bluuebunny/crossref_metadata_2025 huggingface dataset:
Kant's Quasi‐Transcendental Argument for a Necessary and Universal Evil Propensity in Human Nature
Authors: Palmquist Stephen R.
Published: March 2010

In Part One of Religion within the Bounds of Bare Reason, Kant repeatedly refers to a “proof” that human nature has a necessary and universal “evil propensity,” but he provides only obscure hints at its location. Interpreters have failed to identify such an argument in Part One. After examining relevant passages, summarizing recent attempts to reconstruct the argument, and explaining why these do not meet Kant's stated needs, I argue that the elusive proof must have a transcendental form (called quasi‐transcendental because Kant never uses “transcendental” in Religion). With deceptive simplicity, the section titles of Part One, viewed as components in an architechtonic system of religion, constitute steps in just such a proof.
That “Ought” Does Not Imply “Right”: Why It Matters for Virtue Ethics
Authors: Russell Daniel C.
Published: March 2010

Virtue ethicists sometimes say that a right action is what a virtuous person would do, characteristically, in the circumstances. But some have objected recently that right action cannot be defined as what a virtuous person would do in the circumstances because there are circumstances in which a right action is possible but in which no virtuous person would be found. This objection moves from the premise that a given person ought to do an action that no virtuous person would do, to the conclusion that the action is a right action. I demon‐strate that virtue ethicists distinguish “ought” from “right” and reject the assumption that “ought” implies “right.” I then show how their rejection of that assumption blocks this “right but not virtuous” objection. I conclude by showing how the thesis that “ought” does not imply “right” can clarify a further dispute in virtue ethics regarding whether “ought” implies “can.”
Hegel and Gadamer on Bildung
Authors: Odenstedt Anders
Published: March 2010

Hegel argues that Bildung (cultivation or education) involves an ability to reflect on one's habitual beliefs in a detached, uncommitted way. According to Hegel, the educated (gebildete) individual is able to consider a manifold of standpoints on a given issue through awareness of the historical and cultural variability of beliefs. Hans‐Georg Gadamer invokes Hegel's account of Bildung in arguing that historical study permits current presuppositions (Vorurteile) to become reflected through the awareness of cognitive plurality and change that such study brings about. The paper mainly tries to show three things: (i) that Hegel is a source of inspiration for Gadamer in this regard but that there are also important differences between their accounts of Bildung; (ii) that these accounts are not unambiguous; and (iii) that Gadamer, in particular, makes somewhat elusive claims on the power of Bildung.
On Post‐Heideggerean Difference: Derrida and Deleuze
Authors: Barber Daniel Colucciello
Published: March 2010

This paper takes up the Heideggerean question of difference. I argue that while Heidegger raises this question, his response to the question remains ambiguous and that this ambiguity pivots around the question of time. The bulk of the paper then looks at how Derrida and Deleuze respectively attempt to advance beyond Heidegger's ambiguity regarding the questions of difference and time. Derrida is able to demonstrate the manner in which time—as delay—is constitutive of any attempt to think difference. I argue, however, that his innovative articulation of “différance” maintains an extrinsic rather than intrinsic relation to difference in‐itself. To achieve an intrinsic relation, it is necessary to turn to the work of Deleuze, particularly to his discussion of “nonsense” and “singularity.”
In Defense of the Ideal of a Life Plan
Authors: Mintoff Joe
Published: March 2010

Aristotle claims at Eudemian Ethics 1.2 that everyone who can live according to his own choice should adopt some goal for the good life, which he will keep in view in all his actions, for not to have done so is a sign of folly. This is an opinion shared by other ancients as well as some moderns. Others believe, however, that this view is false to the human condition, and provide a number of objections: (1) you can't plan love; (2) nor life's surprises; (3) planning a whole life is of no use since the world changes too much; (4) as do our values; and (5) planning a life is something only dreary people would do. The aim of this paper is to examine these objections, as part of a broader attempt to defend the relevance of a eudaimonistic approach to the question of how to live well.
Stalnaker on Mathematical Information
Authors: Nuffer Gerhard
Published: March 2010

Robert Stalnaker has argued that mathematical information is information about the sentences and expressions of mathematics. I argue that this metalinguistic account is open to a variant of Alonzo Church's translation objection and that Stalnaker's attempt to get around this objection is not successful. If correct, this tells not only against Stalnaker's account of mathematical truths, but against any metalinguistic account of truths that are both necessary and informative.
On the Pragmatic Explanation of Concessive Knowledge Attributions
Authors: Benbaji Hagit
Published: March 2010

On Lewis's reading, fallibilism is the contradictory view that it is possible that S knows that p, even though S cannot eliminate some remote scenarios in which not‐p. The pragmatic strategy is to make the alleged contradiction a mere pragmatic implicature, which is explained by false conversational expectations. I argue that the pragmatic strategy fails.
Recognition, Attachment, and the Social Bases of Self‐Worth
Authors: Ferkany Matt
Published: March 2010

