bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of menopause on the chemical control of breathing and its relationship with acid-base status
Authors: Preston Megan E. , Jensen Dennis , Janssen Ian , Fisher John T.
Published: December 2008

This study examined the role of alterations in the chemoreflex control of breathing, acid-base balance, and their interaction in postmenopausal ventilatory adaptations. A modified iso-oxic hyperoxic and hypoxic CO2-rebreathing procedure was employed to evaluate central and peripheral chemoreflex drives to breathe, respectively, in 15 healthy postmenopausal and 20 premenopausal women of similar age. Arterialized venous blood samples were collected at rest for the estimation of arterial Pco2 (PaCO2) and H+ concentration ([H+]), plasma strong ion difference ([SID]) and total weak acid ([A]tot) concentrations, and serum progesterone ([P4]) and 17β-estradiol ([E2]) concentrations. In post- compared with premenopausal women, PaCO2, [SID], and the central chemoreflex ventilatory recruitment threshold for Pco2 (VRTco2) were higher, whereas [P4] and [E2] were lower (all P < 0.05), with no significant change in central or peripheral chemoreflex sensitivity, peripheral chemoreflex VRTco2, and [A]tot. The acidifying effect of an increased PaCO2 was offset by the alkalizing effect of an increased [SID], such that [H+] was preserved in post- compared with premenopausal women. PaCO2 correlated positively with the central chemoreflex VRTco2 ( r = 0.67, P < 0.01), which in turn correlated positively with [SID] ( r = 0.53, P < 0.01) within the pooled data. In conclusion, the relative alveolar hypoventilation and attendant arterial hypercapnia in healthy post- compared with premenopausal women could be explained, in part, by the interaction of 1) reduced central, but not peripheral, chemoreflex VRTco2, 2) increased [SID], and 3) reduced circulating female sex steroid hormone concentrations.
Adjustments of Motor Pattern for Load Compensation Via Modulated Activations of Muscle Synergies During Natural Behaviors
Authors: Cheung Vincent C. K. , d'Avella Andrea , Bizzi Emilio
Published: December 2008

It has been suggested that the motor system may circumvent the difficulty of controlling many degrees of freedom in the musculoskeletal apparatus by generating motor outputs through a combination of discrete muscle synergies. How a discretely organized motor system compensates for diverse perturbations has remained elusive. Here, we investigate whether motor responses observed after an inertial-load perturbation can be generated by altering the recruitment of synergies normally used for constructing unperturbed movements. Electromyographic (EMG, 13 muscles) data were collected from the bullfrog hindlimb during natural behaviors before, during, and after the same limb was loaded by a weight attached to the calf. Kinematic analysis reveals the absence of aftereffect on load removal, suggesting that load-related EMG changes were results of immediate motor pattern adjustments. We then extracted synergies from EMGs using the nonnegative matrix factorization algorithm and developed a procedure for assessing the extent of synergy sharing across different loading conditions. Most synergies extracted were found to be activated in all loaded and unloaded conditions. However, for certain synergies, the amplitude, duration, and/or onset time of their activation bursts were up- or down-modulated during loading. Behavioral parameterizations reveal that load-related modulation of synergy activations depended on the behavioral variety (e.g., kick direction and amplitude) and the movement phase performed. Our results suggest that muscle synergies are robust across different dynamic conditions and immediate motor adjustments can be accomplished by modulating synergy activations. An appendix describes the novel procedure we developed, useful for discovering shared and specific features from multiple data sets.
Postsynaptic Receptive Field Size and Spike Threshold Determine Encoding of High-Frequency Information Via Sensitivity to Synchronous Presynaptic Activity
Authors: Middleton Jason W. , Longtin André , Benda Jan , Maler Leonard
Published: December 2008

Parallel sensory streams carrying distinct information about various stimulus properties have been observed in several sensory systems, including the visual system. What remains unclear is why some of these streams differ in the size of their receptive fields (RFs). In the electrosensory system, neurons with large RFs have short-latency responses and are tuned to high-frequency inputs. Conversely, neurons with small RFs are low-frequency tuned and exhibit longer-latency responses. What principle underlies this organization? We show experimentally that synchronous electroreceptor afferent (P-unit) spike trains selectively encode high-frequency stimulus information from broadband signals. This finding relies on a comparison of stimulus-spike output coherence using output trains obtained by either summing pairs of recorded afferent spike trains or selecting synchronous spike trains based on coincidence within a small time window. We propose a physiologically realistic decoding mechanism, based on postsynaptic RF size and postsynaptic output rate normalization that tunes target pyramidal cells in different electrosensory maps to low- or high-frequency signal components. By driving realistic neuron models with experimentally obtained P-unit spike trains, we show that a small RF is matched with a postsynaptic integration regime leading to responses over a broad range of frequencies, and a large RF with a fluctuation-driven regime that requires synchronous presynaptic input and therefore selectively encodes higher frequencies, confirming recent experimental data. Thus our work reveals that the frequency content of a broadband stimulus extracted by pyramidal cells, from P-unit afferents, depends on the amount of feedforward convergence they receive.
High-Resolution Three-Dimensional Extracellular Recording of Neuronal Activity With Microfabricated Electrode Arrays
Authors: Du Jiangang , Riedel-Kruse Ingmar H. , Nawroth Janna C. , Roukes Michael L. , Laurent Gilles , Masmanidis Sotiris C.
Published: December 2008

