cssi/SciSciGPT-SciSciNet huggingface dataset:
Self-serving prototypes of social categories.

Why and when do people disagree on their conceptions or prototypes of social categories? In 6 studies, it was revealed that such differences tend to be self-serving. Ss tended to endorse self-descriptive attributes as central to their prototypes of desirable social concepts and emphasize features that were not self-descriptive in their conceptions of undesirable categories. Such disagreements were constrained to attributes potentially central to the domain in question and did not occur for clearly peripheral features. Self-serving differences in prototype structure were exhibited in social information processing tasks and led to disagreements in judgments of others. Potential mechanisms underlying the development of these egocentric cognitive structures and their implications for self-serving judgments of ability are discussed. The act of social judgment is often one of classification. People often find themselves asking such questions as these: Is this person intelligent? Is this politician a trustworthy individual? Would I make a good lawyer? Would that person be a good
The UPC2 promoter in Candida albicans contains two cis-acting elements that bind directly to Upc2p, resulting in transcriptional autoregulation.

In Candida albicans, ergosterol biosynthetic genes, including ERG11 , which encodes the target of azole antifungal drugs, are regulated by the transcriptional regulator Upc2p. To initially characterize the promoter of the UPC2 gene, 5′ rapid amplification of cDNA ends was used to identify two transcriptional initiation sites upstream of the ATG codon. The regions within the UPC2 promoter required for azole regulation of the UPC2 promoter were then identified using nested deletions fused to a luciferase reporter which were tested for azole inducibility in wild-type (WT) and upc2 Δ /upc2 Δ strains. Two distinct regions important for azole induction were identified: a Upc2p-dependent region (UDR) between bp −450 and −350 upstream of the ATG codon and a Upc2p-independent region (UIR) between bp −350 and −250 upstream of the ATG codon. Within the UDR, loss or mutation of the sterol response element (SRE), so named because of homology to the Saccharomyces cerevisiae Upc2p binding site, resulted in a decrease in both basal and induced expression in the WT strain but did not affect azole inducibility in the upc2 Δ/ upc2 Δ deletion strain. Gel shift analyses using the DNA binding domain of Upc2p confirmed binding of the protein to two SRE-related sequences within the UPC2 promoter, with strongest binding to the UDR SRE. Detailed gel shift analyses of the UDR SRE shows that Upc2p binds to a bipartite element within the UPC2 promoter, including the previously identified SRE and a new, adjacent element, the short direct repeat (SDR), with partial homology to the SRE.
Expression of a human coxsackie/adenovirus receptor transgene permits adenovirus infection of primary lymphocytes

Replication-defective adenoviruses are effective vehicles for gene transfer, both for the repair of defective genes and for studies of gene function in primary cells. Many cell types, including lymphocytes, are refractory to adenovirus infection because they lack the Coxsackie/adenovirus receptor (CAR) needed for virus attachment. To extend the advantages of adenovirus-mediated gene transfer to primary lymphoid populations and other cell types lacking endogenous CAR, we produced a mouse that expresses human (h) CAR as a transgene under control of a murine MHC class I promoter. hCAR protein is expressed on T and B lymphocytes from a variety of organs (spleen, lymph node, bone marrow, thymus, and peritoneum). These lymphocytes are susceptible to adenovirus infection, as demonstrated by reporter green fluorescent protein gene expression, with the fraction of expressing cells as high as 70%. Some lymphocyte subpopulations required stimulation subsequent to adenovirus infection for reporter expression. This activation requirement is a restriction imposed by the promoter used in the adenovirus construct. In subpopulations requiring activation, the elongation factor 1 promoter was far superior to a hCMV promoter for directing green fluorescent protein production. We also find that hCAR mRNA is produced in nonlymphoid tissues from all founder lines, including tissues that do not express endogenous murine CAR, suggesting the opportunity for effecting gene delivery to and testing gene function in a wide variety of primary cell types previously resistant to gene transfer.
The design of guided learner-adaptable scaffolding in interactive learning environments

In the field of Human-Computer Interaction, a new methodology has been proposed for learner-centered design (LCD) of software, to address the needs of a population of users who are also learners [Soloway et al. 1994]. An emphasis is the design of interactive learning environments as "cognitive tools"---tools that support constructive tasks, and foster learners' development of higher-order skills and strategies [Lajoie 1993, Jonassen 1995]. For example, computer-based dynamic modeling has been recognized as an educational activity that promotes such cognitive activities as system analysis, cause-and-effect relational reasoning, and generating and testing hypotheses about scientific phenomena [Hestenes 1992, Tinker 1990]. The problem for LCD is how to design tools that support these activities, and that also promote the mastery of the associated cognitive skills and strategies, so that the support will eventually be unnecessary.
Differential expression of platelet-activating factor acetylhydrolase in macrophages and monocyte-derived dendritic cells.

