cssi/SciSciGPT-SciSciNet huggingface dataset:
Single Laboratory Method Performance Evaluation for the Analysis of Total Food Folate by Trienzyme Extraction and Microplate Assay

Single laboratory method performance parameters, including the calibration curve, accuracy, recovery, precision, limit of detection (LOD), and limit of quantification (LOQ), were evaluated for the analysis of total food folate by the trienzyme extraction and microplate assay with Lactobacillus casei subsp. rhamnosus. Standard Reference Material (SRM) 1546 (meat homogenate), SRM 2383 (baby food composite), SRM 1846 (infant formula), Certified Reference Material (CRM) 121 (wholemeal flour), and CRM 485 (mixed vegetables), representing a broad selection of food matrices, were used to evaluate the performance of the method. A generated 4-parameter logistic equation of the calibration curve was y= (0.0705 - 1.0396)/(1 + (x/0.0165) (1.3072)) + 1.0396 (P < 0.0001). The test of parallelism demonstrated that matrix components in the food extracts did not affect the accuracy. Measured values of the SRMs and CRMs were within their certified or reference values. Recoveries for all reference materials met the requirements of the AOAC guidelines for single laboratory validation. Precision measured as repeatability, including simultaneous and consecutive replicates for each SRM and CRM, met the Horwitz criterion. LOD and LOQ values were 0.3 and 0.6 mug/100 g, respectively. The results showed that trienzyme digestion using alpha-amylase, Pronase(R), and conjugase from chicken pancreas coupled with a 96-well microplate assay provided a highly accurate, reproducible, and sensitive method for the determination of folate in a variety of foods.
Deafferentation-induced expression of GAP-43, NCAM, and NILE in the adult rat dorsal horn following pronase injection of the sciatic nerve.

The expression of growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), and nerve-growth-factor-inducible large external glycoprotein (NILE) in the adult rat dorsal horn was examined at several survival times after unilateral pronase injection of the sciatic nerve. Pronase injection produces a permanent major loss of sciatic primary afferents in the dorsal horn, and there is a later sprouting of saphenous afferents into the sciatic territory. Small-diameter myelinated and nonmyelinated saphenous afferents sprout within the superficial dorsal horn, and larger, myelinated afferents sprout within the deep dorsal horn. In the present study, GAP-43 and NCAM immunoreactivity increased in the superficial dorsal horn by 10 days after injection. By 20 days, the increase spread into the deep dorsal horn; NCAM returned to normal after 1-2 months, but GAP-43 persisted up to 4 months. NILE immunoreactivity appeared in laminae I and II by 10 days and increased up to 30 days; by 2 months no NILE r...
Neurodevelopment after Fetal Growth Restriction

Fetal growth restriction (FGR) can emerge as a complication of placental dysfunction and increases the risk for neurodevelopmental delay. Marked elevations of umbilical artery (UA) Doppler resistance that set the stage for cardiovascular and biophysical deterioration with subsequent preterm birth characterize early-onset FGR. Minimal, or absent UA Doppler abnormalities and isolated cerebral Doppler changes with subtle deterioration and a high risk for unanticipated term stillbirth are characteristic for late-onset FGR. Nutritional deficiency manifested in lagging head growth is the most powerful predictor of developmental delay in all forms of FGR. Extremes of blood flow resistance and cardiovascular deterioration, prematurity and intracranial hemorrhage increase the risks for psychomotor delay and cerebral palsy. In late-onset FGR, regional cerebral vascular redistribution correlates with abnormal behavioral domains. Irrespective of the phenotype of FGR, prenatal tests that provide precise and independent stratification of risks for adverse neurodevelopment have yet to be determined.
A multidisciplinary design experience that addresses several ABET outcomes also provides a framework for international student collaboration

The faculty at Western New England College in the industrial engineering and biomedical engineering departments have developed a multidisciplinary laboratory design experience that integrates several ABET outcomes and serves to prepare students for the capstone senior design project. The ABET Outcomes addressed include c, d, e, f, g, and h, however others could be incorporated depending on the project. In addition, this experience serves to reinforce design concepts learned in previous courses and requires the students to develop real-world prototypes for implementation. The specific projects focus on designing and developing assistive technologies for disabled individuals employed at not-for-profit agencies. The devices provide the individuals with increased accessibility to employment opportunities. The students employ a variety of design tools including Manhattan, a web-based forum for sharing designs and communication. Recent projects in the area of manual work have included box folding, screw packaging, tape cutting, and folder assembly. The projects are successful in several ways. The students gain valuable interdisciplinary design experience, the not-for-profit agency gains needed assistance in their production, and the individuals with disabilities become more productive employees. This design experience provides a framework for emulating a modern product development environment with participating team members located at different universities around the world.
Gravitational radiation from nonaxisymmetric instability in a rotating star

We present the first calculations of the gravitational radiation produced by nonaxisymmetric dynamical instability in rapidly rotating compact star. The star deforms into a bar shape, shedding \ensuremath{\sim}4% of its mass and \ensuremath{\sim}17% of its angular momentum. The gravitational radiation is calculated in the quadrupole approximation. For a mass M\ensuremath{\sim}1.4${\mathit{M}}_{\mathrm{\ensuremath{\bigodot}}}$ and radius R\ensuremath{\sim}10 km, the gravitational waves have frequency \ensuremath{\sim}4 kHz and amplitude h\ensuremath{\sim}2\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}22}$ at the distance of the Virgo Cluster. They carry off energy \ensuremath{\Delta}E/M\ensuremath{\sim}0.1% and radiate angular momentum \ensuremath{\Delta}J/J\ensuremath{\sim}0.7%.
Sera from Cameroon induce crisis forms during Plasmodium falciparum growth inhibition studies in vitro.

