cssi/SciSciGPT-SciSciNet huggingface dataset:
Astatine-211 labeled anti-HER2 5F7 single domain antibody fragment conjugates: radiolabeling and preliminary evaluation.

Abstract Introduction Derived from heavy chain only camelid antibodies, ~15-kDa single-domain antibody fragments (sdAbs) are an attractive platform for developing molecularly specific imaging probes and targeted radiotherapeutics. The rapid tumor accumulation and normal tissue clearance of sdAbs might be ideal for use with 211 At, a 7.2-h half-life α-emitter, if appropriate labeling chemistry can be devised to trap 211 At in cancer cells after sdAb binding. This study evaluated two reagents, [ 211 At]SAGMB and iso -[ 211 At]SAGMB, for this purpose. Methods [ 211 At]SAGMB and iso -[ 211 At]SAGMB, and their radioiodinated analogues [ 131 I]SGMIB and iso -[ 131 I]SGMIB, were synthesized by halodestannylation and reacted with the anti-HER2 sdAb 5F7. Radiochemical purity, immunoreactivity and binding affinity were determined. Paired-label internalization assays on HER2-expressing BT474M1 breast carcinoma cells directly compared [ 131 I]SGMIB-5F7/[ 211 At]SAGMB-5F7 and iso -[ 131 I]SGMIB-5F7/ iso -[ 211 At]SAGMB-5F7 tandems. The biodistribution of the two tandems was evaluated in SCID mice with subcutaneous BT474M1 xenografts. Results Radiochemical yields for Boc 2 - iso -[ 211 At]SAGMB and Boc 2 -[ 211 At]SAGMB synthesis, and efficiencies for coupling of iso -[ 211 At]SAGMB and [ 211 At]SAGMB to 5F7 were similar, with radiochemical purities of [ 211 At]SAGMB-5F7 and iso -[ 211 At]SAGMB-5F7 >98%. iso -[ 211 At]SAGMB-5F7 and [ 211 At]SAGMB-5F7 had immunoreactive fractions >80% and HER2 binding affinities of less than 5 nM. Internalization assays demonstrated high intracellular trapping of radioactivity, with little difference observed between corresponding 211 At- and 131 I-labeled 5F7 conjugates. Higher BT474M1 intracellular retention was observed from 1-6 h for the iso -conjugates ( iso -[ 211 At]SAGMB-5F7, 74.3 ± 2.8%, vs. [ 211 At]SAGMB-5F7, 63.7 ± 0.4% at 2 h) with the opposite behavior observed at 24 h. Peak tumor uptake for iso -[ 211 At]SAGMB-5F7 was 23.4 ± 2.2% ID/g at 4 h, slightly lower than its radioiodinated counterpart, but significantly higher than observed with [ 211 At]SAGMB-5F7. Except in kidneys and lungs, tumor-to-normal organ ratios for iso -[ 211 At]SAGMB-5F7 were greater than 10:1 by 2 h, and significantly higher than those for [ 211 At]SAGMB-5F7. Conclusion These 211 At-labeled sdAb conjugates, particularly iso -[ 211 At]SAGMB-5F7, warrant further evaluation for targeted α-particle radiotherapy of HER2-expressing cancers.
Health, Health Care and Health Disparities

Understand medicine as a social institution. Understand the causes and consequences of health disparities by race, class, and gender. Understand the causes and consequences of health care disparities by race, class and gender.
Abstract 14889: Ckit Expression in Vascular Smooth Muscle Cells Protects Mice Against Excessive Atherosclerosis

Introduction: We have previously demonstrated that global deficiency of cKit, an important receptor tyrosine kinase, exacerbates atherosclerosis in hyperlipidemic mice. This study aims at demonstrating the protective role of c-Kit in smooth muscle cells (SMCs) against atherogenesis, and the mechanism underlying. Methods and Results: Atherosclerosis was assessed in triple transgenic mice with cKit targeted deletion in SMCs. In this model, atherosclerotic burden was significantly increased in c-Kit deficient mice versus control littermates. The loss of cKit was associated with medial SMCs hypertrophy, hypercellularity, and reduced expression of “contractile” proteins in aortas. In vitro, cKit-deficient aortic SMCs proliferated faster and migrated more than those from wild type controls. The absence of cKit made SMCs prone to acquire a foam-like phenotype secondary to increased activity of the Kruppel like factor 4 (KLF4), a transcriptional factor that favors SMC pathological synthetic phenotype. Rescue of cKit in deficient SMCs led to decreased level of KLF4, restored contractile markers, and prevented foam cell formation. Conclusion: This study provides mechanistic evidence that vascular cKit is involved in controlling SMCs phenotype and is atheroprotective in hyperlipidemic mice.
From me to we: embracing coperformative witnessing and critical love in the classroom

Swartz and Ware McGuffey's essay in this issue offer an overview of the current landscape in higher education and, in particular, the challenges immigrant students face, historically and in the pre...
Contralateral Delay Activity Tracks Fluctuations in Working Memory Performance

