cssi/SciSciGPT-SciSciNet huggingface dataset:
UDP-glucose 6-dehydrogenase regulates hyaluronic acid production and promotes breast cancer progression

An improved understanding of the biochemical alterations that accompany tumor progression and metastasis is necessary to inform the next generation of diagnostic tools and targeted therapies. Metabolic reprogramming is known to occur during the epithelial-mesenchymal transition (EMT), a process that promotes metastasis. Here, we identify metabolic enzymes involved in extracellular matrix remodeling that are upregulated during EMT and are highly expressed in patients with aggressive mesenchymal-like breast cancer. Activation of EMT significantly increases production of hyaluronic acid, which is enabled by the reprogramming of glucose metabolism. Using genetic and pharmacological approaches, we show that depletion of the hyaluronic acid precursor UDP-glucuronic acid is sufficient to inhibit several mesenchymal-like properties including cellular invasion and colony formation in vitro, as well as tumor growth and metastasis in vivo. We found that depletion of UDP-glucuronic acid altered the expression of PPAR-gamma target genes and increased PPAR-gamma DNA-binding activity. Taken together, our findings indicate that the disruption of EMT-induced metabolic reprogramming affects hyaluronic acid production, as well as associated extracellular matrix remodeling and represents pharmacologically actionable target for the inhibition of aggressive mesenchymal-like breast cancer progression.
“Tell Me About Your Picture”: Using Drawings to Support Expressive Language in Children With Autism Spectrum Disorder:

Thirty-one children with and without autism spectrum disorder were asked to draw the meaning of 10 basic concepts. Following each drawing, children explained their drawing to the experimenter. Tran...
4D- quantitative structure-activity relationship modeling: making a comeback

Introduction: Predictive Quantitative Structure-Activity Relationship (QSAR) modeling has become an essential methodology for rapidly assessing various properties of chemicals. The vast majority of these QSAR models utilize numerical descriptors derived from the two- and/or three-dimensional structures of molecules. However, the conformation-dependent characteristics of flexible molecules and their dynamic interactions with biological target(s) is/are not encoded by these descriptors, leading to limited prediction performances and reduced interpretability. 2D/3D QSAR models are successful for virtual screening, but typically suffer at lead optimization stages. That is why conformation-dependent 4D-QSAR modeling methods were developed two decades ago. However, these methods have always suffered from the associated computational cost. Recently, 4D-QSAR has been experiencing a significant come-back due to rapid advances in GPU-accelerated molecular dynamic simulations and modern machine learning techniques. Areas covered: Herein, the authors briefly review the literature regarding 4D-QSAR modeling and describe its modern workflow called MD-QSAR. Challenges and current limitations are also highlighted. Expert opinion: The development of hyper-predictive MD-QSAR models could represent a disruptive technology for analyzing, understanding, and optimizing dynamic protein-ligand interactions with countless applications for drug discovery and chemical toxicity assessment. Therefore, there has never been a better time and relevance for molecular modeling teams to engage in hyper-predictive MD-QSAR modeling.
Clinical studiesNeurological assessment

Neurological assessment of certain movement disorders is described with emphasis on Parkinson's disease. In addition, abnormal behavior and changes in affect are given. Changes in neurological status, i.e., Bradykinesia, rigidity, gait changes, handwriting irregularity, postural reflexes are outlined. The differential diagnosis of the disease is also indicated in addition to prognosis and to the biochemical correlates of Parkinson's disease.
The Eris/Dysnomia system I: The orbit of Dysnomia

Abstract We present new results on the Eris/Dysnomia system including analysis of new images from the WFC3 instrument on the Hubble Space Telescope (HST). Seven HST orbits were awarded to program 15171 in January and February 2018, with the intervals between observations selected to sample Dysnomia over a full orbital period. Using relative astrometry of Eris and Dysnomia, we computed a best-fit Keplerian orbit for Dysnomia. Based on the Keplerian fit, we find an orbital period of 15.785899±0.000050 days, which is in good agreement with recent work. We report a non-zero eccentricity of 0.0062 at the 6.2-σ level, despite an estimated eccentricity damping timescale of ≤17 Myr. Considering the volumes of both Eris and Dysnomia, the new system density was calculated to be 2.43±0.05 g cm−3, a decrease of ~4% from the previous value of 2.52±0.05 g cm−3. The new astrometric measurements were high enough precision to break the degeneracy of the orbit pole orientation, and indicate that Dysnomia orbits in a prograde manner. The obliquity of Dysnomia's orbit pole with respect to the plane of Eris' heliocentric orbit was calculated to be 78.29±0.65∘ and is in agreement with previous work; the next mutual events season will occur in 2239. The Keplerian orbit fit to all the data considered in this investigation can be excluded at the 6.3-σ level, but identifying the cause of the deviation was outside the scope of this work.
Few-nucleon matrix elements in pionless effective field theory in a finite volume

