cssi/SciSciGPT-SciSciNet huggingface dataset:
Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 Inhibitors

Insertion mutations in EGFR and HER2 both occur at analogous positions in exon 20. Non-small cell lung cancer (NSCLC) patients with tumors harboring these mutations seldom achieve clinical responses to dacomitinib and afatinib, two covalent quinazoline-based inhibitors of EGFR or HER2, respectively. In this study, we investigated the effects of specific EGFR and HER2 exon 20 insertion mutations from NSCLC patients that had clinically achieved a partial response after dacomitinib treatment. We identified Gly770 as a common feature among the drug-sensitive mutations. Structural modeling suggested that this mutation may facilitate inhibitor binding to EGFR. Introduction of Gly770 into two dacomitinib-resistant EGFR exon 20 insertion mutants restored sensitivity to dacomitinib. Based on these findings, we used afatinib to treat an NSCLC patient whose tumor harbored the HER2 V777_G778insGSP mutation and achieved a durable partial response. We further identified secondary mutations in EGFR (T790M or C797S) and HER2 (C805S) that mediated acquired drug resistance in drug-sensitive EGFR or HER2 exon 20 insertion models. Overall, our findings identified a subset of EGFR and HER2 exon 20 insertion mutations that are sensitive to existing covalent quinazoline-based EGFR/HER2 inhibitors, with implications for current clinical treatment and next-generation small-molecule inhibitors. Cancer Res; 77(10); 2712-21. ©2017 AACR.
Strength, character, and directionality of halogen bonds involving cationic halogen bond donors

Halogen bonds involving cationic halogen bond donors and anionic halogen bond acceptors have recently been recognized as being important in stabilizing the crystal structures of many salts. Theoretical characterization of these types of interactions, most importantly in terms of their directionality, has been limited. Here we generate high-quality symmetry adapted perturbation theory potential energy curves of a H3N-C[triple bond, length as m-dash]C-Br+Cl- model system in order to characterize halogen bonds involving charged species, in terms of contributions from electrostatics, exchange, induction, and dispersion, with special emphasis on analyzing contributions that are most responsible for the directionality of these interactions. It is found that, as in the case of neutral halogen bonds, exchange forces are important contributors to the directionality of charged halogen bonds, however, it is also found that induction effects, which contribute little to the stability and directionality of neutral halogen bonds, play a large role in the directionality of halogen bonds involving charged species. Potential energy curves based on the ωB97X-D/def2-TZVP/C-PCM method, which includes an implicit solvation model in order to mimic the effects of the crystal medium, are produced for both the H3N-C[triple bond, length as m-dash]C-Br+Cl- model system and for the 4-bromoaniliniumCl- dimer, which is based on the real 4-bromoanilinium chloride salt, whose crystal structure has been determined experimentally. It is found that, within a crystal-like medium, charged halogen bond are significantly weaker than in the gas phase, having optimum interaction energies up to approximately -20 kcal mol-1.
Abstract P305: Detrimental Effects of Chronic Activation of AKT in Hearts from Ozone-Exposed Healthy Adult Rats

Death of cardiomyocytes results in decreased cardiac function, which correlates with overall morbidity and mortality in many different clinical settings. For these reasons, understanding the intracellular signaling pathways that control cardiomyocyte survival has significant clinical implications. Each year in the US 60,000 cardiovascular deaths have been linked to environmental pollutants such as ozone (O 3 ). Earlier studies from our laboratory have shown that myocardial dysfunction, subsequent to chronic O 3 exposure, in normal adult rats. This attenuation of cardiac function was associated with increased myocardial TNF-alpha (TNF-α) levels. Progressive increases in the expression of myocardial TNF-α in 4 and 8 week O 3 exposed animals were followed by decreases in cardiac caveolin-1 levels. Acute activation of the serine-threonine kinase Akt is cardioprotective and reduces both infarction and dysfunction after ischemia/reperfusion injury (IRI). Akt is activated in samples from patients with chronic heart failure, however, less is known about the chronic effects of Akt activation in the hearts from ozone exposed patients. Although caveolin-1 has been shown to negatively regulate AKT expression; a cell survival pathway, regulatory role of AKT in hearts from ozone exposed subjects has never been studied. Sprague Dawley rats were exposed 8 hr/day for 28 and 56 days to filtered air or 0.8 ppm O 3 . In order to assess the chronic effects to O 3 , expressions of AKT and p-AKT were determined by wetern blotting in hearts extracted from rats, 24 hr after termination of air or O 3 exposure. Compared to rats exposed to filtered air, total AKT levels were significantly increased in all O 3 exposed animals. Similar results were seen with pAKT levels. Since earlier studies have determined detrimental effects of chronic activation of AKT in ischemia reperfusion injury, our novel findings suggest the interesting possibility of a mechanism by which chronic Akt activation can become maladaptive after exposure to chronic levels of ozone. It is possible that PI3K-dependent but Akt-independent effectors are required for full cardioprotection. Studies are currently in progress to prove this hypothesis and complete study will be presented at the meeting in New Orleans in 2011.
Implementation Using Digital Signal Processors

