bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel technique for positioning multiple cell types by liquid handling
Authors: Luong-Van Emma , Kang Ryan Kok Chuan , Birch William R.
Published: June 2009

The spatial control of cells on a surface and the patterning of multiple cell types is an important tool for fundamental biological research and tissue engineering applications. A novel technique is described for the controlled seeding of multiple cell types at specific locations on a surface without requiring the use of specialized equipment or materials. Small-volume, quasi-hemispherical drops of cell solution are deposited onto a cell culture surface immersed under barrier oil, which serves to contain the drop and prevents evaporation of the cell culture medium during the time necessary for cells to attach to the cell culture surface. Subsequent flooding with an aqueous cell-compatible buffer displaces the barrier oil, allowing the cells to grow freely across the surface. This technique offers a simple and easily implemented solution for defining the initial position of cultured cells. The coculture of multiple cell types may be carried out by incorporating different cell types in each drop. A suitable drop volume was found to be 1 μl dispensed with a standard 0.5–10 μl pipette. The drop formed resulted in a footprint diameter of approximately 2 mm. Mineral oil and silicone oil do not compromise the viability of cultured cells when used in this technique. Moreover, a surface with heparin-immobilized FGF2 is shown to retain its bioactivity following drying of the substrate and contact with mineral oil.
Versatile synthesis and micropatterning of nonfouling polymer brushes on the wafer scale
Authors: Hucknall Angus , Simnick Andrew J. , Hill Ryan T. , Chilkoti Ashutosh , Garcia Andres , Johannes Matthew S. , Clark Robert L. , Zauscher Stefan , Ratner Buddy D.
Published: June 2009

In this article, the authors describe new approaches to synthesize and pattern surfaces with poly[oligo(ethylene glycol) methyl methacrylate] (POEGMA) polymer brushes synthesized by surface-initiated atom transfer radical polymerization. These patterned coatings confer “nonfouling” properties protein and cell resistance—to the surface in a biological milieu. The versatile routes for the synthesis of POEGMA demonstrated here offer clear advantages over other techniques previously used in terms of their simplicity, reliability, and ability to pattern large-area substrates. They also demonstrate that POEGMA polymer brushes can be patterned directly by photolithography, plasma ashing, and reactive ion etching to create patterns at the micro- and nanoscale over large areas with high throughput and repeatability, while preserving the protein and cell resistance of the POEGMA brush.
AC-driven Brownian motors: A Fokker-Planck treatment
Authors: Denisov S. , Hänggi P. , Mateos J. L.
Published: June 2009

We consider a model of AC-driven Brownian motors consisting of a classical particle which is placed in a potential that is periodic in space and time and which is coupled to a heat bath. The effects of fluctuations and dissipation are studied by a time-dependent Fokker-Planck equation. The approach lets us map the original stochastic problem onto a system of ordinary linear algebraic equations. The solution of the equations provides complete information about ratchet transport, avoiding the disadvantages of direct stochastic calculations such as long transients and large statistical fluctuations. The Fokker-Planck approach to dynamical ratchets opens the possibility for further generalizations.
Making sense of the Legendre transform
Authors: Zia R. K. P. , Redish Edward F. , McKay Susan R.
Published: June 2009

The Legendre transform is a powerful tool in theoretical physics and plays an important role in classical mechanics, statistical mechanics, and thermodynamics. In typical undergraduate and graduate courses the motivation and elegance of the method are often missing, unlike the treatments frequently enjoyed by Fourier transforms. We review and modify the presentation of Legendre transforms in a way that explicates the formal mathematics, resulting in manifestly symmetric equations, thereby clarifying the structure of the transform. We then discuss examples to motivate the transform as a way of choosing independent variables that are more easily controlled. We demonstrate how the Legendre transform arises naturally from statistical mechanics and show how the use of dimensionless thermodynamic potentials leads to more natural and symmetric relations.
A simple method for Bragg diffraction in volume holographic gratings
Authors: Heifetz Alexander , Shen John T. , Shahriar M. S.
Published: June 2009

We discuss a simple beam interference approximation method for deriving the angular selectivity of diffraction in weakly modulated volume holographic gratings. The results obtained using the multiple beam interference model agree qualitatively with the results obtained from a physical optics treatment of the coupled-wave theory for volume holographic gratings.
Response to Comment on “Tail Reconnection Triggering Substorm Onset”
Authors: Angelopoulos Vassilis , McFadden James P. , Larson Davin , Carlson Charles W. , Mende Stephen B. , Frey Harald , Phan Tai , Sibeck David G. , Glassmeier Karl-Heinz , Auster Uli , Donovan Eric , Mann Ian R. , Rae I. Jonathan , Russell Christopher T. , Runov Andrei , Zhou Xu-Zhi , Kepko Larry
Published: June 2009

Lui challenges our conclusion that magnetic reconnection triggered the onset of a magnetospheric substorm. However, Lui incorrectly uses the auroral electrojet index instead of ground auroral and magnetic field pulsation signatures to determine substorm onset; single velocity and magnetic field components instead of full vectors and particle distributions to identify reconnection onset; and preliminary auroral electrojet–low index (AL) instead of ground magnometer, auroral, and magnetotail data to claim pre-existing activity.
Colloidal Nanocrystals with Molecular Metal Chalcogenide Surface Ligands
Authors: Kovalenko Maksym V. , Scheele Marcus , Talapin Dmitri V.
Published: June 2009

Colloidal Nanocrystal Compounds

Colloidal nanocrystals have properties that fall between those of the individual atoms but also differ from bulk due to confinement effects. They can thus be thought of as analogs of atoms, and, like atoms, there is a desire to bond together neighboring particles, which will also affect their properties. During synthesis, organic ligands are used to prevent the colloidal nanocrystals from growing too large or agglomerating, but these ligands result in poor interparticle coupling and communication.

