cssi/SciSciGPT-SciSciNet huggingface dataset:
A non-catalytic role of choline kinase alpha is important in promoting cancer cell survival

Choline kinase alpha (ChoKα) is regarded as an attractive cancer target. The enzyme catalyses the formation of phosphocholine(PCho), an important precursor in the generation of phospholipids essential for cell growth. ChoKα has oncogenic properties and is critical for the survival of cancer cells. Overexpression of the ChoKα protein can transform noncancer cells into cells with a cancerous phenotype, and depletion of the ChoKα protein can result in cancer cell death. However, the mechanisms underlying the tumourigenic properties of ChoKα are not fully understood. ChoKα was recently demonstrated to associate with other oncogenic proteins, raising the possibility that a non-catalytic protein scaffolding function drives the tumourigenic properties of ChoKα rather than a catalytic function. In order to differentiate these two roles, we compared the impact on cancer cell survival using two tools specific for ChoKα: (1) small interfering RNA (siRNA) to knockdown the ChoKα protein levels; and (2) compound V-11-0711, a novel potent and selective ChoKα inhibitor (ChoKα IC50 20 nM), to impede the catalytic activity. Both treatments targeted the endogenous ChoKα protein in HeLa cells, as demonstrated by a substantial reduction in the PCho levels. siRNA knockdown of the ChoKα protein in HeLa cells resulted in significant cell death through apoptosis. In contrast, compound V-11-0711 caused a reversible growth arrest. This suggests that inhibition of ChoKα catalytic activity alone is not sufficient to kill cancer cells, and leads us to conclude that there is a role for the ChoKα protein in promoting cancer cell survival that is independent of its catalytic activity.
Expression of Adiponectin and Its Receptors Is Altered in Epithelial Ovarian Tumors and Ascites-Derived Ovarian Cancer Cell Lines

Objectives Recent evidence suggests that higher body mass index is associated with a modest increase in ovarian cancer risk. Reduced serum levels of adiponectin are correlated with obesity and increased cancer risk. The objectives of the present study are to determine if expressions of adiponectin and its receptors, AdipoR1 and AdipoR2, are altered in epithelial ovarian tumors and ascites-derived ovarian cancer cell lines and to determine if plasma adiponectin levels are altered in the chicken model of ovarian cancer. Methods Adiponectin, AdipoR1, and AdipoR2 mRNA concentrations in ovaries and chicken ovarian cancer (COVCAR) cell lines were determined by quantitative real-time polymerase chain reaction analysis. Existence of adiponectin isoforms in the ovaries and COVCAR cells was identified by nondenaturing gel electrophoresis. Adiponectin, AdipoR1, and AdipoR2 protein amounts were determined by Western blot analysis. Plasma total adiponectin levels were determined by an enzyme immunoassay. Results Adiponectin, AdipoR1, and AdipoR2 mRNA concentrations were significantly lower in cancerous ovaries and COVCAR cell lines compared with normal ovaries and normal ovarian surface epithelial (NOSE) cells, respectively. Adiponectin in ovary and COVCAR cell lines appeared as a heavy-molecular-weight isoform that is greater than 720-kd mass. In addition, a lower-molecular-weight adiponectin isoform was found in COVCAR cells but not in NOSE cells. Adiponectin and AdipoR1 protein concentrations were not different in COVCAR cell lines compared with NOSE cells. However, AdipoR2 protein concentrations were significantly higher in cancerous ovaries but lower in COVCAR cell lines compared with normal ovaries and NOSE cells, respectively. Plasma adiponectin concentrations were not different in chickens that had ovarian carcinoma compared with control animals. Conclusions Expression of adiponectin in ovarian tumors and in metastatic ovarian tumor cells is likely to affect cellular metabolism and proliferation through activating AdipoR1 and/or AdipoR2. Plasma adiponectin levels may not be predictive of advanced stages of ovarian tumor in the chicken model.
Aneuploidy and isochromosome formation in drug-resistant Candida albicans

Resistance to the limited number of available antifungal drugs is a serious problem in the treatment of Candida albicans. We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of chromosome 5, were associated with azole resistance. The isochromosome forms around a single centromere flanked by an inverted repeat and was found as an independent chromosome or fused at the telomere to a full-length homolog of chromosome 5. Increases and decreases in drug resistance were strongly associated with gain and loss of this isochromosome, which bears genes expressing the enzyme in the ergosterol pathway targeted by azole drugs, efflux pumps, and a transcription factor that positively regulates a subset of efflux pump genes.
Rules for agrarian change: Negri Sembilan Malays and agricultural innovation