Abstract Sera collected from 176 children and adults from 3 different regions of Cameroon were used in inhibition assays against Plasmodium falciparum in vitro. The individuals had been classified clinically as malarious or non-malarious. Of the 58 non-malarious persons questioned, 39 claimed never to have had symptoms of the disease. Sera were tested for inhibitory effects on either merozoite entry and retardation of growth or inhibition of intraerythrocytic growth. The sera from malarious individuals showed only 9% and 29% mean inhibition values at 24 and 48 h, respectively, while those from the non-malarious persons showed 59% and 73% inhibition for the same periods. Of the 58 sera from non-malarious persons, 34 produced typical crisis forms by 24–36 h. Some sera also inhibited merozoite entry into erythrocytes. Our data suggest an important relationship between acquired immunity to P. falciparum in Cameroon and the types of inhibition described here.
Construction and characterization of versatile cloning vectors for efficient delivery of native foreign proteins to the periplasm of Escherichia coli.

Abstract Induction of the wild type cholera toxin operon ( ctxAB ) from multicopy clones in Escherichia coli inhibited growth and resulted in low yields of cholera toxin (CT). We found that production of wild type CT or its B subunit (CT-B) as a periplasmic protein was toxic for E. coli, but by replacing the native signal sequences of both CT-A and CT-B with the signal sequence from the B subunit of E. coli heat-labile enterotoxin LTIIb we succeeded for the first time in producing CT holotoxin in high yield in E. coli. Based on these findings, we designed and constructed versatile cloning vectors that use the LTIIb-B signal sequence to direct recombinant native proteins with high efficiency to the periplasm of E. coli. We confirmed the usefulness of these vectors by producing two other secreted recombinant proteins. First, using phoA from E. coli, we demonstrated that alkaline phosphatase activity was 17-fold greater when the LTIIb-B signal sequence was used than when the native leader for alkaline phosphatase was used. Second, using the pspA gene that encodes pneumococcal surface protein A from Streptococcus pneumoniae, we produced a 299-residue amino-terminal fragment of PspA in E. coli in large amounts as a soluble periplasmic protein and showed that it was immunoreactive in Western blots with antibodies against native PspA. The vectors described here will be useful for further studies on structure–function relationships and vaccine development with CT and PspA, and they should be valuable as general tools for delivery of other secretion-competent recombinant proteins to the periplasm in E. coli.
An enantioselective approach to ring a of taxol using the wieland-miescher ketone

Abstract The selective protection of the S-(+)-enantiomer of the Wieland Miescher ketone ( 2 ) as the tert-butyldimethylsilyl-protected cyanohydrin 7 and the oxidative cleavage of an α-ketol 8 that was derived from 7 provided a model 10 for the A ring of the taxol ( 1 ) possessing the correct C-1 stereochemistry of taxol and functionality suitable for further elaboration.
Variations in stoichiometry in Hg(1-x) Cd(x) Te using electrolyte electroreflectance: a topographical investigation.

We have developed a unique approach for evaluating the local composition x as a function of position on the surface of crystals of Hg1−xCdxTe utilizing electrolyte electroreflectance. The method is nondestructive and can be employed at room temperature. The technique is sensitive enough to determine changes of composition Δx ≈ 0.002 for samples in which x ≈ 0.2–0.3 with a spatial resolution of about 150 μm. This approach has a number of advantages over the microprobe technique.
Diffusion of Er3+ in porous sol-gel glass

Abstract The diffusion coefficients of Er 3+ inside porous sol-gel glass of average pore diameters about 3 nm were determined from concentration profiles within monoliths impregnated by 1.6 M rare earth salts dissolved in either acetone or water. To study the effects of ligands on the diffusion, four different erbium salts were used: nitrate, chloride, bromide and perchlorate. It is shown that surface interactions are more important than geometrical restrictions in determining the diffusion rates. Inside the pores, nitrate and perchlorate anions diffuse at the same rate as cations, suggesting that anions are members of cation coordination sphere. Absorption spectra of erbium doped porous gels were recorded at various stages of drying and sintering processes for temperatures up to 800°C. Those spectra indicate that in bulk phase and in wet gels cations are surrounded by coordination spheres of similar compositions, but as temperature is increased, interactions become different as contacts between cations and pore surface become increasingly important. Gels sintered at 800°C exhibit similar absorption and emission spectra independent of the salt used for impregnation. The impregnation of stabilized gels by diffusing metal salts in to the pores results in samples of similar properties as those obtained by the wet sol-gel process.
The Education Reform Act of 1988

