cssi/SciSciGPT-SciSciNet huggingface dataset:
Cell-Intrinsic Inflammation Drives Progression from Myelodysplastic Syndromes to Leukemia

Myelodysplastic Syndromes (MDS) often progress to Acute Myeloid leukemia (AML) typically following acquisition of mutations in RUNX1, NRAS/KRAS or AXSL1. Inflammatory processes associated with autoimmune diseases or natural aging are thought to contribute to the development of MDS and progression to AML. Moreover, dysregulation of innate immune signaling is broadly observed in hematopoietic stem and progenitor cells (HSPC) from MDS patients. However, how dysregulation of innate immune signaling and/or inflammatory signals might lead to malignant transformation and overt AML has not been fully elucidated. We have developed a mouse model of cell-intrinsic inflammation-driven progression from MDS to AML that will allow us to determine the mechanisms of oncogenic transformation. MicroRNA miR-146a is a 5q gene that is frequently deleted in MDS and AML and its deletion promotes dysregulation of innate immune signaling and a systemic inflammatory state. Deletion of miR-146a results in myeloproliferation and marrow failure in mice associated with attrition of HSPC, but alone is insufficient to induce overt AML. Using a genetically engineered approach, we show that deficiency of miR-146a (miR-146a-/-) combined with a C-terminal truncation of the RUNX1 (S291fsX300) protein causes anemia, thrombocytopenia and ineffective erythropoiesis mimicking human MDS in younger mice, but then the mice progresses to a fatal AML. The inflammatory environment induced by miR-146a deletion was exacerbated in mice with miR-146a-/-expressing RUNX1-S291fsX300 (RUNX1-mut) and correlated with the increased incidence and aggressiveness of hematologic malignancies. In particular, the levels of IFNγ were increased in plasma in mice with miR-146a-/-expressing RUNX1-mut in comparison to mice reconstituted with miR-146a-/-or RUNX1-mut-expressing BM cells. As previously reported, miR-146a-/-cells exhausted during serial transplantation, however RUNX1-mut rescued the hematopoietic repopulation deficiency of miR-146a-/-HSPC, suggesting that the RUNX1 mutation promotes malignant transformation to AML under inflammatory conditions. To establish whether cell-intrinsic immune signaling is required for RUNX1-mut;miR-146a-/- leukemic cells, we evaluated an inhibitor (NSC697923) that targets TRAF6, a key target of miR-146a in MDS/AML, via inhibition of its co-factor UBE2N. Treatment with NSC697923 or a RUNX1 inhibitor (Ro 5-3335) abolished colony formation by RUNX1-mut;miR-146a-/- leukemic cells, indicating that cell-intrinsic innate immune signaling is not only required for initiating AML, but is also critical for sustaining the leukemic phenotype. These findings describe the first evidence that dysregulation of innate immune signaling and/or inflammatory signals contribute to the progression and maintenance of AML. Disclosures Starczynowski: Kurome Therapeutics: Consultancy.
Theorizing from Cases: A Commentary

This commentary has several aims. First, it clarifies theorizing from cases by sharpening the insights of Welch and colleagues (Journal of International Business Studies 42 (5): 740–762, 2011) regarding context while also indicating inaccuracies. More importantly, the commentary outlines recent advances in case study methods including greater use of intermediate theorizing (e.g., abduction, elaboration) between theory building and testing. A major point is that the use of case methods is becoming richer and more diverse with both more sophisticated research designs, such as natural experiments that improve causal identification, and more complex causal explanations (e.g., configurations, equifinality). Another point is the movement away from artificial distinctions among inductive methods towards understanding similarities and genuine differences. Assumptions, boundary conditions, inductive methods, and language emerge as important for meeting the challenge of context in international business. Finally, this commentary looks to the future, including the roles of machine learning and big data in expanding how theorizing from cases can occur.
Foraging in urban environments increases bactericidal capacity in plasma and decreases corticosterone concentrations in white ibises

As humans continue to infringe on natural habitats, more animals are exposed to urban habitats and associated challenges. It is still unclear, however, whether the movement of animals into urban habitats negatively influences the health and/or survival of those animals, however those animals often experience shifts in resource availability, diet composition, and exposure to stimuli that are new and potentially stressful. Recently, white ibises (Eudocimus albus) have become increasingly common in urban habitats where they forage in close proximity to humans and even interact with them, collecting food handouts. We hypothesized that foraging in urban habitats would negatively impact measures of health, impair innate immunity, trigger elevated concentrations of corticosterone, and depress physiological responses to stressors in white ibises. We found that birds captured from urban sites had lower ectoparasite scores and higher bactericidal capacity against Escherichia coli than those captured in natural sites. Additionally, adults captured in urban habitats had a significantly lower baseline corticosterone concentrations during the post-breeding season, and corticosterone responses to a handling challenge were lower for birds captured from urban sites during year 2 of the study. These results indicate that exposure to urban habitats impacts ibis health, though in the opposite direction of what was predicted.
Assessing the links between human rights and global tobacco control through statements made on global fora

