cssi/SciSciGPT-SciSciNet huggingface dataset:
Analysis and modeling of biological systems using fractal geometry

Fractal objects which, by definition, are objects that have scale-invariant shapes and fractional scaling dimensions (fractal dimension) with magnitudes related to the complexity of the objects, are ubiquitous in nature. In particular, many biological structures and systems have fractal properties and therefore may be well studied and modelled using fractal geometry. In the box counting algorithm, one of several different approaches to calculate the fractal dimension, one determines, for several values of?, the number of boxesN(?) with side length? needed to completely cover the studied object. IfN(?) andr are found to be related by the power law relationshipN(r) ~r ?D, whereD is the scaling dimension, and ifD is a non-integer, then the object is fractal andD is the fractal dimension. In certain circumstances in which one may need to calculate the fractal dimension of a three-dimensional fractal from a two-dimensional projection (e.g. an X-ray), a new mathematical relationship may be utilized to obtain the actual dimensionD; it readsD=?log[1?(1?R 2? D p) R ]/logR + 3, whereD p is the fractal dimension of the two-dimensional planar projection of the object andR is the box size used in calculating the box-counting dimension. Fractal dimension calculations have been found to be particularly useful as quantitative indices of the degree of coronary vascularity and the degree of heart interbeat interval variability. Fractal growth models such as diffusion limited aggregation (DLA) can be used to model artery growth. To sum up, fractal geometry is very useful in studying and modeling certain scale-invariant biological structures or systems which may not be easily described with Euclidean shapes.
A Knowledge Comparison of Nursing Students in Perioperative Versus Other Rotations

ABSTRACT • AS MORE PATIENTS UNDERGO surgical interventions in ambulatory facilities and patients in acute care settings have shorter lengths of stay, nursing students may have limited interaction with the surgical patient population. • THIS STUDY USED a repeated measure, experimental design to compare knowledge of surgical patient care among undergraduate nursing students who experienced a perioperative clinical rotation (ie, experimental groups) with knowledge among students who experienced rotations in other clinical settings (ie, control groups). • RESULTS DEMONSTRATED a significant change in mean knowledge scores over time and a significant difference in mean scores between the experimental and control groups. Students in the perioperative group scored higher in all four testing periods. AORN J 80 (October 2004) 699–707.
DNA-dependent RNA polymerase I from Acanthamoeba castellanii: Comparison of the catalytic properties and subunit architectures of the trophozoite and cyst enzymes☆

Abstract The actively growing cells (trophozoites) of the amoeba Acanthamoeba castellanii were found to contain one major form of class I RNA polymerase. This enzyme was purified to near homogeneity and had a subunit architecture of (182,000)1, (122,000)1, (35,000)2, (20,800)2, (19,900)1, (18,100)1, and (16,400)2. The subcellular localization and catalytic properties of the enzyme suggest it to be a cognate of the eucaryotic class I polymerases previously reported. When Acanthamoeba castellanii is transferred to a medium lacking nutrients, the cells undergo a cellular differentiation resulting in the formation of metabolically inactive cells (cyst formation). During this process, the rate of ribosomal RNA synthesis decreases, ceasing by the seventh hour after cyst induction. During this time polymerase II and III activity remains constant and the cells are metabolically active. In contrast to this decrease in rRNA synthesis, we found no change in the level of extractable polymerase I activity ( S. Detke and M. R. Paule, 1975, Biochim. Biophys. Acta, 383, 67–77 ) or in the specific activity of the purified enzyme. Furthermore, the catalytic and chromatographic properties and the subunit architecture of the polymerase remain unchanged. These findings suggest that the rate of rRNA synthesis in Acanthamoeba is not controlled by modifying the number or the structure of the polymerase I molecules present in the cell.
Modeling the Dependence of Fabric Reflectance on Denier per Filament

A ray trace model for predicting fiber optical properties has been previously described. This model, which treats each filament in a yarn bundle independently, has been extended to include multifil...
Serious complications of uterine artery embolization for conservative treatment of fibroids.

Abstract Objective Document major complications following treatment of fibroids by uterine artery embolization (UAE). Design Two case reports. Setting University medical center. Patient(s) Two women with symptomatic fibroid uteri. Intervention(s) Selective bilateral uterine artery embolization. Main outcome measure(s) Complications attributable to UAE. Result(s) Two patients experienced significant morbidity requiring hysterectomy due to infection and/or partial bowel obstruction resulting from UAE. Conclusion(s) Reports of the management of symptoms related to fibroids with UAE infrequently include adverse outcomes and/or complications. The two cases we managed reinforce that UAE is not free of the risk of life-threatening complications that require emergency hysterectomy. Increasing surveillance for complications may help define the selection criteria that decrease the risks of UAE.
Continuous Monitoring ofin VivoNitric Oxide Formation Using EPR Analysis in Biliary Flow

