bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing open source software as a scholarly contribution
Authors: Hafer Lou , Kirkpatrick Arthur E.
Published: November 2009

Introduction

Academic computer science has an odd relationship with software: Publishing papers about software is considered a distinctly stronger contribution than publishing the software. The historical reasons for this paradox no longer apply, but their legacy remains. This limits researchers who see the open-source software movement as an opportunity to make a scholarly contribution. Expanded definitions of scholarship acknowledge both application and discovery as important components.
1
One obstacle remains: evaluation. To raise software to the status of a first-class contribution, we propose "best practices" for the evaluation of the scholarly contribution of open-source software.

Typically, scholars who develop software do not include it as a primary contribution for performance reviews. Instead, they write articles about the software and present the articles as contributions. This conflation of articles and software serves neither medium well. An article describes an original intellectual contribution consisting of an idea, the argument for its importance and correctness, and supporting data. In contrast, software is more often an implementation of prior ideas in a usable form. It bridges the often considerable gap between an idea and the practical application of that idea. The original idea and its implementation represent distinct kinds of contribution.

The critical gap is the perceived incomparability of these two contributions. Lacking a concise description adapted to the traditional practices of performance review committees, software is difficult to evaluate as a scholarly contribution and is often relegated to second-class status. We propose a framework for common assessment based on widely accepted definitions of scholarship. Within this general framework, we consider the material and procedures that a performance review committee uses to evaluate a publication. We then describe how software can be summarized in a compatible form of bibliographic citation and supplementary material.
Temporal privacy in wireless sensor networks
Authors: Kamat Pandurang , Xu Wenyuan , Trappe Wade , Zhang Yanyong
Published: November 2009

Although the content of sensor messages describing “events of interest” may be encrypted to provide confidentiality, the context surrounding these events may also be sensitive and therefore should be protected from eavesdroppers. An adversary armed with knowledge of the network deployment, routing algorithms, and the base-station (data sink) location can infer the temporal patterns of interesting events by merely monitoring the arrival of packets at the sink, thereby allowing the adversary to remotely track the spatio-temporal evolution of a sensed event. In this paper we introduce the problem of temporal privacy for delay-tolerant sensor networks, and propose adaptive buffering at intermediate nodes on the source-sink routing path to obfuscate temporal information from the adversary. We first present the effect of buffering on temporal privacy using an information-theoretic formulation, and then examine the effect that delaying packets has on buffer occupancy. We observe that temporal privacy and efficient buffer utilization are contrary objectives, and then present an adaptive buffering strategy that effectively manages these tradeoffs. Finally, we evaluate our privacy enhancement strategies using simulations, where privacy is quantified in terms of the adversary's mean square error.
Connectivity-based localization of large-scale sensor networks with complex shape
Authors: Lederer Sol , Wang Yue , Gao Jie
Published: November 2009

We study the problem of localizing a large sensor network having a complex shape, possibly with holes. A major challenge with respect to such networks is to figure out the correct network layout, that is, avoid global flips where a part of the network folds on top of another. Our algorithm first selects landmarks on network boundaries with sufficient density, then constructs the landmark Voronoi diagram and its dual combinatorial Delaunay complex on these landmarks. The key insight is that the combinatorial Delaunay complex is provably
globally rigid
and has a
unique
realization in the plane. Thus an embedding of the landmarks by simply gluing the Delaunay triangles properly recovers the faithful network layout. With the landmarks nicely localized, the rest of the nodes can easily localize themselves by trilateration to nearby landmark nodes. This leads to a practical and accurate localization algorithm for large networks using only network connectivity. Simulations on various network topologies show surprisingly good results. In comparison, previous connectivity-based localization algorithms such as multidimensional scaling and rubberband representation generate globally flipped or distorted localization results.
Robust and distributed stochastic localization in sensor networks
Authors: Paschalidis Ioannis Ch. , Guo Dong
Published: November 2009

We present a robust localization system allowing wireless sensor networks to determine the physical location of their nodes. The coverage area is partitioned into regions and we seek to identify the region of a sensor based on observations by stationary clusterheads. Observations (e.g., signal strength) are assumed random. We pose the localization problem as a composite multihypothesis testing problem, develop the requisite theory, and address the problem of optimally placing clusterheads. We show that localization decisions can be distributed by appropriate in-network processing. The approach is validated in a testbed yielding promising results.
Creating a lightweight user interface description language
Authors: Nichols Jeffrey , Myers Brad A.
Published: November 2009

Over six years, we iterated on the design of a language for describing the functionality of appliances, such as televisions, telephones, VCRs, and copiers. This language has been used to describe more than thirty diverse appliances, and these descriptions have been used to automatically generate both graphical and speech user interfaces on handheld computers, mobile phones, and desktop computers. In this article, we describe the final design of our language and analyze the key design choices that led to this design. Through this analysis, we hope to provide a useful guide for the designers of future user interface description languages.
What is analytic infrastructure and why should you care?
Authors: Grossman Robert L.
Published: November 2009

