bluuebunny/crossref_metadata_2025 huggingface dataset:
Addition of Carbon Dioxide to Dairy Products to Improve Quality: A Comprehensive Review
Authors: Hotchkiss Joseph H. , Werner Brenda G. , Lee Edmund Y.C.
Published: September 2006

ABSTRACT:  Changes in distribution patterns and demand for increased food quality have resulted in a desire to improve the shelf life of nonsterile dairy products. Refrigerated shelf life extension typically requires, at a minimum, reductions in the growth rate of spoilage microorganisms and subsequent product deterioration. Reducing initial bacterial loads, increasing pasteurization regimes, and reducing postprocessing contamination have all been employed with measured success. The use of antimicrobial additives has been discouraged primarily due to labeling requirements and perceived toxicity risks. Carbon dioxide (CO2) is a naturally occurring milk component and inhibitory toward select dairy spoilage microorganisms; however, the precise mechanism is not fully understood. CO2 addition through modified atmosphere packaging or direct injection as a cost‐effective shelf life extension strategy is used commercially worldwide for some dairy products and is being considered for others as well. New CO2 technologies are being developed for improvements in the shelf life, quality, and yield of a diversity of dairy products, including raw and pasteurized milk, cheeses, cottage cheese, yogurt, and fermented dairy beverages. Here we present a comprehensive review of past and present research related to quality improvement of such dairy products using CO2.
Mechanisms and Factors for Edible Oil Oxidation
Authors: Choe Eunok , Min David B.
Published: September 2006

ABSTRACT:  Edible oil is oxidized during processing and storage via autoxidation and photosensitized oxidation, in which triplet oxygen (3O2) and singlet oxygen (1O2) react with the oil, respectively. Autoxidation of oils requires radical forms of acylglycerols, whereas photosensitized oxidation does not require lipid radicals since 1O2 reacts directly with double bonds. Lipid hydroperoxides formed by 3O2 are conjugated dienes, whereas 1O2 produces both conjugated and nonconjugated dienes. The hydroperoxides are decomposed to produce off‐flavor compounds and the oil quality decreases. Autoxidation of oil is accelerated by the presence of free fatty acids, mono‐ and diacylglycerols, metals such as iron, and thermally oxidized compounds. Chlorophylls and phenolic compounds decrease the autoxidation of oil in the dark, and carotenoids, tocopherols, and phospholipids demonstrate both antioxidant and prooxidant activity depending on the oil system. In photosensitized oxidation chlorophyll acts as a photosensitizer for the formation of 1O2; however, carotenoids and tocopherols decrease the oxidation through 1O2 quenching. Temperature, light, oxygen concentration, oil processing, and fatty acid composition also affect the oxidative stability of edible oil.
Growth factors and cytokines in autologous platelet concentrate and their correlation to periodontal regeneration outcomes
Authors: Christgau M. , Moder D. , Hiller K.‐A. , Dada A. , Schmitz G. , Schmalz G.
Published: September 2006

Aim: To determine the concentration of naturally available biologic mediators in autologous platelet concentrates and their correlation with periodontal regeneration outcomes.

Material and methods: In 25 patients with two intra‐bony defects each, an autologous platelet concentrate (APC) was prepared by a laboratory thrombocyte apheresis technique pre‐operatively. Both defects were treated using a bioresorbable guided tissue regeneration‐membrane in combination with tricalciumphosphate (TCP). In the test defect, APC was additionally applied. In the APC, platelets were counted and the levels of growth factors and cytokines were determined by ELISA. Correlations between the platelet counts or the growth factor/cytokine levels and the potential clinical and radiographic regeneration outcomes due to APC were calculated after 3, 6, and 12 months.

Results: The APC contained 2.2 × 106 platelets/μl, which was 7.9 times more than in the venous blood. Transforming growth factor‐β1 (TGF‐β1), insulin‐like growth factor‐I (IGF‐I), platelet‐derived growth factor‐AB (PDGF‐AB), PDGF‐BB, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were found in the APC, whereas interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor α (TNFα), IL‐4, and IL‐10 were not detectable. The regression analysis showed a weak correlation between the platelet counts or the growth factor levels and the clinical and radiographic regeneration outcomes (r20.4).

Conclusion: Autologous platelet concentrate contains relatively high concentrations of PDGF‐AB, PDGF‐BB, TGF‐β1, and IGF‐I, but their potential influence on periodontal regeneration remains unclear.
Left ventricular volume and function in cynomolgus monkeys using real‐time three‐dimensional echocardiography
Authors: Tsusaki Hideshi , Yonamine Haruno , Tamai Asako , Shimomoto Mutsuko , Kuwano Koichi , Iwao Hiroshi , Nagata Ryoichi , Kito Go
Published: September 2006

Background  The purpose of this study was to investigate the feasibility of evaluating cardiac function by real time three‐dimensional (RT3D) echocardiography in isoflurane‐anesthetized male cynomolgus monkeys. Additionally differences between inhibitory effects of β‐blockers and a Ca channel blocker on left ventricular (LV) function were examined.

