bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical Process Control Charts for Measuring and Monitoring Temporal Consistency of Ratings
Authors: Omar M. Hafidz
Published: March 2010

Methods of statistical process control were briefly investigated in the field of educational measurement as early as 1999. However, only the use of a cumulative sum chart was explored. In this article other methods of statistical quality control are introduced and explored. In particular, methods in the form of Shewhart mean and standard deviation charts are introduced as techniques for ensuring quality in a measurement process for rating performance items in operational assessments. Several strengths and weaknesses of the procedures are explored with illustrative real and simulated rating data. Further research directions are also suggested.
Enzyme technology for precision functional food ingredient processes
Authors: Meyer Anne S.
Published: March 2010

A number of naturally occurring dietary substances may exert physiological benefits. The production of enhanced levels or particularly tailored versions of such candidate functional compounds can be targeted by enzymatic catalysis. The recent literature contains examples of enhancing bioavailability of iron via enzyme‐catalyzed degradation of phytate in wheat bran, increasing diacyl‐glycerol and conjugated linoleic acid levels by lipase action, enhancing the absorption of the citrus flavonoid hesperetin via rhamnosidase treatment, and obtaining solubilized dietary fiber via enzymatic modification of potato starch processing residues. Such targeted enzyme‐catalyzed reactions provide new invention opportunities for designing functional foods with significant health benefits. The provision of well‐defined naturally structured compounds can, moreover, assist in obtaining the much‐needed improved understanding of the physiological benefits of complex natural substances.
Mass spectrometric–based protein chips for detection of food‐derived bioactive components
Authors: Stagsted Jan , Jørgensen Ann Louise W. , Juul‐Madsen Helle R.
Published: March 2010

Bioactive components in the diet influence our health and well‐being beyond that of simple supply of energy and raw materials for biochemical reactions. However, the complex chemistry and composition of our food does not make the identification of potential bioactive components a straightforward task. Bioassays for a multitude of functionalities have to be performed for thousands of different food‐derived molecules in order to identify important interactions. Our approach is to directly identify those food molecules that interact with cellular targets based on mass spectrometric (MS) techniques through immobilization of cellular target molecules on glass chips and incubation with various foods. Food‐derived molecules that bind with high affinity can then be directly analyzed by MS. We have chosen bovine colostrum, a potent bioactive food, and cellular receptors of the innate immune response as our model for proof of concept.
Ellagic acid and polyphenolics present in walnut kernels inhibit in vitro human peripheral blood mononuclear cell proliferation and alter cytokine production
Authors: Anderson Koren C. , Teuber Suzanne S.
Published: March 2010

Tree nuts, including walnuts, are important elicitors of food allergy. We examined the ability of walnut kernel polyphenolics and purified ellagic acid (EA) to modulate cytokine production and cellular proliferation from stimulated human peripheral blood mononuclear cells (PBMC). IL‐13 and TNF‐α production decreased while no change was observed in IL‐4 production. Paradoxically, EA and the walnut polyphenolics all significantly and dose‐dependently inhibited stimulated [phytohemagglutin (PHA), α‐CD3, and phorbol myristate acetate (PMA)/ionomycin] PBMC proliferation while simultaneously increasing IL‐2 production. When added at time 0 min and 2 h, EA dose‐dependently inhibited PHA‐induced proliferation. However, at 30 min and 1 h, low doses of EA (10 and 1 μM) significantly increased proliferation above that of PHA alone, although higher doses led to inhibition. Our data do not support the hypothesis that walnut polyphenolics skew a cytokine response toward Th2 in an in vitro environment. However, immunomodulatory effects are present, including an inhibition of cellular proliferation despite no decrease in IL‐4 or IL‐2.
Toward tailored synthesis of functional polysaccharides in plants
Authors: Geshi Naomi , Petersen Bent Larsen , Scheller Henrik Vibe
Published: March 2010

Polysaccharides derived from plant cell wall materials play an important role in our diet. Dietary fibers work as prebiotics in the human gut, and some plant polysaccharides are known to have more direct beneficial impacts on human health. In the food industry, plant fiber materials, such as gums are widely used as structural ingredients. Complex polysaccharides account for most of the plant cell wall, and their biosynthetic pathways and their regulation are largely unknown. Systematic collaborative efforts for defining the structure and impact on human health of beneficial fibers and elucidating the biosynthetic pathways and their regulation will open a great potential for biotechnological applications.
Can bioactive foods affect obesity?
Authors: Astrup A. , Kristensen M. , Gregersen N.T. , Belza A. , Lorenzen J.K. , Due A. , Larsen T.M.
Published: March 2010

Many dietary factors or substances exert effects on the three components of energy balance, and one strategy for tackling weight gain could be to use the inherent properties of these substances. Here, we will review the evidence regarding nutritional factors with a potential impact on energy balance, such as wholegrain foods, dietary fiber and protein content, calcium, and certain spices. There is ample evidence to suggest that dietary protein, wholegrain, and fiber promote satiety and either reduce energy absorption or stimulate energy expenditure. Dietary calcium reduces fat absorption, and a sufficient intake may also prevent excessive hunger during weight loss diets. Chili and mustard have beneficial effects on energy balance, although the quantitative importance of this may be modest. Manipulation of diet composition with an aim to prevent weight gain and weight regain is a promising avenue of research.
Phenolic Acids and Methylxanthines Composition and Antioxidant Properties of Mate (Ilex paraguariensis) Residue
Authors: Vieira Manoela A. , Maraschin Marcelo , Pagliosa Cristiane M. , Podestá Rossana , De Simas Karina N. , Rockenbach Ismael Ivan , Amboni Renata D. de M. C. , Amante Edna R.
Published: March 2010