We define analytic infrastructure to be the services, applications, utilities and systems that are used for either preparing data for modeling, estimating models, validating models, scoring data, or related activities. For example, analytic infrastructure includes databases and data warehouses, statistical and data mining systems, scoring engines, grids and clouds. Note that, with this definition, analytic infrastructure does not need to be used exclusively for modeling but simply useful as part of the modeling process. In this article, we discuss the importance of analytic infrastructure and some of the standards that can be used to support analytic infrastructure. We also discuss some specialized analytic infrastructure applications and services, including applications that can manage very large datasets and build models over them and cloud based analytic services.
What's PMML and what's new in PMML 4.0?
Authors: Pechter Rick
Published: November 2009

The Predictive Model Markup Language (PMML) data mining standard has arguably become one of the most widely adopted data mining standards in use today. Two years in the making, the latest release of PMML contains several new features and many enhancements to existing ones. This paper provides a primer on the PMML standard and its applications along with a description of the new features in PMML 4.0 which was released in May 2009.
A kisspeptin-10 analog with greater in vivo bioactivity than kisspeptin-10
Authors: Curtis Annette E. , Cooke Jennifer H. , Baxter Jordan E. , Parkinson James R. C. , Bataveljic Attia , Ghatei Mohammad A. , Bloom Stephen R. , Murphy Kevin G.
Published: November 2009

The kisspeptins are neuropeptides that stimulate the hypothalamo-pituitary-gonadal (HPG) axis. The smallest endogenous kisspeptin, kisspeptin-10 (KP-10), binds to the receptor KISS1R with a similar affinity to the full-length peptide, kisspeptin-54 (KP-54), but is less effective in vivo, possibly because of increased enzymatic breakdown or clearance. The kisspeptin system may have therapeutic potential in the treatment of reproductive disorders and endocrine cancers. We have rationally modified the structure of KP-10 and tested the binding affinity of these analogs for the KISS1R. Those analogs that bound with relatively high affinity to KISS1R were tested for ability to stimulate ERK1/2 phosphorylation in vitro and for their ability to stimulate the HPG axis in vivo. One analog, [dY]1KP-10, bound to KISS1R with lower affinity to KP-10 and exhibited similar bioactivity in vitro. However, in vivo peripheral administration of [dY]1KP-10 increased plasma LH and testosterone more potently than KP-10 itself at 20 min postinjection in mice. In addition, 60 min postinjection, 0.15 nmol [dY]1KP-10 significantly increased total testosterone levels in mice whereas the same dose of KP-10 had no significant effect. Should manipulation of the kisspeptin/KISS1R signaling system prove therapeutically useful, long-lasting analogs such as [dY]1KP-10 may have greater therapeutic potential than endogenous forms of kisspeptin.
Global Bifurcation for Second‐Order Neumann Problem with a Set‐Valued Term
Authors: Ma Ruyun , Li Jiemei
Published: November 2009

We study the global bifurcation of the differential inclusion of the form , where F is a “set‐valued representation” of a function with jump discontinuities along the line segment [0, 1] × {0}. The proof relies on a Sturm‐Liouville version of Rabinowitz′s bifurcation theorem and an approximation procedure.
On Costas Sets and Costas Clouds
Authors: Drakakis Konstantinos
Published: November 2009

We abstract the definition of the Costas property in the context of a group and study specifically dense
Costas sets (named Costas clouds) in groups with the topological property that they are dense in themselves:
as a result, we prove the existence of nowhere continuous dense bijections that satisfy the Costas property on ℚ2, ℝ2, and ℂ2, the latter two being based on nonlinear solutions of Cauchy′s functional equation, as well as on
ℚ, ℝ, and ℂ, which are, in effect, generalized Golomb rulers. We generalize the Welch and Golomb construction
methods for Costas arrays to apply on ℝ and ℂ, and we prove that group isomorphisms on and tensor products of Costas sets result to new Costas sets with respect to an appropriate set of distance vectors. We also give two constructive examples of a nowhere continuous function that satisfies a constrained form of the Costas property (over rational or algebraic displacements only, i.e.), based on the indicator function of a dense subset of ℝ.
Influence of Excitation on Dynamic System Identification for a Multi-Span Reinforced Concrete Bridge
Authors: Alwash M. , Sparling B. F. , Wegner L. D.
Published: November 2009

In vibration-based damage detection, changes to structural modal properties are tracked over time in order to infer the current state of damage or deterioration. As such, the ability to obtain reliable estimates of modal parameters, particularly natural frequencies and mode shapes, is of critical importance. In the present study, the influence of the dynamic excitation source on the accuracy and statistical uncertainty of modal property estimates for a three span reinforced concrete bridge was investigated experimentally and numerically. Comparisons were made between the dynamic responses due to vehicle loading, harmonic and random forcing, impact, and environmental excitation. It was demonstrated that natural frequencies and mode shapes extracted from the free vibration response following vehicle and random loading events were of higher quality than corresponding values determined during the forcing phase of those events. Harmonic excitation at resonant frequencies and impact were also found to produce statistically reliable results.
Differential Expression of Intestinal Genes in Opossums with High and Low Responses to Dietary Cholesterol
Authors: Chan Jeannie , Kushwaha Rampratap S. , VandeBerg Jane F. , Gluhak-Heinrich Jelica , VandeBerg John L.
Published: November 2009