Methods and Results  End‐diastolic volume (EDV), end‐systolic volume (ESV) and ejection fraction (EF) in the control (without any drug effect) were not significantly changed by repetitive measurement at a 30‐day interval. Propranolol and metoprolol (0.1 and 0.3 mg/kg/10 minutes, i.v.) caused a dose‐dependent increase in ESV, but little effect on EDV, resulting in a decrease in EF. Verapamil (0.1 and 0.3 mg/kg/10 minutes, i.v.) increased both EDV and ESV, but decreased EF was noted at 0.3 mg/kg.

Conclusions  These results demonstrate the feasibility of RT3D echocardiography in providing reproducible estimations of LV volume and EF in monkeys when evaluating drugs that may affect cardiac function.
Freeze‐dried platelet‐rich plasma shows beneficial healing properties in chronic wounds
Authors: Pietramaggiori Giorgio , Kaipainen Arja , Czeczuga Joshua M. , Wagner Christopher T. , Orgill Dennis P.
Published: September 2006

Fresh platelet concentrates are used in many centers to treat recalcitrant wounds. To extend the therapeutic shelf‐life of platelets, we analyzed the wound‐healing effects of fresh‐frozen and freeze‐dried (FD) platelet‐rich plasma (PRP) using a diabetic mouse model. Db/db mice with 1.0 cm2 dorsal excisional wounds (n=15/group) were treated with a single application of FD PRP (1.2 × 106 platelets/μL) with or without a stabilization solution, and compared with wounds treated with fresh‐frozen, sonicated PRP, and untreated wounds. Granulation tissue area, thickness, and wound size were analyzed 9 days posttreatment. Immunostained sections were quantified for vascularity and proliferation using antiplatelet endothelial cell adhesion molecule I and antiproliferating cell nuclear antigen antibodies. The results showed that all PRP preparations increased granulation tissue formation as assessed by surface coverage, thickness, and angiogenic response, when compared with untreated wounds. In addition, wounds treated with FD PRP, and biochemically stabilized FD PRP, exhibited higher proliferative levels. The possibility to deliver growth factors using platelets, and the potential to extend the shelf‐life of platelet concentrates makes freeze‐drying methods particularly suitable for enhanced wound care.
SBD.4 stimulates regenerative processes in vitro, and wound healing in genetically diabetic mice and in human skin/severe‐combined immunodeficiency mouse chimera
Authors: Zhao Hui , Mortezaei Reza , Wang Yanrong , Sheng Xinsheng , Aria Fariba , Bojanowski Krzysztof
Published: September 2006

In search of novel angiostimulators, we performed a high‐throughput screening of medicinal plants beneficial for blood circulation. From the panel of positive hits, Angelica sinensis was selected for further investigation. Purified down to a low‐molecular‐weight fraction and characterized by high‐performance liquid chromatography–mass spectrometry, the material, named SBD.4A, revealed a particularly strong wound healing activity in the diabetic mouse wound‐healing model, and in the human/severe combined immunodeficiency mouse chimera wound‐healing model. In both models, SBD.4A compared favorably with the Food and Drug Administration‐approved wound‐healing drug becaplermin, suggesting that this botanical product could be a valuable treatment for difficult‐to‐heal wounds. Further high‐performance liquid chromatography fractionation of SBD.4A yielded a hydrophilic fraction, which strongly stimulated endothelial cell proliferation, tridimensional endothelial cell network formation, as well as the proliferation of human dermal fibroblasts and type I collagen secretion. Because angiogenesis and fibroblast proliferation are essential for wound healing, we propose that this liquid chromatography–mass spectrometry‐defined hydrophilic fraction is at least partially responsible for the wound‐healing activity of SBD.4A.
Crafting a New Alliance with the Muslim World
Authors: Noman Omar
Published: September 2006

Most Muslims now live in democracies—a fact that is rarely acknowledged. The Muslim world has also elected five women heads of state in the past decade. These two indicators are symbolic of the diversity within the Muslim world, and also of the direction in which that world is headed.

Few Muslims wish to be classified in a category that would prevent them from participating in the benefits of modernity. The pull of mass education, commerce, trade, and engagement with the world is strong. But these possibilities are openings that radical Islam is attempting to close off, which has led to an ideological civil war within Islam. In country after country, the middle class, the elite, and most of the poor are frightened by an austere version of theocratic Islam that has managed to gain political leverage. In order to sustain modern governments and access to the world in which they want to be active contributors, Muslims need an alliance with the West—not a confrontation.
Promoting Human Rights
Authors: Ross James D.
Published: September 2006

All wars—and the current war on terrorism is no exception—provide serious tests for the rule of law. The demands of armed conflict, with its instantaneous decisions of life and death, do not lend themselves easily to legal constraint. It is thus not surprising that the United States, which has been outspoken historically on matters of human rights, would become less attentive to those concerns after coming under deadly attack. For Human Rights Watch (HRW) and other human rights organizations, the primary concern since September 11 has been to demonstrate that upholding fundamental rights, whether on the battlefields of Afghanistan or in the detention facilities at Guantánamo Bay, is not only consistent with fighting international terrorism, but is, in essence, what the war is all about. The unwillingness of the Bush administration to embrace this idea bodes ill for the protection of rights as the war on terrorism reaches across the globe.
Access to Medicines and the Rhetoric of Responsibility
Authors: Barry Christian , Raworth Kate
Published: September 2006

There is no cure or vaccine for HIV/AIDS. The only life-prolonging treatment available is antiretroviral (ARV) therapy. WHO estimates, however, that less than 5 percent of those who require treatment in developing countries currently enjoy access to these medicines. In Africa fewer than 50,000 people–less than 2 percent of the people in need–currently receive ARV therapy. These facts have elicited strongly divergent reactions, and views about the appropriate response to this crisis have varied widely.

