning the visible range, makes them good candidates. Calculations are performed using a first-principles band structure method, with the special quasirandom structure approach employed to generate the random alloys. Comparison of LiMgN and LiZnN with their binary nitride analogs is made, and the energetic and electronic effects of alloy ordering are investigated. These alloys exhibit negative mixing enthalpies atypical of traditional binary nitride systems, which is explained in terms of the low lattice strain and the chemical bonding effects of the interstitial Li ions.
A dynamic data production model for the Alaska SAR facility

"Business process design is usually done informally, and individual design decisions are hard to relate to business objectives. [Yu96]" This statement succinctly describes a problem which plagues many businesses today. When a system is designed in a piecemeal fashion from semi-autonomous entities producing heterogeneous components which then are combined into one homogeneous system, an enterprise model is not a luxury. It is a necessity. The recent increase in support for formalized software engineering plans have contributed to a number of businesses backtracking and attempting to produce enterprise models which will enable them to investigate how subsystems operate, analyze why they operate in that manner, identify system bottlenecks, and provide a foundation for future development. Alaska SAR Facility (ASF) is one such entity. A Dynamic Data Production Model (DDPM) is being constructed as an enterprise model in an attempt to better understand the current system and provide a foundation for the creation of a Dynamic Data Load Module (DDLM).
Laser excited Raman spectroscopy of biomolecules. 13—conformational study of α‐chymotrypsin and trypsin

The Raman spectra of bovine pancreatic α-chymotrypsin and trypsin were determined from 7% aqueous solutions and lyophilized solids containing residual sulfate ion. A large amount of β-pleated-sheet structure is present in both molecules, as shown by the contour of the amide III region, but trypsin contains substantially more α-helical conformation than does chymotrypsin. There is evidence of some change in structure of both molecules in solution as compared with the solids. The tyrosines are all or nearly all weakly hydrogen bonded in both enzymes, and the binding of sulfate ion is also weak in the lyophilized solids.
Rate Constants for the Gas-Phase Reactions of OH Radicals with a Series of Hydroxyaldehydes at 296 ± 2 K

Using a relative rate method with in situ generation of the hydroxyaldehydes, rate constants for the reactions of the OH radical with 2-hydroxybutanal [CH3CH2CH(OH)CHO], 3-hydroxybutanal [CH3CH(OH)CH2CHO], 2-hydroxypropanal [CH3CH(OH)CHO], 2-hydroxy-2-methylpropanal [(CH3)2C(OH)CHO], and 3-hydroxypropanal [HOCH2CH2CHO] have been measured at atmospheric pressure and 296 ± 2 K. The hydroxyaldehydes were generated in situ from the OH radical-initiated reactions of precursor compounds (1,2- and 1,3-butanediol, 2-methyl-2,4-pentanediol, 2-methyl-3-buten-2-ol, and cis-3-hexen-1-ol) and the rate constants for the reaction of OH radicals with the hydroxyaldehydes were determined relative to those for reaction of OH radicals with the precursor compound. The rate constants obtained (in units of 10-11 cm3 molecule-1 s-1) were CH3CH2CH(OH)CHO, 2.37 ± 0.23; CH3CH(OH)CH2CHO, 2.95 ± 0.24; CH3CH(OH)CHO, 1.70 ± 0.20; (CH3)2C(OH)CHO, 1.40 ± 0.25; and HOCH2CH2CHO, 1.99 ± 0.29.
Composition problem for differential games

The task of finding a relationship between optimal control problems and differential games is considered. Two classes of differential games are shown to have the property that their solution, the value function, can be constructed from solutions to associated one-player optimal control problems.
A Green’s Function Formulation of Anticracks and Their Interaction With Load-Induced Singularities

This paper provides a Green's function formulation of anticracks (rigid lamellar inclusions of negligible thickness that are bonded to the surrounding elastic material). Apart from systematizing several previously known solutions, the article gives the pertinent fields for concentrated forces, dislocations, and a concentrated couple applied on the line of the anticrack
Systemic glucose and brain energy metabolism after subarachnoid hemorrhage.