Abstract A method to continuously monitor the nitric oxide (NO) level in anesthetized rats, using anin vivotrapping reaction of NO by iron–dithiocarbamate complex, is reported. Previously, we developed a method of monitoring NO in bile samples containing an NO complex excreted from the liver (Anal. Biochem.243, 8–14, 1996). In the present study, we modified the method so that the bile flows directly through the EPR sample cell. Rats were injected with low doses of lipopolysaccharide (LPS) to induce NO formation and were later anesthetized. After cannulation, the bile duct was connected to the inlet of the EPR sample cell and the trapping agent iron complex of d -N-methylglucamine dithiocarbamate (MGD–Fe) was administered. The EPR signal level from NO complex of MGD–Fe in the flowing bile was continuously monitored. Using this method, immediate changes inin vivoNO level in rats were observed following administration of drugs that can affect NO formation. In addition, a continuous intravenous saline containing MGD–Fe made the EPR signal level stable and improved animal condition as well as survival time. Therefore, this method has two merits; (1) one can continuously monitor NO formation until it reaches the maximum level; (2) a rapid change in NO level after intervention can be followed. Using this method, we tested the effect of the substrate l -arginine and inhibitors for NO synthase activity and NO synthase induction. The sensitivity of the present method was tested by monitoring NO formation in rats after exposure to ionizing radiation.
Effects of Greenhouse Gas Emissions on World Agriculture, Food Consumption, and Economic Welfare

Because of many uncertainties, quantitative estimates of agriculturally related economic impacts of greenhouse gas emissions are often given low confidence. A major source of uncertainty is our inability to accurately project future changes in economic activity, emissions, and climate. This paper focuses on two issues. First, to what extent do variable projections of climate generate uncertainty in agriculturally related economic impacts? Second, to what extent do agriculturally related economic impacts of greenhouse gas emissions depend on economic conditions at the time of impacts? Results indicate that uncertainty due to variable projections of climate is fairly large for most of the economic effects evaluated in this analysis. Results also indicate that economic conditions at the time of impact influence the direction and size of as well as the confidence in the economic effects of identical projections of greenhouse gas impacts. The economic variable that behaves most consistently in this analysis is world crop production. Increases in mean global temperature, for example, cause world crop production to decrease on average under both 1990 and improved economic conditions and in both instances the confidence with respect to variable projections of climate is medium (e.g.,67%) or greater. In addition and as expected, CO2 fertilization causesworld crop production to increase on average under 1990 and improved economic conditions. These results suggest that crop production may be a fairly robust indicator of the potential impacts of greenhouse gas emissions.A somewhat unexpected finding is that improved economic conditions are not necessarily a panacea to potential greenhouse-gas-induced damages, particularly at the region level. In fact, in some regions, impacts of climate change or CO2 fertilization that are beneficial undercurrent economic conditions may be detrimental under improved economic conditions (relative to the new economic base). Australia plus New Zealand suffer from this effect in this analysis because under improved economic conditions they are assumed to obtain a relatively large share of income from agricultural exports. When the climate-change and CO2-fertilization scenariosin this analysis are also included, agricultural exports from Australia plus New Zealand decline on average. The resultant declines in agricultural income in Australia plus New Zealand are too large to be completely offset by rising incomes in other sectors. This indicates that regions that rely on agricultural exports for relatively large shares of their income may be vulnerable not only to direct climate-induced agricultural damages, but also to positive impacts induced by greenhouse gas emissions elsewhere.
Explaining the Unpredictable

It has been said — and I was among those saying it — that any theory of explanation worth its salt should be able to make good predictions. If good predictions could not be made, the explanation could hardly count as serious. This is one more attempt at unification I now see as misplaced. I want to examine some principled reasons why the thrust for predictability was mistaken. I begin with the familiar sort of example of explanation, the kind that occurs repeatedly in analyses of the past.
Brain areas involved in the catecholamine mediated regulation of electroshock seizure intensity.

Selective treatments which alter the catecholamine content of discrete areas of the brain were tested for their effect on electroshock seizure intensity in the rat. The data indicate that depletion of noradrenaline and dopamine in near ventricular areas by the intracerebroventricular administration of the benzoquinolizine, Ro 4–1284, enhances electroshock seizure intensity. The enhancement of seizure produced by systemic Ro 4–1284 was antagonized by the intracerebroventricular injection of noradrenaline or dopamine which do not appear to penetrate more than 1 mm into the brain. Further, pretreatment with systemic iproniazid and l-dopa completely antagonized the increased seizure intensity produced by intracerebroventricular Ro 4–1284 and repleted brain catecholamines in both near and far ventricular areas. Thus, the effects of both noradrenaline and dopamine in attenuating electroshock seizure intensity appear to be exerted principally through periventricular structures.
Quantitative Assay for Human Cytoplasmic Islet Cell Antibodies