The intensity of the debate concerning access to life-prolonging medicines for the treatment of HIV/AIDS, and the heated rhetoric with which they are often conducted, suggest that these disagreements may be rooted in deeper disagreements of value. It is not obvious, however, what disagreements of value are at stake in this debate. By analyzing the statements of scholars, public officials, activist organizations, and private sector representatives, each of whom may endorse very different policy recommendations on access to HIV/AIDS drugs, we have identified and created a typology of the different sources of disagreement in the debate. We conclude that the central disagreements concerning access to medicines arise from competing understandings of how responsibilities for bringing remedy to hardships should be allocated to different agents and institutions. A central lesson that emerges from our analysis is that thinking about “health equity” must extend beyond the explanation and justification of goals, values, and ideals, and engage more honestly with the difficult question of how responsibilities for bringing remedy to health crises should be allocated in complex social contexts.
Responsibilities for Poverty-Related Ill Health
Authors: Pogge Thomas W.
Published: September 2006

In a democratic society, the social rules are imposed by all upon each. As “recipients” of the rules, we tend to think that they should be designed to engender the best attainable distribution of goods and ills or quality of life. We are inclined to assess social institutions by how they affect their participants. But there is another, oft-neglected perspective which the topic of health equity raises with special clarity: As imposers of the rules, we are inclined to think that harms we inflict through the rules have greater moral weight than like harms we merely fail to prevent or to mitigate. What matters morally is not merely how we affect people, but how we treat them through the rules we impose. While current (consequentialist and Rawlsian) theorizing is dominated by the first perspective and thus supports purely recipient-oriented moral conceptions, an adequate approach to social justice requires a balancing of both. Such balancing results in a relational conception of justice, which distinguishes various ways in which an institutional scheme may causally affect the quality of life of its participants.

This essay argues that the strength of our moral reason to prevent or mitigate particular medical conditions depends not only on what one might call distributional factors, such as how badly off the people affected by these conditions are in absolute and relative terms, how costly prevention or treatment would be, and how much patients would benefit from given treatment. Rather, it depends also on relational factors, that is, on how we are related to the medical conditions they suffer. It then discusses some implications of this view for understanding responsibilities for international health outcomes.
Liberals, Revolutionaries, and Responsibility
Authors: Lu Catherine
Published: September 2006

This brief response cannot adequately address all of the challenging issues raised by Robert Meister in his reply, so I hope only to clarify our main points of contention that will likely continue beyond this exchange.
Self-Defense in an Imperfect World
Authors: Brown Chris
Published: September 2006

In his address at West Point on June 1, 2002, President George W. Bush appeared to be signaling America's willingness to regard the mere possession of weapons of mass destruction (WMD) by potential enemies as grounds for an anticipatory war. Historically, however, a clear distinction has been drawn between preemptive and preventive, or anticipatory, war, with the latter regarded as illegitimate. The National Security Strategy announced by the president on September 20, 2002, was more conventional in its approach to preemption, but doubts remain as to whether the old distinction can be preserved. And this discussion is taking place in the context of a specific problem, namely the apparent desire of Iraq to obtain WMD and the determination of the United States, and, less clearly expressed, the UN Security Council, to prevent this from happening.
Any Name Illegal and Immoral
Authors: Stein Yael
Published: September 2006

Since November 2000, Israel has been implementing an assassination policy in the occupied territories. The Israeli policy is both illegal and immoral. The legal questions are much more complicated than would appear from David's argument. Although individual killings may be lawful in specific cases, this debate concerns a policy providing systematic justification for such acts. Neither international nor Israeli law ensures any backing for this policy. Armed Palestinians are not combatants according to any known legal definition. They are civilians–which is the only legal alternative–and can only be attacked for as long as they actively participate in hostilities.

The argument that this policy affords the public a sense of revenge and retribution could serve to justify acts both illegal and immoral. Clearly, lawbreakers ought to be punished. Yet, no matter how horrific their deeds, as the targeting of Israeli civilians indeed is, they should be punished according to the law. David's arguments could, in principle, justify the abolition of formal legal systems altogether.

