cssi/SciSciGPT-SciSciNet huggingface dataset:
Serpin-1 splicing isoform J inhibits the proSpätzle-activating proteinase HP8 to regulate expression of antimicrobial hemolymph proteins in Manduca sexta.

The innate immune system of insects include the Toll pathway, which is mediated by an extracellular serine proteinase cascade. In the tobacco hornworm, Manduca sexta, hemolymph proteinase 8 (HP8) promotes the synthesis of antimicrobial proteins by cleaving proSpatzle, the putative ligand of M. sexta Toll. HP8 has been observed to form a complex in hemolymph with M. sexta serpin-1, which has multiple alternative splicing isoforms. To investigate the regulation of HP8 and its processing of proSpatzle, we characterized the interaction of recombinant HP8 with serpin-1 isoform J (serpin-1J). Recombinant serpin-1J formed an SDS-stable complex with HP8 in vitro. The association rate constant of serpin-1J and HP8 was 1.3×10(4)M(-1)s(-1), with a stoichiometry of inhibition of 5.4. Serpin-1J inhibited the cleavage of proSpatzle by HP8. Injection of serpin-1J into M. sexta larvae resulted in decreased bacteria-induced antimicrobial activity in hemolymph and reduced expression of cecropin, attacin and hemolin mRNA in fat body. Altogether, these results suggest that serpin-1J functions to inhibit HP8 and thereby modulates the concentration of active Spatzle to regulate the Toll pathway response in M. sexta.
Free actions on products of spheres: The rational case

Let X = S " ' x . . . x S"" be a product of spheres of total dimension n=nl+n2 +... +nk. A fundamental unanswered question is the determination of which finite groups can act freely on X and what actions on the cohomology so arise. In particular it is conjectured that if an elementary abelian group acts freely, then its rank is less than or equal to k. Great progress has been made recently on this question by Carlsson EC], Adem-Browder [A-B], and Hoffman [HI in the case where all the spheres have the same dimension. In this paper we completely solve the rational analogue of the above question. Given an action of a finite group G on the rational cohomology ring H*(X; •), we give necessary and sufficient conditions for G to act freely on a closed manifold Y having the rational homotopy type of X, so that the G-action induces the specified action on H* (Y; Q)= H* (X; Q). In particular the necessary conditions give new obstructions for G to act freely on X with a specified representation in H*(X; Q). Our method includes a general discussion as to when a space with finite fundamental group has the rational homotopy type of a closed manifold. We now give our necessary and sufficient conditions: (A) For all gEG, for all ni even, g*ESn']=~[S nJ] for some nonzero rational number ~. (B) For all g ~ G { e } , ~ ( 1 ) i ( t r ( g . : H,(X; Q ) ~ Hi(X; Q)) =0. (C) (i) For n even, some n i odd, the equivariant intersection form on H "/2 (X; Q) is hyperbolic, (ii) for all ni even, no further condition, (iii) for n odd, z 89 Q)ea*(O.(G, w) )cL , (~G, w).
REDRAW : a diagrammatic reasoning system for qualitative structural analysis

For preliminary analysis of structures, human engineers often employ diagrams as a visual language to study and to gain intuitive understanding about the behavior of structures. This paper reports a preliminary study and the development of a prototype system for diagrammatic reasoning to better emulate the intuitive visual problem solving techniques of human engineers. Diagrammatic reasoning is a type of reasoning in which the primary means of inference is the direct manipulation and inspection of a diagram. Diagrammatic reasoning is prevalent in human problem-solving behavior, especially for problems involving spatial relationships among physical objects. Our research examines the relationship between diagrammatic reasoning and symbolic reasoning in a computational framework. We have built a system called REDRAW, that emulates the human capability for reasoning with pictures for qualitative analysis of simple frame structures. Diagrammatic representations provide an environment where inferences about the physical results of proposed structural configurations can take place in a more intuitive manner than that possible through purely symbolic representations.
Dynamic Behavior of Metals Under Tensile Impact—Part 1: Elevated Temperature Tests

The mechanical behavior of metals subjected to uniaxial tensile impact at elevated temperatures is reported. Tests were conducted on annealed 1100 aluminum at 200, 350, 550, and 800 deg F; annealed 2024 aluminum at 200, 450, and 600 deg; and annealed C1010 steel at 430, 700, 1050, and 1400 deg F. The materials exhibit a wide range of dynamic behavior, including some in which the stress required to produce a given level of strain is significantly lowered by dynamic loading. The ratios of the dynamic ultimate stresses to the static are found to range from 0.71–6.0.
Discrete-continuous optimization for large-scale structure from motion