Background Brain energy metabolic crisis (MC) and lactate–pyruvate ratio (LPR) elevations have been linked to poor outcome in comatose patients. We sought to determine if MC and LPR elevations after subarachnoid hemorrhage (SAH) are associated with acute reductions in serum glucose.
Macropipelined Multicomputer Systems For Image Analysis

We present a scheme for macropipelining in multicomputer systems to achieve high speeds in processing multiple images. Most image processing applications consist of a sequence of tasks - - e.g., preprocessing, detection, segmentation, feature extraction, and classification. This sequence lends itself to a pipelining strategy. To minimize the effects of bottlenecks in this pipeline, we introduce a performance model for data partitioning which includes both the computation and the communication aspects of parallel processing. With the help of this model, we assign the appropriate number of processors to each task so that the workloads are well-balanced. Then we generate a problem graph describing the relationships among tasks and subtasks. We use an estimator of the frame processing time of the image processing system as an objective function for choosing a mapping of the problem graph to a system graph. This estimator takes account of computation times and communication intensities among the subtasks in the problem graph, and accounts for link contentions. To find an efficient mapping, we use a heuristic optimization technique in which possible bottlenecks are given high priority in the mapping procedure. We tested our macropipelining scheme on a typical image processing application in a simulated hypercube computer system. The results support our belief that this scheme yields effective architectures for high-speed processing of long sequences of images.
Mitochondrial ATP measurements

The following is an abstract of the article discussed in the subsequent letter: Drew, Barry and Christiaan Leeuwenburgh. Method for measuring ATP production in isolated mitochondria: ATP production in brain and liver mitochondria of Fischer-344 rats with age and caloric restriction. Am J Physiol
The hidden costs of implementing and maintaining information systems

There are costs associated with the acquisition, implementation, and operation of information systems beyond the price of hardware and software. As these costs sometimes account for budget shortfall, it is important to recognize problem areas and minimize their impact on the organization. Potential hidden costs, including costs that may be hidden by managers, as well as costs that may be hidden from them, are identified and recommendations offered for avoiding serious consequences.
Gender bias in the observation of experimental pain.

Abstract The aim of this study was to examine how men and women observe experimentally induced pain in male and female participants and to specifically determine the accuracy of observed pain ratings, the possible interactions between the sex of the viewer and the sex of the individual being observed, and the influence of gender role expectations on observed pain ratings. The sample comprised 29 participants (15 females). They each completed a battery of psychological questionnaires and viewed a presentation of 10 randomly ordered video clips. Each presentation consisted of 10 video clips, lasting 30 s, of a participant (five males and five females) in the cold pressor task. The participants viewing the videos were asked to provide several ratings, including observed pain intensity and gender role related characteristics of the individual in the video. In terms of sex of the video participant, results indicated that viewers rated male videos as having less pain than female videos although the effect was small. Regarding sex of the viewer, results indicated that for both male and female videos, female viewers rated observed pain intensity significantly higher than did male viewers. In terms of accuracy, results indicated that on average, female video participants' pain was underestimated by 14 points, while male videos participants' pain was underestimated by 22 points (on a 0–100-point scale). Pain intensity ratings and pain tolerance from the participants in the videos did not differ significantly with respect to sex, though women had shorter tolerance times and higher pain ratings than men. Hierarchical regression analyses indicated that expectations of gender related ‘endurance of pain’ significantly predicted ratings of both male and female videos. When endurance expectations were controlled, sex of the viewer no longer significantly predicted observed pain ratings. The ‘willingness to report pain’ variable was not a significant predictor of observed pain ratings. Our results show that women are perceived to have more pain than men, that there was a tendency by both sexes to underestimate pain in others, but men showed even greater underestimation, and that gender role expectations of pain endurance given by the video observers accounted for substantial variance in their ratings of pain in the videos.
Phospholipid – Driven gene regulation

