cssi/SciSciGPT-SciSciNet huggingface dataset:
Promoting autophagic clearance: viable therapeutic targets in Alzheimer's disease.

Many neurodegenerative disorders are characterized by the aberrant accumulation of aggregate-prone proteins. Alzheimer’s disease (AD) is associated with the buildup of β-amyloid peptides and tau, which aggregate into extracellular plaques and neurofibrillary tangles, respectively. Multiple studies have linked dysfunctional intracellular degradation mechanisms with AD pathogenesis. One such pathway is the autophagy–lysosomal system, which involves the delivery of large protein aggregates/inclusions and organelles to lysosomes through the formation, trafficking, and degradation of double-membrane structures known as autophagosomes. Converging data suggest that promoting autophagic degradation, either by inducing autophagosome formation or enhancing lysosomal digestion, provides viable therapeutic strategies. In this review, we discuss compounds that can augment autophagic clearance and may ameliorate disease-related pathology in cell and mouse models of AD. Canonical autophagy induction is associated with multiple signaling cascades; on the one hand, the best characterized is mammalian target of rapamycin (mTOR). Accordingly, multiple mTOR-dependent and mTOR-independent drugs that stimulate autophagy have been tested in preclinical models. On the other hand, there is a growing list of drugs that can enhance the later stages of autophagic flux by stabilizing microtubule-mediated trafficking, promoting lysosomal fusion, or bolstering lysosomal enzyme function. Although altering the different stages of autophagy provides many potential targets for AD therapeutic interventions, it is important to consider how autophagy drugs might also disturb the delicate balance between autophagosome formation and lysosomal degradation.
Pulmonary clear cell carcinoid tumor: Another entity in the differential diagnosis of pulmonary clear cell neoplasia

A clear cell variant of primary pulmonary carcinoid tumor is described. The tumor arose in a 53-year-old woman who was incidentally found to have a solitary pulmonary nodule in the left upper lobe during routine chest roentgenography. Histologically, the tumor was composed of predominantly clear
Locating an obnoxious facility within a polygonal region

The purpose of this paper is to review some of the many instances in which a location analyst must make a decision as to where an obnoxious facility should be placed. An obnoxious facility is one that can be defined as a facility which has undesirable interactions with existing facilities. Examples include equipment which emit pollutants such as particulates, noise and radiation or warehouses that contain flammable materials. Other obnoxious facilities include machines that are potential sources of hazards to nearby machines and workers. The interaction between the obnoxious facility and each existing facility is reflected through a weighting factor. The feasible region is considered to be continuous in the form of a convex or nonconvex simple polygon. Since the new facility is to be located away from the existing facilities, an appropriate criterion for optimization is the MAXIMIN or the MAXISUM criterion. Algorithms are reviewed for two common metrics under both criteria, i.e. Euclidean and rectilinear.
Post-transcriptional regulation of interleukin 1 alpha in various strains of young and senescent human umbilical vein endothelial cells.

Abstract Human umbilical vein endothelial cell (HUVEC) senescence in vitro is characterized by the loss of proliferative potential and an increase in cell size. Because HUVEC senescence in one strain (H101) has been characterized by the increase in the steady-state mRNA level for the signal-peptideless cytokine, interleukin (IL) 1 alpha, we have examined young and senescent populations of five additional HUVEC strains (H3605, H103, H928, H929, and H930) to determine whether the elevated levels of IL-1 alpha mRNA could be observed in all HUVEC strains. Consistent with the data from strain H101, strains H3605 and H930 also exhibited a low steady-state level of the IL-1 alpha mRNA in young populations compared to elevated levels of IL-1 alpha mRNA in the senescent populations. However, three strains (H103, H928, and H929) did not exhibit reduced levels of IL-1 alpha mRNA in the young populations, and interestingly, strain H928, at times, expressed relatively high IL-1 alpha mRNA levels in the young populations. In addition, expression of the steady-state level of plasminogen activator inhibitor 1 and cyclooxygenase 2 was elevated in senescent populations of all HUVEC strains examined, whereas young populations exhibited a low level of expression for these genes regardless of the IL-1 alpha mRNA level. Further, the level of the IL-1 alpha polypeptide was elevated in senescent HUVEC populations relative to young populations that expressed either a high or low level of the IL-1 alpha mRNA. We have also demonstrated that the elevated level of IL-1 alpha mRNA in the senescent population of strain H3605 may be regulated by mRNA stability; however, this mechanism does not apply to all the HUVEC strains examined in this study. Thus, we suggest that while mRNA levels of the IL-1-response genes for plasminogen activator inhibitor 1 and cyclooxygenase 2 are appropriate markers for HUVEC senescence, HUVEC strain-specific post-transcriptional mechanisms may exist to regulate the function of IL-1 alpha as a modifier of HUVEC senescence in vitro.
Results from the scaled final focus experiment