(1997). The Education Reform Act of 1988. Assessment in Education: Principles, Policy & Practice: Vol. 4, No. 2, pp. 307-314.
Fishing for Tigers: A Method for Collecting Tiger Beetle Larvae Holds Useful Applications for Biology and Conservation

ABSTRACT A series of field studies examined the effectiveness of using a grass blade/stem to extract tiger beetle larvae (Coleoptera: Carabidae: Cicindelinae) from their burrows without damaging the larva or the burrow — a procedure often called fishing. We found that larvae of many species can be efficiently sampled at rates equal to or exceeding other methods. Extracted larvae have a low percentage of injury and can be assessed for parasitism and condition. They can be returned to either their own burrow or an alternative burrow where they can be re-sampled. The results of these studies indicate that fishing for tiger beetle larvae can be an effective tool for monitoring populations where larvae can be returned to existing burrows. In addition, the fishing technique allows for relocation of organisms while eliminating the impacts associated with excavating threatened species or larvae from rare habitats.
Mean-variance based ranking and selection

The traditional approach in ranking and selection procedures is to compare simulated systems based on the mean performance of a metric of interest. The system with the largest (or smallest) mean performance is deemed as the best system. However, the system with the best mean performance may be an undesirable choice because of its large variance. Variance is a measure of risk. A highly variable system performance shows that the system is not under control. Both mean and variance of a performance metric need to be compared to determine the best system. We present a statistically valid selection procedure for comparing simulated systems based on a mean-variance dominance relationship. The system with the best mean and smallest variance is deemed as the best system. If there is not a unique best system, the procedure identifies a set of nondominant systems. In both cases, a prespecified probability of correct selection is guaranteed.
Expanding the Genetic Alphabet: Pyrazine Nucleosides That Support a Donor ? Donor ? Acceptor Hydrogen‐Bonding Pattern

The 6-aminopyrazin-2(1H)-one, when incorporated as a pyrimidine-base analog into an oligonucleotide chain, presents a H-bond donordonoracceptor pattern to a complementary DNA or RNA strand. When paired with the corresponding acceptoracceptordonor purine in oligonucleotides, the heterocycle selectively contributes to the stability of the duplex, presumably by forming a base pair of WatsonCrick geometry joined by a nonstandard H-bonding pattern, expanding the genetic alphabet. Reported here is a short, high yielding, β-D-selective synthesis of a 6-aminopyrazin-2(1H)-one nucleoside via the glycine riboside derivative 28. The key steps include a WittigHorner reaction of an appropriately protected ribose derivative (Scheme 10, 1921) followed by a Michael-like ring closure (Scheme 12, 301a and 321b). Thus, a variety of pyrazine nucleosides (Scheme 13) including the target 6-aminopyrazin-2(1H)-one riboside 1a, and its 5-methyl derivative 1b, 6-amino-5-methylpyrazin-2(1H)-one riboside, are obtained.
Respiration and Acid-Base Physiology of the Spotted Gar, a Bimodal Breather: II. Responses to Temperature Change and Hypercapnia

SUMMARY Elevation of temperature from 20 to 30 °C, increased the pulmonary ventilation and pulmonary oxygen consumption (from 0-18 to 0-43 ml Oj.kg- 1 . min -1 ). The total CO2 excretion also rose, but branchial ventilation and branchial oxygen consumption did not change significantly. The blood pH dropped quickly when temperature was elevated, with a slope (dpH/dT°) of -0-015, but the OH~/H+ ratio did not change significantly. This change in pH resulted from an elevation in arterial PQQ^, without any concomitant change in plasma HCO3~. Arterial PCOl per se was probably not actively regulated, but rose passively as a consequence of the gar's utilization of the lung for increased oxygen uptake, and the inefficiency of the lung in COa exchange. The lung had an exchange ratio (R) of about o-i. Temperature change produced no significant alteration in the net acid excretion from either the kidney or the gills, despite an increased ammonia excretion rate at 30 °C. The urine formation rate was very low (74 fi\. 100 g^.h" 1 ) which imposed a limitation on the importance of the kidney in acid-base regulation. Hypercapnia produced a respiratory acidosis which was partially compensated by an elevation in blood HCO3~ after 24 h of exposure. The gill ventilation rose only slightly, and later fell as compensation proceeded. Air-breathing frequencies were not greatly affected by hypercapnia.
MBE growth and characterization of Mg-doped InGaN and InAlN

We report on the growth of high quality Mg-doped InGaN and InAlN alloys on (0001) sapphire substrates by molecular beam epitaxy. Phase separation does not occur in InxGa1-xN films with Indium content up to 0.88. Hall measurement shows that a hole concentration of 7.7x1017 cm–3 is achieved on Mg-doped In0.04Ga0.96N. When x > 0.11, the Hall samples exhibit strong n-type polarity, whereas p-type polarity is confirmed by hot probe measurement for all of Mg-doped InGaN. Ni/Au film is deposited on Mg-doped InxGa1-xN as the p contact met al. A contact resistivity as high as 9.95 Ωcm2 is obtained when x = 0.25 while it is only 6.81x10–5 Ωcm2 when x = 0.85. High quality crack-free InAlN films are also grown on sapphire substrates with AlN/InN quantum-well buffer layers. When Mg is incorporated near the solid solubility limit, donor defects form and In0.62Al0.38N films show n-type polarity by Hall measurement, however lower Mg flux yields p-type polarity. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Carpal collapse and Sudeck's atrophy