The chapter speaks about the definition of digital signal processor. It is a special form of microprocessor that is optimized to perform digital signal processing (DSP) operations. Often called “DSPs” due to the function they perform, they are designed to perform DSP functions in an efficient method, using conventional software programming design and verification techniques discussed in the chapter. Owing to the special features and parallelism added for DSP operations, conventional programming languages such as C do not always produce the most optimal results, and rely on pre-optimized library calls for common algorithms and functions. Although advanced compilers developed by the DSP processor manufacturers do try to interpret the programmer's intent and map the DSP processor features in the most effective manner. For this reason, a vendor-specific language, known as assembly, is instead used to code the most DSP-intensive portions of the software. But the writing in assembly code does require knowledge of the DSP processor hardware architecture and how to optimally write code that takes advantage of the DSP processor architecture features.
Prices, policies, and place: What drives greenfield development?

While the recent global financial crisis heightened awareness of the linkages between global financial capital and urban spatial pattern, the timing of urban development – largely thought to be market driven – is not fully understood. Parcel-level studies of urban land-use change, which often use hazard models to investigate if and when development occurs, offer an opportunity to juxtapose the extent to which decisions to develop individual plots of farmland into housing are driven by market forces, the unique characteristics of the land and its intraurban location, or policies such as transportation infrastructure and municipal annexation. Using residential completion data in the Phoenix, Arizona region from 1992 to 2014, a period of dramatic commodity, fuel, and home price swings, and land cover imagery, we develop a parcel-level hazard model to gauge the relative impacts of market, policy, and place-based drivers of land change. We find limited evidence of induced development associated with freeway planning, that annexation and development are closely linked and moreso during economic booms, high fuel prices spur development in the region's core, and agricultural and urban land rents affect the timing of development. This study advances our understanding of development decision- making, policy impacts, and urban land-use change modeling and provides an empirical connection between local and global drivers of Greenfield development.
TIARA Coding and Scoring: Instructions for Data Transformation and Analysis

This chapter provides instructions for coding and scoring data collected with the TIARA method. This includes prescreening the data to identify outliers as well as suggestions for analyzing the reaction time distribution and transforming reaction time data to standard Likert-type scores.
Depot Medroxyprogesterone Acetate Administration Alters Immune Markers for HIV Preference and Increases Susceptibility of Peripheral CD4+ T Cells to HIV Infection

Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. In a longitudinal study, we investigated the impact of Depo-Provera use by healthy women on expression of immune markers for HIV preference and on HIV infection ex vivo at baseline (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment. We found a significant increase in the frequency and expression of integrin α4β7 on CD4+ T cells at visit 2. Interestingly, Hispanic but not black women exhibited a significant increase in integrin α4β7 cell numbers and expression levels at visit 2, whereas, black but not Hispanic women exhibited a significant change in CCR5 and CD38 expression levels between visit 2 and visit 3. The frequency of terminal effector memory CD4+ T cells decreased significantly in black women from visit 1 to visit 3. Virus production following ex vivo HIV infection of PBMCs was increased at visit 3 compared to visit 1. In black women, the frequency of HIV p24+CD4+ T cells was higher at visit 3 than at visit 1. Expression of integrin α4β7 on HIV p24+CD4+ T cells following ex vivo infection at visit 2 was significantly less than at visit 1. These results demonstrate that Depo-Provera alters the immune profile of peripheral CD4+ T cells and increases susceptibility to HIV infection ex vivo. The observation that these effects differed between women of different ethnicities has implications for developing effective and targeted strategies for HIV prevention.
Is All That Glitters the Lex Oppia

The lex Oppia of 215 BC is known largely through Livy’s report of the debate centering on its repeal 20 years later. The details of the legislation are somewhat sketchy but it has become a focal point for discussing fragments of the fabulae togatae which refer to gold and purple. In this piece pertinent fragments of the Barbatus of Titinius are examined to see whether or not perceived allusions to the law are sound.
A cry and an outcry: Oplakvane (complaining) as a term for communication practice

This study examined the term oplakvane in Bulgarian discourse. It refers to a communication practice – similar to complaining – and a range of associated cultural meanings for ways to construct a s...
A possible social relative reward effect: Influences of outcome inequity between rats during operant responding