Abstract Vacuum ballistic focusing is the straightforward method to obtain a heavy-ion beam spot size necessary to drive an inertial confinement fusion target. The beam is first expanded then focused to obtain the desired convergence angles at the exit of the last element. This is done in an attempt to achieve a focal spot size in which emittance is the limiting factor; however, aberrations and space charge will influence the spot radius. Proper scaling of particle energy, mass, beam current, beam emittance, and magnetic field replicates the dynamics of a full driver beam at the focus in a small laboratory experiment. By scaling the beam current to ∼100 A, 160 keV Cs + has been used to study experimentally a proposed driver design at one-tenth scale. Once a nominal focal spot is achieved, the magnet strengths are deliberately de-tuned to simulate the effect of an off-momentum slice of the beam. Additionally, several methods will be used to inject electrons into beam following the last focusing element in order to study the neutralization of space charge and its effect on the focus. Transverse phase space and beam current density measurements at various stages of the focus will be presented as well spot size measurements from the various trials. This data will be compared to the results of a PIC model of the experiment.
Male sex, African American race or ethnicity, and triiodothyronine levels at diagnosis predict weight gain after antithyroid medication and radioiodine therapy for hyperthyroidism.

Objective: To determine whether racial or ethnic differences affect weight gain after treatment of hyperthyroidism and to reassess established risk factors such as sex, age, and cause of hyperthyroidism.Methods: We conducted a retrospective review of medical records of 111 patients treated with radioiodine (RAI) for hyperthyroidism, with or without preceding antithyroid medication, during 2002 to 2005. We ascertained age, sex, race or ethnicity, insurance status, compliance with visits, serum triiodothyronine (T3) level at diagnosis, and cause of hyperthyroidism. Weights and serum thyroidstimulating hormone levels were obtained at diagnosis, at time of RAI therapy, and at 0 to 4 months, 4 to 8 months, 8 to 12 months, and 24 months after RAI treatment.Results: There was a significant weight increase after treatment of hyperthyroidism. Levels of T3 at initial diagnosis of hyperthyroidism, male sex, and black or Hispanic ethnicity were found to be independent predictors of weight gain after RAI treatment. We...
housewife, Mother, Other: Needs and Helpers

Throughout the country many women with school-age children are attempting to find a means of becoming active outside the home. In this article the authors describe these women and discuss the impact of the women's movement on them. They also discuss the new agencies and the counselors that have been helping these women in their quest for liberation, and they point out the challenges that counselors have the opportunity to meet.
Differential Contributions of the Outer Membrane Receptors PhuR and HasR to Heme Acquisition in Pseudomonas aeruginosa

Pseudomonas aeruginosa PAO1 encodes two outer membrane receptors, PhuR (Pseudomonas heme uptake) and HasR (heme assimilation system). The HasR and PhuR receptors have distinct heme coordinating ligands and substrate specificities. HasR is encoded in an operon with a secreted hemophore, HasAp. In contrast the non-hemophore-dependent PhuR is encoded within an operon along with proteins required for heme translocation into the cytoplasm. Herein we report on the contributions of the HasR and PhuR receptors to heme uptake and utilization. Employing bacterial genetics and isotopic [13C]heme labeling studies we have shown both PhuR and HasR are required for optimal heme utilization. However, the unique His-Tyr-ligated PhuR plays a major role in the acquisition of heme. In contrast the HasR receptor plays a primary role in the sensing of extracellular heme and a supplementary role in heme uptake. We propose PhuR and HasR represent non-redundant heme receptors, capable of accessing heme across a wide range of physiological conditions on colonization of the host.
The Wisdom Tradition and the Synoptic Gospels

An earlier generation of New Testament scholarship found the generalizing tendency of Wisdom quite congenial, and indeed interpreted the New Testament, or at least the message of Jesus, as a kind of higher wisdom.' In reaction against the tendency to reduce the New Testament message to general truths, New Testament study today looks for other ways of bringing the New Testament into relation with its environment, and pays little attention to Wisdom, except that inverted Wisdom, Gnosticism. Let us first then say that Jewish Wisdom was indeed characterized by the attempt to formulate brief general statements about recurring processes in man's life in a word, to formulate proverbs but that Wisdom is a much richer and more complex phenomenon than the description "general truths" suggests. Old Testament scholarship is now recognizing the complexity and religious vitality of the Wisdom tradition,2 a fact that can provide incentive to a renewed examination of the use of, or parallels to, this tradition in the Synoptic Gospels. We may characterize the Wisdom tradition briefly, in two respects. First, though it was not historical in the sense of being concerned with the history of the covenant community, the Wisdom tradition was, in its own way, "historical." That is, it was concerned with the individual man in his "little history," in the context in which he made his decisions as a responsible human being. Man's real existence is lived in concrete interaction with his fellow-men. This concrete understanding of life underlies the general rules that are often supposed to be the basis of wisdom.
Education in Post-war Bosnia: The Nexus of Societal Security, Identity and Nationalism

The notion of security in international relations has been broadened and reconceptualized and now rightly includes an understanding of education as a potential security threat, not just a socializing tool. In post-war Bosnia-Herzegovina, the education system is decentralized, politicized and nationalistic, and promotes competing visions and identities of Bosnia. Some students attend segregated schools, while almost all study only with others from their same ethnonational group and learn from a mono-ethnic curriculum that does not foster understanding or tolerance of others, but breeds suspicion. This paper argues that these educational practices constitute a societal security dilemma. Many Bosnian Muslims, Croats and Serbs use the education system to gain rights and security for their group, which is viewed by others as a potential threat to their own security and identity within a fractured state. This paper shows that while these attempts to reinforce group security and identity (and increase power) may...
Experimental eosinophilia. IV. Eosinotactic influences of polysaccharides.

