cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacodynamic separation (PDS) of gemcitabine (Gem) and the epidermal growth factor receptor (EGFR) inhibitor erlotinib (E) in patients (Pts) with advanced pancreatic cancer: Phase II results.

e15073 Background: Continuously dosed E given concurrently with Gem results in only a modest survival improvement in pts with advanced pancreatic cancer. Preclinical data suggest that there is antagonism between chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) when these are delivered concurrently due to cell cycle effects. Work by our group and others has shown that EGFR TKIs induce cytostasis due to G1 arrest, which reduces subsequent cell cycle phase-dependent activity of chemotherapy. We tested a PDS approach for E + Gem as a means of overcoming the hypothesized negative interaction of EGFR TKIs and chemotherapy. Methods: Pts with measurable, previously untreated locally advanced unresectable/metastatic pancreatic cancer with adequate organ function and PS 0-2 were eligible. Tumor tissue was collected for molecular studies. PDS Regimen: Gem 1000 mg/m2 IV days 1, 8, 15, and E 150 mg/day on days 2-5, 9-12, 16-26 of each 28-day cycle. Primary endpoint was PFS; secondary endpoints included response...
Killing A Child: Neuropsychological Profiles of Murderers of Children:

This study examined neuropsychological characteristics of offenders who killed children. Although prior studies have focused on filicide and neonaticide, children are killed in a variety of context...
A −236.3dB FoM sub-sampling low-jitter supply-robust ring-oscillator PLL for clocking applications with feed-forward noise-cancellation

A 2–2.8GHz 65nm CMOS ring oscillator PLL occupies an active area of 0.022mm2, consumes 5.86mW and achieves a 633fs RMS jitter at 2.36 GHz and an FOM jitter of −236.3dB. It implements a low-overhead feed-forward phase and supply-noise cancellation scheme by leveraging the noise extraction inherently done by the sub-sampling phase detector. Cancellation reduces the jitter by 1.4x, the phase noise by 10.2dB to −123.5dBc/Hz at a 300KHz offset, and the ring oscillator supply sensitivity by 19.5dB for a 1mV p-p 100KHz supply noise tone.
Improvement in Quality Metrics by the UPMC Enhanced Care Program: A Novel Super-Utilizer Program.

Abstract The aim was to evaluate pre–post quality of care measures among super-utilizer patients enrolled in the Enhanced Care Program (ECP), a primary care intensive care program. A pre–post analysis of metrics of quality of care for diabetes, hypertension, cancer screenings, and connection to mental health care for participants in the ECP was conducted for patients enrolled in ECP for 6 or more months. Patients enrolled in ECP showed statistically significant improvements in hemoglobin A1c, retinal exams, blood pressure measurements, and screenings for colon cancer, and trends toward improvement in diabetic foot exams and screenings for cervical and breast cancer. There was a significant increase in connecting patients to mental health care. This study shows that super-utilizer patients enrolled in the ECP had significant improvements in quality metrics from those prior to enrollment in ECP.
Clinical Reasoning: A common cause for Phelan-McDermid syndrome and neurofibromatosis type 2: One ring to bind them.

An 8-year-old girl with mild dysmorphic features presented for evaluation of developmental delay and staring spells. She had been born late preterm and spent 1 month in the neonatal intensive care unit. She was generally healthy other than her developmental delay, which improved somewhat with physical, occupational, and speech therapy. At the first clinic visit, her mother reported loss of previously mastered vocabulary and struggles with fine motor skills such as buttoning. She also noted repetitive movements, obsessive behaviors, and hand flapping.
Governmental and Academic Efforts to Advance the Field of Pharmacogenomics

Abstract With the completion of the Human Genome Project in 2003 came significant interest in elucidating genetic contributors to drug response. Data from the subsequent International HapMap Project allowed pharmacogenomic studies to extend beyond a candidate gene focus. Genome-wide association studies, enriched with data from the 1000 Genomes Project, have led to discoveries of previously unsuspected genes linked to drug response. Both the National Institutes of Health (NIH) and U.S. Food and Drug Administration (FDA) have invested significant resources toward further advancing the field of pharmacogenomics. This chapter will discuss efforts by the NIH, FDA, and non-U.S. regulatory agencies to promote pharmacogenomic research, encourage the integration of genetic data in the drug development process, and address the scientific and regulatory challenges associated with clinical implementation of pharmacogenomic data.
Biosynthesis and metabolic engineering of pseudo-oligosaccharides

Pseudo-oligosaccharides are microbial-derived secondary metabolites whose chemical structures contain pseudosugars (glycomimetics). Due to their high resemblance to the molecules of life (carbohydrates), most pseudo-oligosaccharides show significant biological activities. Some of them have been used as drugs to treat human and plant diseases. Because of their significant economic value, efforts have been put into understanding their biosynthesis, optimizing their fermentation conditions, and engineering their metabolic pathways to obtain better production yields. A number of unusual enzymes participating in diverse biosynthetic pathways to pseudo-oligosaccharides have been reported. Various methods and conditions to improve the production yields of the target compounds and eliminate byproducts have also been developed. This review article describes recent studies on the biosynthesis, fermentation optimization, and metabolic engineering of high-value pseudo-oligosaccharides.
Investigation of Issues for the Accurate and Precise Measurement of an Analyte Using Surface-Enhanced Raman Scattering (SERS):

