cssi/SciSciGPT-SciSciNet huggingface dataset:
Routine argyrophil techniques detect Rickettsia rickettsii in tissues of patients with fatal Rocky Mountain spotted fever

Rickettsia rickettsii, a bacterial tickborne pathogen that causes Rocky Mountain spotted fever (RMSF), stains poorly or not at all with conventional tissue Gram techniques, and contemporary visualization of the pathogen in formalin-fixed, paraffin-embedded tissues has relied almost entirely on immunohistochemical staining methods that are generally limited to specialized research laboratories or national reference centers. To our knowledge, previously described argyrophil-based histochemical techniques have not successfully detected rickettsiae in formalin-fixed, paraffin-embedded tissues. To investigate the ability of standard silver impregnation techniques to demonstrate the occurrence and distribution of R. rickettsii in tissues of patients with RMSF confirmed by molecular and immunohistochemical methods, three widely recognized and commercially available silver impregnation methods (Warthin-Starry, Steiner, and Dieterle's) were applied to various tissues obtained at autopsy from 10 patients with fatal RMSF. R. rickettsii bacteria were demonstrated in one or more tissues of all patients, using each of the argyrophil-based methods, and appeared as small, dark brown-to-black lanceolate rods, often in pairs and occasionally surrounded by a faint halo. Rickettsiae were identified most consistently in small arteries and arterioles of liver, kidney, and leptomeninges, and were localized predominantly to the cytoplasm of endothelial cells and less often within the internal elastic lamella and smooth muscle of the media. This validation of argyrophilic techniques to detect R. rickettsii demonstrates the utility of inexpensive core histochemical methods in the diagnosis of infectious agents in pathology specimens and may have utility in certain resource-limited settings where RMSF is endemic.
A model to analyze the challenge of using cyber insurance

This work analyzes and extends insurance dynamics in the context of cyber risk. Cyber insurance contracts, when used as a means to manage residual cyber risk, could behave differently from other traditional (e.g., property) insurance. One important difference arises from the complexity involved in the post-breach decision of whether and how a firm should optimally plan to claim indemnity in the event of a cyber breach. We define different types of cyber breaches leading to different claiming scenarios, whose roots lie in the impact of secondary loss caused by certain but not all types of breaches. We build a model to capture the impact of secondary loss in structuring the use of cyber insurance and then combine the backward analysis of myriad breach scenarios to derive the overall optimal decision to purchase cyber insurance. We demonstrate that the optimal purchase decision depends on the mix of the types of cyber breaches that a firm faces. Numerical experiments corroborate market observation of limited use of cyber insurance after 20 years from when these products became available.
Fascism as Action through Time (Or How It Can Happen Here)

The purpose of this paper is to discuss how fascism may be identified by its actions, the stages through which a fascist rule takes power, and how to recognize it before it does so. The thesis is that a fascist takeover of a democratic government is rapid and unexpected. Its goal is a revolutionary reversal of representative government in the name of the people, while it accomplishes the opposite: a single-party corporate regime that replaces individual liberty with subtle, bureaucratic, and overt types of coercion. Rather than generate a generic definition of the many types of fascism, it is more useful to study how it affects the lives of ordinary people, the milieu out of which it develops, and what its precursors look like. Understanding fascism entails studying it from the point of view of those who lived under it and recorded their experiences, as well as from the analytic perspectives of social scientists. As Robert O. Paxton observes: “The fascist phenomenon was poorly understood at the beginning ...
Beyond Body Mass Index: Using Anthropometric Measures and Body Composition Indicators to Assess Odds of an Endometriosis Diagnosis

Abstract Background: Body mass index (BMI) and endometriosis have been inversely associated. To address gaps in this research, we examined associations among body composition, endometriosis, and physical activity. Materials and Methods: Women from 14 clinical sites in the Salt Lake City, Utah and San Francisco, California areas and scheduled for laparoscopy/laparotomy were recruited during 2007–2009. Participants (N = 473) underwent standardized anthropometric assessments to estimate body composition before surgery. Using a cross-sectional design, odds of an endometriosis diagnosis (adjusted odds ratio [aOR]; 95% confidence interval [CI]) were calculated for anthropometric and body composition measures (weight in kg; height in cm; mid upper arm, waist, hip, and chest circumferences in cm; subscapular, suprailiac, and triceps skinfold thicknesses in mm; arm muscle and fat areas in cm2; centripetal fat, chest-to-waist, chest-to-hip, waist-to-hip, and waist-to-height ratios; arm fat index; and BMI in kg/m2)....
Psychosis (Schizophrenia Spectrum and Other Psychotic Disorders)