High and low responding opossums (Monodelphis domestica) differ in their plasma very low density lipoprotein and low density lipoprotein (VLDL+LDL) cholesterol concentrations when they consume a high cholesterol diet, which is due in part to absorption of a higher percentage of dietary cholesterol in high responders. We compared the expression of a set of genes that influence cholesterol absorption in high and low responders fed a basal or a high cholesterol and low fat (HCLF) diet. Up-regulation of theABCG5,ABCG8, andIBABPgenes by the HCLF diet in high and low responders may reduce cholesterol absorption to maintain cholesterol homeostasis. Differences in expression of the phospholipase genes (PLA2andPLB) and phospholipase activity were associated with differences in cholesterol absorption when opossums were fed cholesterol-enriched diets. HigherPLA2andPLBmRNA levels and higher phospholipase activity may increase cholesterol absorption in high responders by enhancing the release of cholesterol from bile salt micelles for uptake by intestinal cells.
Differential Midgut Attachment ofLeishmania (Viannia) braziliensisin the Sand FliesLutzomyia (Nyssomyia) whitmaniandLutzomyia (Nyssomyia) intermedia
Authors: Soares Rodrigo P. , Margonari Carina , Secundino Nágila C. , Macêdo Maria E. , Costa Simone M. da , Rangel Elizabeth F. , Pimenta Paulo F. , Turco Salvatore J.
Published: November 2009

The interaction betweenLeishmaniaand sand flies has been demonstrated in many Old and New World species. Besides the morphological differentiation from procyclic to infective metacyclic promastigotes, the parasite undergoes biochemical transformations in its major surface lipophosphoglycan (LPG). An upregulation ofβ-glucose residues was previously shown in the LPG repeat units from procyclic to metacyclic phase inLeishmania (Viannia) braziliensis, which has not been reported in anyLeishmaniaspecies. LPG has been implicated as an adhesion molecule that mediates the interaction with the midgut epithelium of the sand fly in the SubgenusLeishmania. These adaptations were explored for the first time in a species from the SubgenusViannia, L. (V.) braziliensiswith its natural vectorsLutzomyia (Nyssomyia) intermediaandLutzomyia (Nyssomyia) whitmani. Using two in vitro binding techniques, phosphoglycans (PGs) derived from procyclic and metacyclic parasites were able to bind to the insect midgut and inhibitL. braziliensisattachment. Interestingly,L. braziliensisprocyclic parasite attachment was∼11-fold greater in the midgut ofL. whitmanithan inL. intermedia. The epidemiological relevance ofL. whitmanias a vector of American Cutaneous Leishmaniasis (ACL) in Brazil is discussed.
Interleukin-1 Gene –511 CT Polymorphism and the Risk of Alzheimer’s Disease in a Polish Population
Authors: Klimkowicz-Mrowiec A. , Marona M. , Wołkow P. , Maruszak A. , Styczynska M. , Barcikowska M. , Zekanowski C. , Szczudlik A. , Slowik A.
Published: November 2009

Interleukin-1 is a potent proinflammatory cytokine involved in the pathophysiology of Alzheimer’s disease (AD). We genotyped IL-1β (–511 C/T) and the apolipoprotein E (APOE) common polymorphisms in a large case-controlled study in a Polish population. We included 332 patients with late-onset AD and 220 controls without any neurological deficit, cognitive complaints and history of neurological diseases, aged ≥ 65 years. The distribution of the IL-1β (–511 C/T) genotypes was similar to that in the controls (AD: C/C = 45.8%, C/T = 44.6%, T/T = 9.6% vs. controls: C/C = 53.9%, C/T = 38.3%, T/T = 7.3%, p > 0.05). Our study confirms previous reports that APOE ε4 is strongly related to the risk of AD (odds ratio = 6.60, 95% confidence interval 4.19–10.41). APOE status did not affect the distribution of the studied IL-1β polymorphism. The IL-1β (–511 C/T) polymorphism is not a risk factor for late-onset AD in a Polish population.
Syntagmatische Phonemtypologie
Authors: Kempgen Sebastian
Published: November 2009

Based on the recent developments of the distributional calculus of Harary and Paper, a method is proposed to discover the constructional mechanism underlying the phonemic distribution of a language. The phonemes are classified hierarchically and the mutual interdependence of their distributional characteristics is studied. To this end, the technics of correlation and regression are being used. In this way, a ‘typology’ of phonemes in the sense of Hempel and Oppenheim is arrived at.
A Relationship between Coarticulation and Compensatory Shortening
Authors: Fowler Carol A.
Published: November 2009

A comparison of the literatures on coarticulatory influences of a stressed vowel on consonants and unstressed vowels and on ‘compensatory shortening’ of stressed vowels in the contexts of consonants and unstressed vowels suggests that the two timing effects may be related. An experiment was conducted to provide an explicit comparison and to test a hypothesis that compensatory shortening aand coarticulation are not separate timing phenomena. The two timing effects were found to pattern very similarly and both to be predicted by Lindblom and Rapp’s compensatory shortening formula. 5 of 6 subjects showed significant correlations between coarticulation and shortening.
Prosodic Aspects of American English Speech Rhythm
Authors: Nakatani Lloyd H. , O’Connor Kathleen D. , Aston Carletta H.
Published: November 2009

We studied American English speech rhythm using reiterant speech with the prosody of normal speech but without its segmental variations. Syllable duration was strongly influenced by stress and by final positions in words and phrases, but negligibly by nonfinal positions within words and phrases. Word duration increased linearly with word size, and varied with stress pattern for words of constant size. Metrical foot duration increased approximately linearly with foot size. Feet of the same type and size were of constant duration.
Segmental and Temporal Aspects of Utterance-Final Lengthening
Authors: Cooper William E. , Danly Martha
Published: November 2009