Neural measures of working memory storage, such as the contralateral delay activity (CDA), are powerful tools in working memory research. CDA amplitude is sensitive to working memory load, reaches an asymptote at known behavioral limits, and predicts individual differences in capacity. An open question, however, is whether neural measures of load also track trial-by-trial fluctuations in performance. Here, we used a whole-report working memory task to test the relationship between CDA amplitude and working memory performance. If working memory failures are due to decision-based errors and retrieval failures, CDA amplitude would not differentiate good and poor performance trials when load is held constant. If failures arise during storage, then CDA amplitude should track both working memory load and trial-by-trial performance. As expected, CDA amplitude tracked load (Experiment 1), reaching an asymptote at three items. In Experiment 2, we tracked fluctuations in trial-by-trial performance. CDA amplitude was larger (more negative) for high-performance trials compared with low-performance trials, suggesting that fluctuations in performance were related to the successful storage of items. During working memory failures, participants oriented their attention to the correct side of the screen (lateralized P1) and maintained covert attention to the correct side during the delay period (lateralized alpha power suppression). Despite the preservation of attentional orienting, we found impairments consistent with an executive attention theory of individual differences in working memory capacity; fluctuations in executive control (indexed by pretrial frontal theta power) may be to blame for storage failures.
Introduction to Linear Regression Analysis

(1994). Introduction to Linear Regression Analysis. Journal of Quality Technology: Vol. 26, No. 1, pp. 71-72.
Implementing Connectivist Teaching Strategies in Traditional K-12 Classrooms

Connectivism is a learning theory that is designed for the digital age. Students in today’s classrooms are digital natives who have unique learning styles. Connectivism has been studied primarily in online college classes and has been shown to increase motivation and student achievement. However, connectivism has not been widely explored in traditional K-12 classroom settings. Implementing connectivist learning strategies in traditional K-12 classrooms can bridge the gap between the needs of digital natives and K-12 education. The purpose of this paper is to present practical strategies for implementing connectivist learning strategies in the traditional K-12 classroom. Five strategies for implementing connectivism in the traditional K-12 classrooms are (1) shifting from teacher-centered to student-centered pedagogy, (2) incorporating technology with readily-available devices, (3) never providing information that students can access themselves, (4) incorporate and practice utilizing technology networks, and (5) incorporate and practice utilizing social networks.
The Transcription Factor Zfx Regulates Peripheral T Cell Self-Renewal and Proliferation

Peripheral T lymphocytes share many functional properties with hematopoietic stem cells (HSCs), including long-term maintenance, quiescence, and latent proliferative potential. In addition, peripheral T cells retain the capacity for further differentiation into a variety of subsets, much like HSCs. While the similarities between T cells and HSC have long been hypothesized, the potential common genetic regulation of HSCs and T cells has not been widely explored. We have studied the T cell-intrinsic role of Zfx, a transcription factor specifically required for HSC maintenance. We report that T cell-specific deletion of Zfx caused age-dependent depletion of naive peripheral T cells. Zfx-deficient T cells also failed to undergo homeostatic proliferation in a lymphopenic environment, and showed impaired antigen-specific expansion and memory response. In addition, the invariant natural killer T cell compartment was severely reduced. RNA-Seq analysis revealed that the most dysregulated genes in Zfx-deficient T cells were similar to those observed in Zfx-deficient HSC and B cells. These studies identify Zfx as an important regulator of peripheral T cell maintenance and expansion and highlight the common molecular basis of HSC and lymphocyte homeostasis.
Preliminary evaluation of antimicrobial agents for treatment of Leptospira interrogans serovar pomona infection in hamsters and swine.

Objective To evaluate antimicrobial agents for treatment of models of acute and persistent leptospirosis caused by Leptospira interrogans serovar pomona. Design Randomized trials comparing dosages and regimens of various antimicrobial agents for treatment of acute and persistent leptospirosis. Animals 245 Golden hamsters to model acute leptospirosis and 121 mixed-breed swine to model persistent leptospirosis. Procedure Hamsters and swine were inoculated with L interrogans serovar pomona. Antimicrobial agents were given to hamsters for 3 or 5 days after inoculation, with necropsy at 14 days after inoculation. Swine were treated for 1, 3, or 5 days beginning at 3 weeks after inoculation, and were necropsied 7 to 10 days after completion of antimicrobial agent treatment. Hamster tissue and swine tissue and urine specimens were examined by culture, fluorescent antibody testing, and histologic examination for presence of leptospires. Results All untreated control hamsters became infected and manifested clinical signs and lesions of acute leptospirosis. Leptospires were not detected in hamsters treated with dihydrostreptomycin/penicillin G (25 mg/kg of body weight). Administration of ampicillin at all dosages reduced the number of hamsters infected, as confirmed at necropsy; the other agents tested required dosages greater than label recommendations to reduce the number infected. All untreated control swine became infected and shed leptospires in urine through the time of necropsy. Leptospires were not detected in kidneys or urine of swine treated with dihydrostreptomycin/penicillin G (25 mg/kg) for 1, 3, or 5 days, or in swine treated with oxytetracycline (40 mg/kg for 3 or 5 days), tylosin (44 mg/kg for 5 days), or erythromycin (25 mg/kg for 5 days). Treatment with ceftiofur and ampicillin was not effective in elimination of L interrogans serovar pomona in swine. Conclusions Dihydrostreptomycin/penicillin G is effective for treatment of acute and persistent leptospirosis. Differences between the effectiveness of antimicrobial agents in the acute and persistent model of leptospirosis emphasize the importance of using the appropriate model for treatment evaluation. Antimicrobial agents evaluated for treatment of persistent leptospirosis in swine required the use of dosages above those recommended by the manufacturer. Clinical relevance Use of antimicrobial agents at extra-label dosages for treatment of persistent leptospirosis may cause residue problems in food animals; however, these regimens may be useful for treatment of breeding stock or animals destined for import/export.
Beyond the Frontier: The Convergence of Military and Civilian R&D in the United States