The symptoms and signs of psychosis are perceptual, cognitive, and behavioral abnormalities that suggest an involuntary break with reality. Cardinal symptoms include hallucinations, delusions, illusions, and bizarre behavior. Loose associations, tangentiality, flight of ideas, and illogical or incoherent speech may be present. Anxiety, agitation, insomnia, depression, euphoria, and suicidal or homicidal behavior may occur, often secondary to the delusions or hallucinations. Though patients with psychosis may seem bizarre, all normal people have at times experiences such as hallucinations and delusions, for example, during dreaming. Most normal people are capable of having psychotic experiences while awake, under the influence of psychotomimetic drugs such as d-lysergic acid (LSD) or under sensory deprivation conditions. In fact, delirium due to any cause is often associated with psychotic symptoms. We all possess the capacity for the psychotic mode of experiencing reality-the difference between this and psychosis as a syndrome the lack of control over the experience in the latter. The lack of control seen in psychosis may be due to endogenous or exogenous toxins, extreme stress, or neurodevelopmental abnormality. The diagnosis and treatment of psychotic syndromes are discussed.
Persuasion in crowdfunding: An elaboration likelihood model of crowdfunding performance

This study draws upon the elaboration likelihood model of persuasion (ELM) to develop and test a model of persuasive influence in crowdfunding. To test our hypothesized relationships, we drew upon a sample of 383 ventures taken directly from Kickstarter, coupled with a decision experiment conducted in a simulated crowdfunding context. Results suggest that issue-relevant information, such as entrepreneurs' education, matters most when funders possess greater ability and motivation to make careful evaluations. In contrast, cues, such as adopting a group identity, have their strongest influence among inexperienced, first-time funders, and when requested funding amounts are smaller.
Mathematical simulation of efficiency of various shapes of solar panels for NASA geostationary satellites

The purpose of this research is to analyze mathematically cylindrical shapes of flexible solar panels and compare their efficiency to the flat panels. The efficiency is defined to be the flux density, which is the ratio of the mathematical flux and the surface area. In addition we describe the trajectory of the Sun at specific locations: the North Pole, The Equator and a geostationary satellite above the Equator. The calculations were performed with software: Maple, Mathematica, and MATLAB.
Improved durability of soil humidity sensor for agricultural IoT environments

Soil humidity is the most important factor for plant growth. Therefore, the soil humidity sensor is an important part of smart farm application using agricultural IoT environments. Since soil humidity sensors are applied wet underground and the sensor consists of copper, rust eats away the copper surface of sensors. From rusting of sensors, wrong information of soil humidity can be collected on smart farm system based on agricultural IoT Environments. It makes that smart farm is not reliable. In this paper, we propose a new type of soil humidity sensor in order to extend life time.
Three Tiered Network Architecture for PACS Clusters

A three tiered network architecture is used at UCLA for our PACS project. Ethernet is used for connection to radiological imaging devices and as a global backup. FDDI is used to connect related computers in what is termed a PACS “cluster.” UltraNet is used as a high-speed backbone to connect the PACS clusters and the various image display stations within them.
An Effective Educational Model for Tuberculosis in the Ambulatory Care Clinic: Documentation of Clinical Competence and Skills

Tuberculosis (TB) is on the rise worldwide and preliminary studies indicate that many physicians are ill equipped to provide appropriate care for patients with TB. Physicians lack proper knowledge regarding the epidemiology, diagnosis and treatment of this illness. Because of these factors, development of serious complications including an onslaught of multidrug resistant TB cases has occurred. Prior to the implementation of this educational and assessment program, no formal instruction or skills documentation program existed for TB with the curriculum at the University of Missouri-Kansas City School of Medicine. The implemented program utilized cost-free items available from the Centers for Disease Control, Atlanta, Georgia USA (Core Curriculum, PPD audiovisual tape) and’ see and touch artificial arms with mantoux tb skin test reactions’ (American Lung Association, Western Pennsylvania). The program resulted in a statistically significant improvement in performance compared to controls.
On Describing Human White Matter Anatomy: The White Matter Query Language

The main contribution of this work is the careful syntactical definition of major white matter tracts in the human brain based on a neuroanatomist’s expert knowledge. We present a technique to formally describe white matter tracts and to automatically extract them from diffusion MRI data. The framework is based on a novel query language with a near-to-English textual syntax. This query language allows us to construct a dictionary of anatomical definitions describing white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This enables automated coherent labeling of white matter anatomy across subjects. We use our method to encode anatomical knowledge in human white matter describing 10 association and 8 projection tracts per hemisphere and 7 commissural tracts. The technique is shown to be comparable in accuracy to manual labeling. We present results applying this framework to create a white matter atlas from 77 healthy subjects, and we use this atlas in a proof-of-concept study to detect tract changes specific to schizophrenia.
A BODIPY-functionalized PdII photoredox catalyst for Sonogashira C–C cross-coupling reactions

We report for the first time a BODIPY-functionalized dichloro(1,10-phenanthroline)palladium(II) complex as an efficient photoredox catalyst for the Sonogashira C–C cross-coupling between phenylacetylene derivatives and iodobenzene derivatives with yields up to 92% under visible light illumination at room temperature.
Assessment of Student Performance on Core Concepts in Organic Chemistry