Kovalenko
et al.

(p.
1417
) show that chalcogenide complexes (compounds based on S, Se, or Te) can effectively link together neighboring particles. Upon gentle heating, the ligands can be converted from insulating to semiconducting without altering the chemistry of the nanocrystals.
Extensive Demethylation of Repetitive Elements During Seed Development Underlies Gene Imprinting
Authors: Gehring Mary , Bubb Kerry L. , Henikoff Steven
Published: June 2009

Dynamic Imprinting

Gene imprinting—the silencing of either a maternally derived or paternally derived gene allele—is controlled in large part by DNA methylation. In plants, imprinting occurs in the endosperm, which nourishes the embryonic plant.

Gehring
et al.

(p.
1447
) and

Hsieh
et al.

(p.
1451
) analyzed the dynamics of DNA methylation in the endosperm and embryo of
Arabidopsis
and found extensive demethylation in the endosperm, suggesting that many imprinted genes are likely to exist. Gehring
et al.
characterized five imprinted genes in detail. Four of the 10 known imprinted genes are related homeodomain transcription factors. Furthermore, 5′ sequences demethylated in several of the genes were found to be derived from transposable elements, which supports the idea that imprinting arose as a by-product of silencing invading DNA.
Isotopic Homojunction Band Engineering from Diamond
Authors: Watanabe H. , Nebel C. E. , Shikata S.
Published: June 2009

Confining Carriers in Diamond

Charge carriers can be confined in thin layers created by quantum wells. These multilayer structures alternate nanoscale layers of materials with slightly different band-gap energies, such as AlGaAs and GaAs, and create a confining potential.

Watanabe
et al.

(p.
1425
) demonstrate quantum confinement of electrons by diamond multilayers that vary only in isotopic composition; the carbon-12 and carbon-13 layers differ in band-gap energy by ∼17 millielectron volts. Cathodoluminescence experiments performed at 80 kelvin showed that in alternating layers (as thin as 30 nanometers or as thick as 350 nanometers), emission comes from charge carriers recombining in the carbon-12 layer, which has a lower band gap. Carriers from the carbon-13 layer appear to transfer with little loss into carbon-12 layers.
Meningococcal Type IV Pili Recruit the Polarity Complex to Cross the Brain Endothelium
Authors: Coureuil Mathieu , Mikaty Guillain , Miller Florence , Lécuyer Hervé , Bernard Christine , Bourdoulous Sandrine , Duménil Guillaume , Mège René-Marc , Weksler Babette B. , Romero Ignacio A. , Couraud Pierre-Olivier , Nassif Xavier
Published: June 2009

Breaking the Barrier

Being able to deliver drugs into the brain to treat degenerative diseases such as Alzheimer's or Parkinson's requires the ability to traverse the blood-brain barrier (BBB). Understanding the formation of the very specific adherent junctions (AJ) and tight junctions present at the BBB cell junctions is a prerequisite to the design of such therapeutics. However, diminishing the expression of any one component involved in the formation of these intercellular junctions destroys them.

Coureuil
et al.

(p.
83
, published online 11 June) exploited the specific recruitment of AJ proteins by
Neisseria meningitidis
to dissect this process. Adhesion of the bacteria to human brain endothelial cells recruited the polarity complex Par3/Par6/PKCζ required for the establishment of eukaryotic cell polarity and the formation of intercellular junctions. The bacterial recruitment of the polarity complex depleted junctional proteins at the cell-cell interface opening the intercellular junctions at the brainendothelial interface.
Leading-Edge Vortices Elevate Lift of Autorotating Plant Seeds
Authors: Lentink D. , Dickson W. B. , van Leeuwen J. L. , Dickinson M. H.
Published: June 2009

Helicopter Seed Lift

The “helicopter” seeds of maple trees and other similar autorotating seeds detach from their parent tree under windy conditions and gyrate as they are dispersed by the wind. The reproductive success of the tree depends on the flight performance of its seeds. Autorotating seeds are known to generate high lift as they slowly descend through the air, but the means by which they do so is unclear.

Lentink
et al.

(p.
1438
, see the cover) have elucidated the aerodynamic mechanism for high lift in autorotating seeds using a robot model seed and a three-dimensional flow measurement technique. Maple seeds and a hornbeam seed create a prominent leading-edge vortex that is similar to the flow structures that are responsible for the high lift generated by the wings of hovering insects and bats. Thus, both animals and plants have converged on an identical aerodynamic solution for generating lift.
Self-Assembling Sequence-Adaptive Peptide Nucleic Acids
Authors: Ura Yasuyuki , Beierle John M. , Leman Luke J. , Orgel Leslie E. , Ghadiri M. Reza
Published: June 2009

Adaptable DNA Analogs

The defining feature of DNA as a genetic blueprint is its capacity for self-replication. In the cell, however, the replication process requires the assistance of multiple elaborate enzymes. How then at the origin of life could DNA or its precursor replicate before enzymes were present?

Ura
et al.

