bluuebunny/crossref_metadata_2025 huggingface dataset:
Russian Phenomenology, or The Interrupted Flight
Authors: Kuznetsov Valery
Published: January 2013

In this article the author notes that Russian phenomenology has a long history that has contributed to European progress in philosophy. He presents the main ideas of Gustav Shpet, a well‐known Russian thinker and original follower of Husserl. The heart of Shpet's positive philosophy is a special, skeptical state of mind—hermeneutic phenomenology. This positive philosophy, with its synthesis of hermeneutics and phenomenology, opposes Kant's negative, relativistic thought. In his work, Shpet focuses on the concept of a text. A text's meaning is objective and grasped via the nonpsychological methods of hermeneutics. Language largely determines the development of the human spiritual world, and so the problematics of language merge with the problematics of consciousness. Because texts are human products that express the influence of linguistic consciousness, our understanding of texts should be based on the analysis of language consciousness. Shpet characterizes the whole culture as a sign‐symbolical, objectified expression of the human spirit.
Syntactical Constraints on Definitions
Authors: Jacquette Dale
Published: January 2013

This essay considers arguments for and against syntactical constraints on the proper formalization of definitions, originally owing to Alfred Tarski. It discusses and refutes an application of the constraints generalized to include a prohibition against not only object‐place but also predicate‐place variables in higher‐order logic in a criticism of a recent effort to define the concept of heterologicality in a strengthened derivation of Grelling's paradox within type theory requirements. If the objections were correct, they would offer a more general moral for the proper formal definition of terms in philosophical logic. The criticism nevertheless seems mistaken both in the substance and specific application with respect to legitimate synctactical constraints on definitions of key concepts in the case of Grelling's paradox. As such, the critique provides no justification for overturning previous conclusions concerning the possibility of resurrecting a type‐observant version of Grelling's heterologicality paradox.
Lies, Damned Lies, and Genocide
Authors: Nash‐Marshall Siobhan , Mahdessian Rita
Published: January 2013

This article analyzes the claim that “deliberate denial [of genocide] is a form of aggression that ought to be regarded as a contribution to genocidal violence in its own right.” Its objective is to demonstrate that the claim is substantially correct: there are instances of genocide negation that are genocidal acts. The article suggests that one such instance is contained in a letter sent to Professor Robert Jay Lifton by Turkey's ambassador to the United States. The article is divided into three parts. In the first part, it delineates and discusses the unexpected contents of the letter to Lifton. In the second, it primarily deals with three topics: lying, genocide, and Austinian performatives. In the third part, it takes the points made in the second part and applies them to the contents of the letter to Lifton, and demonstrates that the letter is an instance of genocide negation that is genocidal.
A P.S. on B.S.: Some Remarks on Humbug and Bullshit
Authors: Wreen Michael
Published: January 2013

While lies have attracted philosophical attention since antiquity, phenomena in the near area have generated considerably less interest. Lately, however, Max Black and Harry Frankfurt have visited a close relative: humbug or bullshit, as it's either more politely or more rudely called. In this article their views on humbug and bullshit are exposed, explained, critiqued, and, ultimately, rejected. An alternative view is then proposed and defended.
Intermittent therapy with terbinafine and nail abrasion for dermatophyte toe onychomycosis: a pilot study
Authors: Succi Isabella B. , Bernardes‐Engemann Andréa R. , Orofino‐Costa Rosane
Published: January 2013

Onychomycosis constitutes up to 50% of all nail disorders. Toenails are generally affected, mostly due to dermatophytes. Terbinafine is the most potent antifungal agent in vitro against dermatophytes. There are few randomised controlled trials using a non‐continuous dose of terbinafine. The aim of this open‐label pilot study was to reduce the total drug amount, the collateral effects and, specially, the costs; albeit maintaining the same efficacy of the standard regimens. Compare the outcomes of two different intermittent regimens with the same total amount of the medication (42 tablets in 6 months). Forty‐one patients were divided into the following groups: terbinafine 250 mg day−1, for 7 days, monthly or terbinafine 500 mg day−1, once daily, for 7 days, every 2 months, both plus nail abrasion during 6 months. The efficacy was evaluated at months 6, 12 and 18 using the disease free nail criteria. Total cure = group I: eight patients (44.4%) and group II: eight patients (44.4%). Partial cure = group I: five patients (27.8%) and group II: four patients (22.2%). Treatment failure = group I: five patients (27.8%) and group II: three patients (16.7%). Recurrence = group I: zero patients (0.0%) and group II: three patients (16.7%). Two intermittent dosing regimens of terbinafine plus nail abrasion proved to be an alternative statistically effective, safe and with reduced drug costs for dermatophytes toenail onychomycosis.
Health Insurance in California, Its Effect on Public Health Nursing
Authors: Russell Marion E.
Published: January 2013