Abstract The administration of heterologous and homologous species glycogen, soluble starch amylodextrin, starch amylopectin, laminarin, inulin, or high molecular weight dextran into the rabbit foot pad resulted in 4-hour eosinophilic granular cell infiltrations into the sinuses of regional popliteal lymph nodes. Similar histologic alterations could not be demonstrated with component monosaccharides or with other non-carbohydrate macromolecular histamine-releasing agents including acacia, stilbamadine, peptone, trypsin, polyvinylpyrrolidone, or polymyxin B. The eosinotactic effects of glycogen were studied through the use of chemical inhibitors and antagonists. These effects could not be related to release of histamine, serotonin, or heparin. Precipitation of amylodextrin and amylopectin by normal sera suggests the possibility of participation of some polysaccharides in immune reactions with preformed antibody. However, the eosinotactic effects of polysaccharides could not be related to any delineated immunologic phenomena or chemotactic action.
The fat and the skinny on acute lung injury.

In this issue of Blood, Ortiz-Munoz et al take a critical step in evaluating an advanced model of acute lung injury (ALI) pathology, implicating the accumulation of leukocyte-platelet aggregates (LPAs) in alveolar spaces, a central role of bioactive lipids in this process, and a particular identification of 15-epi-lipoxin A4 (LXA4) as a central player in the efficacy of aspirin-regulated protection from ALI.1 These events have been previously described in isolation,2-4 but this report synthesizes them together into a central model that sheds new light on the multifactorial landscape of ALI pathogenesis.
Phosphorylation of the Proteasome Activator PA28 Is Required for Proteasome Activation

Abstract PA28, also referred to as 11S regulator, is a potent activator of the peptidase activities of the proteasome (multicatalytic proteinase complex). Although the role(s) of PA28-20S proteasome complexes in cellular proteolytic processes remain to be defined, these particles have been implicated in antigen processing of major histocompatibility complex (MHC) class I molecules. Our results demonstrate that PA28 is phosphorylated as evidenced by32P incorporation into a single PA28 species in rabbit reticulocytes. In reticulocytes as well as human erythrocytes, PA28 is normally found in a phosphorylated state as detected by phosphoserine antibody. In human erythrocytes, this antibody recognizes three polypeptides which are also detected by antibody to PA28 on Western blot analysis. Dephosphorylation with alkaline phosphatase treatment completely abolishes the ability of PA28 to activate hydrolysis of Suc-Leu-Leu-Val-Tyr by proteasomes. After exposure to phosphatase, the three polypeptides are no longer recognized by phosphoserine antibody, although binding to PA28 antibody is unaffected. These results suggest that phosphorylation may function in transduction of cytokine and growth factor signals that, in turn, modulate antigen presentation and other processes which involve PA28-20S proteasome complexes.
Vitamin D and ageing

Within the past three to four decades a revolution has occurred in our understanding of vitamin D and its effects. Sundry laboratory and epidemiologic studies have revealed that the active metabolite of vitamin D controls and/or ameliorates various pathologies. As presented here, there is substantive evidence that vitamin D may play a positive and important role in the ageing process. This evidence arises from detailed consideration of various biological mechanisms and processes by which vitamin D operates as well as specific examples of its exerting control/amelioration of various human maladies which contribute to ageing. Arguments are advanced that vitamin D appears to play a major positive role in biogerontology by reducing susceptibility in the elderly to chronic degenerative diseases. It is strongly recommended that the positive role of vitamin D in ageing be taken into account by gerontologists and biogerontology researchers.
Effects of food supplies and water temperature on growth rates of two species of freshwater tropical shrimps