Phospholipids (PLs), well known for their fundamental role in cellular structure, play critical signaling roles via their derivatives and cleavage products acting as second messengers in signaling cascades. Recent work has shown that intact PLs act as signaling molecules in their own right by modulating the activity of nuclear hormone transcription factors responsible for tuning genes involved in metabolism, lipid flux, steroid synthesis and inflammation. As such, PLs have been classified as novel hormones. This review highlights recent work in PL-driven gene regulation with a focus on the unique structural features of phospholipid-sensing transcription factors and what sets them apart from well known soluble phospholipid transporters.
Is Optimal Functioning a Distinct State

Many languages and cultures have labels for individuals who have achieved a superior state of functioning, sometimes referred to as enlightenment or wisdom. This conceptualization of optimal functioning as a distinct state is implicit to several well-known psychological models, as well. This study evaluated whether self-reported strengths of character revealed evidence of such a state. A sample of 83,576 US residents completed the Values in Action Inventory of Strengths (Peterson & Seligman, 2004). On the basis of multiple statistical tests, the results consistently indicated that level of functioning is dimensional, rather than categorical. The findings do not provide support for the existence of a distinct state of superior functioning.
Computational Analysis of Dissipative Heating Due to Impact Between a Micro‐Particle Cluster and a Deformable Wall

A combined finite and discrete element method is used to examine the energetics of a micro-particle cluster that impacts a deformable planar wall. The method combines conservation principles with a penalty based, two-dimensional (2-D) distributed potential force algorithm, and an elastic-viscoplastic and friction constitutive theory, to predict thermomechanical fields within the wall and cluster resulting from both particle-wall and particle-particle contact. Emphasis is placed on characterizing the temporal and spatial partitioning of wall and cluster energy for both normal (0 = 0°, where 0 is incidence angle) and oblique (0 = 45°) impact. Predictions for an initially close-packed-cluster of well-resolved particles, each having an initial radius and speed of 50 μm and 500 m/s, indicate that particles adjacent to the wall experience significant dissipative heating due to plastic and friction work. Frictionally induced temperature rises in excess of 2,000 K are predicted for cluster mass located in the immediate vicinity of sliding contact surfaces, even for normal impact, whereas temperature rises near 200 K are predicted for significantly larger cluster mass due to plastic work. Friction is shown to significantly affect cluster kinetic energy, and to weakly affect its elastic potential energy and plastic work. This analysis highlights the importance of friction as a viable heating mechanism that may trigger combustion of energetic clusters.
Ankle sprain discharge instructions from the emergency department.

OBJECTIVES (1) To describe the incidence of inclusion of early mobilization components in emergency department (ED) discharge instructions; (2) to describe the prescribed follow-up appointments; and (3) to analyze the differences between the treatment of pediatric and adult patients. METHODS A 1-year retrospective chart review of ED records of a large urban hospital was performed. Medical records of 374 (95%) of the 397 adult and pediatric patients with ICD-9 code for ankle sprains were reviewed (213 males and 171 females, mean age 28.4 +/- 14.5; 291 adults, 93 pediatric). RESULTS Sixteen percent of records contained discharge instructions that included rest, ice, compression, elevation, and medications (RICEM). Twenty percent included RICE. Pediatricians (33.7%) were more likely than adult physicians (10.3%) to have given RICEM (P < 0.0001) and RICE (P = 0.05, pedi = 45.8%, adult = 13.1%). Follow-up referrals were recommended as needed 50% of the time. Follow-up referrals were made to community clinics (59%), orthopedic clinic (23%), the ED (14%), and others (4%). Pediatricians were more likely to recommend routine scheduled follow up (pedi = 62%, adult = 47%, P = 0.018), suggest follow-up in a community clinic or doctors office (pedi = 68.6%, adult = 51.2%, P < 0.0001), and to recommend earlier follow up (pedi = 1.6 weeks +/- 1.1, adult = 2.0 weeks +/- 1.1, P = 0.002) than adult physicians. CONCLUSIONS Programs that train physicians who work in the ED need to include education on the proper treatment, rehabilitation, and follow up of patients with acute ankle sprains. Providing easy-to-complete discharge instruction templates can help providers give patients discharge instructions that may help patients minimize the risk of long-term sequelae.
Screening Early Reading Skills in Preschool Children: Get Ready to Read