Health insurance coverage and the means by which it is paid have been topics of intense interest in recent years, but in the United States, creation of a uniform system for provision of medical care has been debated for nearly a century. During the Great Depression, before large group insurance plans, workers who formerly had been able to adequately support their families found themselves without employment or in low income jobs that barely put food on the table and a roof over their heads. Medical care was a luxury they could not afford. Health professionals suffered the effects of the economy too. Published in Public Health Nursing in 1936, this paper reflects a time period when the ravages of the Great Depression were manifest. California had received an influx of poor, migrant workers from other states hoping to provide for their families as pickers, canners, and manual laborers. The author, Marion E. Russell, described a 1935 health insurance proposal to cover all state residents. Selected excerpts illustrate differences in philosophy still evident in current considerations of national health care reform, particularly as related to mandated coverage. Russell worked in the State Relief Administration in San Francisco.
Mammal‐Derived Respiratory Lipocalin Allergens do not Exhibit Dendritic Cell‐Activating Capacity
Authors: Parviainen S. , Kinnunen T. , Rytkönen‐Nissinen M. , Nieminen A. , Liukko A. , Virtanen T.
Published: January 2013

Most mammal‐derived respiratory allergens belong to the lipocalin family of proteins. Determinants of their allergenic capacity are still unknown. Innate immune cells, in particular dendritic cells, have been shown to be involved in the allergenicity of some proteins. As recognition by dendritic cells is one of the few plausible mechanisms for the allergenicity of proteins, we wanted to investigate their role in the allergenicity of lipocalin allergens. Therefore, we first incubated human monocyte‐derived dendritic cells with immunologically functional recombinant allergens mouse Mus m 1, dog Can f 1 and 2, cow Bos d 2, horse Equ c 1 and natural Bos d 2. Then, the surface marker expression and cytokine production of dendritic cells and their capacity to promote T cell proliferation and Th2 immune deviation in naïve CD4+ T cells were examined in vitro. We found that near to endotoxin‐free lipocalin allergens had no effect on the activation, allostimulatory capacity or cytokine production of dendritic cells. The dendritic cells could not induce immune deviation in naïve CD4+ T cells. In contrast, lipopolysaccharide activated the dendritic cells efficiently. However, lipocalin allergens were not able to modify the lipopolysaccharide‐induced responses. We conclude that an important group of mammal‐derived respiratory allergens, lipocalins, appear not to be able to activate dendritic cells, a major component involved in the allergenicity of some proteins. It is conceivable that this incapacity of lipocalin allergens to arouse innate immunity may be associated with their poor capacity to induce a strong T cell response, verified in several studies.
Pro‐IL‐16 is Associated withMHCClassII‐Mediated Negative Regulation of Mouse Resting B Cell Activation throughMAPKinases,NF‐κB and Skp2‐Dependent p27kipRegulation
Authors: Yang H.‐Y. , Kim J. , Kim S.‐H. , Choe C.‐H. , Jang Y.‐S.
Published: January 2013

MHCclassIImolecules, in addition to their essential role as antigen‐presenting molecules toCD4+T cell receptor, have a signal‐transducing role related to B cell function. We identified pro‐IL‐16 as one of the proteins associated withMHCclassII‐mediated signalling in an analysis ofMHCclassII‐associated molecules using immunoprecipitation and proteomics data obtained from the 38B9 resting B cell line, and investigated the role of pro‐IL‐16 in resting B cell activation. We found that pro‐IL‐16, rather than mature form ofIL‐16, is present both in the cytoplasm and nucleus of resting B cells, and its expression is influenced byMHCclassII‐mediated signalling. In addition, overexpression of pro‐IL‐16 impaired resting B cell proliferation and this inhibitory effect was mediated through regulating nuclear factor (NF)‐κB activation. Knock‐down of pro‐IL‐16 expression using siRNAdecreased the level of cell‐cycle inhibitor p27kipand increased the level of Skp2. In addition, knock‐down of pro‐IL‐16 modulated mitogen‐activated protein kinase activation. Given thatIL‐16 acts as an immunomodulator by impairing antigen‐induced T cell activation and its precursor, pro‐IL‐16, plays a role in regulating the cell cycle in T lymphocytes and T cell lymphoma, we concluded that pro‐IL‐16 is involved in resting B cell proliferation, similar to its function in T lymphocytes.
At‐home resistance tubing strength training increases shoulder strength in the trained and untrained limb
Authors: Magnus C. R. A. , Boychuk K. , Kim S. Y. , Farthing J. P.
Published: January 2013

The purpose was to determine if an at‐home resistance tubing strength training program on one shoulder (that is commonly used in rehabilitation settings) would produce increases in strength in the trained and untrained shoulders via cross‐education. Twenty‐three participants were randomized to TRAIN (strength‐trained one shoulder; n = 13) or CONTROL (no intervention; n = 10). Strength training was completed at home using resistance tubing and consisted of maximal shoulder external rotation, internal rotation, scaption, retraction, and flexion 3 days/week for 4 weeks. Strength was measured via handheld dynamometry and muscle size measured via ultrasound. For external rotation strength, the trained (10.9 ± 10.9%) and untrained (12.7 ± 9.6%) arm of TRAIN was significantly different than CONTROL (1.6 ± 13.2%; −2.7 ± 12.3%; pooled across arm; P < 0.05). For internal rotation strength, the trained (14.8 ± 11.3%) and untrained (14.6 ± 10.1%) arm of TRAIN was significantly different than CONTROL (6.4 ± 11.2%; 5.1 ± 8.8%; pooled across arm; P < 0.05). There were no significant differences for scaption strength (P = 0.056). TRAIN significantly increased muscle size in the training arm of the supraspinatus (1.90 ± 0.32 to 1.99 ± 0.31 cm), and the anterior deltoid (1.08 ± 0.37 to 1.21 ± 0.39 cm; P < 0.05). This study suggests that an at‐home resistance tubing training program on one limb can produce increases in strength in both limbs, and has implications for rehabilitation after unilateral shoulder injuries.
Thinking Outside the Disciplinary Box in Coping with Dilemmas in Geoinformation Management for Public Policy
Authors: de Man W.H. Erik
Published: January 2013