ABSTRACT:  Ilex paraguariensis is known to contain compounds with antioxidant properties, such as phenolic acids, and its stimulant properties are attributed to methylxanthines, such as caffeine. The aims of this study were to evaluate the phenolic, methylxanthinic, and tannin composition of a mate residue (mate powder), to compare the quali‐quantitative phenolic composition and the antioxidant potential of extracts obtained from distinct solvent systems. Among the extracts prepared with different solvents, the 80% methanol extract showed the highest total polyphenol content (11.51 g/100 g) and antioxidant activity. HPLC analysis showed that 4,5 dicaffeoylquinic acid is the major component of the phenolic fraction of mate powder. The caffeine, theobromine, and tannin contents in mate powder were 1.01, 0.10, and 0.29 g/100 g, respectively. Consumption of mate powder would significantly contribute to antioxidant and stimulant intake, providing high amounts of phenolic acids, tannins, and methylxanthines with biological effects potentially beneficial for human health.

Practical Application: This article contributes to the minimization of residues in yerba‐mate processing.
Collision Hodgkin lymphoma and Warthin tumour. Report of a case and review of the literature
Authors: Cozzolino I. , Zeppa P. , Cuccuru A. , Picardi M. , Vetrani A. , Palombini L.
Published: March 2010

Association between Warthin tumour (WT) and lymphoma is extremely uncommon and the latter are generally B‐cell type non‐Hodgkin lymphoma. We describe a case of collision of WT and Hodgkin's lymphoma (HL) of the parotid gland. A 60‐year‐old man complained of slow progressive swelling of the right parotid gland. The ultrasound (US) examination detected a well‐defined, bilobated hypoechoic mass located in the anterior lobe of the parotid gland. A US‐guided fine‐needle cytology (FNC) was performed and a cytological diagnosis of WT was made. The histological sections revealed two nodules: the main one showed a classical WT and the smaller, adjacent to the WT and separated from the later by a fibrotic band, showed residual gland and lymphoid tissue with microscopic and phenotypic features of HL. This is the third report in the literature describing a collision of WT and HL, likely representing a simple coincidence rather than a possible association between the two entities.
Intravitreal bevacizumab alone versus in combination with photodynamic therapy for the treatment of neovascular maculopathy in patients aged 50 years or older: 1‐year results of a prospective clinical study
Authors: Lim Jong Yoon , Lee Sun Young , Kim June‐Gone , Lee Joo Yong , Chung Hyewon , Yoon Young Hee
Published: March 2010

Purpose:  To compare the outcomes of treatment with intravitreal bevacizumab alone (BEVA group) or in combination with photodynamic therapy (PDT) (COMB group), in patients aged at least 50 years with neovascular maculopathy.

Methods:  Forty‐one patients with neovascular age‐related macular degeneration (AMD) (n = 31) or polypoidal choroidal vasculopathy (PCV) (n = 10) were randomized to either the BEVA group (n = 18) or the COMB group (n = 23). A total of three intravitreal bevacizumab injections (1.25 mg/0.05 ml) were given at 6‐week intervals. In the COMB group, PDT was included near the time of one injection. Patients underwent best‐corrected visual acuity (BCVA) measurement and optical coherence tomography (OCT) at every visit. Fluorescein angiography and indocyanine green angiography were repeated every 3 months.

Results:  Overall BCVA (p = 0.001) and central foveal thickness (CFT) (p < 0.001) measured by OCT improved significantly at 12 months, and there was no between‐group difference in BCVA or CFT between the BEVA and COMB groups. Whereas AMD patients showed significant improvement in BCVA (p = 0.001) and CFT (p = 0.004), PCV patients failed to improve. The effect of bevacizumab alone on neovascular AMD was similar to that of combination therapy, when measured by both BCVA and CFT. The total number of bevacizumab injections was not reduced when PDT was given, either among all patients or in a subgroup of naïve patients (p > 0.05). No serious complication was noted.

Conclusion:  The results of our 12‐month prospective study indicate that intravitreal bevacizumab alone has similar efficacy and safety to bevacizumab plus PDT for treatment of patients with neovascular AMD, even treatment‐naïve patients. The addition of PDT did not assist in reducing the required total number of bevacizumab injections.
Children's Art for Peace: Exhibit
Authors: Clarke Andrew
Published: March 2010

Children's Art for Peace: Arab and Jewish Children's Drawings from the Givat Haviva Institute in Israel
The Democratic Islamic Republic of Iran in Exile
Authors: Piazza James A.
Published: March 2010

This paper examines the political, organizational, and ideological shifts necessitated by the chief Iranian oppositional group, the progressive Islamist Mojahedin‐e Khalq (People's Mojahedin) organization, beginning with its exile from the Islamic Republic starting in June of 1981 through the present day. An analysis of these shifts is presented as a chronological series of evolving relationships including the Mojahedin's collaboration with a broad‐base of oppositional groups and individuals during its Paris exile and founding of the National Council of Resistance (NCR); the Mojahedin's relocation to Baghdad and subsequent foundation of the National Liberation Army (NLA); and the Mojahedin's courtship of Western governments and international organizations to promote its cause. Following the depiction of the transformations undertaken by the Mojahedin throughout these three phases is an analysis of both the status of the organization as a result of these changes and an assessment of the price of exile.
The Relevance of Happiness to Eternal Existence: Some Reflections on Ibn Sina's View
Authors: Inati Shams C.
Published: March 2010

The task of this paper is to determine Ibn Sina's view on the following issues: the nature of the object of human happiness, the method for attaining this object, and the consequence of attaining or of falling short of attaining this object.
Review
Authors: Gunderson Gil
Published: March 2010