Summary Growth rates of individual freshwater shrimp of the species Atya lanipes and Xiphocaris elongata were measured in a second-order stream in the Luquillo Experimental Forest in Puerto Rico over 10 years (1997–2007). Shrimp living at lower altitudes in warmer water and wider stream channels with more algal and detrital foods were predicted to grow and reproduce more rapidly. Shrimp were marked and recaptured periodically in pools located at three altitudes to determine whether temperature affected growth rates among individual A. lanipes and X. elongata. Mean annual water temperatures ranged from 20 to 24 °C with the uppermost pool being cooler than the lower pools. Mean annual growth rates for Atya and Xiphocaris were 0.27 and 0.1 mm carapace length, respectively, for all three populations. Differences in growth were partially influenced by how each species obtains its food. Atya is a filter feeder and scraper and has continuous access to suspended organic particles and biofilms. The slower growth rate for Xiphocaris elongata is most likely a result of the wider range in quality and accessibility of food resources. Differences in pool morphology and depths probably affected differences in food availability. Increased leaf litter retention in the deeper upper and lower pools probably increased shrimp growth rates, while washout of leaf litter from the relatively shallow, elongate mid-altitude pool decreased Atya lanipes growth rates. These long-lived, slow-growing shrimp species transform a wide range of organic materials into their biomass. Because of the slow growth rates of these detritivores shrimp, tropical storms, hurricanes, droughts or other disturbances could have persistent, long-term impacts on detrital processing and on the populations of their predators.
Planning viewpoints that simultaneously satisfy several feature detectability constraints for robotic vision

The authors present results of a method developed which automatically determines viewpoints for a robotic vision system so that object features of interest are simultaneously visible, inside the field-of-view, in-focus and magnified as required. The authors previously (1990, 1991) analytically characterized the domain of admissible camera locations, orientations and optical settings for which each of these feature detectability requirements is satisfied separately. In addition, they presented a technique that poses the problem in an optimization setting in order to determine viewpoints that satisfy all requirements simultaneously and with a margin. In this paper, they present results of this technique when all the feature detectability constraints are included. In order to verify that all the constraints are indeed satisfied, camera views are taken from the computed viewpoints by a robot vision system that is positioned and its lens is set according to the results of this method. >
A study of the effects of non-specific filtering on the gene expression data prior to statistical testing

The overall variance filtering together with five different multiple testing procedures are examined using simulation studies. The results show that filtering do increase the power of detection without losing control of Type I error rates. The Benjamimi & Hochberg step-up procedure is the best among the five tested ones.
Severe frontal sinus barotrauma in an airline passenger: a case report and review

The problems of sinus barotrauma in air travelers have received little attention in the literature of emergency medicine. Presented here is a report of severe (Grade III) frontal sinus barotrauma in an airline passenger. The pathophysiology and treatment of frontal sinus barotrauma are reviewed. Emergency physicians should strongly consider a diagnosis of sinus barotrauma in patients who present with symptoms of sinusitis and a history of recent flight.
Direct Care Worker’s Perceptions of Job Satisfaction Following Implementation of Work-Based Learning

The purpose of this study was to understand the impact of a work-based learning program on the work lives of Direct Care Workers (DCWs) at assisted living (AL) residences. The research questions were addressed using focus group data collected as part of a larger evaluation of a work-based learning (WBL) program called Jobs to Careers. The theoretical perspective of symbolic interactionism was used to frame the qualitative data analysis. Results indicated that the WBL program impacted DCWs’ job satisfaction through the program curriculum and design and through three primary categories: relational aspects of work, worker identity, and finding time. This article presents a conceptual model for understanding how these categories are interrelated and the implications for WBL programs. Job satisfaction is an important topic that has been linked to quality of care and reduced turnover in long-term care settings.
Painting a portrayal of narrators with learning disabilities from two narrative perspectives

Two narrative perspectives, high point analysis and episodic analysis, were used to compare the ability of narrators with and without learning disabilities to fulfill the referential and evaluative narrative functions. The participants were 82 students with learning disabilities and their typically achieving peers matched on age, grade, gender, and ethnicity. The participants (48 Caucasian, 34 African American) attended urban and suburban schools (Grades 4-7). Narratives were collected within the context of a naturalistic conversation. The findings across the two narrative perspectives showed areas of incongruence in specific narrative competencies. While these findings expand the portrayal of narrators with learning disabilities, they also imply the impact of using specific narrative analyses and genres for the narrative assessment and intervention outcomes.
Induction of Flexibility through Protein-Protein Interactions

The dimerization/docking (D/D) domain of the cyclic AMP-dependent protein kinase (PKA) holoenzyme mediates important protein-protein interactions that direct the subcellular localization of the enzyme. A kinase anchoring proteins (AKAPs) provide the molecular scaffold for the localization of PKA. The recent solution structures of two D/D AKAP complexes revealed that the AKAP binds to a surface-exposed, hydrophobic groove on the D/D. In the present study, we present an analysis of the changes in hydrogen/deuterium exchange protection and internal motions of the backbone of the D/D when free and bound to the prototype anchoring protein, Ht31(pep). We observe that formation of the complex results in significant, but small, increases in H/D exchange protection factors as well as increases in backbone flexibility, throughout the D/D, and in particular, in the hydrophobic binding groove. This unusual observation of increased backbone flexibility and marginal H/D exchange protection, despite high affinity protein-ligand interactions, may be a general effect observed for the stabilization of hydrophobic ligand/hydrophobic pocket interactions.
Energy-efficient communication for high density networks