Two experiments were conducted to examine the manner in which utterance-final lengthening is exhibited by the durations of words containing various fricatives and vowels in different phonetic environments. In experiment 1, utterance-final lengthening was measured for words containing the fricatives /f/, /v/, /s/, and /z/ in word-initial, word-medial, and word-final positions in both phrase-final and utterance-final locations. The results showed small amounts of utterance-final lengthening for words containing fricatives in word-initial and word-medial positions, with much greater elongation when fricatives appeared in word-final position. In experiment 2, utterance-final lengthening was measured for words containing a word-medial long versus short vowel followed by a word-final voiced versus voiceless stop consonant. The results showed a greater amount of utterance-final lengthening for words containing a terminal voiced versus voiceless stop. The findings are discussed in terms of constraints on the speaker’s programming of segment durations in sentence contexts.
Durations and Contexts as Cues to Word-Final Cognate Opposition in English
Authors: Raphael Lawrence J.
Published: November 2009

Many perceptual and acoustic studies of word-final cognate opposition have relied mainly on isolated synthetic utterances and have usually concluded that one or another of the potential cues is primary. Recent studies of natural speech segment durations in samples of connected discourse have raised questions about the efficacy of such cues. In the experiments reported here, naturally produced tokens of the word peg were excised from two different contexts and acoustically analyzed. One representative token from each context was then edited in several ways in order to ascertain the cue values of a number of variables. The stimuli were tested in isolation, in their original contexts and in contexts from which the word peck had been deleted. The results of the experiments indicate that a number of variables can be sufficient cues to cognate opposition, and that the efficacy of a particular cue depends in a large measure both on the context from which it was extracted and on the context in which it is heard. The potentially large number of cues, their temporal distribution and their variable effectiveness suggest that future research should be focussed on discovering and describing a general articulatory strategy underlying both the production and perception of cognate oppositions.
Mechanisms in the Control of Speech Rate
Authors: Gay Thomas
Published: November 2009

Mechanisms of speech rate control are discussed from the point of view that unidimensional models are inadequate to explain the extensive physiological and acoustical effects observed during changes in speech rate. Evidence is presented to demonstrate that changes in speech rate can result in changes in segmental duration, articulatory displacement, atriculatory velocity, and intrasyllabic coarticulation, and that these changes represent nonlinear transformations produced by a reorganization of speech motor strategies.
Speech Timing as a Tool in Phonology
Authors: Ohala John J.
Published: November 2009

Phonological questions of the sort ‘Is segment or feature [x] a surface-phonetic event or a property of the underlying mental representation?’ may be answered in some cases by considering the durations of the speech sounds in the word in which [x] appears. Here the status of the epenthetic stop [p] in words such as teamster [––thimpstÉš] was clarified by measurement of the duration of the preceding vowel + nasal (VN) sequence: a shortened VN implies the [p] is underlying; a long VN implies that it is a surface-phonetic event.
Kidney Volume and Albuminuria as Markers of Birth Weight-Blood Pressure Relationship in Essential Hypertension
Authors: Laganović Mario , Kuzmanić Duško , Željković-Vrkić Tajana , Pećin Ivan , Dika Živka , Jelaković Bojan
Published: November 2009

Our aim was to analyze whether birth weight contributes to future hypertension through reduced kidney volume, and whether albuminuria could be a marker of this pathway. We included 103 patients with newly diagnosed essential hypertension and 92 normotensive controls. Blood pressure (BP) was measured using a mercury sphygmomanometer and a ABP monitor. Kidney volume was determined by ultrasound. Data on birth weight were obtained from mothers. Albuminuria was determined in 24-hour urine samples. Hypertensive patients had lower birth weight and higher albuminuria than normotensives. There was no difference in kidney volume between the two groups. We found a negative correlation between birth weight and systolic BP in the hypertensive group. BP was significantly correlated with BMI and albuminuria in the hypertensive group. Multiple regression analysis had shown the greatest impact of BMI on BP and had also demonstrated that 24-hour systolic BP showed the greatest risk for developing albuminuria in hypertensive patients. In conclusion, birth weight influences BP values in adult age, but it is not mediated by a reduced kidney volume. A strong correlation, independent of birth weight, was observed between albuminuria and BP values. Increased BMI is the most important independent risk factor responsible for BP increase, even in an early phase of essential hypertension.
Evaluating Major Depressive Episodes through the Algorithmically Structured Systematic Exploration of Subject’s State of Mind
Authors: Stoleru S. , Kosmadakis C. , Coudert O. , Degras D. , Allilaire J.F.
Published: November 2009