Although macrophages (Mφ) and monocyte-derived dendritic cells (MDDC) come from a common precursor, they are distinct cell types. This report compares the two cell types with respect to the metabolism of platelet-activating factor (PAF), a biologically active lipid mediator. These experiments were prompted by our studies of localized juvenile periodontitis, a disease associated with high IgG2 production and a propensity of monocytes to differentiate into MDDC. As the IgG2 Ab response is dependent on PAF, and MDDC selectively induce IgG2 production, we predicted that PAF levels would be higher in MDDC than in Mφ. To test this hypothesis, human MDDC were prepared by treating adherent monocytes with IL-4 and GM-CSF, and Mφ were produced by culture in M-CSF. Both Mφ and MDDC synthesized PAF; however, MDDC accumulated significantly more of this lipid. We considered the possibility that PAF accumulation in MDDC might result from reduced turnover due to lower levels of PAF acetylhydrolase (PAFAH), the enzyme that catabolizes PAF. Although PAFAH increased when monocytes differentiated into either cell type, MDDC contained significantly less PAFAH than did Mφ and secreted almost no PAFAH activity. The reduced levels of PAFAH in MDDC could be attributed to lower levels of expression of the enzyme in MDDC and allowed these cells to produce PGE2 in response to exogenous PAF. In contrast, Mφ did not respond in this manner. Together, these data indicate that PAF metabolism may impinge on regulation of the immune response by regulating the accessory activity of MDDC.
Secure chaotic transmission of electrocardiography signals with acousto-optic modulation under profiled beam propagation

Electrocardiography (ECG) signals are used for both medical purposes and identifying individuals. It is often necessary to encrypt this highly sensitive information before it is transmitted over any channel. A closed-loop acousto-optic hybrid device acting as a chaotic modulator is applied to ECG signals to achieve this encryption. Recently improved modeling of this approach using profiled optical beams has shown it to be very sensitive to key parameters that characterize the encryption and decryption process, exhibiting its potential for secure transmission of analog and digital signals. Here the encryption and decryption is demonstrated for ECG signals, both analog and digital versions, illustrating strong encryption without significant distortion. Performance analysis pertinent to both analog and digital transmission of the ECG waveform is also carried out using output signal-to-noise, signal-to-distortion, and bit-error-rate measures relative to the key parameters and presence of channel noise in the system.
Local Overexpression of Thrombomodulin for In Vivo Prevention of Arterial Thrombosis in a Rabbit Model

-Endothelial thrombomodulin plays a critical role in hemostasis by binding thrombin and subsequently converting protein C to its active form, a powerful anticoagulant. Thrombomodulin thus represents a central mechanism by which patency is maintained in normal vessels. However, thrombomodulin expression decreases in perturbed endothelial cells, predisposing to thrombotic occlusion. An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on in vivo thrombus formation was subsequently examined in a stasis/injury model of arterial thrombosis. The construct prevented arterial thrombosis formation in all animals, while viral and nonviral controls typically developed occluding thrombi. By histological analysis, nonviral controls exhibited intravascular thrombus occluding a mean of 70.52+/-3.72% of available lumen, while viral controls reached 86. 85+/-2.82% thrombotic occlusion; in contrast, Adv/RSV-THM reduced thrombosis to 28.61+/-3.31% of lumen in cross section. No significant intima-to-media ratio was observed in the thrombomodulin group relative to controls. Local infiltration of granulocytes and macrophages significantly decreased in the Adv/RSV-THM group relative to controls, while neutrophilic infiltration increased in viral controls relative to nonviral controls. This construct thus offers a viable technique for promoting a locally thromboresistant small-caliber artery, without the inflammatory damage that has limited many other adenoviral applications.
Design and Use of an Inducibly Activated Human Immunodeficiency Virus Type 1 Nef To Study Immune Modulation

The Nef protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to enhance the infectivity of virus particles, downmodulate cell surface proteins, and associate with many intracellular proteins that are thought to facilitate HIV infection. One of the challenges in defining the molecular events regulated by Nef has been obtaining good expression of Nef protein in T cells. This has been attributed to effects of Nef on cell proliferation and apoptosis. We have designed a Nef protein that is readily expressed in T-cell lines and whose function is inducibly activated. It is composed of a fusion between full-length Nef and the estrogen receptor hormone-binding domain (Nef-ER). The Nef-ER is kept in an inactive state due to steric hindrance, and addition of the membrane-permeable drug 4-hydroxytamoxifen (4-HT), which binds to the ER domain, leads to inducible activation of Nef-ER within cells. We demonstrate that Nef-ER inducibly associates with the 62-kDa Ser/Thr kinase and is localized to specific membrane microdomains (lipid rafts) only after activation. Using this inducible Nef, we also compared the specific requirements for CD4 and HLA-A2 downmodulation in a SupT1 T-cell line. Half-maximal downmodulation of cell surface CD4 required very little active Nef-ER and occurred as early as 4 h after addition of 4-HT. In contrast, 50% downmodulation of HLA-A2 by Nef required 16 to 24 h and about 50- to 100-fold-greater concentrations of 4-HT. These data suggest that HLA-A2 downmodulation may require certain threshold levels of active Nef. The differential timing of CD4 and HLA-A2 downmodulation may have implications for HIV pathogenesis and immune evasion.
Efficient fault tolerant broadcasting algorithm for the cube-connected cycles network