Increasingly, international health bodies frame public health measures, including tobacco control, in the context of human rights (HR). It is unclear how prevalent is the connection between human rights and tobacco control within global health governance. This paper describes the inclusion of HR in tobacco control governance, and the inclusion of tobacco control in HR treaty oversight. We depict the current reach of HR’s normative influence in framing the tobacco epidemic in global, regional, and country-specific contexts. We reviewed documents (agenda, reports) from 2010 to 2019 from the World Health Assembly (WHA); the WHO Western Pacific Regional Committee Meetings (RCM); the WHO Framework Convention on Tobacco Control (WHO FCTC) Conferences of the Parties (COP); and documents provided by Pacific Island Countries party to, or by committees overseeing, HR treaties. We purposively selected the Western Pacific Region, and Pacific Island Countries specifically, to represent countries of varying populations, capacities, and governance. Tobacco control and HR are infrequently mentioned together in the WHAs, and primarily in only one COP. Tobacco control is mentioned in 47 HR treaty committee documents for Pacific Island Countries, mostly under the Convention of the Rights of the Child recognizing or calling for ratification of the WHO FCTC. HR and tobacco control are connected in WHO Western Pacific RCM, particularly through their two most-recent action plans adopted by respective RCMs. Tobacco control as a HR concern is gaining traction within HR treaty bodies, at least with respect to children’s health in the Western Pacific Region. Globally, HR is just emerging as an influence in global health governance for tobacco discussions. Within the Western Pacific Region however tobacco control is seen by some authorities as a HR issue. Similarly, to HR experts, tobacco control is becoming important to how Pacific Island Countries fulfill their treaty obligations, suggesting tobacco control advocates might explore these mechanisms to further influence the development of strong tobacco control measures to implement the WHO FCTC.
Training classifiers for feedback control with safety in mind

Abstract The sensors of many autonomous systems provide high-dimensional and information-rich measurements. The state of the system is a part of this information, however it is challenging to extract it from such measurements. An autonomous system cannot use traditional feedback control algorithms without knowledge of the state. We propose computational algorithms for the analysis and synthesis of classifier-enabled control architectures. We show how to train classifiers based on criteria that relate to both learning from data and properties of the resulting closed-loop system. The approach to deriving these algorithms involves modeling the resulting closed-loop system as a piecewise affine differential inclusion . The training method is based on the projected gradient descent algorithm. An application of this method to a navigation problem for a mobile robot demonstrates the capabilities of this approach.
Editorial Commentary: Preoperative Patient-Reported Outcomes Measurement Information System Scores Predict Which Patients Will Benefit From Arthroscopic Meniscectomy: To Scope or Not to Scope?

Abstract Despite its widespread use and low complication rates, arthroscopic meniscectomy has not been uniformly successful in all patients, especially in those with concurrent osteoarthritis. The Patient-Reported Outcomes Measurement Information System (PROMIS) is an initiative funded by the National Institutes of Health to develop and validate patient-reported outcomes for clinical research and practice. PROMIS has shown the ability to enhance and standardize measurement of a variety of health domains affecting musculoskeletal function and in discriminating between various orthopaedic procedures through the use of computer adaptive testing. Preoperative PROMIS scores are valid predictors of postoperative minimal clinically important difference in patients undergoing arthroscopic meniscectomy based on preoperative decreased physical function and increased pain interference. PROMIS score cutoffs may be used by arthroscopic surgeons to counsel patients considering arthroscopic meniscectomy.
Setting ethical limits on human gene editing after the fall of the somatic/germline barrier

The ethical debate about what is now called human gene editing (HGE) has gone on for more than 50 y. For nearly that entire time, there has been consensus that a moral divide exists between somatic and germline HGE. Conceptualizing this divide as a barrier on a slippery slope, in this paper, I first describe the slope, what makes it slippery, and describe strong barriers that arrest the slippage down to the dystopian bottom of pervasive eugenic enhancement. I then show how the somatic/germline barrier in the debate has been weakened to the level of ineffectiveness, with no replacement below. I examine a number of possible barriers on the slope below the somatic/germline barrier, most of which lack sufficient strength. With the exception of the minority of people in the HGE debate who see the eugenic society as utopia, the majority will need a barrier on the slope to stop the slide to dystopia.
Acute Kidney Injury in the Modern Era of Allogeneic Hematopoietic Stem Cell Transplantation.