The end of the Cold war has inaugurated as significant a change in US science and technology policy as was brought about by the end of World War II. Just as a lack of land closed the frontier in the late nineteenth century, a lack of funds threatens its substitute, the so-called ‘endless frontier’ of science (Bush, 1970). The scientific frontier, based on an inexhaustible supply of funds for military research, and militarily legitimated basic research, was similarly subject to closure in the late twentieth century. During the early post-war era a nominally independent defence RD Kevles 1988). This scientific establishment was tied to the military but separated from civilian life even though it was officially under civilian control (Swomley, 1964; Nieburg, 1966: Melman, 1970; 1974).
A Dynamic Microeconomic System Design for Markets in Patents

We are well familiar with the economic analysis of a patent system in terms of a temporary monopoly on products, typically benefitting from marginal process inventions, formulated under conditions of certain future demands and fully excludable rights. This chapter develops an experimental and dynamic microeconomic model useful for studying the patent system as a trade – exchange – system, where patented technology is exchanged in organized competitivemarkets, under uncertain future demands and limited presumed validity on patent rights. An economic system design is developed to study transparent (public) priceson patents, dynamic gains from using a patent in multiple industries and the coordination of invention, intermediary (Trader) and innovation activities using a linear contract on patents (fixed fee plus royalty on future revenues). An intermediary Trader, or Investor, is introduced together with Inventor and Innovator agents in order to multiply the value (usage) of the technology. Three mechanism designs (institutions) and two levels of presumption of validity of the underlying patent right are proposed. The analysis differs from the previous work on patents, trade, and economics in that the focus is on the competitive pricingof the rights themselves, using demand-side bidding. An informal theory is outlined for pricing the dual values of a patent (investing and blocking). Based on this proposition, tentative hypothesis are outlined for two experiments using the outlined economic system design. The research thus attempts to shed light on the dynamicgains from coordination of development, trade, and use of patented technology between hierarchies through markets with prices. The general theme adds to understanding of a transition from personal exchange to an impersonal exchange in technology.
Heart Transplant Recipients Prefer a Telemental Health Cognitive-Behavioral Therapy Intervention Delivered by Telephone.

Abstract Background: Depression and anxiety are common after heart transplant, and in a regional heart transplant center servicing northern California, willingness to participate in treatment can b...
The effectiveness of light-emitting diode lighting for providing circadian stimulus in office spaces while minimizing energy use:

Architectural lighting has traditionally addressed visual performance and horizontal illuminance on the work plane, later focussing on energy efficiency, while only recently paying particular regar...
The Epidemiology of Depressive Symptoms in the Last Year of Life

Background/objective Depression impacts quality of life at all life stages, but the epidemiology of depression in the last year of life is unknown. This study's objectives were to document the epidemiology of depressive symptoms in the year prior to death and to assess how the trajectory of depressive symptoms varies by sociodemographic and clinical factors. Design Observational, cross-sectional, cohort study using the Health and Retirement Study. Setting Population-based survey. Participants A total of 3274 individuals who died within 12 months after assessment. Measures Primary outcome: eight-item Center for Epidemiologic Studies Depression Scale (CESD-8). Covariates included sociodemographics, self-reported illnesses, and activity of daily living (ADL) limitations. Results Average CESD-8 score increased over the last year of life, with 59.3% screening positive for depression in the last month before death. Depression symptoms increased gradually from 12 to 4 months before death (increase of 0.05 points/month; 95% confidence interval [CI] = 0.01-0.08 points/month) and then escalated from 4 to 1 months before death (increase of 0.29 points/month; 95% CI = 0.16-0.39 points/month). Women, younger adults, and nonwhite adults all demonstrated higher rates of depressive symptoms. Individuals with cancer reported escalating rates of depressive symptoms at the end of life, while individuals with lung disease and ADL impairment demonstrated persistently high rates throughout the year before death. Conclusions This study revealed high rates of depressive symptoms in the last year of life as well as differences in the burden of depressive symptoms. A public health approach must be taken to screen for and appropriately treat symptoms of depression across the lifespan. J Am Geriatr Soc 68:321-328, 2020.
The Effect of Inventory Risk on Supply Chain Performance

In this analysis we experimentally investigate how altering the inventory risk in a two-tier supply chain affects both the total supply chain profits and the distribution of profits between the two parties. We evaluate three wholesale-price contracts, each differing in which party incurs the risk associated with unsold inventory; a Push contract where the retailer incurs the risk, a Pull contract where the supplier incurs the risk, and an Advance-Purchase Discount (APD) contract where both parties share the risk. Our primary results are that total supply chain profits increase when switching from the Push contract to the Pull contract, as theory suggests, but that there is no improvement in supply chain profits when moving from the Pull contract to the APD contract. We also find that, contrary to standard theory, the APD contract is superior to the Push contract in terms of both retailer and supplier profits, suggesting that a Push contract should never be considered when an APD contract is a possibility.
Dichotomy in Fasciotomy: Practice Patterns Among Trauma/Acute Care Surgeons With Performing Fasciotomy With Peripheral Arterial Repair.