Acute posttraumatic (Sudeck's) atrophy of the upper extremity is well known. The symptoms and signs are out of proportion to what is to be expected from the inciting event. Typically, bone atrophy is characterized by a focal, patchy, periarticular demineralization pattern, which is usually transient. Remineralization occurs after successful treatment. This report describes a typical case of the clinical syndrome after a wrist sprain but with carpal dissolution and collapse before remineralization.
A low-cost concurrent error detection technique for processor control logic

This paper presents a concurrent error detection technique targeted towards control logic in a processor with emphasis on low area overhead. Rather than detect all modeled transient faults, the technique selects faults which have a high probability of causing damage to the architectural state of the processor and protects the circuit against these faults. Fault detection is achieved through a series of assertions. Each assertion is an implication from inputs to the outputs of a combinational circuit. Fault simulation experiments performed on control logic modules of an industrial processor suggest that high reduction in damage causing faults can be achieved with a low overhead.
The Effect of a Multidisciplinary Head and Neck Cancer Clinic on Compliance with Speech Pathology Treatment

Methods: Patients with newly diagnosed oropharyngeal HNCA referred for pretreatment SLP evaluation comprised the study population. Compliance was measured by participation in SLP therapy during and after head and neck treatment, as well as by the number of missed and completed visits. Outcomes were compared between patients who were initially evaluated through the multidisciplinary clinic and those evaluated outside of the multidisciplinary clinic format.
Code-carrying theory

Code-Carrying Theory (CCT) is an alternative to the Proof-Carrying Code (PCC) approach to secure delivery of code. With PCC, code is accompanied by assertions and a proof of correctness or of other required properties. The code consumer does not accept delivery unless it first succeeds in generating theorems, called verification conditions, from the code and assertions and checking that the supplied proof proves these theorems. With CCT, instead of transmitting code explicitly, only assertions and proofs are transmitted to the consumer. If proof checking succeeds, code is then obtained by applying a simple tool called CodeGen to the resulting theory. This paper explains the design and implementation of CCT and shows how it can be used to achieve secure delivery of code with required correctness or safety properties. All the tools used in the verification steps are implemented in Athena, which is both a traditional programming language and a deduction language.
Evaluation of fatty acid amide hydrolase inhibition in murine models of emotionality.

Rationale Manipulations of the endocannabinoid/fatty acid amide hydrolase (FAAH) signaling systems result in conflicting and paradoxical effects in rodent models of emotional reactivity.
Enhanced availability in randomly deployed wireless sensor networks via hybrid uni/omni-directional antennas

Availability is a critical requirement in any modern information system. For many classes of sensor networks, random deployment cannot be avoided and the associated wireless network connectivity characteristics significantly impact system availability. A highly available network must be able to sustain services such as data gathering and event-detection even during link losses owing to reasons that include intermittent interference and network attacks. Improved availability is often achieved by rerouting the traffic along alternative paths. Accordingly, k-connectivity is a key property of highly available networks. In this paper, we analyze k-connectivity of hybrid wireless networks that incorporate both omniand sectorized uni-directional antennas. We present results that help understand the relationship between node density, transmission radius, antenna beam width and the existence of disjoint paths between the networkpsilas member nodes and a sink. Analytical and simulation-based results are provided to motivate the use of this emerging paradigm. We demonstrate that under a broad class of conditions, a hybrid approach significantly improves k-connectivity and has a larger average number of disjoint paths between member nodes and the network sink even at lower node densities and transmission radii.
Fast, deterministic routing, on hypercubes, using small buffers

A deterministic routing scheme for a communications network based on the k-dimensional hypercube is proposed. The author presents two formulations of the scheme. The first formulation delivers messages in O(k/sup 2/) bit times using O(K) bits of buffer space at each node in the hypercube. The second formulation assumes that there are several batches of messages to be delivered, and makes certain assumptions about the cost of sending messages along the various dimensions of the cube. In this case, the latency for delivery time is still O(k/sup 2/) bit times, but the throughput is increased to one set of messages every O(k) bit times. For the first formulation, the author restricts himself to routings which are subsets of permutations (i.e. every node sends at most one message and receives at most one message). The second formulation indicates a way to perform routings which are subsets of H-permutations (i.e. every node sends at most H messages and receives at most H messages). >
A General (Syntactic-Semantic) Approach to Picture Analysis

Many mathematical methods have been proposed for solving pictorial pattern analysis problems [1]. They can be grouped into two major approaches, decision-theoretic or statistical approach and structural or syntactic approach [1–6]. From the point of pictorial view of pattern representation or description, we can discuss picture analysis in terms of single-entity representation versus multiple-entity representation, and suggest a combined syntactic-semantic approach on the basis of using attributed languages.
Area of Origin Protection in Transbasin Diversions: An Evaluation of Alternative Approaches

This article examines the laws that apply to the development of water for use in another water basin. Based on a review of existing laws, it offers a recommended approach
Fuller Usage of Punch-Card Equipment in Social Science Research through Improving Techniques