Introduction This paper explores receptivity to agrarian change in a Malay rice farming village in Negri Sembilan in 1958-59. Villagers, who earlier were extremely resistant to agricultural change, were at that time experiencing an acceleration and con vergence of several trends, among them population growth, governmental attempts to introduce new techniques in food production and increasing reliance on cash crops to buy food. A gradual acceptance of agricultural change was beginning to occur1 but acceptance was highly selective and the basis of selectivity was not immediately apparent. This paper attempts to specify factors responsible for the selective use of new techniques as well as those crucial to overall change. Studies of the relationship between technical change and population growth have generally cast either one or the other as the determinative variable.2 However, neither an approach which assigns primacy to technology3 or to population4 ade quately conveys the complexities of the relationship between population, technologi cal change and culture. This is exemplified by Geertz's study of agricultural development in Indonesia which analyzes the importance of political, commercial and intellectual influences as well as ecological and population changes.5 It is also illustrated in Bender's comparison of the tropical forests of Africa and South America, two areas of the world similar in habitats and in agricultural techniques, but very different in population densities and levels of societal complexity. Bender suggests that factors such as the availability of cash crops and of labour for subsistence cultivation significantly affect both population growth and societal development.6
Perceptually guided expressive facial animation

Most of current facial animation approaches largely focus on the accuracy or efficiency of their algorithms, or how to optimally utilize pre-collected facial motion data. However, human perception, the ultimate measuring stick of the visual fidelity of synthetic facial animations, was not effectively exploited in these approaches. In this paper, we present a novel perceptually guided computational framework for expressive facial animation, by bridging objective facial motion patterns with subjective perceptual outcomes. First, we construct a facial perceptual metric (FacePEM) using a hybrid of region-based facial motion analysis and statistical learning techniques. The constructed FacePEM model can automatically measure the emotional expressiveness of a facial motion sequence. We showed how the constructed FacePEM model can be effectively incorporated into various facial animation algorithms. For the sake of clear demonstrations, we choose data-driven expressive speech animation generation and expressive facial motion editing as two concrete application examples. Through a comparative user study, we showed that comparing with the traditional facial animation algorithms, the introduced perceptually guided expressive facial animation algorithms can significantly increase the emotional expressiveness and perceptual believability of synthesized facial animations.
Typicality effects in artificial categories: Is there a hemisphere difference?

In category classification tasks, typicality effects are usually found: accuracy and reaction time depend upon distance from a prototype. In this study, subjects learned either verbal or nonverbal dot pattern categories, followed by a lateralized classification task. Comparable typicality effects were found in both reaction time and accuracy across visual fields for both verbal and nonverbal categories. Both hemispheres appeared to use a similarity-to-prototype matching strategy in classification. This indicates that merely having a verbal label does not differentiate classification in the two hemispheres.
Modeling the information-seeking behavior of social scientists: Ellis's study revisited

This paper revises David Ellis's information-seeking behavior model of social scientists, which includes six generic features: starting, chaining, browsing, differentiating, monitoring, and extracting. The paper uses social science faculty researching stateless nations as the study population. The description and analysis of the information-seeking behavior of this group of scholars is based on data collected through structured and semistructured electronic mail interviews. Sixty faculty members from 14 different countries were interviewed by e-mail. For reality check purposes, face-to-face interviews with five faculty members were also conducted. Although the study confirmed Ellis's model, it found that a fuller description of the information-seeking process of social scientists studying stateless nations should include four additional features besides those identified by Ellis. These new features are: accessing, networking, verifying, and information managing. In view of that, the study develops a new model, which, unlike Ellis's, groups all the features into four interrelated stages: searching, accessing, processing, and ending. This new model is fully described and its implications on research and practice are discussed. How and why scholars studied here are different than other academic social scientists is also discussed.
Dynamic Thermal and Timeliness Guarantees for Distributed Real-Time Embedded Systems

Distributed real-time embedded systems have stringent requirements for key performance properties, such as end-to-end timeliness and reliability, in order to operate properly. In recent years, with the continuously decreasing feature size and increasing demand for computation capabilities, today's real-time embedded systems face an increasing probability of overheating and even thermal failures. As a result, their temperature must be explicitly controlled for improved reliability. While a variety of control algorithms have been proposed for either real-time guarantees or thermal management in an isolated manner, this paper proposes a coordinated control solution that can provide simultaneous thermal and timeliness guarantees for distributed real-time embedded systems running in unpredictable environments. Our control solution features a novel coordination design, which allows the thermal and timeliness control loops to run on their respective desired small timescales for prompt control actions and yet achieve theoretically guaranteed control accuracy and system stability. In addition, while most existing work relies solely on simulations, we present empirical results on a physical testbed to demonstrate the efficacy of our control solution.
The Usefulness of Selection for Yield and Functional Type Traits

Abstract Udder depth, teat placement, foot angle, and milk yield measured in first lactation were evaluated in an index to improve a breeding goal consisting of milk yield and involuntary culling. Efficiencies of response for full and reduced indices were calculated for various economic values and genetic parameters from the literature. Sire and individual (based only on cow's performance) indices were calculated. Selection only for milk would result in 87 to 97% of the expected progress in the breeding goal when all four traits were included. Standardized b-values (index coefficients) for milk were about two to three times the sum of the standardized b-values for the type traits. Predicted response in the aggregate genotype was sensitive to genetic correlations between involuntary culling and type traits. Predicted response was insensitive to small changes in heritability for involuntary culling or changes in genetic correlations between milk and type traits. Selection on udder traits, foot angle, and production would result in only a small increase in efficiency above selection on production alone. However, these type traits may help reduce involuntary culling or limit correlated increases in involuntary culling associated with increased milk yield.
Laboratory Forum: Cavernous Nerve Injury Using Rodent Animal Models