Recent work in structure from motion (SfM) has successfully built 3D models from large unstructured collections of images downloaded from the Internet. Most approaches use incremental algorithms that solve progressively larger bundle adjustment problems. These incremental techniques scale poorly as the number of images grows, and can drift or fall into bad local minima. We present an alternative formulation for SfM based on finding a coarse initial solution using a hybrid discrete-continuous optimization, and then improving that solution using bundle adjustment. The initial optimization step uses a discrete Markov random field (MRF) formulation, coupled with a continuous Levenberg-Marquardt refinement. The formulation naturally incorporates various sources of information about both the cameras and the points, including noisy geotags and vanishing point estimates. We test our method on several large-scale photo collections, including one with measured camera positions, and show that it can produce models that are similar to or better than those produced with incremental bundle adjustment, but more robustly and in a fraction of the time.
Toward the detection of abnormal chest radiographs the way radiologists do it

Computer Aided Detection (CADe) and Computer Aided Diagnosis (CADx) are relatively recent areas of research that attempt to employ feature extraction, pattern recognition, and machine learning algorithms to aid radiologists in detecting and diagnosing abnormalities in medical images. However, these computational methods are based on the assumption that there are distinct classes of abnormalities, and that each class has some distinguishing features that set it apart from other classes. However, abnormalities in chest radiographs tend to be very heterogeneous. The literature suggests that thoracic (chest) radiologists develop their ability to detect abnormalities by developing a sense of what is normal, so that anything that is abnormal attracts their attention. This paper discusses an approach to CADe that is based on a technique called anomaly detection (which aims to detect outliers in data sets) for the purpose of detecting atypical regions in chest radiographs. However, in order to apply anomaly detection to chest radiographs, it is necessary to develop a basis for extracting features from corresponding anatomical locations in different chest radiographs. This paper proposes a method for doing this, and describes how it can be used to support CADe.
Pattern similarity in shared codas from sperm whales (Physeter catodon)

: Codas (patterned click sequences) produced by sperm whales (Physeter catodon) were recorded during four research cruises in the southeast Caribbean. Two coda patterns comprised more than 50% of the codas analyzed from 46 h of recording. These two patterns were called “shared” codas because they were produced by numerous whales throughout the area, both as repeated sequences by individual whales, at times simultaneously by two or more whales, and occasionally in overlapping series. Analyses of both the absolute timing and the relative timing of click intervals indicate equivalent variability in the temporal patterns of similar shared codas, whether produced by the same or different whales. The shared codas appear to have a function that is different from individual identification as hypothesized previously for some coda patterns.
The Sea Ranch

A hundred miles north of San Francisco on California Coast Highway 1, the Sonoma County coast meets the Pacific Ocean in a magnificent display of nature. Waves crash upon the rocks or wash up on beautiful stretches of sandy beaches. This is the location of The Sea Ranch, an area covering several thousand acres of large, open meadows and forested natural settings interspersed with award-winning architecture. When the area, a sheep ranch well into the last century, was rediscovered for its beauty in the 1960s, it came to be envisioned as a home community that harmonized with the environment. Renowned landscape designer Lawrence Halprin's master plan for The Sea Ranch community accordingly incorporated a set of building guidelines that minimized the visual as well as physical impact upon the landscape. Subsequent buildings by architects such as Joseph Esherick, Charles Moore, William Turnbull, Obie Bowman, Donlyn Lyndon, and others have been recognized worldwide for environmentally sensitive planning and architecture. They sparked a generation of imitators that became part of what is known as "The Sea Ranch style," epitomizing what many people imagine when they think of Northern Californian architecture. This beautiful monograph, lavishly illustrated with over 300 newly commissioned photographs and including maps, plans, detailed descriptions of the houses, and essays by Donald Canty and Lawrence Halprin, presents the definitive record of The Sea Ranch community.
The Relationship between Life Events and Indices of Classroom Performance

I investigated the relationship between stressful life events (e.g., personal injury or illness, death of a close friend) and student performance in the classroom. A t the beginning of the semester, 159 students enrolled in a psychology course specified the amount of life stress they experienced during the previous year. Their responses were later correlated with measures of classroom performance at the completion of the course. A s hypothesized, life stress was inversely related to exam scores, extra credit points, and total course points. A x2 analysis also revealed that final course grades were predicted by life stress. It was suggested that teachers must recognize that students do not exist in a social, academic vacuum. Life events outside the classroom may directly affect performance in it.
Uncertainty analysis of the estimated ingestion rates used to derive the methylmercury reference dose.

The U.S. EPA's Reference Dose (RfD) for methylmercury (MeHg) uses a simple one-compartment toxicokinetic model to estimate ingestion doses in mg/kg-day from measured concentrations of mercury in hair. The model includes a number of input variables for which point estimates are made. Uncertainty in the inputs is addressed by the use of a 3-fold uncertainty factor. There are, however, published ranges for each variable which are used to develop distributions for each of the inputs. Monte Carlo output of the model is generated. The 90% confidence interval spans a 3-fold to 5-fold range of ingestion doses for any given concentration of mercury in hair. The hair:blood mercury concentration ratio contributes most to the variance of the output. The results indicate that the uncertainty factor of three is appropriate.
Regulation of Na,K-ATPase by endogenous ouabain-like materials.