The cube-connected cycles network is discussed as a cube whose 2k vertices are cycles of k nodes each. It is suitable for realization for VLSI since it satisfies the properties of degree boundedness of nodes (=3). Broadcasting is a procedure by which a processor can pass a message to all other processors in the network nonredundantly. This is extremely important for diagnosis of the network, distribution agreement or clock synchronization. A simple yet efficient algorithm is developed for broadcasting in the cube-connected cycles network. Another broadcasting algorithm for the cube-connected cycles network in the presence of some faulty processors is also developed. >
DFT for Low Cost SOC Test

Growing test costs impact the design and implementation of large and complex IP (intellectual property) modules, (often reused as embedded cores), as well as the construction of SOCs (systems-on-chip) using them. The modules must be designed for re-use in different devices, and the SOCs using them too must be designed to support various end applications, with diverse requirements of performance, power, reliability and cost, within the constraints of the budgetted design and test costs and product development cycle times. These constraints often make the DFT (design for testability) process a very critical and differentiating component of the overall design cycle, as well as a key enabler for robust designs.
Chemo-mechanical Model for Actuation Based on Biological Membranes*

Plants have the ability to develop large mechanical force from chemical energy available with bio-fuels. The energy released by adenosine tri-phosphate (ATP) hydrolysis assists the transport of ions and fluids to achieve volumetric expansion and homeostasis. Materials that develop pressure and hence strain similar to bio-materials are classified as nastic materials. Recent calculations for controlled actuation of an active material inspired by biological transport mechanism demonstrated the feasibility of developing such a material with actuation energy densities on the order of 100 kJ/m 3 . The initial investigation was based on capsules that generate pressure, thus causing strain in the surrounding matrix material. This paper focuses on our efforts to fabricate a representative actuation structure and describes the chemo-mechanical constitutive equation for such a material. The actuator considered in this work is a laminated plate dispersed with biological transporters. The initial design and a mathematical model to predict the fluid flux and strain developed in such an actuator are presented here.
Clinical/Scientific Notes

Immunoglobulin G4-related disease (IgG4-RD) is a novel clinical entity characterized by elevated serum IgG4 levels and histopathologic features of storiform fibrosis, obliterative phlebitis, tissue eosinophilia, and infiltration of IgG4-positive plasma cells. Although it can involve almost any organ, IgG4-RD rarely involves the nervous system. The principal neurologic manifestations include hypophysitis and hypertrophic pachymeningitis (HP). In some patients, previously known idiopathic HP may in fact be IgG4-related. Acknowledgment: The authors thank Dr. Suzanne Z. Powell for her assistance in IgG4 antibody staining.
Decreased peritoneal macrophage NF-κB translocation to the nucleus in protein energy malnutrition—a role for the glucocorticoid response?

Abstract Background & aims: Protein energy malnutrition (PEM) induces immune suppression leading to increased morbidity and mortality. The mechanism(s) underlying PEM-mediated immune suppression remain unclear. Plasma glucocorticoid levels are elevated in PEM and it has been postulated that these increased levels may mediate macrophage (MO) dysfunction in PEM. We have previously shown that nuclear factor kappa B (NF-κB) activation in response to LPS stimulation is diminished in peritoneal macrophages (PMOs) from PEM mice. We hypothesized that decreased NF-κB activation in lipopolysaccharide (LPS)-stimulated PMOs in PEM is mediated through increased circulating glucocorticoid levels. Methods: Mice were randomized to six groups of n=15 each as follows: (1) control diet (24% casein) (C); (2) protein-free diet (PF); (3) mice with subcutaneously implanted corticosterone pellet on the control diet; (4) mice with subcutaneously implanted placebo pellet on the control diet; (5) adrenalectomized mice on the control diet; (6) adrenalectomized mice on the PF diet. Within each group, the mice were pair-fed for 7 days. At the end of the experimental time period, PMOs were harvested and NF-κB activation determined by electrophoretic mobility shift assay (EMSA). Results: Elevated circulating glucocorticoids diminished NF-κB activation but adrenalectomy failed to restore this diminution in a murine model of PEM. Conclusion: NF-κB translocation to the nucleus in PEM is independent of elevated circulating glucocorticoid levels.
A Perfect Marriage: Molecular Genetics Ties the Knot with Electrophysiology in Studies of Visual Transduction

In recent years, the combination of classical electrophysiological techniques and targeted gene manipulations have provided for novel, powerful ways to address key questions in visual transduction. Electrophysiological techniques allow precise characterization of the electrical and chemical events
In vivo recovery and survival of red cells after photodynamic treatment with thiopyrylium and red light using a canine model.