ABSTRACT Introduction With the advance of the “nerve sparing” technique in radical pelvic surgeries, medically unaided rates of normal erectile function following surgery have improved. Precise determinations of post‐surgery erection recovery, however, continue to be problematic and rates of normal erectile function range from 9% to 86%. It is understood that injury to cavernous nerves (CNs) occurs despite modern modifications of the surgery, although the precise pathophysiologic mechanisms of surgical erectile dysfunction are not completely understood. Aim To describe the experimental models of CN injury in small rodents, including both survival surgery (CN injury) and non‐survival surgery (monitoring of intracavernosal pressure and arterial blood pressure) models. We also summarize studies on experimental procedures relating to these CN injury models and critique techniques according to their advantages and disadvantages. Main Outcome Measure Data from a peer review literature search on the topic of CN injury in rodent models. Methods A comprehensive review of the literature was performed using PubMed. “Cavernous nerve injury” and “animal model” were used as search terms, and a manual bibliographic review of cross‐referenced items was performed. Results Assorted molecular, morphological, and physiological changes are measurable after CN injury in rodent models. Conclusion Various models of CN injury have been applied successfully and offer insights regarding erectile function recovery effects. Canguven O, and Burnett A. Cavernous nerve injury using rodent animal models. J Sex Med 2008;5:1776–1785.
Grafting starch xanthate with vinyl monomers and hydrogen peroxide in foam rubber production

Starch xanthate with degrees of substitution (D.S.) ranging from 0.12 to 0.56 reacted with vinyl monomers (acrolein, acrylarnide, acrylic acid, acrylonitrile, methyl acrylate, or styrene) and hydrogen peroxide to form aqueous gels of starch-polyvinyl monomer graft copolymer. The same reactions conducted in a rubber latex medium resulted in a self-acidifying, self-heating, and self-foaming coagulation to give a foam rubber. Such products were formed from several synthetic latices (NBR, SBR, polyisoprene, and polychloroprene types) and natural rubber latex; noted for each were the effects of the D.S., of monomer and peroxide concentrations, and of starch:elastomer ratios. The dried foams were evaluated by standard strength tests. Foam rubber of acceptable extensibility and enhanced tensile strength (up to 110 psi) was obtained with 0.12-0.15 D.S. xanthate and with proper balance of vinyl monomer, peroxide, and starch:elastomer ratio. Resilience was fair to good, but compression set was rather poor compared to most foam rubbers of general use.
2-D transform-domain resolution translation

The extensive use of discrete transforms in image and video coding suggests the investigation on filtering before downsampling (FBDS) and filtering after upsampling (FAUS) methods directly acting on the transform domain. We describe the "transform-damain resolution translation" technique that gives flexibility to resize windows of each video conferencing session for a server compositing without explicit decompression, spatial domain processing, and compression. We generalize transform-domain filtering (TDF) to include nonuniform and multirate cases to implement the transform-domain resolution translator. The former is defined as a TDF problem in which the original transform-domain is of different size from the target one, while the latter considers the implementation of sampling rate conversion in the transform-domain. The implementation architecture is based on a pipeline that involves matrix-vector product blocks and vector addition, but is not limited to particular hardware. Such techniques are particularly useful for fast algorithms for processing compressed images and video where transform coding is extensively used (e.g., in JPEG, H.261, MPEG-1, MPEG-2, and H.363).
Modification of a Volume-Overload Heart Failure Model to Track Myocardial Remodeling and Device-Related Reverse Remodeling

Purpose. To provide an ovine model of ventricular remodeling and reverse remodeling by creating congestive heart failure (CHF) and then treating it by implanting a left ventricular assist device (LVAD). Methods. We induced volume-overload heart failure in 2 sheep; 20 weeks later, we implanted an LVAD and assessed recovery 11 weeks thereafter. We examined changes in histologic and hemodynamic data and levels of cellular markers of CHF. Results. After CHF induction, we found increases in LV end-diastolic pressure, LV systolic and diastolic dimensions, wall thickness, left atrial diameter, and atrial natriuretic protein (ANP) and endothelin-1 (ET-1) levels; β-adrenergic receptor (BAR) and dystrophin expression decreased markedly. Biopsies confirmed LV remodeling. After LVAD support, LV systolic and diastolic dimensions, wall thickness, and mass, and ANP and ET-1 levels decreased. Histopathologic and hemodynamic markers improved, and BAR and dystrophin expression normalized. Conclusions. We describe a successful sheep model for ventricular and reverse remodeling.
A formal approach to designing secure software architectures