Book reviewed in this article:

Contemporary Syria, Eberhard Kienle, editor with Preface by Patrick Seale

State and Society in Syria and Lebanon, 1919–1991, Yousef M. Choueiri, editor
To Fashion Identity
Authors: Hibbard Allen
Published: March 2010

Book reviewed in this article:

The Hostage, Zayd Mutee' Dammaj, Translated by May Jayyusi and Christopher Tingley

Ramza, Out el Kouloub, Translated with an Introduction by Nayra Atiya
From Peasants to the PLO
Authors: Silverburg Sanford
Published: March 2010

Book reviewed in this article:

Palestinian Peasants and Ottoman Officials: Rural Administration Around Sixteenth‐Cent ury Jerusalem, Amy Singer

Politics in Palestine: Arab Factionalism and Social Disintegration, 1939–1948, Issa Khalaf

U.S.‐PLO Dialogue: Secret Diplomacy and Conflict Resolution, Mohamed Rabie
Review
Authors: Aman Mohammed M.
Published: March 2010

Book reviewed in this article:

Musées, Civilisation et Développement: useums, Civilization and Development

Directory of Museums in the Arab Countries:
Power and Security Issues in the Middle East
Authors: Rigsbee W. Lynn
Published: March 2010

Book reviewed in this article:

Middle Eastern Security: Prospects for an Arms Control Regime, Efraim Inbar and Shmuel Sandler, editors

The Quest for Hegemony in the Arab World: The Struggle over the Baghdad Pact, Elie Podeh
Three Books on Israel and Palestine
Authors: Silverburg Sanford R.
Published: March 2010

Book reviewed in this article:

The Palestinian Entity, 1959–1974: Arab Politics and the PLO: Moshe Shemesh
Envoy to Moscow: Memoirs of an Israeli Ambassador, 1988‐92: Aryeh Levin
Authors: Kumaraswamy P. R.
Published: March 2010

Book reviewed in this article:

Security Challenges in the Mediterranean Region: Roberto Aliboni, George Joffe and Tim Niblock, editors
Television Programs For Women in The United Arab Emirates and The City Of Milwaukee, U.S.A
Authors: Al‐Ali Fawzia
Published: March 2010

To know more about the role of the television in dealing with women's problems in both United Arab Emirates (UAE) television and television in Milwaukee, Wisconsin U.S.A., a comparative analytical study was made for such programs in both countries. The researcher believes that developing local women's programs can benefit from the experiences of others, along with comparative studies between women's programs on UAE television and Milwaukee television. The study covers public television programs during the period from September 15 to October 30, 1997. The investigation relies on the survey and content analysis methods. These methods are usually adopted to survey and compare television programs in studies similar to this one.
Voices of Change: Short Stories by Saudi Arabian Women Writers: Edited and translated by Abubaker Bagader, Ava M. Heinrichsdorf, Deborah S. Akers. Additional Translations by Abdul‐Aziz Al‐Sebail
Authors: Simon Rachel , Simon Rachel
Published: March 2010

Book reviewed in this article:

Within the Circle: Parents and Children in an Arab Village: Andrea B. Rugh
War in the Land of Egypt: Yusuf al‐Qa'id: Translated by Olive and Lorne Kenney and Christopher Tingley
Authors: Gordon Joel
Published: March 2010

Book reviewed in this article:

Houses Behind the Trees: Mohamed El‐Bisatie: Translated by Denys Johnson‐Davies
Imperial Istanbul: A Traveller's Guide: Jane Taylor
Authors: Khalidi Omar
Published: March 2010

Book reviewed in this article:

The Revolt of Afrian Slaves in Iraq in the 3rd/9th Century: Alexandre Popovic
Desert Victory: The War for Kuwait: Norman Friedman
Authors: Ovendale Ritchie
Published: March 2010

Book reviewed in this article:

The Scourging of Iraq: Sanctions, Law and Natural Justice, 2nd ed: Geoff Simons
Review
Authors: Ibrahim Eman
Published: March 2010

Saddam's Secrets: The Hunt for Iraq's Hidden Weapons, Tim Trevan

The Greatest Threat: Iraq, Weapons of Mass Destruction, and the Crisis of Global Security, Richard Butler
Lebanon's Quest: The Road to Statehood 1926–1939: Meir Zamir
Authors: Divine Donna Robinson
Published: March 2010

Book reviewed in this article:

Lebanon: The Challenge of Independence: Eyal Zisser
Middle Eastern Minorities and Diasporas: Moshe Mo'az and Gabriel Sheffer, eds.
Authors: Simon Rachel
Published: March 2010

Book reviewed in this article:

Muslim Minorities in the West: Visible and Invisible: Yvonne Yazbeck Haddad and Jane I. Smith, eds.
Iraq: Past, Present and Uncertain Future: a Review Essay
Authors: Aman Mohammed M.
Published: March 2010

Dancing with Saddam: The Strategic Tango of Jordanian‐Iraqi Relations. David Schenker. Lanham, MD

Dark Victory: America's Second War against Iraq. Jeffrey Record. Annapolis, MD

Ignorant Armies: Sliding into War in Iraq. Gwynne Dyer.

The Gulf War Chronicles: a Military History of the First War with Iraq. Richard S. Lowry.

The Iraq War: a Military History. William Murray and Major General Robert H. Scales, Jr.

The Iraq War: Hidden Agendas and Babylonian Intrigue, the Regional Impact on Shi'ites, Kurds, Sunnis and Arabs. Raphael Israeli.