Pionless effective field theory in a finite volume (${\mathrm{FVEFT}}_{\overline{)\ensuremath{\pi}}}$) is investigated as a framework for the analysis of multinucleon spectra and matrix elements calculated in lattice QCD (LQCD). By combining ${\mathrm{FVEFT}}_{\overline{)\ensuremath{\pi}}}$ with the stochastic variational method, the spectra of nuclei with atomic number $A\ensuremath{\in}{2,3}$ are matched to existing finite-volume LQCD calculations at heavier-than-physical quark masses corresponding to a pion mass ${m}_{\ensuremath{\pi}}=806\text{ }\text{ }\mathrm{MeV}$, thereby enabling infinite-volume binding energies to be determined using infinite-volume variational calculations. Based on the variational wave functions that are constructed in this approach, the finite-volume matrix elements of various local operators are computed in ${\mathrm{FVEFT}}_{\overline{)\ensuremath{\pi}}}$ and matched to LQCD calculations of the corresponding QCD operators in the same volume, thereby determining the relevant one- and two-body effective field theory counterterms and enabling an extrapolation of the LQCD matrix elements to infinite volume. As examples, the scalar, tensor, and axial matrix elements are considered, in addition to the magnetic moments and the isovector longitudinal momentum fraction.
The Central Scientific Company and its Apparatus

Look along the shelves holding your laboratory apparatus and into the demo-prep room, and you will find apparatus by “Cenco” and “The Central Scientific Company” sharing space with your new PASCO equipment. At the 1989 AAPT meeting in San Luis Obispo I was asked to talk about Cenco in honor of one of its long-term employers and innovators, Paul E. Klopsteg, and I was hard put to limit my talk to the allotted 55 minutes. (It was one of our best meetings ever, and many wished that there were openings for us at the California Polytechnic State University!) In this article I want to remember the company and the apparatus that it made and sold.
Metabolic Adaptations to Weight Loss: Relative Changes in Resting Metabolic Rate and Energy Expenditure for Physical Activity and Association With Weight Loss Maintenance

Objectives There is persistent controversy over the extent to which different components of energy expenditure disproportionately decrease after weight loss and contribute to weight regain through decreased energy requirements. We conducted a secondary analysis of the CALERIE I study to test the hypothesis that decreased resting metabolic rate (RMR) and energy expenditure for physical activity (EEPA) after a 6-month calorie restriction intervention would predict weight regain at 12 months, with a greater decrease in RMR than EEPA.
Intrinsic and growth-mediated cell and matrix specialization during murine meniscus tissue assembly

The incredible mechanical strength and durability of mature fibrous tissues and their extremely limited turnover and regenerative capacity underscores the importance of proper matrix assembly during early postnatal growth. In tissues with composite extracellular matrix (ECM) structures, such as the adult knee meniscus, fibrous (Collagen-I rich), and cartilaginous (Collagen-II, proteoglycan-rich) matrix components are regionally segregated to the outer and inner portions of the tissue, respectively. While this spatial variation in composition is appreciated to be functionally important for resisting complex mechanical loads associated with gait, the establishment of these specialized zones is poorly understood. To address this issue, the following study tracked the growth of the murine meniscus from its embryonic formation through its first month of growth, encompassing the critical time-window during which animals begin to ambulate and weight bear. Using histological analysis, region specific high-throughput qPCR, and Col-1, and Col-2 fluorescent reporter mice, we found that matrix and cellular features defining specific tissue zones were already present at birth, before continuous weight-bearing had occurred. These differences in meniscus zones were further refined with postnatal growth and maturation, resulting in specialization of mature tissue regions. Taken together, this work establishes a detailed timeline of the concurrent spatiotemporal changes that occur at both the cellular and matrix level throughout meniscus maturation. The findings of this study provide a framework for investigating the reciprocal feedback between cells and their evolving microenvironments during assembly of a mechanically robust fibrocartilage tissue, thus providing insight into mechanisms of tissue degeneration and effective regenerative strategies.
Implicit ruminations

Various points of agreement and disagreement with the two target papers are indicated. Support is voiced for Dienes and Berry’s (1997) argument that the implicit-explicit dissociation should be determined by invoking subjective criteria and for Neal and Hesketh’s (1997) outlining of the problems associated with the very concept of consciousness. However, criticisms are offered for Neal and Hesketh’s proffered solution to that problem and their unhappy decision not to include the transfer literature, and for the failure of the authors of both papers to recognize the importance of neurocognitive evidence.
Cultivating Medical Education Research Mentorship as a Pathway Towards High Quality Medical Education Research

The lack of effective and consistent research mentorship and research mentor training in both undergraduate medical education (UME) and graduate medical education (GME) is a critical constraint on the development of innovative and high quality medical education research. Clinical research mentors are often not familiar with the nuances and context of conducting education research. Clinician-educators, meanwhile, often lack the skills in developing and conducting rigorous research. Mentors who are not prepared to articulate potential scholarship pathways for their mentees risk limiting the mentee’s progress in early stages of their career. In fact, the relative paucity of experienced medical education research mentors arguably contributes to the perpetuation of a cycle leading to fewer well-trained researchers in medical education, a lack of high quality medical education research, and relative stagnation in medical education innovation. There is a path forward, however. Integration of doctoral-level educators, structured inter-departmental efforts, and external mentorship provide opportunities for faculty to gain traction in their medical education research efforts. An investment in medical education research mentors will ensure rigorous research for high quality innovation in medical education and patient care.
MI-PVT: A Tool for Visualizing the Chromosome-Centric Human Proteome.