Social interactions/situations have dramatic influences on motivation. Creating animal models examining these influences promotes a better understanding of the psychological and biological underpinnings of social motivation. Rodents are sensitive to social history/experience during associative conditioning and food-sharing tasks. Would reward-oriented operant behavior be sensitive to social influences by showing a negative contrast-like effect when another organism obtains a greater value outcome? We used a side-by-side arrangement of operant response chambers wherein one animal obtained consistently high reward signaled by a discrete cue. The neighboring, experimental rat experienced different combinations of high and low reward trial sequences. Control conditions included distraction from a conspecific in the neighboring chamber (rat distractor) or cue/food dispenser operating without a conspecific (program distractor) in addition to testing subjects alone. Results support an influence of the other animal actively performing the task on the experimental subject's behavior. Primarily, responding was significantly slower for the low reward trials while the neighboring rat was receiving the higher magnitude reward. The lever-press and not food-cup retrieval latency was significantly slower during exposure to a conspecific neighbor performing the operant task. The effect was not obtained in all session sequences and was more pronounced using longer series of consecutive low reward trials. The slowing effect was also obtained with the program-distractor experience in a different trial sequence. These findings suggest a social-induced negative incentive contrast effect in rats possibly mediated by an outcome inequity process that could have key similarities to complex situational-affective effects on motivation involving frustration or jealously.
Enhancing student learning using concept mapping and learning by teaching environment

This paper describes our effort to incorporate concept maps into a Computer Science introductory course. Studies were conducted that analyze student performance in relation to concept map activities to determine the benefit of concept maps as a learning tool. Our results not only support the idea of concept mapping as a teaching tool, they also suggest that students gain the most when they are directly involved in creating the concept map. A long term objective of this research project is to create a generic Learning-by-Teaching Environment (LTE) that can function in a variety of domains including general Computer Science. Our experience also suggests that a sophisticated and adaptive LTE could be successful in helping college students acquire a deeper understanding of course material and a better clarification of any prior topic-based misconceptions.
Identifying Cultural Effects in Psychological Treatments Using Aptitude-Treatment Interactions

The purpose of this chapter is to pose, and then address, a basic research question that describes the general basis for examining one aspect of treatment effectiveness: does a treatment work differently across population subgroups? The chapter discusses different aspects of the study design and highlights the aptitude-treatment interaction (ATI) approach as one method for analyzing this type of data. The chapter covers the development and interpretation of the basic ATI model, criteria for determining if an ATI exists, criticisms of the framework, and some extensions of the basic model that may be necessary for some common clinical situations. The chapter concludes with a didactic example of analyzing and interpreting data to determine if an ATI is present.
Suffering and Sacrifice: The Hermeneutics of Yisurin in the Babylonian Talmud

This article offers the argument that suffering (yisurin) in the Babylonian Talmud functions as a locus for the relationship between God and rabbinic Jews. Scholars of rabbinic martyrdom and asceticism have tended to claim that the Talmud9s positive portrayal of suffering is a theodical apology for unexplained evil in the world. However, the article argues that the Talmud—in contrast to earlier rabbinic texts—presents suffering as spiritually relevant not primarily to justify preexisting suffering, but rather to develop a site at which to interpret information about an individual9s spiritual status. The article draws on theories of sacrifice9s structure and function, in conjunction with close analysis of rabbinic texts that relate suffering to sacrifice. The pericope at the core of the article9s argument demonstrates a strikingly technical approach to the human experience of suffering, describing four examples of yisurin in which no real physical suffering occurs; in each instance the “victim” experiences extremely mild discomfort at most, and at the least barely registers an experience of inconvenience. Nonetheless, these experiences all qualify as “suffering,” and are thus still understood to bear indisputable soteriological import. Physical suffering in the Talmud is thus open for interpretation, yielding information about the status of the sufferer9s spiritual self. Human suffering is viewed as religiously desirable in both late rabbinic and early Christian literatures. By developing an understanding of its hermeneutical function for the rabbis, this article helps to elucidate the value of suffering for rabbinic literature as a subset of late antique religious discourse.
Viable and Total Bacterial Populations Undergo Equipment- and Time-Dependent Shifts during Milk Processing.