Microelectrode array recordings of neuronal activity present significant opportunities for studying the brain with single-cell and spike-time precision. However, challenges in device manufacturing constrain dense multisite recordings to two spatial dimensions, whereas access to the three-dimensional (3D) structure of many brain regions appears to remain a challenge. To overcome this limitation, we present two novel recording modalities of silicon-based devices aimed at establishing 3D functionality. First, we fabricated a dual-side electrode array by patterning recording sites on both the front and back of an implantable microstructure. We found that the majority of single-unit spikes could not be simultaneously detected from both sides, suggesting that in addition to providing higher spatial resolution measurements than that of single-side devices, dual-side arrays also lead to increased recording yield. Second, we obtained recordings along three principal directions with a multilayer array and demonstrated 3D spike source localization within the enclosed measurement space. The large-scale integration of such dual-side and multilayer arrays is expected to provide massively parallel recording capabilities in the brain.
Starring Nero as Nero: Poetry, Role-Playing and Identity in Juvenal 8.215-21
Authors: Cowan Robert
Published: December 2008

Juvenal's synkrisis between Orestes and Nero climaxes with the statement that the former never played Orestes; the implied antithesis, that Nero did play Nero, gains point from the princeps' practice of wearing masks resembling his own face. This blurring of the distinction between 'playing Nero' and 'playing Orestes' problematizes the princeps' identity. This problematization is furthered by the peculiarities of Orestes, who in various tragic plots repeatedly either plays other roles or is himself impersonated. This is part of Satire 8's wider exploration of identity as underdetermined by ancestry and the inadequacy of names as signifiers. The further statement that Orestes never wrote a Troica is illuminated by its intertextual engagement with Callimachus Epigr. 59 G-P, in which the poet's loss of his 'Pyladeses' through writing a play contrasts with Orestes' omission of this final act of madness. The Callimachean Orestes thus keeps distinct the roles of tragedian and tragic hero, poet and character, thereby foregrounding Nero's failure to maintain this distinction. By blurring his identity with that of Paris in both his epic and his alleged burning of Rome, Nero confuses the categories of artist and perpetrator, creator and character, just as he and Orestes confuse those of actor and role.
Plato Theaetetus 182e1-2: The Meaning of μενειν
Authors: Boter Gerard
Published: December 2008

In Pl. Tht. 182c1-183b5 Socrates deals with the implications of the Heraclitean doctrine of flux for the thesis (attributed to Protagoras) that knowledge is perception. After having illustrated that, according to the flux theory, the perceived object is subject to constant change (182d1-5), he deals with perception itself (182e1-2): μενειν ποτε εν αυτω τω οραν η ακουειν. It is generally believed that this phrase means that sight, for instance, does not remain within the domain of sight, but changes into another kind of perception. Thus the words εν αυτω τω οραν η ακουειν are taken as an obligatory constituent belonging to μενειν; the whole phrase is supposed to mean, 'Shall we say that it ever stays in the condition of seeing or hearing?' (Sedley). This contribution shows why this interpretation is untenable. As an alternative, it is argued that μενειν is used absolutely as 'remain as one was'; the phrase εν αυτω τω οραν η ακουειν serves to indicate that a perception, while constantly changing, does remain within its own domain; that is, sight is never stable, but it does remain within the domain of sight. The whole sentence means, 'Does it ever remain the same within sight or hearing itself?'
“The Idumaeans” in Josephus' The Jewish War
Authors: Appelbaum Alan
Published: December 2008

“The Idumaeans” constitute a single, although collective, character in Josephus' The Jewish War. This article discusses whom Josephus meant by “the Idumaeans,” and considers whether, in his mind, they were, as others have suggested, “Jews” from Idumaea or a separate nation or ethnic group. It argues that the character “the Idumaeans” is not in fact a representative picture of Idumaeans of Josephus' time, but may be understood in terms of modern ethnic stereotyping, and that Josephus' stereotype of “the Idumaeans” as bloodthirsty hooligans is ultimately drawn from a continuous Idumaean military tradition. The article concludes by re-reading the War stripped of Josephus' ethnic prejudice against Idumaeans to learn more about the role of Idumaean fighting men in the first war against Rome.
Ritual Baths Adjacent to Tombs: An Analysis of the Archaeological Evidence in Light of the Halakhic Sources
Authors: Adler Yonatan
Published: December 2008

This study surveys the archaeological evidence of Jewish ritual baths (miqwa'ot) built adjacent to tombs, dating variously from the late Second Temple period through the 3rd-4th centuries C.E., and analyses this evidence in light of the halakhic sources. At first glance, this archaeological phenomenon would seem to stand at odds with normative halakhah, which mandates miqweh ablutions for corpse-impurity only at the end of a seven-day purification process. A careful reading of the scriptural and rabbinic sources, however, reveals that while a seven-day purification process is required for one who has contracted impurity directly from a corpse or a grave, impurity conveyed through an intermediary source (i.e. physical contact with one who has contracted direct corpse-impurity) may be purged through ablutions on the same day that the impurity was incurred. This study suggests that miqwa'ot adjacent to tombs were utilized at the conclusion of burial ceremonies by funeral participants who had contracted such “second-degree” impurity.
Will Satan Be Saved? Reconsidering Origen's Theory of Volition in Peri Archon
Authors: Holliday Lisa
Published: December 2008