AbstractSodium, potassium-ATPase (NKA) is an essential energy transduction mechanism in which the free energy released by hydrolysis of ATP is transferred to an electrochemical gradient across the cell membrane. The asymmetry of sodium in this gradient is coupled to membrane transport mechanisms which affect transmembrane movement of a range of solutes and electrolytes. Recent advances in the molecular biology of NKA have revealed important new aspects of structure-function relationships as well as illuminating the basis for variations in cardiac glycoside sensitivity of the enzyme. The search for endogenous mammalian counterparts of the cardiac glycosides, which regulate the activity of the enzyme by interacting from the extracellular surface at this receptor site, has moved ahead dramatically with evidence that ouabain is an endogenous product of the mammalian adrenal cortex. These advances, and problems raised by them, are explored in this review.
FGF signaling is required for brain left-right asymmetry and brain midline formation

Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure.
The Influence of Sociology on Economics: Selected Themes and Instances from Classical Sociological Theory

This article presents selected pertinent instances of the influence of (especially classical) sociological theory on economics. Its explicit justification and goal is to detect and illustrate the a...
Effects of perinatal bisphenol A exposure during early development on radial arm maze behavior in adult male and female rats

Previous work has shown that exposure to bisphenol A (BPA) can affect anxiety behavior. However, no studies have examined whether administration of this endocrine disruptor during the perinatal period has the potential to induce alterations in cognitive behavior in both adult males and females as assessed in an appetitive task. The goal of the current study was to determine whether exposure to different doses of BPA during early development alters performance on the 17-arm radial maze in adulthood in Long-Evans rats. Oral administration of corn oil (vehicle), 4 μg/kg, 40 μg/kg, or 400 μg/kg BPA to the dams occurred daily throughout pregnancy, and the pups received direct oral administration of BPA between postnatal days 1-9. Blood was collected from offspring at weaning age to determine levels of several hormones (thyroxine, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone). One male and one female from each litter were evaluated on the 17-arm radial maze, a working/reference memory task, in adulthood. Results indicated that after exposure to BPA at both 4 and 400 μg/kg/day, rats of both sexes had decreased levels of FSH at weaning. There were no significant effects of BPA on performance on the radial arm maze in males or females. In conclusion, exposure to BPA during early development had modest effects on circulating hormones but did not affect performance on a spatial learning and memory task.
Correction: Plasmon-enhanced water splitting on TiO2-passivated GaP photocatalysts

Correction for ‘Plasmon-enhanced water splitting on TiO2-passivated GaP photocatalysts’ by Jing Qiu et al., Phys. Chem. Chem. Phys., 2014, 16, 3115–3121.
Melanocyte-stimulating hormone promotes activation of pre-existing tyrosinase molecules in cloudman s91 melanoma cells.

TYROSINASE activity is greatly enhanced in cultured Cloudman S91 melanoma cells following addition of melanocyte-stimulating hormone (MSH) to the culture medium1. The increased activity occurs in the G2 phase of the cell cycle2 because membrane receptors for MSH are available only in this phase3. The response to MSH is mediated through cyclic AMP (refs 1–4). It is well documented that many peptide hormones function by activating membrane-bound adenyl cyclase molecules, causing net increases in intracellular cyclic AMP concentrations. These increases in turn have profound effects on cell division, morphology, and the expression of differentiated functions in a wide variety of cells and tissues. Little is known, however, about the levels at which genetic expression is regulated or the molecular intermediates involved in the regulation. For example, it is generally assumed that cyclic AMP-dependent protein kinases are involved in many of the responses because most tissues contain such enzymes5. The regulation of glycogenolysis is the best known example supporting this assumption6–7. But it cannot be taken as fact that in eukaryotes all cyclic AMP-mediated processes are post-translational in nature.
Catastrophe Theory A Quasi-Quantitative Methodology

The mathematical theory of catastrophes was developed by Rene Thom and consists of models suitable for explaining the abrupt changes of discontinuous dependent variables. Such variables are called catastrophic and have been difficult to analyze because mathematics has traditionally assumed that both the independent and dependent variables are continuous. Catastrophe theory has been highly touted as being particularly suitable for the less exact sciences, such as sociology, where measurement and conceptual difficulties make the assumption of a continuous dependent variable somewhat dubious in many cases. This paper explicates the nature of catastrophe theory in a nontechnical way, emphasizing the simplest model, the cusp. Both an inductive and deductive approach in applying the cusp model to sociological data are developed and illustrated, and the paper concludes with a discussion of how catastrophe theory might contribute to sociological understanding.
High-temperature kinetics of ammonia-air combustion