Background/Aims: Whereas instruments are available to diagnose depression and to rate its severity, there is a lack of instruments to assess the phenomenology of depression, i.e. a set of mental phenomena that constitute subjective experience. The Algorithmically Structured Systematic Exploration of Subject’s State of Mind (Assess_Mind) is based on open questions asked via a structured algorithm. Here, we evaluated its reliability and its validity to assess the phenomenology of major depressive episodes. Methods: Scales were constructed to evaluate various aspects of major depressive episodes, and an Assess_Mind score was derived from these scales. Thirty-five patients presenting a major depressive episode were assessed with the Hamilton Depression Rating Scale, Clinical Global Impressions (CGI) scale, Beck Depression Inventory and Symptom Checklist-90R. Two series of assessments were conducted, separated by 3 weeks. Results: Interrater reliability was good to excellent and test-retest reliability was acceptable. Whereas construct validity was poor at the first time point (first day of the patient’s inclusion), it was adequate for the second day and 3 weeks later. The change in the Assess_Mind score predicted the change in the CGI rating as well as the other instruments did. These results should be confirmed in larger samples. Conclusion: The Assess_Mind provided a useful assessment of the phenomenology of depression and of the course of major depressive episodes.
Psychiatric Profile in Rubinstein-Taybi Syndrome
Authors: Verhoeven W.M.A. , Tuinier S. , Kuijpers H.J.H. , Egger J.I.M. , Brunner H.G.
Published: November 2009

Background:The diagnosis of Rubinstein-Taybi syndrome (RTS) is primarily clinical and based on the characteristic phenotype that is often combined with a variety of somatic anomalies and psychiatric disorders. Sampling and Methods:In this paper, a review is presented of the psychiatric and behavioural aspects of RTS. This is illustrated with a case report. Results:Behavioural aspects of about 150 patients are described, and include a variable degree of mental retardation, impulsivity, distractibility, instability of mood and stereotypies. In general, patients with RTS are described as sociable and friendly. Information about brain pathology is virtually absent. In about half of the cases, the syndrome is caused by a mutation or deletion of the CREB-binding protein (CBP) gene (16p13.3). The case report deals with an adult male who was referred for impulsivity and temper outbursts. A provisional diagnosis of atypical depression was made, and treatment with citalopram resulted in a remarkable amelioration of his mood and behaviour that persisted for more than 2 years (last observation). Conclusion:Patients with undetected genetic syndromes do occur in clinical psychiatry, and the clinician has to consider such disorders in cases with disturbed development, dysmorphias and somatic comorbidity.
Influence of Gum Chewing on Postoperative Bowel Activity after Cesarean Section
Authors: Kafali Hasan , Duvan Candan İltemir , Gözdemir Elif , Simavli Serap , Onaran Yüksel , Keskin Esra
Published: November 2009

Objective: To assess the effects of gum chewing on postoperative bowel function after cesarean section. Material and Methods: Women who underwent cesarean section were randomized to either a gum-chewing group (n = 74) or a non-gum-chewing group (n = 76). The two groups were compared with respect to the return of bowel activity, postoperative analgesic and antiemetic drug requirement and postoperative hospital stay. Results: Bowel sounds appeared in a significantly shorter duration of time in the study group, the mean being 5.9 h as compared to 6.7 h in the control group (p < 0.01). The first passage of flatus postoperatively was 22.4 h in the gum-chewing group and 31 h in the control group (p < 0.001). The total length of hospital stay was shorter in the gum-chewing group (2.1 days) than in the control group (2.3 days), but it was not statistically significant (p > 0.05). Postoperative analgesic requirement in both groups was similar, but the postoperative antiemetic need in the gum-chewing group was lower than in the control group (p < 0.01). Conclusion: On the basis of the tolerability and results on bowel function, gum chewing provides a simple method for early recovery of bowel function after cesarean section.
Neuroendocrine Carcinomas Arising in Solid-Organ Transplant Recipients: Rare but Aggressive Malignancies
Authors: Fiebiger Wolfgang , Kaserer Klaus , Rödler Suzanne , Oberbauer Rainer , Bauer Claudia , Raderer Markus
Published: November 2009

Organ transplant recipients are at an increased risk of developing malignancies due to prolonged immunosuppression. However, the rate and clinical course of neuroendocrine tumors (NETs) following organ transplantation has not been assessed so far. We have retrospectively analyzed patients undergoing organ transplantation between 1985 and 2001 in order to assess the frequency and clinical course of NETs in organ transplant recipients. 3,190 organ transplant recipients with sufficient clinical data were identified (2,521 kidney and 669 heart transplants). In total, 161/3,190 patients (5%) developed malignancies, with 6 of them being classified as NETs (0.18%). Interestingly, all 6 patients were diagnosed with undifferentiated neuroendocrine carcinomas, while no indolent NETs were seen. Four of these patients had undergone renal, 1 patient heart and 1 patient both heart and renal transplantation. All 6 patients were given chemotherapy, but none of them responded, as all patients showed disease progression after a median of 3 cycles of chemotherapy (range 1–4) with the median survival being 4.8 months (range 2–11). The occurrence of NETs/undifferentiated neuroendocrine carcinomas following organ transplantation appears to be rare, with an incidence comparable with the normal population. Our data suggest a highly aggressive course with a dismal prognosis and unresponsiveness to chemotherapy.
Hypercoagulable State and Methylenetetra- hydrofolate Reductase (MTHFR) C677T Mutation in Patients with Beta-Thalassemia Major in Kuwait
Authors: Mustafa Nada Y. , Marouf Rajaa , Al-Humood Salah , Al-Fadhli Suad M. , Mojiminiyi Olusegun
Published: November 2009