Background and objectives AKI is a major complication of allogeneic hematopoietic stem cell transplantation, increasing risk of nonrelapse mortality. AKI etiology is often ambiguous due to heterogeneity of conditioning/graft versus host disease regimens. To date, graft versus host disease and calcineurin inhibitor effects on AKI are not well defined. We aimed to describe AKI and assess pre–/post–hematopoietic transplant risk factors in a large recent cohort. Design, setting, participants, & measurements We performed a single-center, retrospective study of 616 allogeneic hematopoietic cell transplant recipients from 2014 to 2017. We defined AKI and CKD based on Kidney Disease Improving Global Outcomes (KDIGO) criteria and estimated GFR using the Chronic Kidney Disease Epidemiology Collaboration equation. We assessed AKI pre–/post–hematopoietic transplant risk factors using cause-specific Cox regression and association of AKI with CKD outcomes using chi-squared test. AKI was treated as a time-dependent variable in relation to nonrelapse mortality. Results Incidence of AKI by day 100 was 64%. Exposure to tacrolimus and other nephrotoxins conferred a higher risk of AKI, but tacrolimus levels were not associated with severity. Reduced-intensity conditioning carried higher AKI risk compared with myeloablative conditioning. Most stage 3 AKIs were due to ischemic acute tubular necrosis and calcineurin inhibitor nephrotoxicity. KRT was initiated in 21 out of 616 patients (3%); of these 21 patients, nine (43%) recovered and five (24%) survived to hospital discharge. T cell–depleted transplants, higher baseline serum albumin, and non-Hispanic ethnicity were associated with lower risk of AKI. CKD developed in 21% (73 of 345) of patients after 12 months. Nonrelapse mortality was higher in those with AKI (hazard ratio, 2.77; 95% confidence interval, 1.8 to 4.27). Conclusions AKI post–hematopoietic cell transplant remains a major concern. Risk of AKI was higher with exposure to calcineurin inhibitors. T cell–depleted hematopoietic cell transplants and higher serum albumin had lower risk of AKI. Of the patients requiring KRT, 43% recovered kidney function. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_09_07_CJN19801220.mp3
Phase-Shedding Control Scheme for Wide Voltage Range Operation of Extended-Duty-Ratio Boost Converter

In this paper, a phase shedding control scheme for extended-duty-ratio (EDR) boost converter is proposed to achieve wide input and output voltage range operation of the converter. EDR converters can achieve very high gain, for example above 20 for a 4-phase converter, but have limitations on the lowest allowable gain. The proposed scheme allows operation at gain as low as unity while retaining the main benefits of EDR boost such as low voltage stress across switches. The phase shedding control can be optimized based on the application requirements. In this paper, the phase shedding control is optimized for low device voltage stress over wide input and output voltage range operation. The converter control implementation is discussed in detail. The control scheme is verified with a 4-phase EDR boost converter with input voltage varying between 20 V–40 V and output voltage ranging between 50 V–400 V. Experimental results of closed loop operation with adaptive PI controller are presented and the phase shedding scheme is verified by showing the transition from one configuration to another based on the converters varying gain.
Juvenile Economic Sanctions

Research Summary Economic sanctions, particularly restitution, can help juvenile offenders both learn the extent of the harm they caused and assume responsibility for repairing that harm. If that assumption is true, then restitution should be imposed in every case for which it is appropriate, other factors should not affect imposition, and paying restitution should be negatively related to recidivism. This analysis of 921 juvenile cases in five Pennsylvania counties found that restitution was imposed in only 33% of cases for which it was appropriate, whereas fees were imposed in 66% of cases. Consistent with expectations, restitution was more likely to be imposed for property offenses, but contrary to expectations, restitution was more likely to be imposed for felonies and for males. Judges were less likely to revoke the sentences of juveniles who paid a greater percentage of their total economic sanctions and of juveniles whose violation of sentencing conditions was for nonpayment of economic sanctions. Policy Implications Given that support for both punitive and progressive policies exists, policy makers have a unique opportunity to pursue alternatives, like economic sanctions, that appeal to both perspectives. Economic sanctions are particularly important for juveniles because they are less likely to interfere with other financial obligations (in large part because juveniles have fewer financial obligations than do adults) and because they avoid the stigma associated with more punitive sentences, such as incarceration. The negative relationship between payment of economic sanctions and recidivism, found in this study and in other studies, also suggests that, in both the short and the long term, economic sanctions are more cost-effective. Furthermore, the restorative aspect of economic sanctions, particularly restitution, suggests that policy makers should consider how best to impose and collect economic sanctions, as they also are consistent with efforts to improve the treatment of crime victims.
Comparing Classroom Problem-Solving with No Feedback to Web-Based Homework Assistance

It is common for math teachers to give students time in class to practice problem solving skills. Some studies have shown that intelligent tutoring systems (ITS) can be superior to traditional classroom instruction. In this study, we compare problem solving with little or no feedback in the classroom to problem solving using a web-based ITS for homework. The system provides students with coached practice that is meant to scaffold "learning by doing" while students practice their problem solving skills. We found evidence that using the web-based ITS to practice problem solving at home was better than the classroom problem solving with an effect size of 0.5.
Rule definition for managing ontology development

This paper presents an approach to ontology development through the application of declarative logic programming. Our method employs rules for the purpose of prototyping new ontology versions by decoupling the process of concept definition from the application of descriptive logics (DL) and advanced class representations. By generating new ontology versions on-the-fly we can test updates to the ontology design. This employment of rules expands on current efforts of translation and merging of ontologies. By employing this technique, we can support a pragmatic approach to the management and integration of instance data thus realizing a rapid-prototyping approach to the testing of potential updates to ontologies. Examples of this technique are presented utilizing a subset of the OWL-DL specification through the implementation of the Jena API. Advantages include the rapid testing of updated ontology representations (including the efficient remapping of instance data) and an efficient means of Ontology querying. Eventual benefits include Ontology versioning support and tool development to support the automatic engineering of instance data.
Functional avidity maturation of CD8 + T cells without selection of higher affinity TCR