The Israeli government has not endorsed the minor changes of policy that David suggests, and for a reason. Israel's initial refusal to acknowledge the very existence of this policy and even its later hesitant admission suggest it is aware of the problems the policy entails and of the difficulties of dismissing them. Assassinations have been part of Israel's security policy for many years, and Israel is currently the only democratic country that regards such measures as legitimate. The Palestinian violations of international law, however, cannot be used to grant legal and/or moral legitimation to these violations when perpetrated by others.
Analyzing the Use of Race and Ethnicity in Biomedical Research from a Local Community Perspective
Authors: Foster Morris W.
Published: September 2006

Most discussions of the use of race and ethnicity in biomedical research and clinical care focus on broad national and transnational populations. Looking at the problem from the perspective of large populations, however, misses the rest of a continuum that runs from the global human population to local communities. If race and ethnicity are fundamental categories for biomedical analyses, they should be informative at all points along that continuum, much as the definition of a gene remains unchanged whether analyzed in the context of an individual, a group, or the total human population. By examining the utility of racial and ethnic categories at a local community level, we can better evaluate whether those categories are indeed fundamental units for analysis. Alternatively, these categories may be analytic proxies useful primarily for approximating aggregate biological and social features of large populations at national and transnational levels of analysis.
Race and Ethnicity in Medical Research: Requirements Meet Reality
Authors: Winker Margaret A.
Published: September 2006

Race and ethnicity are commonly reported variables in biomedical research, but how they were initially determined is often not described and the rationale for analyzing them is often not provided. JAMA improved the reporting of these factors by implementing a policy and procedure for doing so. However, still lacking are careful consideration of what is actually being measured when race/ethnicity is described, consistent terminology, hypothesis-driven justification for analyzing race/ethnicity, and a consistent and generalizable measurement of socioeconomic status. Furthermore, some studies continue to use race/ethnicity as a proxy for genetics. Research into appropriate measures of race/ethnicity and socioeconomic factors, as well as education of researchers regarding issues of race/ethnicity, is necessary to clarify the meaning of race/ethnicity in the biomedical literature.
Disclosing Conflicts of Interest in Clinical Research: Views of Institutional Review Boards, Conflict of Interest Committees, and Investigators
Authors: Weinfurt Kevin P. , Friedman Joëlle Y. , Dinan Michaela A. , Allsbrook Jennifer S. , Hall Mark A. , Dhillon Jatinder K. , Sugarman Jeremy
Published: September 2006

Investigator and institutional financial conflicts of interest have raised concerns about both the integrity of clinical research and protecting the rights and welfare of research participants. In response, professional groups and governmental bodies have issued guidance for managing conflicts of interest to minimize their potential untoward effects. Although a variety of approaches have been offered, a common protection is to disclose financial interests in research to potential research participants as part of the recruitment and informed consent process. This approach reinforces a basic norm of candor, ideally allowing potential research participants to evaluate whether financial interests should affect their decision to participate in research. Disclosure to potential research participants is viewed as an alternative to having regulators or research institutions limit or prohibit all financial interests in research, assuming that not all such interests are unacceptable.
Modelling spinal circuitry involved in locomotor pattern generation: insights from deletions during fictive locomotion
Authors: Rybak Ilya A. , Shevtsova Natalia A. , Lafreniere‐Roula Myriam , McCrea David A.
Published: September 2006

The mammalian spinal cord contains a locomotor central pattern generator (CPG) that can produce alternating rhythmic activity of flexor and extensor motoneurones in the absence of rhythmic input and proprioceptive feedback. During such fictive locomotor activity in decerebrate cats, spontaneous omissions of activity occur simultaneously in multiple agonist motoneurone pools for a number of cycles. During these ‘deletions’, antagonist motoneurone pools usually become tonically active but may also continue to be rhythmic. The rhythmic activity that re‐emerges following a deletion is often not phase shifted. This suggests that some neuronal mechanism can maintain the locomotor period when motoneurone activity fails. To account for these observations, a simplified computational model of the spinal circuitry has been developed in which the locomotor CPG consists of two levels: a half‐centre rhythm generator (RG) and a pattern formation (PF) network, with reciprocal inhibitory interactions between antagonist neural populations at each level. The model represents a network of interacting neural populations with single interneurones and motoneurones described in the Hodgkin‐Huxley style. The model reproduces the range of locomotor periods and phase durations observed during real locomotion in adult cats and permits independent control of the level of motoneurone activity and of step cycle timing. By altering the excitability of neural populations within the PF network, the model can reproduce deletions in which motoneurone activity fails but the phase of locomotor oscillations is maintained. The model also suggests criteria for the functional identification of spinal interneurones involved in the mammalian locomotor pattern generation.
Functional segregation of synaptic GABAA and GABAC receptors in goldfish bipolar cell terminals
Authors: Palmer Mary J.
Published: September 2006