New generations of AmI devices will need to deliver unprecedented system lifetime from increasingly smaller and constrained energy sources. Energy-efficient system design, and energy-efficient wireless communication in particular, will therefore be key enablers of next-generation AmI devices. Using the microsensor network as our design driver, we present the impact of accurate system models, dynamic energy vs. performance trade-offs, and application-specific design, each applied to the protocol and application layers. Comprehensive models of wireless communication hardware reveal surprising discrepancies between expectations and realities of the energy consumption of multihop routing. An abstraction layer encourages performance trade-offs at the protocol level that translate into energy agility at the hardware level. Application-specific design, applied to protocols, enables an efficient protocol for data propagation in microsensor networks.
A compact IGFET charge model

A new IGFET charge model, consistent with the recently published Compact Short-Channel IGFET Model [1], [2], is presented. It is simple, accurate, and suitable for circuit simulation applications. Charge conservation is guaranteed by using charge as the state variable. The partitioning of channel charge into drain and source components is given significant attention. This partitioning changes smoothly from 40/60 in the saturation region asymptotically to 50/50 in the triode region. The terminal charges are well behaved over all regions of operation. This charge model and its dc characteristic counterpart, derived from the same considrerations of MOS device physics, form a unified model previously unavailable.
Evanescent coupling to the slow-light modes in periodically patterned silicon microring resonators

We demonstrate evanescent coupling between a strip waveguide and a periodically-patterned ring resonator in the slow light regime. Resonances with a group index >22 are efficiently coupled with an extinction ratio of >20 dB.
Adaptive Registration of Very Large Images

The main difficulty in image registration is in determining the geometric difference between the given images. An image registration method is introduced that determines the geometric difference between two images in a coarse-to-fine fashion. The global transformation needed to register the images is defined in terms of a collection of local transformations, each describing the geometric difference between corresponding local neighborhoods in the images. Preliminary experimental results of the proposed method are presented and discussed.
Recovery of decomposition and soil microarthropod communities in an Appalachian watershed two decades after a clearcut

We examined decomposition rates of three substrates (Quercus prinus L., Acer rubrum L., and Cornus florida L.) in a watershed 21 years after it had been clearcut, and compared them to an adjacent control watershed. Previous investigations at these sites had shown that microarthropod populations, important components of the decomposer community, were considerably less dense in the clearcut watershed and that decomposition rates were reduced. Twenty-one years after clearcut decomposition rates in the clearcut watershed had reconverged with the control, and in the case of one substrate (C. florida) now exceeded the control. Microarthropods maintained denser populations in the clearcut watershed, and oribatid assemblages, the most abundant taxonomic group, were more diverse in that watershed. A contrast of the decomposition of the substrates 8 and 21 years after cable-logging revealed that decomposition was slower in the control watershed in the more recent observations, though this may reflect lower precipitation that year. These results seem to confirm that microarthropod recovery may be indicative of a restored decomposer community functioning, and that this may be reflective of reconverged abiotic conditions at the site.
Can Knowledge Improve Population Forecasts at Subcounty Levels

Recent developments in urban and regional planning require more accurate population forecasts at subcounty levels, as well as a consideration of interactions among population growth, traffic flow, land use, and environmental impacts. However, the extrapolation methods, currently the most often used demographic forecasting techniques for subcounty areas, cannot meet the demand. This study tests a knowledge-based regression approach, which has been successfully used for forecasts at the national level, for subcounty population forecasting. In particular, this study applies four regression models that incorporate demographic characteristics, socioeconomic conditions, transportation accessibility, natural amenities, and land development to examine the population change since 1970 and to prepare the 1990-based forecast of year 2000 population at the minor civil division level in Wisconsin. The findings indicate that this approach does not outperform the extrapolation projections. Although the regression methods produce more precise projections, the least biased projections are often generated by one of the extrapolation techniques. The performance of the knowledge-based regression methods is discounted at subcounty levels by temporal instability and the scale effect. The regression coefficients exhibit a statistically significant level of temporal instability across the estimation and projection periods and tend to change more rapidly at finer geographic scales.
Variational Inference for Crowdsourcing

Crowdsourcing has become a popular paradigm for labeling large datasets. However, it has given rise to the computational task of aggregating the crowdsourced labels provided by a collection of unreliable annotators. We approach this problem by transforming it into a standard inference problem in graphical models, and applying approximate variational methods, including belief propagation (BP) and mean field (MF). We show that our BP algorithm generalizes both majority voting and a recent algorithm by Karger et al. [1], while our MF method is closely related to a commonly used EM algorithm. In both cases, we find that the performance of the algorithms critically depends on the choice of a prior distribution on the workers' reliability; by choosing the prior properly, both BP and MF (and EM) perform surprisingly well on both simulated and real-world datasets, competitive with state-of-the-art algorithms based on more complicated modeling assumptions.
C3 or Not C3. That Is the Question