We have developed the web-based Michigan Proteome Visualization Tool (MI-PVT) to visualize and compare protein expression and isoform-level function across human chromosomes and tissues (http://guanlab.ccmb.med.umich.edu/mipvt). As proof of principle, we have populated the tool with Human Proteome Map (HPM) data. We were able to observe many biologically interesting features. From the vantage point of our chromosome 17 team, for example, we found more than 300 proteins from chromosome 17 expressed in each of the 30 tissues and cell types studied, with the highest number of expressed proteins being 685 in testis. Comparisons of expression levels across tissues showed low numbers of proteins expressed in esophagus, but esophagus had 12 cytoskeletal proteins coded on chromosome 17 with very high expression (>1000 spectral counts). This customized MI-PVT should be helpful for biologists to browse and study specific proteins and protein data sets across tissues and chromosomes. Users can upload any data of int...
Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist

In the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF in an HPLC injector loop to produce the radiotracer in a good yield (6 ± 3% uncorrected radiochemical yield) and high specific activity (143 ± 90 GBq·µmol-1 at end-of-synthesis). PET imaging of normal rats revealed rapid brain uptake at baseline (0.37 ± 0.08% ID/cc (percent of injected dose per cubic centimeter) at peak, 15-60 s), which was followed by fast washout. After pretreatment with isradipine (2 mg·kg-1, i.p.), whole brain radioactivity uptake was diminished by 25%-40%. This preliminary study confirms that [11C]isradipine can be synthesized routinely for research studies and is brain penetrating. Further work on Ca2+-channel radiotracer development is planned.
Laboratory Verification of the Optical Turbulence Sensor (OTS): Particulate Volume Scattering Function and Turbulence Properties of the Flow

Abstract : Our goal is an extensive tank validation of the Optical Turbulence Sensor (OTS). This sensor uses a Hartman optical wavefront sensor to determine turbulence characteristics and to characterize the particulate field. The OTS has recently undergone successful field testing. The ocean trials indicate that the OTS surpasses in many ways current microstructure based instruments to quantify turbulence. Furthermore, it is able to measure particles. As is natural for a novel measurement, a number of questions have arisen with respect to both turbulence measurements and the particle characterization that we address in our effort. We have two-fold objectives: Particle field characterization: We plan to develop new methods to fully exploit the raw OTS images, including the projection flow velocity and the near-forward Volume Scattering Function (VSF) of particles that cross the light path. From the measured VSF (Volume Scattering Function) at small angles we can recover the particle size distribution from the field data for larger particles (>100 microns). The simultaneous measurement of the particle size distribution and the flow velocity, using a single instrument, allows for unprecedented determination of particle volume transport on very small scales and turbulence /particle interaction. Turbulence characterization: In this part of the effort we plan to compare independent and highly accurate thermistor and Particle Imaging Velocimetry (PIV) measurements of the Turbulent Kinetic Energy dissipation rate and the temperature dissipation rate with concurrent OTS measurements of the same variables. The studies will be performed in well-controlled tank experiments in the lab. The comparisons will allow detailed characterization of the OTS, including its sensitivity and the applicability of the assumptions of isotropy and homogeneity used in the data processing.
Linear filtering and nonlinear fuzzy logic filtering for sample identification with Raman spectroscopy

Raman spectroscopy provides detail information on molecular structure and chemical composition of the samples. It can be used to characterize the normal issue and the malignant tissue for decision-making and medical diagnosis. The goal in this research is to eliminate the noise to an acceptable level. This article is also about some preliminary work of Raman signal processing for sample identification. The whole procedure includes spectrum capturing by Raman spectrometer, spectrum calibration, slowly varying noise filtering using linear least squares estimation, fast varying noise filtering using nonlinear fuzzy control. The long-term objective is to create a real-time approach for sample analysis using a Raman spectrometer directly mounted at the end-effector of the medical robot, which enhances the remote controlled robot strategy.
Postoperative Rehabilitation and Return to Play After Anterior Cruciate Ligament Reconstruction