Recognition theorists have often sought to justify calls for the recognition of identities or cultures on grounds that a culturally egalitarian societal environment is a crucial social basis of a sense of self‐worth. In doing so they have often drawn on noncognitivist social‐psychological theorizing. This paper argues that this theorizing does not support the recognition theorist's position. It is argued that attachment theory together with recent empirical evidence support a more attachment‐ focused and Rawlsian vision of self‐worth's social bases according to which secure parent‐child attachment, associational ties, equal basic rights and liberties, and economic and educational opportunities are what really matter.
Pedro's Significance
Authors: Woodard Christopher
Published: March 2010

Williams's famous story of Jim exemplifies a general class of dilemmas caused by recalcitrant agents. Like Williams himself, most commentators have focused on Jim and the idea that he has special responsibility for his actions. This paper shifts attention to Pedro, exploring his significance in the story and arguing that Jim has a reason not to shoot that depends on Pedro's best possible response. In so doing, it sketches a new approach to the general class of dilemmas posed by recalcitrant agents, drawing attention to the advantages of this approach and to the difficulties it faces and comparing it to rival views associated with Ross and Kamm.
The Metaphysical Irrelevance of the Compatibilism Debate (and, More Generally, of Conceptual Analysis)
Authors: Balaguer Mark
Published: March 2010

It is argued here that the question of whether compatibilism is true is irrelevant to metaphysical questions about the nature of human decision‐making processes—for example, the question of whether or not humans have free will—except in a very trivial and metaphysically uninteresting way. In addition, it is argued that two other questions—namely, the conceptual‐analysis question of what free will is and the question that asks which kinds of freedom are required for moral responsibility—are also essentially irrelevant to metaphysical questions about the nature of human beings.
The Proper Structure of the Intellectual Virtues
Authors: Wright Sarah
Published: March 2010

If we adopt a virtue approach to epistemology, what form should the intellectual virtues take? In this paper, I argue that the proper structure of the intellectual virtues should be one that follows the tradition of internalism in epistemology. I begin by giving a general characterization of virtue epistemology and then define internalism within that framework. Arguing for internalism, I first consider the thought experiment of the new evil demon and show how externalist accounts of intellectual virtue, though constructed to accommodate our intuitions in such cases, cannot fully do so. I further argue that only adopting an internalist structure of the virtues will provide intellectual virtues that appropriately mirror the structure of the classical moral virtues. Finally, I argue that only an internalist structure of the virtues can explain why the intellectual virtues are valuable in themselves.
Two Kinds of Completeness and the Uses (and Abuses) of Exclusion Principles
Authors: Haug Matthew C.
Published: March 2010

I argue that the completeness of physics is composed of two distinct claims. The first is the commonly made claim that, roughly, every physical event is completely causally determined by physical events. The second has rarely, if ever, been explicitly stated in the literature and is the claim that microphysics provides a complete inventory of the fundamental categories that constitute both the causal features and intrinsic nature of all the events that causally affect the physical universe. After showing that these claims are distinct, I argue that they can be used to solve a difficulty with existing responses to the exclusion problem—namely, that these existing responses also undermine the powerful causal argument for physicalism. Recognizing that there are two kinds of completeness opens up room for the nonreductive physicalist to solve the exclusion problem while also endorsing a modified, cogent causal argument for a kind of physicalism compatible with her position.
Functional interplay between NMDA receptors, SK channels and voltage‐gated Ca2+ channels regulates synaptic excitability in the medial prefrontal cortex
Authors: Faber E. S. L.
Published: March 2010

Synaptic activity in the medial prefrontal cortex (mPFC) is fundamental for higher cognitive functions such as working memory. The present study shows that small conductance (SK) calcium‐activated potassium channels attenuate excitatory synaptic transmission at layer 2/3 and layer 5 inputs to layer 5 pyramidal neurons in the mPFC. SK channels are located postsynaptically at synapses where they are activated during synaptic transmission by calcium influx through NMDA receptors, L‐type calcium channels, R‐type calcium channels and by calcium release from IP3‐sensitive stores. Removal of the SK channel‐mediated shunt of synaptic transmission reveals significant NMDA receptor‐mediated activation during basal synaptic transmission, which is greater at layer 5 inputs (approximately 30%) than at layer 2/3 inputs (approximately 20%). These findings show that interactions between NMDA receptors, SK channels and voltage‐gated calcium channels play a critical role in regulating excitatory synaptic transmission in layer 5 pyramidal neurons in the mPFC.
Keeping H
2
O
2
Where You Need It
Authors: Wong Wei
Published: March 2010

Tyrosine phosphorylation of an H
2
O
2
-detoxifying enzyme enables localized accumulation of H
2
O
2
involved in signal transduction.
MHC Receptor for Retinal Circuitry
Authors: Gough Nancy R.
Published: March 2010

Glutamate-dependent organization of the visual input requires molecules traditionally associated with immune responses.
Kibra Prevents Hippos
Authors: Wong Wei
Published: March 2010

Kibra interacts with Expanded and Merlin in the Hippo pathway to control organ size.
Legume Symbiosome
Authors: Hines Pamela J.
Published: March 2010

Products encoded by the leguminous plant
Medicago
direct the differentiation of the bacterial partner in symbiosis.
Limiting Inflammatory Signaling
Authors: Ray L. Bryan
Published: March 2010