ABSTRACT We set out to identify the viable and total bacterial content in milk as it passes through a large-scale, dairy product manufacturing plant for pasteurization, concentration, separation, blending, and storage prior to cheese manufacture. A total of 142 milk samples were collected from up to 10 pieces of equipment for a period spanning 21 h on two collection dates in the spring and late summer of 2014. Bacterial composition in the milk was determined by 16S rRNA marker gene, high-throughput DNA sequencing. Milk samples from the late summer were paired such that half were treated with propidium monoazide (PMA) to enrich for viable cells prior to quantification by PCR and identification by DNA sequence analysis. Streptococcus had the highest median relative abundance across all sampling sites within the facility on both sampling dates. The proportions of Anoxybacillus , Thermus , Lactococcus , Lactobacillus , Micrococcaceae , and Pseudomonas were also elevated in some samples. Viable cells detected by PMA treatment showed that Turicibacter was enriched after high-temperature short-time pasteurization, whereas proportions of Staphylococcus were significantly reduced. Using clean-in-place (CIP) times as a reference point, Bacillus , Pseudomonas , and Anoxybacillus were found in high relative proportions in several recently cleaned silos ( 19 h after CIP), 10 of 11 silos containing elevated viable cell numbers were enriched in Acinetobacter and/or Lactococcus . These results show the tremendous point-to-point and sample-dependent variations in bacterial composition in milk during processing. IMPORTANCE Milk undergoes sustained contact with the built environment during processing into finished dairy products. This contact has the potential to influence the introduction, viability, and growth of microorganisms within the milk. Currently, the population dynamics of bacteria in milk undergoing processing are not well understood. Therefore, we measured for total and viable bacterial composition and cell numbers in milk over time and at different processing points in a cheese manufacturing facility in California. Our results provide new perspectives on the dramatic variations in microbial populations in milk during processing even over short amounts of time. Although some of the changes in the milk microbiota were predictable (e.g., reduced viable cell numbers after pasteurization), other findings could not be easily foreseen based on knowledge of bacteria contained in raw milk or when the equipment was last cleaned. This information is important for predicting and controlling microbial spoilage contaminants in dairy products.
Pharmacokinetics and Clinical Pharmacology Considerations of GalNAc3-Conjugated Antisense Oligonucleotides

Introduction: Triantennary N-acetyl galactosamine (GalNAc3) - conjugated antisense oligonucleotides (ASOs) have demonstrated improved hepatocyte uptake and pharmacologic activity over their parent unconjugated ASOs in animals and humans. Areas covered: In this review, the ADME (absorption, distribution, metabolism, and excretion) characteristics of GalNAc3-conjugated ASOs in animals and in humans are summarized, and their clinical relevance is evaluated from the clinical pharmacology perspectives. Expert opinion: ASOs distribute to tissues via receptor-mediated processes, and conjugation to a ligand specific to certain cell types can improve target tissue delivery. GalNAc3-conjugation represents a good example on this regard and has demonstrated ideal characteristics of a prodrug to target delivery of ASOs to hepatocytes via the asialoglycoprotein receptor (ASGPR). The improved potency and safety margin permit more flexible dosing (e.g. monthly or less frequently if needed) taking full advantage of the long half-life of the parent ASO in humans. However, while still speculative, it should be noted that ASGPR-mediated uptake could become nonlinear with dose and factors that impact ASGPR expression or compete with ASGPR-mediated uptake could potentially affect the uptake of GalNAc3-conjugated ASOs, further studies are warranted.
On the Ecology of Selenium Accumulation in Plants.

Plants accumulate and tolerate Se to varying degrees, up to 15,000 mg Se/kg dry weight for Se hyperaccumulators. Plant Se accumulation may exert positive or negative effects on other species in the community. The movement of plant Se into ecological partners may benefit them at low concentrations, but cause toxicity at high concentrations. Thus, Se accumulation can protect plants against Se-sensitive herbivores and pathogens (elemental defense) and reduce surrounding vegetation cover via high-Se litter deposition (elemental allelopathy). While hyperaccumulators negatively impact Se-sensitive ecological partners, they offer a niche for Se-tolerant partners, including beneficial microbial and pollinator symbionts as well as detrimental herbivores, pathogens, and competing plant species. These ecological effects of plant Se accumulation may facilitate the evolution of Se resistance in symbionts. Conversely, Se hyperaccumulation may evolve driven by increasing Se resistance in herbivores, pathogens, or plant neighbors; Se resistance also evolves in mutualist symbionts, minimizing the plant’s ecological cost. Interesting topics to address in future research are whether the ecological impacts of plant Se accumulation may affect species composition across trophic levels (favoring Se resistant taxa), and to what extent Se hyperaccumulators form a portal for Se into the local food chain and are important for Se cycling in the local ecosystem.
Pulmonary Vascular Disease

Pulmonary vascular disease is characterized by partial or complete obstruction of the pulmonary arteries and arterioles. This results in elevated pulmonary vascular resistance and ventilation/perfusion mismatch. As the disease progresses, these vascular changes may result in right ventricular dysfunction. These abnormalities may have profound consequences upon the physiologic measurements obtained during an exercise. Data from exercise testing also carries important clinical implications.
Current and Emerging Treatment Strategies for Primary Mediastinal B-Cell Lymphoma