Introduction: Patients with thalassemia major often present with a hypercoagulable state, the pathogenesis of which is still not understood. Materials and Methods: This study evaluates the risk factors for hypercoagulability in 50 β-thalassemia major patients and 50 healthy controls. Fasting total homocysteine, protein C (PC), protein S (PS), antithrombin (AT), activated protein C resistance (APCR) and lupus anticoagulant (LA) were assessed. MTHFR C677T mutation was determined. Results: Significant reductions in PC, PS and AT were noted in patients. Only 4% of the patients had hyperhomocysteinemia. Thirty-two percent of the patients were heterozygous and 4% were homozygous for MTHFR C677T mutation. Conclusion: The natural coagulation inhibitors PC, PS and AT were significantly reduced in patients with β-thalassemia major and were thus important risk factors for the hypercoagulable state, but hyperhomocysteinemia and MTHFR mutation do not seem to be significant risk factors for thromboembolic events.
Hydrogen Sulfide Opens the KATP Channel on Rat Atrial and Ventricular Myocytes
Authors: Zhong Guang-Zhen , Li Yan-Bing , Liu Xiu-Lan , Guo Lei-Sheng , Chen Mu-lei , Yang Xin-Chun
Published: November 2009

Objective: Hydrogen sulfide (H2S), an endogenous gaseous transmitter, was found to protect the heart from various forms of injury, but the underlying mechanism is not known. H2S can open the KATP channel on vascular smooth muscle cells, and the objective of this study was to determine whether H2S can open the KATP channel on myocardiocytes. Methods: The whole-cell patch-clamp technique was used to record IK,ATP and action potentials of atrial and ventricular myocytes isolated from the hearts of male Wistar rats. Sodium hydrogen sulfide (NaHS) was used as a donor of H2S to observe the effect of exogenous H2S on IK,ATP. DL-propargylglycine (PPG), an inhibitor of the synthesis of H2S, was used at a concentration of 200 µM to observe the effect of endogenous H2S on IK,ATP. Results: NaHS at concentrations (in µM) of 9.375, 18.75, 37.5, 75 and 150 increased IK,ATP by 12.8% (p > 0.05), 28.4% (p < 0.05), 38.8% (p < 0.01), 51.2% (p < 0.01) and 58.6% (p< 0.01) on ventricular myocytes, respectively, and by 6.8% (p > 0.05), 10.4% (p > 0.05), 18.9% (p < 0.01), 24.8% (p < 0.01) and 37.2% (p < 0.01) on atrial myocytes, respectively. The H2S-induced decrease in the duration of action potentials (APD90) of ventricular myocytes was concentration-dependent, although only NaHS at a concentration of 150 µM decreased the APD90 significantly (15%, p < 0.05). The H2S-induced decrease in APD90 on atrial myocytes was concentration dependent, but the statistical difference was not significant. Inhibition of IK,ATP by PPG was time dependent and the level of inhibition was: ventricular myocytes, 7% (p > 0.05), 10% (p < 0.05), 15.3% (p < 0.01), 24.0% (p < 0.01) and 28.9% (p < 0.01); atrial myocytes, 15.8% (p > 0.05), 21.3% (p > 0.05), 26.5% (p < 0.01), 34.0% (p < 0.01) and 43.2% (p < 0.01) measured at 5, 10, 15, 20 and 25 min, respectively. The increase in the APD90, by PPG was time dependent for ventricular myocytes [increased by 12.8% (p < 0.05) at 25 min]. The same was true for atrial myocytes, although only the value at 25 min was significant (15%, p < 0.05). Conclusions: H2S decreased the APD90,and both the endogenous and exogenous H2S-induced increase in IK,ATP on both atrial and ventricular myocytes was concentration dependent. These results may help to explain, at least in part, how H2S protects heart cells from various forms of injury.
Electrocorticographic Frequency Alteration Mapping of Speech Cortex during an Awake Craniotomy: Case Report
Authors: Breshears J. , Sharma M. , Anderson N.R. , Rashid S. , Leuthardt E.C.
Published: November 2009

Objective: Traditional electrocortical stimulation (ECS) mapping is limited by the lengthy serial investigation (one location at a time) and the risk of afterdischarges in localizing eloquent cortex. Electrocorticographic frequency alteration mapping (EFAM) allows the parallel investigation of many cortical sites in much less time and with no risk of afterdischarges because of its passive nature. We examined its use with ECS in the context of language mapping during an awake craniotomy for a tumor resection. Clinical Presentation: The patient was a 61-year-old right-handed Caucasian male who presented with headache and mild aphasia. Imaging demonstrated a 3-cm cystic mass in the posterior temporal-parietal lobe. The patient underwent an awake craniotomy for the mapping of his speech cortex and resection of the mass. Intervention: Using a 32-contact electrode array, electrocorticographic signals were recorded from the exposed cortex as the patient participated in a 3-min screening task involving active (patient naming visually presented words) and rest (patient silent) conditions. A spectral comparison of the 2 conditions revealed specific cortical locations associated with activation during speech. The patient was then widely mapped using ECS. Three of 4 sites identified by ECS were also identified passively and in parallel by EFAM, 2 with statistical significance and the third by qualitative inspection. Conclusion: EFAM was technically achieved in an awake craniotomy patient and had good concordance with ECS mapping. Because it poses no risk of afterdischarges and offers substantial time savings, EFAM holds promise for future development as an adjunct intraoperative mapping tool. Additionally, the cortical signals obtained by this modality can be utilized for localization in the presence of a tumor adjacent to the eloquent regions.
Radiation Schedules in Relation to Obliteration and Complications in Hypofractionated Conformal Stereotactic Radiotherapy of Arteriovenous Malformations
Authors: Lindvall Peter , Bergström Per , Blomquist Michael , Bergenheim A. Tommy
Published: November 2009