An anterior cruciate ligament (ACL) disruption of the knee can be a devastating injury to the athletes, as they are faced with possible reconstructive surgery and the extensive months of physical rehabilitation that follows. Within the first postoperative year, many athletes are unable to return to their previous level of athletic performance and some athletes are unable to return to play at all. Strength and Conditioning (S&C) Professionals utilize specific exercises and training principles to enhance an athlete’s athletic performance in the arena of competition. As a major component of the ACL rehabilitation process involves the implementation of exercises for the athlete to execute, these S&C exercises and training principles should also be a consideration for utilization by the rehabilitation professional during the ACL rehabilitation. These S&C exercises and training principles may not only assist in a desired return-to-play outcome, but would also familiarize or refamiliarize the athletes with the training program design that may be instituted during their off-season athletic performance-enhancement training.
Restoration and enhancement of arbitrary finite-energy images from incomplete spatial and spectral information

In this paper we extend the generalized image restoration theory developed by Youla (1) to arbitrary L 2 (i.e., square-integrable) images or signals. Specifically we furnish recursive algorithms to restore images from (1) extended segments and low-pass spectra and (2) short segments and high-pass spectra. We also assert that it is not possible to restore an arbitrary image from only its low-pass spectrum and a short segment.
Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae.

The soh1, soh2 and soh4 mutants were isolated as suppressors of the temperature-dependent growth of the hyperrecombination mutant hpr1 of Saccharomyces cerevisiae. Cloning and sequence analysis of these suppressor genes has unexpectedly shown them to code for components of the RNA polymerase II transcription complex. SOH2 is identical to RPB2, which encodes the second largest subunit of RNA polymerase II, and SOH4 is the same as SUA7, encoding the yeast transcription initiation factor TFIIB. SOH1 encodes a novel 14-kD protein with limited sequence similarity to RNA polymerases. Interestingly, SOH1 not only interacts with factors involved in DNA repair, but transcription as well. Thus, the Soh1 protein may serve to couple these two processes. The Soh1 protein interacts with a DNA repair protein, Rad5p, in a two-hybrid system assay. Soh1p may functionally interact with components of the RNA polymerase II complex as suggested from the synthetic lethality observed in soh1 rpb1Δ104, soh1 soh2-1 (rpb2), and soh1 soh4 (sua7) double mutants. Because mutations in SOH1, RPB2 and SUA7 suppress the hyperrecombination phenotype of hpr1 mutants, this suggests a link between recombination in direct repeats and transcription.
The Standardization of the Van Den Bergh Reaction for Serum Bilirubin

Using commercially available bilirubin preparations, calibration curves for the van den Bergh reaction were obtained that differed significantly from many previously reported, The bilirubin preparations used were not considered the cause. Rather the indicator properties of azobilirubin and the instability of bilirubin pigment in conventionally employed solvents appear to account for the differences noted.
Barriers Operating in the Present: A Way to Rethink the Licensing Exception for Teacher Credentialing Examinations

Notwithstanding Title VII legal remedies, structural barriers have driven many teachers of color out of the workforce in recent decades. Legislative changes in education policy — particularly The No Child Left Behind Act — have exacerbated the problem, notably by mandating teacher certification exams. These exams often can generate adverse outcomes disproportionately for teachers of color. Many teachers suing under a Title VII disparate impact claim, however, cannot name states — the actors that create and promulgate the tests — as defendants because of the way courts have interpreted Title VII’s employment relationship requirement. This Note proposes a framework that involves a real-world analysis of the extent to which states control local school governance. This framework encourages courts to allow state-defendants in these Title VII disparate impact claims when the test at issue is a state-mandated teacher certification test.
Growth of mallards fed phosphamidon for 13-day periods during three different developmental stages

Abstract Mallard ducklings ( Anas platyrhynchos ) were exposed to a 13-day dietary treatment of 0, 0·5 or 5·0 ppm phosphamidon at one of three successive age intervals (5–17 days, 18–30 days, or 31–43 days) during a 10-week growth period. Weekly measurements of body weight, wing length, primary feather length, and bill length revealed slower development of primary feathers in those birds treated from 5 to 17 days; treatment effects on body weight and wing length from 6 to 8 weeks of age were observed among those birds treated from 18 to 30 days of age. Some differences in growth patterns among birds treated with the same phosphamidon level, but at different growth stages, were attributed to the varying size of the group with which a duckling was housed at different times in the growth process. No brain cholinesterase depression was observed in any group either 24h after phosphamidon treatment was terminated or at 10 weeks of age.
Intermediate mass fragments emitted in the reaction Ag+14N at 100, 160 and 250 MeV bombarding energy☆