Primary mediastinal B-cell lymphoma is rare, representing less than 5% of all non-Hodgkin lymphomas. Given its rarity, the only studies from which to derive optimal management are single arm, retrospective, or subgroup analyses of larger studies. Despite the paucity of high-level evidence, the historical standard frontline treatment is R-CHOP followed by consolidative mediastinal radiotherapy. Recent data suggest that increased intensity chemoimmunotherapy may obviate the need for mediastinal radiotherapy in the frontline setting and that combinations or sequences of novel immunotherapies, small molecule inhibitors, and monoclonal antibodies may improve outcomes in the relapsed or refractory setting which otherwise carries a dismal prognosis.
Promoter-Proximal Chromatin Domain Insulator Protein BEAF Mediates Local and Long-Range Communication with a Transcription Factor and Directly Activates a Housekeeping Promoter in Drosophila

BEAF (Boundary Element-Associated Factor) was originally identified as a Drosophila melanogaster chromatin domain insulator-binding protein, suggesting a role in gene regulation through chromatin organization and dynamics. Genome-wide mapping found that BEAF usually binds near transcription start sites, often of housekeeping genes, suggesting a role in promoter function. This would be a nontraditional role for an insulator-binding protein. To gain insight into molecular mechanisms of BEAF function, we identified interacting proteins using yeast two-hybrid assays. Here, we focus on the transcription factor Serendipity δ (Sry-δ). Interactions were confirmed in pull-down experiments using bacterially expressed proteins, by bimolecular fluorescence complementation, and in a genetic assay in transgenic flies. Sry-δ interacted with promoter-proximal BEAF both when bound to DNA adjacent to BEAF or > 2-kb upstream to activate a reporter gene in transient transfection experiments. The interaction between BEAF and Sry-δ was detected using both a minimal developmental promoter (y) and a housekeeping promoter (RpS12), while BEAF alone strongly activated the housekeeping promoter. These two functions for BEAF implicate it in playing a direct role in gene regulation at hundreds of BEAF-associated promoters.
Spitzer/IRAC observations of the variability of Sgr A* and the object G2 at 4.5 μm

We present the first detection from the Spitzer Space Telescope of 4.5 μm variability from Sgr A^*, the emitting source associated with the Milky Way's central black hole. The >23 hr continuous light curve was obtained with the Infrared Array Camera (IRAC) instrument in 2013 December. The result characterizes the variability of Sgr A^* prior to the closest approach of the tidally deformed G2 object, a putative infalling gas cloud that orbits close to Sgr A^*. The high stellar density at the location of Sgr A^* produces a background of ~250 mJy at 4.5 μm in each pixel with a large pixel-to-pixel gradient, but the light curve for the highly variable Sgr A^* source was successfully measured by modeling and removing the variations due to pointing wobble. The observed flux densities range from the noise level of ~0.7 mJy rms in a 6.4 s measurement to ≳10 mJy. Emission was seen above the noise level ~34% of the time. The light-curve characteristics, including the flux density distribution and structure function, are consistent with those previously derived at shorter infrared wavelengths. We see no evidence in the light curve for activity attributable to the G2 interaction at the observing epoch, ~100 days before the expected G2 periapsis passage. The IRAC light curve is more than a factor of two longer than any previous infrared observation, improving constraints on the timescale of the break in the power spectral distribution of Sgr A^* flux densities. The data favor the longer of the two previously published values for the timescale.
Treating MS after surviving PML: Discrete strategies for rescue, remission, and recovery patient 2: From the National Multiple Sclerosis Society Case Conference Proceedings.

The patient is a right-handed White woman with relapsing-remitting MS diagnosed subsequent to left acute optic neuritis (AON). She described a previous transient episode of severe, electrical, and paroxysmal facial pain consistent with trigeminal neuralgia. Initial MRI demonstrated supratentorial
Antiseizure Drugs and Seizure Aggravation

Specific situations exist where the addition of antiseizure medications (ASM) worsens seizures instead of reducing or eliminating them. Common examples of seizure aggravation from ASM occur in the context of inappropriate selection of medication chosen for treating a patient with epilepsy. Traditional ASM that block the sodium channel such as phenytoin or carbamazepine products (i.e., oxcarbazepine and eslicarbazepine) may exacerbate seizures in some patients with genetic generalized epilepsies by aggravating or triggering new generalized seizure types such as absence and myoclonus. Other ASM such as ethosuximide used to treat patients with absence seizure are ineffective for the treatment of focal seizures and may appear to aggravate or exacerbate this seizure type. Additionally, drug-drug interactions may occur and result in lowering effective circulating serum concentrations of ASM leading to an apparent worsening of seizure control. A working knowledge of these situations, an accurate epilepsy diagnosis and classification, and awareness of pharmacology are essential to optimize medical therapy for patients with epilepsy.
Survey of Transverse Range Fire Scars in 10 Years of UAVSAR Polarimetry

Because cross-polarized radar returns are highly associated with volume scatter, radar polarimetry returns tend to show strong evidence of wildfire scars and recovery in forest and chaparral. We fo...
Do Corporate Insiders Take Advantage of Their Political Connections? Evidence from Insider Trading