Notwithstanding optimistic rhetoric about integrating geospatial data from different sources and supporting good governance, much of the literature on geoinformation management is limited to a technical orientation with a positivist paradigm. Complex geoinformation management, like public policy, must go beyond these boundaries. The article calls attention to the underexposed role of dilemmas in geoinformation management and how to cope with them. It uses lessons from the development of ‘integrated surveys’ at the former International Training Centre for Aerial Survey (ITC) in TheNetherlands as an early and practical case of managing geoinformation for public policy some 40 years ago. These lessons are apparently also relevant to modern digital geoinformation management, as inSDI. Focus on public policy requires not only integration of geospatial data from different sources but also integration of geoinformation into complex decision‐making processes. This complexity probably creates dilemmas because of mutually incompatible perspectives between different actors on what is to be managed. Geoinformation management for public policy therefore requires the ability to find, over and over again, a common ground between and beyond incompatible perspectives. The article proposes a ‘transdisciplinary’ framing of geoinformation management to support the required thinking outside the box.
Using Pattern‐oriented Modeling (POM) to Cope with Uncertainty in Multi‐scale Agent‐based Models of Land Change
Authors: Magliocca Nicholas R. , Ellis Erle C.
Published: January 2013

Local land‐use and ‐cover changes (LUCCs) are the result of both the decisions and actions of individual land‐users, and the larger global and regional economic, political, cultural, and environmental contexts in which land‐use systems are embedded. However, the dearth of detailed empirical data and knowledge of the influences of global/regional forces on local land‐use decisions is a substantial challenge to formulating multi‐scale agent‐based models (ABMs) of land change. Pattern‐oriented modeling (POM) is a means to cope with such process and parameter uncertainty, and to design process‐based land change models despite a lack of detailed process knowledge or empirical data.POMwas applied to a simplified agent‐based model ofLUCCto design and test model relationships linking global market influence to agents’ land‐use decisions within an example test site. Results demonstrated that evaluating alternative model parameterizations based on their ability to simultaneously reproduce target patterns led to more realistic land‐use outcomes. This framework is promising as an agent‐based virtual laboratory to test hypotheses of how and under what conditions driving forces of land change differ from a generalized model representation depending on the particular land‐use system and location.
Does Indeterminacy Matter?
Authors: Buford Christopher T.
Published: January 2013

Derek Parfit has offered numerous arguments in an attempt to establish that identity is not what matters. Jens Johannson has recently argued that Parfit's various arguments for the claim that identity is not what matters fail to establish what Parfit takes such arguments to establish. Johannson contends that this is due in part to the invalidity of one of Parfit's key arguments, and the fact that Parfit ignores a position that is compatible with the conclusions of his successful arguments and the claim that identity is in fact what matters, namely, that I survive fission as either one of the fission products or the other, but it is indeterminate which one I survive as. I aim to establish here that both of Johannson's assertions are problematic. As a corollary of this task, I hope to shed some light on the relationship between indeterminacy and fission‐based arguments for the claim that identity is not what matters.
Editorial: Can we afford to overlook hand hygiene again?
Authors: Greenland Katie , Cairncross Sandy , Cumming Oliver , Curtis Valerie
Published: January 2013

L'accès à l'eau potable et fiable et à l'assainissement, Objectif 7 du Millénaire pour le Développement, cible 7c, est essentiel pour la santé et le bien‐être et est reconnu comme un droit humain. L'hygiène offre de nombreux avantages pour la santé, liés à l'eau et à l'assainissement et pourtant elle est encore absente des Objectifs du Millénaire pour le Développement. En 2013, l'Assemblée Générale des Nations Unies se réunira pour convenir des objectifs et cibles de développement durable postérieurs à 2015. La santé ne devrait pas être mise à l’écart de ce processus.
The Aquilegia FRUITFULL‐like genes play key roles in leaf morphogenesis and inflorescence development
Authors: Pabón‐Mora Natalia , Sharma Bharti , Holappa Lynn D. , Kramer Elena M. , Litt Amy
Published: January 2013

The APETALA1/FRUITFULL (AP1/FUL) MADS box transcription factors are best known for the role of AP1 in Arabidopsis sepal and petal identity, the canonical A function of the ABC model of flower development. However, this gene lineage underwent multiple duplication events during angiosperm evolution, providing different taxa with unique gene complements. One such duplication correlates with the origin of the core eudicots, and produced the euAP1 and euFUL clades. Together, euAP1 and euFUL genes function in proper floral meristem identity and repression of axillary meristem growth. Independently, euAP1 genes function in floral meristem and sepal identity, whereas euFUL genes control phase transition, cauline leaf growth and fruit development. To investigate the impact of the core eudicot duplication on the functional diversification of this gene lineage, we studied the role of pre‐duplication FUL‐like genes in columbine (Aquilegia coerulea). Our results show that AqcFL1 genes are broadly expressed in vegetative and reproductive meristems, leaves and flowers. Virus‐induced gene silencing of the loci results in plants with increased branching, shorter inflorescences with fewer flowers, and dramatic changes in leaf shape and complexity. However, aqcfl1 plants have normal flowers and fruits. Our results show that, in contrast to characterized AP1/FUL genes, the AqcFL1 loci are either genetically redundant or have been decoupled from the floral genetic program, and play a major role in leaf morphogenesis. We analyze the results in the context of the core eudicot duplication, and discuss the implications of our findings in terms of the genetic regulation of leaf morphogenesis in Aquilegia and other flowering plants.
Gating of long‐term depression by Ca2+/calmodulin‐dependent protein kinase II through enhanced cGMP signalling in cerebellar Purkinje cells
Authors: Kawaguchi Shin‐ya , Hirano Tomoo
Published: January 2013