The Modern History of Iraq, 2nd. ed. Phebe Marr. Boulder

The New Iraq: Rebuilding the Country for Its People, The Middle East, and the World. Joseph Braude.
The Doomed Ugly Duckling Will Never Turn into a Swan: Meir Vizeltir Writes Holocaust
Authors: Mazor Yair
Published: March 2010

When I was a child Reed and masts were erecting by the seashore And I, while lying down there, Failed to tell the difference among them, Since all of them ascended to the sky over my head. Yehuda Amichai. “When I Was a Child”
Iraq and Hubris: Avoiding History a Review Essay
Authors: Rich Paul
Published: March 2010

Book reviewed in this article:

Hubris: The Inside Story of Spin, Scandal, and the Selling of the Iraq War: Michael Isiko. and David Corn

Blind into Baghdad: America's War in Iraq: James Fallows

Overthrow: America's Century of Regime Change from Hawaii to Iraq: Stephen Zinzer

The Politics of Truth: Inside the Lies that Led to War and Betrayed My Wife;s CIA Identity: Joseph Wilson

The Italian Letter: How the Bush Administration Used a Fake to Build the Case for War in Iraq: Peter Eisner and Knut Royce

Iraq and the Lessons of Vietnam: or, How Not to Learn From the Past: Lloyd C. Gardner, Marilyn B. Young, Eds.
Enrichment Training Program and Successful Marriage in Kuwait: a Field Study on Kuwaiti Couples
Authors: Alqashan Humoud
Published: March 2010

The main purpose of the current study was to determine whether a marriage enrichment program could effectively increase and improve marital satisfaction and marital communication of Kuwaiti couples. In addition, most of the previous studies which focused on marriage enrichment programs have been conducted with predominantly white, North American married couples (Yelsma, 1988). The study of the impact of the marriage enrichment will provide insight into the ways couples from other cultural backgrounds interact with each other in achieving marital satisfaction, especially, couples from Muslim countries. Participants were 62 married couples (16 couples in the experimental group; 16 couples in the control group) — their marital duration ranging from one year to thirty‐one years. The study examined whether a marital enhancement program could make any change in the marital satisfaction of Kuwaiti couples. The study focused on the following research questions: 1) Do socio‐demo‐graphic factors (age, income, education, duration of marriage, children) play a role on the marital satisfaction level of Kuwaiti couples? 2) Is there a difference in the marital satisfaction scale between male and female in the pre‐test, post‐test marital satisfaction scale? 3) Does the marriage enhancement training program in the Social Development Office (SDO) influence the post‐test level of the marital satisfaction of the participants? The study concluded that the marriage enrichment program in the SDO of Kuwait has had a significant positive effect on marital communication and marital adjustment immediately following the enrichment experience.
Political Security Issues at the Concluding Statements of the Gulf Cooperation Council (GCC) Sessions 1981–2001: an Analytical Study of the Content
Authors: Al‐Musfir Muhammad Saleh
Published: March 2010

The purpose of this paper is to investigate the contents of the concluding statements of the Gulf Cooperation Council (GCC) sessions from 1981 to 2001 concerning political and security issues. In particular, the study reviews six topics, including cooperation in the military field, cooperation in the field of security, the Iraqi‐Kuwaiti issue, the Arab‐Israeli conflict, cooperation in the field of fighting terrorism, and GCC Iranian relations. The GCC Supreme Council affirmed the right of the Palestinians to establish their independent state whose capital would be Eastern Jerusalem. The GCC demanded the elimination of weapons of mass destruction when it came to the issue of the Iraqi ‐ Kuwait problem. Concerning the relations between the GCC and Iran, the emphasis was on calling for a peaceful resolution to the problems of the islands [Abu Musa, Tunb Major and Tunb Minor]. The GCC stressed the importance of intensive communications among the security agencies in the member states, and condemning terrorism in all its forms and types. Finally, the GCC expressed satisfaction with the accomplishments in the military and defense sector.
Contemporary Civil Conflicts in the Nile Basin States
Authors: Hadyia Abdallah
Published: March 2010

This topic deals with the reasons for the civil conflicts in the Nile Basin Area in Africa. From the geographical point of view, these countries are suffering from the lack of demarcation of boundaries among them. From an economic point of view, they would fight over the abundant economic resources that were taken away wholly by the foreign companies, leaving the crumbs to be disputed over. Additionally, ethnic differences kindle ethnic and religious contradictions. This research will also ascertain some of these reasons, and then review examples of the civil conflicts in the area. Unless these contradictions can be rectified, or mitigated, they will continue to simmer and periodically re‐emerge as a full‐fledged civil war.
Gendered Structures of Local Politics in Turkey
Authors: Alkan Ayten
Published: March 2010

Indicators offered by available international statistical data and observations of many researchers point out that women's formal political involvement at the local level is stronger than that at the national level for the majority of states. However, gendered political patterns in Turkey have been following a rather different path. One and the most significant contradictory aspect is that women's representation at local elected organs is weaker than the national parliament. This article, first, investigates the reasons for this relatively weak existence in formal local politics. The references of this relativity are both national formal politics of Turkey, and the dominant worldwide model. Secondly, the article tries to establish country‐specific links between formal and informal local politics concerning women's participation. The experience in Turkey has proven that women's local engagement does not necessarily propel decision‐making power and women's empowerment. Women's local mobilization in Turkey has been mostly limited to socio‐cultural and charity activities instead of central decisions on the settlement, and of efforts for establishing women's local political agendas. Moreover, as a very prominent factor concerning the maintenance of asymmetric gendered structures of local politics, women's movement at the national level has been lacking in systematic political interest in the issue until very recently. In this article, these pretensions and future prospects are discussed in terms of the actual global‐national circumstances affecting local politics as well as women's local conditions. To these ends, existing quantitative‐qualitative research, data and analysis, and relevant findings of the author's recent (2000–2003) original research, as well as her observations through participation in recent feminist activism targeting local politics are being evaluated.
Nuclear Iran is Not an Option: A new negotiating strategy to prevent Iran from developing nuclear weapons
Authors: Ben‐Meir Alon
Published: March 2010