T HIS paper is primarily concerned with methodology in the use of IBM equipment especially adaptable to social science research. No attempt is made at completeness of treatment. Rather, the discussion is in the nature of a preview. Detailed treatment on specific phases of punchcard techniques will appear in a later series of papers. The methodology described has been developed largely through "trial and error." Procedures recommended, in most instances, have evolved from application of practices now discarded as inadequate and outmoded. In an age of mechanization, IBM offers the "machine way" to research workers. Of concern in the matter of whether or not to adopt the punchcard method is the question of how far machine operations may be substituted for hand work. In the main this involves three factors: (1) techniques to facilitate the transferring of data and coded information from schedules to punch cards; (2) methods of preparing and handling of coding in all its aspects and applications; and (3) procedures insuring the most direct and complete machine sorts and tabulations.
Incidence and Demographic and Tumor Characteristics of HER2-Positive Invasive Breast Cancer in a Large, Unselected Population, 2000-2006.

BACKGROUND: Most HER2 data have been generated from populations of invasive breast cancer (IBC) patients with selected patient and tumor characteristics (clinical trials, referral centers). The average age of women in US adjuvant trastuzumab trials was 49. Pre 2000, clinical trials of adjuvant chemotherapy included 25-40% HER2+ cases. We used an unselected population of women with IBC to estimate the age-specific incidence rates of HER2+ IBC and compare patient and tumor characteristics of HER2+ and HER2- disease.METHODS: Among female members of Kaiser Permanente Northern California (KPNC) 20 years or older (n=1.22 million), we identified all those diagnosed with a new primary IBC in 2000-2006 (n=16,975). During this period, all IBCs were routinely tested for HER2 by KPNC9s regional IHC laboratory (center of excellence for HercepTest, CLIA licensed and CAP certified) and those that were IHC 2+ were sent for FISH testing; IHC 3+ or IHC 2+/FISH+ (ratio ≥ 2.0) were considered HER2+. Demographic and tumor characteristics were derived from the KPNC tumor registry. *Complete HER2 testing available for 94% of IBCs.RESULTS: Incidence of HER2+ IBC increased less dramatically with age and peaked 20 years earlier than incidence of all IBC (Table 1). Among those with IBC, the percent that were HER2+ decreased with age. Of all HER2+ IBCs, 69% were ≥50 years old and 42% were ≥60 years old.The percent of tumors that were HER2+ increased with stage (local=11%, regional=18%, distant =25%), tumor differentiation (well =2%, moderate =12%, poor=26%, undifferentiated=30%), and generally with size ( 5 cm=20%). ER- and PR- tumors were more likely to be HER2+ (of all ER- tumors, 29% were HER2+; of all PR- tumors, 25% were HER2+; of all ER+ tumors, 10% were HER2+; of all PR+ tumors, 9% were HER2+). Among all IBC patients, percent of disease that was HER2+ was highest for Asians (20%) and lowest for Caucasians (12%).CONCLUSION: In a large, unselected, population of invasive breast cancer patients, the incidence of HER2+ disease was highest among women aged 60-69 years. Among breast cancer patients, HER2+ disease was highest in Asians. The percent HER2+ was 13.6% for all breast cancer patients in this population based cohort and highest (24.7%) in the 20-39 year age group. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3058.
Preparation and Property of Xylan/Poly(Methacrylic Acid) Semi-Interpenetrating Network Hydrogel

Xylan/poly(methacrylic acid) semi-interpenetrating network hydrogels were synthesized, and these hydrogels were fabricated using various ratios of xylan and methacrylic acid and cross-linked by N,N′-methylenebisacrylamide. The chemical structure and morphology of the prepared hydrogels were characterized by FT-IR spectroscopy and SEM analysis. The porous structure of the prepared hydrogels was found, and the interconnected porous channels increased when the content of xylan was increased in the hydrogels. The hydrogels presented excellent pH sensitivity and swelling reversibility. The dynamic swelling kinetics were also studied, and all obtained results indicated that the prepared xylan/poly(methacrylic acid) semi-IPN hydrogel could be used in biomedical fields, especially for drug release.
Overcoming the MUM effect in it project reporting: The effect of time pressure and blame shifting

Troubled projects are a common problem in the information systems field. While there is a natural reluctance to report the actual status of a troubled project, doing so is sometimes the only way th...
Equilibrium Folding of an Individual Bacteriorhodopsin into and out of its Native Lipid Bilayer Resolves Energy Landscapes and Hidden Dynamics