Software architecture plays a central role in developing software systems that provide basic functionality and satisfy critical properties such as reliability and security. However, little has been done to formally model software architectures and to systematically enforce required properties. We aim to propose a formal approach to designing secure software architectures. We use the software architecture model (SAM), a general software architecture model combining Petri nets and temporal logic, as the underlying formalism. Architecture design consists of the functionality part and the security part. Guidelines are proposed to design functionality of software architectures at both element level and composition level. Software security is enforced by stepwise refinement.
Software algorithm and hardware design for real-time implementation of new spectral estimator

Background: Real-time spectral analyzers can be difficult to implement for PC computer-based systems because of the potential for high computational cost, and algorithm complexity. In this work a new spectral estimator (NSE) is developed for real-time analysis, and compared with the discrete Fourier transform (DFT). Method: Clinical data in the form of 216 fractionated atrial electrogram sequences were used as inputs. The sample rate for acquisition was 977 Hz, or approximately 1 millisecond between digital samples. Real-time NSE power spectra were generated for 16,384 consecutive data points. The same data sequences were used for spectral calculation using a radix-2 implementation of the DFT. The NSE algorithm was also developed for implementation as a real-time spectral analyzer electronic circuit board. Results: The average interval for a single real-time spectral calculation in software was 3.29 μs for NSE versus 504.5 μs for DFT. Thus for real-time spectral analysis, the NSE algorithm is approximately 150× faster than the DFT. Over a 1 millisecond sampling period, the NSE algorithm had the capability to spectrally analyze a maximum of 303 data channels, while the DFT algorithm could only analyze a single channel. Moreover, for the 8 second sequences, the NSE spectral resolution in the 3-12 Hz range was 0.037 Hz while the DFT spectral resolution was only 0.122 Hz. The NSE was also found to be implementable as a standalone spectral analyzer board using approximately 26 integrated circuits at a cost of approximately $500. The software files used for analysis are included as a supplement, please see the Additional files 1 and 2. Conclusions: The NSE real-time algorithm has low computational cost and complexity, and is implementable in both software and hardware for 1 millisecond updates of multichannel spectra. The algorithm may be helpful to guide radiofrequency catheter ablation in real time.
William V. O'Brien

William V. O'Brien, Professor of Government Emeritus at Georgetown University, died on July 8, 2003, at his home in Washington of head injuries suffered in a fall.
Simultaneous motion-disparity estimation and segmentation from stereo

Both motion/structure estimation from monocular video and disparity estimation from still-frame stereo are known to be ill-posed problems. Further, because disparity varies by depth, and motion parameters are different for independently moving objects, they can both benefit from scene segmentation. To this effect, we present a framework for simultaneous motion and disparity estimation including scene segmentation in stereo video. In this formulation, pairs of disparity and motion parameter vector values are segmented into K regions, where within each region a single set of motion parameters is defined, and the disparity field is allowed to vary smoothly. The algorithm iterates between computing the maximum a posteriori probability (MAP) estimates of the disparity and segmentation fields conditioned on the present motion parameter estimates, and the maximum likelihood (hit) estimates of the motion parameters via simulated annealing (SA). Simulation results are provided. >
Management of diabetes mellitus in patients with chronic kidney disease

Glycemic control is essential to delay or prevent the onset of diabetic kidney disease. There are a number of glucose-lowering medications available but only a fraction of them can be used safely in chronic kidney disease and many of them need an adjustment in dosing. The ideal target hemoglobin A1c is approximately 7 % but this target is adjusted based on the needs of the patient. Diabetes control should be optimized for each individual patient, with measures to reduce diabetes-related complications and minimize adverse events. Overall care of diabetes necessitates attention to multiple aspects, including reducing the risk of cardiovascular disease, and often, multidisciplinary care is needed.
Monoclonal antibody confirmation of a primary leiomyoma of the testis.

Primary mesenchymal tumors of the testis are rare, with fewer than 30 cases reported in the world literature. Although the data are scant, primary mesenchymal testis tumors appear to exhibit the same clinical characteristics as their counterparts in other tissues and organs.' Leiomyoma has been reported throughout the genitourinary tract, yet it is extremely rare in the testis, with only 6 cases reported. Previous authors have based their diagnosis on nonspecific histological stains or gross histological analy~is.~,~ We report diagnostic confirmation of a testis leiomyoma using novel monoclonal antibodies. CASE RE PORT An 18-year-old man presented with a 3-year history of a painless right testicular mass. He denied any constitutional symptoms, weight loss, lower urinary tract symptoms or gynecomastia. Physical examination was remarkable for a 1 cm. indurated mass located over the upper pole of the right testis. Serum lactic dehydrogenase, a-fetoprotein and p-human chorionic gonadotropin were within normal limits. The chest x-ray was normal. Scrota1 ultrasound revealed a 1 cm. hypoechoic mass in the superomedial aspect of the right testis (fig. 1). Inguinal exploration with wedge resection of the mass was performed. A frozen section of the mass was interpreted as a spindle cell neoplasm of uncertain malignant potential and radical orchiectomy was completed. Followup was uneventful 1 year after surgery. DISCUSSION Previously, the diagnosis of a primary testis leiomyoma was based on nonspecific histological stain^,^,^ which leads to uncertainty with regard to neoplasm identity, especially in view of its rarity. In our case actin specific monoclonal antibodies were used to detect smooth muscle specific actin in the neoplastic cells (fig. 2). Previous study has proved that the monoclonal antibodies used in our case (clone 14A and HHF 35) reliably mark the product of the a and y isoactin genes, thus detecting neoplastic cells of smooth muscle origin.4 The morphological appearance of the tumor did not reveal mitotic figures, hemorrhage or necrosis, thus supporting the diagnosis of a clinically benign leiomyoma. The patient is diseasefree at 1 year postoperatively. Myoid cells, or potentially their progenitors, may give rise to these particular tumors in the testis. Myoid cells can be found in the tunica albuginea, tunica propria of the seminiferous tubules and smooth muscle of blood vessel walls. Testis leiomyomas most likely originate from the progenitors of smooth muscle cells and not the actual smooth muscle cells themselves. These progenitor cells remain to be identified.
Variability of Stratospheric Water Vapor Inferred from SAGE II, HALOE, and Boulder (Colorado) Balloon Measurements