(p.
73
, published online 11 June) have achieved the long-sought goal of preparing a synthetic DNA analog that can dynamically adapt its sequence in free solution. Their analog (as yet only studied in relatively short, 20-unit oligomers) replaces DNA's sugar and phosphate backbone by a peptide strand in which cysteines reversibly bind the conventional DNA bases through thioester tethers. These strands can pair with complementary sequences of true DNA and furthermore swap one tethered base for another if different DNA templating strands are added to the solution in succession.
Reset Cooperation with Russia
Authors: Schweitzer Glenn
Published: June 2009

On 17 and 18 June 2009, in Moscow, The U.S. National Academies and the Russian Academy of Sciences will celebrate the 50th anniversary of the signing of the first interacademy agreement on scientific cooperation between the National Academy of Sciences and the Soviet Academy of Sciences. An important goal of this jubilee is to help revitalize bilateral cooperation in science and technology (S&T), which has declined in recent years. The anniversary comes just before President Obama and President Medvedev meet next month in Moscow to continue efforts to reset U.S.-Russian relations on a broad basis.
Scientists Seek Easier Access to Seed Banks
Authors: Finkel Elizabeth
Published: June 2009

Last week, the governing body of the International Treaty on Plant Genetic Resources for Food and Agriculture met in Tunis to review implementation and coax reluctant nations to open their seed banks and contribute to a "doomsday vault" on Norway's Svalbard island.
Authors Scramble to Make Textbooks Conform to Texas Science Standards
Authors: Bhattacharjee Yudhijit
Published: June 2009

The Texas market is so large that publishers must pay heed to new guidelines on what students should learn.
Minority Retention Rates in Science Are Sore Spot for Most Universities
Authors: Koenig Robert
Published: June 2009

A few universities have demonstrated what it takes to help more minority students earn science degrees. But their efforts are only beginning to be widely replicated.
Specific Distribution within the
Enterobacter cloacae
Complex of Strains Isolated from Infected Orthopedic Implants
Authors: Morand Philippe C. , Billoet Annick , Rottman Martin , Sivadon-Tardy Valérie , Eyrolle Luc , Jeanne Luc , Tazi Asmaa , Anract Philippe , Courpied Jean-Pierre , Poyart Claire , Dumaine Valérie
Published: June 2009

Bacteria belonging to the
Enterobacter
genus are frequently isolated from clinical samples but are unusual causative agents of orthopedic implant infections. Twelve genetic clusters (clusters I to XII) and one sequence crowd (sequence crowd
xiii
) can be distinguished within the
Enterobacter cloacae
nomenspecies on the basis of
hsp60
sequence analysis, and until now, none of these clusters could be specifically associated with a disease. In order to investigate if specific genetic clusters would be involved in infections of orthopedic material, two series of bacterial clinical isolates identified as
E. cloacae
by routine phenotypic identification methods were collected either from infected orthopedic implants (
n
= 21) or from randomly selected samples of diverse anatomical origins (control;
n
= 52). Analysis of the
hsp60
gene showed that genetic clusters III, VI, and VIII were the most frequent genetic clusters detected in the control group, whereas cluster III was poorly represented among the orthopedic implant isolates (
P
= 0.006). On the other hand,
E. hormaechei
(clusters VI and VIII), but not cluster III, is predominantly associated with infections of orthopedic implants and, more specifically, with infected material in the hip (
P
= 0.019). These results support the hypothesis that, among the isolates within the
E. cloacae
complex,
E. hormaechei
and
hsp60
gene sequencing-based cluster III are involved in pathogenesis in different ways and highlight the need for more accurate routine
Enterobacter
identification methods.
A Strongly Transdominant Mutation in the Human Immunodeficiency Virus Type 1
gag
Gene Defines an Achilles Heel in the Virus Life Cycle
Authors: Lee Sook-Kyung , Harris Janera , Swanstrom Ronald
Published: June 2009

The human immunodeficiency virus type 1 (HIV-1) protease (PR) makes five obligatory cleavages in the viral Gag polyprotein precursor. The cleavage events release the virion structural proteins from the precursor and allow the virion to undergo maturation to become infectious. The protease cleavage between the matrix protein (MA) domain and the adjacent capsid protein (CA) domain releases CA from the membrane-anchored MA and allows the N terminus of CA to refold into a structure that facilitates the formation of hexamer arrays that represent the structural unit of the capsid shell. In this study, we analyzed the extent to which each of the HIV-1 Gag processing sites must be cleaved by substituting the P1-position amino acid at each processing site with Ile. A mutation that blocks cleavage at the MA/CA processing site (Y132I) displayed a strong transdominant effect when tested in a phenotypic mixing strategy, inhibiting virion infectivity with a 50% inhibitory concentration of only 4% of the mutant relative to the wild type. This mutation is 10- to 20-fold more potent in phenotypic mixing than an inactivating mutation in the viral protease, the target of many successful inhibitors, and more potent than an inactivating mutation at any of the other Gag cleavage sites. The transdominant effect is manifested as the assembly of an aberrant virion core. Virus containing 20% of the Y132I mutant and 80% of the wild type (to assess the transdominant effect on infectivity) was blocked either before reverse transcription (RT) or at an early RT step. The ability of a small amount of the MA/CA fusion protein to poison the oligomeric assembly of infectious virus identifies an essential step in the complex process of virion formation and maturation. The effect of a small-molecule inhibitor that is able to block MA/CA cleavage even partially would be amplified by this transdominant negative effect on the highly orchestrated process of virion assembly.
A Charged Second-Site Mutation in the Fusion Peptide Rescues Replication of a Mutant Avian Sarcoma and Leukosis Virus Lacking Critical Cysteine Residues Flanking the Internal Fusion Domain
Authors: Melder Deborah C. , Yin Xueqian , Delos Sue E. , Federspiel Mark J.
Published: June 2009