This study examined a new screening tool (Get Ready to Read) for assessing early reading skills in 73 three-year-old and 79 four-year-old children from low-income families and relating performance ...
Subcellular distribution of isocitrate dehydrogenases in neonatal and adult mouse brain.

— The activity and subcellular distribution of NADP- and NAD-isocitrate de-hydrogenases (ICDH) (EC 1.1.1.42 and 1.1.1.41, respectively) in brains of adult and newborn mice have been determined. In the adult, NAD-ICDH activity in whole brain homogeantes was 1–17 mol/kg wet wt of brain/h (MKH), whereas the NADP-ICDH activity was 0.223 MKH. In the newborn, the activity of the NAD-dependent enzyme was only 0.246 MKH, whereas the NADP-dependent enzyme activity was 1.23 MKH. At both ages, 66 per cent of the NADP-ICDH activity was in the cytosol, less than 10 per cent was in the purified mitochondrial fraction and the remainder was in the crude synaptosomal fraction. Less than 10 per cent of the NAD-ICDH activity was in the cytosol in both the newborn and adult, whereas 50 per cent was in the purified mitochondrial fraction. The crude synaptosomal fraction from the newborn and adult brains contained 28 and 22 per cent, respectively, of the total NAD-ICDH activity. The activities of these enzymes in the cytosol and mitochondria were compared with those of succinate dehydrogenase and with three other enzymes which utilize the product, 2-oxoglutarate, as substrate. The relationship of the isocitrate dehydrogenases to the metabolism of adult and newborn brain is discussed.
Some problems and issues in geophysical turbulence

Velocity fluctuations in the large scales of the atmosphere's meso-scale have turbulent characteristics of random fluctuations and a scale-size distribution near k−5/3 (Gage, 1979. J. Atmos. Sci. 36, 1950–1954; Lilly, 1983. J. Atmos. Sci. 40, 749–761; Lilly et al., 1998. Theoret. Comput. Fluid Dyn. 11, 139–153). Explanations of this motion field have ranged from inverse cascading quasi-geostrophic (i.e. quasi-two-dimensional) turbulence, to gravity waves (VanZandt, 1982. Geophys. Res. Lett. 9, 575–578). We describe efforts to relate observational spectra to various theories ranging from quasi-geostrophic turbulence to gravity waves. We note that at the larger scales quasi-geostrophic theory may suffice, but at smaller scales, a quasi-geostrophic explanation becomes untenable because the importance of rotation becomes progressively weaker as scales of the flow becomes smaller (the Rossby number approaches unity). We then discuss numerical simulations designed to discriminate between alternative explanations of the flow. Several simulations are reviewed, starting with those of Herring and Metais (1989. J. Fluid Mech. 202, 97–115), and finally those described by Lilly et al. (1998. Theoret. Comput. Fluid Dyn. 11, 139–153).
Assaying the catalytic potential of transition metal sulfides for abiotic carbon fixation