The transmission of light responses to retinal ganglion cells is regulated by inhibitory input from amacrine cells to bipolar cell (BC) synaptic terminals. GABAA and GABAC receptors in BC terminals mediate currents with different kinetics and are likely to have distinct functions in limiting BC output; however, the synaptic properties and localization of the receptors are currently poorly understood. By recording endogenous GABA receptor currents directly from BC terminals in goldfish retinal slices, I show that spontaneous GABA release activates rapid GABAA receptor miniature inhibitory postsynaptic currents (mIPSCs) (predominant decay time constant (τdecay), 1.0 ms) in addition to a tonic GABAC receptor current. The GABAC receptor antagonist (1,2,5,6‐tetrahydropyridin‐4‐yl)methylphosphinic acid (TPMPA) has no effect on the amplitude or kinetics of the rapid GABAA mIPSCs. In addition, inhibition of the GAT‐1 GABA transporter, which strongly regulates GABAC receptor currents in BC terminals, fails to reveal a GABAC component in the mIPSCs. These data suggest that GABAA and GABAC receptors are highly unlikely to be synaptically colocalized. Using non‐stationary noise analysis of the mIPSCs, I estimate that GABAA receptors in BC terminals have a single‐channel conductance (γ) of 17 pS and that an average of just seven receptors mediates a quantal event. From noise analysis of the tonic current, GABAC receptor γ is estimated to be 4 pS. Identified GABAC receptor mIPSCs exhibit a slow decay (τdecay, 54 ms) and are mediated by approximately 42 receptors. The distinct properties and localization of synaptic GABAA and GABAC receptors in BC terminals are likely to facilitate their specific roles in regulating the transmission of light responses in the retina.
Computational principles of sensorimotor control that minimize uncertainty and variability
Authors: Bays Paul M. , Wolpert Daniel M.
Published: September 2006

Sensory and motor noise limits the precision with which we can sense the world and act upon it. Recent research has begun to reveal computational principles by which the central nervous system reduces the sensory uncertainty and movement variability arising from this internal noise. Here we review the role of optimal estimation and sensory filtering in extracting the sensory information required for motor planning, and the role of optimal control, motor adaptation and impedance control in the specification of the motor output signal.
Large Eddy Simulation of Flow and Heat Transfer in the 180‐Deg Bend Region of a Stationary Gas Turbine Blade Ribbed Internal Cooling Duct
Authors: Sewall Evan A. , Tafti Danesh K.
Published: September 2006

Large eddy simulation of the 180 deg bend in a stationary ribbed duct is presented. The domain studied includes three ribs upstream of the bend region and three ribs downstream of the bend with an outflow extension added to the end, using a total of 8.4 million cells. Two cases are compared to each other: one includes a rib in the bend and the other does not. The friction factor, mean flow, turbulence, and heat transfer are compared in the two cases to help explain the benefits and disadvantages of the wide number of flow effects seen in the bend, including flow separation at the tip of the dividing wall, counter-rotating Dean vortices, high heat transfer at areas of flow impingement, and flow separation at the upstream and downstream corners of the bend. Mean flow results show a region of separated flow at the tip of the dividing region in the case with no rib in the bend, but no separation region is observed in the case with a rib. A pair of counter-rotating Dean vortices in the middle of the bend is observed in both cases. Turbulent kinetic energy profiles show a 30% increase in the midplane of the bend when the rib is added. High gradients of heat transfer augmentation are observed on the back wall and downstream outside wall, where mean flow impingement occurs. This heat transfer is increased with the presence of a rib. Including a rib in the bend increases the friction factor in the bend by 80%, and it increases the heat transfer augmentation by approximately 20%, resulting in a trade-off between pressure drop and heat transfer.
Toward Defining Objective Criteria for Assessing the Adequacy of Assumed Axisymmetry and Steadiness of Flows in Rotating Cavities
Authors: Snowsill G. D. , Young C.
Published: September 2006

The need to make a priori decisions about the level of approximation that can be accepted—and subsequently justified—in flows of industrial complexity is a perennial problem for computational fluid dynamics (CFD) analysts. This problem is particularly acute in the simulation of rotating cavity flows, where the stiffness of the equation set results in protracted convergence times, making any simplification extremely attractive. For example, it is common practice, in applications where the geometry and boundary conditions are axisymmetric, to assume that the flow solution will also be axisymmetric. It is known, however, that inappropriate imposition of this assumption can lead to significant errors. Similarly, where the geometry or boundary conditions exhibit cyclic symmetry, it is quite common for analysts to constrain the solutions to satisfy this symmetry through boundary condition definition. Examples of inappropriate use of these approximating assumptions are frequently encountered in rotating machinery applications, such as the ventilation of rotating cavities within aero-engines. Objective criteria are required to provide guidance regarding the level of approximation that is appropriate in such applications. In the present work, a study has been carried out into: (i) The extent to which local three-dimensional features influence solutions in a generally two-dimensional (2D) problem. Criteria are proposed to aid in decisions about when a 2D axisymmetric model is likely to deliver an acceptable solution; (ii) the influence of flow features which may have a cyclic symmetry that differs from the bounding geometry or imposed boundary conditions (or indeed have no cyclic symmetry); and (iii) the influence of unsteady flow features and the extent to which their effects can be represented by mixing plane or multiple reference frame approximations.
Impact of Inactive Empiric Antimicrobial Therapy on Inpatient Mortality and Length of Stay
Authors: Scarsi Kimberly K. , Feinglass Joe M. , Scheetz Marc H. , Postelnick Michael J. , Bolon Maureen K. , Noskin Gary A.
Published: September 2006