Key points

Long‐term depression (LTD) at parallel fibre synapses on a cerebellar Purkinje cell has been regarded as a cellular basis for motor learning.

Although Ca2+/calmodulin‐dependent protein kinase II (CaMKII) has been implicated in the LTD induction and motor learning, the underlying molecular mechanism remains unclear.

By combined application of simulation and experiments, we have attempted to explore the potential signalling pathway underlying the CaMKII involvement in LTD. Our data show that CaMKII supports the LTD‐inducing signalling pathway consisting of other protein kinases such as protein kinase C and mitogen‐activated protein kinase.

The gating of the LTD‐inducing pathway by CaMKII is mediated by negative regulation of phosphodiesterase 1, and the resultant facilitation of the cGMP/protein kinase G (PKG) pathway. As a result, protein phosphatase 2A activity was suppressed, supporting the LTD induction.

In addition, nitric oxide‐mediated cGMP/PKG activation compensated for the lack of CaMKII activation in LTD induction.

This study provides a comprehensive understanding of elaborate intracellular signalling mechanisms for LTD regulation.

Abstract  Long‐term depression (LTD) at parallel fibre synapses on a cerebellar Purkinje cell has been regarded as a cellular basis for motor learning. Although Ca2+/calmodulin‐dependent protein kinase II (CaMKII) has been implicated in the LTD induction as an important Ca2+‐sensing molecule, the underlying signalling mechanism remains unclear. Here, we attempted to explore the potential signalling pathway underlying the CaMKII involvement in LTD using a systems biology approach, combined with validation by electrophysiological and FRET imaging experiments on a rat cultured Purkinje cell. Model simulation predicted the following cascade as a candidate mechanism for the CaMKII contribution to LTD: CaMKII negatively regulates phosphodiesterase 1 (PDE1), subsequently facilitates the cGMP/protein kinase G (PKG) signalling pathway and down‐regulates protein phosphatase 2A (PP‐2A), thus supporting the LTD‐inducing positive feedback loop consisting of mutual activation of protein kinase C (PKC) and mitogen‐activated protein kinase (MAPK). This model suggestion was corroborated by whole‐cell patch clamp recording experiments. In addition, FRET measurement of intracellular cGMP concentration revealed that CaMKII activation causes sustained increase of cGMP, supporting the signalling mechanism of LTD induction by CaMKII. Furthermore, we found that activation of the cGMP/PKG pathway by nitric oxide (NO) can support LTD induction without activation of CaMKII. Thus, this study clarified interaction between NO and Ca2+/CaMKII, two important factors required for LTD.
Genetically encoded pH‐indicators reveal activity‐dependent cytosolic acidification of Drosophila motor nerve termini in vivo
Authors: Rossano Adam J. , Chouhan Amit K. , Macleod Gregory T.
Published: January 2013

Key points

Changes in pH occur within neurons during nerve activity and in response to hypoxic insult.

Many aspects of neurophysiology are potentially influenced by intracellular pH changes.

At the fruit fly larval neuromuscular junction, fluorescent genetically encoded pH‐indicators (GEpHIs) revealed significant cytosolic acidification of presynaptic termini during nerve activity.

GEpHIs revealed that presynaptic pH changes occur in live intact larvae, indicating for the first time that such pH changes are not an artifact of experimental conditions.

The pH changes in presynaptic termini are substantial and are likely to influence synaptic function.

Abstract  All biochemical processes, including those underlying synaptic function and plasticity, are pH sensitive. Cytosolic pH (pHcyto) shifts are known to accompany nerve activity in situ, but technological limitations have prevented characterization of such shifts in vivo. Genetically encoded pH‐indicators (GEpHIs) allow for tissue‐specific in vivo measurement of pH. We expressed three different GEpHIs in the cytosol of Drosophila larval motor neurons and observed substantial presynaptic acidification in nerve termini during nerve stimulation in situ. SuperEcliptic pHluorin was the most useful GEpHI for studying pHcyto shifts in this model system. We determined the resting pH of the nerve terminal cytosol to be 7.30 ± 0.02, and observed a decrease of 0.16 ± 0.01 pH units when the axon was stimulated at 40 Hz for 4 s. Realkalinization occurred upon cessation of stimulation with a time course of 20.54 ± 1.05 s (τ). The chemical pH‐indicator 2′,7′‐bis‐(2‐carboxyethyl)‐5‐(and‐6)‐carboxyfluorescein corroborated these changes in pHcyto. Bicarbonate‐derived buffering did not contribute to buffering of acid loads from short (≤4 s) trains of action potentials but did buffer slow (∼60 s) acid loads. The magnitude of cytosolic acid transients correlated with cytosolic Ca2+ increase upon stimulation, and partial inhibition of the plasma membrane Ca2+‐ATPase, a Ca2+/H+ exchanger, attenuated pHcyto shifts. Repeated stimulus trains mimicking motor patterns generated greater cytosolic acidification (∼0.30 pH units). Imaging through the cuticle of intact larvae revealed spontaneous pHcyto shifts in presynaptic termini in vivo, similar to those seen in situ during fictive locomotion, indicating that presynaptic pHcyto shifts cannot be dismissed as artifacts of ex vivo preparations.
Mathematical Modeling of Cutting Forces in Microdrilling
Authors: Sambhav Kumar , Tandon Puneet , Kapoor Shiv G. , Dhande Sanjay G.
Published: January 2013