Abstract The fragments produced in the reaction between a 14 N beam of various energies and a natural Ag target have been studied. The atomic numbers of the fragments have been identified up to Z = 17 by means of a E - ΔE counter telescope. The cross sections, the kinetic energy distributions as well as the angular distributions have been measured for each atomic number. The kinetic energy distributions show two components: a high-energy component (quasi-elastic), prevailing at angles close to the grazing angles and for atomic numbers close to Z = 7, and a low-energy component (relaxed), at energies close to the Coulomb repulsion energy, present at all angles and for all the Z . A detailed study of the relaxed components of the kinetic energy seems to account for both them means and the widths of these distributions on a purely statistical basis. The cross sections of the relaxed components appear to be quite large at low Z and to decrease rapidly to a fairly constant value in the region of 10 ≦ Z ≦ 17. A marked even-odd alternation in the cross sections is observed. The angular distributions are strongly forward peaked for Z Z > 7 the forward peaking decreases rapidly until, for Z > 13, the limiting form 1/sin θ is attained. Evidence for the existence of a diffusion process along the mass asymmetry coordinate is discussed.
ATM Gene Variations Predict Differences in Pretreatment Lung Inflammation in Non-Small Cell Lung Cancer (NSCLC) Patients

repopulation kinetics. Analyses utilized WT C57Bl/6 mice and B6.S129 p21-/mice. Results: We found that LCs do not undergo apoptosis following IR as do other DC subsets, but instead persist and migrate to skin-draining lymph nodes. Subsequent analysis in migration deficient CCR7-/mice revealed a constant number of epidermal LCs, indicating that changes in LC number following IR is due solely to migration and not to cell death. Further, the percentage of BrdU+ LCs doubles in the epidermis by day 7, contributing to full LC repopulation at day 14-post IR. Moreover, we show for the first time that LCs are resistant to the formation of DNA damage as measured by induction of H2AX foci and COMET assay. In contrast, other members of the myeloid lineage, notably lymphoid tissue-resident DCs, are exquisitely sensitive to IR-induced DNA damage. In addition, both steady state and post-lethal IR LCs express a unique repertoire of pro-survival and stress related proteins (Foxo3, p21, Bcl-xL, FGFR2) and diminished levels of pro-apoptotic molecules (Casp3, p53, Bim, Bid) by microarray analysis. Of interest, we found that LCs uniquely express p21 in the steady state myeloid compartment. Accordingly, we extended our analysis of the cellular effects of IR on LCs from p21-/-. We found that p21-/LCs had an impaired recovery following IR and were more radiosensitive. Conclusions: These data suggest that LCs uniquely express an IR-resistance module of genes that permit LCs to persist and repopulate the epidermal niche following IR. Future analyses will seek to elaborate the functional implications of LC and IR-sensitive DC IR-exposure as it relates to the priming and development of GVHD and local anti-tumor immunity following radiation therapy. Author Disclosure: J. Price: None. B. Hogstad: None. J. Idoyaga: None. M. LeBoeuf: None. C. Bigarella: None. S. Ghaffari: None. M.Merad: None.
Procedures for reproducible detection of rabies virus antigen mRNA and genome in situ in formalin-fixed tissues

Procedures allowing the reproducible in situ detection of rabies virus antigen and RNAs (both genome and message) in formalin-fixed tissue are described. These procedures can be used on sequential tissue sections and thereby permit comparison of results from tests detecting both antigen and RNA in the same tissue. This antigen-detecting procedure has also been used to identify both the phylogenetically distant rabies viruses from silver-haired bat and vampire bat and the rabies-related viruses Mokola, Duvenhage, and Lagos bat. One of the critical steps in these procedures is the digestion (and the resulting exposure of the target molecules) with proteinase K. These methods may be useful for the identification of other viruses of public health importance. Because in many situations only formalin-fixed tissue is available for postmortem diagnosis, the technical ability to identify a virus antigen and nucleic acid in such tissues greatly extends potential diagnostic capabilities.
The importance of doing well in whatever you do: A commentary on the special section, “Implementation research in early childhood education”

Abstract This commentary on the special section, “Implementation research in early childhood education,” discusses 10 major conclusions drawn from implementation research and 7 additional issues needing clarification. Some major conclusions are that: (1) the level of implementation achieved can have a strong influence on program outcomes, (2) implementation is a multi-dimensional construct, (3) adaptation occurs frequently and may improve outcomes, and (4) many factors present across multiple ecological levels can affect the implementation process. Some of the major issues needing attention in future research involve determining what are the best ways to (1) measure the multiple aspects of implementation, (2) evaluate the relative importance of factors affecting implementation, and (3) clarify which participant characteristics may influence the relationship between implementation and different outcomes.
On characterizing the 4 C's in supply chain management

Abstract Supply chain management is a field at the confluence of many other disciplines; it has been studied under a number of perspectives, which has played a role for the crossbreeding of the discipline. In this paper, we propose a typology of supply chain configurations that contributes to tie together terms that have been used disjointedly for describing various forms of supply chain. It also enables researchers to develop theories related to the identified typology, rather than continue expanding efforts on separate, unconnected studies. The typology is configurational, consistent, and based on the correspondence ( Sheppard and Sherman, 1998 ) between Fiske's theory of relational forms (1990) and the concept of interdependence, analyzed in the context of supply chain management. Our framework encompasses four main configurations – the communicative, coordinated, collaborative, and co-opetitive – and we refer to these as the 4 C's in supply chain management. We discuss the benefits of the proposed typology from managerial and research perspectives, and suggest some research extensions.
Extending total life-cycle thinking to sustainable supply chain design