Assessments can provide instructors and students with valuable information regarding student’s level of knowledge and understanding, in order to improve both teaching and learning. In this study, we analyzed departmental assessment quizzes given to students at the start of Organic Chemistry 2, over an eight year period. This assessment quiz was designed to test students on core concepts from Organic Chemistry 1 that require the use of symbolic representations, such as drawing Lewis structures and using curved arrows. Using statistical analysis, it was found that students performed significantly lower than expected on the assessment quiz, and there was no significant difference in scores on the quiz over the eight years analyzed. Analysis of each individual question revealed that approximately one-third of the students made mistakes when converting a condensed formula or a chemical name to a chemical structure. For questions that involved more detailed answers such as drawing structures and showing simple ...
The role of macrophage production of transforming growth factor-ß in epithelial ovarian cancer progression.

e17100Background: Increased Transforming Growth Factor- s (TGF-s) signaling is associated with poorer prognosis in advanced stage epithelial ovarian carcinoma (EOC). Macrophages are known to produc...
Multivariate Iyengar Inequalities for Radial Functions

Here we present a variety of multivariate Iyengar type inequalities for radial functions defined on the shell and ball. Our approach is based on the polar coordinates in \(\mathbb {R}^{N}\), \(N\ge 2\), and the related multivariate polar integration formula. Via this method we transfer well-known univariate Iyengar type inequalities and univariate author’s related results into multivariate Iyengar inequalities. See also [3].
A benzenesulfonamide derivative as a novel PET radioligand for CXCR4.

Abstract CXCR4 is involved in various diseases such as inflammation, tumor growth, and cancer metastasis through the interaction with its natural endogenous ligand, chemokine CXCL12. In an effort to develop imaging probes for CXCR4, we developed a novel small molecule CXCR4-targeted PET agent (compound 5) by combining our established benzenesulfonamide scaffold with a labeling component by virtue of click chemistry. 5 shows nanomolar affinity (IC50 = 6.9 nM) against a known CXCR4 antagonist (TN14003) and inhibits more than 65% chemotaxis at 10 nM in vitro assays. Radiofluorinated compound 5 ([18F]5) demonstrates a competitive cellular uptake against CXCL12 in a dose-dependent manner. Further, microPET images of [18F]5 exhibits preferential accumulation of radioactivity in the lesions of λ-carrageenan-induced paw edema, human head and neck cancer orthotopic xenograft, and metastatic lung cancer of each mouse model.
Polymorphic Access Permissions

Abstract : This paper presents a polymorphic extension to a type system that prevents the misuse of object protocols. Polymorphism allows classes to be generic in the Access Permissions in their specifications. Access Permissions describe both the current state of an object and whether or not references to the object alias. Polymorphic Access Permissions allow programmers to specify certain patterns that we have encountered in practice, for example a collection of open, unaliased files. This paper also describes an implementation of this system as a static typestate checker for the Java programming language.
Reconstruction of the Renal Pelvis and Ureter

Ureteral strictures could be caused by many etiologies. Conservative option for management of strictures can be placement of double J ureteral stent, either plastic or metallic. The reconstructive surgical management of renal pelvis and ureteral strictures depends on the location and length of the defect as well as the quality of adjacent tissues. In summary, for short, uncomplicated ureteropelvic junction (UPJ) obstruction and proximal ureteral strictures, pyeloplasty and ureteroureterostomy (UU) are gold standards. For short defects involving the upper or mid-ureter, a ureteroureterostomy or transureterureterostomy (TUU) is appropriate. A short defect involving the lower ureter is usually managed by ureteroneocystotomy (UNC) with or without a psoas hitch and/or Boari flap. For long ureteral defects, reconstructive options include renal auto transplantation, TUU, or ureteral reconstruction using bowel segments such as an ileal ureter.
An Experience Report on Running a Pre-College Computer Science Summer Program

The demand for Information Technology professionals has continued to grow. Unfortunately, the study of Computer Science within the high school education curriculum is limited causing incoming college Freshmen students who are majoring in Computer Science or in related STEM fields to be unprepared. Additionally, the means to meet the employment demand is worsen with women and some ethnic groups being under-represented, especially within the Computer Science field. Offering students a pre-college summer experience has been a means to better prepare the students. This paper outlines the experience of setting up such a program. The goal is to engage the students, better prepare them for success, as well as bringing them together as a cohort which is essential during their first critical year in a Computer Science engineering field of study.
The Relationship of First-Year Residence Hall Roommate Assignment Policy with Interactional Diversity and Perceptions of the Campus Environment

A heterogeneous student body is valued in part because diverse interactions among students help create educated and competent citizens and promote learning and development. Campus housing is a prim...
Challenges and Opportunities in the Detection of Safety-Critical Cyberphysical Attacks

Cyberphysical systems (CPSs) are increasingly used in various application domains and face the threat of cyberphysical attacks. In this article, we discuss challenges in detecting these attacks. We use power grids and surgical robots to clarify our analysis, and we use this analysis to identify ongoing challenges and future research directions.
31 – Design of Plastic Parts