In drilling, the primary and secondary cutting lips of the drill shear the material while the central portion of the chisel edge indents the workpiece, making the cutting process complex to understand. As we go for microdrilling, it exhibits an added complexity to the cutting mechanism as the edge radius gets comparable to chip thickness at low feeds. The presented work models the forces by the primary cutting lip of a microdrill analytically using slip-line field that includes the changes in the effective rake angle and dead metal cap during cutting for cases of shearing as well as ploughing. To study the variation of forces experimentally, the primary cutting lip and chisel edge forces are separated out by drilling through pilot holes of diameter slightly above the drill-web thickness. Finally, the analytical and experimental results are compared and the model is calibrated.
Evaluation of System-Directed Multimodal Systems for Vehicle Inspection
Authors: Cairco Dukes Lauren , Banic Amy Ulinski , McClendon Jerome , Bloodworth Pence Toni , Mathieson James , Summers Joshua , Hodges Larry F.
Published: January 2013

Multimodal systems have been previously used as an aid to improve quality and safety inspection in various domains, though few studies have evaluated these systems for accuracy and user comfort. Our research aims to combine our software interface designed for high usability with multimodal hardware configurations and to evaluate these systems to determine their user performance benefits and user acceptance data. We present two multimodal systems for using a novel system-directed interface to aid in inspecting vehicles along the assembly line: (1) wearable monocular display with speech input and audio output and (2) large screen display with speech input and audio output. We conducted two evaluations: (a) an experimental evaluation with novice users, resulting in accuracy, timing, user preferences, and other performance results and (b) an expert-based usability evaluation conducted on and off the assembly line providing insight on user acceptance, preferences, and performance potential in the production environment. We also compared these systems to current technology used in the production environment: a handheld display without speech input/output. Our results show that for visual and tactile tasks, benefits of system-directed interfaces are best realized when used with multimodal systems that reduce visual and tactile interaction per item and instead deliver system-directed information on the audio channel. Interface designers that combine system-directed interfaces with multimodal systems can expect faster and more efficient user performance when the delivery channel is different from channels necessary for task completion.
A Porous-Restricted Aerostatic Lead Screw Actuator for High Performance Microscale Machine Tools
Authors: Zhu James , Kapoor Shiv G. , DeVor Richard E. , Park Jong-Kweon
Published: January 2013

The design and manufacturing process for a porous-restricted aerostatic lead screw actuator (ALSA) is presented. The ALSA provides near-frictionless motion with submicron positioning accuracy, high stiffness at low inlet air pressures (<827 kPa), and a travel length of 50 mm. Porous graphite disk inserts are held in a helical pattern in an aerostatic nut housing against a lead screw thread to create multiple simultaneous air bearing surfaces. A wave spring flexure is inserted behind each graphite disk to provide a preload and ensure full contact between the porous graphite disk surface and the lead screw flank. When the wave spring flexures and graphite disks are potted in combination with a slow-curing epoxy, this creates a self-aligning method to consistently match all graphite disk insert surfaces to the helical profile of the lead screw thread. Experimental trials were performed to evaluate the performance of the manufactured ALSA. It was found that a stable nut with a per-thread stiffness of 9.7 N/μm was achievable with a 3.5 μm air gap and an overall permeability of 5.4 × 10−15 m2. Applications requiring higher stiffness may couple two or more single-threaded nuts to achieve the desired actuator stiffness.
Observations From Radical Innovation Projects Considering the Company Context
Authors: Yannou Bernard , Jankovic Marija , Leroy Yann , Okudan Kremer Gül E.
Published: January 2013

The development of product-service innovation projects within the context of a company is not yet supported by clear theories and methodologies. Our objective is to analyze innovation and idea generation for such projects from the fuzzy front end to the selected design concept, assessing their potential to be successfully developed and launched on the market. We present a protocol study, using which data derived from 19 innovation projects of five types and conducted by 86 students are analyzed. Sixty-one variables are observed, thus generating 700 data vectors. Bayesian network learning is used to explore conditional inferences among these variables. We examine conditional probabilities between the innovation process means and the significant results produced for the company, modulated by the influence of contextual variables. A number of surprising findings are drawn about the link between problem setting and problem solving processes, the importance of certain contextual variables, and the potential discrepancies between the apparent and produced results of innovative projects. Conducted analyses imply the need for novel innovation evaluation frameworks.
Designing and Manufacturing Spiral Bevel Gears Using 5-Axis Computer Numerical Control (CNC) Milling Machines
Authors: Teixeira Alves Joël , Guingand Michèle , de Vaujany Jean-Pierre
Published: January 2013