The noncatalytic, gas-phase combustion reaction between ammonia and air was studied in an adiabatic, well-stirred reactor. Results indicated an Arrhenius expression for the over-all reaction of the form −(d/dt)[NH3]=10B exp(−E/RT)[NH3]f[O2]n−f (mole/cm3-sec) with best fit values B=13.63±0.22 standard deviation E=34.77 (kcal/mole)±1.65 f=0.75±0.12 n=1.95±0.11 Inlet temperatures were varied from 350° to 470°K, gas temperatures from 1550° to 1900°K, ammonia concentrations from 0.5×10−4 to 3.25×10−4 mole/liter, oxygen concentrations from 1.5×10−4 to 4.0×10−4 mole/liter, and pressure from 1/2 to 1 atm. A blowout or stability map was also obtained, and an empirical correction for variation of inlet temperature was established, of the form I4=I exp[(400−Ti)/ψ()]. Experience with both the slow and fast oxidation reactions indicate that interaction with the reactor wall plays an important role in the kinetic mechanism for the slow reaction, but not for the fast reaction.
Application of jetting technology to pavement deicing

Winter maintenance of pavement surfaces consists of plowing and the application of corrosive deicing agents. These chemicals are hazardous to the environment, and thus their use should be minimal. More than 20 years ago, the Connecticut Department of Transportation (ConnDOT) investigated the use of 2.1 MPa (300 psi) pressurized salt brine jets to enhance deicing performance. Despite promising results from several field trials, technical difficulties led to abandonment of this technology in the early 1980s. Recent advances in high-pressure jetting technology suggest that the use of high-pressure jets in conjunction with improved chemical agents for pavement deicing may now be practical. In this study, the application of modern high-pressure jetting technology to deice pavement is explored. The proposed system removes ice and snow through the combined action of mechanical jetting forces and controlled use of deicing chemicals. Appropriate operating parameters and consumption rates are identified and compared with the ConnDOT system developed in the 1970s.
Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials.

ContextProgressive heart failure is the most common mechanism of death among patients with advanced heart failure. Cardiac resynchronization, a pacemaker-based therapy for heart failure, enhances cardiac performance and quality of life, but its effect on mortality is uncertain.ObjectiveTo determine whether cardiac resynchronization reduces mortality from progressive heart failure.Data SourcesMEDLINE (1966-2002), EMBASE (1980-2002), the Cochrane Controlled Trials Register (Second Quarter, 2002), The National Institutes of Health ClinicalTrials.gov database, the US Food and Drug Administration Web site, and reports presented at scientific meetings (1994-2002). Search terms included pacemaker, pacing, heart failure, dual-site, multisite, biventricular, resynchronization, and left ventricular preexcitation.Study SelectionEligible studies were randomized controlled trials of cardiac resynchronization for the treatment of chronic symptomatic left ventricular dysfunction. Eligible studies reported death, hospitalization for heart failure, or ventricular arrhythmia as outcomes. Of the 6883 potentially relevant reports initially identified, 11 reports of 4 randomized trials with 1634 total patients were included in the meta-analysis.Data ExtractionTrial reports were reviewed independently by 2 investigators in an unblinded standardized manner.Data SynthesisFollow-up in the included trials ranged from 3 to 6 months. Pooled data from the 4 selected studies showed that cardiac resynchronization reduced death from progressive heart failure by 51% relative to controls (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.93). Progressive heart failure mortality was 1.7% for cardiac resynchronization patients and 3.5% for controls. Cardiac resynchronization also reduced heart failure hospitalization by 29% (OR, 0.71; 95% CI, 0.53-0.96) and showed a trend toward reducing all-cause mortality (OR, 0.77; 95% CI, 0.51-1.18). Cardiac resynchronization was not associated with a statistically significant effect on non–heart failure mortality (OR, 1.15; 95% CI, 0.65-2.02). Among patients with implantable cardioverter defibrillators, cardiac resynchronization had no clear impact on ventricular tachycardia or ventricular fibrillation (OR, 0.92; 95% CI, 0.67-1.27).ConclusionsCardiac resynchronization reduces mortality from progressive heart failure in patients with symptomatic left ventricular dysfunction. This finding suggests that cardiac resynchronization may have a substantial impact on the most common mechanism of death among patients with advanced heart failure. Cardiac resynchronization also reduces heart failure hospitalization and shows a trend toward reducing all-cause mortality.
SDS: a framework for scientific data services

Large-scale scientific applications typically write their data to parallel file systems with organizations designed to achieve fast write speeds. Analysis tasks frequently read the data in a pattern that is different from the write pattern, and therefore experience poor I/O performance. In this paper, we introduce a prototype framework for bridging the performance gap between write and read stages of data access from parallel file systems. We call this framework Scientific Data Services, or SDS for short. This initial implementation of SDS focuses on reorganizing previously written files into data layouts that benefit read patterns, and transparently directs read calls to the reorganized data. SDS follows a client-server architecture. The SDS Server manages partial or full replicas of reorganized datasets and serves SDS Clients' requests for data. The current version of the SDS client library supports HDF5 programming interface for reading data. The client library intercepts HDF5 calls using the HDF5 Virtual Object Layer (VOL) and transparently redirects them to the reorganized data. The SDS client library also provides a querying interface for reading part of the data based on user-specified selective criteria. We describe the design and implementation of the SDS client-server architecture, and evaluate the response time of the SDS Server and the performance benefits of SDS.
Preference for Information under Varying Conditions of Outcome Uncertainty, Intensity, and Delay:

Two studies examined the effects of outcome uncertainty (H), intensity, and delay on S's preference for information over no-information. Ss were instructed to depress either an information or no-information key on each of 60 trials prior to the scheduled occurrence of one of several possible (positive, neutral, mildly negative, strongly negative) outcomes. An information choice resulted in an outcome-correlated signal 0, 10, or 15 sec. prior to the outcome. Although unable to affect overtly application of the outcome when informed, S's preference for information increased with uncertainty but only limited effects of outcome intensity and delay were found.
High-energy mechanical milling-induced crystallization in Fe32Ni52Zr3B13

Abstract Amorphous Fe32Ni52Zr3B13, prepared by rapid solidification, undergoes crystallization during high-energy mechanical milling. The resulting structure consists of face-centered cubic (fcc) FeNi and Zr3Ni20B6 nanocrystallites. Structural evolution and defect analysis of as-solidified Fe32Ni52Zr3B13 ribbons with different milling times is investigated. From the differential thermal analysis (DTA) curve of amorphous ribbons, exothermic peaks were observed at 415 °C and 475 °C corresponding to the crystallization of fcc Zr3Ni20B6 phase and fcc FeNi phase, respectively. However, high-energy mechanical milling induces the formation of FeNi within the first 2 h of mechanical milling. Further milling induces the crystallization of Zr3Ni20B6. Doppler broadening positron annihilation spectroscopy (DBPAS) was used to investigate vacancy-type defects. The milling-induced crystallization appears to be related to enhanced vacancy-type defect concentrations allowing growth of pre-existing Fe(Ni) nuclei. The milling and enhanced vacancy concentration also de-stabilizes the glass, leading to decreased crystallization temperatures for both phases, and ultimately eliminating the glass transition altogether.
Triolein emboli clearance from the mouse lung: Effect of heparin and heparitin sulfate☆

Abstract We have designed a model system in mice in which one can study the localization, accumulation, and clearance of experimentally induced pulmonary fat emboli. When 125 I-labeled triolein emulsions are injected via the caudal vein, the lipid is trapped predominantly in the lung vasculature. Both heparin and heparitin sulfate significantly lowered the level of trapped 125 I-labeled triolein in the lungs compared to control mice and caused the release of significant amounts of lipoproptein lipase into the plasma. We suggest that a possible mechanism for clearance of triglycerides from the lung vasculature may involve the release of plasma lipoprotein lipase. This in turn hydrolyzes the localized glycerides into more water-soluble components, so they can be removed from the site of embolization.
Planetary exploration sensor systems

Most of the instruments that have been used in planetary exploration have been either spectrometers or imaging devices. Instruments of these types are being developed for the Galileo and VOIR (Venus Orbiting Imaging Radar) missions. Galileo will take advantage of new CCD (charge-coupled device) technology, and VOIR will use techniques of synthetic aperture radar developed for Seasat. For determining the macrostructure of mineral resources, the best approach is believed to involve acoustic imaging, essentially a seismic data processing technique. Determinations of microstructure would require a light microscope and an electron microscope. For determining the nature and form of volatiles, a differential scanning calorimeter could be used. To determine the mineral composition, an electron beam microprobe with X-ray fluorescence and spectroscopy would be used.
On estimating pressure build‐up in severely accelerated, shocked flow

SUMMARY A new approach to the calculation of the high pressures characterizing the flow field in front of a piston undergoing severe acceleration over the short term is presented. In contrast with previous approaches where the computational domain is altered but which stop short of transforming velocities, here the problem is solved in an accelerating non-Euclidean co-ordinate system where the piston is stationary. The method is applied to a study of the problem of premature sabot separation. Through use of Harten's second-orderaccurate TVD scheme, flow simulations are performed for both 1D and 3D axisymmetric geometries. The simple 1D model gives pressure profiles surprisingly close to those of the more physical 3D model.
Caffeine-induced re-initiation of phage λ DNA replication