Though the list of Origen's mistakes varies among authors, perhaps one of the most notorious accusations is that he proposed salvation for the devil, despite his protestations to the contrary. Though in PArch his discussion of Satan is secondary to his larger aims, Origen does provide evidence that validates his claim that the devil could not be saved, especially in his exploration of volition. By considering the devil within Origen's stance on volition and the nature of the soul, it is clear that while the devil technically retained the possibility of salvation, he did not wish to attain it, due to the degree to which he pursued his own desires.
Blistering of Moisture Saturated Graphite/Polyimide Composites Due to Rapid Heating
Authors: Czabaj Michael W. , Zehnder Alan T. , Chuang Kathy C.
Published: December 2008

Polyimide matrices extend the role of composite materials to applications in extreme temperature environments. However, composites can be susceptible to damage under extreme hygrothermal environments such as rapid heating of moisture saturated materials. Here, rapid is defined as reaching high temperature in less than the drying time at that temperature. A new method to predict initiation of steam-pressure induced damage for rapidly heated neat resin and graphite/polyimide composites is proposed. This method entails comparing the calculated, available steam pressure within the laminate to an experimentally determined critical pressure—temperature envelope. Through experiments performed in a thermal mechanical analyzer it is shown that the onset of steam-induced damage can be detected by measuring the expansion of moisture-saturated specimens subjected to a rapid temperature ramp. Optical microscopy of damaged samples shows that the process of initiation and evolution of damage in neat resin and laminates begins with void growth and coalescence in the polyimide resin matrix. Data from tests performed over a range of heating rates and initial moisture saturations are used to develop a critical pressure—temperature envelope. With this envelope we show the dependence of damage on initial moisture content and heating rate and propose an application of this envelope to failure prediction and design of laminated structures subjected to rapid heating.
Gramsci and the Labor-Managed Firm
Authors: Jossa Bruno
Published: December 2008

According to Antonio Gramsci, workers' councils were transitional institutions expected to carry on business in a market economy and thereby prepare the ground for the revolution. However, upon seizing power, workers were expected to establish a centrally planned system and, hence, to renounce autonomous firm management. Finding fault with this approach, the author upholds modern labor management theory, in which Vanek's LMF-type firms are looked upon as socialist firms operating in a market economy.
Tracking Online Workpiece Machining Procedure in a Mobile Collaborative Environment
Authors: Huibin Sun  , Pingyu Jiang
Published: December 2008

To increase the agility in manufacturing, we propose a method of tracking the online workpiece machining procedure in a mobile collaborative environment. Here, how to enable both machining quality tracking and machining information tracking are two key problems that need to be solved in this research. The first problem deals with information handling and visualizing technologies related to SPC-based quality controlling and error sourcing for big-batch production and Bayesian-forecasting-based dynamic quality controlling for small-batch production. The second problem depends on information searching and managing mechanisms for visualizing time, task, batch and equipment data synthetically based on several machining information engines. As a result, a ubiquitous machining tracking implementation is unified under the mobile collaborative infrastructure. Then users with different roles-playing are able not only to track the machining quality and progress, but also to cooperate with each other, despite of their geographical places where they stay and collaborative tools they are using. Finally, a running example is given to verify the feasibility of the proposed method.
Intracellular cotrafficking of factor VIII and von Willebrand factor type 2N variants to storage organelles
Authors: van den Biggelaar Maartje , Meijer Alexander B. , Voorberg Jan , Mertens Koen
Published: December 2008

Weibel-Palade bodies (WPBs) are the endothelial storage organelles that are formed upon von Willebrand factor (VWF) expression. Apart from VWF, WPBs contain a variety of hemostatic and inflammatory proteins. Some of these are thought to be targeted to WPBs by directly interacting with VWF in the secretory pathway. Previous studies have demonstrated that coexpression of factor VIII (FVIII) with VWF results in costorage of both proteins. However, whether cotrafficking is driven by intracellular FVIII-VWF assembly has remained unclear. We now have addressed this issue using recombinant VWF type 2N variants that are known to display reduced FVIII binding in the circulation. Binding studies using purified fluorescent FVIII and VWF type 2N variants revealed FVIII binding defects varying from moderate (Arg854Gln, Cys1060Arg) to severe (Arg763Gly, Thr791Met, Arg816Trp). Upon expression in HEK293 cells, all VWF variants induced formation of WPB-like organelles that were able to recruit P-selectin, as well as FVIII. WPBs containing FVIII did not display their typical elongated shape, suggesting that FVIII affects the organization of VWF tubules therein. The finding that VWF type 2N variants are still capable of cotargeting FVIII to storage granules implies that trafficking of WPB cargo proteins does not necessarily require high-affinity assembly with VWF.
Characterization of the ompL1 gene of pathogenic Leptospira species in China and cross-immunogenicity of the OmpL1 protein
Authors: Dong Haiyan , Hu Ye , Xue Feng , Sun Dexter , Ojcius David M , Mao Yafei , Yan Jie
Published: December 2008

Background

The usefulness of available vaccine and serological tests for leptospirosis is limited by the low cross-reactivity of antigens from numerous serovars of pathogenic Leptospira spp. Identification of genus-specific protein antigens (GP-Ag) of Leptospira would be important for development of universal vaccines and serodiagnostic methods. OmpL1, a transmembrane porin of pathogenic leptospires, was identified as a possible GP-Ag, but its sequence diversity and immune cross-reactivity among different serovars of pathogenic leptospires remains largely unknown.