Unlike B cells, T cells lack the capacity to improve the affinity of their antigen receptors by somatic mutation. It is, therefore, believed that optimization of cellular immunity is mediated almost exclusively through selective expansion of T cells bearing receptors with the highest affinity for antigen. We show here that T cell responsiveness to peptide (termed "functional avidity") increased>50-fold during the early stages of viral infection. This indicated that T cells, like B cells, undergo extensive functional maturation in vivo. However, in contrast to B cells, maturation of the T cell response can occur without any appreciable change in T cell receptor affinity.
Planarity and the Four-Color Theorem

March 16. A graph is said to be planar if it can be drawn in the plane with no crossing edges. A classic problem based on planarity is the “utility problem”. Suppose there are three people–Jack, Jill, and Judy–living in separate houses, and also three utilities–water, gas, and electricity–each supplied by a different plant. We wish to connect each of the three houses to each of the three plants, but we don’t want any of the nine connections to cross each other. (Perhaps all of the utilities are supplied by cables or pipes buried just beneath the surface, and if two were to cross we might damage one conduit while installing the other.
The assembly of tetrameric prolyl hydroxylase in tendon fibroblasts from newly synthesized α-subunits and from preformed cross-reacting protein

Embryonic-chick tendon cells were incubated in suspension for 4h with 14C-labelled amino acids, cell extracts were subjected to gel filtration, and the effluent was examined by rocket immunoelectrophoresis by using antibodies specific for the β-subunit of chick prolyl hydroxylase. Two peaks of immunoreactive protein were found. The first peak contained 40% of the immunoreactive protein eluted from the column and 100% of the enzyme activity. Polyacrylamide-slab-gel electrophoresis in sodium dodecyl sulphate of an immunoprecipitate of this peak demonstrated that it consisted of the tetrameric form of prolyl hydroxylase, subunit composition α2β2 where α and β are non-identical subunits. Only the α-subunits were labelled, indicating that they were synthesized during the 4h labelling period. The β-subunits were unlabelled, indicating that they had been synthesized before the labelling period. The second peak eluted from the gel-filtration column contained 60% of the immunoreactive protein eluted from the column and was enzymically inactive. Polyacrylamide-slab-gel electrophoresis of an immunoprecipitate of this peak indicated that it consisted of a single labelled polypeptide chain, identified as cross-reacting protein, which was related to, but not identical with, the β-subunit of prolyl hydroxylase. Pulse–chase experiments were performed on cultured chick tendon cells to demonstrate that α-subunits and cross-reacting protein had half-lives of about 60h. The half-life of β-subunits was considerably longer, and the kinetic pattern was consistent with their being derived from a labelled precursor such as cross-reacting protein. The data presented here indicate that the active tetrameric form of prolyl hydroxylase in cells is assembled from α-subunits which are newly synthesized, and from β-subunits which are derived from cross-reacting protein.
Some Properties of a Testosterone-binding Component of Human Pregnancy Serum

Abstract Human pregnancy serum was previously reported to exhibit a high binding affinity for testosterone; steroid binding was measured by a semimicrotechnique, based on the principle of equilibrium dialysis but utilizing Sephadex G-25 in a batchwise fashion. This property may be ascribed to a testosterone-binding component, presumably a protein, present in very low concentration in serum. The testosterone-binding component was readily separated from corticosteroid-binding globulin (both steroid-binding proteins are present at elevated levels in late pregnancy) by column chromatography of pooled pregnancy serum on microgranular diethylaminoethyl cellulose. Stepwise elution furnished four major fractions: γ-globulin, β-globulin, albumin, and α-globulin, in that sequence. The testosterone-binding component appeared in the β-globulin fraction, whereas the corticosteroid-binding globulin (measured by its cortisol- and progesterone-binding activities) appeared in the albumin fraction; the latter fraction also exhibited considerable testosterone-binding activity, attributable to albumin itself and, in part, to corticosteroid-binding globulin. A portion of the β-globulin fraction (after precipitation in 50% ammonium sulfate) was chromatographed on a column of Sephadex G-100; the testosterone-binding protein was thereby separated from the bulk of the protein (the former emerged last from the column). Considerable losses in testosterone-binding activity were, however, encountered at each stage of purification, and so the over-all increase in specific binding activity (i.e. testosterone-binding activity per g of total protein) was only about 4-fold. Other fractionation procedures, i.e. column chromatography on hydroxylapatite and on fibrous DEAE-cellulose, were not as efficacious, but nonetheless informative; the testosterone-binding component is readily precipitated from whole serum in 50% saturated ammonium sulfate. The testosterone-binding component is distinctly different from corticosteroid-binding globulin in its chromatographic behavior and steroid-binding properties. There is also an appreciable difference in molecular size according to gel filtration studies: the testosterone-binding component has a Stokes molecular radius of about 47 A compared to 36 A for corticosteroid-binding globulin; the same value was obtained for the latter protein from the sedimentation and diffusion data of other investigators.
High power 1060-nm raised-ridge strained single-quantum-well lasers

We report a high kink-free facet power of 852 mW and a high single-wavelength facet power of 350 mW for 1060-nm raised-ridge Fabry-Perot (FP) and distributed-feedback (DFB) lasers, respectively.
The comparative morphology of the larynx in snakes