Introduction Failure to perform adequate fasciotomy for a presumed or diagnosed compartment syndrome after revascularization of an acutely ischemic limb is a potential cause of preventable limb loss. When required, outcomes are best when fasciotomy is conducted with the initial vascular repair. Despite over 100 years of experience with fasciotomy, the actual indications for its performance among acute care and trauma surgeons performing vascular repairs are unclear. The hypothesis of this study was that there are many principles of fasciotomy that are uniformly accepted by surgeons and that consensus guidelines could be developed. Methods A 20-question survey on fasciotomy practice patterns was distributed to trauma and acute care surgeons of a major surgical society which had approved distribution. Results The response to the survey was 160/1066 (15 %). 92.5% of respondents were fellowship trained in trauma and acute care surgery, and 74.9% had been in practice for fewer than 10 years. Most respondents (71.9%) stated that they would be influenced to perform a preliminary fasciotomy (fasciotomy conducted prior to planned exploration and arterial repair) based upon specific signs and symptoms consistent with compartment syndrome-including massive swelling (55.6%), elevated compartment pressures (52.5%), delay in transfer >6 hours (47.5%), or obvious distal ischemia (33.1%). 20.6% responded that they would conduct exploration and repair first, regardless of these considerations. Prophylactic fasciotomies (fasciotomy without overt signs of compartment syndrome) would be performed by respondents in the setting of the tense compartment (87.5%), ischemic time >6 hours (88.1%), measurement of elevated compartment pressures (66.9%), and in the setting of large volume resuscitation requirements (31.3%). 69.4% of respondents selectively measure compartment pressures, with nearly three-fourths utilizing a Stryker needle device (72.5%). The most common sequence of repairs following superficial femoral artery injury with a >6-hour limb ischemia was cited as the initial insertion of a shunt, followed by fasciotomy, then vein harvest, and finally interposition repair. Conclusions While there is some general consensus on indications for fasciotomy, there is marked heterogeneity in surgeons' opinions on the precise indications in selected scenarios. This is particularly surprising in light of the long history with fasciotomy in association with major arterial repairs and strongly suggests the need for a consensus conference and/or meta-analysis to guide further care.
Research and Exploratory Analysis Driven—Time-data Visualization (read-tv) software

Motivation Research & Exploratory Analysis Driven Time-data Visualization (read-tv) is an open source R Shiny application for visualizing irregularly and regularly spaced longitudinal data. read-tv provides unique filtering and changepoint analysis (CPA) features. The need for these analyses was motivated by research of surgical work-flow disruptions in operating room settings. Specifically, for the analysis of the causes and characteristics of periods of high disruption-rates, which are associated with adverse surgical outcomes. Materials and methods read-tv is a graphical application, and the main component of a package of the same name. read-tv generates and evaluates code to filter and visualize data. Users can view the visualization code from within the application, which facilitates reproducibility. The data input requirements are simple, a table with a time column with no missing values. The input can either be in the form of a file, or an in-memory dataframe- which is effective for rapid visualization during curation. Results We used read-tv to automatically detect surgical disruption cascades. We found that the most common disruption type during a cascade was training, followed by equipment. Discussion read-tv fills a need for visualization software of surgical disruptions and other longitudinal data. Every visualization is reproducible, the exact source code that read-tv executes to create a visualization is available from within the application. read-tv is generalizable, it can plot any tabular dataset given the simple requirements that there is a numeric, datetime, or datetime string column with no missing values. Finally, the tab-based architecture of read-tv is easily extensible, it is relatively simple to add new functionality by implementing a tab in the source code. Conclusion read-tv enables quick identification of patterns through customizable longitudinal plots; faceting; CPA; and user-specified filters. The package is available on GitHub under an MIT license.
Determination of Effective Magnetization and Gyromagnetic Ratio of Yttrium Iron Garnet From Multi-Mode Ferromagnetic Resonance S ₂₁ Spectra

We acquire ferromagnetic resonance (FMR) spectra for an out-of-plane magnetized yttrium iron garnet sample with a vector network analyzer at microwave frequencies ranging from 4.2 to 5.2 GHz. The applied static magnetic field varies from approximately 253.6 to 260.1 kA/m. Based on an empirical model for resonant features in the $S_{21}$ spectrum produced by the excitation of multiple modes and instrumental effects, we predict measured values of $S_{21}$ -parameters. For each of many microwave frequencies, for each of multiple modes, we determine the resonant field value of the applied magnetic field, an amplitude, and an FMR linewidth. Based on the frequency-dependent resonant field values produced by excitation of the main mode, we determine the effective magnetization and the gyromagnetic ratio of the sample.
A Fast Word Embedding Based Classifier to Profile Target Gene Databases in Metagenomic Samples