The multifunctional A20 protein can act in diverse ways to limit receptor-induced inflammatory signaling.
Allosteric Protein Kinase Regulation by Pseudokinases: Insights from STRAD
Authors: Rajakulendran Thanashan , Sicheri Frank
Published: March 2010

A kinase becomes activated when it binds as the “substrate” of a pseudokinase.
In Tanzania, Hemolysis after a Single Dose of Primaquine Coadministered with an Artemisinin Is Not Restricted to Glucose-6-Phosphate Dehydrogenase-Deficient (G6PD A−) Individuals
Authors: Shekalaghe Seif A. , ter Braak Roel , Daou Modibo , Kavishe Reginald , van den Bijllaardt Wouter , van den Bosch Sven , Koenderink Jan B. , Luty Adrian J. F. , Whitty Christopher J. M. , Drakeley Chris , Sauerwein Robert W. , Bousema Teun
Published: March 2010

The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature
P
lasmodium falciparum
gametocytes, the parasite stage responsible for transmission. Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment. As part of a mass drug intervention, we determined the hemolytic effect of sulfadoxine-pyrimethamine (SP) plus artesunate (AS) plus a single dose of primaquine (PQ; 0.75 mg/kg of body weight) in children aged 1 to 12 years. Children were randomized to receive SP+AS+PQ or placebo; those with a hemoglobin (Hb) level below 8 g/dl were excluded from receiving PQ and received SP+AS. The Hb concentration was significantly reduced 7 days after SP+AS+PQ treatment but not after placebo or SP+AS treatment. This reduction in Hb was most pronounced in G6PD-deficient (G6PD A−) individuals (−2.5 g/dl; 95% confidence interval [95% CI], −1.2 to −3.8 g/dl) but was also observed in heterozygotes (G6PD A) (−1.6 g/dl; 95% CI, −0.9 to −2.2 g/dl) and individuals with the wild-type genotype (G6PD B) (−0.5 g/dl; 95% CI, −0.4 to −0.6 g/dl). Moderate anemia (Hb level of <8 g/dl) was observed in 40% (6/15 individuals) of the G6PD A−, 11.1% (3/27 individuals) of the G6PD A, and 4.5% (18/399 individuals) of the G6PD B individuals; one case of severe anemia (Hb level of <5 g/dl) was observed. PQ may cause moderate anemia when coadministered with artemisinins, and excluding individuals based on G6PD status alone may not be sufficient to prevent PQ-induced hemolysis.
Expansion and Evolution of the
Streptococcus pneumoniae
Spain
9V
-ST156 Clonal Complex in Poland
Authors: Sadowy Ewa , Kuch Alicja , Gniadkowski Marek , Hryniewicz Waleria
Published: March 2010

In this study, we analyzed 118 penicillin-nonsusceptible
Streptococcus pneumoniae
(PNSP) isolates (MICs, ≥0.12 μg/ml) recovered in Poland in 2003 to 2005 from patients with respiratory tract diseases and invasive infections. Seven different serotypes (14, 9V, 23F, 19F, 6B, 19A, and 6A, in order of descending frequency), seven alleles of the
murM
gene (
murMA
,
murMB6
, and the new
murMB12
to -
16
alleles), and 31 multilocus sequence types (STs) were observed. The vast majority of the PNSP isolates (90.7%) belonged to the international multiresistant clones, and among these, the Spain
9V
-ST156 clonal complex was the most prevalent (56 isolates) and was significantly overrepresented in invasive infections. The clone has been evolving rapidly, as demonstrated by the observed number of STs, the diversity in multiple-locus variable-number-tandem-repeat analysis (MLVA) types, and the polymorphism of
pbp
and
pspA
genes (coding for penicillin-binding proteins and the pneumococcal surface protein A, respectively). The presence and structure of the
rlrA
islet (encoding the pneumococcal pilus) were very well conserved. The Spain
9V
-ST156 clonal complex has been largely responsible for a decreasing susceptibility to penicillin among pneumococci in Poland in recent years, in spite of a relatively moderate antimicrobial use.
Genetic Basis of Multidrug Resistance in
Acinetobacter
Clinical Isolates in Taiwan
Authors: Lin Yu-Chi , Hsia Ko-Chiang , Chen Yee-Chun , Sheng Wang-Huei , Chang Shan-Chwen , Liao Mei-Hui , Li Shu-Ying
Published: March 2010