Results

PCR analysis demonstrated that the ompL1 gene existed in all 15 official Chinese standard strains as well as 163 clinical strains of pathogenic leptospires isolated in China. In the standard strains, the ompL1 gene could be divided into three groups (ompL1/1, ompL1/2 and ompL1/3) according to their sequence identities. Immune electron microscopy demonstrated that all products of the different gene types of ompL1 are located on the surface of leptospires. The microscopic agglutination test revealed extensive yet distinct cross-immunoagglutination among the antisera against recombinant OmpL1 (rOmpL1) and leptospiral strains belonging to different ompL1 gene types. These cross-immunoreactions were further verified by ELISAs using the OmpL1 proteins as the coated antigens in serum samples from 385 leptospirosis patients. All the antisera against rOmpL1 proteins could inhibit L. interrogans strain Lai from adhering to J774A.1 cells. Furthermore, immunization of guinea pigs with each of the rOmpL1 proteins could cause cross-immunoprotection against lethal challenge with leptospires from different ompL1 gene types.

Conclusion

Three types of the ompL1 gene are present in pathogenic leptospires in China. OmpL1 is an immunoprotective GP-Ag which should be considered in the design of new universal vaccines and serodiagnostic methods against leptospirosis.
Response of the cytoplasmic and membrane proteome of Corynebacterium glutamicum ATCC 13032 to pH changes
Authors: Barriuso-Iglesias Mónica , Schluesener Daniela , Barreiro Carlos , Poetsch Ansgar , Martín Juan F
Published: December 2008

Background

C. glutamicum has traditionally been grown in neutral-pH media for amino acid production, but in a previous article we reported that this microorganism is a moderate alkaliphile since it grows optimally at pH 7.0–9.0, as shown in fermentor studies under tightly controlled pH conditions. We determined the best pH values to study differential expression of several genes after acidic or basic pH conditions (pH 6.0 for acidic expression and pH 9.0 for alkaline expression). Thus, it was interesting to perform a detailed analysis of the pH-adaptation response of the proteome of C. glutamicum ATCC 13032 to clarify the circuits involved in stress responses in this bacterium. In this paper we used the above indicated pH conditions, based on transcriptional studies, to confirm that pH adaptation results in significant changes in cytoplasmatic and membrane proteins.

Results

The cytoplasmatic and membrane proteome of Corynebacterium glutamicum ATCC 13032 at different pH conditions (6.0, 7.0 and 9.0) was analyzed by classical 2D-electrophoresis, and by anion exchange chromatography followed by SDS-PAGE (AIEC/SDS-PAGE). A few cytoplasmatic proteins showed differential expression at the three pH values with the classical 2D-technique including a hypothetical protein cg2797, L-2.3-butanediol dehydrogenase (ButA), and catalase (KatA). The AIEC/SDS-PAGE technique revealed several membrane proteins that respond to pH changes, including the succinate dehydrogenase complex (SdhABCD), F0F1-ATP synthase complex subunits b, α and δ (AtpF, AtpH and AtpA), the nitrate reductase II α subunit (NarG), and a hypothetical secreted/membrane protein cg0752. Induction of the F0F1-ATP synthase complex β subunit (AtpD) at pH 9.0 was evidenced by Western analysis. By contrast, L-2.3-butanediol dehydrogenase (ButA), an ATPase with chaperone activity, the ATP-binding subunit (ClpC) of an ATP-dependent protease complex, a 7 TMHs hypothetical protein cg0896, a conserved hypothetical protein cg1556, and the dihydrolipoamide acyltransferase SucB, were clearly up-regulated at pH 6.0.

Conclusion

The observed protein changes explain the effect of the extracellular pH on the growth and physiology of C. glutamicum. Some of the proteins up-regulated at alkaline pH respond also to other stress factors suggesting that they serve to integrate the cell response to different stressing conditions.
Genomic analysis of bacteriophage ε34 of Salmonella entericaserovar Anatum (15+)
Authors: Villafane Robert , Zayas Milka , Gilcrease Eddie B , Kropinski Andrew M , Casjens Sherwood R
Published: December 2008

Background

The presence of prophages has been an important variable in genetic exchange and divergence in most bacteria. This study reports the determination of the genomic sequence of Salmonella phage ε34, a temperate bacteriophage that was important in the early study of prophages that modify their hosts' cell surface and is of a type (P22-like) that is common in Salmonella genomes.

Results

The sequence shows that ε34 is a mosaically related member of the P22 branch of the lambdoid phages. Its sequence is compared with the known P22-like phages and several related but previously unanalyzed prophage sequences in reported bacterial genome sequences.