The consequences of inactive empiric antimicrobial therapy are not well-described and may cause prolonged hospitalization or infection-related mortality. In vitro susceptibility results for 884 patients hospitalized at an academic medical center with gram-negative bloodstream infections (GNBI) from 2001 to 2003 were matched to antimicrobial orders within 24 h of culture. Clinical characteristics, organism, inpatient mortality, and length of stay after culture for patients with GNBI were compared between patients receiving active versus inactive empiric antimicrobial therapy. A total of 14.1% of patients with GNBI received inactive empiric therapy, defined as no antimicrobial therapy within 24 h of the culture active against the identified organism based on in vitro microbiology reports. Patients who received inactive therapy were more likely to be younger, to be infected with
Pseudomonas aeruginosa
, to have a nosocomial infection, and to receive antimicrobial monotherapy but less likely to be bacteremic with
Escherichia coli
or to have sepsis (
P
< 0.05). There were no significant differences in mortality between patients receiving active versus inactive empiric therapy (16.1% versus 13.6%, respectively) or in length of stay after positive culture (11.5 days versus 12.6 days, respectively). Only 45 patients had greater than 2 days of exposure to inactive therapy; however, 8/30 patients (26.7%) who never received active antimicrobial therapy died while in the hospital. Inactive empiric therapy was more common in healthier patients. Inactive antimicrobial therapy in the first 24 h did not significantly impact average outcomes for GNBI among hospitalized patients but may have caused harm to specific individuals.
Alternate Polypurine Tracts Affect Rous Sarcoma Virus Integration In Vivo
Authors: Oh Jangsuk , Chang Kevin W. , Alvord W. Gregory , Hughes Stephen H.
Published: September 2006

When the endogenous polypurine tract (PPT) of the Rous sarcoma virus (RSV)-derived vector RSVP(A)Z was replaced with alternate retroviral PPTs, the fraction of unintegrated viral DNA with the normal consensus ends significantly decreased and the retention of part of the PPT significantly increased. If the terminus of the U3 long terminal repeat (LTR) is aberrant, RSV integrase can correctly process and integrate the normal U5 LTR into the host genome. However, the canonical CA is not involved in joining the aberrant U3 LTR to the host DNA, generating either large duplications or deletions of the host sequences instead of the normal 5- or 6-bp duplication.
DNA Vaccination Can Break Immunological Tolerance to PrP in Wild-Type Mice and Attenuates Prion Disease after Intracerebral Challenge
Authors: Fernandez-Borges Natalia , Brun Alejandro , Whitton J. Lindsay , Parra Beatriz , Diaz-San Segundo Fayna , Salguero Francisco J. , Torres Juan M. , Rodriguez Fernando
Published: September 2006

Transmissible spongiform encephalopathies (TSEs) can be ameliorated by prion protein (PrP)-specific antibodies, but active immunization is complicated by immune tolerance to the normal cellular host protein (PrPC). Here, we show that DNA immunization of wild-type mice can break immune tolerance against the prion protein, resulting in the induction of PrP-specific antibody and T-cell responses. PrP immunogenicity was increased by fusion to the lysosomal targeting signal from LIMPII (lysosomal integral membrane protein type II). Although mice immunized with a PrP-LIMPII DNA vaccine showed a dramatic delay in the onset of early disease signs after intracerebral challenge, immunization against PrP also had some deleterious effects. These results clearly confirm the feasibility of using active immunization to protect against TSEs and, in the absence of effective treatments, indicate a suitable alternative for combating the spread of these diseases.
The Big Finger: the second to fourth digit ratio is a predictor of sporting ability in women
Authors: Paul S N , Kato B S , Hunkin J L , Vivekanandan S , Spector T D
Published: September 2006

Background:The second to fourth finger length ratio (2d:4d) is thought to be related to diverse traits including cognitive ability, disease susceptibility, and sexuality.

Objective:To examine the relationship between 2d:4d and sports ability in women.

Methods:Hand radiographs from 607 women (mean age 54 years) were used to estimate 2d:4d. Ranking of sports ability was on a scale (1–5).

Results:The highest achieved level of participation in any sport was significantly negatively associated with 2d:4d (b  =  −4.93, p  =  0.01) as was the relationship between 2d:4d and running level (b  =  −6.81, p  =  0.034). Ability in other sports also showed a negative relationship albeit non-significant.

Conclusions:These results suggest that a low 2d:4d ratio is related to increased female sports ability. It can be postulated that this ratio may predict potential sports ability. Understanding the mechanisms underpinning this relationship may give important insights into musculoskeletal fitness, health and disease.
A multivariate morphometric analysis of the Symphyotrichum boreale – S. nahanniense – S. welshii complex (Asteraceae: Astereae)
Authors: Owen Elliott , Semple John C. , Baum Bernard R.
Published: September 2006