Conventional supply chain management (SCM) practices have focused only on three life-cycle stages: pre-manufacturing, manufacturing and use. The fourth stage, post-use, probably the most important from a sustainability perspective, is often addressed on a piece-meal basis, only when such practices deliver economic benefits. This paper introduces a total life-cycle-based approach to sustainable SCM (SSCM) that extends beyond the 3R's of reduce, reuse and recycle to 6R's that includes recover, redesign and remanufacture. A new definition for SSCM that adopts the total life-cycle approach and triple bottom-line (TBL) is presented. Two existing supply chain frameworks: supply chain operations reference (SCOR) model and the global supply chain forum (GSCF) framework, are evaluated in the context of SSCM to improve economic growth while ensuring environmental protection and societal well-being. The review finds that neither framework explicitly captures the non-economic aspects of SSCM, but the broader view of the GSCF framework offers much promise.
Accuracy evaluation of the unified P-value from combining correlated P-values.

Meta-analysis methods that combine -values into a single unified -value are frequently employed to improve confidence in hypothesis testing. An assumption made by most meta-analysis methods is that the -values to be combined are independent, which may not always be true. To investigate the accuracy of the unified -value from combining correlated -values, we have evaluated a family of statistical methods that combine: independent, weighted independent, correlated, and weighted correlated -values. Statistical accuracy evaluation by combining simulated correlated -values showed that correlation among -values can have a significant effect on the accuracy of the combined -value obtained. Among the statistical methods evaluated those that weight -values compute more accurate combined -values than those that do not. Also, statistical methods that utilize the correlation information have the best performance, producing significantly more accurate combined -values. In our study we have demonstrated that statistical methods that combine -values based on the assumption of independence can produce inaccurate -values when combining correlated -values, even when the -values are only weakly correlated. Therefore, to prevent from drawing false conclusions during hypothesis testing, our study advises caution be used when interpreting the -value obtained from combining -values of unknown correlation. However, when the correlation information is available, the weighting-capable statistical method, first introduced by Brown and recently modified by Hou, seems to perform the best amongst the methods investigated.
Quality of life of adult patients with sickle cell disease

Purpose: The purpose of this descriptive study was to examine quality of life (QOL) in adult patients with sickle cell anemia, hemoglobin SC, or hemoglobin S beta thalassemia. Data sources: Data were collected from a convenience sample of 62 adult patients (18 years of age and older) with sickle cell disease (SCD) in an outpatient clinic devoted to the care of hematological and oncological disorders. Burckhardt and Anderson's 16-item self-report Quality of Life Scale (QOLS) and a demographic questionnaire were used for data collection. Conclusions: The average QOLS scores for healthy populations are 90. The overall mean QOL score in this study of 83.6 (SD = 13.2) was lower than those of the general population. In this study, scores ranged from 52 to 112. Approximately 35% (n = 22) of participants’ scores ranged from 52 to 75; approximately 35% (n = 22) of participants’ scores ranged from 75 to 85; and approximately 30% (n = 17) of participants’ scores ranged from 85 to 112. Other results were nonsignificant for all variables except the variable that assessed the extent to which participants consider themselves to be spiritual. Future research is needed to further the understanding of the impact of QOL in adults with SCD. Implications for practice: A better understanding of adult patients with SCD QOL may ultimately improve healthcare services for this population. The findings could lead to future research that can identify factors that most impact the QOL of people living with SCD.
High efficiency detection of bi-stranded abasic clusters in γ-irradiated DNA by putrescine

Bi-stranded abasic clusters, an abasic (AP) site on one DNA strand and another nearby AP site or strand break on the other, have been quantified using Nfo protein from Escherichia coli to produce a double-strand break at cluster sites. Since recent data suggest that Nfo protein cleaves inefficiently at some clusters, we tested whether polyamines, which also cut at AP sites, would cleave abasic clusters at higher efficiency. The data show that Nfo protein cleaves poorly at clusters containing immediately opposed AP sites and those separated by 1 or 3 bp. Putrescine (PUTR) cleaved more efficiently than spermidine or spermine, and did not cleave undamaged DNA. It cleaved abasic clusters in oligonucleotide duplexes more effectively than Nfo protein, including immediately opposed or closely spaced clusters. PUTR cleaved more efficiently than Nfo protein by a factor of approximately 1.7 or approximately 2 for DNA that had been gamma-irradiated in moderate or non-radioquenching conditions, respectively. This suggests that the DNA environment during irradiation affects the spectrum of cluster configurations. Further comparison of PUTR and Nfo protein cleavage may provide useful information on abasic cluster levels and configurations induced by ionizing radiation.
Pharmacological evidence for GABA as the transmitter in granule cell inhibition in the olfactory bulb.