Conclusion

These comparisons indicate that there has been little if any genetic exchange within the procapsid assembly gene cluster with P22-like E. coli/Shigella phages that are have orthologous but divergent genes in this region. Presumably this observation reflects the fact that virion assembly proteins interact intimately and divergent proteins can no longer interact. On the other hand, non-assembly genes in the "ant moron" appear to be in a state of rapid flux, and regulatory genes outside the assembly gene cluster have clearly enjoyed numerous and recent horizontal exchanges with phages outside the P22-like group. The present analysis also shows that ε34 harbors a gtrABC gene cluster which should encode the enzymatic machinery to chemically modify the host O antigen polysaccharide, thus explaining its ability to alter its host's serotype. A comprehensive comparative analysis of the known phage gtrABC gene clusters shows that they are highly mobile, having been exchanged even between phage types, and that most "bacterial" gtrABC genes lie in prophages that vary from being largely intact to highly degraded. Clearly, temperate phages are very major contributors to the O-antigen serotype of their Salmonella hosts.
Role of MAPT mutations and haplotype in frontotemporal lobar degeneration in Northern Finland
Authors: Kaivorinne Anna-Lotta , Krüger Johanna , Kuivaniemi Katja , Tuominen Hannu , Moilanen Virpi , Majamaa Kari , Remes Anne M
Published: December 2008

Background

Frontotemporal lobar degeneration (FTLD) consists of a clinically and neuropathologically heterogeneous group of syndromes affecting the frontal and temporal lobes of the brain. Mutations in microtubule-associated protein tau (MAPT), progranulin (PGRN) and charged multi-vesicular body protein 2B (CHMP2B) are associated with familial forms of the disease. The prevalence of these mutations varies between populations. The H1 haplotype of MAPT has been found to be closely associated with tauopathies and with sporadic FTLD. Our aim was to investigate MAPT mutations and haplotype frequencies in a clinical series of patients with FTLD in Northern Finland.

Methods

MAPT exons 1, 2 and 9–13 were sequenced in 59 patients with FTLD, and MAPT haplotypes were analysed in these patients, 122 patients with early onset Alzheimer's disease (eoAD) and 198 healthy controls.

Results

No pathogenic mutations were found. The H2 allele frequency was 11.0% (P = 0.028) in the FTLD patients, 9.8% (P = 0.029) in the eoAD patients and 5.3% in the controls. The H2 allele was especially clustered in patients with a positive family history (P = 0.011) but did not lower the age at onset of the disease. The ApoE4 allele frequency was significantly increased in the patients with eoAD and in those with FTLD.

Conclusion

We conclude that although pathogenic MAPT mutations are rare in Northern Finland, the MAPT H2 allele may be associated with increased risks of FTLD and eoAD in the Finnish population.
Anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating factor: a case report
Authors: Nakajima Atsushi , Takahashi Hirokazu , Inamori Masahiko , Abe Yasunobu , Kobayashi Noritoshi , Kubota Kensuke , Yamanaka Shoji
Published: December 2008

Introduction

The granulocyte-colony stimulating factor-producing tumor was first reported in 1977, however, anaplastic pleomorphic type carcinoma of the pancreas producing granulocyte-colony stimulating factor is still rare.

Case presentation

A 63-year-old man was admitted to our hospital with body weight loss (-10 kg during months) and upper abdominal pain from 3 weeks. Abdominal computed tomography demonstrated a pancreatic tumor 10 cm in size and multiple low-density areas in the liver. On admission, the peripheral leukocyte count was elevated to 91,500/mm3 and the serum concentration of granulocyte-colony stimulating factor was 134 pg/mL (normal, < 18.1 pg/mL). Based on liver biopsy findings, the tumor was classified as an anaplastic pleomorphic-type carcinoma. Immunohistochemical staining showed that pancreatic carcinoma cells were positive for granulocyte-colony stimulating factor. The patient developed interstitial pneumonia, probably caused by granulocyte-colony stimulating factor, and died 11 days after admission.

Conclusion

This is a rare case report of anaplastic pleomorphic-type carcinoma of the pancreas producing granulocyte-colony stimulating factor and confirmed by immunohistochemistry.
Quantitative protein expression profiling reveals extensive post-transcriptional regulation and post-translational modifications in schizont-stage malaria parasites
Authors: Foth Bernardo J , Zhang Neng , Mok Sachel , Preiser Peter R , Bozdech Zbynek
Published: December 2008

Background

Malaria is a one of the most important infectious diseases and is caused by parasitic protozoa of the genus Plasmodium. Previously, quantitative characterization of the P. falciparum transcriptome demonstrated that the strictly controlled progression of these parasites through their intra-erythrocytic developmental cycle is accompanied by a continuous cascade of gene expression. Although such analyses have proven immensely useful, the correlations between abundance of transcripts and their cognate proteins remain poorly characterized.

Results

Here, we present a quantitative time-course analysis of relative protein abundance for schizont-stage parasites (34 to 46 hours after invasion) based on two-dimensional differential gel electrophoresis of protein samples labeled with fluorescent dyes. For this purpose we analyzed parasite samples taken at 4-hour intervals from a tightly synchronized culture and established more than 500 individual protein abundance profiles with high temporal resolution and quantitative reproducibility. Approximately half of all profiles exhibit a significant change in abundance and 12% display an expression peak during the observed 12-hour time interval. Intriguingly, identification of 54 protein spots by mass spectrometry revealed that 58% of the corresponding proteins - including actin-I, enolase, eukaryotic initiation factor (eIF)4A, eIF5A, and several heat shock proteins - are represented by more than one isoform, presumably caused by post-translational modifications, with the various isoforms of a given protein frequently showing different expression patterns. Furthermore, comparisons with transcriptome data generated from the same parasite samples reveal evidence of significant post-transcriptional gene expression regulation.