Abstract A suite of nickel, cobalt, iron, copper, and zinc containing sulfides are assayed for the promotion of a model carbon fixation reaction with relevance to local reducing environments of the early Earth. The assay tests the promotion of hydrocarboxylation (the Koch reaction) wherein a carboxylic acid is synthesized via carbonyl insertion at a metal-sulfide-bound alkyl group. The experimental conditions are chosen for optimal assay, i.e., high reactant concentrations and pressures (200 MPa) to enhance chemisorption, and high temperature (250°C) to enhance reaction kinetics. All of the metal sulfides studied, with the exception CuS, promote hydrocarboxylation. Two other significant reactions involve the catalytic reduction of CO to form a surface-bound methyl group, detected after nucleophilic attack by nonane thiol to form methyl nonyl sulfide, and the formation of dinonyl sulfide via a similar reaction. Estimation of the catalytic turnover frequencies for each of the metal sulfides with respect to each of the primary reactions reveals that NiS, Ni3S2, and CoS perform comparably to commonly employed industrial catalysts. A positive correlation between the yield of primary product to NiS and Ni3S2 surface areas provides strong evidence that the reactions are surface catalytic in these cases. The sulfides FeS and Fe(1−x)S are unique in that they exhibit evidence of extensive dissolution, thus, complicating interpretation regarding heterogeneous vs. homogeneous catalysis. With the exception of CuS, each of the metal sulfides promotes reactions that mimic key intermediate steps manifest in the mechanistic details of an important autotrophic enzyme, acetyl-CoA synthase. The relatively high temperatures chosen for assaying purposes, however, are incompatible with the accumulation of thioesters. The results of this study support the hypothesis that transition metal sulfides may have provided useful catalytic functionality for geochemical carbon fixation in a prebiotic world (at least intially) devoid of peptide-based enzymes.
Motion primitives for human-inspired bipedal robotic locomotion: walking and stair climbing

This paper presents an approach to the development of bipedal robotic control techniques for multiple locomotion behaviors. Insight into the fundamental behaviors of human locomotion is obtained through the examination of experimental human data for walking on flat ground, upstairs and downstairs. Specifically, it is shown that certain outputs of the human, independent of locomotion terrain, can be characterized by a single function, termed the extended canonical human function. Optimized functions of this form are tracked via feedback linearization in simulations of a planar robotic biped walking on flat ground, upstairs and downstairs — these three modes of locomotion are termed “motion primitives.” A second optimization is presented, which yields controllers that evolve the robot from one motion primitive to another — these modes of locomotion are termed “motion transitions.” A final simulation is given, which shows the controlled evolution of a robotic biped as it transitions through each mode of locomotion over a pyramidal staircase.
Hypoxic cell death in the human NT2-N neuronal cell line

Background: Important species differences make a human model of in vitro hypoxic neuronal cell death desirable.
Incidence, timing and site of infections among pancreas transplant recipients

The incidence, timing and site of infections among the different categories of pancreas transplant recipients were investigated. Patients were divided into three groups: pancreas transplant alone (PTA), pancreas after kidney transplant (PAK), or simultaneous pancreas and kidney (SPK) transplants. Length of follow-up, time to death, pancreas graft survival, incidence, timing and site of bacterial infections were noted. Our study showed that at least 75% of pancreas transplant recipients experienced at least one infection (range from 77.8% in the PTA group to 86.7% in the PAK group). The SPK group presented the highest rate of infections with 35.1 infections per 1000/patient-days. Symptomatic urinary tract infections were the most common cause of infection in all patients. The incidence of infections was higher during the first month after transplantation, except for the SPK transplant group, where infections occurred over a longer time period.
The Voice in the Night Unheard by Scholars: Herb Jepko and the Genesis of National Talk Radio

Radio scholarship is an emerging field of study among broadcast historians and much remains unexplored. There exists little investigation into how early FCC clear-channel radio stations provided the first platform for national radio communication. Much of historical scholarship recognizes Larry King's satellite-distributed program as the pioneering stride in national overnight talk radio. This study examines new archival evidence that reveals Herb Jepko used clear-channel signals to broadcast the first national overnight talk radio program.
Nav1.7 is the predominant sodium channel in rodent olfactory sensory neurons