This paper builds on an earlier examination of the influence of sampling size and analyte surface density on the accuracy and precision of measurements using surface-enhanced Raman scattering (SERS) to read out heterogeneous immunoassays. Quantitation using SERS typically relies on interrogating a small area on the sample surface by using a micrometer-sized laser spot for signal generation. The information obtained using such a small portion of sample is then projected as being representative of the much larger sample, which can compromise the accuracy and precision of the measurement due to undersampling. For a heterogeneous immunoassay interrogated by SERS, quantitation is, therefore, sensitive to the size of the analyzed area and the surface density of the measured analyte. To identify conditions in which sampling error poses a threat to accuracy and precision, a simulation of a SERS immunoassay was developed and compared to experimental results. The simulation randomly distributes adsorbates across the capture surface and then measures the density of adsorbates inside areas of analysis of different sizes. This approach mimics the analysis of a heterogeneous immunoassay when using a Raman microscope with different laser spot sizes. The results of the simulations, which were confirmed experimentally by comparison to an immunoassay of human immunoglobulin G (IgG) show that the accuracy and precision of the measurement improved with larger analysis areas and higher analyte concentrations due to the increased apparent homogeneity of the analyte within the area of analysis. By imposing a threshold on precision (5%), we also begin to establish a framework for the parameters necessary to achieve reliable quantitative measurements (e.g., laser spot size, analyte concentration, and sample volume).
Antibiotic Prophylaxis for Dental Treatment in Patients with Immunodeficiency

Routine antibacterial prophylaxis is recommended before dental procedures in select patient populations. Currently, no guidelines are in place for routine prophylaxis before dental procedures in patients with primary immunodeficiency diseases. We review risk factors and provide recommendations on routine dental care and antibacterial prophylaxis in patients with primary immunodeficiency diseases.
Dynamics of a Small-Scale Hydrogen Peroxide Vapor Propulsion System

A novel thruster concept for CubeSats and other small satellites using hydrogen peroxide vapor as a propellant is presented and evaluated. This concept leads to the highest theoretical vacuum speci...
How Do Firms Feel About Participation by Their Peers in the Regulatory Design Process? An Online Survey Experiment Testing the Substantive Change and Spillover Mechanisms

This paper examines two concerns with calls for increased participation by firms in the government design of regulations in emerging markets. First, given the profit maximization goals of firms, ca...
Transposition of the common carotid artery in standing cattle

OBJECTIVE To describe a method for permanent transposition of the common carotid artery (CCA) in standing cattle. STUDY DESIGN Experimental study. ANIMALS Eight healthy, adult, lactating Holstein-Friesian cows. METHODS Cows were restrained with the head and neck extended by using halters, head catch, and squeeze chute. Surgery was performed under local anesthesia and intravenous sedation. The right CCA was approached through a skin incision dorsal and parallel to the jugular vein. The skin incision was extended through the brachiocephalicus and longus capitus muscles. When the vessel was present, ligation of accessory vessels of the CCA and internal jugular vein was performed to facilitate exposure. The artery was sharply dissected from the carotid sheath and elevated by using Penrose drains. The muscles were closed in two layers, leaving the artery in a subcutaneous position. The incision was protected with a tie-over bandage for 1 week. Sampling from the CCA was initiated approximately 6 weeks after surgery. RESULTS The CCA was successfully transposed and used for repeated arterial blood sampling in all eight cows. No cows had intraoperative complications or evidence of surgical site infection. One cow had a postoperative suture reaction at the site of a suture used for maintaining the tie-over bandage. All arteries remained patent for use in subsequent studies. CONCLUSION Permanent translocation of the CCA was successful in all cows in this study and consistently allowed serial arterial blood sampling. CLINICAL SIGNIFICANCE Common carotid artery translocation is possible without general anesthesia in adult cattle and is useful in studies requiring serial sampling of arterial blood.
Mental Illness Is Not Anyone’s Fault: A Review of NAMI, the National Alliance on Mental Illness

AbstractThe National Alliance on Mental Illness (NAMI) was established in 1979 and has since grown into a national foundation supporting both online and physical resources for those with mental dis...
Medical school hotline: promoting medical student research using a searchable database of research projects at the John A.Burns School of Medicine.

Participation in research activities while in medical school is endorsed by medical students.1 Curricular programs aimed at supporting medical student research have been effective and well received.2,3 Research support is provided on a multitude of fronts, including central coordination by the office of medical education, faculty-student matching, financial support, and tailoring projects sensitive to student schedules. Students are able to build meaningful relationships with faculty mentors and develop systematic thinking, data analysis, and literature review skills. In addition, research is a means for students to contribute to their area of interest by demonstrating a zeal for scientific inquiry, thus enhancing their competitiveness for residency positions.4,5 For those willing to commit the time, participation in research is an invaluable medical school experience. Medical students founded the Research Interest Group (RIG) at University of Hawai‘i John A. Burns School of Medicine (JABSOM) to improve medical student access to research opportunities. An informal survey, conducted in 2010, indicated high levels of research interest and participation amongst JABSOM medical students. Students also desired more research opportunities in clinical, community health, primary care, and community outreach.6 RIG continues to provide educational opportunities through a series of research seminars and strives to streamline the research process for all medical students. The purpose of this study was to assess medical student support for an online, searchable, and continually updated database of research opportunities at JABSOM. In addition, information on student satisfaction with current resources for research opportunities was collected.
Integrated CO2 capture and one-pot production of methanol