Numerous investigators have studied the potential genetic causes of essential hypertension, and several genes have been described as candidates.1,2 These genes may contribute to the inappropriate and exaggerated growth of arterial smooth muscle cells in genetically hypertensive individuals and thus ultimately contribute to the disease by supporting creation of stronger, more muscular, and sometimes narrowed arteries. The article by Lin et al in this issue of Hypertension 3 describes selective expression of the complement protein complement 3 (C3) in arterial cells from the spontaneously hypertensive rat (SHR) and clear involvement of this protein in mediating enhanced arterial smooth muscle growth in the SHR. The complement system is a major effector of humoral immunity and innate immunity. Complement proteins, normally found in the plasma, are inactive and become active through classical stimulation (antibody-activated) pathways or alternative (cell surface–activated) pathways. Proteolysis of C3 represents an early and essential event in complement activation through either pathway. Cleavage of C3 by spontaneous breakdown, binding to a microbial surface, or through binding a C3 convertase leads to generation of 2 proteolytic proteins called C3a and C3b. These effectors act ultimately to cause phagocytosis of opsonized particles, activate later stages of complement (through formation of C5 convertase), …
The elevated mRNA content as a potential indicator of precancerous states of the gallbladder mucosa in patients with pancreaticobiliary maljunction.

Pancreaticobiliary maljunction (PBM) patients have a high incidence of cancer in the gallbladder. In the present study, we showed that precancerous lesions in the gallbladder of PBM such as hyperplasia or metaplasia, indicated high concentration of the amount of total mRNA. The mRNA content could be easily measured by our new technique utilizing a GenePlate®, which is a poly (dT) oligonucleotide immobilizcd plastic plate, and Yoyo-1, a fluorescent DNA intercalator. To standardize the mRNA contents, we utilized 'mRNA index' which was defined as the ratio of total mRNA contents to total nucleic acids in a same sample. The mRNA index of the proliferating cells was significantly higher than that of the resting cells, and the mRNA index of cancer cells, such as gastric cancer, colon cancer, bile duct cancer, and gallbladder cancer also showed significantly higher concentration than that of normal mucosa. In the study of precancerous lesion, PBM, the mRNA index was significantly higher than that of mild cholecystitis but less than that of gallbladder cancer, suggesting that in the gallbladder mucosa of PBM, a precancerous state was able to be diagnosed by the mRNA index.
Individual differences in Macaques' responses to stressors based on social and physiological factors: implications for primate welfare and research outcomes

Primates are used extensively in a variety of research settings. Federal regulations in the US mandate that caretakers provide for the 'psychological well-being of laboratory primates'. One of the difficulties in implementing this law has been both in the definition of psychological well-being and in the need to deal with each primate species and, in some cases, age or sex class, uniquely. Non-human primates exhibit distinct individual differences in their behavioural and physiological responses to experimental challenges and caretaking procedures. We have been investigating what factors can predict some of these individual differences, and have found that factors both intrinsic and extrinsic are significant. Extrinsic factors found to predict individual differences in response to stressors include the nature and prior experience with the challenge, the presence of familiar peers and availability of social support. Intrinsic factors include cognitive interpretations of the challenge and temperamental differences in reactivity. These studies highlight the importance of understanding the context and individual psychology of macaques in order to provide laboratory environments conducive to their welfare, and in order to understand the impact experimental and caretaking procedures are likely to have on the health and welfare of our subjects.
A new dynamic adaptive hyperpolarized noble gas magnetic resonance imaging technique

A new dynamic magnetic resonance imaging method was developed to image rat lung dynamics using hyperpolarized noble gases. Spatially selective encoding methods were developed for imaging hyperpolarized noble gases. These methods were customized for dynamic imaging using an adaptive approach, so that temporal and spatial resolution could be improved.
Plans to increase source brightness of NSLS X-ray ring

We discuss plans to increase the NSLS X-ray ring source brightness by an order of magnitude. Proposed improvements include doubling current from 250 mA to 500 mA, reducing vertical emittance by a factor of 6 and reducing insertion device gaps and periods by up to a factor of two. Experimental results are reported which indicate we have succeeded in reducing the vertical emittance below 2 /spl Aring/. >
Detailed characterization of antibody responses against HIV-1 group M consensus gp120 in rabbits