Aims: The purpose of this investigation was to assess the obliteration rate and complications following different radiation schedules of hypofractionated conformal stereotactic radiotherapy for cerebral arteriovenous malformations (AVMs). Methods: Twenty-five patients were treated with 35 Gy in 5 fractions, whereas 31 patients were treated with 30–32.5 Gy (mean: 31.6 ± 0.23 Gy) in 5 fractions. A complete angiographic follow-up is available for 40 patients. Results: Thirty-seven out of 40 patients (92.5%) have so far shown obliteration of their AVMs after a mean time of 3.2 ± 0.26 years (range: 2–8 years). The mean AVM volume in these patients was 8.2 ± 1.0 cm3 (range: 1.5–29 cm3). There was a higher rate of obliteration (88%) in patients treated with 35 Gy compared to those treated with <35 Gy (78%), even if this was not statistically significant. There was a significantly shorter time to obliteration in patients treated with 35 Gy. All patients who experienced symptomatic radionecrosis belonged to the group treated with 35 Gy. Conclusion: A radiation schedule of 35 Gy in 5 fractions may be more effective than a radiation schedule of <35 (30–32.5) Gy in obliterating AVMs. This may, however, be at the price of an increased risk of symptomatic radionecrosis.
Localization of DNA and RNA in Eosinophil Secretory Granules
Authors: Behzad Ali R. , Walker David C. , Abraham Thomas , McDonough John , Mahmudi-Azer Salahadin , Chu Fanny , Shaheen Furquan , Hogg James C. , Paré Peter D.
Published: November 2009

Background: Although the accepted paradigm is that the proteins stored in eosinophil crystalloid granules are translated from messenger RNA transcribed in the cell nucleus, recent ultrastructural evidence suggests that protein synthesis may also take place within eosinophilic granules. Methods: We used 2 different methods to detect the presence of DNA and RNA in eosinophil secretory granules. Using bromodeoxyuridine, a thymidine analogue, and bromouridine, a uracil analogue, we labeled the DNA and RNA in eosinophils in vivo in rabbits. Immunoelectron microscopy to localize these molecules was performed on ultrathin sections of blood and bone marrow eosinophils using monoclonal anti-bromodeoxyuridine antibody with IgG as a control. The immunogold grain density was measured in each subcellular compartment within the eosinophils and analyzed using image analysis software. A combination of DNA/CD63 immunofluorescence staining and a fluorescently labeled molecular probe that stains RNA was used to examine the presence of DNA and RNA in the secretory granules of human blood eosinophils. Results: The mean density of bromodeoxyuridine-labeled DNA and bromouridine-labeled RNA immunogold grains in the secretory granules of blood and bone marrow eosinophils were significantly higher (p < 0.0005) than cytoplasmic or background staining. We also demonstrated the existence of DNA and RNA in the CD63-positive secretory granules of human peripheral blood eosinophils by means of immunofluorescent staining and a fluorescently labeled molecular probe. Conclusions: These results provide evidence that eosinophil granules are the site of DNA and RNA synthesis and suggest the potential for a new role(s) for eosinophil-secretory granules.
Tryptase Is Not Cleared by the Kidneys into the Urine
Authors: Simon Michael R. , Jan Mindy , Yee Jerry , Nori Uday S. , Hu Jiang , Akin Cem , Schwartz Lawrence B.
Published: November 2009

Background: Patients with chronic kidney disease have been reported to have increased concentrations of blood tryptase. Detection of tryptase in the urine of healthy subjects has been reported. Objective: The objective is to determine whether tryptase is indeed cleared by the kidneys. Methods: Blood and urine collections were performed in healthy and systemic mastocytosis subjects. Total and mature tryptase concentrations in blood and total tryptase concentrations in urine were determined. Results: Total tryptase levels in urine were below the limit of detection in both healthy subjects and those with systemic mastocytosis, even after concentrating the urine 10-fold. Thus, both mature and protryptase levels in urine are <0.2 ng/ml. Conclusion: Tryptase is not cleared by the kidneys into the urine.
Sublingual Immunotherapy Efficacy of Dermatophagoides farinae Vaccine in a Murine Asthma Model
Authors: Yu Hai-qiong , Li Xiang-hui , Guo Hua , Liu Zhi-gang , Ran Pei-xin , Ji Kun-mei , Wang Jun
Published: November 2009