The capture, storage, and utilization (CSU) of CO2 to produce methanol which can be used as a fuel, fuel additive, and precursor in organic synthesis is an area of fascinating research. This directly influences the reduction of the CO2 concentration by capturing CO2 from industrial and automobile emissions. The development of integrated CO2 capture and conversion to a fuel and fuel additive has garnered considerable attention as it eliminates costly processes to produce pure CO2. This contribution presents a summary of integrated CO2 capture and conversion to methanol (MeOH) using amine-assisted and alkali hydroxide-assisted one-pot systems. The superiority of the alkali hydroxide-based system to the amine-based system for the conversion to MeOH is systematically presented.
Four-dimensional tractography animates neural propagations via distinct interhemispheric pathways

Objective: To visualize and validate the dynamics of interhemispheric neural propagations induced by single-pulse electrical stimulation (SPES). Methods: This methodological study included three patients with drug-resistant focal epilepsy who underwent measurement of cortico-cortical spectral responses (CCSRs) during bilateral stereo-electroencephalography recording. We delivered SPES to 83 electrode pairs and analyzed CCSRs recorded at 268 nonepileptic electrode sites. Diffusion-weighted imaging (DWI) tractography localized the interhemispheric white matter pathways as streamlines directly connecting two electrode sites. We localized and visualized the putative SPES-related fiber activation, at each 1-ms time window, based on the propagation velocity defined as the DWI-based streamline length divided by the early CCSR peak latency. Results: The resulting movie, herein referred to as four-dimensional tractography, delineated the spatiotemporal dynamics of fiber activation via the corpus callosum and anterior commissure. Longer streamline length was associated with delayed peak latency and smaller amplitude of CCSRs. The cortical regions adjacent to each fiber activation site indeed exhibited CCSRs at the same time window. Conclusions: Our four-dimensional tractography successfully animated neural propagations via distinct interhemispheric pathways. Significance: Our novel animation method has the potential to help investigators in addressing the mechanistic significance of the interhemispheric network dynamics supporting physiological function.
Stress and Allostatic Load Among Latina/os: Evidence from the Hispanic Community Health Study/Study of Latina/os.

We investigated associations between measures of environmental and psychological stress (i.e., chronic stress and perceived stress) and allostatic load across gender. We also tested whether other important intersectional factors, such as ethnic background and nativity, moderated stress–allostatic load relationships. Data were drawn from the Hispanic Community Health Study/ Study of Latina/os, a representative, multi-ethnic sample of Latina/os living in four urban communities. The final analytic sample consisted of 3848 Latina/os from five ethnic groups: Cuban, Puerto Rican, Dominican, Mexican, and South/ Central American. Findings indicate greater chronic and perceived stress were significantly associated with allostatic load for males but not for females. We also find, in some cases, ethnic background and nativity moderated relationships between types of stress and allostatic load for males. Findings suggest that environmental and psychological stressors can potentially shape health profiles of Latino males, with important differences across ethnic background and nativity.
The Effects of Irrigation and Weather on Agriculture in Haiti: A Machine Learning Approach

Low program uptake and the prevalence of highly non-linear relationships between variables can make the evaluation of development interventions challenging. This study highlights the potential for using Machine Learning (ML) as a supplement to the traditional econometric toolkit for causal inference in such complex settings. We illustrate this approach by using data from an RCT in rural Haiti to measure the causal relationship between access to small-scale irrigation, weather and household outcomes. We use ML techniques to generate predictions of productivity, revenue and high value crop production from the baseline and then estimate treatment effects on the residuals. Our Intent to Treat (ITT) program estimates suggest that irrigation increased crop revenue by 24%. We find no statistically significant effects on maize quantity harvested and the production of high value crops, even though the corresponding point estimates go in the right direction.
Metchnikoff and the phagocytosis theory

Metchnikoff's phagocytosis theory was less an explanation of host defence than a proposal that might account for establishing and maintaining organismal 'harmony'. By tracing the phagocyte's various functions through phylogeny, he recognized that eating the tadpole's tail and killing bacteria was the same fundamental process: preserving the integrity, and, in some cases, defining the identity of the organism.
Logics for Termination and Correctness of Functional Programs

In the literature of logic and theoretical computer science, types are considered both semantically as some kinds of mathematical objects and syntactically as certain kinds of formal terms. They are dealt with in one way or the other, or both, in all programming languages, though most attention has been given to their role in functional programming languages. One difference in treatment lies in the extent to which types are explicitly represented in programs themselves and, further, can be passed as values. Familiar examples, more or less at the extremes, are provided by LISP—an untyped language— and ML—a polymorphic typed language. The aim of this paper (and the more detailed ones to follow) is to provide a logical foundation for the use of type systems in functional programming languages and to set up logics for the termination and correctness of programs relative to such systems. The foundation provided here includes LISP and ML as special cases. I believe this work should be adaptable to other kinds of programming languages, e.g. those of imperative style.
Triclinic form of 1,2,4,5-tetra­cyclo­hexyl­benzene