Abstract The variability of stratospheric water vapor between 1996 and 2004 has been studied using multiyear measurements from the Stratospheric Aerosol and Gas Experiment II (SAGE II) version 6.2 dataset, the Halogen Occultation Experiment (HALOE) version 19 dataset, and the balloon-borne frost point hygrometer data record at Boulder, Colorado (40°N, 105°W). The features derived from SAGE II and HALOE for 20° latitudinal zones from 60°S to 60°N at various altitudes (16–34 km) show good quantitative agreement regarding the phases and magnitudes of annual, semiannual, and quasi-biennial oscillations (QBO). For the latitudinal zones 20°–40° and 40°–60°, the hemispheric asymmetry at 22 km with mainly QBO in the north and predominantly annual oscillations in the south has been revealed by both SAGE II and HALOE observations. Strong correlation exists between SAGE II and HALOE lower-stratospheric H2O anomalies over low latitudes and 100-hPa tropical zonal mean temperature anomalies. The correlation coefficient...
Optimal estimation in DNA microarrays via global optimization

DNA microarray technology relies on affinity between complementary nucleic acids to detect the presence and estimate the amounts of target molecules of interest. Molecular binding is stochastic in nature, having inherent uncertainty manifested as Poisson noise. This, along with interference due to non-specific binding, are among the main obstacles for achieving high accuracy of DNA microarrays. In this paper, optimal target estimation in DNA microarrays is shown to lead to a fractional program. A practically feasible approach which employs a branch-and-bound algorithm solving a convex optimization problem in each step is presented. Simulation results demonstrate that the proposed approach outperforms previously considered methods.
Anomalous septal perforator artery: a source for supportive circulation in severe coronary artery disease--case reports.

Anomalous origin of a septal perforator artery is an infrequent angiographic finding. However, its recognition is important in patients with coronary artery disease in order to avoid misdiagnosis and consequent management mistake. In 2 patients, coronary arteriography demonstrated an anomalous septal perfora tor artery supplying significant blood flow to a myocardial region previously perfused by a severely obstructed major coronary vessel. It appears that an anomalous septal artery can serve as an important source for supportive circu lation in severe coronary artery disease.
A Consequence For Random Polynomials of a Result of De La Peña and Montgomery-Smith

The object of this note is to bring attention to the fact that the remarkable theorem of de la Pena and Montgomery-Smith (1995) on decoupling of tail probabilities of U-statistics implies results, which are best possible up to constants, on decoupling inequalities for tail probabilities of 1) general polynomials in independent normal variables and 2) tetrahedral polynomials in any set of not necessarily symmetric independent random variables. Although these results follow extremely easily from their theorem, I believe they should be recorded because they constitute essentially final answers to questions that have been extensively treated in the literature.
Simple and fast trip generation for large scale traffic simulation

A large-scale traffic simulator with microscopic model requires trip generation for millions of vehicles. To achieve a realistic result, the trip generation should provide a variety of trips between pairs of locations from Origin-Destination (OD) table reflecting the choices of drivers. Shortest paths take long time to generate and often differ from the choices of drivers. We propose a simple and fast tree-based algorithm in this paper. Our algorithm mixes shortest path trees starting from some location nodes in each subarea of the OD table as preprocessing and then generates trips by probabilistically traversing the mixed shortest path trees. Experiments reveal that the tree-based algorithm runs much faster than the naive one. We also confirm that, under certain conditions on the granularity of the OD table, the results of simulation using trips generated by our algorithm do not differ much from traffic conditions observed in the real world.
Managing Up the Hierarchy: US Correctional Institutions and Differences in the Use of Influence Strategies