Background: Allergen-specific sublingual immunotherapy is a potential treatment for allergic diseases. Its effective dose and underlying mechanism are still to be explored. Here, we investigated the efficacy and mechanism of sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine asthma model. Methods: BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by sublingual treatment with Der f vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week. We analyzed their clinical symptoms, antibody levels, cytokine levels, T-cell proliferation and the regulatory T-cell numbers. Results: Mice treated with high-dose Der f sublingual vaccine prior to challenge displayed alleviated symptoms such as airway hyperreactivity, lung inflammation and mucus production, as well as less eosinophilic cells in bronchoalveolar lavage fluid. Interestingly, reduced responses of Der-f-specific IgE and increased responses of Der-f-specific IgA and IgG1 were aroused in the high-dose Der f sublingual vaccine group. We also observed that interleukin-4 was reduced and interferon-γ and interleukin-10 were increased among splenocytes and in bronchoalveolar lavage fluid, which inhibited Der-f-specific T-cell proliferation of the spleen and increased CD4+CD25+Foxp3+regulatory T cells in the spleen. However, mice treated with low-dose Der f sublingual vaccine developed allergic asthma. Conclusion: Our results illustrate that high-doseDer f sublingual vaccine may play a role in immunologic protection in murine allergic asthma, possibly by inducing regulatory T cells and Th1 reaction.
Airborne Study of Grass Allergen (Lol p 1) in Different-Sized Particles
Authors: De Linares C. , Díaz de la Guardia C. , Nieto Lugilde D. , Alba F.
Published: November 2009

Background: The Poaceae family is considered one of the main causes of pollen allergy in industrialized countries. The aim of this study is to establish the dynamics of the Poaceae allergens and determine their distribution in the different-sized particles in the atmosphere. Methods: The air of Granada (southern Spain) was sampled during the pollination period of Poaceae using a cascade impactor and a Hirst-type volumetric collector simultaneously. The sampled airborne allergens were analyzed by indirect ELISA and field emission scanning electron microscopy. Airborne pollen was evaluated with the Spanish Aerobiological Network methodology. Results:Poaceae pollen and allergenic activity have parallel dynamics during the period of maximum pollination, which is reflected in the positive correlations between the 2 variables. In addition, the highest Lol p 1 concentrations were recorded in particle sizes lower than 3.3 µm (stage 4-F). The Spearman correlation test showed that airborne allergens are not dependent on meteorological factors, such as humidity, wind direction or sunshine, however, Lol p 1 allergen correlated positively with Poaceae pollen. Conclusions: The results of the present study confirm that the Lol p 1 allergen is detected more frequently with pollutants than with coarse particles with similar dynamics and a positive correlation between airborne pollen and aeroallergens. Moreover, Lol p 1 is released in stable weather conditions without large changes in humidity or temperature.
Occupational Allergy in Strawberry Greenhouse Workers
Authors: Patiwael J.A. , Vullings L.G.J. , de Jong N.W. , van Toorenenbergen A.W. , Gerth van Wijk R. , de Groot H.
Published: November 2009

Background: Employees in strawberry greenhouses are highly exposed to several (potential) allergenic agents. However, no occupational allergy in this branch has been described before. First, the presence of work-related allergic symptoms in strawberry workers was explored. Second, we aimed to prove the concept that an IgE-mediated allergy could be responsible for work-related symptoms. To test the possibility of an IgE response secondary to cross-reactivity to birch or grass pollen, inhibition experiments were performed. Methods: First, a questionnaire survey concerning work-related allergic symptoms among strawberry workers in the Netherlands was carried out. Second, 3 workers with work-related symptoms were investigated in detail. Skin tests, serum-specific IgE tests with home-made extracts of strawberry pollen and other possible allergenic agents of the strawberry greenhouse environment were executed. Furthermore, immunoblots and nasal provocations with strawberry pollen extract were performed. In addition, inhibition experiments were performed. Results: 29 of 75 questionnaire respondents (38.7%) reported work-related symptoms. Sensitization to strawberry pollen was found in skin tests in all 3 employees with work-related symptoms. ELISA and immunoblotting with strawberry pollen showed positive results in 2 employees. Birch and grass pollen failed to inhibit IgE binding to strawberry pollen in 1 of 2 employees. Partial inhibition was seen in the second employee. Nasal provocation validated clinically relevant allergy to these pollens in 2 of 3 subjects. Conclusions: Allergic symptoms attributable to the workplace are present among a proportion of strawberry greenhouse employees. An IgE-mediated occupational allergy to strawberry pollen may contribute to these symptoms.
Serum Transforming Growth Factor-β Levels Depend on Allergen Exposure in Allergic Rhinitis
Authors: Ciprandi Giorgio , De Amici Mara , Tosca Mariangela , Marseglia Gianluigi
Published: November 2009

Background:Allergic rhinitis (AR) is characterized by inflammation sustained by dysregulated immune response. T-regulatory cells are involved in AR pathogenesis, mainly producing IL-10 and transforming growth factor (TGF)-β. Indeed, there is a functional and allergen-specific defect of T-regulatory cells in AR. However, there are no data about the influence of allergen exposure on TGF-β serum levels. Therefore, the aim of this preliminary study was to evaluate TGF-β serum levels in patients with seasonal AR. Patients were evaluated either outside the pollen season and after 1 preseasonal sublingual immunotherapy (SLIT) course (38 subjects) or during the pollen season (57 subjects). Methods:All patients were allergic to Parietaria and/or grasses alone. TGF-β was measured by a commercially available kit. Symptoms, drug use and eosinophils were evaluated.Serum allergen-specific IgG and IgA levels were also measured by the ELISA method. Results:TGF-β serum levels were significantly lower in patients evaluated outside the pollen season in comparison with the other 2 situations. SLIT induced the significantly highest TGF-β serum levels. There was a significant negative relationship between TGF-β and eosinophils in patients after SLIT. IgG and IgA levels were higher in SLIT-treated patients. Conclusion: This preliminary study provides evidence that TGF-β serum levels are significantly dependent on allergen exposure.