The mol­ecule of the title compound, C30H46, has a crystallographically imposed inversion center and the cyclo­hexyl groups are oriented with their methine H atoms pointing towards one another (H⋯H = 2.04 A).
Marine plant polymers

Abstract A general kinetic expression is presented for the rate of alkaline degradation of linear polysaccharides in terms of mono- and di-anionic species formed from the reducing end-groups. Specific rate constants have been determined for the end-wise depolymerization of the (1→3)-β- D -glucans, laminaran, laricinan, and pachyman, and compared with similar data for amylose degradation. The rate constants of degradative chain-propagation via the mono- and di-anion intermediates have been shown to be essentially equal. The effect of the type and concentration of base on the mechanism of end-wise degradation is described for both (1→3)-linked and (1→4)-linked polysaccharides. Inhibition of alkaline degradation is discussed in terms of chain branching and blockage of reducing end-groups.
Register Bank Assignment for Spatially Partitioned Processors

Demand for instruction level parallelism calls for increasing register bandwidth without increasing the number of register ports. Emerging architectures address this need by partitioning registers into multiple distributed banks, which offers a technology scalable substrate but a challenging compilation target. This paper introduces a register allocator for spatially partitioned architectures. The allocator performs bank assignment together with allocation. It minimizes spill code and optimizes bank selection based on a priority function. This algorithm is unique because it must reason about multiple competing resource constraints and dependencies exposed by these architectures. We demonstrate an algorithm that uses critical path estimation, delays from registers to consuming functional units, and hardware resource constraints. We evaluate the algorithm on TRIPS, a functional, partitioned, tiled processor with register banks distributed on top of a 4 ×4 grid of ALUs. These results show that the priority banking algorithm implements a number of policies that improve performance, performance is sensitive to bank assignment, and the compiler manages this resource well.
Reconstitution of chromatin: The sequential binding of histones to DNA in the presence of salt and urea

Abstract Calf thymus chromatin is dissociated in 3 m -NaCl, 0.05 m -NaHSO3 and 6 m -urea, pH 7.8. The presence of NaHSO3 is necessary to prevent degradation of calf thymus histones. The protein is returned to the DNA by a stepwise dialysis into solutions of lower NaCl concentrations, maintaining constant urea and NaHSO3 concentrations. At a given NaCl concentration, free protein is separated from DNA-bound protein on a Bio-Gel A50 column equilibrated in the same salt and urea concentrations as the dialyzed sample. Both free and DNA-bound histones are analyzed by analytical disc-acrylamide gel electrophoresis. Urea lowers the affinity of histones for DNA. None of the histones return to the DNA until a NaCl concentration of 0.2 m has been reached. The first histone to bind is lysine-rich histone I. The other histones return to the DNA during dialysis from 0.15 m -NaCl, 0.05 m -NaHSO3 and 6 m -urea to 6 m -urea, which is followed by a final dialysis into 2 × 10−4 m -EDTA, pH 6.2. When native chromatin is extracted with NaCl in the presence of 6 m -urea and 0.04 m -NaHSO3, slightly lysine-rich histones IIb1 and IIb2 are removed at 0.15 m -NaCl, lysine-rich histone I at 0.3 m -NaCl and the arginine-rich histones III and IV at 0.6 m -NaCl. Increasing the urea concentration to 7 m lowers the NaCl concentration required to remove histones III and IV to 0.15 m -NaCl, but does not change the NaCl concentration required to remove histones I, IIb1 and IIb2. The NaCl concentration at which histones III and IV associate with DNA appears to be a function of the urea concentration and time used for extraction.
Stochastic Differential Equations Driven by Loops

We study stochastic differential equations of the type $$\displaystyle{ X_{t} = x +\sum _{ i=1}^{d}\int _{ 0}^{t}V _{ i}(X_{s}^{x}) \circ dM_{ s}^{i},\text{ }0 \leq t \leq T, }$$ where (M s )0 ≤ s ≤ T is a semimartingale generating a loop in the free Carnot group of step N and show how the properties of the random variable X T x are closely related to the Lie subalgebra generated by the commutators of the V i ’s with length greater than N + 1. It is furthermore shown that if f is a smooth function, then $$\displaystyle{\lim _{T\rightarrow 0}\frac{\mathbb{E}(\,f(X_{T}^{x})) - f(x)} {T^{N+1}} = (\Delta _{N}\,f)(x),}$$ where \(\Delta _{N}\) is a second order operator related to the V i ′s.
Laser performance operations model (LPOM)