An assay for human islet cell antibodies (ICAs) in serum yielding numerical values and amenable to statistical evaluation has been developed utilizing fluorescence spectrophotomicroscopy (FSPM). The results of the blinded trials by FSPM were compared with those by standard indirect immunofluorescence (IFL). No false-positive or false-negative readings were obtained in 258 observations when the results by FSPM were compared with those by IFL. The intra- and interassay variabilities encountered were not enough to misclassify a specimen. The presence of anti-thyroid, anti-adrenal, or anti-nuclear antibodies did not produce false-positive readings. Twenty-eight additional specimens from diabetic children were also analyzed via three blood group type O pancreases. There was complete agreement concerning the presence or absence of ICA between IFL and FSPM analyses. Analysis of the three pancreases yielded different numbers of results positive for ICA (14/28 vs. 22/28 vs. 15/28, P = .008) in both assays. Thus, selection of pancreatic substrate may influence the outcome of assays for ICA. A matrix of fluorescent microspheres has been devised that allows calibration of the FSPM system. Now, reproducible and comparable readings for ICA values can be obtained from the various reporting laboratories. Should an international reference serum for ICA become available, the remaining problem in the ICA assay, that of substrate (pancreas) variability, should be resolved.
Combinatorics for computing relativistic several complex variable domains

Examples are given of combinatorics involved in computing analytic extensions of several complex variable domains. These domains discussed arise in the relativistic quantum theory of fields. The results are in the form of exact symbolic computation over continuous spaces, namely several complex variable domains C^n. Underlying symmetries, which involve the discrete permutation group on n symbols and the continuous Poincare group, are utilized in the computation. Some insight is obtained regarding factoring out translational and Lorentz invariances even though a semidirect product between them is involved. Extensions of four-point Wightman function domains are obtained explicitly beyond what was previously known. It is also thus illustrated, in a practical sense, that computation over the continuum can involve discrete combinatorial techniques.
What was the first epidemiological study of smoking and lung cancer

Based on his critique of the early case-control study of smoking and lung cancer by Mueller, Morabia questions the priority that has been assigned to this research. I examine Morabia's approach to retrospectively assess quality and question its general applicability and replicability. By citation analyses, the case-control studies published in the 1950s have had far greater impact. Morabia's commentary points to the complexity and subtlety of re-interpreting older literature.
Cluster computing for web-scale data processing

In this paper we present the design of a modern course in cluster computing and large-scale data processing. The defining differences between this and previously published designs are its focus on processing very large data sets and its use of Hadoop, an open source Java-based implementation of MapReduce and the Google File System as the platform for programming exercises. Hadoop proved to be a key element for successfully implementing structured lab activities and independent design projects. Through this course, offered at the University of Washington in 2007, we imparted new skills on our students, improving their ability to design systems capable of solving web-scale problems.
Delayed membranous ossification of the cranium associated with familial translocation (2;3)(p15;q12).

The relationship of delayed membranous cranial ossification to cranium bifidum and parietal foramina syndromes is unclear. We report on a family with delayed cranial membranous ossification (OMIM 155980) that segregates with an apparently balanced reciprocal translocation between chromosomes 2 and 3. The propositus had apparently low-set ears, proptosis, and a soft skull at birth. A radiographic survey of the skeleton showed markedly decreased ossification of the cranial bones and no other skeletal abnormalities. The mother and maternal grandmother of the propositus have brachycephaly, hypertelorism, and a history of a soft skull at birth. Chromosome analysis of peripheral blood from the propositus showed 46,XY,t(2;3)(p15;q12). The propositus, mother, and grandmother carry the same reciprocal translocation, whereas the mother's two phenotypically normal sibs have a normal karyotype. We used an STS-linked BAC resource to define the translocation breakpoint by identifying flanking BAC clones from both chromosomes 2, 1006D24 (D2S2279) and 1060A5 (D2S2231), and chromosome 3, 3D17 (WI8558) and 3D18 [CITB Human BAC Library, J.R.K.]. This represents the second report of a family with delayed membranous ossification of the cranium and the first report of the phenotype segregating with a chromosome rearrangement.
Immunoreactive‘ TSH’ in urinary concentrates of Graves' disease patients: a radioimrnunoassay artefact