The functional profile of metagenomic samples allows the understanding of the role of the microbes in the environment. Sequence alignment of short reads against curated databases has been widely used to profile metagenomic samples. However, this method is time consuming and requires high computing resources. Although several alignment free methods based on k-mer composition have been developed in recent years, they still require a large amount of memory. In this paper, MetaMLP (Metagenomics Machine Learning Profiler), a machine learning method that represents sequences into numerical vectors (embeddings) and uses a simple one hidden layer neural network is proposed to profile functional categories. Unlike other methods, MetaMLP enables partial matching through a reduced alphabet for sequence embeddings. MetaMLP is able to identify a larger number of reads compared to Diamond (one of the fastest sequence alignment methods) while maintaining high performance with a 0.99 precision and a 0.99 recall. MetaMLP can process 100 million reads in around 10 min in a laptop computer, a 50x speed up compared to Diamond. MetaMLP is freely available at https://bitbucket.org/gaarangoa/metamlp/src/master/.
The solution of simultaneous algebraic equations

If there are two variables in an equation, such as F ( x , y ) — O, then the equation can be solved for y as a function of x or x as a function of y, but in order to solve for constant values of both variables, a second equation, such as G ( x , y ) — O, is required, and the two equations must be solved simultaneously. If there are n variables, n independent and consistent equations are required. In this chapter, various methods for finding the roots to sets of simultaneous equations are discussed. The chapter discusses simultaneous equations with more than two unknowns. Solution by matrix inversion is then described. The use of Mathematica to solve simultaneous equations is explained. The chapter presents several methods for solving simultaneous equations. The method of substitution is first considered, but is found not to be practical for more than two or three equations. Several methods which can apply to sets of linear inhomogeneous equations are discussed in the chapter. Cramer's method is a method which uses determinants to obtain the roots. The methods of Gauss elimination and Gauss–Jordan elimination are also presented. Finally, linear homogeneous equations are examined.
Transcription in vaccinia virus cores: The RNA produced during the first round of transcription does not differ from RNA transcribed in subsequent rounds

RNA was synthesized in vitro in vaccinia virus cores for times sufficiently short that only the first round of transcription took place. This RNA was compared to RNA synthesized for longer times (which is mainly comprised of reinitiated RNA) by hybridization to fragments of vaccinia virus DNA obtained with several different restriction endonucleases. Under the conditions studied, the composition of mRNA produced during the first round of transcription was the same as that produced in subsequent (reinitiated) rounds. Thus, there is no special arrangement of polymerase molecules within the cores that would allow, in the first round of transcription, for the synthesis of mRNAs distinct from those made in subsequent rounds of transcription. Thus, attachment of polymerase molecules to DNA is likely to occur during preincubation in a way similar to that during reinitiation.
The Educational Use of Social Media Sites by Pharmacy Students

Social media sites are widely used among professional students and may offer an alternative means ofcommunication for professors to utilize within their courses. Social media site usage has been characterized withinhealthcare education, however, data is lacking on its use within pharmacy programs. The purpose of this study was toevaluate social media use among pharmacy students at distance campus sites in order to determine studentpreferences and ways in which social media could be used within the pharmacy curriculum. A 12-item surveyquestionnaire was administered to first, second and third year students at three distance campus sites at the universityof florida college of pharmacy. Pharmacy students surveyed most commonly reported using the social media siteFacebook® for school purposes, followed by Google+®. The majority of students from each class year reported usingsocial media primarily to connect with fellow students or classmates. First and second year students most commonlyuse social media to keep up to date with events around campus, while third year students most commonly use socialmedia sites to collaborate about a class or case. A common advantage to incorporating social media sites intopharmacy education was identified as keeping up to date with important dates and campus events, while the biggestdisadvantage identified was that social media sites can be too distracting and time consuming. Social media sitesmay be used within pharmacy education as an alternative teaching modality.
Abstract 3653: Nanoparticle-delivered T7-synthesized siRNA enhances cell killing in HER-2 (+) breast cancer

We have previously developed the recombinant fusion protein, HerPBK10, for ligand-directed targeting and penetration of HER2+ breast cancer. HerPBK10 contains a ten lysine (K10) carboxy [C] -terminal tail that allows it to non-covalently bind anionic payloads, such as nucleic acids, by electrophilic interaction. In this study, a modified siRNA capable of both gene silencing and immunostimulation is the payload. Here, we test the hypothesis that ligand-directed, protein-based nanoparticles delivering siRNA launch a three-pronged attack on tumors by combining missile-like targeting (known as “transductional targeting”) with siRNA-mediated gene silencing, and cytokine-mediated cell death. The latter effect will be accomplished by taking advantage of the normally undesirable cytokine-mediated cytotoxicity induced by epigenetic modifications on certain forms of siRNA, and delivering this to tumors. Here we will deliver siRNA produced by T7 phage polymerase transcription, which introduces a 5′ triphosphate cap that triggers cytokine-mediated toxicity within host cells. So far, in vitro data has shown that this approach is more effective in reducing cell proliferation than synthetic siRNA against the same gene. Furthermore, in vivo xenograft data shows that this strategy can control and ablate the growth of HER2+ tumors. Future directions include IHC investigation of resected tumors and testing this hypothesis in an immunocompetent in vivo setting where we envision this immune-sensitive strategy having even greater efficacy. Citation Format: Felix Alonso-Valenteen, Medina-Kauwe. Nanoparticle-delivered T7-synthesized siRNA enhances cell killing in HER-2 (+) breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3653. doi:10.1158/1538-7445.AM2014-3653
Novel frameshift mutations in CRX associated with Leber congenital amaurosis.