The Laser Performance Operations Model (LPOM) has been developed to provide real time predictive capabilities for the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. LPOM uses diagnostic feedback from previous NIF shots to maintain accurate energetics models for each of the 192 NIF beamlines (utilizing one CPU per laser beamline). This model is used to determine the system setpoints (initial power, waveplate attenuations, laser diagnostic settings) required for all requested NIF shots. In addition, LPOM employs optical damage models to minimize the probability that a proposed shot may damage the system. LPOM provides post-shot diagnostic reporting to support the NIF community. LPOM was deployed prior to the first main laser shots in NIF, and has since been used to set up every shot in NIF's first quad (four beamlines). Real-time adjustments of the codes energetics parameters allows the LPOM to predict total energies within 5%, and provide energy balance within the four beamlines to within 2% for shots varying from 0.5 to 26 kJ (1.053 {micro}m) per beamline. The LPOM has been a crucial tool in the commissioning of the first quad of NIF.
Verification Of Combinational Logic in Nuprl

We present a case study of hardware specification and verification in the Nuprl Proof Development System. Within Nuprl we have built a specialized environment consisting of tactics, definitions, and theorems for specifying and reasoning about hardware. Such reasoning typically consists of term-rewriting, case-analysis, induction, and arithmetic reasoning. We have built tools that provide high-level assistance for these tasks. The hardware component that we have proven is the front end of a floating-point adder/subtractor. This component, the MAEC (Mantissa Adjuster and Exponent Calculator), has 5459 transistors and has been proven down to the transistor level. As the circuit has 118 inputs and 107 outputs, verification by traditional methods such as case analysis would have been a practical impossibility.
Nutrient‐dependent requirement for SOD1 in lifespan extension by protein restriction in Drosophila melanogaster

Reactive oxygen species (ROS) modulate aging and aging-related diseases. Dietary composition is critical in modulating lifespan. However, how ROS modulate dietary effects on lifespan remains poorly understood. Superoxide dismutase 1 (SOD1) is a major cytosolic enzyme responsible for scavenging superoxides. Here we investigated the role of SOD1 in lifespan modulation by diet in Drosophila. We found that a high sugar-low protein (HS-LP) diet or low-calorie diet with low-sugar content, representing protein restriction, increased lifespan but not resistance to acute oxidative stress in wild-type flies, relative to a standard base diet. A low sugar-high protein diet had an opposite effect. Our genetic analysis indicated that SOD1 overexpression or dfoxo deletion did not alter lifespan patterns of flies responding to diets. However, sod1 reduction blunted lifespan extension by the HS-LP diet but not the low-calorie diet. HS-LP and low-calorie diets both reduced target-of-rapamycin (TOR) signaling and only the HS-LP diet increased oxidative damage. sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling. Surprisingly rapamycin decreased lifespan in sod1 mutant but not wild-type males fed the standard, HS-LP and low calorie diets, whereas antioxidant N-acetylcysteine only increased lifespan in sod1 mutant males fed the HS-LP diet, when compared to diet-matched controls. Our findings suggest that SOD1 is required for lifespan extension by protein restriction only when dietary sugar is high, and support the context-dependent role of ROS in aging and caution the use of rapamycin and antioxidants in aging interventions.
Existential social work

The existential impact upon social work began in the 1960’s with the emphasis upon freedom, responsibility and a sense of the absurd. It affirmed human potential while faulting the deterministic thinking that was popular with psychological theorists at that time. It was open to the prospects of spirituality, but was less than optimistic concerning great progress among social institutions. It was a forerunner to the strengths-based social work programs of our present day.
Operational Mode Monitoring of Gas Turbines in an Offshore Gas-Gathering Application

A computer-assisted monitoring system has been implemented on GT-61 Gas Turbines employed in offshore gas gathering. Operating load data are continuously recorded at the site and evaluated at the turbine manufacturer's plant on a mainframe computer, where existing analysis and testing techniques are utilized to predict the service fatigue lives of the power turbine structural components. The data acquisition hardware, the data reduction software, and the life prediction techniques are each described. The data collected indicate that offshore gas gathering equipment will experience many more operating load cycles than comparable equipment in pipeline service. The fatigue life predictions reaffirm the suitability of the GT-61 for this more severe service.
Structure determination in "shiftless" solid state NMR of oriented protein samples.

Abstract An efficient formalism for calculating protein structures from oriented-sample NMR data in the torsion-angle space is presented. Angular anisotropies of the NMR observables are treated by utilizing an irreducible spherical basis of rotations. An intermediate rotational transformation is introduced that greatly speeds up structural fitting by rendering the dependence on the torsion angles Φ and Ψ in a purely diagonal form. Back-calculation of the simulated solid-state NMR spectra of protein G involving 15N chemical shift anisotropy (CSA), and 1H–15N and 1Hα–13Cα dipolar couplings was performed by taking into account non-planarity of the peptide linkages and experimental uncertainty. Even a relatively small (to within 1 ppm) random variation in the CSA values arising from uncertainties in the tensor parameters yields the RMSD’s of the back-calculated structures of more than 10 A. Therefore, the 15N CSA has been substituted with heteronuclear dipolar couplings which are derived from the highly conserved bond lengths and bond angles associated with the amino-acid covalent geometry. Using the additional 13Cα–15N and 13C′–15N dipolar couplings makes it possible to calculate protein structures entirely from “shiftless” solid-state NMR data. With the simulated “experimental” uncertainty of 15 Hz for protein G and 120 Hz for a helical hairpin derived from bacteriorhodopsin, back-calculation of the synthetic dipolar NMR spectra yielded a converged set of solutions. The use of distance restraints dramatically improves structural convergence even if larger experimental uncertainties are assumed.
Marine Biodiversity Dynamics over Deep Time