Abstract A significant proportion of bacteriophage λ replicative intermediates undergo reinitiation at the λ origin when 2 m m -caffeine is present. This phenomenon is not observed in the absence of caffeine. Apart from re-initiation, no other obvious change is observed in the replicative intermediates. In view of the above facts, alternative explanations for the effect of caffeine on eukaryote replicating systems are discussed.
Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous, immature myeloid cell population with the ability to suppress immune responses. MDSCs have been characterized in infections, inflammatory diseases, and solid tumors; however, their presence and role in the tumor-promoting, immune-suppressive microenvironment in hematologic malignancies remains unclear. We assessed the presence, frequency, and functional characteristics of MDSCs in patients with newly diagnosed, relapsed, and relapsed/refractory multiple myeloma (MM) compared with healthy donors. Additionally, we evaluated the immunomodulatory effects of lenalidomide and bortezomib on MDSCs in MM. CD11b+CD14-HLA-DR-/lowCD33+CD15+ MDSCs were significantly increased in both the peripheral blood and the bone marrow of patients with active MM compared with healthy donors. Furthermore, MDSCs induced MM growth while suppressing T-cell–mediated immune responses. Conversely, MM cells induced the development of MDSCs from healthy donor peripheral blood mononuclear cells, confirming a bidirectional interaction between MDSCs and MM cells and immune effector cells. Our results further suggest that MDSCs may be associated with the activity of disease in MM. Importantly, our studies suggest that inhibition of the tumor-promoting and immune-suppressive functions of MDSCs in MM may represent a promising novel immune-based therapeutic strategy.
Determinants of Perceived Skin-Color Discrimination in Latin America

Discrimination on the basis of skin color persists as a serious social and political problem in many of the world’s nations. Although numerous consequences of such discrimination have been enumerated, considerably less is known regarding the bases of perceived discrimination. In this study, individuals’ perceptions that they have been the targets of skin-color discrimination are examined. Using 2010 AmericasBarometer data from six nations, a multifaceted account of the possible bases of perceived discrimination is devised and tested. Three classes of predictors are considered: (1) variables related to a person’s skin color, race, and ethnicity; (2) extraneous demographic and psychological factors; and (3) aspects of the individual’s regional social and political context. Results reveal that both skin color and racial and ethnic self-categorization strongly correspond with perceived discrimination, with additional, more modest, effects identified for socioeconomic status (wealth), personality (agreeablenes...
Electromigration in sputtered Al-Cu thin films

Abstract Lifetime predictions for aluminum metallization vary considerably depending on many factors. These include the deposition scheme and resulting microstructure of the film, linewidth and geometric variations, alloying elements and testing procedure. Many experimental techniques have been used to study metallization lifetimes. Most involve mass transport measurements in both bulk and thin film samples. A method has been developed for lifetime predictions using a continuous resistance monitoring technique. This allows for lifetime measurements that are more sensitive and, consequently, more accurate than present techniques.
Orphan GPCRs and Neuromodulation

Most G protein-coupled receptors (GPCRs) started as orphan GPCRs. Matching them to known neuromodulators led to the elucidation of the broad diversity of the neuroreceptor families. Moreover, orphan GPCRs have also been used as targets to discover novel neuromodulators. These discoveries have had profound impact on our understanding of brain function. Here, I present an overview of how some of the novel neuropeptides have enlarged our comprehension of responses that direct sleep/wakefulness, the onset of obesity and the feeding response. I also discuss other advances gained from orphan GPCR studies such as the concept of specificity in neuromodulation or of receptors acting as sensors instead of synaptic transmitters. Finally, I suggest that the recently discovered neuromodulators may hold the keys to our understanding of higher brain functions and psychiatric disorders.
Morphological variation between isolated populations of Becium homblei (De Wild.) Duvign & Plancke growing on heavy metal soils

Populations ofBecium homblei, a metal tolerant plant species, were found to exist in a number of isolated areas in which the soil conditions were very different. Corolla shape and seed weight which are regarded as relatively implastic characters in the species were examined from four populations and the results subjected to a statistical analysis. The greatest differences were found between those populations which grew in widely different soil types. Plants on heavy metal soils showed an overall reduction in flower size. It is suggested that the results indicate ecotypic variation between the populations.
Leber Congenital Amaurosis Caused by Mutations in RPGRIP1

Recessive null mutations in retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) gene are the cause of LCA6 and account for 5% to 6% of the total patient population. RPGRIP1 has an essential role in the photoreceptor connecting cilia, and photoreceptors lacking RPGRIP1 are unable to maintain the light sensing outer segments. As a result, patients lose retinal functions at an early age but retain photoreceptors in the central retina well into adulthood thus holding out the prospect for gene augmentation therapies. Laboratory studies in animal models have demonstrated efficacy of gene therapy in slowing disease progression. With further refinement in the design of the replacement gene construct, clinical trials for Leber congenital amaurosis (LCA) caused by RPGRIP1 mutations could be in the offing in the near future.
Identification of Residues in the Adult Nicotinic Acetylcholine Receptor That Confer Selectivity for Curariform Antagonists

We identify residues in the e and δ subunits of the adult nicotinic acetylcholine receptor that give the αe and αδ binding sites different affinities for the curariform antagonist dimethyl d-tubocurarine (DMT). By constructing e-δ subunit chimeras, coexpressing them with complementary subunits, and measuring DMT binding, we identify two pairs of residues, Ilee58/Hisδ60 and Aspe59/Alaδ61, responsible for DMT site selectivity in the adult receptor. The two determinants contribute approximately equally to the binding site and interact in contributing to the site. Exchange of these residues from one subunit to the other exchanges the affinities of the resulting binding sites. These determinants in the adult receptor are far from those that confer site selectivity in the fetal receptor; determinants in the fetal receptor are Ileγ116/Valδ118, Tyrγ117/Thrδ119, and Serγ161/Lysδ163. Thus, alternative residues confer DMT selectivity in fetal and adult acetylcholine receptors.
Methotrexate in the treatment of pemphigus vulgaris: experience in 23 patients