The negotiations between Iran and the P5+11 over Tehran's nuclear enrichment activities have not only failed to reach an agreement but have brought Iran much closer to the threshold of mastering the technology to produce nuclear weapons. There are many factors that precipitated this breakdown, including the West's inability to understand and deal with the Iranian psychological disposition, the failure to present to Iran the severity of the punitive measures that could be inflicted as a consequence of their defiance, and the US administration's misleading policy that gave Iran the room to maneuver. There is an urgent need to adopt a distinctively new strategy toward Iran consisting of three tracks of separate but interconnected negotiations: The first should focus on the current negotiations on Iran's enrichment program and the economic incentive package; the second should concentrate on regional security and the consequences of continued Iranian defiance; and the third track should address Iran's and the United States' grievances against each other. The United States must initiate all three tracks without which future talks will be as elusive as the previous negotiations, except this time the West and Israel will be facing the unsettling prospect of a nuclear Iran.
Perceptions of Academic Librarians in Kuwait of Library 2.0
Authors: Al‐Daihani Sultan
Published: March 2010

This paper reports the results of a Web‐based survey designed to explore the perceptions of academic librarians in Kuwait of Library 2.0. It investigates their familiarity with Web 2.0 concepts, tools, services and applications as these relate to academic libraries, and also explores the obstacles to their use. A Web‐based questionnaire was administered to all of the librarians in four universities in Kuwait. It was found that these librarians have a low level of familiarity with Library 2.0 applications. Lack of training was found to be the most inhibiting barrier to their use. There is a positive correlation between their years of work experience and their perceptions of Library 2.0 applications in academic libraries but no correlation between their years of work experience and the barriers to its use. The results from this study contribute to an understanding of the effect of these technologies on academic librarians. They could also be used to create and support appropriate initiatives for the integration of these applications in academic libraries.
Zinc inhibition of monomeric and dimeric proton channels suggests cooperative gating
Authors: Musset Boris , Smith Susan M. E. , Rajan Sindhu , Cherny Vladimir V. , Sujai Sukrutha , Morgan Deri , DeCoursey Thomas E.
Published: March 2010

Voltage‐gated proton channels are strongly inhibited by Zn2+, which binds to His residues. However, in a molecular model, the two externally accessible His are too far apart to coordinate Zn2+. We hypothesize that high‐affinity Zn2+ binding occurs at the dimer interface between pairs of His residues from both monomers. Consistent with this idea, Zn2+ effects were weaker in monomeric channels. Mutation of His193 and His140 in various combinations and in tandem dimers revealed that channel opening was slowed by Zn2+ only when at least one His was present in each monomer, suggesting that in wild‐type (WT) HV1, Zn2+ binding between His of both monomers inhibits channel opening. In addition, monomeric channels opened exponentially, and dimeric channels opened sigmoidally. Monomeric channel gating had weaker temperature dependence than dimeric channels. Finally, monomeric channels opened 6.6 times faster than dimeric channels. Together, these observations suggest that in the proton channel dimer, the two monomers are closely apposed and interact during a cooperative gating process. Zn2+ appears to slow opening by preventing movement of the monomers relative to each other that is prerequisite to opening. These data also suggest that the association of the monomers is tenuous and allows substantial freedom of movement. The data support the idea that native proton channels are dimeric. Finally, the idea that monomer–dimer interconversion occurs during activation of phagocytes appears to be ruled out.
Substance P inhibits GABAB receptor signalling in the ventral tegmental area
Authors: Xia Yan‐Fang , Margolis Elyssa B. , Hjelmstad Gregory O.
Published: March 2010

Substance P (SP) and its receptors are involved in anxiety‐related behaviours and regulate the intake of drugs of abuse and alcohol. Within the midbrain ventral tegmental area (VTA), a region that is clearly involved in the control of these behaviours, SP is released by stress and has been shown to trigger relapse. SP activates neurokinin (NK) receptors, which excites midbrain dopamine (DA) neurons and leads to increased DA in target regions. In this study, we have investigated the mechanisms underlying SP actions in the VTA, specifically investigating interactions between SP and GABAB receptors. We show that in VTA neurons, NK receptor activation closes an inwardly rectifying potassium channel, and moreover inhibits GABAB receptor‐mediated transmission through an interaction that depends upon phospholipase C (PLC), intracellular calcium and protein kinase C (PKC).
Cholinergic Augmentation of Insulin Release Requires Ankyrin-B
Authors: Healy Jane A. , Nilsson Kent R. , Hohmeier Hans E. , Berglund Jelena , Davis Jonathan , Hoffman Janis , Kohler Martin , Li Luo-Sheng , Berggren Per-Olof , Newgard Christopher B. , Bennett Vann
Published: March 2010

The scaffolding protein ankyrin-B is needed for maximal insulin release, and loss of function is a risk factor for diabetes.
Ido for Lowering Blood Pressure
Authors: Adler Elizabeth M.
Published: March 2010

Tryptophan metabolism to kynurenine represents a previously unknown pathway for regulation of blood pressure during systemic inflammation.
Signaling by Diffusion
Authors: Wong Wei
Published: March 2010

Actin and ezrin networks limit signaling through the BCR by restricting its mobility.
Moving Signals
Authors: Vinson Valda
Published: March 2010