Publisher Summary Plastics provide many unique advantages when used in product design. From a cost perspective, plastics offer not only a low cost per unit volume of material, but also low manufacturing and assembly costs due to their ability to be easily formed into net shape products containing assembly features. Their light weight and ease of recyclability also often result in the lowest possible life cycle costs compared to product designs based on other types of materials. The selection of plastic parts depends factors such mechanical, electrical and thermal, and processing properties. Once the determination has been made regarding the use of plastic for a part design, the next most important decision is likely the selection of the manufacturing process. The selection of the manufacturing process is critical since the plastic part design must vary accordingly. Extrusion, injection molding, thermoforming, and blow molding each rely on different process mechanisms to shape the plastic. As such, each provides fundamentally different part geometry. In general, the plastic part's geometric complexity and dimensional precision increases with the cost of the tooling used with the process.
Development of a competency model and tailored assessment method for high school science teachers utilizing a flipped learning approach

Many professional development programs aim to improve student outcomes by enhancing teacher competencies. Effective evaluation of these programs requires a clear delineation of the competencies to be gained. A competency model was developed to evaluate the impact of a teacher professional program that aimed to improve teachers' ability to effectively implement technologically engaged modules in a flipped classroom setting. Competencies were identified via participatory evaluation techniques and assessments were aligned to the competencies. The competency of teachers in the knowledge, skills, and abilities needed for creation and delivery of effective flipped lessons can be tracked using a radar graph to guide tailored professional development.
The assessment of service quality for third-party logistics providers in the beverage industry

The assessment of service quality has received increasing attention over the past few decades. The SERVQUAL model is an instrument that is commonly used to quantify the quality of a service. It div...
Poppy Seed Defense and Workplace Drug Testing: Does It Work in the Court?

Abstract In general, morphine is the most abundant alkaloid found in raw opium, followed by noscapine, codeine, papaverine, and thebaine. Morphine, codeine, and thebaine are also found in the opium poppy latex. Opium alkaloids are not found in poppy seeds but are transferred onto the seed coats during harvesting process. As a result, alkaloid content of poppy seeds varies widely with morphine content ranging from 0.1 to 620 mg/kg of seeds and codeine content varying from 0.08 to 57.1 mg/kg of seeds. In general morphine content is significantly higher than codeine. As a result both morphine and codeine are found in urine of subjects eating poppy seed–containing foods. However, both morphine and codeine levels are relatively low in urine after eating poppy seed–containing food because more than 90% morphine present in raw poppy seeds are destroyed during food processing especially baking. Therefore, it is unlikely that after eating poppy seed–containing food, a person will test positive for opiates during immunoassay screening where cutoff concentration for opiate is 2000 ng/mL. Moreover, the presence of 6-monoacetylmorphine, a marker of heroin abuse, is not consistent with eating poppy seed–containing food.
Understanding the Security and Privacy Advice Given to Black Lives Matter Protesters

In 2020, there were widespread Black Lives Matter (BLM) protests in the U.S. Because many attendees were novice protesters, organizations distributed guides for staying safe at a protest, often including security and privacy advice. To understand what advice novice protesters are given, we collected 41 safety guides distributed during BLM protests in spring 2020. We identified 13 classes of digital security and privacy advice in these guides. To understand whether this advice influences protesters, we surveyed 167 BLM protesters. Respondents reported an array of security and privacy concerns, and their concerns were magnified when considering fellow protesters. While most respondents reported being aware of, and following, certain advice (e.g., choosing a strong phone passcode), many were unaware of key advice like using end-to-end encrypted messengers and disabling biometric phone unlocking. Our results can guide future advice and technologies to help novice protesters protect their security and privacy.
Measuring H0 using X-ray and SZ effect observations of dynamically relaxed galaxy clusters

We use a sample of 14 massive, dynamically relaxed galaxy clusters to constrain the Hubble Constant, $H_0$, by combining X-ray and Sunyaev-Zel'dovich (SZ) effect signals measured with Chandra, Planck and Bolocam. This is the first such analysis to marginalize over an empirical, data-driven prior on the overall accuracy of X-ray temperature measurements, while our restriction to the most relaxed, massive clusters also minimizes astrophysical systematics. For a cosmological-constant model with $\Omega_m = 0.3$ and $\Omega_{\Lambda} = 0.7$, we find $H_0 = 67.3^{+21.3}_{-13.3}$ km/s/Mpc, limited by the temperature calibration uncertainty (compared to the statistically limited constraint of $H_0 = 72.3^{+7.6}_{-7.6}$ km/s/Mpc). The intrinsic scatter in the X-ray/SZ pressure ratio is found to be $13 \pm 4$ per cent ($10 \pm 3$ per cent when two clusters with significant galactic dust emission are removed from the sample), consistent with being primarily due to triaxiality and projection. We discuss the prospects for reducing the dominant systematic limitation to this analysis, with improved X-ray calibration and/or precise measurements of the relativistic SZ effect providing a plausible route to per cent level constraints on $H_0$.
Sequencing of a central nervous system tumor demonstrates cancer transmission in an organ transplant