Multidrug-resistant (MDR)
Acinetobacter
spp. have emerged as a threat to public health. We investigated the various genes involved in resistance to fluoroquinolones, aminoglycosides, cephalosporins, and carbapenems in 75 clinical
Acinetobacter
isolates from a Taiwanese hospital. All isolates were tested for the
gyrA
mutations, the presence of integrons,
bla
AmpC
, and carbapenem resistance genes. The Ser83Leu mutation in GyrA accounted for fluoroquinolone resistance. The presence of integrons containing aminoglycoside-modifying enzymes was associated with resistance to gentamicin and tobramycin but not with resistance to amikacin. The presence of an IS
Aba1
element upstream of
bla
AmpC
was correlated with cephalosporin resistance. Although most
Acinetobacter
baumannii
isolates with IS
Aba1
-
bla
OXA-51-
like
were resistant to carbapenems, several isolates remained susceptible to carbapenems. Transformation by the introduction of IS
Aba1
-
bla
OXA-23
or IS
Aba1
-
bla
OXA-66
into
A. baumannii
ATCC 15151 (CIP 70.10), resulting in the overexpression of OXA-23 or OXA-66, respectively, suggested the role of the IS
Aba1
element as a strong promoter. The two transformants showed significantly increased resistance to piperacillin-tazobactam, imipenem, and meropenem. The cefepime resistance conferred by IS
Aba1
-
bla
OXA-23
and the impact of IS
Aba1
-
bla
OXA-66
on carbapenem resistance in
A. baumannii
are reported here for the first time. Continuous surveillance of antibiotic resistance genes in MDR
Acinetobacter
spp. and elucidation of their antibiotic resistance mechanisms are crucial for the development of therapy regimens and for the prevention of further dissemination of these antibiotic resistance genes.
Identification and Characterization of a Glycosyltransferase Involved in
Acinetobacter baumannii
Lipopolysaccharide Core Biosynthesis
Authors: Luke Nicole R. , Sauberan Shauna L. , Russo Thomas A. , Beanan Janet M. , Olson Ruth , Loehfelm Thomas W. , Cox Andrew D. , St. Michael Frank , Vinogradov Evgeny V. , Campagnari Anthony A.
Published: March 2010

Although
Acinetobacter baumannii
has emerged as a significant cause of nosocomial infections worldwide, there have been few investigations describing the factors important for
A. baumannii
persistence and pathogenesis. This paper describes the first reported identification of a glycosyltransferase, LpsB, involved in lipopolysaccharide (LPS) biosynthesis in
A. baumannii
. Mutational, structural, and complementation analyses indicated that LpsB is a core oligosaccharide glycosyl transferase. Using a genetic approach,
lpsB
was compared with the
lpsB
homologues of several
A. baumannii
strains. These analyses indicated that LpsB is highly conserved among
A. baumannii
isolates. Furthermore, we developed a monoclonal antibody, monoclonal antibody 13C11, which reacts to an LPS core epitope expressed by approximately one-third of the
A. baumannii
clinical isolates evaluated to date. Previous studies describing the heterogeneity of
A. baumannii
LPS were limited primarily to structural analyses; therefore, studies evaluating the correlation between these surface glycolipids and pathogenesis were warranted. Our data from an evaluation of LpsB mutant 307::TN17, which expresses a deeply truncated LPS glycoform consisting of only two 3-deoxy-
d
-manno-octulosonic acid residues and lipid A, suggest that
A. baumannii
LPS is important for resistance to normal human serum and confers a competitive advantage for survival
in vivo
. These results have important implications for the role of LPS in
A. baumannii
infections.
Listeriolysin O-Dependent Bacterial Entry into the Cytoplasm Is Required for Calpain Activation and Interleukin-1α Secretion in Macrophages Infected withListeria monocytogenes
Authors: Dewamitta Sita R. , Nomura Takamasa , Kawamura Ikuo , Hara Hideki , Tsuchiya Kohsuke , Kurenuma Takeshi , Shen Yanna , Daim Sylvia , Yamamoto Takeshi , Qu Huixin , Sakai Shunsuke , Xu Yanting , Mitsuyama Masao
Published: March 2010

Listeriolysin O (LLO), anhly-encoded cytolysin ofListeria monocytogenes, plays an essential role in the entry ofL. monocytogenesinto the host cell cytoplasm.L. monocytogenes-infected macrophages produce various proinflammatory cytokines, including interleukin-1α (IL-1α), that contribute to the host immune response. In this study, we have examined IL-1α production in macrophages infected with wild-typeL. monocytogenesor a nonescaping mutant strain deficient for LLO (Δhly). Expression of IL-1α mRNA and accumulation of pro-IL-1α in the cytoplasm were induced by both strains. In contrast, the secretion of the mature form of IL-1α from infected macrophages was observed in infection with wild-typeL. monocytogenesbut not with the Δhlymutant. A recovery of the ability to induce IL-1α secretion was shown in a mutant strain complemented with thehlygene. The Toll-like receptor (TLR)/MyD88 signaling pathway was exclusively required for the expression of pro-IL-1α, independently of LLO-mediated cytoplasmic entry ofL. monocytogenes. The LLO-dependent secretion of mature IL-1α was abolished by addition of calcium chelators, and only LLO-producingL. monocytogenesstrains were able to induce elevation of the intracellular calcium level in infected macrophages. A calcium-dependent protease, calpain, was implicated in the maturation and secretion of IL-1α induced by LLO-producingL. monocytogenesstrains based on the effect of calpain inhibitor. Functional activation of calpain was detected in macrophages infected with LLO-producingL. monocytogenesstrains but not with a mutant strain lacking LLO. These results clearly indicated that LLO-mediated cytoplasmic entry of bacteria could induce the activation of intracellular calcium signaling, which is essential for maturation and secretion of IL-1α in macrophages duringL. monocytogenesinfection through activation of a calcium-dependent calpain protease. In addition, recombinant LLO, when added to macrophages infected with the Δhlystrain, could induce calcium influx and IL-1α secretion at doses exhibiting cytolytic activity, suggesting that LLO produced by intracellularL. monocytogenesmay be implicated in induction of calcium influx through pore formation.
The Proline-Rich Region of Pneumococcal Surface Proteins A and C Contains Surface-Accessible Epitopes Common to All Pneumococci and Elicits Antibody-Mediated Protection against Sepsis
Authors: Daniels Calvin C. , Coan Patricia , King Janice , Hale Joanetha , Benton Kimberly A. , Briles David E. , Hollingshead Susan K.
Published: March 2010