Mechanical forces acting on a cell-surface receptor affect the activation of a signaling pathway involved in breast cancer.
Persistence of Uropathogenic
Escherichia coli
in the Face of Multiple Antibiotics
Authors: Blango Matthew G. , Mulvey Matthew A.
Published: March 2010

Numerous antibiotics have proven to be effective at ameliorating the clinical symptoms of urinary tract infections (UTIs), but recurrent and chronic infections continue to plague many individuals. Most UTIs are caused by strains of uropathogenic
Escherichia coli
(UPEC), which can form both extra- and intracellular biofilm-like communities within the bladder. UPEC also persist inside host urothelial cells in a more quiescent state, sequestered within late endosomal compartments. Here, we tested a panel of 17 different antibiotics, representing seven distinct functional classes, for their effects on the survival of the reference UPEC isolate UTI89 within both biofilms and host bladder urothelial cells. All but one of the tested antibiotics prevented UTI89 growth in broth culture, and most were at least modestly effective against bacteria present within
in vitro
-grown biofilms. In contrast, only a few of the antibiotics, including nitrofurantoin and the fluoroquinolones ciprofloxacin and sparfloxacin, were able to eliminate intracellular bacteria in bladder cell culture-based assays. However, in a mouse UTI model system in which these antibiotics reached concentrations in the urine specimens that far exceeded minimal inhibitory doses, UPEC reservoirs in bladder tissues were not effectively eradicated. We conclude that the persistence of UPEC within the bladder, regardless of antibiotic treatments, is likely facilitated by a combination of biofilm formation, entry of UPEC into a quiescent or semiquiescent state within host cells, and the stalwart permeability barrier function associated with the bladder urothelium.
In Vitro
and
In Vivo
Activities of 1,3,4-Thiadiazole-2-Arylhydrazone Derivatives of Megazol against
Trypanosoma cruzi
Authors: Salomão K. , de Souza E. M. , Carvalho S. A. , da Silva E. F. , Fraga C. A. M. , Barbosa H. S. , de Castro S. L.
Published: March 2010

From a series of 1,3,4-thiadiazole-2-arylhydrazone derivatives of megazol screened
in vitro
against
Trypanosoma cruzi
, eight (S1 to S8) were selected for
in vivo
screening by single-dose oral administration (200 mg/kg of body weight) to infected mice at 5 days postinfection (dpi). Based on significant decreases in both parasitemia levels and mortality rates, S2 and S3 were selected for further assays. Despite having no
in vivo
effect, S1 was included since it was 2-fold more potent against trypomastigotes than megazol
in vitro
. Trypomastigotes treated with S1, S2, or S3 showed alterations of the flagellar structure and of the nuclear envelope. When assayed on intracellular amastigotes, the selectivity index (SI) for macrophages was in the range of >27 to >63 and for cardiac cells was >32 for S1 and >48 for megazol. In noninfected mice, S1 did not alter the levels of glutamic oxalacetic transaminase (GOT), glutamate pyruvate transaminase (GPT), or urea. S2 led to an increase in GOT, S3 to increases in GOT and GPT, and megazol to an increase in GOT. Infected mice were treated with each derivative at 50 and 100 mg/kg from dpi 6 to 15: S1 did not interfere with the course of infection or reduce the number of inflammatory foci in the cardiac tissue, S2 led to a significant decrease of parasitemia, and S3 decreased mortality. There was no direct correlation between the
in vitro
effect on trypomastigotes and amastigotes and the results of the treatment in experimental models, as S1 showed a high potency
in vitro
while, in two different schemes of
in vivo
treatment, no decrease of parasitemia or mortality was observed.
Ethambutol Optimal Clinical Dose and Susceptibility Breakpoint Identification by Use of a Novel Pharmacokinetic-Pharmacodynamic Model of Disseminated Intracellular
Mycobacterium avium
Authors: Deshpande Devyani , Srivastava Shashikant , Meek Claudia , Leff Richard , Gumbo Tawanda
Published: March 2010

Ethambutol, together with a macrolide, is the backbone for treatment of disseminated
Mycobacterium avium
disease. However, at the standard dose of 15 mg/kg of body weight/day, ethambutol efficacy is limited. In addition, susceptibility breakpoints have consistently failed to predict clinical outcome. We performed dose-effect studies with extracellular
M. avium
as well as with bacilli within human macrophages. The maximal kill rate (
E
max
) for ethambutol against extracellular bacilli was 5.54 log
10
CFU/ml, compared to 0.67 log
10
CFU/ml for intracellular
M. avium
, after 7 days of exposure. Thus, extracellular assays demonstrated high efficacy. We created a hollow-fiber system model of intracellular
M. avium
and performed microbial pharmacokinetic-pharmacodynamic studies using pharmacokinetics similar to those of ethambutol for humans. The
E
max
in the systems was 0.79 log
10
CFU/ml with 7 days of daily therapy, so the kill rates approximated those encountered in patients treated with ethambutol monotherapy. Ratio of peak concentration to MIC (
C
max
/MIC) was linked to microbial kill rate. The
C
max
/MIC ratio needed to achieve the 90% effective concentration (EC
90
) in serum was 1.23, with a calculated intramacrophage
C
max
/MIC ratio of 13. In 10,000 patient Monte Carlo simulations, doses of 15, 50, and 75 mg/kg achieved the EC
90
in 35.50%, 76.81%, and 86.12% of patients, respectively. Therefore, ethambutol doses of ≥50 mg/kg twice a week would be predicted to be better than current doses of 15 mg/kg for treatment of disseminated
M. avium
disease. New susceptibility breakpoints and critical concentrations of 1 to 2 mg/liter were identified for the determination of ethambutol-resistant
M. avium
in Middlebrook broth. Given that the modal MIC of clinical isolates is around 2 mg/liter, most isolates should be considered ethambutol resistant.
Carbapenem-Resistant KPC-2-Producing
Escherichia coli
in a Tel Aviv Medical Center, 2005 to 2008
Authors: Goren Moran G. , Navon-Venezia Shiri , Chmelnitsky Inna , Carmeli Yehuda
Published: March 2010