Using corporate insiders’ employment data, I study the impact of political connections on corporate insiders’ trading behavior. I find that purchases (sales) by politically connected corporate insiders are associated with lower (higher) abnormal returns compared with non-politically connected insiders, indicating that politically connected insiders in general are sophisticated and cautious about potential legal risk. This effect is more significant among purchases. I also find that politically connected insiders are more likely to have longer trading horizons, and more likely to make routine trades. The Stop Trading on Congressional Knowledge (STOCK) Act passed in April 2012 effectively decreases (increases) the abnormal returns associated with insider purchases (sales) made by Congress members and staff in short horizons.
The Case For Cadmium and Lead Heavy Metal Screening.

Abstract Exposure to cadmium and lead is widespread, and is related to environmental contamination, occupational sources, food, tobacco and other consumer products. Lower socioeconomic status increases the risk of heavy metal exposure and the diseases associated with cadmium and lead toxicity. Concurrent toxicity with both cadmium and lead is likely but has not often been assessed. There is now substantial evidence linking cadmium and lead to many diseases including hypertension, diabetes mellitus, obesity, cancer, coronary artery disease, chronic kidney disease (CKD) and lung disease. Both chronic renal failure and ischemic heart disease patients have been treated separately in recent studies with calcium disodium ethylenediaminetetraacetic acid (Ca EDTA) chelation therapy. In patients with CKD, serum creatinine 1.5–4.0 mg/dL, and increased body lead burden, weekly low dose chelation with Ca EDTA slowed the rate of decline in renal function in diabetics and non-diabetics. In patients with a history of myocardial infarction, the Trial to Assess Chelation Therapy (TACT) study showed that Ca EDTA chelation decreased the likelihood of cardiovascular events, particularly in diabetics. Ca EDTA chelation administered carefully at lower dosage (
Integrating Humanistic Counseling and Ecotherapy

Counselors continue to incorporate ecotherapy into practice and research. Greater conceptualization of ecotherapy within a humanistic framework can inform counselors on how to incorporate clients’ ...
Menin-MLL inhibitors block oncogenic transformation by MLL-fusion proteins in a fusion partner-independent manner

Menin-MLL inhibitors block oncogenic transformation by MLL-fusion proteins in a fusion partner-independent manner
Nematospiroides dubius: mechanisms of host immunity. II. Skin testing and immunosuppression of orally or subcutaneously sensitized mice.

Abstract The present study was designed to acquire further understanding of the differences in the immune response of mice orally (OS) or subcutaneously (SS) sensitized to Nematospiroides dubius . Two immunosuppressive agents and skin tests were utilized in this regard. Rabbit antimouse thymus serum (RAMTS) and cyproheptadine (antihistamine-antiserotonin) were similarly effective in suppressing the immune response of subcutaneously sensitized mice. When compared to normal rabbit serum and SS control (sensitized, untreated) animals, observations of the intestinal tunica muscularis in the immunosuppressed SS groups revealed granulomatous lesions in which fewer eosinophils enveloped the sequestered parasite. Cyproheptadine was more successful than the other treatments in interrupting the immune expulsion of N. dubius from orally sensitized mice, but this was only at a borderline significance level. The size and intensity of the active cutaneous anaphylactic skin tests in OS mice injected with an adult or larval antigen, was greater than the response elicited in SS mice or uninfected control mice injected with the same preparations. Similarly, the reaction in subcutaneously sensitized mice exceeded that observed in the noninfected controls.
Investigation of the T-5 cable tensiometer grip attachment for measuring strength of college women.

(1969). Investigation of the T-5 Cable Tensiometer Grip Attachment for Measuring Strength of College Women. Research Quarterly. American Association for Health, Physical Education and Recreation: Vol. 40, No. 4, pp. 848-850.
Evaluating Forecasting Methods

Ideally, forecasting methods should be evaluated in the situations for which they will be used. Underlying the evaluation procedure is the need to test methods against reasonable alternatives. Evaluation consists of four steps: testing assumptions, testing data and methods, replicating outputs, and assessing outputs. Most principles for testing forecasting methods are based on commonly accepted methodological procedures, such as to prespecify criteria or to obtain a large sample of forecast errors. However, forecasters often violate such principles, even in academic studies. Some principles might be surprising, such as do not use R-square, do not use Mean Square Error, and do not use the within-sample fit of the model to select the most accurate time-series model. A checklist of 32 principles is provided to help in systematically evaluating forecasting methods.
Fine‐scale environmental variation in species distribution modelling: regression dilution, latent variables and neighbourly advice