Abstract This study generated and tested hypotheses regarding the use of upward influence strategies and gender in a US prison system. The present study focused on the upward influence strategies used by male and female employees across ten different prisons. Kipnis and Schmidt’s Profile of Organizational Influence Strategies was administered to 201 state employees. The sample was 85 % African American and nearly equally distributed by gender. Data was analyzed for differences among demographic groups. Results show that males use Reason, Bargaining and Coalition strategies; whereas, females use Friendliness strategies more frequently to influence their boss. Implications for research on the choice of influence strategies between genders in a predominately African American population are explored.
α1-Adrenergic Receptors in the Mammalian Cochlea

Liu SY, Pitovski DZ, Shivapuja BG. α-adrenergic receptors in the mammalian cochlea. Acta Otolaryngol (Stockh) 1996; 116: 710-713.The presence of α1, -adrenergic receptors in the mammalian cochlea has previously been suggested by physiological experiments using antagonists specific to the receptor. However, the characterises of adrenergic receptors in the cochlea have not been described. by employing [H]-prazosin, high affinity, specific binding sites with characteristics of α1, -adrenergic receptors have now been identified and characterized in the chinchilla cochlea. Analysis of the specific [H]-prazosin binding indicates that prazosin binds to a single class of high-affinity sites with a dissociation constant, kd, of 2.9 10−9 M and a maximum number of binding sites, Bmax, of 30 fmol/mg dry tissue. Furthermore, the binding characteristics suggest that these receptors may be related to the microvasculature of the cochlea. These results provide a rational basis for the observed actions of a-adrenergic drug...
Dealing with Unusual Experiences: A Narrative Perspective on Organizational Learning

Experiences that do not fit squarely into known categories pose a challenge to notions of organizational learning that rely primarily on scientific or experiential approaches. Making sense of, responding to, and learning from such unusual experiences requires reflection and novel action by organizational actors. We argue that narrative development processes make this organizational learning possible. By developing narratives, organizational actors create situated understandings of unusual experiences, negotiate consensual meanings, and engage in coordinated actions. Through the accumulation of narratives about unusual experiences, an organization builds a memory with generative qualities. Specifically, through narratives, actors evoke memories of prior unusual experiences and how they were dealt with, and this generates new options for dealing with emerging unusual experiences. We outline a framework detailing how narrative development processes enable organizational learning from unusual experiences and conclude by summarizing how this approach differs from and yet builds upon scientific and experiential approaches to learning.
Nonlinear stabilization through long input delay—Part I: Forward complete systems

We present an approach for compensating input delay of arbitrary length in nonlinear control systems. This approach, which due to the infinite dimensionality of the actuator dynamics and due to the nonlinear character of the plant results in a nonlinear feedback operator, is essentially a nonlinear version of the Smith Predictor and its various predictor-based modifications for linear plants. Global stabilization in the presence of arbitrarily long delay is achieved for all nonlinear plants that are globally stabilizable in the absence of delay and that satisfy the property of forward completeness (which is satisfied by most mechanical systems, electromechanical systems, vehicles, and other physical systems).
Stress-related growth failure

and neuroendocrine syndrome that is reversible. They propose the descriptive term, hyperphagic short stature, to clearly separate it from the much larger group of children with psychosocial ills who present with poor growth and, commonly, malnutrition. The ability to discriminate a homogeneous group of children is an important contribution that will facilitate patient care and further research, which in turn might lead to substantive progress, perhaps over the next 25 years or so, in our understanding of this fascinating entity and our knowledge of how psychological and physiological factors interact.
An Overview of the Molecular Mechanisms of Recombinational DNA Repair

Recombinational DNA repair is a universal aspect of DNA metabolism and is essential for genomic integrity. It is a template-directed process that uses a second chromosomal copy (sister, daughter, or homolog) to ensure proper repair of broken chromosomes. The key steps of recombination are conserved from phage through human, and an overview of those steps is provided in this review. The first step is resection by helicases and nucleases to produce single-stranded DNA (ssDNA) that defines the homologous locus. The ssDNA is a scaffold for assembly of the RecA/RAD51 filament, which promotes the homology search. On finding homology, the nucleoprotein filament catalyzes exchange of DNA strands to form a joint molecule. Recombination is controlled by regulating the fate of both RecA/RAD51 filaments and DNA pairing intermediates. Finally, intermediates that mature into Holliday structures are disjoined by either nucleolytic resolution or topological dissolution.
Homicide Under the Michigan Revised Criminal Code

The law of homicide in Michigan, as in many states, is replete with obscure common law doctrines such as "malice aforethought," "premeditation and deliberation," "adequate provocation," "heat of passion," and "cooling time." These concepts are confusing and often misleading. The Michigan Revised Criminal Code (Proposed Code) abolishes them, offering instead clear and concise statutory language. This comment attempts to summarize that new code.
Mindfulness during romantic conflict moderates the impact of negative partner behaviors on cortisol responses