A multivariate morphometric study of the Symphyotrichum boreale – S. nahanniense – S. welshii complex was undertaken to assess the morphological differences between members of the complex and compare them with specimens of S. lanceolatum, a close relative. Discriminant analyses of a matrix of 119 specimens including the S. nahanniense – S. boreale – S. welshii complex and Symphyotrichum lanceolatum, provided significant statistical support for recognizing four distinct taxa. Within the S. nahanniense – S. boreale – S. welshii complex itself, discriminant analysis of 103 specimens reinforced treating the three groups as separate species. The analyses also revealed useful morphological traits that could be used to identify each taxon within the complex. Furthermore, comparisons were made among the four known populations of S. nahanniense. The results also indicated that the range of S. welshii is larger than previously reported and includes Utah, western Wyoming, and rarely further north in Montana and Idaho. Chromosome numbers are reported for Symphyotrichum boreale (2n = 16, first report for Wyoming; 2n = 48, first report for this taxon), S. lanceolatum subsp. hesperium (2n = 64, first reports for Northwest Territories, Canada), S. nahanniense (2n = 16, first reports for this taxon), and S. welshii (2n = 16, first reports for this taxon).
SEMICLASSICAL METHODS IN 2D QFT: SPECTRA AND FINITE-SIZE EFFECTS
Authors: RIVA VALENTINA
Published: September 2006

We review some recent results obtained in the analysis of two-dimensional quantum field theories by means of semiclassical techniques, which generalize methods introduced during the '70s by Dashen, Hasllacher and Neveu and by Goldstone and Jackiw. The approach is best suited to deal with quantum field theories characterized by a nonlinear interaction potential with different degenerate minima, that generates kink excitations of large mass in the small coupling regime. Under these circumstances, although the results obtained are based on a small coupling assumption, they are nevertheless nonperturbative, since the kink backgrounds around which the semiclassical expansion is performed are nonperturbative too. We will discuss the efficacy of the semiclassical method as a tool to control analytically spectrum and finite-size effects in these theories.
Carbonyl Reductases: The Complex Relationships of Mammalian Carbonyl- and Quinone-Reducing Enzymes and Their Role in Physiology
Authors: Oppermann Udo
Published: September 2006

Carbonyl groups are frequently found in endogenous or xenobiotic compounds. Reactive carbonyls, formed during lipid peroxidation or food processing, and xenobiotic quinones are able to covalently modify DNA or amino acids. They can also promote oxidative stress, the products of which are thought to be an important initiating factor in degenerative diseases or cancer. Carbonyl groups are reduced by an array of distinct NADPH-dependent enzymes, belonging to several oxidoreductase families. These reductases often show broad and overlapping substrate specificities and some well-characterized members, e.g., carbonyl reductase (CBR1) or NADPH-quinone reductase (NQO1) have protective roles toward xenobiotic carbonyls and quinones because metabolic reduction leads to less toxic products, which can be further metabolized and excreted. This review summarizes the current knowledge on structure and function relationships of the major human and mammalian carbonyl reductases identified.
Understanding Circuit Dynamics Using the Stomatogastric Nervous System of Lobsters and Crabs
Authors: Marder Eve , Bucher Dirk
Published: September 2006

Studies of the stomatogastric nervous systems of lobsters and crabs have led to numerous insights into the cellular and circuit mechanisms that generate rhythmic motor patterns. The small number of easily identifiable neurons allowed the establishment of connectivity diagrams among the neurons of the stomatogastric ganglion. We now know that (a) neuromodulatory substances reconfigure circuit dynamics by altering synaptic strength and voltage-dependent conductances and (b) individual neurons can switch among different functional circuits. Computational and experimental studies of single-neuron and network homeostatic regulation have provided insight into compensatory mechanisms that can underlie stable network performance. Many of the observations first made using the stomatogastric nervous system can be generalized to other invertebrate and vertebrate circuits.
Overview of Structure and Function of Mammalian Cilia
Authors: Satir Peter , Christensen Søren Tvorup
Published: September 2006

Cilia are membrane-bounded, centriole-derived projections from the cell surface that contain a microtubule cytoskeleton, the ciliary axoneme, surrounded by a ciliary membrane. Axonemes in multiciliated cells of mammalian epithelia are 9 + 2, possess dynein arms, and are motile. In contrast, single nonmotile 9 + 0 primary cilia are found on epithelial cells, such as those of the kidney tubule, but also on nonepithelial cells, such as chondrocytes, fibroblasts, and neurons. The ciliary membranes of all cilia contain specific receptors and ion channel proteins that initiate signaling pathways controlling motility and/or linking mechanical or chemical stimuli, including sonic hedgehog and growth factors, to intracellular transduction cascades regulating differentiation, migration, and cell growth during development and in adulthood. Unique motile 9 + 0 cilia, found during development at the embryonic node, determine left-right asymmetry of the body.
Short-form Ron receptor is required for normal IFN-γ production in concanavalin A-induced acute liver injury
Authors: Wetzel Cynthia C. , Leonis Mike A. , Dent Arlene , Olson Meredith A. , Longmeier Angela M. , Ney Paul A. , Boivin Greg P. , Kader Sarah A. , Caldwell Charles C. , Degen Sandra J. F. , Waltz Susan E.
Published: September 2006