Pneumococcal surface protein A (PspA) and PspC of
Streptococcus pneumoniae
are surface virulence proteins that interfere with complement deposition and elicit protective immune responses. The C-terminal halves of PspA and PspC have some structural similarity and contain highly cross-reactive proline-rich (PR) regions. In many PR regions of PspA and PspC, there exists an almost invariant nonproline block (NPB) of about 33 amino acids. Neither the PR regions nor their NPB exhibit the alpha-helical structure characteristic of much of the protection-eliciting N-terminal portions of PspA and PspC. Prior studies of PspA and PspC as immunogens focused primarily on the alpha-helical regions of these molecules that lack the PR and NPB regions. This report shows that immunization with recombinant PR (rPR) molecules and passive immunization with monoclonal antibodies reactive with either NPB or PR epitopes are protective against infection in mice. PR regions of both PspA and PspC were antibody accessible on the pneumococcal surface. Our results indicate that while PspA could serve as a target of these protective antibodies in invasive infections, PspC might not. When antibody responses to rPR immunogens were evaluated by using flow cytometry to measure antibody binding to live pneumococci, it was observed that the mice that survived subsequent challenge produced significantly higher levels of antibodies reactive with exposed PR epitopes than the mice that became moribund. Due to their conservation and cross-reactivity, the PR regions and NPB regions represent potential vaccine targets capable of eliciting cross-protection immunity against pneumococcal infection.
Anthrax Lethal Toxin Impairs CD1d-Mediated Antigen Presentation by Targeting the Extracellular Signal-Related Kinase 1/2 Mitogen-Activated Protein Kinase Pathway
Authors: Khan Masood A. , Gallo Richard M. , Brutkiewicz Randy R.
Published: March 2010

Lethal toxin (LT) is a critical virulence factor of
Bacillus anthracis
and an important means by which this bacterium evades the host's immune system. In this study, we demonstrate that CD1d-expressing cells treated with LT have reduced CD1d-mediated antigen presentation. We earlier showed an important role for the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2 (ERK1/2) in the regulation of CD1d-mediated antigen presentation, and we report here that LT impairs antigen presentation by CD1d in an ERK1/2-dependent manner. Similarly, LT and the ERK1/2 pathway-specific inhibitor U0126 caused a decrease in major histocompatibility complex (MHC) class II-mediated antigen presentation. Confocal microscopy analyses revealed altered intracellular distribution of CD1d and LAMP-1 in LT-treated cells, similar to the case for ERK1/2-inhibited cells. These results suggest that
Bacillus anthracis
has the ability to evade the host's innate immune system by reducing CD1d-mediated antigen presentation through targeting the ERK1/2 pathway.
CCR7-Dependent Immunity during Acute
Toxoplasma gondii
Infection
Authors: Noor Shahani , Habashy Andrew S. , Nance J. Philip , Clark Robin T. , Nemati Kiav , Carson Monica J. , Wilson Emma H.
Published: March 2010

The chemokine receptor CCR7 is a well-established homing receptor for dendritic cells and T cells. Interactions with its ligands, CCL19 and CCL21, facilitate priming of immune responses in lymphoid tissue, yet CCR7-independent immune responses can be generated in the presence of sufficient antigen. In these studies, we investigated the role of CCR7 signaling in the generation of protective immune responses to the intracellular protozoan parasite
Toxoplasma gondii
. The results demonstrated a significant increase in the expression of CCL19, CCL21, and CCR7 in peripheral and central nervous system (CNS) tissues over the course of infection. Unexpectedly, despite the presence of abundant antigen, CCR7 was an absolute requirement for protective immunity to
T. gondii
, as CCR7
−/−
mice succumbed to the parasite early in the acute phase of infection. Although serum levels of interleukin 12 (IL-12), IL-6, tumor necrosis factor alpha (TNF-α), and IL-10 remained unchanged, there was a significant decrease in CCL2/monocyte chemoattractant protein 1 (MCP-1) and inflammatory monocyte recruitment to the site of infection. In addition, CCR7
−/−
mice failed to produce sufficient gamma interferon (IFN-γ), a critical Th1-associated effector cytokine required to control parasite replication. As a result, there was increased parasite dissemination and a significant increase in parasite burden in the lungs, livers, and brains of infected mice. Adoptive-transfer experiments revealed that expression of CCR7 on the T-cell compartment alone is sufficient to enable T-cell priming, increase IFN-γ production, and allow the survival of CCR7
−/−
mice. These data demonstrate an absolute requirement for T-cell expression of CCR7 for the generation of protective immune responses to
Toxoplasma
infection.
Minimal Role for the Circumsporozoite Protein in the Induction of Sterile Immunity by Vaccination with Live Rodent Malaria Sporozoites
Authors: Mauduit Marjorie , Tewari Rita , Depinay Nadya , Kayibanda Michèle , Lallemand Eliette , Chavatte Jean-Marc , Snounou Georges , Rénia Laurent , Grüner Anne Charlotte
Published: March 2010