Mutations in CRX, a photoreceptor-specific transcription factor, can cause Leber congenital amaurosis (LCA), cone-rod dystrophy (CORD), and retinitis pigmentosa (RP), all of which feature severe visual impairment. Upon screening 55 patients with Leber congenital amaurosis, 75 patients with cone-rod dystrophy, 13 with cone dystrophy, and 36 with recessive or isolate RP for changes in the CRX sequence, we found two patients with Leber congenital amaurosis who carried heterozygously one of two novel frameshift mutations. The first mutation, Tyr191(1-bp del), was a de novo change and the second change, Pro263(1-bp del) was inherited from the proband’s affected father. Both mutations are predicted to encode mutant versions of CRX with altered carboxy termini. We also found a previously reported missense mutation, Arg41Gln, heterozygously in a 47-year-old patient with a form of RP. The missense change Val242Met was found in an isolate case of CORD and no controls; however, its pathogenicity remains uncertain because only limited segregation analysis was possible. A nonpathogenic missense change, Ala158Thr, was found to be a variant present at relatively high frequency among African-Americans. © 2001 Wiley-Liss, Inc.
Isotopy and identities in alternative algebras

In this paper we show how to construct an isomorphism between an alternative algebra A over a field of characteristic # 3 and its isotope A(l+c), where c is an element of Zhevlakov's radical of A. This leads to the equivalence of any polynomial identity f 0 in alternative algebras and the isotope identity f (s) = 0. Given an invertible element s of an alternative algebra A, we can form a new algebra by taking the same linear structure but a new multiplication x *8 y = (xs)y. The resulting algebra, denoted A(s), is also alternative (see [1]) and is called an s-isotope. Associative and Cayley isotopes are always isomorphic [2], and an isotope of a finite-dimensional alternative algebra over an algebraically closed field of characteristic $& 3 is isomorphic to the original algebra as well [1]. We consider the case of an arbitrary alternative algebra over a field of characteristic 7& 3 with nonzero Zhevlakov radical, and a particular choice of s, and construct an explicit isomorphism between A and A(S). As a consequence, we derive the equivalence of any polynomial identity and its isotope in an arbitrary alternative algebras over a field of characteristic 7& 3. Th6 paper has benefited from many discussions with J. Ferrar, and I would like to thank him for his valuable help and encouragement. Theorem 1. There is a set of coefficients t', i, j > 0, such that t8 = 1 and for any integer m, any alternative algebra A over a field of characteristic 7 3 and any elements a, b, c from A such that IdA(C)m = 0, the polynomial t(x) = tcIc3 satisfies (1) t(a) *1?c t(b) = t(ab). Proof. We will show the way to calculate the coefficients t' such that (1) holds for any alternative algebra A. Clearly, t(a) *1+c t(b) = t(a)t(b) + (t(a)c)t(b) = t tk (ciac) (Ck bc') + EZtit (ciac9l) (ck bc) Ztk (t' + t-i)(ciac&)(ck bc), Received by the editors March 28, 1995. 1991 Mathematics Subject Classification. Primary 17D05. (D1997 American Mathematical Society 1571 This content downloaded from 157.55.39.144 on Wed, 07 Sep 2016 04:35:29 UTC All use subject to http://about.jstor.org/terms
Algorithms for purchasing AIDS vaccines

We delineate two algorithms for the purchase of an AIDS vaccine depending upon whether a health sector perspective or societal perspective is employed. Projections based on these algorithms show how different policy objectives can lead to vast differences in the number of courses of vaccine needed in the future. We consider a hypothetical vaccine costing $10 to produce and offering 60% 75% and 90% reductions in HIV risk for 10 years. For each of the world’s 10 major geographic divisions we use published estimates of the risk of AIDS the value of avoided medical costs and the value of potential productivity losses for adults teenagers and children. The health sector algorithm is based on allocating vaccine to minimize impact of AIDS/HIV on government health spending. The societal algorithm is based on allocating vaccine to minimize the impact of AIDS/HIV on health spending and GDP. A vaccine allocation algorithm designed to conserve health ministry budgets would purchase 766 million courses of vaccine. An algorithm designed to minimize the impact of AIDS on GDP would purchase over 3.7 billion courses of vaccine. Finally an algorithm that offered vaccination to everyone in the world as though they had the financial resources of Western Europeans would offer vaccine to 4.7 billion people. We conclude that the means to finance both the development and distribution of AIDS vaccines should draw from not just the health sector but the entire economy. If equity in health is valued global cost sharing is necessary. (authors)
Impact of marine biogeochemistry on the chemical mixing state and cloud forming ability of nascent sea spray aerosol