The design of spiral bevel gears remains complex since tooth geometry and the resulting kinematic performance stem directly from the manufacturing process. Spiral bevel gear cutting up to now has relied on the works of several manufacturers. Recent advances in milling machine technology and computer aided manufacturing (CAM) now make it possible to manufacture good quality spiral bevel gears on a standard 5-axis milling machine. This paper describes the computer aided design (CAD) definition and manufacturing of spiral bevel gear tooth surfaces. Process performance is assessed by comparing the resulting surfaces after machining with the predefined CAD surfaces. This manufacturing process makes it possible to obtain geometry analytically, making design easier than with standard spiral bevel gears.
The Meaning of “Near” and “Far”: The Impact of Structuring Design Databases and the Effect of Distance of Analogy on Design Output
Authors: Fu Katherine , Chan Joel , Cagan Jonathan , Kotovsky Kenneth , Schunn Christian , Wood Kristin
Published: January 2013

This work lends insight into the meaning and impact of “near” and “far” analogies. A cognitive engineering design study is presented that examines the effect of the distance of analogical design stimuli on design solution generation, and places those findings in context of results from the literature. The work ultimately sheds new light on the impact of analogies in the design process and the significance of their distance from a design problem. In this work, the design repository from which analogical stimuli are chosen is the U.S. patent database, a natural choice, as it is one of the largest and easily accessed catalogued databases of inventions. The “near” and “far” analogical stimuli for this study were chosen based on a structure of patents, created using a combination of latent semantic analysis and a Bayesian based algorithm for discovering structural form, resulting in clusters of patents connected by their relative similarity. The findings of this engineering design study are juxtaposed with the findings of a previous study by the authors in design by analogy, which appear to be contradictory when viewed independently. However, by mapping the analogical stimuli used in the earlier work into similar structures along with the patents used in the current study, a relationship between all of the stimuli and their relative distance from the design problem is discovered. The results confirm that “near” and “far” are relative terms, and depend on the characteristics of the potential stimuli. Further, although the literature has shown that “far” analogical stimuli are more likely to lead to the generation of innovative solutions with novel characteristics, there is such a thing as too far. That is, if the stimuli are too distant, they then can become harmful to the design process. Importantly, as well, the data mapping approach to identify analogies works, and is able to impact the effectiveness of the design process. This work has implications not only in the area of finding inspirational designs to use for design by analogy processes in practice, but also for synthesis, or perhaps even unification, of future studies in the field of design by analogy.
A Partition Expansion Method for Nonlinear Response Analysis of Stochastic Dynamic Systems With Local Nonlinearity
Authors: Bai Changqing , Zhang Hongyan
Published: January 2013

This paper focuses on the problem of nonlinear dynamic response variability resulting from stochastic system properties and random loads. An efficient and accurate method, which can be employed to analyze the dynamic responses of random finite element systems with local nonlinearity, is presented in this paper. This method, dubbed as the partition expansion method, is based on the partitioned time integration algorithm in conjunction with the Neumann expansion technique within the framework of the Monte Carlo simulation. Two numerical examples involving structural and mechanical stochastic vibration problems are employed to illustrate the advantage of the proposed method with respect to accuracy and efficiency. By comparing the results obtained by the direct Monte Carlo simulation, the dynamic response statistics can be accurately determined using the proposed method with four order expansion while the computational efforts are significantly reduced. The comparison of computing time indicates that the proposed method is efficient and practical for analyzing the statistical quantities of stochastic dynamic systems with local nonlinearity.
Effects of rapid thermal annealing on electrical, optical, and structural properties of Ni-doped In2O3 anodes for bulk heterojunction organic solar cells
Authors: Ho Kim Jun , Seong Tae-Yeon , Kim Han-Ki
Published: January 2013

The authors investigated the effects of rapid thermal annealing (RTA) on the electrical, optical, and structural properties, and work functions of Ni-doped In2O3 (INO) anodes prepared by a DC/RF co-sputtering process for use in bulk heterojunction organic solar cells (OSCs). By RTA processing at 600 °C, the authors obtained the optimized INO anodes with a sheet resistance of 28 Ω/sq, an optical transmittance of 82.93%, and a work function of 5.02 eV, which are acceptable in OSC fabrication. In particular, the 600 °C annealed INO anode showed much higher optical transmittance in the near infrared wavelength region than the conventional ITO film, even though it had a low resistivity of 5.66 × 10−4 Ω cm. The OSC fabricated on the annealed INO anode showed a higher power convention efficiency of 2.65% than the OSC with as-deposited INO anodes (2.19%) because the fill factors of the OSC are critically dependent on the sheet resistance of the anode.
Rectal Swabs Are Suitable for Quantifying the Carriage Load of KPC-Producing Carbapenem-Resistant Enterobacteriaceae
Authors: Lerner A. , Romano J. , Chmelnitsky I. , Navon-Venezia S. , Edgar R. , Carmeli Y.
Published: January 2013