The entry process of the avian sarcoma and leukosis virus (ASLV) family of retroviruses requires first a specific interaction between the viral surface (SU) glycoproteins and a receptor on the cell surface at a neutral pH, triggering conformational changes in the viral SU and transmembrane (TM) glycoproteins, followed by exposure to low pH to complete fusion. The ASLV TM glycoprotein has been proposed to adopt a structure similar to that of the Ebola virus GP2 protein: each contains an internal fusion peptide flanked by cysteine residues predicted to be in a disulfide bond. In a previous study, we concluded that the cysteines flanking the internal fusion peptide in ASLV TM are critical for efficient function of the ASLV viral glycoproteins in mediating entry. In this study, replication-competent ASLV mutant subgroup A [ASLV(A)] variants with these cysteine residues mutated were constructed and genetically selected for improved replication capacity in chicken fibroblasts. Viruses with single cysteine-to-serine mutations reverted to the wild-type sequence. However, viruses with both C9S and C45S (C9,45S) mutations retained both mutations and acquired a second-site mutation that significantly improved the infectivity of the genetically selected virus population. A charged-amino-acid second-site substitution in the TM internal fusion peptide at position 30 is preferred to rescue the C9,45S mutant ASLV(A). ASLV(A) envelope glycoproteins that contain the C9,45S and G30R mutations bind the Tva receptor at wild-type levels and have improved abilities to trigger conformational changes and to form stable TM oligomers compared to those of the C9,45S mutant glycoprotein.
Structural and Functional Elements of the Promoter Encoded by the 5′ Untranslated Region of the Venezuelan Equine Encephalitis Virus Genome
Authors: Kulasegaran-Shylini Raghavendran , Atasheva Svetlana , Gorenstein David G. , Frolov Ilya
Published: June 2009

Venezuelan equine encephalitis virus (VEEV) is one of the most pathogenic members of the
Alphavirus
genus in the
Togaviridae
family. The pathogenesis of this virus depends strongly on the sequences of the structural proteins and on the mutations in the RNA promoter encoded by the 5′ untranslated region (5′UTR) of the viral genome. In this study, we performed a detailed investigation of the structural and functional elements of the 5′-terminal promoter and analyzed the effect of multiple mutations introduced into the VEEV 5′UTR on virus and RNA replication. The results of this study demonstrate that RNA replication is determined by two synergistically functioning RNA elements. One of them is a very 5′-terminal AU dinucleotide, which is not involved in the stable RNA secondary structure, and the second is a short, G-C-rich RNA stem. An increase or decrease in the stem's stability has deleterious effects on virus and RNA replication. In response to mutations in these RNA elements, VEEV replicative machinery was capable of developing new, compensatory sequences in the 5′UTR either containing 5′-terminal AUG or AU repeats or leading to the formation of new, heterologous stem-loops. Analysis of the numerous compensatory mutations suggested that at least two different mechanisms are involved in their generation. Some of the modifications introduced into the 5′ terminus of the viral genome led to an accumulation of the mutations in the VEEV nsPs, which suggested to us that there is a direct involvement of these proteins in promoter recognition. Furthermore, our data provide new evidence that the 3′ terminus of the negative-strand viral genome in the double-stranded RNA replicative intermediate is represented by a single-stranded RNA. Both the overall folding and the sequence determine its efficient function as a promoter for VEEV positive-strand RNA genome synthesis.
Balancing Reversion of Cytotoxic T-Lymphocyte and Neutralizing Antibody Escape Mutations within Human Immunodeficiency Virus Type 1 Env upon Transmission
Authors: Peut Viv , Campbell Shahan , Gaeguta Adriana , Center Rob J. , Wilson Kim , Alcantara Sheilajen , Fernandez Caroline S. , Purcell Damian F. J. , Kent Stephen J.
Published: June 2009

Human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) is subject to both neutralizing antibody (NAb) and CD8 T-cell (cytotoxic T-lymphocyte [CTL]) immune pressure. We studied the reversion of the Env CTL escape mutant virus to the wild type and the relationship between the reversion of CTL mutations with N-linked glycosylation site (NLGS)-driven NAb escape in pigtailed macaques. Env CTL mutations either did not revert to the wild type or only transiently reverted 5 to 7 weeks after infection. The CTL escape mutant reversion was coincident, for the same viral clones, with the loss of NLGS mutations. At one site studied, both CTL and NLGS mutations were needed to confer NAb escape. We conclude that CTL and NAb escape within Env can be tightly linked, suggesting opportunities to induce effective multicomponent anti-Env immunity.
Phage Display Selection of Cyclic Peptides That Inhibit Andes Virus Infection
Authors: Hall Pamela R. , Hjelle Brian , Njus Hadya , Ye Chunyan , Bondu-Hawkins Virginie , Brown David C. , Kilpatrick Kathleen A. , Larson Richard S.
Published: June 2009