Recently, we have shown that thiopyrylium has robust inactivation capabilities against a broad spectrum of pathogens in the human red blood cell (RBC) suspensions while retaining key RBC in vitro properties. The 24-h recovery and survival of canine red cells were measured upon autologus reinfusion of control and phototreated units. The 24-h recovery of control and phototreated RBCs was 75.7 ± 6.4% and 87.5 ± 8.5%, respectively. The time for 50% survival of labelled control RBCs was similar to that of phototreated group (206 ± 58 h vs. 255 ± 63 h, respectively). Results suggest that thiopyrylium phototreatment does not negatively affect canine RBC in vivo recovery.
Gatt Non-Violation Issues in the WTO Dispute Settlement Framework: Are They the Achilles’ Heel of the WTO Dispute Settlement Process?

This article argues that the WTO’s ambiguous non-violation provisions, which allow a Member to bring a nullification or impairment proceeding against another Member despite the lack of any explicit breach, are a relic of the formation of the GATT, and that their incorporation into the WTO’s dispute settlement mechanism represents an anachronistic and potentially problematic over-expansion of the WTO’s jurisdiction. The inherent ambiguity and resultant over-expansion of jurisdiction stemming directly from the non-violation provisions may very well result in an over-burdening of the dispute settlement mechanism’s panels or Appellate Bodies, as well as the proliferation of harmful cases where Members have yet to establish substantive norms upon which panels can decide cases. To remedy the situation, the WTO should focus on 'violationizing' issues that could be adjudicated under the non-violation provisions. That is, a panel should transform non-violation issues into violation cases.
COX-2 gene promoter haplotypes and prostate cancer risk

Cyclooxygenase-2 (COX-2) is a key rate-limiting enzyme that converts arachidonic acid into pro-inflammatory prostaglandins. COX-2 expression is strongly correlated with increased tumor microvasculature density and plays an important role in inhibiting apoptosis, stimulating angiogenesis and promoting tumor cell metastasis and invasion. However, little is known about the role that sequence variation of the COX-2 gene contributes to prostate cancer. Thus, we searched for polymorphisms in the promoter region of the COX-2 gene using denaturing high-performance liquid chromatography. Four single nucleotide polymorphisms (SNPs), -1285A/G, -1265G/A, -899G/C and -297C/G, were detected and confirmed by direct sequencing. Three of the SNPs in the promoter region of COX-2 gene create at least three putative transcription factor binding sites and eliminate CCAAT/enhancer binding protein alpha (C/EBP alpha) and NF-kappa B binding sites. A case-control study of the four SNPs in African American (n = 288), Bini Nigerian (n = 264) and European American (n = 184) prostate cancer cases and age-matched controls revealed that SNP -297G was associated with a decreased risk for prostate cancer [odds ratio (OR) = 0.49; CI = 0.2-0.9; P = 0.01]. The effect on risk was observed in both African Americans (OR = 0.51; CI = 0.2-0.9; P = 0.01) and European Americans (OR = 0.33; CI = 0.1-0.9; P = 0.02). In addition, SNPs -1265A and -899C were associated with increased prostate cancer risk in African Americans (OR = 2.72; CI = 1.3-5.8; P = 0.007 and OR = 3.67; CI = 1.4-9.9; P = 0.007, respectively). Haplotype analyses revealed modest effects on susceptibility to prostate cancer across populations. Haplotype GGCC conferred increased risk in the African American and Nigerian populations. Conversely, haplotype AGGG exhibited a negative association with prostate cancer risk in African Americans (OR = 0.4; CI = 0.1-0.9; P = 0.02) and European Americans (OR = 0.2; CI = 0.1-0.9; P = 0.03). These data suggest that variation of the COX-2 promoter may influence the risk and development of prostate cancer.
The Analytics of Export Promotion Policies Designed to Reduce Search Costs

This study examines the economic effects of export subsidy policy in an environment where exporters must expend resources to find foreign consumers. Within a sequential search model we find that export promotion policies specifically designed to lower an exporter’s search costs (e.g., government-sponsored trade missions) have very different effects than non-targeted subsidies. For example, subsidies that lower search costs induce exporters to increase their price. However, this result is sensitive to model specification and may even be reversed when the analysis allows for foreign competition.
The United States-Peru Trade Promotion Agreement: What Did You Expect?