This study was designed to test whether romantic partners' mindfulness-present moment, nonjudgmental awareness-during a conflict discussion could buffer the effects of negative partner behaviors on neuroendocrine stress responses. Heterosexual couples (n=88 dyads) provided 5 saliva samples for cortisol assay during a laboratory session involving a conflict discussion task. Conflict behaviors were coded by outside observers using the System for Coding Interactions in Dyads, and partners rated their mindfulness during the task using the Toronto Mindfulness Scale. Interactions tested using multilevel modeling revealed that participants with higher levels of mindfulness during the conflict showed either quicker cortisol recovery or an absence of slowed recovery in the presence of more negative partner behaviors. Whereas the attitudinal component of mindfulness (curiosity) moderated effects of negative partner engagement in the conflict (i.e., attempts to control, coerciveness, negativity and conflict), the attentional component of mindfulness (decentering) moderated the effect of partner disengagement (i.e., withdrawal). These findings lend support to the idea that mindfulness during a stressful interaction can mitigate the physiological impacts of negative behaviors.
In situ-formed Li2S in lithiated graphite electrodes for lithium-sulfur batteries.

Rechargeable lithium–sulfur (Li–S) batteries have the potential to meet the high-energy demands of the next generation of batteries. However, the lack of lithium in the sulfur cathode requires the use of lithium metal anode, posing safety hazards. Use of Li2S as the cathode can eliminate this problem, but it is hampered by intrinsic challenges (e.g., high electrical resistivity and reactivity in air). We report here the use of a lithiated graphite electrode to chemically reduce in situ the polysulfide Li2S6 in liquid electrolyte to insoluble Li2S. The chemical reduction slowly draws lithium out of graphite, resulting in a reduction of the d002 spacing of graphite from 3.56 to 3.37 A and an increase in the open-circuit voltage of cells from 60 mV to 2.10 V after stabilizing over 6 days. X-ray photoelectron spectroscopic analysis shows 48.4% of sulfur in the polysulfide was converted to Li2S. The formed amorphous Li2S shows good cyclability with low charge overpotential. The results demonstrate that lithiat...
99 METABOLIC PHENOTYPING WITH POSITRON EMISSION TOMOGRAPHY FOR PREDICTION OF TUMOR RESPONSE TO THE EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR ERLOTINIB (TARCEVA).

Objectives Recent studies have demonstrated that inhibition of epidermal growth factor receptor (EGFR) kinase activity rapidly reduces tumor glucose metabolism in sensitive cell lines. This suggests that imaging of tumor metabolism with positron emission tomography (PET) with the glucose analog [ 18 F]fluorodeoxyglucose (FDG) could be used clinically to monitor treatment with EGFR kinase inhibitors. In this study, I investigated whether EGFR kinase inhibition specifically affects glucose metabolism or whether it also affects lipid and amino acid metabolism. In doing so, I am attempting to determine the best PET tracers to identify malignancies responding to EGFR kinase inhibitors in the clinics. Methods The lung cancer cell lines H3255 and A549 served as models for tumors that are sensitive and resistant to EGFR kinase inhibition, respectively. Glucose, amino acid, and lipid metabolism were studied by measuring the uptake of radiolabeled analogs of glucose, tyrosine, and choline. Uptake of these tracers was assayed in vitro after incubating cells with increasing doses of the EGFR kinase inhibitor erlotinib and in vivo by PET imaging of tumor bearing mice before and after erlotinib treatment. In vitro blocking studies with specific reagents were performed to elucidate the mechanisms of tyrosine and choline uptake. Results In sensitive H3255 cells, erlotinib decreased glucose uptake 54 ± 2% within 4 hours, whereas tyrosine and choline uptake were unaffected. In resistant A549 cells, no reduction of tracer uptake was observed for any of the studied tracers. These in vitro findings were confirmed in H3255 xenografted mice, which demonstrated a selective reduction of glucose uptake by 50 ± 5% after two doses of erlotinib. In A549 xenografts, erlotinib had no measurable metabolic effects. In H3255 and A549 cells, 2-amino-2-norbornanecarboxylic acid, a specific inhibitor of l-type amino acid transport, reduced tyrosine uptake by 83 ± 1% and 75 ± 1%, and cold choline inhibited choline uptake with IC50s of 5 μM and 6 μM, respectively. Conclusion These observations suggest that efficacious erlotinib treatment specifically modulates glucose, but not amino acid or lipid metabolism, as EGFR kinase inhibition may not affect the l-type amino acid transport system or the high-affinity choline transport system. Thus, the glucose analog FDG is the most promising tracer for monitoring treatment with EGFR kinase inhibitors in the clinics.
Acetazolamide-Induced Renal Calculi

The occurrence of urinary calculi associated with acetazolamide therapy is described. Patients with a history of urinary stones or surgery are a significant risk for further calculus formation when treated with acetazolamide. The concurrent use of sodium bicarbonate further potentiates this risk.
Ojibwe Gichigami (“Ojibwa’s Great Sea”): an intersecting history of treaty rights, tribal fish harvesting, and toxic risk in Keweenaw Bay, United States