Abstract. A double antibody radioimmunoassay was used to analyse immunoreactive thyrotrophin in urinary concentrates from fourteen patients with hyperthyroid-ism due to Graves' disease, in three subjects with primary hypothyroidism, and in six normal subjects. Immunoreactive thyrotrophin was detectable in eleven subjects with Graves' disease, in one subject with primary hypothyroidism, and in four normal subjects. The mean urinary thyrotrophin concentration was significantly higher in Graves' disease (492 ± 99.9 μU/24h (SEM) (n= 11)) than in normal subjects ((177 ± 26.4 μU/ 24 h (SEM) (n = 4) (P<0.01)). The fact that bioassay-able thyrotrophin was undetectable in urinary concentrates in Graves' disease and that radioimmunoassay of other polypeptide hormones in urine can be influenced nonspecifically, led to the suspicion that the immunoreactive thyrotrophin measured in urinary concentrates was an assay artefact. This was strongly supported by the absence of a radioimmunoassayable thyrotrophin in urinary concentrates after extensive dialysis (96 h) without loss of added 131I-labelled thyrotrophin, differences between the elution pattern on Sephadex G-100 columns of 131I-labelled thyrotrophin and the immunoreactive thyrotrophin detected after chromato-graphy of the urinary concentrates on the same column, and the ability of different salts in various concentration to mimic dose-response curves in the radioimmunoassay for thyrotrophin as well as for thyroglobulin. In addition, since urinary proteins and IgG levels were elevated in concentrates of Graves' disease when compared with normal subjects, it has been suggested that the filtering mechanism of kidney is affected in Graves' disease, a disorder which has recently been associated with circulating antigen—antibody complexes.
Methylglyoxal Enhances Cisplatin-induced Cytotoxicity by Activating Protein Kinase Cδ

The cytotoxic side effects of anti-neoplastic drugs are increased in patients with either type 1 or type 2 diabetes mellitus by a mechanism that is not clearly defined. We report that the circulating glucose metabolite, methylglyoxal (MGO), enhances cisplatin-induced apoptosis by activating protein kinase Cdelta (PKCdelta). We found that treatment of myeloma cells with the antioxidant N-acetylcysteine completely blocked cisplatin-dependent intracellular GSH oxidation, reactive oxygen species (ROS) generation, poly(ADP-ribose) polymerase cleavage, and apoptosis. Importantly, co-treatment of cells with the reactive carbonyl MGO and cisplatin increased apoptosis by 90% over the expected additive effect of combined MGO and cisplatin treatment. This same synergism was also observed when ROS generation was examined. MGO and cisplatin increased PKCdelta activity by 4-fold, and this effect was blocked by the PKCdelta inhibitor rottlerin but not by NAC. Furthermore, rottlerin blocked combined MGO and cisplatin-induced ROS generation and apoptosis. Finally, MGO and cisplatin induced c-Abl activation and c-Abl:PKCdelta association. Rottlerin blocked c-Abl activation, but the c-Abl inhibitor STI-571 increased MGO and cisplatin-induced apoptosis by 50%. Taken together these data indicate that MGO synergistically enhances cisplatin-induced apoptosis through activation of PKCdelta and that PKCdelta is critical to both cell death and cell survival pathways. These findings suggest that in the patient with diabetes mellitus heightened oxidative stress can enhance the cytotoxicity of agents that induce DNA damage.
Romantic relationship status and alcohol use and problems across the first year of college.

Objective:We examined the associations between romantic relationship status and alcohol use and problems in a large sample of first-year college students.Method:Participants (n = 2,056) came from a longitudinal study of college students who answered questions about relationship status (single, in an exclusive relationship, or dating several people), alcohol use, and alcohol problems at two time points across their first year.Results:After we controlled for a number of covariates (parental alcohol problems, high school conduct problems, peer deviance, and extraversion), we found that dating several people was associated with higher alcohol use and problems, compared with being single or being in an exclusive relationship, at the follow-up assessment only, with modest effect sizes. Being in an exclusive relationship was not associated with lower alcohol use or problems compared with being single. Relationship dissolution was associated with a modest longitudinal increase in alcohol problems.Conclusions:It i...
Studies on the biology and ultrastructure of nosema transitellae sp. n. (microsporidia: Nosematidae) in the navel orangeworm, paramyelois transitella (lepidoptera: Pyralidae)1

Nosema transitellae sp. n. was originally isolated from larvae of the navel orangeworm, Paramyelois transitella , reared on contaminated trash almonds. The life cycle of the pathogen includes the formation of quadrinucleate schizonts and sporonts that divide to form twin binucleate sporoblasts typical of the genus Nosema . The pathogen primarily invades fat and the silk and salivary glands. Larvae with heavy infections frequently develop melanized encapsulated fat lobes that are visible beneath the transparent cuticle. In laboratory tests, only the navel orangeworm and the red flour beetle, Tribolium castaneum , acquired lethal infections. The almond moth, Cadra cautella , the raisin moth, Cadra figulilella , the tobacco moth, Ephestia elutella , and the greater wax moth, Galleria mellonella , acquired benign infections. The sawtoothed grain beetle, Oryzaephilus surinamensis , was not susceptible. The ultrastructure of the spores of N. transitellae is similar to that of spores of N. whitei and N. oryzaephili .
Notable Silicon-Related Anniversaries