[1] The composition and properties of sea spray aerosol, a major component of the atmosphere, are often controlled by marine biological activity; however, the scope of impacts that ocean chemistry has on the ability for sea spray aerosol to act as cloud condensation nuclei (CCN) is not well understood. In this study, we utilize a mesocosm experiment to investigate the impact of marine biogeochemical processes on the composition and mixing state of sea spray aerosol particles with diameters < 0.2 µm produced by controlled breaking waves in a unique ocean-atmosphere facility. An increase in relative abundance of a distinct, insoluble organic particle type was observed after concentrations of heterotrophic bacteria increased in the seawater, leading to an 86 ± 5% reduction in the hygroscopicity parameter (κ) at 0.2% supersaturation. Aerosol size distributions showed very little change and the submicron organic mass fraction increased by less than 15% throughout the experiment; as such, neither of these typical metrics can explain the observed reduction in hygroscopicity. Predictions of the hygroscopicity parameter that make the common assumption that all particles have the same bulk organic volume fractions lead to overpredictions of CCN concentrations by 25% in these experiments. Importantly, key changes in sea spray aerosol mixing state that ultimately influenced CCN activity were driven by bacteria-mediated alterations to the organic composition of seawater.
Hypoferremia in Mice and Its Application to the Bioassay of Endotoxin

Baker, Phillip J. (University of Wisconsin, Madison), and J. B. Wilson. Hypoferremia in mice and its application to the bioassay of endotoxin. J. Bacteriol. 90:903-910. 1965.-The ability of endotoxin to induce hypoferremia in mice was used for the bioassay of endotoxin. A marked depression in the serum-iron levels of mice occurred 12 hr after the intraperitoneal injection of 0.01 to 100 mug of Escherichia coli endotoxin; similar results were obtained with 1.0 to 100 mug of Brucella abortus endotoxin. This biological response to endotoxin appeared to be specific, reproducible, and dose-dependent. As heat-killed cells of B. abortus and E. coli were also able to induce hypoferremia, this bioassay could be employed for the determination of the endotoxin content of killed-cell preparations. Treatment of endotoxin by acid hydrolysis, acetylation, or pyridine-formic acid greatly diminished the hypoferremic response as well as its lethality for mice. Pretreatment of mice with Thorotrast had little effect upon the ability of endotoxin to induce hypoferremia; however, a stimulation of the activity of the reticuloendothelial system (RES) by treatment of mice with triolein markedly reduced the ability of endotoxin to induce hypoferremia. The relationship between the hypoferremic response to endotoxin and alterations in the activity of the RES are discussed.
BOHM' S ONTOLOGICAL INTERPRETATION AND ITS RELATIONS TO THREE FORMULATIONS OF QUANTUM MECHANICS *

The standard mathematical formulation of quantum mechanics is specified. Bohm's ontological interpretation of quantum mechanics is then shown to be incapable of providing a suitable interpretation of that formulation. It is also shown that Bohm's interpretation may well be viable for two alternative mathematical formulations of quantum mechanics, meaning that the negative result is a significant though not a devastating criticism of Bohm's interpretation. A preliminary case is made for preferring one alternative formulation over the other.
Modeling and Characterization of Elastic, Coupling, and Dissipative Nonlinearities in PZT Bimorphs for Vibration Energy Harvesting

In numerous applications of lead zirconate titanate (PZT)-based devices, such as dynamic actuation, vibration control, sensing, and energy harvesting, inherent nonlinearities are inevitably pronounced for a broad range of mechanical and electrical excitation levels. Even in the absence of any geometric nonlinearity, researchers observed and reported nonlinear behavior in PZT-based devices for moderate-to-high excitation levels. Over the past two decades, the softening nonlinearities have been attributed to different phenomena by different research groups, such as purely elastic nonlinear terms and coupling nonlinearity. Dissipative effects of quadratic order have been observed but often attributed to air damping in symmetric structures. In an effort to develop a global nonlinear, non-conservative modeling framework, we combined elastic, coupling, and dissipative nonlinearities to explore primary resonance behavior in bimorph cantilevers for problems of mechanical and electrical excitation. We use this model to characterize the nonlinearities in piezoelectric bimorphs for energy harvesting with a focus on a symmetric brass-reinforced PZT-5A sample under base excitation. Specifically we point out the importance of quadratic nonlinearities in both stiffness and damping. Coupling and higher-order elastic nonlinearities from the electric enthalpy are observed to become effective only for the highest excitation levels close to physical limits of the device with high linear stiffness tested in this work.Copyright © 2014 by ASME
DR. WILLIAM HANAFEE

It is our deepest sorrow and sadness to inform all of the recent death of Dr. William N. Hanafee, a founding member of the American Society of Neuroradiology (ASNR) and the American Society of Head and Neck Radiology (ASHNR). Dr. Hanafee died in Pauma Valley, California, after battling a series of
Reversed Spatial Asymmetries between El Niño and La Niña and Their Linkage to Decadal ENSO Modulation in CMIP3 Models