Bilateral free trade agreements have generally been analyzed as instances of preferential reciprocal tariff liberalization. Viewed through this lens, such agreements raise concerns both about new competition and about trade diversion. The United States-Peru Trade Promotion Agreement, an example of a serious North-South accord, demonstrates that new market access was not a principal Peruvian goal in the trade negotiations. Instead, the agreement was intended to encourage investment by locking in Peru’s economic reforms. This motivation has very different implications for the global trading system than a quest for preferential access.
The Perils of Wishful Thinking about Abortion

This essay reviews The Politics of Abortion, a recent book by a sociologist. Although we could use a careful assessment of the current status of that divisive issue, this book does not fill the void. The author argues that most Americans are pro-life on the basis of fragmentary and anecdotal evidence, but a careful analysis of trends in public opinion over the past two decades suggests that attitudes have not changed dramatically despite a slight recent decline in approval of abortion. Moreover, gaps and omissions in the discussion of political trends and legal developments make the book an unreliable guide even for those who share the author's pro-life views.
Intensive Auditory Cognitive Training Improves Verbal Memory in Adolescents and Young Adults at Clinical High Risk for Psychosis

Objective Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population. Methods In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood estimation, given the high study attrition rate (42%). Results Participants in the targeted cognitive training group showed a significant improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time. Conclusions CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on symptoms and functioning over time. Clinical Trials Number: NCT00655239. URL: https://clinicaltrials.gov/ct2/show/NCT00655239?term=vinogradov&rank=5.
Evidence for uptake of nonceruloplasminic copper in the brain: effect of ionic copper and amino acids.

SummaryThe initial net uptake of Cu(II) into the brain was studied in rats using the single microcirculatory pass technique of Oldendorf. The results indicate that the net influx of Cu(II) is facilitated by a nonsaturable process over a wide range of concentrations. Several amino acids enhance the uptake or early retention of Cu(II). However, the amino acids which promote Cu uptake in brain appear to be different from those previously shown to be effective in other cell systems in vitro.
Intrarenal blood flow distribution: effect of carotid occlusion.

SummaryIn this study we have examined the influence of bilateral carotid occlusion on intrarenal blood flow distribution. Using labeled microspheres to determine intrarenal hemodynamics, bilateral carotid ligation in mannitol or saline expanded dogs resulted in an increase in outer cortical blood flow and a decrease in inner cortical flow. Total renal blood flow and glomerular filtration rate did not change significantly during carotid occlusion whereas the average mean arterial blood pressure rose from 130 to 166 mmHg. Inner cortical flow resistance increased substantially after carotid occlusion; outer cortical resistance was unchanged. These results suggest that bilateral carotid occlusion selectively activates inner cortical renal sympathetic fibers.
The role of ovarian conservation in the treatment of carcinoma of the cervix with radical surgery

This paper is an analysis of 95 cases treated surgically at the University of California Hospitals and at Children's Hospital between 1949 and 1971; 92 had abdominal radical surgery and three were done vaginally. Figures are analyzed by age, cell type, pregnancy status, and survival data. The numbers surviving for 5 years were 27 in the control group (26 living five years and over) and 50 in the study group.
Operational Performance Measurement in Supply Chain Distribution

The effect of internal sub-processes on efficiency of enterprises(Decision Making Units, DMUs) in supply chain distribution was studied with network data envelopment analysis(Network DEA), and the optimal configuration approaches of allocable input resource among internal sub-processes were presented.
Study on epidemic isolates and antibiotic resistance of Vibrio cholerae from 2007 to 2008 in Maoming City of Guangdong Province

Objective:To understand the epidemic isolates and antibiotic resistance of Vibrio cholerae from 2007 to 2008 in Maoming City of Guangdong Province,and provide the references for prevention and control of cholerae.Methods:Samples were collected and tested from the general surveillance and epidemic situation of cholerae.Bacterial strains were isolated according to the "Manual for the Prevention and Control of Cholera"(version 5).The vibrio cholerae isolates were tested for their resistance to 20 different common antibiotics using the automatic microorganism identification machine.Results:3924 samples were collected.Among those samples,12 isolates of 01 group of El Tor vibrio sero type Inaba 1d were detected in 2007 and nothing was detected in 2008.The antibiotic resistance of cholerae 12 isolates to the 20 kinds antibiotic was completely consistent.Among the antibiotics,the isolates showed the highest susceptibility to 11 kinds such as Ceftriaxone,and Gentamicin,with proportion of 55percent(11/20),and moderate susceptibility to 8 kinds such as Ampicillin,with proportion is 40 percent(8/20).The isolates only showed 100% resistance antibiotics to sulfamethoxazole,with a proportion is 5 percent(1/20).Conclusion:The disease is mainly transmitted by contaminated food and the epidemic isolates of Vibrio cholerae is identified as 01 group of El Tor vibrio cholerae sero type Inaba 1d from 2007 to 2008 in Maoming City.Those epidemic isolates are susceptibile(or moderate susceptibility)to most of the 20 commonly used antibiotics,except sulfamethoxazole.No epidemic isolates show multiple resistance to antibiotics.
Reappraisal of effective refractory period testing.