In protein folding, the complete characterization of all a protein's folding intermediates and their dynamics is an essential prerequisite to developing an accurate model. An over-simplified view of folding processes emerges if briefly populated states and their dynamics remain undetected due to ensemble averaging and/or limited instrumental precision. We studied the folding of individual bacteriorhodopsins embed in their native lipid bilayer using cantilevers optimized for force spectroscopy with ∼1-µs resolution. Improving temporal resolution has led not only to newly resolved intermediates and pathways, but also to new dynamics between states. For example, the number of detected intermediates in a pair of transmembrane helices increased from 2 to 14, and helix segments were observed to refold against high forces (F=60-140 pN) at standard pulling rates (v=0.1-5 µm/s). True equilibrium measurements characterized the extraction and insertion of small sections of different transmembrane helices. Cooperative folding and unfolding of a 3-amino-acid structural element was resolved in <15 μs at the C-terminal end of helix E. The transition's underlying energy landscape was deduced using a recently developed reconstruction method based on pfold analysis, from which the water-to-bilayer folding free energy of hydrophobic helices were obtained. Similar back-and-forth transitions were observed within a portion of the folding pathway of helix A. These observations provide direct evidence that transmembrane helix segments can dynamically equilibrate between the aqueous and membrane phases, which has been proposed to play important roles in helix cotranslational integration via translocon. Our results demonstrate a new regime in studies of protein-folding dynamics: equilibrium folding and unfolding at 1-µs resolution. Moreover, we applied this technique to the important problem of measuring a membrane protein fold into its native membrane environment.
A Case of Sweet’s Syndrome in a Young Child

A 2 years and 7 months old boy had presented with abrupt onset of red edematous papules and plaques on his face,neck and back of hand for two weeks. Histopathologic examination of the lesion showed edema of upper dermis and a diffuse neutrophilic infiltrate with nuclear dust in upper and middle dermis. The child was diagnosed as Sweet’s syndrome. Glucocorticosteroid had a good effect on him.
Computational Modeling of Small Molecule Ligand Binding Interactions and Affinities

Understanding and controlling biological phenomena via structure-based drug screening efforts often critically rely on accurate description of protein-ligand interactions. However, most of the currently available computational techniques are affected by severe deficiencies in both protein and ligand conformational sampling as well as in the scoring of the obtained docking solutions. To overcome these limitations, we have recently developed MedusaDock, a novel docking methodology, which simultaneously models ligand and receptor flexibility. Coupled with MedusaScore, a physical force field-based scoring function that accounts for the protein-ligand interaction energy, MedusaDock, has reported the highest success rate in the CSAR 2011 exercise. Here, we present a standard computational protocol to evaluate the binding properties of the two enantiomers of the non-selective β-blocker propanolol in the β2 adrenergic receptor's binding site. We describe details of our protocol, which have been successfully applied to several other targets.
“Sudden holes” in time: the epistemology of temporality

“Eternity is a damned hole. It's time that you need.” The Secret Agent Throughout his works, Conrad is concerned with various objects of consciousness. In addition to events, physical objects, and human subjects, he also investigates the human experience of time and its relationship to knowledge of the external world. J. M. Kertzer argues, “For Conrad, time is always in some sense ‘human time’ … The world empty of human activity and judgment is a timeless void.” As was true of objects, subjects, and events, Conrad identifies a gap between objectivity and subjectivity when experiencing time because time can only be accessed through human consciousness. Using impressionist techniques, Conrad considers how human beings experience time in an individual and contextualized manner. Furthermore, he inquires into the relationship between western civilization and the human experience of time. In his inquiry, Conrad considers three different temporal representations: human time, mechanical time, and narrative time. He investigates each of these – and more important how they interrelate. In particular, the relationship between human time and mechanical time attracts much of his attention. Conrad associates human time with the primitive and mechanical time with the civilized, and as is true of primitive and civilized perception in general, primitive time is time experienced without cultural influence, while civilized time is time experienced with cultural influence. Human time appears in two forms in Conrad's works: personal time and cyclical time, and both blur the boundaries between subject, time, and context.
Time-Minimal Motion: Basics

We have seen in Chap. 2 that the visibility graph plays an important role in planning shortest paths among stationary obstacles in a two-dimensional world. In this chapter, we study the concept of accessibility (Fujimura and Samet 1988), which is a generalization of the concept of visibility. Making use of accessibility, we define a graph called the accessibility graph to represent moving objects for the purpose of planning the motion of a robot. The robot is assumed to be a point that moves in a two-dimensional world in which polygonal obstacles, as well as the destination point, are in motion. The accessibility graph is shown to be a generalization of the visibility graph in the sense that paths to the destination point are found as sequences of edges of the graph. In fact, when all the obstacles have zero velocity, the accessibility graph becomes the visibility graph of these polygonal obstacles. More importantly, if the robot is able to move faster than any of the obstacles, then the graph exhibits a property: a time-minimal motion is represented as a sequence of edges of the accessibility graph. In this chapter, we describe an algorithm for generating a time-minimal motion, prove its timeminimality, and analyze its execution time. The utility of the concept of accessibility is further demonstrated in Chap. 4 and Chap. 5 by solving a number of motion planning problems in dynamic domains.
A Center-Level Approach to Estimating the Effect of Center Characteristics on Center Outcomes

This paper introduces a center-level approach to estimating the effect of center characteristics on outcomes. The proposed method applies to studies where the effect of center characteristics is of primary focus and centers rather than individual patients are entities of interest. Although these studies focus on practices and policies at the center level, it is important to account for the differences in outcomes due to varying patient case-mix. The proposed approach includes two steps. The first step estimates the effect of patient-level characteristics on outcomes so that the variability in patient case-mix can be adjusted prior to estimating the effect of center-level factors. The second step aggregates outcomes (adjusted for patient-level factors) of patients from the same center into a distribution of outcomes representing the response for each center. The outcome distributions are multi-valued responses on which the effects of center-level characteristics are modeled using a symbolic data framework. This method can be used to model the effect of center characteristics on the center-mean outcome as well as the within-center outcome variance. It models the effect of patient characteristics at the patient level and the effect of center characteristics at the center level. The method performs well even when the data come from a classical linear regression model or from a linear mixed effect model. The proposed approach is illustrated using a bone marrow transplant example.
Final Results of Lower Dose Fludarabine (F) and Cyclophosphamide (C), and High Dose Rituximab (R), (FCR-Lite) for Patients with Untreated Chronic Lymphocytic Leukemia (CLL).