Conclusions

Together, our data indicate that both post-transcriptional and post-translational events are widespread and of presumably great biological significance during the intra-erythrocytic development of P. falciparum.
Differential lymphopenia-induced homeostatic proliferation for CD4+ and CD8+ T cells following septic injury
Authors: Unsinger Jacqueline , Kazama Hirotaka , McDonough Jacquelyn S , Hotchkiss Richard S , Ferguson Thomas A
Published: December 2008

Sepsis is a severe, life-threatening infection and a leading cause of death in hospitals. A hallmark of sepsis is the profound apoptosis-induced depletion of lymphocytes generating a lymphopenic environment. As lymphopenia can induce nonantigen-driven homeostatic proliferation (HP), we examined this process during sepsis. CD4+ and CD8+ T cells, which were depleted within 24 h of sepsis induction, remained at significantly reduced levels until Day 21 when normal numbers were detected. When HP was examined, naïve CD8+ T cells proliferated between Day 7 and Day 21 post-cecal ligation and puncture, developing into memory cells with relatively few cells expressing an activation phenotype. Conversely, naïve CD4+ T cells did not undergo HP, but proportionally higher numbers expressed activation markers. Adoptive transfer studies revealed that T cells from mice that had recovered from sepsis were not protective when transferred to naïve mice undergoing sepsis. In addition, the TCR repertoire was not skewed toward any specific Vβ type but resembled the repertoire found in normal mice, suggesting that T cells were not primed to antigens resulting from the infection. Interestingly, depletion of endogenous CD8+ but not CD4+ T cells restored the ability of naive CD4+ T cells to undergo HP, increasing the number of CD4+ T cells with memory but not activation markers. We conclude that homeostatic control in the postseptic environment permits recovery of the T cell repertoire to normal levels without generating antigen-specific memory or aberrant T cell specificities. Restoration of homeostatic control mechanisms might be a rational therapy for this disorder.
Age-related enlargement of lymphoid tissue and altered leukocyte composition in serglycin-deficient mice
Authors: Wernersson Sara , Braga Tiago , Sawesi Osama , Waern Ida , Nilsson Kajsa E , Pejler Gunnar , Åbrink Magnus
Published: December 2008

Serglycin (SG) is a proteoglycan that is located predominantly in the secretory granules of hematopoietic cells. Previous studies have established a crucial role for SG in promoting the storage of various secretory granule compounds that are of importance in the immune defense system. Here, we show that mice lacking SG spontaneously develop enlargement of multiple lymphoid organs, including the spleen, Peyer’s patches (PP), and bronchus-associated lymphoid tissue. In the spleen, the lack of SG resulted in a significant decrease in the proportion of CD4+ cells as well as an increase of the CD45RC+ leukocyte population, indicating an expansion of naïve lymphocytes. In the PP, the lack of SG resulted in a general increase in cellularity, without significant alterations in the proportion of individual leukocyte populations. The enlargement of lymphoid tissues was not accompanied by increased serum levels of inflammatory cytokines. The number of mast cells in the peritoneum was not affected by the lack of SG, as judged by surface staining for CD117 (c-kit). However, the intensity of c-kit staining was reduced significantly in SG null animals. Moreover, the number of peritoneal macrophages, defined by morphological criteria and by CD11b staining, was decreased markedly in older, SG-deficient animals. Finally, experiments in which airway inflammation was induced by bacterial LPS revealed a more pronounced inflammatory response in old, SG-deficient as compared with wild-type mice. Taken together, our data show that SG deficiency causes multiple, age-related effects on the lymphoid system.
3D seismic volume visualization and interpretation: An integrated workflow with case studies
Authors: Gao Dengliang
Published: December 2008

One of the major problems in subsurface seismic exploration is the uncertainty (nonuniqueness) in geologic interpretation because of the complexity of subsurface geology and the limited dimension of the data available. Case studies from worldwide exploration projects indicate that an integrated, three-dimensional (3D) seismic volume visualization and interpretation workflow contributes to resolving the problem by mining and exposing critical geologic information from within seismic data volumes. Following 3D seismic data acquisition and processing, the interpretation workflow consists of four integrated phases from data selection and conditioning, to structure and facies characterization, to prospect evaluation and generation, to well-bore planning. In the data selection and conditioning phase, the most favored and frequently used data are the full-angle, limited-angle, and limited-azimuth stack amplitude with significant structure and facies enhancements. Signal-to-noise ratio, color scheme, dynamic range, bit resolution, and visual contrast all affect thevisibility of features of interest. In the structure and facies characterization phase, vertical slicing along arbitrary traverses demonstrates structure styles, stratigraphic architecture, and reservoir geometry in the cross-sectional view. Time/depth slicing defines lateral and vertical variability in the structural trend and areal extent in the map view. Stratal slicing and fault slicing map chronostratigraphic seismic facies and cross-stratal, along-fault seismic signature. Volume flattening and structure restoration aid in unraveling paleostructural framework and stratigraphic architecture and their growth histories. In the prospect evaluation and generation phase, a combination of volume trimming, co-rendering, transparency, attribute analysis, and attribute-body detection is instrumental in delineating volumetric extent and evaluating spatial connectivity of critical seismic features. Finally, in the well-bore planning phase, informed decision-making relies on the integration of all the information and knowledge interrogated from 3D seismic data. Most importantly, interpreters’ geologic insight and play concept are crucial to optimal well-bore planning with high geologic potential and low economic risk.
The Bax/Bak ortholog inDrosophila, Debcl, exerts limited control over programmed cell death
Authors: Galindo Kathleen A. , Lu Wan-Jin , Park Jae H. , Abrams John M.
Published: December 2008