Four organ transplant recipients from an organ donor diagnosed with anaplastic pleomorphic xanthoastrocytoma developed fatal malignancies for which the origin could not be confirmed by standard methods. We identified the somatic mutational profiles of the neoplasms using next-generation sequencing technologies and tracked the relationship between the different samples. The data were consistent with the presence of an aggressive clonal entity in the donor and the subsequent proliferation of descendent tumors in each recipient. Deleterious mutations in BRAF, PIK3CA, SDHC, DDR2, and FANCD2, and a chromosomal deletion spanning the CDKN2A/B genes, were shared between the recipients' lesions. In addition to demonstrating that DNA sequencing tracked a donor/recipient cancer transmission, this study established that the genetic profile of a donor tumor and its potential aggressive phenotype could have been determined before transplantation was considered. As the genetic correlates of tumor invasion and metastases become better known, adding genetic profiling by DNA sequencing to the data considered for transplant safety should be considered.
On "Decisions and Revisions Which a Minute Will Reverse": Consciousness, The Unconscious and Mathematical Modeling of Thinking.

This article considers a partly philosophical question: What are the ontological and epistemological reasons for using quantum-like models or theories (models and theories based on the mathematical formalism of quantum theory) vs. classical-like ones (based on the mathematics of classical physics), in considering human thinking and decision making? This question is only partly philosophical because it also concerns the scientific understanding of the phenomena considered by the theories that use mathematical models of either type, just as in physics itself, where this question also arises as a physical question. This is because this question is in effect: What are the physical reasons for using, even if not requiring, these types of theories in considering quantum phenomena, which these theories predict fully in accord with the experiment? This is clearly also a physical, rather than only philosophical, question and so is, accordingly, the question of whether one needs classical-like or quantum-like theories or both (just as in physics we use both classical and quantum theories) in considering human thinking in psychology and related fields, such as decision science. It comes as no surprise that many of these reasons are parallel to those that are responsible for the use of QM and QFT in the case of quantum phenomena. Still, the corresponding situations should be understood and justified in terms of the phenomena considered, phenomena defined by human thinking, because there are important differences between these phenomena and quantum phenomena, which this article aims to address. In order to do so, this article will first consider quantum phenomena and quantum theory, before turning to human thinking and decision making, in addressing which it will also discuss two recent quantum-like approaches to human thinking, that by M. G. D’Ariano and F. Faggin and that by A. Khrennikov. Both approaches are ontological in the sense of offering representations, different in character in each approach, of human thinking by the formalism of quantum theory. Whether such a representation, as opposed to only predicting the outcomes of relevant experiments, is possible either in quantum theory or in quantum-like theories of human thinking is one of the questions addressed in this article. The philosophical position adopted in it is that it may not be possible to make this assumption, which, however, is not the same as saying that it is impossible. I designate this view as the reality-without-realism, RWR, view and in considering strictly mental processes as the ideality-without-idealism, IWI, view, in the second case in part following, but also moving beyond, I. Kant’s philosophy.
Following Heavenly Orders: Heroic Deviance and the Denial of Responsibility in Narratives of Rescue

This case study of heroic deviance focuses onHutu who did not participate in the genocidal violence in 1994 Rwanda and instead risked their lives to rescue Tutsi. Drawing from 45 in-depth interview...
Cognitive Science of Attention: Current Concepts and Approaches

The cognitive science of attention has evolved over the past 2 decades to the point that there are now many well-accepted concepts and methodological approaches available for use in studying attentional processes. Equally important is the fact that attention is now widely accepted as essential to cognition and there is little debate about whether it is a valid topic of scientific study. Various theories and attentional constructs developed over the past 2 decades have been formalized with clear operational definitions and predictions about how attention performance should vary under different conditions, such that it is possible to test their validity and consistency. Accordingly, there is now a relatively vast and rich body of cognitive research on attention. Several of these lines of research that are particularly relevant to the neuropsychology of attention will be considered.
Promoting Social Change through Service-Learning in the Curriculum

Service-learning is a high-impact pedagogical strategy embraced by higher education institutions. Direct service based on a charity paradigm tends to be the norm, while little attention is paid to social change-oriented service. This article offers suggestions for incorporating social justice education into courses designed to promote social change through service-learning. The article delineates the characteristics of social justice education, discusses ways to incorporate social justice and service-learning components into appropriate courses, and provides a blueprint for constructing the syllabus.
Bdellovibrios in Callinectus sapidus, the Blue Crab

Bdellovibrios were recovered from the gill tissue of all of 31 crabs sampled and from all samples of epibiota obtained from the ventral shell surface of 15 crabs. The results suggest that the blue crab is a reservoir for bdellovibrios. The association with crabs may be an important factor in the ecology of the bdellovibrios.
Effect of Eye Dominance on Baseball Batting