Specific therapy is not available for hantavirus cardiopulmonary syndrome caused by Andes virus (ANDV). Peptides capable of blocking ANDV infection in vitro were identified using antibodies against ANDV surface glycoproteins Gn and Gc to competitively elute a cyclic nonapeptide-bearing phage display library from purified ANDV particles. Phage was examined for ANDV infection inhibition in vitro, and nonapeptides were synthesized based on the most-potent phage sequences. Three peptides showed levels of viral inhibition which were significantly increased by combination treatment with anti-Gn- and anti-Gc-targeting peptides. These peptides will be valuable tools for further development of both peptide and nonpeptide therapeutic agents.
The Polycomb Group Protein Bmi1 Binds to the Herpes Simplex Virus 1 Latent Genome and Maintains Repressive Histone Marks during Latency
Authors: Kwiatkowski Dacia L. , Thompson Hilary W. , Bloom David C.
Published: June 2009

The mechanism by which herpes simplex virus 1 (HSV-1) establishes latency in sensory neurons is largely unknown. Recent studies indicate that epigenetic modifications of the chromatin associated with the latent genome may play a key role in the transcriptional control of lytic genes during latency. In this study, we found both constitutive and facultative types of heterochromatin to be present on the latent HSV-1 genome. Deposition of the facultative marks trimethyl H3K27 and histone variant macroH2A varied at different sites on the genome, whereas the constitutive marker trimethyl H3K9 did not. In addition, we show that in the absence of the latency-associated transcript (LAT), the latent genome shows a dramatic increase in trimethyl H3K27, suggesting that expression of the LAT during latency may act to promote an appropriate heterochromatic state that represses lytic genes but is still poised for reactivation. Due to the presence of the mark trimethyl H3K27, we examined whether Polycomb group proteins, which methylate H3K27, were present on the HSV-1 genome during latency. Our data indicate that Bmi1, a member of the Polycomb repressive complex 1 (PRC1) maintenance complex, associates with specific sites in the genome, with the highest level of enrichment at the LAT enhancer. To our knowledge, these are the first data demonstrating that a virus can repress its gene transcription to enter latency by exploiting the mechanism of Polycomb-mediated repression.
Gamma Interferon Signaling in Macrophage Lineage Cells Regulates Central Nervous System Inflammation and Chemokine Production
Authors: Lin Adora A. , Tripathi Pulak K. , Sholl Allyson , Jordan Michael B. , Hildeman David A.
Published: June 2009

Intracranial (i.c.) infection of mice with lymphocytic choriomeningitis virus (LCMV) results in anorexic weight loss, mediated by T cells and gamma interferon (IFN-γ). Here, we assessed the role of CD4+T cells and IFN-γ on immune cell recruitment and proinflammatory cytokine/chemokine production in the central nervous system (CNS) after i.c. LCMV infection. We found that T-cell-depleted mice had decreased recruitment of hematopoietic cells to the CNS and diminished levels of IFN-γ, CCL2 (MCP-1), CCL3 (MIP-1α), and CCL5 (RANTES) in the cerebrospinal fluid (CSF). Mice deficient in IFN-γ had decreased CSF levels of CCL3, CCL5, and CXCL10 (IP-10), and decreased activation of both resident CNS and infiltrating antigen-presenting cells (APCs). The effects of IFN-γ signaling on macrophage lineage cells was assessed using transgenic mice, called “macrophages insensitive to interferon gamma” (MIIG) mice, that express a dominant-negative IFN-γ receptor under the control of the CD68 promoter. MIIG mice had decreased levels of CCL2, CCL3, CCL5, and CXCL10 compared to controls despite having normal numbers of LCMV-specific CD4+T cells in the CNS. MIIG mice also had decreased recruitment of infiltrating macrophages and decreased activation of both resident CNS and infiltrating APCs. Finally, MIIG mice were significantly protected from LCMV-induced anorexia and weight loss. Thus, these data suggest that CD4+T-cell production of IFN-γ promotes signaling in macrophage lineage cells, which control (i) the production of proinflammatory cytokines and chemokines, (ii) the recruitment of macrophages to the CNS, (iii) the activation of resident CNS and infiltrating APC populations, and (iv) anorexic weight loss.
Spurious and counterfeit drugs: a growing industry in the developing world
Authors: Gautam C S , Utreja A , Singal G L
Published: June 2009

Spread of spurious/counterfeit/substandard drugs is a modern day menace which has been recognised internationally, especially so in developing countries. The problem assumes added significance in view of rapid globalisation. The market of spurious and counterfeit drugs is a well-organised, white collar crime. Poverty, high cost of medicines, lack of an official supply chain, legislative lacunae, easy accessibility to computerised printing technology, ineffective law enforcement machinery, and light penalties provide the counterfeiters with an enormous economic incentive without much risk. The consequences of the use of such medicines may vary from therapeutic failure to the occurrence of serious adverse events and even death. Proper drug quality monitoring, enforcement of laws and legislation, an effective and efficient regulatory environment, and awareness and vigilance on part of all stakeholders can help tackle this problem.
Prevalence of diagnosed depression in South Asian and white European people with type 1 and type 2 diabetes mellitus in a UK secondary care population
Authors: Ali S , Davies M J , Taub N A , Stone M A , Khunti K
Published: June 2009

Aim

To examine the prevalence and correlates of diagnosed depression among South Asians and white Europeans with type 1 and type 2 diabetes mellitus, attending a specialist diabetes clinic in the UK.

Study design and methods

A cross-sectional study was conducted using the hospital clinic’s computerised database. Medical and demographic data were extracted for 6230 people with diabetes attending the clinic between 2003 and 2005. Multiple logistic regression was used to model ethnic differences in the probability of diagnosed depression after controlling for demographic and diabetes related factors. Analyses were conducted separately for type 1 and type 2 diabetes.