The Central Regional meeting of the American Chemical Society held at Central Michigan University recently celebrated two important silicon-related anniversaries. These were the synthesis of the first organosilicon compound, tetraethylsilane, in 1863 and the founding of the silicone industry in 1943.
Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a heterogeneous group of metabolic diseases resulting from defects in insulin secretion, insulin action, or both. It comprises most diagnosed cases of diabetes and disproportionately affects minorities. This article describes the classification of diabetes mellitus; defines the metabolic syndrome; and discusses the diagnosis, risk factors, and screening criteria for T2DM. The pathophysiology of T2DM, its acute and chronic complications, and signs and symptoms are presented, along with a brief overview of treatment.
Mesial temporal seizures may enhance complex reaction time test performance

Abstract Objective Probing of cognitive functions during seizures is an underdeveloped area of clinical epileptology. Transient cognitive impairment occurs sometime after electrographic onset in certain localization-related epilepsies, but precisely when and what alterations ensue are unknown. Answers to these questions were sought in the context of assessment of feasibility of automated seizure warning. Methods Subjects undergoing evaluation for invasive epilepsy surgery were administered a complex reaction time test triggered automatically by the detection of seizures. Performance during seizures was compared during randomly chosen interictal periods, using the Kolmogorov–Smirnov test. Results Statistically significant improvement in the performance of certain test metrics was observed in 3 of 14 subjects during seizures of mesial temporal lobe origin. Conclusion Based on these data, it is plausible that activation of central noradrenergic and dopaminergic networks by ictal activity originating from mesial temporal structures may, under particular conditions, optimize certain complex reaction time responses. If reproduced, these findings would a force a revision of the binary tenet that seizures either degrade or spare cognitive functions and open unsuspected research vistas.
Novel CNFET SRAM cell design operating in sub-threshold region using back-gate biasing

This paper proposes a new design of carbon nanotube FETs (CNFETs) based SRAM cell operating in subthreshold region. By using optimum back-gate biasing scheme for each transistor, the proposed SRAM cell achieves the best overall performance considering noise margin, delay and power. Compared with traditional subthreshold CNFET SRAM cell, the proposed SRAM cell increases static voltage noise margin (SVNM) 36%, increases static current noise margin (SINM) 2.5X, and reduces delay 61% with power consumption increasing only 1% for read operation. For write operation, the proposed SRAM cell increases write noise margin (WNM) 2.5X and reduces power consumption and delay 17% and 56% respectively compared with traditional subthreshold CNFET SRAM cell. In terms of total number of nanotubes (area) of CNFET SRAM cell, the proposed subthreshold CNFET SRAM cell can reduce at least half of total number of nanotubes without compromising noise margin, power and delay. New CNFET SRAM cell structure is proposed to dynamically bias each transistor at different operation modes.
The Central Regulation of Bone Remodeling

Abstract For a long time bone remodeling has been thought to be mainly an autocrine–paracrine phenomenon. Yet bone resorption mechanisms are under the control of hormones, suggesting that the same might be true for bone formation. The recent development of molecular endocrinology uncovers a common, central regulation of bone formation, body weight and reproduction mediated by leptin.
TU-C-L100J-02: A Fiber-Optic Coupled Point Dosimetry System for the Characterization of Multi-Detector CT

Purpose: Advances in CT acquisition techniques, primarily multidetector CT (MDCT) and cone beam CT(CBCT), make it highly desirable to develop measurement techniques that provide a more physically meaningful measurement of dose than the traditional CT dose index (CTDI). This study presents data based on a point dosimetrysystem utilizing fiber‐optic‐coupled (FOC) radioluminescent dosimeters to measure fundamental parameters associated with CTdosimetry. This point detector approach provides remote, real‐time dose measurements and allows direct recording of single‐scan dose profiles that contain the essential information required to determine dosimetric quantities for MDCT. Method and Materials: FOC dosimeters based on sensitive elements of either a copper‐doped quartz or coupled scintillation phosphor are characterized for their performance across the CT energy range based on energy dependence, dose linearity, and angular response. A custom Labview program provides a user‐friendly interface to control the system.Measurements were made using traditional CTDI as well as FOC dosimeter measurements for a variety of MDCT acquisition protocols. Results:Measurements along the central axis of a CTDI phantom provide a direct evaluation of the single scan dose profile. FOC peripheral point measurementsdetect intensity variation with tube rotation, a dependence on scanner pitch, and permit the correlation of scan parameters and dose profiles. While CTDI remains an accurate prediction of MSAD for axial CT, it is empirically demonstrated to fail for multiple scan dose profiles when pitch is not equal to one. The development of a small dosimeter that can directly measure the helical dose profile provides a useful characterization of MDCT scanning performance and an accurate prediction of MSAD. Conclusion: FOC dosimeters demonstrate high sensitivity, reproducibility, excellent dose linearity, and combined with their small physical size permit accurate point‐dose measurements. These properties provide a useful tool for the characterization of the dosimetry quantities fundamental to MDCT.
The development of thermoregulation after prenatal exposure to alcohol in rats.