Summary Background The standard treatment for patients with pemphigus vulgaris has long consisted of high-dose glucocorticoids. Studies regarding the use of methotrexate in pemphigus vulgaris date back to 1968, but few have quantitatively described a steroid-sparing effect conferred by methotrexate. Objectives We sought to evaluate the efficacy of methotrexate in 23 patients with pemphigus vulgaris, using the drug's steroid-sparing effect as the primary indicator of clinical improvement. We investigated whether methotrexate could be used as monotherapy in some patients. Methods Retrospective chart review was used to analyse the records of patients with pemphigus vulgaris treated with methotrexate at the New York University Langone Medical Center for at least three consecutive months between 2000 and 2012. Diagnosis was made by tissue biopsy and either direct or indirect immunofluorescence tests and enzyme-linked immunosorbent assay. Results Improvement in clinical symptoms was observed in 91% of patients. Sixteen patients (70%) were eventually weaned completely off prednisone, with a mean time to discontinuation of 18 months. In total 23% of patients enjoyed a partial steroid-sparing effect, requiring a mean maintenance dose of prednisone of 6·75 mg daily. Two patients (9%) developed possible adverse events requiring cessation of the drug, and one patient received no therapeutic benefit from the drug. Conclusions Methotrexate is a useful and well-tolerated therapy with considerable steroid-sparing effect in patients with pemphigus vulgaris. It may be considered a first-line adjuvant therapy in the treatment of this difficult disease.
Variational integrators for constrained dynamical systems

A variational formulation of constrained dynamics is presented in the continuous and in the discrete setting. The existing theory on variational integration of constrained problems is extended by aspects on the initialization of simulations, the discrete Legendre transform and certain postprocessing steps. Furthermore, the discrete null space method which has been introduced in the framework of energy-momentum conserving integration of constrained systems is adapted to the framework of variational integrators. It eliminates the constraint forces (including the Lagrange multipliers) from the timestepping scheme and subsequently reduces its dimension to the minimal possible number. While retaining the structure preserving properties of the specific integrator, the solution of the smaller dimensional system saves computational costs and does not suffer from conditioning problems. The performance of the variational discrete null space method is illustrated by numerical examples dealing with mass point systems, a closed kinematic chain of rigid bodies and flexible multibody dynamics and the solutions are compared to those obtained by an energy-momentum scheme.
An In Vivo Injury Model of Posterolateral Knee Instability

Background: Posterolateral knee instability is a difficult clinical problem to diagnose and treat. To best evaluate its natural history and the effects of interventional treatments, it is important to develop an in vivo model in an attempt to validate human cadaveric and clinical observational studies.Purpose: To develop an in vivo model of posterolateral knee instability in the rabbit and to determine the natural history of untreated posterolateral knee injuries at 6 months postoperatively.Study Design: Controlled laboratory study.Methods: The fibular collateral ligament and popliteus tendon were surgically transected in 1 knee in each of 10 skeletally mature New Zealand White rabbits, with the contralateral knee serving as a control knee. At 6 months postoperatively, the rabbits were euthanized, the knees were removed, and biomechanical testing of knee joint stability was performed. After biomechanical testing, histological sections of each proximal tibia and distal femur were evaluated, and each proxim...
Isaiah Berlin's Challenge to the Zhuangzian Freedom

Isaiah Berlin is known for articulating two competing notions of freedom operative within the modern Western political philosophy, negative and positive. He provides a powerful defense of modern liberal tradition that elevates negative freedom in its attempt to preserve personal space for one's actions and choices while regarding positive freedom as suppressive due to its potentially collective orientation. This article uses Berlin as an interlocutor to challenge Zhuangzi, known for his portrayal of spiritual freedom in the Chinese tradition, prodding modern Zhuangzians to bring the Zhuangzian spiritual freedom into the sociopolitical arena by reimagining new possibilities about politics.
Exploring the onset of high-impact mega-fires through a forest land management prism