Bcl-2 family members are pivotal regulators of programmed cell death (PCD). In mammals, pro-apoptotic Bcl-2 family members initiate early apoptotic signals by causing the release of cytochrome c from the mitochondria, a step necessary for the initiation of the caspase cascade. Worms and flies do not show a requirement for cytochrome c during apoptosis, but both model systems express pro- and anti-apoptotic Bcl-2 family members. Drosophilaencodes two Bcl-2 family members, Debcl (pro-apoptotic) and Buffy(anti-apoptotic). To understand the role of Debcl in Drosophilaapoptosis, we produced authentic null alleles at this locus. Although gross development and lifespans were unaffected, we found that Debcl was required for pruning cells in the developing central nervous system. debclgenetically interacted with the ced-4/Apaf1 counterpart dark, but was not required for killing by RHG (Reaper, Hid, Grim)proteins. We found that debclKO mutants were unaffected for mitochondrial density or volume but, surprisingly, in a model of caspase-independent cell death, heterologous killing by murine Bax required debcl to exert its pro-apoptotic activity. Therefore, although debcl functions as a limited effector of PCD during normal Drosophila development, it can be effectively recruited for killing by mammalian members of the Bcl-2 gene family.
The bHLH transcription factor Olig3 marks the dorsal neuroepithelium of the hindbrain and is essential for the development of brainstem nuclei
Authors: Storm Robert , Cholewa-Waclaw Justyna , Reuter Katja , Bröhl Dominique , Sieber Martin , Treier Mathias , Müller Thomas , Birchmeier Carmen
Published: December 2008

The Olig3 gene encodes a bHLH factor that is expressed in the ventricular zone of the dorsal alar plate of the hindbrain. We found that the Olig3+ progenitor domain encompassed subdomains that co-expressed Math1, Ngn1, Mash1 and Ptf1a. Olig3+ cells give rise to neuronal types in the dorsal alar plate that we denote as class A neurons. We used genetic lineage tracing to demonstrate that class A neurons contribute to the nucleus of the solitary tract and to precerebellar nuclei. The fate of class A neurons was not correctly determined in Olig3 mutant mice. As a consequence, the nucleus of the solitary tract did not form, and precerebellar nuclei, such as the inferior olivary nucleus, were absent or small. At the expense of class A neurons, ectopic Lbx1+ neurons appeared in the alar plate in Olig3 mutant mice. By contrast, electroporation of an Olig3 expression vector in the chick hindbrain suppressed the emergence of Lbx1+ neurons. Climbing fiber neurons of the inferior olivary nucleus express Foxd3 and require Olig3 as well as Ptf1a for the determination of their fate. We observed that electroporation of Olig3 and Ptf1a expression vectors, but not either alone, induced Foxd3. We therefore propose that Olig3 can cooperate with Ptf1a to determine the fate of climbing fiber neurons of the inferior olivary nucleus.
Ancestry-independent fate specification and plasticity in the developmental timing of a typicalDrosophilaneuronal lineage
Authors: Gaziova Ivana , Bhat Krishna Moorthi
Published: December 2008

In the Drosophila CNS, combinatorial, interdependent, sequential genetic programs in neuroectodermal (NE) cells, prior to the formation of neuroblasts (NBs), determine the initial identity of NBs. Temporal factors are then sequentially expressed to change the temporal identity. It is unclear at what levels this positional and temporal information integrates to determine progeny cell identity. One idea is that this is a top-down linear process: the identity of a NB determines the identity of its daughter, the ganglion mother cell (GMC), the asymmetric division of the GMC and the fate specification of daughter cells of the GMC. Our results with midline (mid),which encodes a T-box protein, in a typical lineage,NB4-2→GMC-1→RP2/sib, suggest that at least part of the process operates in GMCs. That is, a GMC or a neuronal identity need not be determined at the NB or NE level. This is demonstrated by showing that Mid is expressed in a row 5 GMC (M-GMC), but not in its parent NB or NE cell. In midmutants, M-GMC changes into GMC-1 and generates an RP2 and a sib without affecting the expression of key genes at the NE/NB levels. Expression of Mid in the M-GMC in mid mutants rescues the fate change, indicating that Mid specifies neurons at the GMC level. Moreover, we found a significant plasticity in the temporal window in which a neuronal lineage can develop. Although the extra GMC-1 in mid mutants is born ∼2 hours later than the bona fide GMC-1, it follows the same developmental pattern as the bona fide GMC-1. Thus, a GMC identity can be independent of parental identity and GMC formation and elaboration need not be strictly time-bound.
microRNAs and muscle disorders
Authors: Chen Jian-Fu , Callis Thomas E. , Wang Da-Zhi
Published: December 2008