Abstract The purpose of this study was to determine the effect of eye dominance on baseball batting. After determining their dominant hand and eye, 28 players from two college baseball teams were divided into groups according to their particular laterality. The resulting groups were composed of crossed laterals and unilaterals. The two laterality groups were then compared in their batting performance. Comparisons were made in such batting departments as: on-base-average; batting average; strike-outs; called strike-outs and missed swings. The unilaterals scored better than the crossed laterals in most batting categories. The batting stances of the unilateral players significantly affected their performances in certain batting categories. The results indicate that eye dominance may have some effect on certain aspects of baseball batting.
Discovery of 2,4-diaryl-2,5-dihydropyrrole inhibitors of the mitotic kinesin KSP

Proc Amer Assoc Cancer Res, Volume 46, 2005 SY13-1 Mitotic kinesins are involved in bipolar spindle assembly, maintenance and elongation, chromosome alignment and segregation, and microtubule depolymerization, among other functions during cell division. KSP is a mitotic kinesin that causes centrosome separation, a process required for bipolar spindle formation and maintenance. Inhibition of KSP results in collapse of bipolar spindles and gives rise to monopolar spindle arrays, referred to as monoasters. Importantly, this phenotype is accompanied by cell cycle arrest in mitosis, and prolonged mitotic arrest in tumor cells can lead to apoptosis. KSP inhibitors therefore have potential as general antiproliferative agents useful for the treatment of cancer. Additionally, KSP inhibition represents a novel and specific mechanism by which to target the mitotic spindle that may be devoid of the neuropathy-associated, mechanism-based side effects common to the taxanes and other natural products that target microtubules. KSP inhibitors may also offer advantages over these agents with regard to formulation and tumor resistance. In this presentation, we disclose the development of 2,4-diaryl-2,5-dihydropyrroles as novel, potent and selective inhibitors of KSP. The evolution of this class from a 3,5-diaryl-4,5-dihydropyrazole lead structure will be described with emphasis on modifications to the N-1 substituent of the dihydropyrrole nucleus that provided potency and aqueous solubility simultaneously. Initial optimization efforts in this series led to the identification of compound 1 (KSP IC50 = 2.0 nM). Compound 1 caused mitotic arrest in vitro in A2780 human ovarian carcinoma cells (EC50 = 8.6 nM) and upon prolonged exposure activated caspase-3 (EC50 = 11 nM) and induced apoptosis as determine by FACS analysis. Furthermore, compound 1 caused mitotic arrest, induced apoptosis and inhibited tumor growth in vivo in A2780 tumors in mice. An analysis of the novel binding mode of compound 1 will be provided along with a summary of its physiochemical properties and pharmacokinetics in animals. A scalable asymmetric synthetic route to compound 1 will also be highlighted in this presentation.
AMP-Activated Protein Kinase Restricts IFN-γ Signaling

Inflammation in the CNS contributes to neurologic disorders. Neuroinflammation involves the release of inflammatory molecules from glial cells, such as astrocytes and microglia, and can lead to neuronal damage if unabated. In multiple sclerosis, peripheral immune cells, including IFN-γ-producing Th1 cells, infiltrate the CNS and are important in shaping the inflammatory microenvironment, in part through cytokine-mediated interactions with glial cells. Recent evidence suggests that AMP-activated protein kinase (AMPK), a central regulator of energetic metabolism, can regulate inflammatory gene expression. In this study, we identified that IFN-γ induces biphasic AMPK signaling, suggestive of negative-feedback mechanisms. Activation of AMPK suppresses several IFN-γ-induced cytokines and chemokines in primary astrocytes and microglia. IFN-γ regulates gene expression through activation of STAT1, and deletion of AMPK results in a marked increase in basal expression of STAT1. Conversely, activation of AMPK blocks IFN-γ-induced STAT1 expression. Deletion of AMPK leads to increased basal and IFN-γ-induced expression of inflammatory molecules, including TNF-α, CXCL10, and CCL2. AMPK does not affect the phosphorylation of STAT1, but instead attenuates nuclear translocation of STAT1, DNA binding, and subsequent gene expression. In vivo, AMPK signaling during experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, is downregulated in the brain at onset and peak of disease. Diminution of AMPK signaling in vivo correlates with increased expression of IFN-γ and CCL2 in the CNS. Overall, these findings provide the first link between AMPK and STAT1 and may provide important clues about how bioenergetics and inflammation are linked.
Axial osteomalacia: Clinical, laboratory and genetic investigation of an affected mother and son