To test the hypothesis that effective refractory period (ERP) testing is an accurate and reproducible measure of the cardiac refractory period, 4 pigs and 12 dogs were studied. We define the conven...
Vertical Pathway Targeting in Cancer Therapy

Abstract Malignant cells arise from particular mutations in genes controlling cell proliferation, invasion, and survival. Older antineoplastic drugs were designed to target vital cellular processes, such as DNA maintenance and repair and cell division. As a result, these drugs can affect all proliferating cells and are associated with unavoidable toxicities. Recent discoveries in cancer research have identified “driver” mutations in some types of cancer, and efforts have been undertaken to develop drugs targeting these oncogenes. In most cases, due to escape mechanisms and adaptive responses, single oncogene targeting is insufficient to induce prolonged responses in solid tumors. Drug combinations are therefore used to enhance the growth inhibitory and cytotoxic effects of the targeted therapies. Depending on the position of additional targets within the signaling network, drug combinations may target either different signaling pathways (parallel targeting) or the same pathway at several fragile nodes (vertical targeting). In this review, we discuss strategies of multitarget inhibition with a focus on vertical signaling pathway targeting.
Analysis of a Thin Optical Lens Model

In this article a thin optical lens model is considered. It is shown that the limits of its applicability are determined not only by the ratio between the thickness of the lens and the modules of the radii of curvature, but above all its geometric type. We have derived the analytical criteria for the applicability of the model for different types of lenses. Quantitative estimations were made for practically important cases оf a glass lens in air and air lens in water.
Screening for medication errors using an outlier detection system.

Objective: The study objective was to evaluate the accuracy, validity, and clinical usefulness of medication error alerts generated by an alerting system using outlier detection screening. Materials and Methods : Five years of clinical data were extracted from an electronic health record system for 747 985 patients who had at least one visit during 2012–2013 at practices affiliated with 2 academic medical centers. Data were screened using the system to detect outliers suggestive of potential medication errors. A sample of 300 charts was selected for review from the 15 693 alerts generated. A coding system was developed and codes assigned based on chart review to reflect the accuracy, validity, and clinical value of the alerts. Results : Three-quarters of the chart-reviewed alerts generated by the screening system were found to be valid in which potential medication errors were identified. Of these valid alerts, the majority (75.0%) were found to be clinically useful in flagging potential medication errors or issues. Discussion : A clinical decision support (CDS) system that used a probabilistic, machine-learning approach based on statistically derived outliers to detect medication errors generated potentially useful alerts with a modest rate of false positives. The performance of such a surveillance and alerting system is critically dependent on the quality and completeness of the underlying data. Conclusion : The screening system was able to generate alerts that might otherwise be missed with existing CDS systems and did so with a reasonably high degree of alert usefulness when subjected to review of patients’ clinical contexts and details.
Further Evidence for Tuning Mechanisms of High Dynamic Order in Lower Vertebrates

In recent years, data from individual hair cells have suggested that frequency selectivity in lower vertebrates is accomplished by the amplitude tuning peaks of underdamped electrical resonances (Crawford and Fettiplace, 1981; Lewis and Hudspeth, 1983; Pitchford and Ashmore, 1987). In the present study we have used the reverse-correlation (REVCOR) method (Evans, 1989; Eggermont et al, 1983; de Boer and Kuyper, 1968; de Boer and de Jongh, 1977) to study linear tuning responses from primary afferent axons of the three inner-ear organs in which these resonances were first reported -- the turtle basilar papilla and the frog sacculus and amphibian papilla. The characteristic signature of a single (undcrdamped) resonance comprises the following features: (I) impulse response in the fonn of a sinusoid with exponentially declining amplitude, (2) sinusoidal steady-state phase shift limited to one-half cycle, (3) convexity of the gain (amplitude) tuning curve limited to the highest three decibels (where the tuning curve is plotted on the conventional log-log coordinates), and (4) absolute values of the limiting slopes of the gain tuning curve which sum to two (decades per decade). If the outputs of resonances were added (not subtracted) in parallel, producing a tuning structure of high dynamic order, the characteristic signature of that structure would comprise features (2) and (4) from the previous list, plus (5) global concavity of the gain tuning curve (convexity only within approximately 3 dB of the tuning peaks). Among 155 axons included in this study, all displayed the following properties: (I) impulse responses that are more complex than exponentially decaying sinusoids, (2) sinusoidal steady-state phase shifts ranging over one or more cycles, (3) gain tuning curves exhibiting global convexity (with occasional, local concavity) and, (4) limiting gain-tuning-curve slopes whose absolute values sum to numbers considerably greater than two. We conclude that frequency selectivity in these axons is not accomplished by underdamped resonance peaks acting alone or in parallel combination (through positive addition), but rather by the asymptotic slopes of amplitude tuning curves, made steep by high dynamic order.
Confocal reflectance quantitative phase microscope system for cellular membranes dynamics study (Conference Presentation)