Immunization with live
Plasmodium
sporozoites under chloroquine prophylaxis (Spz plus CQ) induces sterile immunity against sporozoite challenge in rodents and, more importantly, in humans. Full protection is obtained with substantially fewer parasites than with the classic immunization with radiation-attenuated sporozoites. The sterile protection observed comprised a massive reduction in the hepatic parasite load and an additional effect at the blood stage level. Differences in the immune responses induced by the two protocols occur but are as yet little characterized. We have previously demonstrated that in mice immunized with irradiated sporozoites, immune responses against the circumsporozoite protein (CSP), the major component of the sporozoite's surface and the leading malaria vaccine candidate, were not essential for sterile protection. Here, we have employed transgenic
P
lasmodium berghei
parasites in which the endogenous CSP was replaced by that of
P
lasmodium yoelii
, another rodent malaria species, to assess the role of CSP in the sterile protection induced by the Spz-plus-CQ protocol. The data demonstrated that this role was minor because sterile immunity was obtained irrespective of the origin of CSP expressed by the parasites in this model of protection. The immunity was obtained through a single transient exposure of the host to the immunizing parasites (preerythrocytic and erythrocytic), a dose much smaller than that required for immunization with radiation-attenuated sporozoites.
Alkali Metal Cation Transport and Homeostasis in Yeasts
Authors: Ariño Joaquín , Ramos José , Sychrová Hana
Published: March 2010

The maintenance of appropriate intracellular concentrations of alkali metal cations, principally K
+
and Na
+
, is of utmost importance for living cells, since they determine cell volume, intracellular pH, and potential across the plasma membrane, among other important cellular parameters. Yeasts have developed a number of strategies to adapt to large variations in the concentrations of these cations in the environment, basically by controlling transport processes. Plasma membrane high-affinity K
+
transporters allow intracellular accumulation of this cation even when it is scarce in the environment. Exposure to high concentrations of Na
+
can be tolerated due to the existence of an Na
+
, K
+
-ATPase and an Na
+
, K
+
/H
+
-antiporter, which contribute to the potassium balance as well. Cations can also be sequestered through various antiporters into intracellular organelles, such as the vacuole. Although some uncertainties still persist, the nature of the major structural components responsible for alkali metal cation fluxes across yeast membranes has been defined within the last 20 years. In contrast, the regulatory components and their interactions are, in many cases, still unclear. Conserved signaling pathways (e.g., calcineurin and HOG) are known to participate in the regulation of influx and efflux processes at the plasma membrane level, even though the molecular details are obscure. Similarly, very little is known about the regulation of organellar transport and homeostasis of alkali metal cations. The aim of this review is to provide a comprehensive and up-to-date vision of the mechanisms responsible for alkali metal cation transport and their regulation in the model yeast Saccharomyces cerevisiae and to establish, when possible, comparisons with other yeasts and higher plants.
H. & R. Johnson (India) Limited in Gujarat
Authors: Singh Ramendra
Published: February 2010

This case is written at a time when organized retailing in India was booming, opening up opportunities for numerous big indigenous and foreign players. Also, with the rising disposable incomes of the Indian middle class and their changing tastes and preferences, they were becoming more and more demanding. The case is written at this crucial juncture of the changing economy wherein a mammoth like H. & R. Johnson, with a rich lineage of product and process innovations and international and domestic (Indian) market leadership needed to make the best out of the changing economy. Should HRJIL ride the retail wave by offering different products from its broad range of products, like ready-made kitchens, living rooms and the like; or should the company, given its dreams and present capabilities, utilize the unmet customer service gaps to provide services required of laying tiles, and in the process, develop servicing capabilities to become an end-to-end solution provider to its customers. The purpose of this case is to enable students to practice making decisions for the company at this important point in time with regard to the market opportunities by considering the capabilities and the core competencies of the company, its business model, and the existing distribution network.
Too much programming too soon?
Authors: Guzdial Mark , Robertson Judy
Published: March 2010

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish excerpts from selected posts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

Mark Guzdial and Judy Robertson discuss the role of programming in introductory computer science.
CS and biology's growing pains
Authors: Goth Gregory
Published: March 2010

Biologists can benefit from learning and using the tools of computer science, but several real-world obstacles remain.
The ethics beat
Authors: Hollander Rachelle
Published: March 2010

Surveying the increasing variety and nature of ethical challenges encountered by computing researchers and practitioners.
Privacy on the data web
Authors: O'Hara Kieron , Shadbolt Nigel
Published: March 2010

Considering the nebulous question of ownership in the virtual realm.
Chasing the AIDS virus
Authors: Lengauer Thomas , Altmann André , Thielen Alexander , Kaiser Rolf
Published: March 2010

With no HIV vaccine in sight, virologists need to know how the virus will react to a given combination drug therapy.
Using the forest to see the trees
Authors: Torralba A. , Murphy K. P. , Freeman W. T.
Published: March 2010

Recognizing objects in images is an active area of research in computer vision. In the last two decades, there has been much progress and there are already object recognition systems operating in commercial products. However, most of the algorithms for detecting objects perform an exhaustive search across all locations and scales in the image comparing local image regions with an object model. That approach ignores the semantic structure of scenes and tries to solve the recognition problem by brute force. In the real world, objects tend to covary with other objects, providing a rich collection of contextual associations. These contextual associations can be used to reduce the search space by looking only in places in which the object is expected to be; this also increases performance, by rejecting patterns that look like the target but appear in unlikely places.