The fossil record provides our only direct window into how Earth's biodiversity has changed over the past 530 million years. Efforts to dissect diversity dynamics, however, have been impeded by gaps in the fossil record and uneven sampling by paleontologists. As a result, two of the most fundamental questions in paleobiology remain contentious. How, in detail, has diversity changed over geologic time? And what is the nature of the rules that governed these diversity changes? More specifically, was the diversification of most groups of organisms unconstrained, or was it subject to some sort of limit? On page 1191 of this issue, Alroy ( 1 ) presents a new analysis of the marine fossil record that goes to the heart of these questions. The results are unlikely to be universally accepted, but they help to pinpoint the critical issues.
Panther Peer: A Web-Based Tool for Peer and Self Evaluation

Panther Peer is a novel web based tool for peer evaluation. It has been developed at the Florida Institute of Technology to enable students (specifically those involved in capstone design projects) to give one another anonymous feedback on their team performance. Panther Peer is simple to implement and completely automated. Panther Peer automates the process of peer evaluation and minimizes the workload for both instructors and students. With the benefits of automation students can gain feedback more quickly. Moreover, the reduction in workload for course instructors enables them to encourage peer evaluations. The primary advantage of this system is the feedback students receive from their peers which helps them identify their weaknesses and focus on their strengths. The automated process means that the collection and dissemination of information is highly efficient. From the peer evaluations by students, instructors can have a fair idea about the teams progress and intervene where deemed necessary.© 2011 ASME
Design and manufacture of ultra-low-mass, cryogenic heat exchangers

Abstract Custom, precision, manufacturing methods now allow novel heat exchangers (HXs) to operate in the laminar-flow regime which has enabled the recent production of high-effectiveness, gas-to-gas, cryogenic exchangers with a factor-of-four decrease in mass relative to comparable high-performance exchangers. The exchangers operate under laminar conditions, even at high levels of power and flow, by using hundreds (or thousands) of parallel micro-tubes (hence titled “micro-tube strip (MTS)” type exchangers). Although the theory behind the potential for low-mass MTS performance was characterized over a decade ago (briefly summarized herein), the actual repeatable fabrication of cryogenic recuperators using this technology is new, and interesting technical hurdles in performance and manufacturing are discussed herein.
Acid-catalyzed reductive amination of aldoses with 8-aminopyrene-1,3,6-trisulfonate

The reductive amination of monosaccharides with 8-aminopyrene-1,3,6-trisulfonate (APTS) in seven different organic acids including the commonly used acetic acid was investigated by capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection. The correlation between the yields of the saccharide-APTS adducts and pKa of the organic acid catalyst is consistent with general acid catalysis of the rate-determining step of the reductive amination reaction. Derivatization in the presence of organic acids of higher strength than acetic acid produced substantially higher yields of APTS-sugar adducts, an effect which is more pronounced for N-acetylamino sugars. Optimum yields were obtained using citric acid as a catalyst. Conversion of a few nanomoles of neutral saccharides to the APTS derivatives is achieved at 75°C in less than 60 min.
Differences in neuromuscular junctions of laryngeal and limb muscles in rats

Objectives/Hypothesis Laryngeal muscles are specialized for fine control of voice, speech and swallowing, and may differ from limb muscles in many aspects. Since muscles and their controlling motor neurons communicate via neuromuscular junctions (NMJ), we hypothesized that NMJs in laryngeal muscles have specialized characteristics different from limb muscles.
INCORPORATING PRIOR BELIEF IN THE GENERAL PATH MODEL: A COMPARISON OF INFORMATION SOURCES

The general path model (GPM) is one approach for performing degradation-based, or Type III, prognostics. The GPM fits a parametric function to the collected observations of a prognostic parameter and extrapolates the fit to a failure threshold. This approach has been successfully applied to a variety of systems when a sufficient number of prognostic parameter observations are available. However, the parametric fit can suffer significantly when few data are available or the data are very noisy. In these instances, it is beneficial to include additional information to influence the fit to conform to a prior belief about the evolution of system degradation. Bayesian statistical approaches have been proposed to include prior information in the form of distributions of expected model parameters. This requires a number of run-to-failure cases with tracked prognostic parameters; these data may not be readily available for many systems. Reliability information and stressor-based (Type I and Type II, respectively) prognostic estimates can provide the necessary prior belief for the GPM. This article presents the Bayesian updating framework to include prior information in the GPM and compares the efficacy of including different information sources on two data sets.
Photoabsorption spectrum of Mg i in the range 226–170 Å (54–70 eV)

The photoabsorption spectrum of Mg i has been observed in the spectral region 226–170 A (54–70 eV) using synchrotron radiation as a background source. The one-electron excitation levels associated with the series: 1s2 2s2 2p63s2 1So → 1s2 2s2 2p5 [2P3/2,1/2]3s2n s, n d were observed as well as 29 two- and three-electron excitation resonances. A critical analysis of the one-electron excitation spectrum was made and classifications for all the multiple electron excitations have been suggested on the basis of their quantum defects to known limits in Mg ii.
TrkB activation by brain-derived neurotrophic factor inhibits the G protein-gated inward rectifier Kir3 by tyrosine phosphorylation of the channel.