Quantitative phase microscopy (QPM) techniques developed so far primarily belongs to high speed transmitted light based systems that has enough sensitivity to resolve membrane fluctuations and dynamics, but has no depth resolution. Therefore, most biomechanics studies using QPM today is confined to simple cells, such as RBCs, without internal organelles. An important instrument that will greatly extend the biomedical applications of QPM is to develop next generation microscope with 3D capability and sufficient temporal resolution to study biomechanics of complex eukaryotic cells including the mechanics of their internal compartments. For eukaryotic cells, the depth sectioning capability is critical and should be sufficient to distinguish nucleic membrane fluctuations from plasma membrane fluctuations. Further, this microscope must provide high temporal resolution since typical eukaryotes membranes are substantially stiffer than RBCs. A confocal reflectance quantitative phase microscope is presented based on multi-pinhole scanning, with the capabilities of higher temporal resolution and sensitivity for nucleic and plasma membranes of eukaryotic cells. System hardware is developed based on an array of confocal pinhole generated by using the ‘ON’ state of subset of micro-mirrors of digital micro-mirror device (DMD, from Texas Instruments) and high-speed raster scanning provides 14ms imaging speed in wide-field mode. A common path interferometer is integrated at the imaging arm for detection of specimens’ quantitative phase information. Theoretical investigation of quantitative phase reconstructed from system is investigated and application of system is presented for dimensional fluctuations measurements of both cellular plasma and nucleic membranes of embryonic stem cells.
Exploring procedural justice as a predictor of satisfaction and performance in supply chain relationships

In challenging times, firms are drawn to partners to help determine the best procedures and practices that can enhance the resiliency and competitiveness of the supply chain. The present study adds to literature by addressing calls to examine procedural justice and cohesion at the supply chain level. Partial least squares modelling was used to test a model in which cohesion was hypothesised to mediate the relationship between procedural justice and performance outcomes. Data from 235 firms was analysed. Results showed supply chain procedural justice is a predictor of relationship satisfaction and performance and supply chain cohesion mediates the relationships between the independent variable and the dependent variables. When supply chain members are fair in their dealings the supply chain becomes a more cohesive unit that can improve reliability, relationship satisfaction, and overall performance effectiveness. Firms should leverage resources and develop capabilities that generate reliable and satisfying relationships that lead the supply chain toward resilient growth and sustained competitive advantage.
Completions of l-Groups

Lattice-ordered groups admit a rich variety of completeness notions; some examples are conditional completeness (every bounded subset has a supremum), lateral completeness (every pairwise disjoint subset has a supremum), and projectability (each polar is a cardinal summand). For a completeness property C one then hopes for a completion result of the following form.
Tissue-engineered vascular grafts for congenital cardiac disease: Clinical experience and current status

Congenital heart disease is a leading cause of death in the newborn period, and man-made grafts currently used for reconstruction are associated with multiple complications. Tissue engineering can provide an alternative source of vascular tissue in congenital cardiac surgery. Clinical trials have been successful overall, but the most frequent complication is graft stenosis. Recent studies in animal models have indicated the important role of the recipient׳s immune response in neotissue formation, and that modulating the immune response can reduce the incidence of stenosis.
Octenylsuccinate hydroxypropyl phytoglycogen enhances the solubility and in-vitro antitumor efficacy of niclosamide

Niclosamide is a promising antitumor agent, but its low aqueous solubility places limit on its antitumor efficacy. The aim of this study was to improve the solubility and dissolution of niclosamide through using octenylsuccinate hydroxypropyl phytoglycogen (OHPP), an amphiphilic dendrimer-like biopolymer. The niclosamide-OHPP solid dispersion (niclo-OHPP SD) was prepared and characterized in terms of crystallinity, molecular interactions, solubility and dissolution profile, in-vitro antitumor efficacy, and in-vitro transdermal amount. X-ray powder diffraction analysis showed the amorphous state of niclosamide in niclo-OHPP SD. FTIR showed the formation of hydrogen bonding between niclosamide and OHPP. Solubility of niclosamide with niclo-OHPP SD was about 11,914 times that of niclosamide alone, and 61% of niclosamide with niclo-OHPP SD dissolved in 3 h upon dissolution. Against three cancer cell lines, cytotoxicity assays indicated greater inhibition by using niclo-OHPP SD than by using DMSO-assisted niclosamide solution. The cumulative transdermal amount of niclosamide with niclo-OHPP SD was 5.3 times that with niclosamide alone. This study showed that the use of OHPP could provide strong support for the development of niclosamide-based drug formulations.
Hepatitis C virus knowledge improves hepatitis C virus screening practices among primary care physicians

Hepatitis C virus knowledge improves hepatitis C virus screening practices among primary care physicians
Scaling Kinetic Inductance Detectors (KIDs)