The effect of prenatal exposure to alcohol on the development of thermoregulation and behavioral thermogenesis was assessed in rats. Pups at 5, 10, 15, and 20 days of age were chosen from litters with one of three prenatal treatment histories: liquid diet with 35% ethanol-derived-calories (35% EDC), pair-fed control (0% EDC), or lab chow control (LC). Subjects were removed from the home nest and had their initial rectal temparatures recorded before placement alone in the center of an observational chamber in a testing room maintained at 23–24° C. Rectal temperatures were recorded again every hour for the next 4 h. Speed to reach the wall for behavioral thermogenesis (wall-huddling) was also measured at each hourly interval. With increasing age, all pups displayed increasing ability to maintain their initial core temperature, but prenatal exposure to alcohol had a significant effect in retarding the development of thermoregulation. At 5 and 10 days of age, alcohol-exposed pups had significantly lower rectal temperatures at 1–4 h out of the nest compared to control pups. In addition, the speed to reach the wall was slower in 35% EDC pups than in pups from the two control groups, suggesting a deficit in behavioral thermogenesis as well. These results agree with others demonstrating alcohol-induced developmental delays, and may have implications for other behavioral deficits seen after prenatal exposure to alcohol.
The aptamer-siRNA conjugates: reprogramming T cells for cancer therapy.

Harnessing the body’s own immune system has the potential to generate diverse, yet highly specific antitumor responses with protective long-term effects. Recent clinical advances demonstrated that new cancer immunotherapies can achieve impressive therapeutic effects, even in patients with advanced tumors of various types [1]. The rapid progress in this area was enabled by our improved understanding of the mechanisms underlying tumor immune evasion. Cancers evolved multiple strategies to block the activity of T lymphocytes and adaptive immune responses. These include upregulation and the triggering of inhibitory receptors on CD8 T cells, such as CTLA-4 or PD-1, or direct induction of effector T-cell death, which altogether shift the balance of T-cell-mediated responses from cytotoxic T cells to Tregs [2,3]. Targeting of the CTLA-4 and PD-1 immune checkpoint pathways in T cells provided the first effective tools to disengage tumor defense systems [1]. Nevertheless, the antibody-mediated neutralization of critical immunoregulatory cell populations carries a potential risk of collateral damage or autoimmune manifestations [1]. Growing evidence suggests that targeting intracellular signaling and transcriptional regulators can provide safer methods to correct T-cell dysfunctions, such as Th2 or Treg bias [4]. Transcription factors, such as STAT3, FoxP3, SMAD2/3 or HIF-1a, are commonly activated in the tumor microenvironment and promote Treg functions [5–9]. Due to their intracellular localization and lack of enzymatic activity, the targeting of transcriptional regulators using antibodies or small-molecule drugs is challenging. Oligonucleotide-based therapeutics provide alternative strategies to target the expression of transcription factors (siRNA and antisense oligonucleotides) or their binding to target DNA sequences (decoy oligonucleotides) with high specificity. However, the broad application of oligonucleotide therapeutics is limited by the difficulty in efficient and cell-specific delivery. T cells resist the delivery of formulated oligonucleotides using conventional transfection methods. The delivery of oligonucleotides using viral vectors, which has been successfully employed in some T-cell-specific gene therapies, is less suitable for cancer therapy due to potential carcinogenic effects, broad tropism and difficulty in large-scale production [10].
Interactions Between Equivalence Relations and the Development of Analytic Units

Two experiments investigated possible interactions between existing equivalence relations among stimuli and the acquisition of simple discriminations involving the same stimuli. During the first phase of Experiment 1, two adult humans learned two sets of six conditional relations among arbitrary visual stimuli designed to produce two independent sets of three, three-member equivalence classes (Set 1 and Set 2). Subjects whose performance met accuracy criteria on tests for equivalence relations proceeded to a second phase in which subjects were taught, via reinforcement, to make the same response to a cluster of three stimuli (e.g., response 1 in the presence of A1, B1, and C1). The clusters of three stimuli were initially consistent with documented equivalence relations for both Set 1 and Set 2 stimuli. In the second half of this phase, the contingencies were realigned such that the simple discriminations being established were consistent with documented equivalence relations for Set 1 stimuli but inconsistent for Set 2 stimuli. Results showed that the simple discriminations were acquired faster for Set 1 stimuli than for Set 2 stimuli. Experiment 2 introduced a third set of stimuli as a control set and systematically replicated Experiment 1 with four subjects. This study found that three of four subjects acquired simple discriminations faster when the cluster of stimuli were drawn from within equivalence classes rather than across equivalence classes. The development of equivalence relations with Set 3 stimuli constrained the utility of the control condition in this experiment. The results are best interpreted as suggesting that existing equivalence relations among stimuli can interact with the development of analytic units such as simple discriminations to either facilitate or retard their development.
Loss of thick filaments from fast‐twitch glycolytic muscle fibers of the pigeon pectoralis after chronic administration of dantrolene sodium