Abrogation of Ron receptor tyrosine kinase function results in defects in macrophage activation and dysregulated acute inflammatory responses in vivo. Several naturally occurring constitutively active alternative forms of Ron have been identified, including from primary human tumors and tumor cell lines. One of these alternative forms, short-form (SF) Ron, is generated from an alternative start site in intron 10 of the Ron gene that eliminates most of the extracellular portion of the receptor and is overexpressed in several human cancers. To test the physiological significance of SF-Ron in vivo, mice were generated that solely express the full-length form of Ron (FL-Ron). Our results show that elimination of the capacity to express SF-Ron in vivo leads to augmented production of IFN-γ from splenocytes following stimulation ex vivo with either concanavalin A or anti-CD3/T cell receptor monoclonal antibody. Moreover, in a concanavalin A-induced murine model of acute liver injury, FL-Ron mice have increased production of serum INF-γ and serum alanine aminotransferase levels and worsened liver histology and overall survival compared with wild-type control mice. Taken together, these results suggest for the first time that SF-Ron impacts the progression of inflammatory immune responses in vivo and further support a role for the Ron receptor and its various forms in liver pathophysiology.
Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: role of sterol regulatory element binding protein 2
Authors: Alrefai Waddah A. , Annaba Fadi , Sarwar Zaheer , Dwivedi Alka , Saksena Seema , Singla Amika , Dudeja Pradeep K. , Gill Ravinder K.
Published: September 2006

Niemann-Pick C1-like 1 (NPC1L1) is an essential intestinal component of cholesterol absorption. However, little is known about the molecular regulation of intestinal NPC1L1 expression and promoter activity. We demonstrated that human NPC1L1 mRNA expression was significantly decreased by 25-hydroxycholesterol but increased in response to cellular cholesterol depletion achieved by incubation with Mevinolin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase) in human intestinal Caco-2 cells. We also showed that a −1741/+56 fragment of the NPC1L1 gene demonstrated high promoter activity in Caco-2 cells that was reduced by 25-hydroxycholesterol and stimulated by cholesterol depletion. Interestingly, we showed that the NPC1L1 promoter is remarkably transactivated by the overexpression of sterol regulatory element (SRE) binding protein (SREBP)-2, suggesting its involvement in the sterol-induced alteration in NPC1L1 promoter activity. Finally, we identified two putative SREs in the human NPC1L1 promoter and established their essential roles in mediating the effects of cholesterol on promoter activity. Our study demonstrated the modulation of human NPC1L1 expression and promoter activity by cholesterol in a SREBP-2-dependent mechanism.
Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress
Authors: Galili Offer , Versari Daniele , Sattler Katherine J. , Olson Monica L. , Mannheim Dallit , McConnell Joseph P. , Chade Alejandro R. , Lerman Lilach O. , Lerman Amir
Published: September 2006

Obesity is independently associated with increased cardiovascular risk. However, since established obesity clusters with various cardiovascular risk factors, configuring the metabolic syndrome, the early effects of obesity on vascular function are still poorly understood. The current study was designed to evaluate the effect of early obesity on coronary endothelial function in a new animal model of swine obesity. As to method, juvenile domestic crossbred pigs were randomized to either high-fat/high-calorie diet (HF) or normal chow diet for 12 wk. Coronary microvascular permeability and abdominal wall fat were determined by using electron beam computerized tomography. Epicardial endothelial function and oxidative stress were measured in vitro. Systemic oxidative stress, renin-angiotensin activity, leptin levels, and parameters of insulin sensitivity were evaluated. As a result, HF pigs were characterized by abdominal obesity, hypertension, and elevated plasma lysophosphatidylcholine and leptin in the presence of increased insulin sensitivity. Coronary endothelium-dependent vasorelaxation was reduced in HF pigs and myocardial microvascular permeability increased compared with those values in normal pigs. Systemic redox status in HF pigs was similar to that in normal pigs, whereas the coronary endothelium demonstrated higher content of superoxide anions, nitrotyrosine, and NADPH-oxidase subunits, indicating increased tissue oxidative stress. In conclusion, the current study shows that early obesity is characterized by increased vascular oxidative stress and endothelial dysfunction in association with increased levels of leptin and before the development of insulin resistance and systemic oxidative stress. Vascular dysfunction is therefore an early manifestation of obesity and might contribute to the increased cardiovascular risk, independently of insulin resistance.
Similar acute molecular responses to equivalent volumes of isometric, lengthening, or shortening mode resistance exercise
Authors: Garma T. , Kobayashi C. , Haddad F. , Adams G. R. , Bodell P. W. , Baldwin K. M.
Published: September 2006

The present study was undertaken to test the hypothesis that the contraction mode of action [static-isometric (Iso), shortening-concentric (Con), or lengthening-eccentric (Ecc)] used to stress the muscle provides a differential mechanical stimulus eliciting greater or lesser degrees of anabolic response at the initiation of a resistance training program. We performed an acute resistance training study in which different groups of rodents completed four training sessions in either the Iso, Con, or Ecc mode of contraction under conditions of activation and movement specifically designed to elicit equivalent volumes of force accumulation. The results of this experiment indicate that the three modes of contraction produced nearly identical cell signaling, indicative of an anabolic response involving factors such as increased levels of mRNA for IGF-I, procollagen III α1, decreased myostatin mRNA, and increased total RNA concentration. The resulting profiles collectively provide evidence that pure mode of muscle action, in and of itself, does not appear to be a primary variable in determining the efficacy of increased loading paradigms with regard to the initiation of selected muscle anabolic responses.