Young, B.A. 2000. The comparative morphology of the larynx in snakes. —Acta Zoologica (Stockholm) 81: 177–193 The larynx and glottal tube were examined in 10 specimens each of 22 snake species. Qualitative analysis through dissection and clearing and staining revealed distinct morphological variation in the cartilage and intrinsic musculature of the larynx. Quantitative analysis of nine morphometric characters revealed laryngeal sexual dimorphism in three species, significant interspecific differences in the coefficients for every morphometric feature regressed on body size, no significant intraspecific differences in the log transformed means, and poor discrimination of species using principal component analysis. The observed variations in laryngeal morphology did not correlate with the phylogeny of the species, or with habitat preferences.
Use of herbivore‐induced plant volatiles as search cues by Tiphia vernalis and Tiphia popilliavora to locate their below‐ground scarabaeid hosts

Japanese beetle, Popillia japonica Newman, and oriental beetle, Anomala orientalis (Waterhouse) (both Coleoptera: Scarabaeidae) are considered invasive species and have been reported as key pests of urban landscapes in the Northeastern USA. Tiphia vernalis Rohwer and Tiphia popilliavora Rohwer (Hymenoptera: Tiphiidae) were introduced as biocontrolagents against these beetles. Theseparasitic waspsburrowinto thesoil and search for grubs. When a host is found, thewaspattaches an egg in a location that is specific for the wasp species. It is unknown if these wasps can detect patches of concealedhostsfromadistanceabovegroundandwhatrole,ifany,herbivore-inducedplantvolatiles play in their host location. This study evaluated the responses of femaleT. vernalis and T. popilliavora togrub-infestedandhealthyplants inY-tubeolfactometer bioassays. Alsotheeffectofrootherbivory on the composition of turfgrass (Poaceae) volatile profiles was investigated by collecting volatiles from healthy and grub-infested grasses. Tiphia wasps were highly attracted to volatiles emitted by grub-infested tallfescue (FestucaarundinaceaSchreb.)andKentuckybluegrass(PoapratensisL.)over healthy grasses. In contrast, wasps did not exhibit a significant preference for grub-infested perennial ryegrass (Lolium perenne L.) as compared with the control plants. The terpene levels emitted by grub-infested Kentucky bluegrass and tall fescue were greater than that of control plants. Low levels of terpenes were observed for both test and control perennial ryegrass. The elevated levels of terpenes emitted by grub-infested Kentucky bluegrass and tall fescue coincided with the attractiveness to the tiphiid wasps. Here, we provide evidence that plant exposure to root-feeding insects P. japonica and A. orientalis resulted in an increase in terpenoid levels in turfgrasses, which strongly attracts their above-groundparasitoids.
Bäcklund Algebra and the KdV Hierarchy

This article presents the Korteweg-de Vries hierarchy in the framework of the Lie algebra of Backlund transformations and points to the problems raised by its vanishing residues characterization.
Mechanical Properties of Fine-Grained Structures Using Computational Cell Elements

Mechanical properties of fine-grained microstructure are predicted using a phase mixture model. The constitutive model is implemented into commercial finite element analysis code ABAQUS as a UMAT subroutine. A unified constitutive model based on dislocation density evolution describes the matrix phase behavior. The yield criterion of the Gurson-Tvergaard-Needleman material model for porous materials is applied to the boundary phase. The boundary phase is assumed to behave like a quasi-amorphous material. The effect of the grain size on the material property is studied using a numerical example.Copyright © 2006 by ASME
Satellite multiangle cumulus geometry retrieval: Case study

Most satellite-based analyses have been conducted using near nadir-viewing sensors. The Multi-angle Imaging SpectroRadiometer (MISR), recently launched on the National Aeronautics and Space Administration (NASA) Terra platform, provides high-resolution measurements of reflectance at nine different viewing angles. In this study, we examine the possible retrieval of detailed cumulus geometry using the new and unique MISR datasets. We suggested one approach and apply it to an early MISR dataset of small marine cumulus clouds. This paper also presents validation analysis of this technique with both independent ground-based radar measurements and a model-output inverse problem. Collocated and coincident MISR data and ground-based observations at the Atmospheric Radiation Measurement (ARM) Tropical Western Pacific (TWP) site form the basis of this validation. Future work will attempt to test the suggested approach with additional MISR scenes.
Angiogenesis in wound repair: Angiogenic growth factors and the extracellular matrix

Angiogenesis is critical to wound repair. Newly formed blood vessels participate in provisional granulation tissue formation and provide nutrition and oxygen to growing tissues. In addition, inflammatory cells require the interaction with and transmigration through the endothelial basement membrane to enter the site of injury. Angiogenesis, in response to tissue injury, is a dynamic process that is highly regulated by signals from both serum and the surrounding extracellular matrix (ECM) environment. Vascular endothelial growth factor, angiopoietin, fibroblast growth factor, and transforming growth factor beta are among those most potent angiogenic cytokines in wound angiogenesis. The cooperative regulation of them is essential for wound repair. Migration of endothelial cells and development of new capillary vessels during wound repair is dependent on not only the cells and cytokines present but also the production and organization of ECM components both in granulation tissue and in endothelial basement membrane. The ECM regulates angiogenesis by providing scaffold support and signaling roles. They also serve as a reservoir and modulator for growth factors. Laminins are the major noncollagenous ECM of endothelial basement membrane. Two newly recognized laminins, 8 and 10, are the major laminins produced by human dermal microvascular endothelial cells. Laminin 10 is highly expressed in blood vessels around skin wounds. Laminin 8 promotes dermal endothelial cell attachment, migration, and tubule formation. Integrins with either beta 1 or alpha v subunits are the major cellular surface receptors for ECM molecules and mediate the interactions between cells and ECM during wound angiogenesis.
Does low-dose heparin maintain central venous access device patency?: a comparison of heparin versus saline during a period of heparin shortage.