For the last few decades, micro-channel plates (MCPs), charged coupled devices (CCDs), and hybrid complementary metal-oxide-semiconductor (CMOS) detectors have been the workhorses for collecting photons. More recently, the development of superconducting detectors such as the superconducting tunnel junctions (STJs) and transition edge sensors (TESs) has generated excitement in the imaging community. These detectors provide for simultaneous timing and spectral information as well as relatively good spectral energy resolution. However, STJs and TESs suffer from the major challenge of constructing large format arrays which are required for most imaging applications. Kinetic Inductance Detectors (KIDs) are a relatively new alternative superconducting technology that has many of the same desirable characteristics of STJs and TESs, and offer great promise for creating large-scale formats like current CCDs and CMOS detectors. The current approach for photon detection with KIDs uses a multiple frequency component activation signal. While this method has been proven to enable detection of photons, it has three key drawbacks that limit its utility in remote, size and power constrained applications. The first drawback is that each element of a KID array must be individually characterized under precisely controlled conditions. A second, even greater challenge is that the response of each KID element changes with temperature, necessitating in-system recalibration. Finally, current KIDs require 4-stage cryo-coolers in order to operate at mK temperatures, which are more challenging for space applications. New stimulation and detection approaches for arrays of high-temperature (∼4K) KID sensors are being investigated to simplify the electronics required for the source signal and reduce the impact of even small changes in temperature. Simplification of sensor electronics will enable large and robust arrays of high-temperature KID sensors, opening new photon sensing opportunities in size, mass, and power-constrained applications. This paper describes the current state of SwRI's Internal Research and Development effort to develop a KID detector and associated support hardware.
Neurogenetic Studies of Ion Channels in Drosophila

The enormous information handling capacity of nervous systems depends on the proper function of a rich variety of neurons and other excitable cells that display distinctive signal processing characteristics. This physiological complexity reflects cellular differences in the expression and regulation of ion channels. Genetic dissection has been successfully applied in elucidation of mechanisms underlying many biological processes in model systems. Drosophila has been a favored organism for such an approach to complex problems in higher organisms, such as function and development of the nervous system (Benzer, 1973; Pak and Pinto, 1976).
STAT5b Controls IgE-mediated Mast Cell Functions In Vitro and In Vivo

Signal Transducers and Activators of Transcription (STATs) are latent transcription factors that mediate a number of cellular responses including but not limited to cell survival, proliferation and differentiation. This protein family consists of seven members, STATs 1 – 6 including two closely related molecules, STAT5a and STAT5b, that show 96% amino acid sequence homology and are critical for lymphoid, myeloid, and erythroid cell development and function. We recently identified Stat5b as the critical regulator of IgE-mediated cytokine production in mast cells. STAT5b knockout (KO) cells show decreased cytokine production in vitro. In vivo STAT5b KO mice demonstrate decreased sensitivity to IgE-mediated passive systemic anaphylaxis accompanied with decreased production of IL-6 and IL-13 compared to wildtype counterparts. There was no difference in MAR-1-mediated passive systemic anaphylaxis or mast cell number and distribution. Interestingly STAT5b KO mice demonstrate elevated levels of serum IgE and an exacerbated response to histamine-mediated passive systemic anaphylaxis. We previously found that Fyn-mediated Stat5 tyrosine phosphorylation is critical for Stat5-dependent effects. The current work demonstrates that Stat5b is also phosphorylated on serine residues during IgE signaling in mast cells, via a Src-independent pathway requiring PI3-kinase function. Preliminary data show that STAT5b tyrosine and serine phosphorylation either independently or in tandem regulate IgE-induced cytokine production. Elucidating the role of STAT5b in the inflammatory response as well as the key players in STAT5b serine phosphorylation will yield new targets for mast cell-associated diseases.
Using interactive activities to foster deep learning in computer networking

In "What the Best College Teachers Do", author Ken Bains notes that the best teachers use techniques in the classroom that encourage students to "compare, apply, evaluate, analyze, and synthesize, but never only to listen and remember." (Bains, 102) Additionally, students learn deeper when they are given real problems to solve rather than just being told how others solved them in the past. (Bains, 128) In my computer networking course, before assigning the next section of the text for the students to read, I first engage the students with a set of questions to answer or a problem to solve. These problems are similar to the problems the original TCP/IP designers had to solve when they were inventing the TCP/IP protocols initially.
Metabolism and DNA adduct formation of carcinogenic tobacco-specific nitrosamines found in smokeless tobacco products

Abstract Tobacco-specific nitrosamines are the most abundant strong carcinogens in smokeless tobacco products. This chapter focuses on three of the most important of these compounds: N′-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The carcinogenic activities of NNN, NNK, and NNAL are discussed, and the metabolic pathways of these carcinogens are presented. Specific metabolite biomarkers have been developed to assess exposure to tobacco-specific nitrosamines in smokeless tobacco users; these are presented and discussed. DNA and protein adduct formation by tobacco-specific nitrosamines are also summarized, based mainly on studies in laboratory animals.