Axial osteomalacia--a rare osteosclerotic bone disorder characterized by axial skeleton pain, coarsening of the trabecular bone pattern on radiographs of the axial but not appendicular skeleton, and osteomalacia on biopsy of a rib or iliac crest--has been reported in 10 apparently sporadic cases, all of which were in middle-aged or elderly Caucasian men. The etiology is unknown but has been postulated to be a bone cell defect. We describe the clinical, laboratory, pathologic and family study of a black mother and son with axial osteomalacia associated with polycystic liver and kidney disease. Investigation of the son suggested that radiographic osteosclerosis can be detected in early adulthood. Limited skeletal survey of his three children revealed no abnormalities. Examination of undecalcified iliac crest bone after in vivo tetracycline labeling revealed severe osteomalacia in the son despite normal circulating calcium, inorganic phosphate and vitamin D metabolite levels and persistently elevated alkaline phosphatase activity. Although osteoblasts appeared flat and inactive, histochemical studies showed intense alkaline phosphatase activity in the osteoblasts along most trabecular bone surfaces. Electron microscopy revealed intact matrix vesicles within unmineralized osteoid. The presence also of unexplained myopathy in the son--characterized by proximal muscle weakness, persistently elevated circulating creatine phosphokinase levels and pathogenic changes of myopathy on biopsy of quadriceps muscle--together with impaired bone mineralization, suggests that a disorder of vitamin D action may be involved in the pathogenesis of this unusual condition. Axial osteomalacia affects blacks as well as Caucasians, women as well as men, may be familial, and may perhaps be a developmental abnormality inherited in association with polycystic kidney and liver disease.
Estimating the Influence of Selection on the Variable Amino Acid Sites of the Cytochrome b Protein Functional Domains

We evaluated the effects of selection on the molecular evolution of the functional domains of the mammalian cytochrome b gene as it relates to physicochemical properties shown to correlate with rates of amino acid replacement. Two groups of mammals were considered: pocket gophers of the rodent family Geomyidae, and cetaceans and ungulates of the monophyletic taxon Cetartopdactyla. Several characteristics of cytochrome b evolution were common to both mammal groups. The evolution of the matrix domain reflected the region's relative lack of function. Goodness of fit to neutral expectations indicated that external influences have had very little effect on the evolution of the matrix, although in some cases conservative and moderate changes have been favored. Although rates of synonymous nucleotide substitution have been relatively high, the transmembrane domain exhibited poor goodness of fit to neutral expectations. However, the evolution of the transmembrane domain has been constrained by negative selection, allowing a preponderance of conservative and moderate amino acid replacements. We hypothesize that a high rate of substitution is maintained in spite of negative selection because the codons of the transmembrane coding region are predisposed to conservative changes in all amino acid properties. The evolutionary patterns of the intermembrane domain in pocket gophers and cetartiodactyls, however, were very different. Changes inferred from the pocket gopher phylogenetic tree exhibited a significant fit to neutral expectations for each of the amino acid properties. Changes inferred from the cetartiodactyl tree exhibited significant fit to neutral expectations for polarity and isoelectric point, but not for composition, molecular volume, polar requirement, or hydropathy. In each case, lack of fit was due to selection that promoted conservative or moderate change, with the noteworthy exception of polar requirement. We detected an unexpectedly large change in polar requirement (from aspartic acid to threonine) in two separate lineages (Camelus bactrianus and all cetaceans) at amino acid position 159. This inferred change occurred in a region of the cyt-b protein that directly interacts with external surface proteins of the cytochrome bc(1) complex and resulted in a reversion to a more common character state in vertebrates.
Electrothermal analysis: A neglected thermal analysis technique?

Abstract This is a review of the electrothermal analysis (ETA) techniques used in this author's laboratory during the past 10–14 years. Most of the ETA techniques employed the detection and measurement of the d.c. or a.c. current flow through the sample as a function of temperature. These measurements, at constant EMF, varied with the change of resistance of the system; the latter being dependent on the nature of the thermal reaction being investigated. A new technique, thermovoltaic detection (TVD), in which the EMF of the reacting system in contact with two dissimilar electrodes is recorded as a function of temperature, is also described.
ROLES OF SURFACE HYDROPHOBIC RESIDUES IN THE INTERFACIAL CATALYSIS OF BOVINE PANCREATIC PHOSPHOLIPASE A2

The interfacial binding is a unique and important step in the phospholipase A2 (PLA2) catalyzed hydrolysis of phospholipids which is distinct from the binding of a substrate to the active site. To ...
In Vivo Visualization of Mismatch Repair in Bacillus Subtilis using Single-Molecule Fluorescence Microscopy

The high fidelity of DNA replication is vital to genomic integrity and ultimately to the survival of species. Errors occurring during DNA replication can have severe consequences such as producing certain types of cancers, and the correction of these errors is carried out by various DNA repair systems, one of which is the mismatch repair (MMR) system that exists in both prokaryotes and eukaryotes. Mismatched nucleotides are recognized by MutS, an MMR system protein that first binds to the mismatched DNA and then recruits other MMR proteins responsible for the downstream repair process. Despite its crucial role in this process, little is known about how MutS first locates mismatched base pairs. Two competing models have been proposed in the literature: the replisome-associated model argues that MutS is bound to and travels with the replication fork and can bind mismatches immediately as they are produced, while the scanning model states that MutS binds and scans the DNA strands on its own to search for mistakes long after the DNA polymerase complex has synthesized DNA. To address this question, we apply single-molecule fluorescence microscopy to reveal the in vivo distributions and dynamics of MutS and the replisome in live Bacillus subtilis bacterial cells. Based on photoactivated localization microscopy (PALM), PAmCherry-labeled MutS and mCitrine-labeled DnaX (a subunit of the replisome) are tracked with nanometer-scale precision to reveal the spatial relationship between these two as well as their motional correlations. Our preliminary results suggest transient yet significant co-localization between MutS-PAmCherry and DnaX-mCitrine and thus support the replisome-associated model.
Allometric patterns in Acer platanoides (Aceraceae) branches