Background: A common problem that complicates use of central venous access devices (CVADs) is occlusion by thrombosis. Alteplase, a recombinant tissue plasminogen activator, is used to restore line patency when thrombosis occurs. Heparin flush is commonly used to prevent this complication, but the effectiveness of this practice is unclear. A recent heparin shortage allowed examination of heparin effectiveness in reducing CVAD thrombosis. Methods: A retrospective cohort study was performed by querying a pharmacy database for alteplase use for CVAD thrombosis in adult patients during periods when heparin flushes (10 units/mL) were used and when saline flushes were used instead because of a nationwide heparin shortage. The number of patients receiving alteplase, the number of doses administered, and the total amount of alteplase used were compared over 1-month intervals of heparin flush use and 1-month intervals of saline flush use. Patient days and critical care patient days were compared between these time...
The decomposition of 2-pentyl and 3-pentyl radicals

Abstract The isomerization and decomposition reactions of 2-pentyl and 3-pentyl radicals have been studied in a single-pulse shock tube over a temperature range of 973–1121 K and pressures of 120–800 kPa. The results represent the first direct study of the alkene product branching ratio resulting from the kinetics of the competition between isomerization and beta C–C bond scission for a secondary straight-chain alkyl radical at high temperatures. Such species are representative of intermediates important in the combustion of typical hydrocarbon fuels. In the present work, a small quantity of precursor (∼45 μL/L) is used to thermally generate H atoms in the presence of excess ( E )-2-pentene, leading to the radicals of interest via addition of H to the double bond. Decomposition of the chemically activated pentyl radicals results in the stable olefin products ethene, propene, and 1-butene, which are detected in postshock gas chromatographic analyses utilizing flame-ionization and mass-spectrometric detection. It is shown that the olefin product ratios can be related to the isomerization and decomposition reactions of the 2-pentyl and 3-pentyl radicals and the results are consistent with the existence of distinct non-overlapping cracking patterns for the two radicals. The data are compared with predictions made on the basis of a model developed from experiments on the decomposition of thermal (i.e. not chemically activated) 1-pentyl radicals. Good agreement is observed. In conjunction with an RRKM/Master Equation analysis, the results for 2-pentyl and 3-pentyl radicals are projected over a wide range of temperatures. In addition, the rate constants for addition of H atoms to the alternate double bond positions of ( E ) - 2-pentene are derived relative to a standard reaction and absolute rate constants for these processes are reported.
Melittin-induced changes in Na and Cl movements across the skin and cornea (in vitro) of the toad Bufo marinus

Abstract 1. Melittin, from bee venom, increases short-circuit current (Isc) across the skin and cornea of toads. 2. In skin this reflects a rise in the influx of Na and is inhibited by meclofenamic acid (inhibits prostaglandin synthetase). 3. In corneas with melittin on the inside the rise in Isc is inhibited by bumetanide (inhibits Cl transport) and meclofenamic acid. 4. Melittin on the tear side of the cornea causes a biphasic change in Isc, and a rise in all undirectional fluxes of Na and Cl. 5. This effect was not changed by bumetanide or meclofenamic acid. 6. Melittin apparently has two types of effects, one mediated by prostaglandins while the other is more direct.
The Minimum Number of Edges in Graphs with Prescribed Paths

LetM be anm-by-n matrix with entries in {0,1,⋯,K}. LetC(M) denote the minimum possible number of edges in a directed graph in which (1) there arem distinguished vertices calledinputs, andn other distinguished vertices calledoutputs; (2) there is no directed path from an input to another input, from an output to another output, or from an output to an input; and (3) for all 1 ≤i ≤m and 1 ≤j ≤n, the number of directed paths from thei-th input to thej-th output is equal to the (i,j)-th entry ofM. LetC(m,n,K) denote the maximum ofC(M) over allm-by-n matricesM with entries in {0,1,⋯,K}. We assume (without loss of generality) thatm ≥n, and show that ifm=(K+1) 0(n) andK=22 0(m) , thenC(m,n,K)= H/logH + 0(H/logH), whereH=mnlog(K + 1) and all logarithms have base 2. The proof involves an interesting problem of Diophantine approximation, which is solved by means of an unusual continued fraction expansion.
Polycarbonate carbon nanofiber composites