MicroRNAs (miRNAs) are a class of non-coding regulatory RNAs of ∼22 nucleotides in length. miRNAs are highly conserved across a number of species, including plants, worms and humans. miRNAs regulate gene expression post-transcriptionally, primarily by associating with the 3′ untranslated region (UTR) of their regulatory target mRNAs. Recent work has begun to reveal roles for miRNAs in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. miRNAs are expressed in cardiac and skeletal muscle, and dysregulated miRNA expression has been correlated with muscle-related disorders. Genetic studies have identified distinct roles for specific miRNAs during cardiogenesis, cardiac hypertrophy and electrical conduction. Furthermore, conditionally inhibiting the maturation of miRNAs in mouse cardiac and skeletal muscles has revealed that miRNAs are essential for the development and function of those muscles. These previously unrecognized regulators shed new light on the molecular mechanisms that underlie muscle development and pathology, and suggest the potential importance of miRNAs as diagnostic markers and therapeutic targets for muscle-related disease.
Residual stress measurement by deep hole drilling and trepanning – analysis with distributed dislocations
Authors: Paynter R , Mahmoudi A H , Pavier M J , Hills D A , Nowell D , Truman C E , Smith D J
Published: December 2008

It is shown that the conventional ‘sheet by sheet’ analysis of residual stress measurement by the deep hole drilling method is inaccurate when in-plane stress gradients exist. The influence of the interfacial tractions is analysed by the distributed dislocation technique. Finite element modelling is used to provide data for an example residual stress field with radial variation.
Eigenstrain-based model for prediction of laser peening residual stresses in arbitrary three-dimensional bodies Part 1: Model description
Authors: DeWald A T , Hill M R
Published: December 2008

This paper presents a methodology for predicting the residual stress within three-dimensional parts caused by laser peening treatment. The inputs to the model are the elastic material properties and shape of the part as well as an eigenstrain (also called ‘initial strain’ or ‘stress-free strain’) field specific to the material and parameters of laser peening treatment. The eigenstrain field is known from a library of fields developed prior to the residual stress prediction, either from detailed physical process modelling or from residual stress measurements of simple coupons of the parent material subject to the same laser peening treatment. The eigenstrain is assumed insensitive to part geometry, depending only on the part material and the laser peening treatment parameters. Given the eigenstrain field, residual stress is predicted by an elastic finite element analysis of the part that includes its detailed geometry and material composition. The eigenstrain is input into the finite element model in stated treatment areas where laser peening is applied. Solving for stress equilibrium provides an estimate of the residual stress field at all points within the treated part. The proposed modelling procedure is verified through a test on flat-plate geometry, where measured residual stress compares favourably with model predictions. In addition, the model is used to predict the residual stress produced by laser peening of a specimen containing a corner fillet. A companion paper (Part 2) presents detailed experimental verification of the model over a range of common part geometry.
From the Editor
Authors: Bitran Gabriel R.
Published: December 2008

Editorial about the redesign of Management Science, in effect from the first issue of 1993.
Judith E. Larrivee 1947–1993
Authors: Morrison Donald G.
Published: December 2008

In memoriam for Judith Larrivee (1947–1993), Technical Editor of Management Science.
Is Management Science International: In Search of Universal Rules
Authors: Aharoni Yair , Burton Richard M.
Published: December 2008

In management science, as in all of science, a fundamental issue is the generalizability of what we know. It is a never-ending quest to discover and create knowledge and rules which are universal. Yet, frequently what we hold to be universal is quite specific when examined with scientific scrutiny. In this special issue of Management Science we want to develop more precisely the dimension and the extent to which what we know in management science is generalizable, e.g., is our knowledge about managing universal or specific? Is our knowledge limited to a particular firm, an industry, a given country, or a culture? The universality/specificity issue remains a dilemma. The theme of this special issue is the generalizability of management science. Management Science publishes research on theory, methodology and empirical results.
Outcome, following significant delays in initial surgery, of ballistic femoral fractures managed without internal or external fixation
Authors: Clasper J. C. , Rowley D. I.
Published: December 2008

We reviewed the clinical details and radiographs of 52 patients with ballistic fractures of the femur admitted to the International Committee of the Red Cross Hospital in Kenya (Lopiding), who had sustained injuries in neighbouring Sudan. In all cases there had been a significant delay in the initial surgery (> 24 hours), and all patients were managed without stabilisation of the fracture by internal or external fixation.

Of the 52 patients, three required an amputation for persisting infection of the fracture site despite multiple debridements. A further patient was treated by an excision arthroplasty of the hip, but this was carried out at the initial operation as a part of the required debridement.

All of the remaining 48 fractures healed. Four patients needed permanent shoe adaptation because of limb shortening of functional significance.

Although we do not advocate delaying treatment or using traction instead of internal or external fixation, we have demonstrated that open femoral fractures can heal despite limited resources.