Introduction Standard FCR therapy in untreated CLL patients (F-25 mg/m 2 d1–3 q 4wk; C-250 mg/m 2 d 1–3 q 4wk; R-500 mg/m 2 d1 q 4wk for 6 cycles) was reported to have complete remissions (CR) of 70% and overall responses (OR) of 95% (J Clin Oncol2005;23:4079). The major toxicity was grade 3/4 neutropenia during 52% of treatment courses. One approach to decrease neutropenia without compromising efficacy could be by reducing the doses of F and C and increasing the dose of R. Methods We conducted a phase II study for previously untreated advanced CLL patients treated with FCR-Lite (F-20mg/m 2 d1–3 q 4 wk; C-150 mg/m 2 d1–3 q 4 wk; R-500mg/m 2 d1 and d14 q 4wks; maintenance R-500 mg/m 2 ×1 q 3 months until progression). A Simon two-stage design was used where 15 patients were accrued in the first stage and because of acceptable toxicity and response rate in stage I an additional 35 patients were treated. The primary endpoint was response rate. Results A total of 50 patients were entered into this study and 42 are currently evaluable. There were 29 male and 13 female patients with an age range of 36–85 years (median 58) treated with a total of 236 courses of FCR-Lite. All 42 patients were evaluable for toxicity. Grade 3/4 neutropenia occurred during 29 (12%) courses with two episodes of neutropenic fever. One patient had cellulitis, another had pneumonia (not neutropenic). Grade 3/4 thrombocytopenia occurred during 7 (3%) courses and grade III/IV anemia during 6 (2.5%) courses. Among the 40 evaluable patients for response, the CR rate was 85%, PR rate was 15% with an OR rate of 100%. All of the CR patients were tested by flow cytometry and had + /CD19 + cells in their bone marrow after therapy. One patient with potential CR was excluded due to the absence of follow up bone marrow biopsy. Minimal residual disease (MRD) was tested by four color flow cytometry (sensitivity 0.01%) in 8 patients with CR (Genzyme Genetics Corp.). Seven had no evidence of MRD at 7, 8, 8, 14, 22, 25 and 30 months respectively, post CR, and one patient had 0.03% and 0.06% when tested at 12 and 18 months post CR respectively. Conclusions Our results in 42 patients suggest FCR-Lite is highly effective with considerably less grade 3/4 neutropenia than standard FCR. Complete responders had no detectable CD5+/CD19+ cells in their bone marrow following FCR-Lite. MRD testing is currently underway for all patients.
In Vivo and In Vitro Analysis of an Aγ-Globin Gene Silencer in Human β-Yac Transgenic Mice.

Abstract Autonomous silencing of gene expression is one mechanism operative in the control of human β-like globin gene switching and is best exemplified by the e-globin gene. Experiments using variously truncated Aγ-globin genes linked to LCR sequences suggested that a region of the Aγ-globin gene between −730 to −378 relative to the mRNA CAP site may function as an adult stage-specific silencer element. A 5.4 Kb marked Aγ-globin gene (Aγm) inserted between LCR 5′HS1 and the e-globin gene in a β-YAC (Aγm 5′ e β-YAC) was silenced in transgenic mice during adult definitive erythropoiesis, even in the absence of an adult β-globin gene. In contrast, when a marked β-globin gene (βm) was inserted in this same location in another β-YAC (βm 5′ e β-YAC), the βm-globin gene was expressed throughout ontogeny. From these data we concluded that: 1) any gene located near the LCR will be strongly expressed throughout ontogeny, unless some gene-specific silencing mechanism exists, 2) competition between the γ- and β-globin genes for interaction with the LCR is not the exclusive mechanism controlling γ- to β-globin gene switching, and 3) that the Aγm-globin gene was autonomously silenced. A -730 to -378 deletion of the Aγm-globin gene was introduced into the Aγm 5′ e β-YAC via homologous recombination to produce a Δ1s Aγm 5′ e β-YAC. This YAC was microinjected and six founders were obtained. Four transgenic lines were established carrying at least one full-length β-globin locus and two were established that lacked the adult β-globin gene. All founders containing an intact β-globin gene expressed the Δ1s Aγm-globin during adult erythropoiesis (45% – 122% relative to human β-globin expression). In one line examined in detail, the Δ1s Aγm-globin gene was expressed in the embryonic yolk sac, fetal liver, and adult blood. e-globin gene expression was not detected in the embryonic yolk sac and expression of the normally located γ-globin genes was not observed at any developmental stage. β-globin gene expression was observed in the fetal liver and adult blood, although its expression was decreased. To further delineate the function of the Δ1s fragment, transient transfection assays to test silencer function and protein-DNA interaction assays were performed. Silencer activity of the352 bp Δ1s fragment was examined using a series of pGL2 luciferase reporter plasmids that were synthesized to include the Δ1s fragment; these were electroporated into various cells. Electrophoretic mobility shift assays (EMSAs) and DNAse I footprinting were employed to begin assessment of protein binding within the Δ1s fragment. A 50 bp DNA fragment spanning −713 to −664 of the Δ1s element was used in EMSAs; DNA binding activity was observed in K562 nuclear extracts. These preliminary data suggest that the −730 to −378 γ-globin gene silencer binds a repressor protein complex.
Self-reported Receipt of Dilated Fundus Examinations Among Patients With Diabetes: Medicare Expenditure Panel Survey, 2002–2013