All of the carbapenem-resistant
Escherichia coli
(CREC) isolates identified in our hospital from 2005 to 2008 (
n
= 10) were studied. CREC isolates were multidrug resistant, all carried
bla
KPC-2
, and six of them were also extended-spectrum beta-lactamase producers. Pulsed-field gel electrophoresis indicated six genetic clones; within the same clone, similar transferable
bla
KPC-2
-containing plasmids were found whereas plasmids differed between clones. Tn
4401
elements were identified in all of these plasmids.
Azithromycin Alters Macrophage Phenotype and Pulmonary Compartmentalization during Lung Infection withPseudomonas
Authors: Feola David J. , Garvy Beth A. , Cory Theodore J. , Birket Susan E. , Hoy Heather , Hayes Don , Murphy Brian S.
Published: March 2010

Infection with mucoid strains ofPseudomonas aeruginosain chronic inflammatory diseases of the airway is difficult to eradicate and can cause excessive inflammation. The roles of alternatively activated and regulatory subsets of macrophages in this pathophysiological process are not well characterized. We previously demonstrated that azithromycin induces an alternatively activated macrophage-like phenotypein vitro. In the present study, we tested whether azithromycin affects the macrophage activation status and migration in the lungs ofP. aeruginosa-infected mice. C57BL/6 mice received daily doses of oral azithromycin and were infected intratracheally with a mucoid strain ofP. aeruginosa. The properties of macrophage activation, immune cell infiltration, and markers of pulmonary inflammation in the lung interstitial and alveolar compartments were evaluated postinfection. Markers of alternative macrophage activation were induced by azithromycin treatment, including the surface expression of the mannose receptor, the upregulation of arginase 1, and a decrease in the production of proinflammatory cytokines. Additionally, azithromycin increased the number of CD11b+monocytes and CD4+T cells that infiltrated the alveolar compartment. A predominant subset of CD11b+cells was Gr-1 positive (Gr-1+), indicative of a subset of cells that has been shown to be immunoregulatory. These differences corresponded to decreases in neutrophil influx into the lung parenchyma and alteration of the characteristics of peribronchiolar inflammation without any change in the clearance of the organism. These results suggest that the immunomodulatory effects of azithromycin are associated with the induction of alternative and regulatory macrophage activation characteristics and alteration of cellular compartmentalization during infection.
In Vitro
Activity of a New Isothiazoloquinolone, ACH-702, against
Mycobacterium tuberculosis
and Other Mycobacteria
Authors: Molina-Torres Carmen A. , Ocampo-Candiani Jorge , Rendón Adrian , Pucci Michael J. , Vera-Cabrera Lucio
Published: March 2010

In this work, we describe the activity of ACH-702 against clinical isolates of
Mycobacterium tuberculosis
and six different nontuberculous mycobacteria. The MIC
50
and MIC
90
of both susceptible and drug-resistant
M. tuberculosis
strains tested were 0.0625 and 0.125 μg/ml, respectively. The MIC
50
and MIC
90
values for
Mycobacterium fortuitum
isolates were 0.0625 μg/ml in both cases;
Mycobacterium avium
complex isolates showed MIC
50
and MIC
90
values of 0.25 and 4 μg/ml, respectively.
Antimicrobial Susceptibilities of Health Care-Associated and Community-Associated Strains of Methicillin-Resistant
Staphylococcus aureus
from Hospitalized Patients in Canada, 1995 to 2008
Authors: Simor Andrew E. , Louie Lisa , Watt Christine , Gravel Denise , Mulvey Michael R. , Campbell Jennifer , McGeer Allison , Bryce Elizabeth , Loeb Mark , Matlow Anne
Published: March 2010

We determined the
in vitro
antimicrobial susceptibilities of 7,942 methicillin-resistant
Staphylococcus aureus
(MRSA) isolates obtained from patients hospitalized in 48 Canadian hospitals from 1995 to 2008. Regional variations in susceptibilities were identified. The dissemination of community-associated strains in Canada appears to have contributed to increased susceptibility of MRSA to several non-β-lactam antimicrobial agents in the past decade. Reduced susceptibility to glycopeptides was not identified.
The Small RNA Chaperone Hfq Is Required for the Virulence of
Yersinia pseudotuberculosis
Authors: Schiano Chelsea A. , Bellows Lauren E. , Lathem Wyndham W.
Published: March 2010

Bacterial small, noncoding RNAs (sRNAs) participate in the posttranscriptional regulation of gene expression, often by affecting protein translation, transcript stability, and/or protein activity. For proper function, many sRNAs rely on the chaperone Hfq, which mediates the interaction of the sRNA with its target mRNA. Recent studies have demonstrated that Hfq contributes to the pathogenesis of a number of bacterial species, suggesting that sRNAs play an essential role in the regulation of virulence. The enteric pathogen
Yersinia pseudotuberculosis
causes the disease yersiniosis. Here we show that Hfq is required by
Y. pseudotuberculosis
to cause mortality in an intragastric mouse model of infection, and a strain lacking Hfq is attenuated 1,000-fold compared to the wild type. Hfq is also required for virulence through the intraperitoneal route of infection and for persistence of the bacterium in the Peyer's patches, mesenteric lymph nodes, and spleen, suggesting a role for Hfq in systemic infection. Furthermore, the Δ
hfq
mutant of
Y. pseudotuberculosis
is hypermotile and displays increased production of a biosurfactant-like substance, reduced intracellular survival in macrophages, and decreased production of type III secretion effector proteins. Together, these data demonstrate that Hfq plays a critical role in the virulence of
Y. pseudotuberculosis
by participating in the regulation of multiple steps in the pathogenic process and further highlight the unique role of Hfq in the virulence of individual pathogens.
Multiple Host Proteins That Function in Phosphatidylinositol-4-Phosphate Metabolism Are Recruited to the Chlamydial Inclusion
Authors: Moorhead Andrew M. , Jung Joo-Yong , Smirnov Asya , Kaufer Susanne , Scidmore Marci A.
Published: March 2010