G protein-activated inwardly rectifying potassium channels (Kir3) are widely expressed throughout the brain, and regulation of their activity modifies neuronal excitability and synaptic transmission. In this study, we show that the neurotrophin brain-derived neurotrophic factor (BDNF), through activation of TrkB receptors, strongly inhibited the basal activity of Kir3. This inhibition was subunit dependent as functional homomeric channels of either Kir3.1 or Kir3.4 were significantly inhibited, whereas homomeric channels composed of Kir3.2 were insensitive. The general tyrosine kinase inhibitors genistein, Go 6976, and K252a but not the serine/threonine kinase inhibitor staurosporine blocked the BDNF-induced inhibition of the channel. BDNF was also found to directly stimulate channel phosphorylation because Kir3.1 immunoprecipitated from BDNF-stimulated cells showed enhanced labeling by anti-phosphotyrosine-specific antibodies. The BDNF effect required specific tyrosine residues in the amino terminus of Kir3.1 and Kir3.4 channels. Mutations of either Tyr-12, Tyr-67, or both in Kir3.1 or mutation of either Tyr-32, Tyr-53, or both of Kir3.4 channels to phenylalanine significantly blocked the BDNF-induced inhibition. The insensitive Kir3.2 was made sensitive to BDNF by adding a tyrosine (D41Y) and a lysine (P32K) upstream to generate a phosphorylation site motif analogous to that present in Kir3.4. These results suggest that neurotrophin activation of TrkB receptors may physiologically control neuronal excitability by direct tyrosine phosphorylation of the Kir3.1 and Kir3.4 subunits of G protein-gated inwardly rectifying potassium channels.
An approach to modeling asymmetric multivariate spatial covariance structures

We propose a framework in light of the delay effect to model the asymmetry of multivariate covariance functions that is often exhibited in real data. This general approach can endow any valid symmetric multivariate covariance function with the ability of modeling asymmetry and is very easy to implement. Our simulations and real data examples show that asymmetric multivariate covariance functions based on our approach can achieve remarkable improvements in prediction over symmetric models.
Robust supplier relationships: Key lessons from the economic downturn

Abstract Recent events in the economic and natural environments have tested buyer-supplier relationships like never before. Based on dyadic buyer-supplier case data from a variety of industries that were deeply affected by the 2008–2009 recession, this article explores how long-term relationships responded to an economic downturn. Prior to the downturn, these mutually dependent relationships all appeared to be very similar to each other and were characterized by significant value-added and social capital stores. However, due to varying degrees of bounded rationality, the relationships were affected differently and responded differently to the downturn. Based on the characteristics of the relationship, we develop a framework of three types of close supplier alliances. This framework can be used to assess such relationships and likely responses to adversity to reduce unpleasant surprises for the alliance partners. This article also provides a set of lessons learned for managers.
Equivocal Death Investigation: Case Study Analyses

Abstract An equivocal death investigation should be comprised of an extensive and thoroughly documented analysis of the body recovery scene, the autopsy, the forensic evidence, laboratory tests, and the victimology and behavioral history of the deceased. Equivocal death analysis is an investigative process that can aid in determining the manner of death by examining existing forensic evidence and the behavioral and psychological history of the deceased. Although equivocal death analysis has long been regarded as an effective process that can assist investigators in many cases, it has recently received increased scrutiny from members of the scientific community. This scrutiny is likely the result of the limited research and literature that exists on the topic of equivocal deaths and the techniques used to investigate them.
Quantification of Serum IgG Subclasses by Use of Subclass-Specific Tryptic Peptides and Liquid Chromatography–Tandem Mass Spectrometry

BACKGROUND: Measurement of IgG subclasses is a useful tool for investigation of humoral immune deficiency in the presence of total IgG within reference intervals and IgG4-related disease. Nephelometry has been the method of choice for quantification. We describe an LC-MS/MS method that can multiplex all 4 subclasses along with total IgG by use of either IgG subclass-specific peptide stable isotope–labeled internal standards or a surrogate digest standard for quantification and does not rely on antigen/antibody reactions. METHODS: We combined serum with labeled internal peptide standards and intact purified horse IgG. Samples were denatured, reduced, alkylated, and digested. We analyzed the digested serum by LC-MS/MS for IgG subclasses 1–4 and total IgG. RESULTS: We assayed 112 patient sera by LC-MS/MS and immunonephelometry. The mean of the slopes and R 2 values for IgG1, IgG2, IgG3, IgG4, and IgG were 1.18 and 0.93, respectively. Interassay imprecision for the LC-MS/MS method was <15% for total IgG and subclasses and was slightly improved by use of a calibrator peptide from an exogenous horse IgG. Summed total IgG correlated with the measured total IgG within 10%. Reference intervals and analytical measuring range were all similar to our previous validation data for the immunonephelometry assays. CONCLUSIONS: Total IgG and IgG subclasses 1, 2, 3, and 4 can be quantified by LC-MS/MS with performance comparable to nephelometry.
Mammalian Neuromuscular Development Accelerated with Early but Slowed with Late Gestational Administration of ACTH Peptide