Adult pigeons received dantrolene sodium, a skeletal muscle relaxant which blocks the release of calcium during excitation-contraction coupling, for 12 to 16 weeks. The pectoralis muscles of these birds were analyzed for changes occurring in the various fiber types of the muscle. Both histochemistry (ATPase and SDH activity) and electron microscopy (mitochondrial and lipid volume percentages) differentiated two fiber types. The two fiber-types consisted of fast-twitch glycolytic fibers (FG) and fast-twitch oxidative-glycolytic (FOG) fibers. After dantrolene treatment some FG fibers showed little or no ATPase activity. Dantrolene treatment also produced a disappearance of thick filaments in some FG fibers. We infer that the fibers without thick filaments are the ones lacking ATPase activity. The FOG fibers were nearly normal. Since drug-fed birds lose weight, a few birds were starved to determine whether the filament loss was related solely to the bird's loss in weight. No fibers in starved birds showed reduced ATPase activity or loss of thick filaments. In fibers that showed thick filament disappearance, the I-bands remained organized and intact, suggesting that the I-band maintains its integrity without interaction with the thick filaments. Changes in activity patterns may cause loss of thick filaments by inhibiting either their synthesis or assembly.
Axial variation in the threespine stickleback: relationship to Hox gene expression.

Despite mounting evidence that key developmental regulator genes are involved in significant macroevolutionary changes, there have been few studies demonstrating the functional significance of variation in such genes for the generation of population-level variation. In this study we examined and compared the expression domains of three Hox gene homeobox sequences in embryos derived from two morphologically distinct populations of the threespine stickleback, Gasterosteus aculeatus. We found within-population variation in the location of anterior limits, particularly in more 5’Hox genes whose anterior expression domains showed graded distributions of transcripts over several somites. However, despite considerable and statistically significant differences in the anteroposterior pattern of the axial and median skeletons between the two stickleback populations, this phenotypic variation was not found to be correlated with any of the variation in Hox gene expression. The possible functional significance of the combinatorial Hox code in fish species is discussed with respect to the buffering of development in fluctuating environments, and it is argued that population and quantitative genetic perspectives should also be taken into account in considering the function and evolution of Hox genes.
Photo identity tag suggestion using only social network context on large-scale web services

Recently, uploading photos and adding identity tags on social network services are prevalent. Although some researchers have considered leveraging context to facilitate the process of tagging, these approaches still rely mainly on face recognition techniques that use visual features of photos. However, since the computational and storage costs of these approaches are generally high, they cannot be directly applicable to large-scale web services. To resolve this problem, we explore using only social network context to generate the top-k list of photo identity tag suggestion. The proposed method is based on various co-occurrence contexts that are related to the question of who may appear in this photo. An efficient ranking algorithm is designed to satisfy the real-time needs of this application. We utilize public album data of 400 volunteers from Facebook to verify that our approach can efficiently provide accurate suggestions with less additional storage requirement.
In vitro pharmacodynamics of novel rifamycin ABI-0043 against Staphylococcus aureus.

Objectives ABI-0043 is a novel benzoxazinorifamycin derivative, which derives its potent bactericidal activity by the specific inhibition of bacterial RNA polymerase. We evaluated the in vitro pharmacodynamics and bactericidal activity of ABI-0043 against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Methods Using time-kill studies at a wide range of concentrations of ABI-0043, we evaluated the killing activity against four clinical isolates of S. aureus over 24 h. An integrated pharmacokinetic/pharmacodynamic area measure was applied to all cfu data and was fitted to a Hill-type mathematical model to evaluate pharmacodynamics. Results Bacterial killing for ABI-0043 occurred rapidly and in a concentration-dependent manner. Bactericidal activity was achieved within 4 h at > or =16 x MIC against all isolates. Bacterial reductions were greatest at > or =64 x MIC against MRSA and MSSA isolates, as a >4 log(10) cfu/mL reduction was observed as early as 2 h, and sustained throughout 24 h. The pharmacodynamics of ABI-0043 was well described by a Hill-type model, with a steep sigmoidicity constant and a low EC(50) against all isolates. Conclusions ABI-0043 displayed rapid and sustained bactericidal activity against S. aureus clinical isolates. ABI-0043 represents a promising antistaphylococcal agent to combat serious S. aureus infections. Further, pharmacokinetic, pharmacodynamic and in vivo studies are warranted to determine its ultimate place in antibacterial therapy.
Correlation of visual acuity and ocular pigmentation with the 16-bp duplication in the HPS-1 gene of Hermansky-Pudlak syndrome, a form of albinism.