It is more convenient and practical to collect rectal swabs than stool specimens to study carriage of colon pathogens. In this study, we examined the ability to use rectal swabs rather than stool specimens to quantify
Klebsiella pneumoniae
carbapenemase (KPC)-producing carbapenem-resistant
Enterobacteriaceae
(CRE). We used a quantitative real-time PCR (qPCR) assay to determine the concentration of the
bla
KPC
gene relative to the concentration of 16S rRNA genes and a quantitative culture-based method to quantify CRE relative to total aerobic bacteria. Our results demonstrated that rectal swabs are suitable for quantifying the concentration of KPC-producing CRE and that qPCR showed higher correlation between rectal swabs and stool specimens than the culture-based method.
Preliminary Pharmacokinetic Study of Repeated Doses of Rifampin and Rifapentine in Guinea Pigs
Authors: Dutta Noton K. , Alsultan Abdullah , Peloquin Charles A. , Karakousis Petros C.
Published: January 2013

Substitution of rifapentine (RFP) for rifampin (RIF) in the standard antituberculous regimen reduces the time required to cure chronic tuberculosis (TB) infection in mice, but not in guinea pigs. In order to gain insight into these discrepant findings, we conducted a steady-state pharmacokinetic (PK) study in healthy guinea pigs to study the metabolism and autoinduction of RIF and RFP. Both RFP and RIF 25-desacetyl metabolites (desRFP and desRIF, respectively), were detected at low concentrations in the serum of guinea pigs. The metabolite concentrations in guinea pigs are much lower than those seen in humans at steady state.
Discovery of a Novel Class of Boron-Based Antibacterials with Activity against Gram-Negative Bacteria
Authors: Hernandez Vincent , Crépin Thibaut , Palencia Andrés , Cusack Stephen , Akama Tsutomu , Baker Stephen J. , Bu Wei , Feng Lisa , Freund Yvonne R. , Liu Liang , Meewan Maliwan , Mohan Manisha , Mao Weimin , Rock Fernando L. , Sexton Holly , Sheoran Anita , Zhang Yanchen , Zhang Yong-Kang , Zhou Yasheen , Nieman James A. , Anugula Mahipal Reddy , Keramane El Mehdi , Savariraj Kingsley , Reddy D. Shekhar , Sharma Rashmi , Subedi Rajendra , Singh Rajeshwar , O'Leary Ann , Simon Nerissa L. , De Marsh Peter L. , Mushtaq Shazad , Warner Marina , Livermore David M. , Alley M. R. K. , Plattner Jacob J.
Published: January 2013

Gram-negative bacteria cause approximately 70% of the infections in intensive care units. A growing number of bacterial isolates responsible for these infections are resistant to currently available antibiotics and to many in development. Most agents under development are modifications of existing drug classes, which only partially overcome existing resistance mechanisms. Therefore, new classes of Gram-negative antibacterials with truly novel modes of action are needed to circumvent these existing resistance mechanisms. We have previously identified a new a way to inhibit an aminoacyl-tRNA synthetase, leucyl-tRNA synthetase (LeuRS), in fungi via the oxaborole tRNA trapping (OBORT) mechanism. Herein, we show how we have modified the OBORT mechanism using a structure-guided approach to develop a new boron-based antibiotic class, the aminomethylbenzoxaboroles, which inhibit bacterial leucyl-tRNA synthetase and have activity against Gram-negative bacteria by largely evading the main efflux mechanisms inEscherichia coliandPseudomonas aeruginosa. The lead analogue, AN3365, is active against Gram-negative bacteria, includingEnterobacteriaceaebearing NDM-1 and KPC carbapenemases, as well asP. aeruginosa. This novel boron-based antibacterial, AN3365, has good mouse pharmacokinetics and was efficacious againstE. coliandP. aeruginosain murine thigh infection models, which suggest that this novel class of antibacterials has the potential to address this unmet medical need.
Arrested Protein Synthesis Increases Persister-Like Cell Formation
Authors: Kwan Brian W. , Valenta John A. , Benedik Michael J. , Wood Thomas K.
Published: January 2013

Biofilms are associated with a wide variety of bacterial infections and pose a serious problem in clinical medicine due to their inherent resilience to antibiotic treatment. Within biofilms, persister cells comprise a small bacterial subpopulation that exhibits multidrug tolerance to antibiotics without undergoing genetic change. The low frequency of persister cell formation makes it difficult to isolate and study persisters, and bacterial persistence is often attributed to a quiescent metabolic state induced by toxins that are regulated through toxin-antitoxin systems. Here we mimic toxins via chemical pretreatments to induce high levels of persistence (10 to 100%) from an initial population of 0.01%. Pretreatment of
Escherichia coli
with (i) rifampin, which halts transcription, (ii) tetracycline, which halts translation, and (iii) carbonyl cyanide
m
-chlorophenylhydrazone, which halts ATP synthesis, all increased persistence dramatically. Using these compounds, we demonstrate that bacterial persistence results from halted protein synthesis and from environmental cues.
High Prevalence of Fluoroquinolone-Resistant Group B Streptococci among Clinical Isolates in China and Predominance of Sequence Type 19 with Serotype III
Authors: Wang Hui , Zhao Chunjiang , He Wenqiang , Zhang Feifei , Zhang Liyan , Cao Bin , Sun Ziyong , Xu Yingchun , Yang Qing , Mei Yaning , Hu Bijie , Chu Yunzhuo , Liao Kang , Yu Yunsong , Hu Zhidong , Ni Yuxing
Published: January 2013