The neuropeptide ACTH 4-10, a nonsteroidogenic fragment of adrenocorticotropic hormone, has two distinct and opposite effects on developing nerve and muscle. Muscle is positively influenced by ACTH during the first part of gestation (G days 3-12) before innervation occurs. Subsequent effects on innervation are largely depressive and exerted only during G13-21. Treatment during G3-12 increases twitch amplitude, rise time and speed of contraction of directly and indirectly stimulated extensor digitorum longus (EDL) muscle of two wk old rats. Treatment during G13-21 slows contractions of indirectly stimulated EDL, whereas treatment throughout gestation (G3-G21) shows little effect. Thus, ACTH first accelerates muscle development then modulates this development through neuronal depression.
Modeling Sea Level During El Niño

Abstract We test the hypothesis that sea level variations associated with EL Nino events are a response to wind changes in the central Pacific and that the signal is transmitted to the coast of South America by packets of equatorial Kelvin waves. A linear model is forced by wind stress anomalies composited from six EL Ninos occurring between 1951 and 1972 (Rasmusson and Carpenter). Model sea level is compared with similar composites of tidegage measurements from selected equatorial Pacific stations. Although several vertical modes are included in the calculation, only the two gravest baroclinic modes make significant contributions to the sea level signal. Model results duplicate the pattern and timing of the observed sea level anomalies but amplitudes are systematically low. This is especially true at central and western Pacific stations, and it is suggested that the poor quality of the forcing data may be at fault there. Results at the east provide better support for the theory: in particular, the twin-p...
The carbohydrate-protein linkage in the α1-glycoprotein of human plasma

Abstract After prolonged digestion with Pronase, over 50% of the carbohydrate of the α1-glycoprotein was isolated as glycopeptide fractions with molecular weight near 1800. One of the fractions yielded asparagine (aspartic acid plus NH3) as the sole amino acid residue. Some of the aspargine had been cleaved from the carbohydrate unit (octasaccharide) by Pronase leaving N-acetylglucosamine in the reducing position. It was proposed that aspargine is joined through its amide group to form a 8-aspartyl N-acetylglucosaminylamine linkage. Some of the asparagine residues of the other fraction appear to be in peptide linkage with threonine which is N-terminal. This report does not concur with the proposal ( Winzler and Inoue, 1961 ) that glutamic acid is joined to the amino group of glucosamine in the α1-glycoprotein. Recently glycopeptides in which aspartic acid predominated were isolated from the α1-glycoprotein ( Kamiyama and Schmid, 1962 ).
STEREOTYPE-BIASED SEARCH AND PROCESSING OF INFORMATION ABOUT GROUP MEMBERS

Abstract Two studies examined the contribution of biased information search and biased information processing to stereotyping of individual group members. Participants were free to ask any question they thought would help them make an accurate judgment about a target person's attitudes. Despite this opportunity to acquire individuating information, participants' judgments about group members were strongly influenced by their stereotypes. The findings further show that both the content of the questions addressed to stereotyped targets and the manner in which the answers to these questions were processed contributed to stereotyping. It is argued that biased information search is a major obstacle to the reduction of stereotyping in many real-life situations.
Hepatocyte resistance to oxidative stress is dependent on protein kinase C-mediated down-regulation of c-Jun/AP-1.

The prevention of injury from reactive oxygen species is critical for cellular resistance to many death stimuli. Resistance to death from the superoxide generator menadione in the hepatocyte cell line RALA255–10G is dependent on down-regulation of the c-Jun N-terminal kinase (JNK)/AP-1 signaling pathway by extracellular signal-regulated kinase 1/2 (ERK1/2). Because protein kinase C (PKC) regulates both oxidant stress and JNK signaling, the ability of PKC to modulate hepatocyte death from menadione through effects on AP-1 was examined. PKC inhibition with Ro-31-8425 or bisindolylmaleimide I sensitized this cell line to death from menadione. Menadione treatment led to activation of PKCμ, or protein kinase D (PKD), but not PKCα/β, PKCζ/λ, or PKCδ/θ. Menadione induced phosphorylation of PKD at Ser-744/748, but not Ser-916, and translocation of PKD to the nucleus. PKC inhibition blocked menadione-induced phosphorylation of PKD, and expression of a constitutively active PKD prevented death from Ro-31-8425/menadione. PKC inhibition led to a sustained overactivation of JNK and c-Jun in response to menadione as determined by in vitro kinase assay and immunoblotting for the phosphorylated forms of both proteins. Cell death from PKC inhibition and menadione treatment resulted from c-Jun activation, since death was blocked by adenoviral expression of the c-Jun dominant negative TAM67. PKC and ERK1/2 independently down-regulated JNK/c-Jun, since inhibition of either kinase failed to affect activation of the other kinase, and simultaneous inhibition of both pathways caused additive JNK/c-Jun activation and cell death. Resistance to death from superoxide therefore requires both PKC/PKD and ERK1/2 activation in order to down-regulate proapoptotic JNK/c-Jun signaling.