Purpose To evaluate self-reported adherence to diabetic retinopathy screening examinations among diabetic subjects. Design Retrospective, population-based cross-sectional study. Methods Medical Expenditure Panel Survey (MEPS) consolidated full-year and prescribed drugs data from 2002–2013 were reviewed; multivariable logistic regression was used to identify patient characteristics as potential barriers to receiving examinations. Results Of 13 299 persons in the MEPS sample, only 39.62% (95% confidence interval [CI] 38.56%–40.67%) reported receiving annual dilated eye examinations, and 90.31% (CI 89.70%–90.91%) reported ever having received an eye examination. Significant factors related to ever receiving an eye examination included completed high school (odds ratio [OR] = 1.53; CI, 1.33–1.75), bachelor's degree or higher (OR = 1.94; CI, 1.56–2.41), private health insurance (OR = 2.07; CI, 1.70–2.52), public insurance (OR = 1.90; CI, 1.56–2.31), household income >400% of the poverty threshold (OR = 1.75; CI, 1.36–2.25), prescribed diabetes medication (OR = 1.45; CI, 1.27–1.65), diabetic kidney disease (OR = 1.31; CI, 1.08–1.59), prior foot examination (OR = 1.49; CI, 1.28–1.74), prior hemoglobin A1c test (OR = 1.45; CI, 1.28–1.64), and having a usual care provider (OR = 1.50; CI, 1.25–1.80). Self-reported Asian ethnicity (OR = 0.51; CI, 0.39–0.65), needing assistance for at least 3 months (OR = 0.79; CI, 0.62–1.00), and proxy needed to fill out the survey (OR = 0.72; CI, 0.61–0.85) were associated with lower odds of reporting ever having received a dilated eye examination. Conclusions In this national-representative sample, 90.31% of patients with diabetes reported ever having a dilated eye examination; only 39.62% reported receiving one annually as recommended. These low rates appear associated with possibly modifiable factors, including having a regular care provider, increasing access to care, enrollment in health insurance, and higher education.
Abstract 2502: Liquid diet introduction of tracers into mice for stable isotope-resolved metabolomics (SIRM) investigations

Tracer-based mapping of metabolic networks in vivo is a powerful approach for revealing metabolic reprogramming in human cancer. However, current in vivo labeling techniques for model animals face important challenges including insufficient depth of pathway coverage (e.g. inability to detect labeled nucleotides, proteins, and lipids) and stress-related artifacts. Here, we report stress-free administration of 13C6-glucose via liquid diet into mice. 13C enrichment was observed in metabolites of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, as well as macromolecules glycogen, lipids, and proteins from major organs in NSG mice. We have applied the liquid diet method to map the glucose metabolic networks in NSCLC tumors in a patient-derived xenograft (PDX) model. We observed a high enrichment in the metabolites of glycolysis, Krebs cycle, and PPP as well as de novo synthesized nucleotides and amino acids by IC-UHR-FTMS analysis. Lung PDX displayed unexpected metabolic complexity, such as the use of pyruvate to fuel anaplerosis as well as gluconeogenesis. We also found high 13C enrichment in both tumor and plasma glutamine, which implies that glutamine in the PDX tumors largely came from other organs via the blood rather than being synthesized in situ. Our data showed that liquid diet is an effective and noninvasive means for comprehensive analysis of glucose-associated metabolic networks in human tumor xenografts, which can also be extended to SIRM studies with other fuel sources. Acknowledgements: This work was supported in part by grants: 1R01ES022191-01 (to TWMF and RMH), 1P01CA163223-01A1 (to ANL and TWMF), and 1U24DK097215-01A1 (to RMH, TWMF, and ANL) R.C. Sun was supported by a T32 training grant to M. Vore (5T32ES007266-25) Citation Format: Ramon C. Sun, Marc O. Warmoes, Ye Yang, Pan Deng, Qiushi Sun, Andrew N. Lane, Richard M. Higashi, Teresa W-M Fan. Liquid diet introduction of tracers into mice for stable isotope-resolved metabolomics (SIRM) investigations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2502. doi:10.1158/1538-7445.AM2017-2502
Incidents and Accidents: The Way of the Single Event Tester

When performing a single event effect (SEE) test during a test campaign, flexibility and out of the box thinking is often required for unexpected and unplanned events.