Results

The unadjusted prevalence of depression in people with type 1 and type 2 diabetes was 8.0% and 9.3%, respectively. Risk factors for depression in type 1 diabetes included female gender, diabetes related complications, and comorbidities. In people with type 2 diabetes the risk factors for depression included younger age, diabetes related complications, comorbidities, insulin use and deprivation. In addition, white Europeans were significantly more likely to be diagnosed with depression compared to South Asians (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.21 to 2.08; p<0.001). Further interaction analyses revealed no evidence that the association between ethnicity and depression differed according to any of the other factors examined in this study.

Conclusions

The findings add to the limited body of knowledge regarding ethnic differences in depression and diabetes. Among those with type 2 diabetes, white Europeans had nearly 60% higher adjusted odds of diagnosed depression compared to South Asians. Disparities may be due to differences in presentation or identification of depression between these two ethnic groups.
Ruptured abdominal aortic aneurysm: a surgical emergency with many clinical presentations
Authors: Assar A N , Zarins C K
Published: June 2009

Ruptured abdominal aortic aneurysm (AAA) is one of the most fatal surgical emergencies, with an overall mortality rate of 90%. Most AAAs rupture into the retroperitoneal cavity, which results in the classical triad of pain, hypotension, and a pulsatile mass. However, this triad is seen in only 25–50% of patients, and many patients with ruptured AAA are misdiagnosed. It is likely that different sites of rupture of AAA determine a variety of common and uncommon clinical presentations, the recognition of which can save many lives. This article reviews the different sites of rupture of infrarenal AAA and explores the evidence behind the various clinical presentations seen in patients with ruptured AAA.
Novel therapeutic agents and strategies for the management of chronic kidney disease mineral and bone disorder
Authors: Connor A
Published: June 2009

Abnormalities in the serum concentrations of calcium, phosphate, parathyroid hormone and vitamin D develop with declining renal function, leading in turn to renal osteodystrophy. Observational data now suggest that these disturbances in bone and mineral metabolism play an important role in the development of vascular calcification and subsequent cardiovascular disease, contributing to the high burden of cardiovascular disease within this population. A new nomenclature—“chronic kidney disease mineral and bone disorder”—has been introduced to describe this broader clinical syndrome and reflect the new emphasis that has been placed upon its management. This article describes the current therapeutic options for this condition, focusing particularly on the novel medications and strategies that have recently been introduced, and highlighting promising therapeutic possibilities for the future.
PALEOMAGNETIC EVIDENCE ON THE ORIGIN OF THE MARQUETTE AND STEEP ROCK HARD HEMATITE AND GOETHITE DEPOSITS
Authors: Symons D. T. A.
Published: June 2009

Hard hematite ore is mined at the Cliff-Shaft mine, Marquette Range, Michigan, and hard goethite ore is mined at the Caland and Steep Rock mines. Steep Rock Range, Ontario. A paleomagnetic study was made on 67 samples from the ore horizons and associated rocks of these deposits. Alternating-current demagnetization and other standard paleomagnetic procedures were used. Geologists have proposed several theories to explain the genesis of these iron deposits of direct-shipping grade. Both ore deposits have a prefolding remanence that differs in age from any of the associated rock units. This indicates that both deposits were formed as laterites resulting from the oxidation and leaching of primary iron formation by meteoric solutions. The hard hematite ore was derived from the primary magnetite-banded oxide facies of iron formation which underlies the ore at the Cliff-Shaft mine, and the hard goethite ore was derived from the primary pyrite facies at the Caland or Steep Rock mines. The laterites were subsequently buried, folded, faulted, and intruded, but the mineralogy, structure, and texture of the ores were essentially unchanged during these events.
THE TECTONIC SIGNIFICANCE OF MESOSCOPIC SUBFABRICS IN THE SOUTHERN ROCKY MOUNTAINS OF ALBERTA AND BRITISH COLUMBIA
Authors: Price R. A.
Published: June 2009

Deformation throughout much of the southern Rocky Mountains was characterized by brittle failure in a strongly anisotropic layered sequence of non-metamorphic rocks. On a megascopic scale, the overall structure is dominated by an interlocking system of imbricate thrust plates that have moved relatively eastward or northeastward and upward. On a mesoscopic scale, the principal elements in the fabric of these rocks are fractures that are statistically parallel or perpendicular to the bedding, or else intersect it at preferred angles of approximately 25° or 70°. During deformation many of these fractures obviously were kinematically active, as discrete surfaces of slip that became slickensided, as zones of dilation that became filled with vein minerals, or as surfaces of pressure solution that are now marked by stylolites. Each of these fractures provides a partial record of the kinematics of some stage of the deformation, even when they are considered individually rather than as components in a fracture array whose symmetry is related to that of the movement picture during deformation. Each defines a unique line of slip and axis of rotation for slip, or a unique direction of relative extension or compression. Collectively, they provide a direct and succinct record of the kinematic history of an individual fabric domain, and a sound basis for dynamic analyses of deformation.Some preliminary results of a reconnaissance study of these mesoscopic subfabrics illustrate their tectonic significance.A movement picture can be established for the deformation that occurs within an individual thrust plate during its development and translation. Kinematic relationships between and among the interlocking thrust plates can. be studied.Within a broad area centered along the prominent structural reentrant that crosses the Rocky Mountains near Crowsnest Pass, two different movement pictures occur in superposition. Movement about both northerly and north westerly trending axes can be outlined on the basis of the mesoscopic subfabrics of rocks which, on a megascopic scale, have either a northwesterly or a northerly trending fabric axis. Movement patterns for the deformation associated with each of two regional structural salients converge in the vicinity of the reentrant.The mesoscopic subfabrics associated with transverse faults in parts of the Front Ranges outline a pattern of movement which indicates that they did not originate as tear faults related to the translation of the thrust plates, but instead are probably older gravity faults, whose orientation may be controlled by the fabric of the Hudsonian basement extending beneath the mountains from the Canadian Shield.
SULFIDES IN THE MUSKOX INTRUSION
Authors: Chamberlain J. A.
Published: June 2009