Voltage-gated sodium channel Nav1.7 is preferentially expressed in dorsal root ganglion (DRG) and sympathetic neurons within the peripheral nervous system. Homozygous or compound heterozygous loss-of-function mutations in SCN9A, the gene which encodes Nav1.7, cause congenital insensitivity to pain (CIP) accompanied by anosmia. Global knock-out of Nav1.7 in mice is neonatal lethal reportedly from starvation, suggesting anosmia. These findings led us to hypothesize that Nav1.7 is the main sodium channel in the peripheral olfactory sensory neurons (OSN, also known as olfactory receptor neurons). We used multiplex PCR-restriction enzyme polymorphism, in situ hybridization and immunohistochemistry to determine the identity of sodium channels in rodent OSNs. We show here that Nav1.7 is the predominant sodium channel transcript, with low abundance of other sodium channel transcripts, in olfactory epithelium from rat and mouse. Our in situ hybridization data show that Nav1.7 transcripts are present in rat OSNs. Immunostaining of Nav1.7 and Nav1.6 channels in rat shows a complementary accumulation pattern with Nav1.7 in peripheral presynaptic OSN axons, and Nav1.6 primarily in postsynaptic cells and their dendrites in the glomeruli of the olfactory bulb within the central nervous system. Our data show that Nav1.7 is the dominant sodium channel in rat and mouse OSN, and may explain anosmia in Nav1.7 null mouse and patients with Nav1.7-related CIP.
A computational strategy for active control of dynamic systems via minimizing the displacement magnitudes of dominent harmonics of vibration

An active control strategy is proposed to attenuate the undesirable vibrations of dynamic systems. In this approach the dynamic system is treated as a black-box, whose modal characteristics are not included in the control process. Instead, the control of the system is pursued via utilizing optimization techniques to minimize an objective function formulated based on the response of the system at several locations on the vibrating system. The decision variables of the formulated optimization problem are the magnitudes and phase angles of alternative force components to be exerted at proper location of the system. The proposed method is applied to simulated active control of a rotor system whose unbalance response is to be minimized.
Evaluation of two flexible colonoscopy simulators and transfer of skills into clinical practice.

Introduction Surgical residents have learned flexible endoscopy by practicing on patients in hospital settings under the strict guidance of experienced surgeons. Simulation is often used to “pretrain” novices on endoscopic skills before real clinical practice; nonetheless, the optimal method of training remains unknown. The purpose of this study was to compare endoscopic virtual reality and physical model simulators and their respective roles in transferring skills to the clinical environment. Methods At the beginning of a skills development rotation, 27 surgical postgraduate year 1 residents performed a baseline screening colonoscopy on a real patient under faculty supervision. Their performances were scored using the Global Assessment of Gastrointestinal Endoscopic Skills (GAGES). Subsequently, interns completed a 3-week flexible endoscopy curriculum developed at our institution. One-third of the residents were assigned to train with the GI Mentor simulator, one-third trained with the Kyoto simulator, and one-third of the residents trained using both simulators. At the end of their rotations, each postgraduate year 1 resident performed one posttest colonoscopy on a different patient and was again scored using GAGES by an experienced faculty. Results A statistically significant improvement in the GAGES total score (p Conclusion Colonoscopy simulator training with the GI Mentor platform exclusively or in combination with a physical model simulator improves skill performance in real colonoscopy cases when measured with the GAGES tool.
Gender differences in the effectiveness of online trust building information cues: An empirical examination

Abstract Building trust with customers is essential for the success of business-to-consumer e-commerce (B2C) ventures. Entrepreneurial B2C e-commerce ventures face a particularly daunting challenge in building trust given the liability of newness and legitimacy concerns arising from lack of name recognition in the marketplace. To address this issue, recent research has suggested that certain online information cues may be useful in influencing perceptions of new/small e-commerce vendor trustworthiness. Perplexingly though, such research has paid scant attention to whether gender differences exist with regard to the effectiveness of such trust building information cues. Hence, the present study adds to the literature by using a sample of 536 potential internet shoppers to examine whether gender differences exist in the effectiveness of online B2C trust building information cues. Participants were asked to assess the importance of 14 different trust building information cues in influencing their perceptions of e-commerce vendor trustworthiness. Factor analysis reduced the data to four factors representing different aspects of perceived trustworthiness. Results of the study show that, when controlling for internet usage, disposition to trust, trust in the Internet and trust in e-commerce, women reported statistically significant higher values on three of the four factors examined. Specifically, women reported higher values on factors related to communication (or information flow), security, and functionality than did their male counterparts. Study results suggest that entrepreneurial B2C online ventures may promote themselves more effectively to women in particular by carefully managing information cues on or about their website.
The C. elegans gene pan-1 encodes novel transmembrane and cytoplasmic leucine-rich repeat proteins and promotes molting and the larva to adult transition