Abstract Objective Patients with the Hermansky-Pudlak syndrome (HPS), a form of albinism, were studied. The first purpose of this investigation was to determine if visual acuity was related to the presence or absence of the 16-bp duplication in the HPS-1 gene. The second was to study the correlation between the degree of ocular pigmentation and visual acuity within the two genetic groups described above. Design Cross-sectional study of a series of consecutive patients. Participants Forty-nine patients with HPS with or without the 16-bp duplication in HPS-1 . Methods Best corrected visual acuity (VA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, photographic gradings of iris transillumination and of visibility of choroidal vessels in the macula (macular transparency). Main outcome measures Association between VA and the presence or absence of the 16-bp duplication in HPS-1 and correlation between VA and the degree of iris transillumination (iris score) and macular transparency (fundus score), as determined by masked reading of photographs, with respect to the presence or absence of the 16-bp duplication in HPS-1 were the main outcome measures. Results The VA of the better eye did not differ between the two genetic groups ( P = 0.322, two-sided t test). Spearman's rank correlation between VA and iris scores in 39 eyes of 20 patients with the duplication was not statistically significant ( P = 0.698) but was statistically significant in 36 eyes of 19 patients without the duplication ( P r = −0.36 in RE and r = −0.51 in LE). Spearman's rank correlation between VA and fundus scores in 36 eyes of 19 patients with and 34 eyes in 18 patients with and without the duplication was statistically significant ( P = 0.035 and P = 0.008, respectively). Among all patients, it was also statistically significant ( r = −0.39 in RE and r = −0.45 in LE). Conclusions The mean VA of the better eye did not differ in patients with the 16-bp duplication compared with those without the duplication. There were statistically significant associations between VA and the iris score and the fundus score except for the VA and iris scores in patients with the 16-bp duplication. However, because of the variability of VA, these associations were not large enough for useful prediction of VA based on the degree of ocular pigmentation.
Pixelplexing: Gaining Display Resolution Through Time

Animation is frequently utilized to visually depict change in time- varying data sets. For this task, it is a natural fit. Yet explicit animation is rarely employed for static data. We discuss the use of animation to overcome three common limitations faced by information visualization applications in the context of small-display devices: constraints on the output display, limited interaction possibilities, and high data density. We provide concrete examples of applying animation to combat such limitations for four common visualization types: geospatial data, treemaps, parallel coordinate displays, and large graphs. Unlike previous work which examines animation for maintaining user orientation during view changes or for displaying data variables, we discuss animation's utility for multiplexing available screen space. In the context of constrained displays, we demonstrate its ability to effectively gain screen resolution, to quickly uncover trends, to help find unexpected data patterns, and to reduce visual clutter.
Arabic Language Teachers in the State of Michigan: Views of Their Professional Needs

A full-day summer conference directed by this investigator took place in Dearborn city under the umbrella of Western Michigan University for professional development of Arabic teachers serving public, private, and academic charter schools in Michigan. The theoretical framework for conducting the conference was focused on the issue of teaching strategies as well as the needs assessment of teachers for improving their professional development. A group of fifty teachers volunteered to participate in the conference and were asked to complete a twelve-item questionnaire designed to provide their professional profile and their preference in developing professional development. Their professional profile included years of Arabic teaching experience in the United States, teaching level (elementary school, middle school, or high school), teaching certificate, academic credentials, and type of school (public, private, or charter school). The findings indicated that among the ten sub-items related to the professional development skills of the teachers, “Implementing differentiated language instruction” was rated by the participating teachers as the most important components of their professional development skills; followed in order by “Integrating technology and Arabic instruction”; “Using effective learner-centered teaching strategies”; “Using and maintaining Arabic language”; “Implementing a standards-based curriculum”; “Developing curriculum and thematic units”; “Implementing performance assessment methods”; “Conducting constructive action research in Arabic instruction”; “Conducting the Oral Proficiency Interview”; and “Learning how to be a certified Arabic language teacher in Michigan”. In response to the questions regarding the role of Council in supporting Arabic teachers, the participating teachers made a number of constructive suggestions to help improve the quality of teaching Arabic with special focus on facilitating appropriate teaching materials and other instructional tools as a part of curriculum development.
A Unified Analytic Drain–Current Model for Multiple-Gate MOSFETs

In this paper, a unified analytic drain-current model is presented for various kinds of multiple-gate (MG) MOSFETs, including quadruple-gate (QG), triple-gate (TG), Pi-gate, and Omega-gate MOSFETs. The basis of the unified model lies in the analytic potential models previously developed for highly symmetric double-gate (DG) and surrounding-gate (SG) MOSFETs. A common characteristic for all MG MOSFETs is that the inversion charge in subthreshold is proportional to the silicon cross- sectional area (volume inversion), whereas the inversion charge above threshold is proportional to the gated perimeter of the silicon body. It is shown that the inversion charge in a QG MOSFET can be modeled by multiplying the inversion charge of SG MOSFET by a function that changes smoothly from unity in subthreshold to a factor larger than unity above threshold. Inasmuch as the inversion charge is expressed as a function of the gate voltage, the drain-current can be evaluated by using the Pao-Sah integral approach. Once the QG model is obtained, other TG, Pi-gate, and Omega-gate MOSFET models can be formulated as a linear combination of DG and QG MOSFETs. Numerical simulation results that validate the unified model are presented.