The Muskox intrusion is a layered, dominantly ultramafic pluton, in northern Canada. Sulfide phases belonging to the Ni–Cu–Fe–S system are concentrated along its margins and in chromite-rich horizons within its central layered series. They are sparsely disseminated through the rest of the intrusion, except in a core zone, which is almost barren of sulfides.The primary sulfide assemblages in the layered series range from nickel-rich at the base, through copper-rich at intermediate levels, to iron-rich near the roof. Nickel:copper ratios in the sulfides vary sympathetically with those of the host silicates. A similar but inverted sequence of sulfide assemblages occurs in the marginal zone. This and textural evidence indicate that the disseminated sulfides in the main body of the intrusion formed by segregation of sulfides from inter-cumulous magma and that they crystallized in equilibrium with their respective host silicates. The ultimate origin of the sulfur is not known. Sulfides in the upper part of the layered series and upper border zone appear to have formed by late replacement of the host rocks at temperatures below 675 °C.The concentration of sulfides along the intrusive contacts, and in adjacent wallrocks, developed during the primary cooling cycle by a process of desulfidization of the Muskox magma. Sulfide transfer in these locations was controlled primarily by the temperature gradient, not by gravity settling of a separate sulphide fluid.During subsequent serpentinization of the intrusion, the introduced fluid phase became progressively more oxygen depleted. The effect was most pronounced in the central regions, where primary sulfides ultimately decomposed to form native metals. Sulfur so released migrated as H2S to more peripheral parts of the intrusion, where it entered into various reactions with primary sulfides, oxides, and silicates.Separate processes thus operated to achieve desulfidization and desulfurization at magmatic and submagmatic temperatures, respectively, of the main body of the intrusion and to favor development of sulfide-enriched zones towards its margins.Sulfides in both the Muskox feeder dyke and the diabase dykes of the area are disseminated relatively uniformly through these rocks. These sulfides appear to have crystallized in situ and show no obvious zoning relationships.
Fossil Snakes from the Upper Milk River Formation (Upper Cretaceous), Alberta
Authors: Fox Richard C.
Published: June 2009

Isolated vertebrae collected from the early Campanian (Aquilan) Upper Milk River Formation, Alberta, are referred to two species of snakes: the first is aniliid-like and probably most closely allied to the late Maestrichtian (Lancian) Coniophis precedens Marsh 1892 from the United States, and the second, although possibly aniliid, is of otherwise indeterminate affinities. The occurrence of these snakes, at present the geologically oldest known in the New World, is consistent with suggestions that the Aniliidae had an origin in Laurasia rather than Gondwana, and that the Aniliidae may be close to the primitive ophidian stock.
K–Ar Dates for Metamorphic Minerals from the Esplanade Range, British Columbia
Authors: Ghent Edward D. , McKee Edwin H.
Published: June 2009

Ten K–Ar dates, including four coexisting mineral pairs, have been obtained for metamorphic rocks of the Horsethief Creek Formation (Proterozoic) of the Esplanade Range, British Columbia.The oldest date obtained is 181 m.y. on a single hornblende, but it is possible that this sample contains excess Ar. The oldest concordant biotite–hornblende date is 113 m.y.Muscovite that coexists with post-tectonic (F2 folding) biotite gave an age of 73 m.y. This age suggests that the temperature of the rocks had dropped below that for argon diffusion 73 m.y. ago.
Geochronology and thermal history of the Coast Plutonic Complex, near Prince Rupert, British Columbia
Authors: Harrison T. Mark , Armstrong Richard Lee , Naeser C. W. , Harakal J. E.
Published: June 2009

Fission track, K–Ar, and Rb–Sr mineral dates for the Ecstall and Quottoon plutons were determined to resolve the different cooling histories indicated by Rb–Sr whole-rock and mineral isochrons and published K–Ar dates.Comparison of mineral dates with previously assigned closure temperatures for the various isotopic chronometers has allowed temperature–time plots for the thermal history of individual samples and sample suites to be constructed.The Quottoon pluton, emplaced approximately 51 Ma ago, cooled rapidly during initial uplift that ended ~46 Ma ago with the present-day land surface at a depth of ~4 km. A second episode of uplift at an average rate of 0.05 cm year−1 (measured in Kasiks pluton that lies immediately to the east) began in the late Miocene. Cooling of the Ecstall pluton, following emplacement approximately 80 Ma ago, was disrupted by a thermal event approximately 65 Ma ago. Biotite in the Ecstall pluton appears to have incorporated extraneous argon during this event so that the calculated K–Ar dates lie between the time of emplacement and time of cooling through the closure temperature for Ar in biotite.The cooling curves and observed dates yield estimates for closure temperatures, at an intermediate cooling rate, for Ar in plagioclase and K-feldspar of ~260 °C and ~160 °C, respectively. For fission tracks in epidote the closure temperature estimate is ~240 °C.
Archaean precious-metal hydrothermal systems, Dome Mine, Abitibi Greenstone Belt. II. REE and oxygen isotope relations
Authors: Kerrich R. , Fryer B. J.
Published: June 2009