We recently reported induction of broadly neutralizing antibodies (bnAbs) against multiple HIV-1 (human immunodeficiency virus type 1) isolates in rabbits, albeit weak against tier 2 viruses, using a monomeric gp120 derived from an M group consensus sequence (MCON6). To better understand the nature of the neutralizing activity, detailed characterization of immunological properties of the protein was performed. Immunogenic linear epitopes were identified during the course of immunization, and spatial distribution of these epitopes was determined. Subdomain antibody target analyses were done using the gp120 outer domain (gp120-OD) and eOD-GT6, a protein based on a heterologous sequence. In addition, refined epitope mapping analyses were done by competition assays using several nAbs with known epitopes. Based on linear epitope mapping analyses, the V3 loop was most immunogenic, followed by C1 and C5 regions. The V1/V2 loop was surprisingly non-immunogenic. Many immunogenic epitopes were clustered together even when they were distantly separated in primary sequence, suggesting the presence of immunogenic hotspots on the protein surface. Although substantial antibody responses were directed against the outer domain, only about 0.1% of the antibodies bound eOD-GT6. Albeit weak, antibodies against peptides that corresponded to a part of the bnAb VRC01 binding site were detected. Although gp120-induced antibodies could not block VRC01 binding to eOD-GT6, they were able to inhibit VRC01 binding to both gp120 and trimeric BG505 SOSIP gp140. The immune sera also efficiently competed with CD4-IgG2, as well as nAbs 447-52D, PGT121 and PGT126, in binding to gp120. The results suggest that some antibodies that bind at or near known bnAb epitopes could be partly responsible for the breadth of neutralizing activity induced by gp120 in our study. Immunization strategies that enhance induction of these antibodies relative to others (e.g. V3 loop), and increase their affinity, could improve protective efficacy of an HIV-1 vaccine.
User-context for adaptive user interfaces

We present results from an empirical user-study with ten users which investigates if information from a user's environment helps a user interface to personalize itself to individual users to better meet usability goals and improve user-experience. In our research we use a microphone and a web-camera to collect this information (user-context) from the vicinity of a subject's desktop computer. Sycophant, our context-aware calendaring application and research test-bed uses machine learning techniques to successfully predict a user-preferred alarm type. Discounting user identity and motion information significantly degrades Sycophant's performance on the alarm prediction task. Our user study emphasizes the need for user-context for personalizable user interfaces which can better meet effectiveness and utility usability goals. Results from our study further demonstrate that contextual information helps adaptive interfaces to improve user-experience.
Device modeling of an optimized monolithic all lattice-matched 3-junction solar cell with efficiency > 50%

Currently, there is a critical need for a photovoltaic design that will convert sunlight into electricity with practical efficiencies higher than 50%. Multijunction Solar Cells (MJSCs) are one of the most promising options to achieve ultra-high efficiencies. III–V compound semiconductors are generally used to fabricate MJSCs; however, limitations imposed by the lattice constants of available substrates strongly restrict which materials can be used for high-quality epitaxial growth. Herein we present an alternative design for an all lattice-matched monolithic 3-junction solar cell formed by (1.93 eV) InAlAs / (1.39 eV) InGaAsP / (0.94 eV) InGaAs, with 5.807 A lattice constant. 1-dimensional device modeling for each individual subcell, as well as for the tandem device were performed under AM 1.5 direct illumination and concentrated sunlight. The role of concentration in each figure of merit was analyzed and Auger recombination was found to play an important role for high-injection levels. For a current match of 1.58 A/cm2 we found that > 51% in efficiency can be achieved under 100-suns (with V oc = 3.34 V). A detailed analysis of the effect of concentration on the device performance is presented.
Viscous interactions of many neutrally buoyant spheres in Poiseuille flow

A theory is developed to predict the motion of N neutrally buoyant spheres suspended in laminar flow between parallel plates. The spheres are at large separation yet nearer each other than the duct walls, and the Reynolds number is small. In this parameter range, viscous interactions are larger than inertial effects, and can be represented in terms of a superposition of ‘strainlets’. Several examples are given to show this viscous interaction effect. Near the leading edge of a front of spheres or near the trailing edge significant lateral migration velocities can occur, being at least one order of magnitude larger than inertially induced migration velocities. This phenomenon may have a negative effect on ‘chromatographic’ separation schemes, affecting particle concentration, recovery and resolution.
Generation of HLA-C-specific cytotoxic T cells in association with marrow graft rejection: analysis of alloimmunity by T-cell cloning and testing of T-cell-receptor rearrangements.

Abstract Peripheral blood mononuclear cells from a patient who rejected a T-cell-depleted marrow graft showed spontaneous cytotoxic activity specific for HLA-Cw4 and HLA-B35 alloantigens of the donor. T-cell-receptor complementarity-determining region 3 length distributions in a blood sample obtained at the time of rejection generally showed distortions in only 1 or 2 peaks, indicating that recipient T cells with a broad repertoire of antigen receptors survived the pretransplantation conditioning regimen. An HLA-Cw4-specific, CD8 T-cell clone was recovered from a blood sample after rejection. The T-cell-receptor-B gene rearrangement expressed by this clone was not readily detectable in other blood samples drawn before or after the transplantation, indicating that this clone was only 1 of many recipient-derived T cells that recognized HLA alloantigens of the donor. These results demonstrate the role of the HLA-C locus in T-cell-mediated alloimmune responses and add to emerging evidence that indicates the need to evaluate HLA-C compatibility in selecting hematopoietic stem cell donors for patients who have an increased risk of rejection. Biol Blood Marrow Transplant 2001;7(7):378-83.
Manganese Utilization in the Chick: Effects of Excess Phosphorus on Chicks Fed Manganese-Deficient Diets