AbstractThis study examines preindustrial simulations from Coupled Model Intercomparison Project, phase 3 (CMIP3), models to show that a tendency exists for El Nino sea surface temperature anomalies to be located farther eastward than La Nina anomalies during strong El Nino–Southern Oscillation (ENSO) events but farther westward than La Nina anomalies during weak ENSO events. Such reversed spatial asymmetries are shown to force a slow change in the tropical Pacific Ocean mean state that in return modulates ENSO amplitude. CMIP3 models that produce strong reversed asymmetries experience cyclic modulations of ENSO intensity, in which strong and weak events occur during opposite phases of a decadal variability mode associated with the residual effects of the reversed asymmetries. It is concluded that the reversed spatial asymmetries enable an ENSO–tropical Pacific mean state interaction mechanism that gives rise to a decadal modulation of ENSO intensity and that at least three CMIP3 models realistically simu...
Cognitive Demand Differences in Causal Inferences: Characters' Plans are More Difficult to Comprehend Than Physical Causation

Readers may draw knowledge-based inferences to connect sentences in text differently depending on the knowledge domain being accessed. Most prior research has focused on the direction of the causal explanation (predictive vs. backward) without regard to the knowledge domain drawn on to support comprehension. We suggest that less cognitive effort is required for physical cause-and-effect inferences than for inferences drawn from goal-directed or planning knowledge. Using a dual task that required readers to hold word lists in memory while reading simple texts, we measured inference processes across knowledge areas by probe word recognitions and knowledge-validating questions. In Experiment 1 a word-recall task of 3 versus 6 items was employed to overload working memory and attention. In Experiment 2, a no-load level was included for comparison. The impact of cognitive loads (high vs. low vs. no) was expected to impair inference processes more for planning than physical knowledge, which our results supporte...
The effects of repeated spectroscopic pressure measurements on fluorescence intensity in the cervix.

Objective Fluorescence spectroscopy is a promising technology for the detection of cervical squamous intraepithelial lesions (SILs). In this study we took repeated measures in the cervix to determine whether the order of measurement produces changes in fluorescence intensity and whether there are differences in variation due to pressure. Methods A pressure sensitive fiber-optic probe to measure fluorescence spectra was calibrated at light, medium, and firm levels (0.2, 0.4, 0.6 N). Measurements were made 3 times at each of 2 sites in the patient's cervix. Spectroscopic data were preprocessed and analyzed to compare order of pressure and intensity variability as a function of pressure on measurements. Results Four providers took 3 measurements from 2 sites each in 18 patients, yielding 108 measurements. After corrections for multiple comparisons, neither the order of probe pressure nor the variability of probe pressure significantly affected variations in fluorescence intensity. Conclusion This study shows that the probe pressure variability is probably not an issue for these devices.
Interocular suppression differentially affects achromatic and chromatic mechanisms.

Results from a series of psychophysical experiments show that interocular suppression produced by continuous flash suppression (CFS) differentially affects visual features of a target viewed by the other eye. When CFS stimuli are defined by luminance contrast, target color can be reliably identified but percent-correct discrimination of target orientation is near chance. When the colored target is moving, color identification deteriorates with motion speed but direction of motion discrimination improves with target speed. Color’s immunity to suppression is also weakened when interocular suppression is induced by equiluminant CFS stimuli that presumably stimulate the chromatic pathway. These results are discussed in terms of functional segregation of achromatic and chromatic processing in the visual system.
Thermomechanical properties, antibiotic release, and bioactivity of a sterilized cyclodextrin drug delivery system

Various local drug delivery devices and coatings are being developed as slow, sustained release mechanism for drugs, yet the polymers are typically not evaluated after commercial sterilization techniques. We examine the effect that commercial sterilization techniques have on the physical, mechanical, and drug delivery properties of polyurethane polymers. Specifically we tested cyclodextrin–hexamethyl diisocyanate crosslinked polymers before and after autoclave, ethylene oxide, and gamma radiation sterilization processes. We found that there is no significant change in the properties of polymers sterilized by ethylene oxide and gamma radiation compared to non-sterilized polymers. Polymers sterilized by autoclave showed increased tensile strength (p < 0.0001) compared to non-sterilized polymers. In the release of drugs, which were loaded after the autoclave sterilization process, we observed a prolonged release (p < 0.05) and a prolonged therapeutic effect (p < 0.05) but less drug loading (p < 0.0001) compared to non-sterilized polymers. The change in the release profile and tensile strength in polymers sterilized by autoclave was interpreted as being caused by additional crosslinking from residual, unreacted, or partially-reacted crosslinker contained within the polymer. Autoclaving therefore represents additional thermo-processing to modify rate and dose from polyurethanes and other materials.
Quantum confined luminescence in Si/SiO2 superlattices.

Superlattices of $\mathrm{Si}/{\mathrm{SiO}}_{2}$ have been grown at room temperature with atomic layer precision using state of the art molecular beam epitaxy and ultraviolet ozone treatment. Photoluminescence was observed at wavelengths across the visible range for Si layer thicknesses $1ldl3\phantom{\rule{0ex}{0ex}}\mathrm{nm}$. The fitted peak emission energy $E(\mathrm{eV}){\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1.60+0.72d}^{\ensuremath{-}2}$ is in accordance with effective mass theory for quantum confinement by the wide-gap ${\mathrm{SiO}}_{2}$ barriers and also with the bulk amorphous Si band gap. Measurements of the conduction and valence band shifts by x-ray techniques correlate with $E(d)$, confirming the role of quantum confinement and indicating a direct band-to-band recombination mechanism.