Summary The convulsants picrotoxin and bicuculline block the depressant action of microelectrophoretically administered GABA and strychnine selectively blocks the depressant action of glycine on olfactory bulb mitral cells. The amino acids, d,l -homocysteate (DLH), glutamate, and aspartate, which excite virtually all other central neurons, often inhibited mitral cells and this effect was blocked by Mg 2+ . The depression produced by excitant amino acids is reversed to excitation by picrotoxin and bicuculline. These results are consistent with the proposal that granule cell synaptic inhibition of mitral cells is mediated by GABA. The granule cell inhibition elicited physiologically, however, proved difficult to antagonize with convulsants, but in some cases a degree of antagonism could be demonstrated. The results suggest that GABA may be the inhibitory transmitter released by granule cells.
Metallic ion transport associated with midlatitude intermediate layer development

[1] Although intermediate layers are frequently observed by the Arecibo Incoherent Radar Observatory and by ionosondes around the world, many questions still remain regarding their formation, structure, and composition. In this paper, we explore the effect of metallic ions, specifically Fe+, on intermediate layer development and evolution. Several studies have demonstrated that layers can form from either molecular or metallic ions. This paper extends these earlier studies by quantifying the effect of metallic ions on intermediate layer morphology. We show that the efficiency of metallic ion transport depends significantly on the amplitude and wavelength of the imposed horizontal wind field. Specifically, larger amplitudes and longer wavelengths result in increased ion transport in the direction of the propagating neutral wind field.
Dissociation of a galactose transport system by warm-water treatment

Abstract When E. coli A is warmed for several minutes at 48°, while suspended in 0.1 M Tris buffer (pH 7.3) containing 10 mM MgCl2, its viability is retained undiminished and its growth is initiated without lag. Little macromolecular substance is released from the cells into the medium, although an appreciable release of soluble nucleotide derivatives and peptidic materials does occur. Galactose uptake, which is usually biphasic, is dissociated by warm-water treatment. The extremely rapid, respiration-independent primary phase is retained, while the slow, respiration-dependent secondary phase is reduced. The secondary phase can be restored by incubating the treated cells in the chloramphenicol-containing uptake medium in air, but not in an atmosphere of N2. As a result of warm-water treatment, the cells may become depleted locally of ATP or its metabolic equivalent, which is needed to activate and sustain the uptake system. However, this interpretation could not be verified by supplementing the treated cells with ATP, MgCl2 or the warm-water extract. Further analysis revealed that the cells contain a constant amount of phosphorylated galactose during transport and that it is free galactose which accumulates. Since it occurs during the secondary phase of uptake, dephosphorylation of the transport intermediate may be coupled to respiration, and it may be this process which is sensitive to warm-water treatment.
Adjunctive TNF inhibition with standard treatment enhances bacterial clearance in a murine model of necrotic TB granulomas.

Background It has been hypothesized that early host-responses during TB treatment may paradoxically promote survival of persistent bacteria. We therefore evaluated whether adjunctive inhibition of tumor necrosis factor alpha (TNF-α)–a key cytokine in host responses against TB–could hasten bacterial clearance in a mouse strain that develops necrotic lesions in response to Mycobacterium tuberculosis infection. Methodology/Principal Findings Six weeks after an aerosol infection, C3HeB/FeJ mice received standard TB treatment with or without adjunctive TNF inhibition (etanercept for the initial six weeks). Functional TNF-α levels and lung pathology were found to be reduced in the mice receiving etanercept. Compared to standard TB treatment, the addition of etanercept resulted in a significantly lower pulmonary bacterial burden, corresponding to the phase when a significant proportion of bacteria are multiplying slowly (p<0.0233). Finally, only 10.5% of mice receiving adjunctive etanercept versus 27.8% receiving standard TB treatment alone relapsed. Conclusion This study provides proof-of-principle that modulation of TNF-α activity can hasten bacterial clearance during standard multi-drug TB treatment. Oral agents that modulate TNF-α should therefore be considered as adjunct therapies for shortening TB treatments. However, due to concerns of reactivation disease, additional studies need to be performed before TNF-α inhibitors are used for TB treatment in humans.
Continuity and Change