Extracellular leucine-rich repeat (eLRR) proteins are a highly diverse superfamily of membrane-associated or secreted proteins. In the membrane-associated eLRR proteins, the leucine-rich repeat motifs interact with the extracellular matrix and other ligands. Characterizing their functions in animal model systems is key to deciphering their activities in various developmental processes. In this study, we identify pan-1 as a critical regulator of C. elegans larval development. pan-1 encodes both transmembrane and cytoplasmic isoforms that vary in the presence and number of leucine-rich repeats. RNAi experiments reveal that pan-1 is required for developmental processes that occur during the mid to late larval stages. Specifically, pan-1 loss of function causes a late larval arrest with a failure to complete development of the gonad, vulva, and hypodermis. pan-1 is also required for early larval ecdysis and execution of the molting cycle at the adult molt. We also provide evidence that pan-1 functionally interacts with the heterochronic gene lin-29 during the molting process. We show that PAN-1 is a critical regulator of larval development. Our data suggests that PAN-1 promotes developmental progression of multiple tissues during the transition from a larva to a reproductive adult. We further demonstrate that the activity of PAN-1 is complex with diverse roles in the regulation of animal development.
Arginine vasotocin enhances influx of testosterone in the newt brain

Abstract Using a new method to assess the movement of steroid hormones through the blood-brain barrier, we found evidence that the influx of testosterone was increased in castrated, androgen-treated newts ( Taricha granulosa ) by intraperitoneal injections of homologous pituitary preparations or arginine-8 vasotocin.
IL-8 responsiveness defines a subset of CD8 T cells poised to kill

CD8 T cells play a key role in host defense against intracellular pathogens. Efficient migration of these cells into sites of infection is therefore intimately linked to their effector function. The molecular mechanisms that control CD8 T-cell trafficking into sites of infection and inflammation are not well understood, but the chemokine/chemokine receptor system is thought to orchestrate this process. Here we systematically examined the chemokine receptor profile expressed on human CD8 T cells. Surprisingly, we found that CXC chemokine receptor 1 (CXCR1), the predominant neutrophil chemokine receptor, defined a novel interleukin-8/CXC ligand 8 (IL-8/CXCL8)–responsive CD8 T-cell subset that was enriched in perforin, granzyme B, and interferon-γ (IFNγ), and had high cytotoxic potential. CXCR1 expression was down-regulated by antigen stimulation both in vitro and in vivo, suggesting antigen-dependent shaping of the migratory characteristics of CD8 T cells. On virus-specific CD8 T cells from persons with a history of Epstein-Barr virus (EBV) and influenza infection, CXCR1 expression was restricted to terminally differentiated effector memory cells. In HIV-1 infection, CXCR1-expressing HIV-1–specific CD8 T cells were present only in persons who were able to control HIV-1 replication during structured treatment interruptions. Thus, CXCR1 identifies a subset of CD8 T cells poised for immediate cytotoxicity and early recruitment into sites of innate immune system activation.
Electron microscopy of boundary structure in calcium zirconate

Various types of boundary in orthorhombic calcium zirconate (CaZrO3) were examined using conventional transmission electron microscopy (CTEM), high-resolution electron microscopy (HREM), selected-area diffraction (SAED) and convergent-beam electron diffraction (CBED). Two types of interface, namelyδ-boundaries and coherent twin boundaries were identified and analysed. Theδ-boundaries were studied using CTEM, SAED and CBED; the twin boundaries were investigated using the additional technique of HREM. Pseudosymmetric twinning was observed in CaZrO3 where the two domains were related to each other by either a 180° or a 90° rotation about an axis perpendicular to (101). A different type of twin boundary, where the adjacent domains were related by a 180° rotation about the normal to (100), was also noted. The observations are compared with previous studies on other ABO3-type compounds isostructural with CaZrO3.
Diversity and Distribution of Freshwater Gastropods in the Bayou Bartholomew Drainage, Arkansas, U.S.A.