Chlamydiae replicate within a nonacidified vacuole, termed an inclusion. As obligate intracellular bacteria, chlamydiae actively modify their vacuole to exploit host signaling and trafficking pathways. Recently, we demonstrated that several Rab GTPases are actively targeted to the inclusion. To define the biological roles of inclusion localized Rab GTPases, we have begun to identify inclusion-localized Rab effectors. Here we demonstrate that oculocerebrorenal syndrome of Lowe protein 1 (OCRL1), a Golgi complex-localized phosphatidylinositol (PI)-5-phosphatase that binds to multiple Rab GTPases, localizes to chlamydial inclusions. By examining the intracellular localization of green fluorescent protein (GFP) fusion proteins that bind to unique phosphoinositide species, we also demonstrate that phosphatidylinositol-4-phosphate (PI4P), the product of OCRL1, is present at the inclusion membrane. Furthermore, two additional host proteins, Arf1, which together with PI4P mediates the recruitment of PI4P-binding proteins to the Golgi complex, and PI4KIIα, a major producer of Golgi complex-localized PI4P, also localize to chlamydial inclusions. Depletion of OCRL1, Arf1, or PI4KIIα by small interfering RNA (siRNA) decreases inclusion formation and the production of infectious progeny. Infectivity is further decreased in cells simultaneously depleted for all three host proteins, suggesting partially overlapping functions in infected cells. Collectively, these data demonstrate that
Chlamydia
species create a unique replication-competent vacuolar environment by modulating both the Rab GTPase and the PI composition of the chlamydial inclusion.
The PB2-E627K Mutation Attenuates Viruses Containing the 2009 H1N1 Influenza Pandemic Polymerase
Authors: Jagger Brett W. , Memoli Matthew J. , Sheng Zong-Mei , Qi Li , Hrabal Rachel J. , Allen Genevieve L. , Dugan Vivien G. , Wang Ruixue , Digard Paul , Kash John C. , Taubenberger Jeffery K.
Published: March 2010

The swine-origin H1N1 influenza A virus emerged in early 2009 and caused the first influenza pandemic in 41 years. The virus has spread efficiently to both the Northern and the Southern Hemispheres and has been associated with over 16,000 deaths. Given the virus’s recent zoonotic origin, there is concern that the virus could acquire signature mutations associated with the enhanced pathogenicity of previous pandemic viruses or H5N1 viruses with pandemic potential. We tested the hypothesis that mutations in the polymerase PB2 gene at residues 627 and 701 would enhance virulence but found that influenza viruses containing these mutations in the context of the pandemic virus polymerase complex are attenuated in cell culture and mice.

IMPORTANCE
Influenza A virus (IAV) evolution is characterized by host-specific lineages, and IAVs derived in whole or in part from animal reservoirs have caused pandemics in humans. Because IAVs are known to acquire host-adaptive genome mutations, and since the PB2 gene of the 2009 H1N1 virus is of recent avian derivation, there exists concern that the pathogenicity of the 2009 H1N1 influenza A pandemic virus could be potentiated by acquisition of the host-adaptive PB2-E627K or -D701N mutations, which have been shown to enhance the virulence of other influenza viruses. We present data from a mouse model of influenza infection showing that such mutations do not increase the virulence of viruses containing the 2009 H1N1 viral polymerase.
Source parameters from shallow events in the Rocky Mountain House earthquake swarm
Authors: Rebollar C. J. , Kanasewich E. R. , Nyland E.
Published: March 2010

We report here source parameters of the Rocky Mountain earthquake swarm derived from three-component digital data. During 6 days in October 1980, 21 events were recorded. Focal depths for these events are in the range of 1 ± 0.8 to 2 ± 2 km. Eleven events with local magnitudes from 2.1 to 2.8 yielded source parameters. Corner frequencies of the S-wave spectra were found in the range 6.2 ± 0.5 Hz, giving source dimensions of 160 ± 10 m. The corresponding P-wave corner frequencies are in the range 8.6 ± 3 Hz. The ratio of P to S corner frequencies varies from 0.9 to 2.1. There is a path effect between 13 and 16 Hz that could have affected these ratios. The average falloff over three components at high frequencies varies from −1.8 to −2.3. High stress drops, ranging from 47 to 263 bar (4.7–26.3 MPa), and apparent stresses, from 2.5 to 23 bar (0.25–2.3 MPa), were calculated. Five events have remarkably similar characteristics in the frequency and time domains. For these events the ratio of minimum strain energy W0, according to Kanamori, to the energy calculated using the integration scheme of Hanks and Thatcher was 3.7 ± 0.5. A theoretical value gives 3.1. The seismic efficiency ranges from 0.2 ± 0.04 to 0.17 ± 0.8. Large seismic moments for relatively small magnitudes were found. Some of these spectral characteristics are best explained as the result of displacement along a smooth fault.