A total of 146 group B streptococcus isolates from 8 cities across China belonged to four serotypes. Serotype Ia was more common in children. A high prevalence of resistance was observed for levofloxacin (37.7%), erythromycin (71.2%), clindamycin, (53.4%), and tetracycline (81.5%). The levofloxacin and clindamycin resistances among the 4 serotypes differed significantly. Eighty percent of fluoroquinolone-resistant isolates belonged to the sequence type 19 (ST19)/serotype III clone, with GyrA-ParC-ParE triple substitutions. This clone carried the
erm
(B),
mef
(E), and
tet
(M) genes.
Protein-Free Efavirenz Concentrations in Cerebrospinal Fluid and Blood Plasma Are Equivalent: Applying the Law of Mass Action To Predict Protein-Free Drug Concentration
Authors: Avery L. B. , Sacktor N. , McArthur J. C. , Hendrix C. W.
Published: January 2013

Efavirenz (EFV) is one of the most commonly prescribed antiretroviral drugs (ARVs) for the treatment of HIV. Highly protein-bound drugs, like EFV, have limited central nervous system (CNS) penetration when measured using total drug concentration gradients between blood plasma (BP) and cerebrospinal fluid (CSF). However, the more relevant pharmacologically active protein-free drug concentrations are rarely assessed directly in clinical studies. Using paired BP and CSF samples obtained from 13 subjects on an EFV-containing regimen, both the protein-free and total concentrations of EFV were determined. Despite a median (interquartile range [IQR]) total EFV BP/CSF concentration ratio of 134 (116 to 198), the protein-free EFV BP/CSF concentration ratio was 1.20 (0.97 to 2.12). EFV median (IQR) protein binding was 99.78% (99.74 to 99.80%) in BP and 76.19% (74.47 to 77.15%) in CSF. In addition, using the law of mass action and an
in vitro
-derived EFV-human serum albumin dissociation constant, we have demonstrated that the predicted median (IQR) protein-free concentration in BP, 4.59 ng/ml (4.02 to 9.44 ng/ml), compared well to that observed in BP, 4.77 ng/ml (3.68 to 6.75 ng/ml). Similar results were also observed in CSF and seminal plasma. This method provides a useful predictive tool for estimating protein binding in varied anatomic compartments. Our results of equivalent protein-free EFV concentrations in BP and CSF do not support prior concerns of the CNS as a pharmacological sanctuary from EFV. As CSF penetration of ARVs may increase our understanding of HIV-associated neurological dysfunction and antiretroviral effect, assessment of protein-free CSF concentrations of other highly protein-bound ARVs is warranted.
The “Silent” Global Burden of Congenital Cytomegalovirus
Authors: Manicklal Sheetal , Emery Vincent C. , Lazzarotto Tiziana , Boppana Suresh B. , Gupta Ravindra K.
Published: January 2013

Human cytomegalovirus (CMV) is a leading cause of congenital infections worldwide. In the developed world, following the virtual elimination of circulating rubella, it is the commonest nongenetic cause of childhood hearing loss and an important cause of neurodevelopmental delay. The seroprevalence of CMV in adults and the incidence of congenital CMV infection are highest in developing countries (1 to 5% of births) and are most likely driven by nonprimary maternal infections. However, reliable estimates of prevalence and outcome from developing countries are not available. This is largely due to the dogma that maternal preexisting seroimmunity virtually eliminates the risk for sequelae. However, recent data demonstrating similar rates of sequelae, especially hearing loss, following primary and nonprimary maternal infection have underscored the importance of congenital CMV infection in resource-poor settings. Although a significant proportion of congenital CMV infections are attributable to maternal primary infection in well-resourced settings, the absence of specific interventions for seronegative mothers and uncertainty about fetal prognosis have discouraged routine maternal antibody screening. Despite these challenges, encouraging results from prototype vaccines have been reported, and the first randomized phase III trials of prenatal interventions and prolonged postnatal antiviral therapy are under way. Successful implementation of strategies to prevent or reduce the burden of congenital CMV infection will require heightened global awareness among clinicians and the general population. In this review, we highlight the global epidemiology of congenital CMV and the implications of growing knowledge in areas of prevention, diagnosis, prognosis, and management for both low (50 to 70%)- and high (>70%)-seroprevalence settings.
Cryptosporidium Pathogenicity and Virulence
Authors: Bouzid Maha , Hunter Paul R. , Chalmers Rachel M. , Tyler Kevin M.
Published: January 2013

Cryptosporidiumis a protozoan parasite of medical and veterinary importance that causes gastroenteritis in a variety of vertebrate hosts. Several studies have reported different degrees of pathogenicity and virulence amongCryptosporidiumspecies and isolates of the same species as well as evidence of variation in host susceptibility to infection. The identification and validation ofCryptosporidiumvirulence factors have been hindered by the renowned difficulties pertaining to thein vitroculture and genetic manipulation of this parasite. Nevertheless, substantial progress has been made in identifying putative virulence factors forCryptosporidium. This progress has been accelerated since the publication of theCryptosporidium parvumandC. hominisgenomes, with the characterization of over 25 putative virulence factors identified by using a variety of immunological and molecular techniques and which are proposed to be involved in aspects of host-pathogen interactions from adhesion and locomotion to invasion and proliferation. Progress has also been made in the contribution of host factors that are associated with variations in both the severity and risk of infection. Here we provide a review comprised of the current state of knowledge onCryptosporidiuminfectivity, pathogenesis, and transmissibility in light of our contemporary understanding of microbial virulence.