Carbon nanofiber (CNF) composites have the potential for creating inexpensive, semiconducting polymers. These composites require a homogeneous dispersion within the polymer. Many groups have focused on high shear methods such as twin screw extrusion. Although high shear methods produce a homogeneous dispersion, the aspect ratio of the nanofibers is reduced by the mechanical force. In this report, we present results for low shear composite formation via in situ polymerization of cyclic oligomeric carbonates. The composites were characterized by thermal gravimetric analysis, electrical conductivity, scanning electron microscopy and transmission electron microscopy. The composites exhibit minimal aggregation of the carbon nanofibers even at high weight percents. The polycarbonate/CNF composites exhibit an electrical conductivity percolation threshold of 6.3 wt% which is higher compared with similar CNF composites. The composites also show an increase in thermal stability of 40 °C as the CNF loading increases from 0 to 9 wt%.
Isolation and Sequence of an Interferon-τ-Inducible, Pregnancy- and Bovine Interferon-Stimulated Gene Product 15 (ISG15)-Specific, Bovine Ubiquitin-Activating E1-Like (UBE1L) Enzyme

Bovine (bov) interferon-stimulated gene product 15 (ISG15) is produced in the endometrium in response to conceptus-secreted interferon (IFN)-tau. ISG15 conjugates to endometrial proteins through an enzymatic pathway that is similar to ubiquitinylation. Ubiquitin-activating enzyme 1-like protein (UBE1L) initiates enzymatic conjugation by forming a thioester bond with ISG15, thus preparing it for transfer to the next series of enzymes. The bovUBE1L has not been described. We hypothesized that bovUBE1L was induced by pregnancy and IFN-tau in the endometrium. A 110-kDa protein was purified from bovine endometrial (BEND) cells based on affinity with recombinant (r) glutathione S-transferase (GST)-ISG15. This protein was digested in gel with trypsin. Seven peptides were purified using HPLC, sequenced using liquid chromatography-mass spectroscopy-mass spectroscopy and found to share 43-100% identity with human UBE1L. The full-length bovUBE1L cDNA was isolated from a BEND cell cDNA library, sequenced, and found to share 83% identity with human UBE1L cDNA. Northern blot revealed two mRNAs that were detected in greater (P<0.05) concentrations in endometrium from Day 17-21 pregnant versus nonpregnant cows. Western blots using antihuman UBE1L antibody revealed a similar pattern of pregnancy-associated expression of UBE1L protein in the uterus. The bovUBE1L mRNA was localized, using in situ hybridization, primarily to glandular and luminal epithelium, with more diffuse localization to stroma of the endometrium from pregnant cows. Because bovUBE1L was purified through its interaction with rGST-ISG15 and shares significant amino acid and cDNA sequence identity with human UBE1L, it is concluded that it mediates conjugation of ISG15 to uterine proteins in response to the developing and attaching conceptus.
The evolution of nonsteroidal antiestrogens to become selective estrogen receptor modulators.

Abstract The discovery of the first nonsteroidal antiestrogen ethamoxytriphetol (MER25) in 1958, opened the door to a wide range of clinical applications. However, the finding that ethamoxytriphetol was a “morning after” pill in laboratory animals, energized the pharmaceutical industry to discover more potent derivatives. In the wake of the enormous impact of the introduction of the oral contraceptive worldwide, contraceptive research was a central focus in the early 1960’s. Numerous compounds were discovered e.g., clomiphene, nafoxidine, and tamoxifen, but the fact that clinical studies showed no contraceptive actions, but, in fact, induced ovulation, dampened enthusiasm for clinical development. Only clomiphene moved forward to pioneer an application to induce ovulation in subfertile women. The fact that all the compounds were antiestrogenic made an application in patients to treat estrogen responsive breast cancer, an obvious choice. However, toxicities and poor projected commercial returns severely retarded clinical development for two decades. In the 1970’s a paradigm shift in the laboratory to advocate long term adjuvant tamoxifen treatment for early (non-metastatic) breast cancer changed medical care and dramatically increased survivorship. Tamoxifen pioneered that paradigm shift but it became the medicine of choice in a second paradigm shift for preventing breast cancer during the 1980’s and 1990’s. This was not surprising as it was the only medicine available and there was laboratory and clinical evidence for the eventual success of this application. Tamoxifen is the first medicine to be approved by the Food and Drug Administration (FDA) to reduce the risk of breast cancer in women at high risk. But it was the re-evaluation of the toxicology of tamoxifen in the 1980’s and the finding that there was both carcinogenic potential and a significant, but small, risk of endometrial cancer in postmenopausal women that led to a third paradigm shift to identify applications for selective estrogen receptor (ER) modulation. This idea was to establish a new group of medicines now called selective ER modulators (SERMs). Today there are 5 SERMs FDA approved (one other in Europe) for applications ranging from the reduction of breast cancer risk and osteoporosis to the reduction of menopausal hot flashes and improvements in dyspareunia and vaginal lubrication. This article charts the origins of the current path for progress in women’s health with SERMs.
Metastatic malignant clear cell hidradenoma associated with bullous pemphigoid.