Summary 1. Developing the next-generation of species distribution modelling (SDM) requires solutions to a number of widely recognised problems. Here, we address the problem of uncertainty in predictor variables arising from fine-scale environmental variation. 2. We explain how this uncertainty may cause scale-dependent ‘regression dilution’, elsewhere a well-understood statistical issue, and explain its consequences for SDM. We then demonstrate a simple, general correction for regression dilution based on Bayesian methods using latent variables. With this correction in place, unbiased estimates of species occupancy vs. the true environment can be retrieved from data on occupancy vs. measured environment, where measured environment is correlated with the true environment, but subject to substantial measurement error. 3. We then show how applying our correction to multiple co-occurring species simultaneously increases the accuracy of parameter estimates for each species, as well as estimates for the true environment at each survey plot – a phenomenon we call ‘neighbourly advice’. With a sufficient number of species, the estimates of the true environment at each plot can become extremely accurate. 4. Our correction for regression dilution could be integrated with models addressing other issues in SDM, e.g. biotic interactions and/or spatial dynamics. We suggest that Bayesian analysis, as employed here to address uncertainty in predictor variables, might offer a flexible toolbox for developing such next-generation species distribution models.
Infrasonic Measurement of Building Air Leakage: A Progress Report

This research compares a new infrasonic method with the conventional blower method for determining the composite effective size of all the air-leakage passages in a house or apartment. In the frequency range used (0.1 to 7 Hz) small buildings are characterized mainly by one acoustic capacitance and one nonlinear leakage resistance. Infrasonic apparatus comprising a motor-driven source having known output, a sensitive pressure pickup, and an electronic signal processor has been constructed and used to measure leakage from several apartments and a house. Under field conditions the results of the infrasonic and blower measurements agree within a factor of two or three. Since the infrasonic system requires no through-the-wall blower vent or pressure taps, it is easier to set up than a blower system.
Phase reconciliation for contended in-memory transactions

Multicore main-memory database performance can collapse when many transactions contend on the same data. Contending transactions are executed serially--either by locks or by optimistic concurrency control aborts--in order to ensure that they have serializable effects. This leaves many cores idle and performance poor. We introduce a new concurrency control technique, phase reconciliation, that solves this problem for many important workloads. Doppel, our phase reconciliation database, repeatedly cycles through joined, split, and reconciliation phases. Joined phases use traditional concurrency control and allow any transaction to execute. When workload contention causes unnecessary serial execution, Doppel switches to a split phase. There, updates to contended items modify per-core state, and thus proceed in parallel on different cores. Not all transactions can execute in a split phase; for example, all modifications to a contended item must commute. A reconciliation phase merges these per-core states into the global store, producing a complete database ready for joined-phase transactions. A key aspect of this design is determining which items to split, and which operations to allow on split items.Phase reconciliation helps most when there are many updates to a few popular database records. Its throughput is up to 38x higher than conventional concurrency control protocols on microbenchmarks, and up to 3x on a larger application, at the cost of increased latency for some transactions.
Inverse plan optimization accounting for random geometric uncertainties with a multiple instance geometry approximation (MIGA).

Radiotherapytreatment plans that are optimized to be highly conformal based on a static patient geometry can be degraded by setup errors and/or intratreatment motion, particularly for IMRT plans. To achieve improved plans in the face of geometrical uncertainties, direct simulation of multiple instances of the patient anatomy (to account for setup and/or motion uncertainties) is used within the inverse planning process. This multiple instance geometry approximation (MIGA) method uses two or more instances of the patient anatomy and optimizes a single beam arrangement for all instances concurrently. Each anatomical instance can represent expected extremes or a weighted distribution of geometries. The current implementation supports mapping between instances that include distortions, but this report is limited to the use of rigid body translations/rotations. For inverse planning, the method uses beamlet dose calculations for each instance, with the resulting doses combined using a weighted sum of the results for the multiple instances. Beamlet intensities are then optimized using the inverse planning system based on the cost for the composite dose distribution. MIGA can simulate various types of geometrical uncertainties, including random setup error and intratreatment motion. A limited number of instances are necessary to simulate Gaussian-distributed errors. IMRT plans optimized using MIGA show significantly less degradation in the face of geometrical errors, and are robust to the expected (simulated) motions. Results for a complex head/neck plan involving multiple target volumes and numerous normal structures are significantly improved when the MIGA method of inverse planning is used. Inverse planning using MIGA can lead to significant improvements over the use of simple PTV volume expansions for inclusion of geometrical uncertainties into inverse planning, since it can account for the correlated motions of the entire anatomical representation. The optimized plan results reflect the differing patient geometry situations which can be important near the surface or heterogeneities. For certain clinical situations, the MIGA optimization approach can correct for a significant part of the degradation of the plan caused by the setup uncertainties.
Sequential decision-making in a computer-controlled task

Twenty-four undergraduate college students participated individually as subjects in a computer-controlled task, intended as an investigation of decision-making under uncertainty in a nonstationary environment. Each subject was required on every trial to predict the value of an unknown P, 0 ≤ P ≤ 1.00, and then to estimate its value after having received partial information about it from a computer. Each P value, for 120 trials, was generated by one of three different beta distributions. A model derived from Bayesian decision theory is presented, tested, and partially confirmed. A learning model was constructed and tried in a computer simulation of the subjects. Implications concerning information seeking and use of computers in experiments are discussed briefly.
Life and death in the gut: more killing, less Crohn's.