Beginning with this issue, a new group of editors, based at Yale Univeristy, have taken the helm at Immunity. We have several new ideas for the direction of the journal. Before we come to these, we believe that one fundamental thing must stay the same: Immunity will continue to publish only the very best and most innovative work in the field of immunology. The highest standards were set by the two previous groups of editors, first at Harvard and then at Washington University. It is this insistence upon quality that has made Immunity stand out as a journal, and this is a tradition that we proudly accept and pledge to maintain.There are two things we do wish to change about the journal. The first of these is the scope. One of us (C. A. J., Jr.) was a member of the founding editors and, in fact, suggested the name. The original conception behind Immunity was to embrace the whole field of immunology. While there has been no formal barrier to publication in any particular aspect of immunology, we believe that many parts of our discipline have been underrepresented in its pages. We welcome new submissions on topics such as innate immunity, the burgeoning area of how the immune system contributes to or ameliorates disease, or how the intentional manipulation of immunity is used to treat disease. We welcome new submissions that address these and other areas of immunology using animal models or patient-based studies. We further signal the renewed commitment of the journal to the whole of our field by increasing the scope (as well as the number) of review articles that will appear under the guidance of our new Reviews Editor, William Paul. We plan for the journal to expand in size to accomodate this broader interest, while sustaining the quality of the publications.The second change we propose is a procedural one. We ask that each new submission be accompanied by an addendum to the cover letter addressing three questions: (1) what is the scientific question being asked by this study, (2) what are the principal new findings that answer this question, and (3) what is the significance of the results for the field? The authors' answers to these questions will not only help the editors in selecting appropriate reviewers, but will be forwarded to the referees along with the manuscript to aid in the review process.We hope over the next several years to expand not only the topics covered and the number of pages published but also the size of readership. We welcome reader comments and suggestions as we work to improve upon an outstanding inheritance. We conclude by thanking our predecessors at Harvard and Washington University for the exceptional job they have done, both in setting the standards and in making our task enormously easier by creating and passing on such a wonderful journal.
Pharmacokinetics relevant to the anti-carcinogenic and anti-tumor activities of glucarate and the synergistic combination of glucarate:retinoid in the rat.

Alone and in synergistic combination with retinoids, dietary glucarate inhibits both the chemical induction and growth of rat mammary tumors. To investigate the pharmacokinetics of glucarate, [14C]glucarate was synthesized, converted to the calcium salt, and administered to rats bearing primary mammary tumors. When given by gavage, [14C]glucarate, as the calcium salt, showed a biphasic response in the blood. After peaking within 1 hr of administration at a level of 0.4 μmol/mL (normal endogenous level is approximately 0.04 μmol/mL), its plasma concentration dropped to 0.1 μmol/mL at 3 hr. In the second phase, there was a semilog increase to 0.6 μmol/mL at 15 hr, followed by a slow rise to 0.75 μmol/mL at 24 hr. Of the 38% of the administered glucarate that was recovered, 38% was excreted in the urine, and 30% remained in the gastrointestinal tract at 24 hr. Glucarate was concentrated 3- to 4-fold in the liver and intestinal mucosa, compared to the level in serum. With minor exception, the pharmacokinetics of [14C]13-cis-retinoic acid administered by gavage to rats was similar whether or not the semipurified diets were supplemented with 64 mmol/kg of calcium glucarate. During the interval between 5 and 10 hr post-administration of [14C]13-cis-retinoid, there was a transient 35–50% rise in the plasma level in rats on the glucarate-supplemented diet. This rise had no observable effect on the level of retinoid in major organs or in the tumor. A glucarate-binding protein was detected in the tumor cytosol. This potential receptor had a Ka of 1.49 × 107 M−1.
Direct coupled dc SQUID magnetometer for ultralow temperature NMR

We have developed a 1 MHz bandwidth dc SQUID magnetometer. By reconfiguring the ground reference leads to the SQUID we increase the maximum signal amplitude, and hence slew rate, by two orders of magnitude without altering any other system parameters.
Alternative Medicine and Herbal Use Among University Students

Abstract. In this study, the authors investigated the predictors of complementary and alternative medicine (CAM) and herbal supplement use among university students. They investigated demographic factors, trait affectivity, symptom reports, and individuals' worries about modernity as potential contributors to use of CAM and herbals. The authors surveyed 506 undergraduates at a large southeastern state universityand administered the following questionnaires to participants in a group setting: a CAM survey, an herbal use survey, a negative affect (NA) and positive affect (PA) scale, Modern Health Worries scale, and the Subjective Health Complaint scale. Overall, 58% of the participants had used at least one type of CAM, and 79% of the students had used at least one herbal substance in the past 12 months. A hierarchical regression determined that increased age, female gender, flu-like symptoms, musculoskeletal symptoms, pseudoneu-rological symptoms, and modern health worries were significantly related to stu...
Ermakov systems and quantum-mechanical superposition laws

Ermakov systems are pairs of coupled, time-dependent, nonlinear dynamical equations possessing a joint constant of the motion called an Ermakov invariant. The invariant provides a link between the two equations and leads to a superposition law between solutions to the Ermakov pair. Extensive studies of Ermakov systems in classical mechanics have been carried out. Here we present a detailed study of Ermakov systems from a quantum point of view, and prove that the solution to the Schr\"odinger equation for a general Ermakov system can be reduced to the solution of a time-independent Schr\"odinger equation involving the Ermakov invariant. We thereby arrive at a quantum-mechanical superposition law analogous to the classical superposition law.