Young chicks were used in a 16-d feeding study to evaluate the effects of excess dietary P on Mn utilization. The basal casein-dextrose diet (1.4 mg Mn/kg) was supplemented with 0, 3.5, 7.0, or 10.5 mg Mn/kg from MnSO4.H2O and was fed in the absence or presence of .8% excess dietary P (equal P contributions from KH2PO4 and NaH2PO4). Diets containing .8% excess P were also supplemented with .8% excess Ca (CaCO3) to keep the Ca:P ratio above 1:25 so as to prevent anorexia associated with excess dietary P per se. Both growth rate and total tibia Mn responded linearly (P < .01) to Mn supplementation in chicks fed the normal level of P, but those fed excess P responded erratically. Excess P did not affect growth or tibia Mn in chicks fed the basal diet, but birds fed diets with supplemental inorganic Mn grew slower (P < .01) and had lower (P < .01) quantities of Mn in tibia when excess P was supplemented. Manganese content in the tibia of chicks fed excess P was 55% of that in chicks fed an adequate level of P.
Active roles for inhibitory κB kinases α and β in nuclear factor-κB–mediated chemoresistance to doxorubicin

Chemotherapy agents have been shown to induce the transcription factor nuclear factor-kappaB (NF-kappaB) and subsequent chemoresistance in fibrosarcomas and other cancers. The mechanism of NF-kappaB-mediated chemoresistance remains unclear, with a previous report suggesting that doxorubicin induces this response independent of the inhibitory kappaB kinases (IKK). Other studies have indicated that IKKbeta, but not IKKalpha, is required. Mouse embryo fibroblasts devoid of IKKalpha, IKKbeta, or both subunits (double knockout) were treated with doxorubicin. The absence of either IKKalpha or IKKbeta or both kinases resulted in impaired induction of NF-kappaB DNA-binding activity in response to doxorubicin. To provide a valid clinical correlate, HT1080 human fibrosarcoma cells were transfected with small interference RNA specific for IKKalpha or IKKbeta and then subsequently treated with doxorubicin. Knockdown of IKKalpha severely impaired the ability of doxorubicin to initiate NF-kappaB DNA-binding activity. However, a decrease in either IKKalpha or IKKbeta resulted in decreased phosphorylation of p65 in response to doxorubicin. The inhibition of doxorubicin-induced NF-kappaB activation by the knockdown of either catalytic subunit resulted in increased cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase and increased apoptosis when compared with doxorubicin alone. The results of this study validate current approaches aimed at NF-kappaB inhibition to improve clinical therapies. Moreover, we show that IKKalpha plays a critical role in NF-kappaB-mediated chemoresistance in response to doxorubicin and may serve as a potential target in combinational strategies to improve chemotherapeutic response.
Ideas of Global Governance and Fear of Imperial Decline

This paper examines the nagging worry about imperial decline present in the work of some of the most influential thinkers of internationalism in Britain during the inter-war years. I suggest that many of these thinkers developed an increasingly state-centered model of global governance (or 'commonwealth') as a rhetorical antidote to their own continued anxiety over the decline of the Empire and the perceived crisis in international order following World War One. I argue that we can see worry over this decline expressed in more than the League of Nations' commitment to the Mandate system but, rather, that we find it woven into the very discursive fabric of British inter-war thinking on the relationship between sovereignty, internationalism, and international institutions. The paper challenges neo-Kantian accounts of global governance and ethics and suggests that we pay close attention to the way these accounts may continue to betray a fear of both imperial decline and international disorder.
Rap Music Use, Perceived Peer Behavior, and Sexual Initiation Among Ethnic Minority Youth

Abstract Purpose Research shows that rap music use is associated with risky sexual behavior in ethnic minority youth; however, it is unknown whether rap music use impacts sexual initiation specifically and, if so, which factors mediate this impact. Thus, we investigated the longitudinal relationship between hours spent listening to rap music in seventh grade and sexual initiation in ninth grade. We also examined the role of perceived peer sexual behavior as a potential mediator of this relationship. Methods We analyzed data from students (n = 443) enrolled in a school-based randomized controlled trial of a sexual health education curriculum collected at baseline and at 18-month follow-up. Rap music use and perceived peer sexual behavior were assessed in seventh grade, whereas sexual initiation was assessed in ninth grade. Univariate, multivariate, and mediation analyses were conducted. Results At baseline, rap music use was significantly associated with race/ethnicity, parental music rules, and sexual behavior, but not with gender or parental education. Rap music use was a significant predictor of sexual initiation on univariate analysis but not multivariate analysis. Mediation analysis showed that the association between hours spent listening to rap music and sexual initiation was significantly mediated by perceived peer sexual behavior. Conclusions Rap music use in early adolescence significantly impacts sexual initiation in late adolescence, partially mediated by perceived peer sexual behavior. More research is needed to understand how rap music influences perceptions of peer sexual behavior, which, in turn, influence early sexual initiation.