Most modeling attempts so far have defined the context of an object in terms of other previously recognized objects. The drawback of this approach is that inferring the context becomes as difficult as detecting each object. An alternative view of context relies on using the entire scene information holistically. This approach is algorithmically attractive since it dispenses with the need for a prior step of individual object recognition. In this paper, we use a probabilistic framework for encoding the relationships between context and object properties and we show how an integrated system provides improved performance. We view this as a significant step toward general purpose machine vision systems.
Puzzled: Solutions and sources
Authors: Winkler Peter
Published: March 2010

Last month (February 2010, p. 120) we posted a trio of brainteasers, including one as yet unsolved, concerning the breaking of a bar of chocolate.
Smart meeting systems
Authors: Yu Zhiwen , Nakamura Yuichi
Published: March 2010

Smart meeting systems, which record meetings and analyze the generated audio--visual content for future viewing, have been a topic of great interest in recent years. A successful smart meeting system relies on various technologies, ranging from devices and algorithms to architecture. This article presents a condensed survey of existing research and technologies, including smart meeting system architecture, meeting capture, meeting recognition, semantic processing, and evaluation methods. It aims at providing an overview of underlying technologies to help understand the key design issues of such systems. This article also describes various open issues as possible ways to extend the capabilities of current smart meeting systems.
Electromigration for microarchitects
Authors: Abella Jaume , Vera Xavier
Published: March 2010

Degradation of devices has become a major issue for processor design due to continuous device shrinkage and current density increase. Transistors and wires suffer high stress, and failures may appear in the field. In particular, wires degrade mainly due to electromigration when driving current. Techniques to mitigate electromigration to some extent have been proposed from the circuit point of view, but much effort is still required from the microarchitecture side to enable wire scaling in future technologies.

This survey brings to the microarchitecture community a comprehensive study of the causes and implications of electromigration in digital circuits and describes the challenges that must be faced to mitigate electromigration by means of microarchitectural solutions.
Serialized parallel code generation framework for MPSoC
Authors: Kwon Seongnam , Ha Soonhoi
Published: March 2010

The models of computations that express concurrency naturally are preferred for initial specification of MPSoC system, since popular programming languages such as C and C++ are designed for sequential execution. In our previous work, we proposed a design framework where two models are used for the initial specification of the system behavior; task model at the top level and dataflow model inside each task. After the partition and mapping process is performed with each architecture candidate, the target code is automatically generated for both Design-Space Exploration (DSE) and final implementation. In this article, we focus on parallel code generation for MPSoC, proposing two main techniques. The first is to express functional and data parallelism differently following the partition and mapping decision. In the proposed technique, the generated code consists of multiple tasks running concurrently, which achieves functional parallelism. On the other hand, we use OpenMP directives to express data parallelism inside a task. Second is to adopt the code serialization technique to execute a multitasking application without OS scheduler, aiming to generate the highly portable code on various platforms for an efficient DSE process. We extend the previous code serialization techniques to multiprocessor systems and utilize the formal properties of the dataflow model for efficient code generation. The experiments including H.263 codec example show the viability of the proposed technique and the efficiency of the generated code.
Benchmarking and evaluating reconfigurable architectures targeting the mobile domain
Authors: Jamieson Peter , Becker Tobias , Cheung Peter Y. K. , Luk Wayne , Rissa Tero , Pitkänen Teemu
Published: March 2010

We present the GroundHog 2009 benchmarking suite that evaluates the power consumption of reconfigurable technology for applications targeting the mobile computing domain. This benchmark suite includes seven designs; one design targets fine-grained FPGA fabrics allowing for quick state-of-the-art evaluation, and six designs are specified at a high level allowing them to target a range of existing and future reconfigurable technologies. Each of the six designs can be stimulated with the help of synthetically generated input stimuli created by an open-source tool included in the downloadable suite. Another tool is included to help verify the correctness of each implemented design. To demonstrate the potential of this benchmark suite, we evaluate the power consumption of two modern industrial FPGAs targeting the mobile domain. Also, we show how an academic FPGA framework, VPR 5.0, that has been updated for power estimates can be used to estimates the power consumption of different FPGA architectures and an open-source CAD flow mapping to these architectures.
Parameterized architecture-level dynamic thermal models for multicore microprocessors
Authors: Li Duo , Tan Sheldon X.-D. , Pacheco Eduardo H. , Tirumala Murli
Published: March 2010