Acer platanoides L. individuals were dissected to determine if branch allometry changed as branches increased in length. Branches were found to transition from a log–log curvilinear relationship to a linear relationship when above 3,000 mm in length. The log–log linear relationship was best modeled with the elastic similarity model. The total number of subordinate lateral branches was found to increase rapidly after the primary branch length surpassed 3,000 mm, suggesting that branches are transitioning to a structural role as size increases. The shift in allometry appears to correspond to a shift from increasing slenderness ratio (length/radius) with increasing branch length to decreasing ratio, and is likely due to a transition from flexible sun branches to stiffer structural branches.
Retinal projections in the Northern Water snake Natrix sipedon sipedon (L.).

Retinal projections were studied experimentally in the Northern water snake using modifications of the Nauta silver impregnation technique. Contralaterally, the retina projects to nucleus geniculatus lateralis pars dorsalis and pars ventralis, nucleus lentiformis mesencephali and nucleus geniculatus pretectalis. A sparse projection was also observed to nucleus ovalis. An additional afferent thalamic projection to nucleus ventrolateralis was found in two cases. The retina projects ipsilaterally to the dorsolateral portion of nucleus geniculatus lateralis pars dorsalis, and sparsely to nucleus lentiformis mesencephali and nucleus geniculatus pretectalis. Nucleus posterodorsalis receives dense bilateral retinal projections. Contralaterally, the retina also projects to the superficial layers of the tectum (layers 8–13 of Ramon) and to nucleus opticus tegmenti. Armstrong's findings that the retinal projections in Natrix are qualittatively similar to those in lizards were confirmed. However there are marked quantitative differences among the various pathways and their corresponding nuclei. These differences are particularly striking in comparing the visual projections to the dorsal thalamus, the retino-tecto-rotundal and the retino-geniculate systems. The first is reduced in volume and the second is markedly increased in volume in comparison with lizards. These data lend support to the theories of Walls that snakes evolved from fossorial lizards and of Underwood that the eyes of these lizards underwent reduction but not complete degeneration. Qualitatively the retinal projections are conservative among lizards and snakes, but a history of reduction of these pathways in ancestral snakes with a selective increase in the retino-geniculate system as a surface niche was reattained is reflected in the anatomy of this ophidian visual system.
Intrinsic volumes and linear contractions

It is shown that intrinsic volumes of a convex body decrease under linear contractions. Let C ⊂ R be a convex body and B 2 the Euclidean ball in R . The Steiner formula expresses the volume of the Minkowski sum C + eB 2 in terms of the intrinsic volumes V0, V1, . . . , VN of C: volN ( C + eB 2 ) = N ∑ n=0 ωnVN−n(C)e . Here volN (·) denotes N -dimensional Lebesgue measure and ωn = voln (B 2 ). Of particular interest are V1, VN−1 and VN , which are multiples of the mean-width, surface area and volume, respectively. We refer the reader to [5] for background on intrinsic volumes. In addition to their role in convex geometry, intrinsic volumes also appear in connection with Gaussian processes; see, e.g., [9], [10] and the references therein. The purpose of this note is to prove the following. Proposition 1.1. Let C ⊂ R be a convex body and let S be a linear contraction, i.e., ‖Sx‖2 6 ‖x‖2 for each x ∈ R . Then for n = 1, . . . , N , Vn(SC) 6 Vn(C). The case of V1 and arbitrary contractions (not necessarily linear) is well-studied [6, Theorem 2 in §5], [1, Theorem 1]; see also [2, pg 177]. Of course for VN one has VN(SC) = |det(S)| volN (C). For other intrinsic volumes, we were unable to find Proposition 1.1 in the literature but noticed that it follows from some results in [4] and thought it was worthwhile to show the details. ∗The first-named author is supported by the US National Science Foundation, grant DMS-0906150. †The second-named author holds a Postdoctoral Fellowship award from the Natural Sciences and Engineering Research Council of Canada.
Bombs, bodies, and biopolitics: securitizing the subject at the airport security checkpoint

The United States Transportation Security Administration (TSA) broadcasts the following warning in airports around the country: ‘Making jokes or statements regarding bombs and/or threats during the screening process may be grounds for both civil and criminal penalties and could cause you to miss your flight.’ Despite the warning, people continue to be arrested for making jokes about bombs, anthrax, and security policy. This paper examines the persistence of these disciplinary mechanisms in the context of the deterritorialized risk analysis, biometric identity banking, and ‘network thinking’ that characterize state security regimes. The article first describes how TSA has incorporated theories of complex adaptive systems, networks, and emergence into its strategy. Second, I trace how air travelers move through a series of risk analysis and inspection practices. By combining passenger pre-screening, check-in, visual inspection and ‘behavior observation,’ TSA seeks to surveil different spatiotemporal slices ...