Ojibwe Gichigami (“Ojibwa’s Great Sea”) is the spirit name for Lake Superior; it is also the homeland of the Keweenaw Bay Indian Community (KBIC) where Gichigami fishing has sustained the people for nearly a millennia. As signatories to the 1842 Treaty With The Chippewa, the KBIC retain rights for hunting, fishing, and gathering, and worship within ten-million acres of ceded land and water territory. However, due to elevated levels of toxics such as methyl-mercury and polychlorinated-biphenyls (PCBs), Lake Superior is currently under numerous fish consumption advisories that inform the public of harmful contamination levels. Thus, harvesting provides socio-cultural and spiritual wellbeing for the KBIC, and simultaneously, places their physical health at great risk. By using ethnographic methods and oral histories, this article illustrates how an intersecting history of KBIC treaty rights, tribal fish harvesting, and toxic risk is the center of their water story. Over the course of several decades, they have encountered dire consequences due to federal assimilation policies, state regulatory control over their harvesting, and environmental degradation and contamination. KBIC present-day perspectives of toxic risk are rooted in this history. In 1971, the Michigan Supreme Court presented a landmark decision: the People v. Jondreau reaffirmed 1842 treaty rights for the KBIC. This precedential decision was followed by Great Lakes states issuing the nation’s first fish advisories. The KBIC historical context is imperative to understanding present day environmental policy and its relevance (or irrelevance) for those most at-risk, emphasizing how social injustices are manifested through a people’s water history.
Correlating Carrier Density and Emergent Plasmonic Features in Cu2–xSe Nanoparticles

Recently, a wide variety of new nanoparticle compositions have been identified as potential plasmonic materials including earth-abundant metals such as aluminum, highly doped semiconductors, as well as metal pnictides. For semiconductor compositions, plasmonic properties may be tuned not only by nanoparticle size and shape, but also by charge carrier density which can be controlled via a variety of intrinsic and extrinsic doping strategies. Current methods to quantitatively determine charge carrier density primarily rely on interpretation of the nanoparticle extinction spectrum. However, interpretation of nanoparticle extinction spectra can be convoluted by factors such as particle ligands, size distribution and/or aggregation state which may impact the charge carrier information extracted. Therefore, alternative methods to quantify charge carrier density may be transformational in the development of these new materials and would facilitate previously inaccessible correlations between particle synthetic r...
Strawson or Straw Man? More on Moral Responsibility and the Moral Community

In a recent article in this journal, I argued against the popular twofold Strawsonian claim that there can be no moral responsibility without a moral community and that, as a result, moral responsibility is essentially interpersonal. Benjamin De Mesel has offered a number of objections to my argument, including in particular the objection that I mischaracterized Strawson’s view. In this article, I respond to De Mesel’s criticisms.
Abstract #2436: Microarray analysis of the expression levels of molecular components of relevant signaling pathways in response to FUra/IFN-gamma treatment protocols in human colon carcinoma cell lines

Colon carcinoma is the third largest cause of death in United States. 5-Fluorouracil (FUra)-based chemotherapy has contributed significantly in improving the prognosis of this disease. Earlier studies performed in our laboratories have established the significant advantage of using FUra/ Leucovorin (LV) + IFN-gamma in obtaining selective and synergistic therapeutic action. In the current study, five different colon carcinoma cell lines (RKO, HT29, GC3, HCT8 and HCT116) were treated with different combinations of FUra/LV and IFN-gamma. A folate-based thymidylate synthase inhibitor (BGC9331) was also utilized in HCT116 cells that induced DNA damage in contrast to FUra/LV, which induced RNA mediated damage. All cell lines were treated for 24 hr and total RNA was isolated after harvesting the cells. All reactions were carried out in triplicate. Total RNA isolated from treated and control cell lines was used for carrying out Illumina cDNA microarray analysis (RF-8). The results obtained were analyzed using Beadstudio software available from Illumina (Gene Expression Analysis module). The data obtained were initially analyzed using Cluster analysis dendrograms to confirm the groups and subgroups of cell lines with different treatment designs. The data were validated using all four clustering metrics: Correlation, Absolute Correlation, Manhattan and Euclidian. Any outlier groups were eliminated from further analysis. Scatter analysis was used to determine genes that were significantly altered in their expression levels in response to a particular drug treatment or in combination. Bar plot analysis was conducted to visualize the change in expression level of a particular gene in response to different treatments in different cell lines. Of specific interest was that a significant reduction in levels of the thymidylate synthase gene expression was detected in response to IFN-gamma. The difference was most pronounced in RKO cells. Similarly other genes of interest are currently being studied individually including those known to be involved in the synergistic interaction between FUra, LV and IFN-gamma. We are also elucidating the differential expression of sets of genes known to be involved in important signaling pathways including Fas, Wnt and Hedgehog as well as elucidating gene signature(s) that will differentiate DNA damage (toxic to colon cancer cells) from RNA damage (that initiates GI toxicity). It is anticipated that these studies will improve our understanding of molecular targets for FUra-based therapy in colon cancer and will aid in elucidating novel drug targets that will be more effective and selective for colon cancer therapy. Supported by NCI awards CA32613 and CA108929 Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2436.