The Porcupine District, Abitibi Greenstone Belt, is one of the most extensive areas of Archaean auriferous mineralisation. At least two stages of lode-gold emplacement are recognised: the first stage involves gold-bearing carbonate–chert chemical sediments within the lower mafic volcanic sequence; the second stage is represented by auriferous hydrothermal quartz veins which postdate deformation of the greenstone assemblage and transect diverse host rocks.Rare-earth element (REE) concentrations in the stratiform carbonates are typical of the distinctive patterns recorded for Archaean chemical sediments. Chert in these rocks has a δ18O value averaging 17.1‰, implying exchange from heavier 18/16 ratios during diagenesis and metamorphism. Metabasic volcanic rocks and quartz–feldspar porphyry stocks with background gold abundances have mean whole-rock δ18O values of 9.1‰ and 10.7‰ respectively. This enrichment in 18O relative to primary igneous rocks is attributed to oxygen isotope exchange with seawater at low temperatures during fluid transport through the oceanic crust.Quartz in all of the five hydrothermal vein systems present has a δ18O of 14‰ to 15‰, and quartz-muscovite fractionations are 3.4‰ to 3.8‰. Ambient temperatures of mineralisation are estimated to have been 400 °C to 450 °C, from oxygen isotope thermometers, fluid inclusion filling temperatures, and metamorphic mineral assemblages. The calculated δ18O of the mineralising solutions is~10‰, implying fluids of metamorphic origin. REE patterns in hydrothermal quartz veins suggest that they have been derived from high-temperature solutions in equilibrium with source rocks having relatively flat (chondrite normalised) REE distributions, such as tholeiitic and komatiitic volcanics. Adjacent to hydrothermal veins, quartz in igneous rocks approaches isotopic equilibrium with vein quartz, at 15‰, and whole-rock δ18O values for metabasalts shift to ~11‰, implying extensive water-rock interaction. Strong depletions in heavy REE of metabasic schists adjacent to veins provides further evidence for pervasive hydrothermal alteration. The Eu enrichment of all lode gold deposits analysed at Dome Mine is consistent with the reduced state of the solutions involved in their deposition, as recorded by the predominance of Fe2+. The gold-bearing veins are believed to have formed by focussed flow of fluids outgassed at the greenschist–amphibolite transition. Source volumes for Au in the Porcupine District exceed 600 km3, the carrier fluid volume for mineralisation was 60–90 km3, the Au solute concentration in the low nanogram mL−1 range, and transport distances were of the order of 10 km. Such veins may be the precursors of precious-metal-bearing chemical sediments if fluids debouche into the hydrosphere.
A paleomagnetic and K–Ar study of the Umfraville Gabbro, Ontario
Authors: Palmer H. C. , Hayatsu A. , Waboso C. E. , Pullan S.
Published: June 2009

Two anti-parallel remanence directions have been isolated from samples of the Umfraville Gabbro situated in the southern part of the Grenville Province, Ontario. The magnetization yields a pole position at 160°E, [Formula: see text], A95 = 9.0°. Because of the dispersion of remanence directions, however, individual site poles plot over much of the Grenville Track. Regardless of direction and polarity of remanence, all samples unblock within a narrow temperature range of 525–560 °C. It is inferred that the magnetization process has involved slow cooling with both TRM and TCRM components being generated. Although one sample of zircon extracted from a genetically related syenite probably provides an estimate of the time of emplacement of 1160 Ma, the magnetization may be more closely related to the K–Ar age. Whole rock K–Ar ages range from 873 Ma to 1130 Ma, but all data points lie close to a 911 Ma isochron, with an initial 40Ar/36Ar ratio of 805. The isochron age is in close agreement with ages of 36Ar-free samples.
Laboratory alteration of titanomagnetites in submarine pillow lavas
Authors: Ryall Patrick J. C. , Hall J. M.
Published: June 2009

Submarine basalts have been heated in water in the laboratory to study the changes of magnetic properties with oxidation of the titanomagnetite. Before heating, the titanomagnetites were cation deficient with z ~ 0.1. With prolonged heating the degree of cation deficiency, as determined from the Curie temperature, increased Further heating in an attempt to produce titanomagnetites with z > 0.6 caused phase-splitting. This phase-splitting was sometimes accompanied by a self-reversal of magnetization. From the results of the experimental alterations we are able to predict the decrease of magnetization with distance from a spreading ridge.
The geochemistry of sediments from Little Traverse Bay, Lake Michigan: influence of physical processes
Authors: Mackin James E. , Owen Robert M.
Published: June 2009

Geochemical and textural analyses on 27 surficial sediment samples from Little Traverse Bay, Lake Michigan, were used to define the factors controlling the geochemistry of a pristine lacustrine embayment. Concentrations of 17 elements, carbonate and organic carbon, and textural data were subjected to an R-mode factor analysis. The first four factors determined by this analysis accounted for 89.1% of the variance in the data and were considered to have geochemical significance. We interpreted these factors as: (1) a fine-grained alumino-silicate and organics factor; (2) a heavy mineral factor; (3) a feldspar factor; and (4) a calcium carbonate factor. These factors are largely associated with detrital minerals, indicating that the physical processes occurring in the bay are of dominant importance in controlling the geochemistry of bottom sediments. Factor score distributions showed that the geochemistry of the sediments is largely controlled by bathymetry and by current circulation patterns.