Bayou Bartholomew is a low-gradient river system that drains much of southeastern Arkansas and northeastern Louisiana, U.S.A. As one of the few southeastern streams remaining un-impounded, the Arkansas reach of the bayou harbors a rich freshwater molluscan fauna. Collecting efforts have historically focused on documenting freshwater mussel and fish diversity, and there was no prior survey focusing on freshwater gastropods. This survey of the drainage yielded 13 gastropod species representing three orders and seven genera. Pulmonates were most abundant in low-order reaches of the drainage, while gill-breathing snails dominated higher-order reaches. Co-occurrence analyses indicated that pulmonates occurred significantly more often with other pulmonates than they did with gill- breathers; this trend was also observed in gill-breathers. Both stream order and predominant substrate influenced species richness and abundance. Our findings were consistent with other published studies on freshwater snail distribution but may be confounded by drought conditions experienced during the survey.
Absence of Supersolidity in Solid Helium in Porous Vycor Glass

In 2004, Kim and Chan carried out torsional oscillator measurements of solid helium confined in porous Vycor glass and found an abrupt drop in the resonant period below 200 mK. The period drop was interpreted as probable experimental evidence of nonclassical rotational inertia. This experiment sparked considerable activities in the studies of superfluidity in solid helium. More recent ultrasound and torsional oscillator studies, however, found evidence that shear modulus stiffening is responsible for at least a fraction of the period drop found in bulk solid helium samples. The experimental configuration of Kim and Chan makes it unavoidable to have a small amount of bulk solid inside the torsion cell containing the Vycor disk. We report here the results of a new helium in Vycor experiment with a design that is completely free from any bulk solid shear modulus stiffening effect. We found no measurable period drop that can be attributed to nonclassical rotational inertia.
Bradykinin Antagonism Inhibits the Antigrowth Effect of Converting Enzyme Inhibition in the Dog Myocardium After Discrete Transmural Myocardial Necrosis

Background Converting enzyme inhibitor (CEI) therapy, but not angiotensin II subtype I receptor blockade, has been shown to attenuate left ventricular remodeling in the dog after transmyocardial direct current (DC) shock. The purpose of this study was to address the importance of preservation of bradykinin to the antiremodeling effect of CEI treatment in this model. Methods and Results Twenty-four hours after DC shock, adult mongrel dogs were assigned to one of three groups: a control group; a group treated with ramipril 10 mg BID; and a group treated with ramipril 10 mg BID along with a continuous subcutaneous infusion of HOE 140, a bradykinin antagonist. To assess change in left and right ventricular structure, a magnetic resonance imaging (MRI) study was performed 4 weeks after DC shock and compared with a baseline MRI study performed before DC shock. The increase in left ventricular mass (mean±SEM) in the control group was similar to that observed in the CEI–HOE 140 group (+0.73±0.19 versus +0.75±0.18...
Online Caregiving Resources

Caregiving the chronically ill, elderly, or disabled is challenging. The number of caregivers in the United States continues to rise. Many caregivers turn to electronic resources for assistance and support. Online, caregivers can access high-quality resources designed to address day-to-day, practical needs as well as help soothe the emotional, mental, physical, and spiritual stress brought on by caregiving. Some sites address general caregiving audiences while others are designed for specific types of caregivers or patient populations. Several sites provide information on assistive technologies or offer video “how-to” clips or documentaries featuring caregivers and their loved ones. If caregivers know where to look, information exists to meet every need.