Abstract In the modern era, high-impact mega-fires are unprecedented for the suppression costs, property losses, natural resource damages, and loss of life often involved. For a number of years, these extraordinary wildfires have been increasing in number and in severity. They affect countries around the world, including those with enormous firefighting capabilities. High-impact mega-fires are frustrating efforts to provide for public safety, slow rates of deforestation, sequester carbon and reduce black carbon emissions. Despite more determined bidding, attempts to match increasing wildfire threats with greater suppression force have not stemmed climbing mega-fire trends. Yet, the majority of after-action reviews, reports, and commissions continue to weight recommendations to correcting emergency response deficiencies, generally through a fire operations lens. This paper explores the mega-fire phenomenon through a forest land management prism. It is an early attempt to focus on the contributory factors that may set the stage for high-impact mega-fires. The paper draws on the results from two coarse-filter overviews of high-impact mega-fires from around the world and the authors’ firsthand experiences dealing with others in the United States. Drought and fire exclusion policies have been implicated in the large fire problem. However, several high-impact mega-fires can be further traced to land management decisions that resulted in dense forest conditions with high biomass and fuel build-ups over extensive areas. As droughts have intensified, more of these accumulated fuels have become available to burn at intensities that exceed suppression capabilities. In contrast, some places have managed to largely avoid high-impact mega-fires. State and federal lands in Florida and Crown lands in Western Australia have better aligned policies and practices with the disturbance regimes that define the forested landscapes that they protect. They use prescribed fire at appropriate intensities, intervals, and scales to reduce fuels as the means to protect people, maintain forest resilience, ensure biodiversity, and increase margins of suppression effectiveness. Forest land management policies and practices that, by design or by default, result in greater volumes of fuel and rely on suppression capabilities to maintain these conditions may no longer be sustainable as droughts deepen and become more widespread. This paper suggests that adapting wildland fire management programs, forest land management policies, and the current regulatory framework to the reality of warmer, drier climate patterns will be essential in reducing mega-fire risks. Protecting fire-prone landscapes can no longer rely on suppression alone; protection will become more dependent on the management of forests where high-impact mega-fires incubate.
14‐3‐3‐β and ‐ε contribute to activation of the osmoprotective transcription factor NFAT5 by increasing its protein abundance and its transactivating activity

Abstract Having previously found that high NaCl causes rapid exit of 14-3-3 isoforms from the nucleus, we used siRNA-mediated knockdown to test whether 14-3-3s contribute to the high NaCl-induced increase in the activity of the osmoprotective transcription factor NFAT5. We find that, when NaCl is elevated, knockdown of 14-3-3-β and/or 14-3-3-e decreases NFAT5 transcriptional activity, as assayed both by luciferase reporter and by the mRNA abundance of the NFAT5 target genes aldose reductase and the sodium- and chloride-dependent betaine transporter, BGT1. Knockdown of other 14-3-3 isoforms does not significantly affect NFAT5 activity. 14-3-3-β and/or 14-3-3-e do not act by affecting the nuclear localization of NFAT5, but by at least two other mechanisms: (1) 14-3-3-β and 14-3-3-e increase protein abundance of NFAT5 and (2) they increase NFAT5 transactivating activity. When NaCl is elevated, knockdown of 14-3-3-β and/or 14-3-3-e reduces the protein abundance of NFAT5, as measured by Western blot, without affecting the level of NFAT5 mRNA, and the knockdown also decreases NFAT5 transactivating activity, as measured by luciferase reporter. The 14-3-3s increase NFAT5 protein, not by increasing its translation, but by decreasing the rate at which it is degraded, as measured by cycloheximide chase. It is not clear at this point whether the 14-3-3s affect NFAT5 directly or indirectly through their effects on other proteins that signal activation of NFAT5.
Lipid Response to a Low-Fat Diet with or without Soy Is Modified by C-Reactive Protein Status in Moderately Hypercholesterolemic Adults

Recent evidence suggests that individuals with high concentrations of C-reactive protein (CRP), a marker of inflammation, are less responsive to cholesterol-lowering diets. CRP concentrations are increased by oral estrogen; however, the effect of soy phytoestrogens on inflammation has not been studied comprehensively, especially in women receiving hormone replacement therapy (HRT). This study was conducted to determine whether adding soy to a low-fat, high-fiber diet affects CRP and interleukin (IL)-6, and to examine the association between CRP levels and lipid response in moderately hypercholesterolemic adults (men = 18, postmenopausal women = 14; 6 receiving HRT). After a 3-wk run-in period with consumption of a Step I diet (27% total fat, 7% saturated fat, 275 mg cholesterol), participants were randomly assigned to diets containing 25 g/d soy protein (+ 90 mg/d isoflavones) or 25 g/d milk protein for 6 wk in a crossover design. Lipids and lipoproteins, CRP, and IL-6 were measured at the end of each diet and participants were categorized into high (>3.5 mg/L) or low CRP groups based on a median split. The addition of soy or milk protein to the Step I diet did not affect lipids or inflammatory markers. Regardless of protein source, those with low CRP exhibited significant decreases in LDL cholesterol (-3.5%) and the LDL:HDL cholesterol ratio (-4.8%), whereas those with high CRP had significant increases in LDL cholesterol (+4.8%), the LDL:HDL cholesterol ratio (+5.2%), apolipoprotein B (+3.8%), and lipoprotein(a) (+13.5%) compared with the run-in diet. These results suggest that inflammation may not only attenuate lipid responses, but also aggravate dyslipidemia in hypercholesterolemic subjects consuming a cholesterol-lowering diet.