SUMMARY The clinicopathological features of a case of mctastatic malignant clear cell hidradenoma (MCCH) occurring in a 72-year-old black male are reported. Unusual features of the case included the location of the tumour on the posterior trunk, the probable origination of the tumour from a benign appendageal tumour, and the occurrence of a bullous eruption immediately after surgical removal of the tumour. Clinicopathological aspects of MCCH are reviewed and treatment modalities, including chemotherapy, are discussed.
THE PREPARATION OF 3-(2-PHENYLETHENYL)-1H-PYRAZOLES FROM DILITHIATED (3E)-4-PHENYL-3-BUTEN-2-ONE HYDRAZONES

The phenyl-, carbomethoxy-, and carboethoxy-hydrazones of (3E)-4-phenyl-3-buten-2-one [benzalacetone] were treated with excess lithium diisopropylamide, and the resulting 1,4-dianions were condensed with several aromatic esters, followed by acid cyclization of C-acylated intermediates, to afford substituted 3-(2-phenylethenyl)-1H-pyrazoles [3-styryl-pyrazoles].
Interest Traitedness as a Moderator of Interest-Occupation Congruence.

Abstract The moderating effect of interest traitedness on the interest–occupation fit with career certainty relation was examined. A representative sample of from 4676 12th-grade students completed the Unisex Edition of the ACT Interest Inventory (UNIACT). Several different indices of traitedness were examined as they interacted with the interest–occupation fit with career certainty relation. A series of hierarchical regressions revealed that although all traitedness indices manifest a significant moderation effect, the magnitude of the effect was small. Results are discussed with respect to applications to other samples and variables.
Impaired activation of thermogenesis in the corpulent rat

The capacity for non-shivering thermogenesis was measured in groups of 12 week-old congenic lean and corpulent LA/N-cp rats of both sexes to determine if their obese state might be associated with an impairment in energy expenditure via non-shivering thermogenesis. Body weights of the corpulent phenotypes were 1.6 to 1.8 times greater than those of the lean phenotype. Measurements of resting oxygen consumption were similar in lean and in corpulent rats, and were greater in female than in male rats. Isoproterenol stimulation resulted in a significant increase in oxygen consumption in lean rats, while the rates of oxygen consumption of isoproterenol-stimulated corpulent rats were unchanged. Acute exposure of male rats to a 5 degrees C cold environment resulted in significant decreases in colonic and in rectal temperature in both phenotypes, but body temperatures recovered more rapidly in lean than in corpulent rats. Urinary VMA excretion was greater in lean than in corpulent rats and increased following cafeteria-feeding in lean but not in corpulent rats. These observations are consistent with an impaired mechanism of sympathetically-mediated thermogenesis in the corpulent phenotype of the LA/N-cp rat, and which may be a contributing factor in the development of their obese state via a decreased capacity for energy expenditure.
On the Theory and Practice of Compradors: The Role of Abbud Pasha in the Egyptian Political Economy

One of the most resilient ideas introduced to the analysis of economic and political change under colonialism and imperialism is the “comprador” and, by extension, the “comprador bourgeoisie.” The comprador in essence embodies or internalizes the basic theoretical problem of the peripheral political economy: economic activity oriented primarily for the benefit of the other.1 By strict definition, compradors are native agents or partners of foreign investors who operate in some form in the local economy. However, in the theoretical context of assessing the possibilities for local industrial development, compradors represent forces that hinder change. As “agents of foreign imperialism,” they act “against the interest of the national economy.”2
Optimizing the location of input/output stations within facilities layout

Abstract This paper proposes a methodology for characterizing and locating input/output stations within a facilities layout, with the objective of maximizing flow efficiency. A set of stations is first defined for each department, each of these stations is restricted to a feasible boundary region. An interstation flow set is generated based on the station characteristics and the interdepartment flows. Then an efficient optimization model, related to the multifacility location model, is solved to obtain a set of station locations minimizing the sum of the rectilinear distance travelled by all interstation flows, given the boundary regions on station location.
Gated SPECT myocardial perfusion imaging in patients referred with isolated complaints of Dyspnea

Abstract Background: Dyspnea is a common indication for referral for cardiovascular stress testing. We sought to characterize the utility of gated SPECT stress perfusion imaging in patients referred because of a chief complaint of dyspnea. In this group comorbidities included cad 22%, hyperternsion 74%, hyperlipidemia 49%, diabetes 38%, chf 20%, copd 17%. Methods: a total of 89 consecutive (66 ± 13 yrs) patients from a total referral population of 870 pts were referred for a chief complaint of dyspnea. Patients underwent dual gated SPECT myocardial imaging utilizing either an exercise protocol or an abbreviated, 4 minute adenosine infusion (140 ug/kg/min; 4 min; 1 mph walk) with simultaneous low level exercise. Coronary artery disease was determined by calculation of summed stress scores (SSS) using the conventional, previously validated 17 segment (0–4 perfusion scale) model with a SSS>4 used as a threshold for an abnormal scan. Results: Perfusion defects diagnostic for CAD were present in 22% of the patients presenting with dyspnea and were of varying degree of severity. While mean systolic function for the overall group was normal (EF=52±15%), compared to patients with a negative nuclear scan (SSS Conclusion: clinically significant perfusion defects are found in a small but significant percentage of patients referred with an isolated complaint of dyspnea. Scan Results and Risk Category Patients Normal (SSS 78% Low risk (SSS 4–8) 12% Intermediate risk (SSS 9–13) 6% High risk (SSS >13) 4%