In this article, we propose a new architecture-level parameterized dynamic thermal behavioral modeling algorithm for emerging thermal-related design and optimization problems for high-performance multicore microprocessor design. We propose a new approach, called
ParThermPOF
, to build the parameterized thermal performance models from the given accurate architecture thermal and power information. The new method can include a number of variable parameters such as the locations of thermal sensors in a heat sink, different components (heat sink, heat spreader, core, cache, etc.), thermal conductivity of heat sink materials, etc. The method consists of two steps: first, a response surface method based on low-order polynomials is applied to build the parameterized models at each time point for all the given sampling nodes in the parameter space. Second, an improved Generalized Pencil-Of-Function (GPOF) method is employed to build the transfer-function-based behavioral models for each time-varying coefficient of the polynomials generated in the first step. Experimental results on a practical quad-core microprocessor show that the generated parameterized thermal model matches the given data very well. The compact models by ParThermPOF offer two order of magnitudes speedup over the commercial thermal analysis tool
FloTHERM
on the given examples. ParThermPOF is very suitable for design space exploration and optimization where both time and system parameters need to be considered.
Reliability analysis of memories protected with BICS and a per-word parity bit
Authors: Reviriego Pedro , Maestro Juan Antonio , Bleakley Chris J.
Published: March 2010

This article presents an analysis of the reliability of memories protected with Built-in Current Sensors (BICS) and a per-word parity bit when exposed to Single Event Upsets (SEUs). Reliability is characterized by Mean Time to Failure (MTTF) for which two analytic models are proposed. A simple model, similar to the one traditionally used for memories protected with scrubbing, is proposed for the low error rate case. A more complex Markov model is proposed for the high error rate case. The accuracy of the models is checked using a wide set of simulations. The results presented in this article allow fast estimation of MTTF enabling design of optimal memory configurations to meet specified MTTF goals at minimum cost. Additionally the power consumption of memories protected with BICS is compared to that of memories using scrubbing in terms of the number of read cycles needed in both configurations.
Persuasive mobile exercise companion for teenagers with weight management issues
Authors: Arteaga Sonia
Published: March 2010

Obesity is a grave problem in our society. A significant increase in prevalence within the last 20 years has resulted in greater mortality, increased stress on our healthcare system, and a decreased quality of life for people dealing with obesity and overweight issues. My dissertation concerns a mobile application that assists teenagers in leading physically active lifestyles to try and combat the risk of becoming obese or overweight as adults. I hope this research will prove to be a viable option to prevent or reduce the risk of obesity for teens so that they lead healthy lives. By reducing the risks of obesity and overweight problems, we also reduce the risk of these individuals developing debilitating diseases such as diabetes and cardiovascular diseases.
Sign language synthesis
Authors: Delorme Maxime
Published: March 2010

In this paper, I describe the summary of what I plan to do for my PhD thesis on sign language synthesis. The modelling of the skeleton of virtual characters would lead to improvements in the quality of animations. Thus the first step is to study how to build such a model, by analysing corpora data and integrating biological data. Then, we will implement the model and confront it to users to evaluate it.
AudioNav
Authors: Fallah Navid
Published: March 2010

This research is to design a novel indoor navigation tool called AudioNav for users with visual impairment. Current navigation systems rely upon expensive physical augmentation of the environment or expensive sensing equipment. The proposed system is infrastructure-free and low cost as it uses only a virtual representation of a building to be navigated.

Our proposed system: 1) extracts a floor-plan and recognizes landmarks in the three-dimensional model of a building, 2) locates and tracks the user inside the building while there is no GPS reception, 3) finds the most suitable path based on the user's special needs, and provides step-by-step direction to the destination using voice, speech, or haptic feedback.
Assistive systems for children with dyslexia and autism
Authors: Sampath Harini , Sivaswamy Jayanthi , Indurkhya Bipin
Published: March 2010

Autism and dyslexia are both developmental disorders of neural origin. As we still do not understand the neural basis of these disorders fully, technology can take two approaches in helping those affected. The first is to compensate externally for a known difficulty and the other is to achieve the same function using a completely different means. To demonstrate the first option, we are developing a system to compensate for the auditory processing difficulties in case of dyslexia and to demonstrate the second option we propose a system for autism where we remove the need for traditional languages and instead use pictures for communication.
Issues in applying computational intelligence
Authors: Kordon Arthur
Published: March 2010

Applying any emerging technology is not trivial and requires some level of risk-taking even when the competitive advantage is clear. In the case of computational intelligence the process is even harder due to the different nature of the comprising methods, the lack of marketing, affordable professional tools and application methodology. Another important factor slowing down computational intelligence applications is the wrong perception of the technology. To many potential users it looks like it's either too expensive or it's rocket science. The pendulum of expectations also swings from one extreme of anticipating a silver bullet to all problems to the other extreme of awaiting the next technology fiasco.
The business of clouds
Authors: Rosen Guy
Published: March 2010

At the turn of the 20th century, companies stopped generating their own power and plugged into the electricity grid. In his now famous book The Big Switch, Nick Carr analogizes those events of a hundred years ago to the tectonic shift taking place in the technology industry today.
General Approach to Regions of Variability via Subordination of Harmonic Mappings
Authors: Chen Sh. , Ponnusamy S. , Wang X.
Published: March 2010

Using subordination, we determine the regions of variability of several
subclasses of harmonic mappings. We also graphically illustrate the regions of variability for
several sets of parameters for certain special cases.