The beneficial effects of infliximab, the tumour necrosis factor antibody, in Crohn's disease may be mediated by apoptosis of activated mucosal T cells The advent of new biological agents for the treatment of autoimmune and chronic inflammatory disorders is drastically altering the approach to management while setting higher standards for therapeutic expectations. Only a fraction of the new biological agents keeps the promise of improved efficacy and specificity but the few that do can generate impressive results as we are currently witnessing for anti-tumour necrosis factor (TNF)-α therapy in rheumatoid arthritis and Crohn's disease.1,2 Based on these results, a number of other conditions where TNF-α biological activity may play a pathogenic role, such as psoriasis, sarcoidosis, spondyloarthropathy, Behcet's syndrome, and sepsis, are being treated using TNF-α blocking antibodies with variable but generally positive results. Since the first report of the use of infliximab in human disease,1 the literature has swelled to over 200 publications on practical applications and theoretical considerations of this humanised antibody. In this enormous body of information however, disappointingly little is found on the mechanisms of action of infliximab. Almost invariably the optimism caused by the feeling of finally having discovered a magic bullet against unyielding diseases causes all interest and resources to be shifted to more clinical trials. Although this reaction is understandable, all too often it comes at the expense of investigating mechanisms of action that would ultimately lead to a safer and more reliable use of the biological agent, or even the discovery of better biologicals. Thus the study of ten Hove et …
Validation of an S-O-R Model for Situation, Enduring, and Response Components of Involvement:

Despite the importance of the concept of involvement, it remains misunderstood. No attempt has been made to establish the reliability and validity of the concept. To resolve apparently conflicting ...
AN UPPER BOUND ON EDGE NUMBERS OF 2-BRIDGE KNOTS AND LINKS

A method is given for economically constructing any 2-bridge knot or link K. This construction gives an upper bound of c(K) + 3 for the edge number of K, except in the case of the unlink and the Hopf link, and has the added advantage of realizing a projection with c(K) crossings.
Thought and world : an austere portrayal of truth, reference, and semantic correspondence

There is an important family of semantic notions that we apply to thoughts and to the conceptual constituents of thoughts - as when we say that the thought that the Universe is expanding is true. Thought and World presents a theory of the content of such notions. The theory is largely deflationary in spirit, in the sense that it represents a broad range of semantic notions - including the concept of truth - as being entirely free from substantive metaphysical and empirical presuppositions. At the same time, however, it takes seriously and seeks to explain the intuition that there is a metaphysically or empirically 'deep' relation (a relation of mirroring or semantic correspondence) linking thoughts to reality. Thus, the theory represents a kind of compromise between deflationism and versions of the correspondence theory of truth. This book will appeal to students and professionals interested in the philosophy of logic and language.
Effect of two stage pressure molding on surface quality of sheet molding compounds

The goal of this work was to investigate the effect of two stage pressure molding on the compression molding of a sheet molding compound (SMC). It has been shown in previous studies that a rapid drop in pressure during SMC curing significantly reduced severity of sink marks. This study concentrated on a method of predicting the optimum time during curing to release pressure by examining material behavior through process data from in-mold sersors. A simple control scheme was them applied for automatic pressure release at the optimum time corresponding with the peak of the material expansion and the onset of the reaction exotherm.
Digital imaging in transmission electron microscopy.

The digital revolution currently under way, as evidenced by the rapid development of the Internet and the world-wide-web technologies, is undoubtedly impacting the field of transmission electron microscopy (TEM). Digital imaging systems based on charge-coupled device (CCD) technologies, with pixel array size up to 2 k × 2 k at the present and increasing, are available for TEM applications and offer many attractions. Is it time to phase out film cameras on TEMs and close the darkrooms for good? This paper reviews digital imaging technologies for TEM at different voltages, and contrasts the performance of digital imaging systems with that of TEM film. The performance characteristics of CCD-based digital imaging systems, as well as methods for assessing them, are discussed. Other approaches to digital imaging are also briefly reviewed.
A New Way of Teaching Statistics

Teaching statistics through computer-assisted simulations eliminates the constraints and challenges associated with teaching the course using mathematics. It also provides students with a practical...
Predicting Cell Types and Genetic Variations Contributing to Disease by Combining GWAS and Epigenetic Data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease.