bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal role of the angular gyrus in insight-driven memory reconfiguration
Authors: Grob Anna-Maria , Heinbockel Hendrik , Milivojevic Branka , Doeller Christian F. , Schwabe Lars
Published: February 2024

Maintaining an accurate model of the world relies on our ability to update memory representations in light of new information. Previous research on the integration of new information into memory mainly focused on the hippocampus. Here, we hypothesized that the angular gyrus, known to be involved in episodic memory and imagination, plays a pivotal role in the insight-driven reconfiguration of memory representations. To test this hypothesis, participants received continuous theta burst stimulation (cTBS) over the left angular gyrus or sham stimulation before gaining insight into the relationship between previously separate life-like animated events in a narrative-insight task. During this task, participants also underwent EEG recording and their memory for linked and non-linked events was assessed shortly thereafter. Our results show that cTBS to the angular gyrus decreased memory for the linking events and reduced the memory advantage for linked relative to non-linked events. At the neural level, cTBS targeting the angular gyrus reduced centro-temporal coupling with frontal regions and abolished insight-induced neural representational changes for events linked via imagination, indicating impaired memory reconfiguration. Further, the cTBS group showed representational changes for non-linked events that resembled the patterns observed in the sham group for the linked events, suggesting failed pruning of the narrative in memory. Together, our findings demonstrate a causal role of the left angular gyrus in insight-related memory reconfigurations.
Affinity-tagged SMAD1 and SMAD5 mouse lines reveal transcriptional reprogramming mechanisms during early pregnancy
Authors: Liao Zian , Tang Suni , Nozawa Kaori , Shimada Keisuke , Ikawa Masahito , Monsivais Diana , Matzuk Martin M.
Published: February 2024

Endometrial decidualization, a prerequisite for successful pregnancies, relies on transcriptional reprogramming driven by progesterone receptor (PR) and bone morphogenetic protein (BMP)-SMAD1/SMAD5 signaling pathways. Despite their critical roles in early pregnancy, how these pathways intersect in reprogramming the endometrium into a receptive state remains unclear. To define how SMAD1 and/or SMAD5 integrate BMP signaling in the uterus during early pregnancy, we generated two novel transgenic mouse lines with affinity tags inserted into the endogenous SMAD1 and SMAD5 loci (

Smad1
HA/HA

and

Smad5
PA/PA
)

. By profiling the genome-wide distribution of SMAD1, SMAD5, and PR in the mouse uterus, we demonstrated the unique and shared roles of SMAD1 and SMAD5 during the window of implantation. We also showed the presence of a conserved SMAD1, SMAD5, and PR genomic binding signature in the uterus during early pregnancy. To functionally characterize the translational aspects of our findings, we demonstrated that SMAD1/5 knockdown in human endometrial stromal cells suppressed expressions of canonical decidual markers (
IGFBP1, PRL, FOXO1)
and PR-responsive genes (
RORB
,
KLF15)
. Here, our studies provide novel tools to study BMP signaling pathways and highlight the fundamental roles of SMAD1/5 in mediating both BMP signaling pathways and the transcriptional response to progesterone (P4) during early pregnancy.
Polysaccharide breakdown products drive degradation-dispersal cycles of foraging bacteria through changes in metabolism and motility
Authors: Stubbusch Astrid Katharina Maria , Keegstra Johannes M , Schwartzman Julia , Pontrelli Sammy , Clerc Estelle E , Charlton Samuel , Stocker Roman , Magnabosco Cara , Schubert Olga T , Ackermann Martin , D'Souza Glen G
Published: February 2024

Most of Earth’s biomass is composed of polysaccharides. During biomass decomposition, polysaccharides are degraded by heterotrophic bacteria as a nutrient and energy source and are thereby partly remineralized into CO2. As polysaccharides are heterogeneously distributed in nature, following the colonization and degradation of a polysaccharide hotspot the cells need to reach new polysaccharide hotspots. Even though many studies indicate that these degradation-dispersal cycles contribute to the carbon flow in marine systems, we know little about how cells alternate between polysaccharide degradation and motility, and which environmental factors trigger this behavioral switch. Here, we studied the growth of the marine bacterium Vibrio cyclitrophicus ZF270 on the abundant marine polysaccharide alginate, both in its soluble polymeric form as well as on its breakdown products. We used microfluidics coupled to time-lapse microscopy to analyze motility and growth of individual cells, and RNA sequencing to study associated changes in gene expression. We found that single cells grow at reduced rate on alginate until they form large groups that cooperatively break down the polymer. Exposing cell groups to digested alginate accelerates cell growth and changes the expression of genes involved in alginate degradation and catabolism, central metabolism, ribosomal biosynthesis, and transport. However, exposure to digested alginate also triggers cells to become motile and disperse from cell groups, proportionally increasing with the group size before the nutrient switch, and this is accompanied by high expression of genes involved in flagellar assembly, chemotaxis, and quorum sensing. The motile cells chemotax toward polymeric but not digested alginate, likely enabling them to find new polysaccharide hotspots. Overall, our findings reveal cellular mechanisms that might also underlie bacterial degradation-dispersal cycles, which influence the remineralization of biomass in marine environments.
Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain
Authors: García-Cuesta Eva M. , Martínez Pablo , Selvaraju Karthik , Gómez Pozo Adrián Miguel , D’Agostino Gianluca , Gardeta Sofía , Quijada-Freire Adriana , Blanco Gabella Patricia , Roca Carlos , Jiménez-Saiz Rodrigo , García-Rubia Alfonso , Soler-Palacios Blanca , Lucas Pilar , Ayala-Bueno Rosa , Santander Acerete Noelia , Carrasco Yolanda R. , Martínez Ana , Campillo Nuria E , Jenssen Lasse , Rodríguez-Frade José Miguel , Santiago César , Mellado Mario
Published: February 2024

CXCR4 is a ubiquitously expressed chemokine receptor that regulates leukocyte trafficking and arrest in homeostatic and pathological states, and also participates in organogenesis, HIV-1 infection and tumor development. Despite the potential therapeutic benefit of CXCR4 antagonists, so far only one, plerixafor (AMD3100), which blocks the ligand-binding site, has reached the clinic. Recent advances in imaging and biophysical techniques have provided a richer understanding of the membrane organization and dynamics of this receptor. CXCL12 activation of CXCR4 reduces the number of CXCR4 monomers/dimers at the cell membrane and increases the formation of large nanoclusters, which are largely immobile and are required for correct cell orientation towards chemoattractant gradients. Mechanistically, CXCR4 activation involves a structural motif defined by residues on TMV and TMVI of CXCR4. Using this structural motif as a template, we performed
in silico
molecular modeling followed by
in vitro
screening of a small compound library to search for allosteric antagonists of CXCR4 that do not affect CXCL12 binding. We identified AGR1.137, a small compound that abolishes CXCL12-mediated receptor nanoclustering and dynamics and blocks the ability of cells to sense CXCL12 gradients both
in vitro
and
in vivo
without altering ligand binding or receptor internalization.CXCR4 is a ubiquitous chemokine receptor that regulates leukocyte trafficking and arrest in homeostatic and pathological states. Yet, the only commercial CXCR4 antagonist approved for clinical use is plerixafor (AMD3100), a small compound that blocks the ligand-binding site. Unfortunately, its clinical application is limited by poor pharmacokinetics and adverse effects associated with long-term administration. Here, we performed
in silico
analyses of a small aromatic compound library followed by
in vitro
screening to identify allosteric CXCR4 antagonists that abrogate the ability of cells to sense chemoattractant gradients without altering other ligand-mediated functions such as blockade of cAMP production or receptor internalization. The selected compounds also acted
in vivo,
as demonstrated by reduced tumorigenesis and metastasis in a zebrafish tumor model. Our study describes a new approach to selectively alter some GPCR functions without the need for abolishing all receptor functionality.
A Myelin Map of Trunk Folds in the Elephant Trigeminal Nucleus
Authors: Reveyaz Noémie , Schneeweiß Undine , Heise Olivia , Gerhardt Ben , Gui Andreea M. , Kaufmann Lena V. , Alfken Jette , Reichmann Jakob , Salditt Tim , Hildebrandt Thomas , Brecht Michael
Published: February 2024

Elephants have elaborate trunk skills and large, but poorly understood brains. Here we study trunk representations in elephant trigeminal nuclei, which form large protrusions on the ventral brainstem. Dense vascularization and intense cytochrome-oxidase reactivity distinguish several elongated putative trunk modules, which repeat in the anterior-posterior direction; our analysis focuses on the most anterior and largest of the units, the putative nucleus principalis trunk module. Module neuron density is low and glia outnumbers neurons by ∼108:1. Dendritic trees are elongated along the axis of axon bundles (myelin stripes) transversing the trunk module. Furthermore, synchrotron X-ray phase contrast tomography suggests myelin-stripe-axons transverse the trunk module. We show a remarkable correspondence of trunk module myelin stripes and trunk folds. Myelin stripes show little relation to trigeminal neurons and stripe-axons appear to often go nowhere; these observations suggest to the possibility that myelin-stripes might serve to separate trunk-fold domains rather than to connect neurons. The myelin-stripes-to-folds mapping allowed to determine neural magnification factors, which changed from 1000:1 proximally to 5:1 in the trunk finger. Asian elephants have fewer (∼640,000) trunk-module neurons than Africans (∼740,000) and show enlarged representations of trunk parts involved in object wrapping. We conclude the elephant trigeminal trunk module is exquisitely organized into trunk-fold-related units.
Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance
Authors: Shiraliyev Rauf , Orman Mehmet A.
Published: February 2024

Aminoglycosides, a class of antibiotics, have been in use for decades, displaying broad-spectrum activity against Gram-negative and Gram-positive bacteria. They target ribosomes and disrupt protein synthesis. Although their use declined due to newer antibiotics with lower toxicity, increasing drug resistance has renewed interest in aminoglycosides. Herein, we have demonstrated that energy metabolism plays a crucial role in aminoglycoside tolerance, as knockout strains with deleted genes associated with the tricarboxylic acid cycle (TCA) and the electron transport chain (ETC) exhibited increased tolerance to aminoglycosides in the mid-exponential growth phase of
Escherichia coli
cells. Our initial hypothesis posited that genetic perturbations would lead to a reduction in the proton motive force, subsequently affecting the uptake of aminoglycosides. This hypothesis is based on the prevailing notion that aminoglycoside uptake is dependent on the distinctive and energy-driven electrochemical potential across the cytoplasmic membrane. However, our results did not support this hypothesis. Despite genetic perturbations in mutant strains, we found no consistent metabolic changes, ATP levels, cytoplasmic pH variations, or membrane potential differences compared to wild-type strains. Additionally, intracellular concentrations of fluorophore-labeled gentamicin remained similar across all strains. To uncover the mechanism responsible for the observed tolerance in mutant strains, we employed untargeted mass spectrometry to quantify the proteins within these mutants and subsequently compared them to their wild-type counterparts. Our comprehensive analysis, which encompassed protein-protein association networks and functional enrichment, unveiled a noteworthy upregulation of proteins linked to the TCA cycle in the mutant strains, suggesting that these strains compensate for the perturbation in their energy metabolism by increasing TCA cycle activity to maintain their membrane potential and ATP levels. Furthermore, our pathway enrichment analysis shed light on local network clusters displaying downregulation across all mutant strains, which were associated with both large and small ribosomal binding proteins, ribosome biogenesis, translation factor activity, and the biosynthesis of ribonucleoside monophosphates. These findings offer a plausible explanation for the observed tolerance of aminoglycosides in the mutant strains. Altogether, this research has the potential to uncover mechanisms behind aminoglycoside tolerance, paving the way for novel strategies to combat such cells.
Fast Evolution of SOS-Independent Multi-Drug Resistance in Bacteria
Authors: Zhang Le , Guan Yunpeng , Cheng Yuen Yee , Cokcetin Nural N , Bottomley Amy L , Robinson Andrew , Harry Elizabeth J , van Oijen Antoine , Su Qian Peter , Jin Dayong
Published: February 2024

The killing mechanism of many antibiotics involves the induction of DNA damage, either directly or indirectly, which triggers the SOS response. RecA, the master regulator of the SOS response, plays a crucial role in driving the evolution of resistance to fluoroquinolone antibiotics treated with a single dose of ciprofloxacin. However, the precise roles of RecA and SOS responses in the development of resistance under short-term β-lactam exposure remain unclear. In the present study, we observed a fast evolution of β-lactam resistance (20-fold increase in MIC in 8 hours) in
E. coli
after deleting RecA and exposing the bacteria to a single dose of ampicillin. Notably, once this type of resistance is established, it remains stable and can be passed on to subsequent generations. Unlike earlier studies, we found that the rapid development of resistance relies on the hindrance of DNA repair, a mechanism that operates independently of the SOS response. Additionally, we identified the rapid emergence of drug resistance associated mutations in the resistant bacterial genome, indicating the impairment of DNA repair. Through comprehensive transcriptome sequencing, we discovered that the expression of numerous antioxidative response genes is repressed in
recA
mutant resistant isolates, resulting in an excessive accumulation of ROS within the cells. This suggests that the induction of ROS drives the fast evolution of antibiotic resistance in RecA-deficient bacteria. Collectively, we show that the hindrance of DNA repair hampers cellular fitness, provides bacteria with genetic adaptability to survive in diverse stressful environments, and accelerates the evolution of antibiotic resistance.
Fast Evolution of SOS-Independent Multi-Drug Resistance in Bacteria
Authors: Zhang Le , Guan Yunpeng , Cheng Yuen Yee , Cokcetin Nural N. , Bottomley Amy L. , Robinson Andrew , Harry Elizabeth J. , van Oijen Antoine , Su Qian Peter , Jin Dayong
Published: February 2024

The killing mechanism of many antibiotics involves the induction of DNA damage, either directly or indirectly, which triggers the SOS response. RecA, the master regulator of the SOS response, plays a crucial role in driving the evolution of resistance to fluoroquinolone antibiotics treated with a single dose of ciprofloxacin. However, the precise roles of RecA and SOS responses in the development of resistance under short-term β-lactam exposure remain unclear. In the present study, we observed a fast evolution of β-lactam resistance (20-fold increase in MIC in 8 hours) in
E. coli
after deleting RecA and exposing the bacteria to a single dose of ampicillin. Notably, once this type of resistance is established, it remains stable and can be passed on to subsequent generations. Contrary to previous findings, it is shown that this accelerated resistance development process is dependent on the hindrance of DNA repair, which is completely orthogonal to the SOS response. Additionally, we identified the rapid emergence of drug resistance associated mutations in the resistant bacterial genome, indicating the impairment of DNA repair. Through comprehensive transcriptome sequencing, we discovered that the expression of numerous antioxidative response genes is repressed in
recA
mutant resistant isolates, resulting in an excessive accumulation of ROS within the cells. This suggests that the induction of ROS drives the fast evolution of antibiotic resistance in RecA-deficient bacteria. Collectively, we show that the hindrance of DNA repair hampers cellular fitness, provides bacteria with genetic adaptability to survive in diverse stressful environments, and accelerates the evolution of antibiotic resistance.
کاوش در اعماق دریای قطب شمال با استفاده از فیلترهای رنگی
Authors: اوس ویبک , زیمرمن هایک جین , پانیری جولیانا , آب نیکی محمد , همتی نژاد فرشته
Published: February 2024

تمرکز:

برای شناخت برخی از موجودات در اعماق دریا که از رنگ و کمبود نور برای استتار خود استفاده می کنند.

 

اهداف آموزشی:

با این دو فعالیت، از بینایی برای کشف اشکال زندگی در اعماق دریا که با شرایط محیطی سخت سازگار شده اند استفاده می کنیم. از طریق این فعالیت‌ها، دانش‌آموزان با برخی از موجوداتی که به خوبی در کف اقیانوس پنهان شده‌اند آشنا می‌شوند.

 

کلیدواژه:

ترفند های استتار،اعماق اقیانوس، اعماق دریا، اثرات فیزیکی نور، ویژگی های شکل های حیات دریایی
کف اقیانوس (باستانی) کجاست؟
Authors: ماریچ فیلیپ , پوتو مارگریتا پائولا , پانیری جولیانا , آب نیکی محمد , همتی نژاد فرشته
Published: February 2024

تمرکز

درک اینکه کف اقیانوس پویا است و در طول زمان تغییر می کند. گاهی دور است، و گاهی بسیار نزدیکتر از آنچه فکر می کنیم. اما کف اقیانوس کجاست؟

 

اهداف آموزشی

در این فعالیت، دانش‌آموزان متوجه خواهند شد که به دلیل فعالیت‌های زمین ساختی، می‌توانیم کف اقیانوس‌های باستانی را در خشکی پیدا کنیم. توجه: این نیاز به برنامه ریزی قبلی دارد و ممکن است اگر مدرسه شما خیلی از این سازندهای زمین ساختی دور باشد انجام فعالیت امکان پذیر نباشد.

 

واژه‌های کلیدی

رسوب‌گذاری، سنگ‌های رسوبی، زمین ساخت، تاریخ زمین.
تأثیر انسانی: آلودگی پلاستیکی
Authors: ماریچ فیلیپ , پوتو مارگریتا پائولا , پانیری جولیانا , آب نیکی محمد , همتی نژاد فرشته
Published: February 2024

تمرکز

درک این موضوع که آلودگی پلاستیکی یک مشکل بزرگ است و بر اقیانوس ها در همه جا تأثیر می گذارد. این تاثیرات در سواحل و خطوط ساحلی و تا عمیق ترین نقاط اقیانوس دیده می شود.

 

اهداف آموزشی

در این فعالیت، دانش آموزان از میزان آلودگی پلاستیکی در داخل و اطراف اقیانوس ها درک پیدا خواهند کرد. آنها متوجه خواهند شد که چگونه آلودگی پلاستیکی می تواند تأثیر منفی بر زندگی زیر سطح دریا داشته باشد.

 

کلمات کلیدی

آلودگی اقیانوس، پلاستیک، میکروپلاستیک.
Primary Monophasic Omental Synovial Sarcoma in Nulliparous Female: A Case Report
Authors: Chowdhary Shambhavi , Khatri Chandrani , Nigam Shashank
Published: February 2024

Synovial Sarcoma (SS) is an uncommon soft-tissue malignancy that primarily occurs near tendon sheaths and bone joints. Its primary intra-abdominal location is infrequent and characterised by non specific clinical signs. The mainstay of treatment remains wide local excision with negative margins. Hereby the authors report a rare case of monophasic omental SS in a 30-year-old nulliparous female who presented with chief complaints of an enlarging lump in the right abdominopelvic region over the past year and constipation for three months. The mass was non mobile and non tender. The rest of the physical and laboratory examinations were normal. She has a history of diagnostic laparoscopic excision (for the same complaint) of bilateral adnexal masses with right salpingectomy done three months ago in an outside set-up where histopathology diagnosed the mass as a low-grade fibromyxoid tumour. Presently, Contrast- enhanced Magnetic Resonance Imaging (CEMRI) revealed a large lobulated heterogeneous mass of 19.5×15.4×20 cm extending into mesorectal fat and encasing the sigmoid colon, rectosigmoid junction, uterus, and bilateral ovaries. The patient was taken for emergency surgery as she started displaying symptoms of acute obstruction. Debulking surgery (R2 resection) with ileostomy was performed. Histopathology and immunohistochemistry confirmed the diagnosis of monophasic SS. The patient was started on doxorubicin and has completed three cycles of chemotherapy. SS is an infrequent entity with high mortality rates. The main course of treatment is surgery with healthy resection margins. Long-term follow-up is required due to the high recurrence rate.
Comparison of GPS radio occultation soundings with radiosondes
Authors: Kuo Y.‐H. , Schreiner W. S. , Wang J. , Rossiter D. L. , Zhang Y.
Published: March 2005

The radio occultation (RO) sounding technique that uses signals transmitted by the Global Positioning System (GPS) has evolved as an important global observing technology. In this paper, we compare RO refractivity profiles from the CHAMP (CHAllenging Minisatellite Payload) satellite mission with those calculated from radiosonde soundings over five geographical areas, each of which uses a different type of radiosonde. CHAMP RO soundings that occur within 2 hours and 300 km of radiosonde soundings are used during the period from June 2001 through March 2004. The comparison was made between the altitudes of 5–25 km, where RO soundings are most accurate. These results indicate that the RO soundings are of sufficiently high accuracy to differentiate performance of various types of radiosonde. The differences in performance among various types of radiosonde present a challenge for climate analysis. In this regard, RO is a considerably more robust measurement technique for climate monitoring.
Refractive indices of ZnSiN2 on r-plane sapphire
Authors: Cook B. P. , Everitt H. O. , Avrutsky I. , Osinsky A. , Cai A. , Muth J. F.
Published: March 2005

II – IV – N 2 wide band gap semiconductors such as ZnSiN2, ZnGeN2, and ZnSiGeN2 have potential uses for nonlinear materials and as lattice matching compounds for the growth of SiC and GaN devices. In this study, the dispersion of the TE and TM indices of refraction has been measured systematically using the prism coupling technique for an orthorhombic ZnSiN2 epitaxial layer grown on r-plane sapphire. The resulting index dispersion is extracted from the measured optical modes using a layered biaxial waveguide analysis, which shows that although the ZnSiN2 crystal is orthorhombic, for practical purposes it can be treated as a uniaxial material.
Fluorine segregation and incorporation during solid-phase epitaxy of Si
Authors: Mirabella S. , Impellizzeri G. , Bruno E. , Romano L. , Grimaldi M. G. , Priolo F. , Napolitani E. , Carnera A.
Published: March 2005

We report on the F incorporation into Si during solid-phase epitaxy (SPE) at 580°C and with the presence of B and∕or As, clarifying the F incorporation mechanism into Si. A strong segregation of F at the moving amorphous–crystalline interface has been characterized, leading to a SPE rate retardation and to a significant loss of F atoms through the surface. In B- or As-doped samples, an enhanced, local F incorporation is observed, whereas in the case of B and As co-implantation (leading to compensating dopant effect), a much lower F incorporation is achieved at the dopant peak. The F enhanced incorporation with the presence of B or As is shown to be a kinetic effect related to the SPE rate modification by doping, whereas the hypothesis of a F–B or F–As chemical bonding is refused. These results shed new light on the application of F in the fabrication of ultrashallow junctions in future generation devices.
Intramolecular interaction between phosphorylated tyrosine-783 and the C-terminal Src homology 2 domain activates phospholipase C-γ1
Authors: Poulin Benoit , Sekiya Fujio , Rhee Sue Goo
Published: March 2005

Phospholipase C-γ1 (PLC-γ1) contains two tandem Src homology 2 (SH2) domains. The NH2-terminal SH2 domain has been known to mediate the binding of PLC-γ1 to receptor protein tyrosine kinases, which then activate PLC-γ1 via phosphorylation at Y783. We now show that the phosphorylated Y783 residue (pY783) associates with the COOH-terminal SH2 domain [SH2(C)] within the same molecule of PLC-γ1. The specificity of this intramolecular interaction is demonstrated in several ways. The mutation of SH2(C), but not of the NH2-terminal SH2 domain, exposes pY783 and makes it available for binding by anti-pY783 antibodies, for intermolecular association with a GST fusion protein containing the tandem SH2 domains of PLC-γ1 and for dephosphorylation by phosphatases. The intramolecular interaction between pY783 and SH2(C) induces a rearrangement of surface charge such that PLC-γ1 molecules phosphorylated at Y783 are retained more strongly by heparin resins than are unphosphorylated molecules. Finally, the intramolecular interaction of pY783 with SH2(C) results in activation of phospholipase activity. Our results thus clarify the molecular mechanism of PLC-γ1 activation, revealing the specific function of pY783 and the distinct roles of the two SH2 domains in this process.
STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFβ-activated kinase 1 for STAT3 Ser-727 phosphorylation
Authors: Kojima Hirotada , Sasaki Takanori , Ishitani Tohru , Iemura Shun-ichiro , Zhao Hong , Kaneko Shuhei , Kunimoto Hiroyuki , Natsume Tohru , Matsumoto Kunihiro , Nakajima Koichi
Published: March 2005

Signal transducer and activator of transcription 3 (STAT3) is activated by the IL-6 family of cytokines and growth factors. STAT3 requires phosphorylation on Ser-727, in addition to tyrosine phosphorylation on Tyr-705, to be transcriptionally active. In IL-6 signaling, the two major pathways that derive from the YXXQ and the YSTV motifs of gp130 cause Ser-727 phosphorylation. Here, we show that TGF-β-activated kinase 1 (TAK1) interacts with STAT3, that the TAK1-Nemo-like kinase (NLK) pathway is efficiently activated by IL-6 through the YXXQ motif, and that this is the YXXQ-mediated H7-sensitive pathway that leads to STAT3 Ser-727 phosphorylation. Because NLK was recently shown to interact with STAT3, we explored the role of STAT3 in activating this pathway. Depletion of STAT3 diminished the IL-6-induced NLK activation by >80% without inhibiting IL-6-induced TAK1 activation or its nuclear entry. We found that STAT3 functioned as a scaffold for TAK1 and NLK
in vivo
through a region in its carboxyl terminus. Furthermore, the expression of the STAT3
534–770
region in the nuclei of STAT3-knockdown cells enhanced the IL-6-induced NLK activation in a dose-dependent manner but not the TGFβ-induced NLK activation. TGFβ did not cause STAT3 Ser-727 phosphorylation, even when the carboxyl region of STAT3 was expressed in the nuclei. Together, these results indicate that STAT3 enhances the efficiency of its own Ser-727 phosphorylation by acting as a scaffold for the TAK1-NLK kinases, specifically in the YXXQ motif-derived pathway.
Into the Fold: Protestant Christian Communities in South India
Authors: Kent Eliza F.
Published: March 2005

This chapter discusses the gendered effects of religious conversion in the areas of domestic, marital, and sartorial practices. It provides a history of Protestant Christianity in south India, focusing on the consequences of Christianization for women. It argues that conversions appear as the movement of marginalized people towards new centers of power that emerged in the social landscape.
Colonial Knowledge and the Creation of Respectable Castes
Authors: Kent Eliza F.
Published: March 2005

Descriptions of the social lives and customs of low castes in the 19th century India come from two main sources: missionary accounts and administrative records. This chapter explores the categories and concepts generated by missionaries and colonial administrators from their studies on Indian culture, religion, physiognomy, economics, etc. It then examines how these were appropriated and deployed by Shanar converts in the creation of a new, respectable identity as Nadar Kshatriyas.
Gold and Cholis: Indian Christian Sartorial Style
Authors: Kent Eliza F.
Published: March 2005

The sartorial styles that Indian Christians adopted in the 19th and early 20th centuries reflected the new social identities that accompanied the conversion to Christianity. Sartorial style functioned an arena for displaying and contesting claims about the social and moral condition of individuals and communities. Men’s and women’s bodies served as vehicles for broadcasting new assertions of respectable community identity, an identity drawn from a pool of signifiers from both Western bourgeois and elite Indian culture.
CHAPTER 2 Emotions and the Ancient Pursuit of Christian Perfection
Authors: Knuuttila Simo
Published: March 2005

Early Christian theories of the emotions were influenced by the Platonic psychology and control oriented therapy as well as by the Stoic theory and therapy. Particularly important were the Stoic doctrine of spontaneous first movements and the ideal of apatheia which the Christian authors qualified by the conception of love. Section 1 deals with the views of emotion, sin, progress, and spiritual experience in Clement and Origen, who were the main representatives of early Alexandrian theology. Sections 2 and 3 deal with the partial reception and modification of this approach by the Cappadocian theologians and the Egyptian desert monks, whose teaching came to influence Western thought through the works of John Cassian. Augustine's view of the emotions and the will is discussed in Sect. 4. Section 5 deals with the ideas of Gregory the Great, Pseudo‐Dionysius, and some other late ancient authors.
CHAPTER 3 Medieval Conceptions of Emotions from Abelard to Aquinas
Authors: Knuuttila Simo
Published: March 2005

The first part deals with the twelfth‐century reception and discussion of ancient themes in theology, logic and medical theory. Among the most significant theological contexts for treating emotions were the doctrine of first movements toward sin (Sect. 1) and the question of the nature of spiritual experiences (Sect. 2). Section 3 involves a general account of the early development of the logic of the will and its relations to the discussion of emotions. The medical theories of emotions and their impact on twelfth‐century philosophy and theology are discussed in Sect. 4. Section 5 contains an analysis of Avicenna's theory of emotions. Avicennian faculty psychology influenced early thirteenth‐century Latin discussions of the nature and taxonomy of emotions (Sect. 6). Section 7 deals with Albert the Great and Sect. 8 with Thomas Aquinas. Aquinas’ theory, which combines Avicennian and Aristotelian themes, is the most extensive medieval contribution to the subject.
Solving the Philosophical Mind‐Body Problem
Authors: McGinn Colin
Published: March 2005

The problem of consciousness is not that there are a number of competing explanatory theories, for which we lack the evidence that would enable us to choose between them; it is that we have no sense of what a possible explanation would even look like. Two senses in which consciousness might be mysterious to us are distinguished: an ontological or metaphysical sense in which consciousness is thought to have an occult non-natural nature; and an epistemological sense, in which we do not or cannot understand the nature of consciousness. It is then argued that consciousness is mysterious in the latter sense but not in the former. Consciousness exists and has an explanation, but its nature is deeply and intractably hidden from us owing to the limitations of our cognitive powers. Accepting these theoretical limitations removes the temptation to postulate a set of variously unacceptable solutions to the mind-body problem, which display a typical form (the ‘DIME shape’): deflationary reductionism, outright irreducibility, the eerily magical, ontological elimination.
Consciousness, Atomism, and the Ancient Greeks
Authors: McGinn Colin
Published: March 2005

Physical atomism, as proposed by Democritus, was a speculative theory, without much empirical support or explanatory success, which much later received serious confirmation. Comparisons are drawn between some ancient Greek responses to puzzling phenomena and modern reductionist responses to the mind-body problem. It is conjectured that atomism with regard to the mental is true in advance of there being any particular evidence for it. According to this theory, conscious states consist of unobserved underlying states, which combine to produce the states that we do observe. If such a theory could be produced, it is argued that it might contribute to a solution to the mind-body problem.
In vitro measurement of rabbit corneal epithelial thickness using ultrahigh resolution optical coherence tomography
Authors: Reiser Bibiana J. , Ignacio Teresa S. , Wang Yimin , Taban Mehran , Graff Jordan M. , Sweet Paula , Chen Zhongping , Chuck Roy S.
Published: March 2005

The objective of this study was to reproducibly measure corneal epithelial thickness centrally and at the limbus in the rabbit cornea using ultrahigh resolution optical coherence tomography (OCT). Twelve freshly enucleated New Zealand white rabbit eyes were kept in a moist chamber at 4 °C. An ultrahigh resolution OCT system with a spatial resolution of 1.3 µm was used to image the cornea and its component layers. The central and peripheral (limbal) regions of all the samples were scanned within 6 h of harvest in order to minimize the post‐mortem degradation of the corneal epithelium. The thickness of the corneal epithelium was determined by measuring the pixel equivalents of the obtained image. Unpaired Student's t‐test was used to evaluate differences. The epithelial thickness centrally was found to be 45.8 ± 2.2 µm, and 37.6 ± 1.4 µm at the limbus (P < 0.001). Rabbit corneal epithelium is thicker centrally than at the limbus when measured by ultrahigh resolution OCT. This technique will aid in delineating the pathophysiology of diseases of the anterior cornea.
Limbal pseudotumor in a Cob Pony
Authors: Saroglu Murat , Aktas Mustafa , Olgun Dilek , Arun Seckin Serdar
Published: March 2005

A tumor‐like tissue mass of lateral–limbal site in the right eye of a 12‐year‐old Cob Pony mare was presented for surgical removal. The mass, covering the lateral limbus, bulbar conjunctiva and part of the cornea, was surgically removed, and the corneal defect repaired with a pedicle bulbar conjunctival graft. The mass was inflammatory in nature containing mononuclear cells. No recurrence or complication occurred at 6‐ and 12‐month follow‐up examination.
Time Resolved Concentration Measurements in an Axial Flow Mixer
Authors: Campbell J. E. , Coppom R. W. , Guilkey J. E. , Klewicki J. C. , McMurtry P. A.
Published: March 2005

Experimental results are reported providing information on the downstream mixing evolution in axial pipe flow mixers where a scalar is introduced into the pipe via a coaxial injection tube. Experiments were conducted in a 25.4 mm diameter water pipe flow loop 25,700>RD>28,500, in which a fluorescein dye was coaxially injected. The injection tube diameter was 1.5 mm. Three velocity ratios, VR=0.5, 1.0, and 2.0 were explored, where VR=Vjet/Vmain. The present results indicate that the effects of velocity ratio on the scalar concentration statistics are mainly evident in the first several outer pipe diameters downstream. In the far field, velocity ratio effects are shown to be insignificant on the concentration statistics. All cases showed a similar trend of an initial increase in variance at the centerline as the injected fluid begins mixing with the main pipe flow. This is followed by a region of rapid “exponential-like” decay, followed by a much slower decay rate after approximately 50 pipe diameters. Space-time correlations of the scalar concentration between far field locations verify the low wavenumber motions as predicted by the recent theory of Kerstein and McMurtry [A. Kerstein and P. McMurtry, “Low-wave-number statistics of randomly advected passive scalars,” Phys. Rev. E 50, 2057 (1994)], and are consistent with the slower than exponential downstream mixing rate.
Turbulent Flow Hydrodynamic Experiments in Near-Compact Heat Exchanger Models With Aligned Tubes
Authors: Wilson L. , Narasimhan Arunn , Venkateshan S. P.
Published: March 2005

Hydrodynamic experiments measuring longitudinal pressure-drop versus flow rate are conducted for turbulent flow of air (channel hydraulic diameter based Reynolds number range of 2300 to 6860) through near-compact heat exchanger models with rod bundles having aligned (inline) arrangement. Effects of the flow (Re), the geometry parameters, and number of rods of the test models on the nondimensional pressure-drop ξ are studied in detail. Treating the near compact heat exchanger model as a porous medium, a dimensional pressure-drop ΔP/L versus average velocity of flow (U) model similar in content to a non-Darcy porous medium model, is shown to fit the experimental data with fair accuracy. Variation in form drag related to, and induced by the flow and geometric parameters are shown to be the reason for the pressure-drop variations of different models. The relation between the porous medium type model (ΔP/L versus U) and the “ξ versus Re” model is discussed with careful attention to the differences in the two transitions viz. laminar to turbulent and viscous-drag to form-drag dominated flow inside the models. A proposed correlation for predicting ξ, ably capturing all of the form effects induced by the flow and geometric parameters, is found to give predictions with ±20% accuracy.
Discrete Sliding-Mode Tracking Control of High-Displacement Piezoelectric Actuator Systems
Authors: Hwang Chih-Lyang , Chen Yung-Ming
Published: March 2005

We consider the modeling and control of a high-displacement piezoelectric actuator system (HDPAS). An HDPAS includes a multilayer LVPZT bender actuator (MLBA) and a low-pass filter. The MLBA is subject to hysteresis, bending modes, measurement noise, and external disturbance. Because the spillover associated with a reduced-order model of the MLBA has been known to have the potential to cause the instability of the closed-loop system, a low-pass filter is applied to reduce its effect. To obtain an acceptable model for the HDPAS, a band-limited input and its corresponding output are fed into a recursive least-squares parameter estimation scheme. The resulting model is then used for a controller design, which includes three features. First, a dead-beat to its filtered switching surface is achieved. Second, the H∞ norm of the sensitivity function between the filtered switching surface and the output disturbance is simultaneously minimized to attenuate the effect of output disturbance. Third, a switching control based on Lyapunov redesign is used to further improve the tracking accuracy. To demonstrate the effectiveness of the proposed control, the experimental results of the HDPAS by using the proposed control are compared with those by a proportional integral differential (PID) control.
Swirling Gas–Liquid Two-Phase Flow—Experiment and Modeling Part II: Turbulent Quantities and Core Stability
Authors: Gomez L. , Mohan R. , Shoham O.
Published: March 2005

In Part I of this two-part paper on swirling gas–liquid two-phase flow, correlations have been developed for the continuous liquid-phase velocity field under swirling conditions, such as that occurring in the lower part of the Gas–Liquid Cylindrical Cyclone (GLCC©1) compact separator. The developed correlations, including the axial, tangential, and radial velocity distributions, are applicable for swirling flow in both cyclones and pipe flow. The first objective of this paper is to extend the study of Part I by developing correlations for the turbulent quantities of the continuous liquid phase, including the turbulent kinetic energy and its dissipation rate and Reynolds shear stresses. The second objective is to study experimentally and theoretically two-phase swirling flow gas-core characteristics and stability. The first objective has been met utilizing local LDV measurements acquired for swirling flow. The developed turbulent quantities correlations have been tested against data from other studies, showing good agreement. For the second objective, experimental data have been acquired under swirling two-phase flow conditions. A model for the prediction of the gas-core diameter and stability in swirling flow field has been developed, based on the turbulent kinetic energy behavior predicted by the developed correlations. Good agreement is observed between the model predictions and the data.
Analysis of multipath scintillations from long range acoustic transmissions on the New England continental slope and shelf
Authors: Fredricks Andrew , Colosi John A. , Lynch James F. , Gawarkiewicz Glen , Chiu Ching-Sang , Abbot Philip
Published: March 2005

Observations of intensity fluctuations for broadband, 400-Hz multipath arrivals observed during the 1996 New England shelfbreak PRIMER study are described. Acoustic signals were generated by two bottom-mounted sources located on the continental slope in roughly 290-m water depth and were received on a 52-m-long vertical-line-array (VLA) located in 93-m water depth. Propagation ranges were 42.2 and 59.6 km. The bathymetry, oceanography, and bottom geology of the PRIMER site are described. Acoustic observables of point intensity, peak intensity, and integrated energy over the VLA are treated in terms of the scintillation index, log-intensity variance, and intensity probability density functions (PDFs). Variability of the observables are decomposed into high and low frequency components with time scales less than and greater than 2 h, to facilitate correlation to ocean processes at different timescales. Parabolic equation numerical simulations using a quasi-random undular tidal bore model are able to reproduce many of the observed intensity fluctuation to within a factor of 2, and they allow investigation of scintillation behavior as a function of range.
Recording depth and signal competition in heterodyne interferometry
Authors: de La Rochefoucauld Ombeline , Khanna Shyam M. , Olson Elizabeth S.
Published: March 2005

A common way to measure submicroscopic motion of the organ of Corti is heterodyne interferometry. The depth over which vibration can be accurately measured with heterodyne interferometry is determined by both the optics, which controls to what extent light from nonfocal planes reaches the photodetectors, and demodulation electronics, which determines to what extent signal generated by out-of-focal-plane light influences the measurements. The influence of a second reflecting surface is investigated theoretically and experimentally. By reviewing the theory of FM demodulation and showing tests with a Revox FM demodulator, it is demonstrated that the influence of a secondary signal on a measurement depends on the modulation index. Both high- and low-modulation index signals are encountered in heterodyne interferometry of the cochlea. Using a He–Ne-like diode laser (λ=638 nm), the border between low- and high-modulation signals is at a displacement of about 25–100 nm. Confocal interferometry reduces the magnitude of out-of-focus signals, and therefore their effect on vibration measurement. The response of the confocal system to reflected signals from two surfaces separated by distances encountered within the cochlear partition is shown. The results underscore the benefit of steep optical sectioning for intracochlear measurements.
Frequency dependency of the relationship between perceived auditory source width and the interaural cross-correlation coefficient for time-invariant stimuli
Authors: Mason Russell , Brookes Tim , Rumsey Francis
Published: March 2005

Previous research has indicated that the relationship between the interaural cross-correlation coefficient (IACC) of a narrow-band sound and its perceived auditory source width is dependent on its frequency. However, this dependency has not been investigated in sufficient detail for researchers to be able to properly model it in order to produce a perceptually relevant IACC-based model of auditory source width. A series of experiments has therefore been conducted to investigate this frequency dependency in a controlled manner, and to derive an appropriate model. Three main factors were discovered in the course of these experiments. First, the nature of the frequency dependency of the perceived auditory source width of stimuli with an IACC of 1 was determined, and an appropriate mathematical model was derived. Second, the loss of perceived temporal detail at high frequencies, caused by the breakdown of phase locking in the ear, was found to be relevant, and the model was modified accordingly using rectification and a low-pass filter. Finally, it was found that there was a further frequency dependency at low frequencies, and a method for modeling this was derived. The final model was shown to predict the experimental data well.
Simulations of temporal patterns of oral airflow in men and women using a two-mass model of the vocal folds under dynamic control
Authors: Lucero Jorge C. , Koenig Laura L.
Published: March 2005

In this study we use a low-dimensional laryngeal model to reproduce temporal variations in oral airflow produced by speakers in the vicinity of an abduction gesture. It attempts to characterize these temporal patterns in terms of biomechanical parameters such as glottal area, vocal fold stiffness, subglottal pressure, and gender differences in laryngeal dimensions. A two-mass model of the vocal folds coupled to a two-tube approximation of the vocal tract is fitted to oral airflow records measured in men and women during the production of /aha/ utterances, using the subglottal pressure, glottal width, and Q factor as control parameters. The results show that the model is capable of reproducing the airflow records with good approximation. A nonlinear damping characteristics is needed, to reproduce the flow variation at glottal abduction. Devoicing is achieved by the combined action of vocal fold abduction, the decrease of subglottal pressure, and the increase of vocal fold tension. In general, the female larynx has a more restricted region of vocal fold oscillation than the male one. This would explain the more frequent devoicing in glottal abduction–adduction gestures for /h/ in running speech by women, compared to men.
Mode coherence at megameter ranges in the North Pacific Ocean
Authors: Wage Kathleen E. , Dzieciuch Matthew A. , Worcester Peter F. , Howe Bruce M. , Mercer James A.
Published: March 2005

This article analyzes the coherence of low-mode signals at ranges of 3515 and 5171 km using data from the Acoustic Thermometry of Ocean Climate (ATOC) and Alternate Source Test (AST) experiments. Vertical line arrays at Hawaii and Kiritimati received M-sequences transmitted from two sources: the 75-Hz bottom-mounted ATOC source on Pioneer Seamount and the near-axial dual-frequency (28/84 Hz) AST source deployed nearby. This study demonstrates that the characteristics of the mode signals at 5171-km range are quite similar to those at 3515-km range. At 75 Hz the mode time spreads are on the order of 1.5 s, implying a coherence bandwidth of 0.67 Hz. The time spread of the 28-Hz signals is somewhat lower, but these signals show significantly less frequency-selective fading than the 75-Hz signals, suggesting that at the lower frequency the multipaths are temporally resolvable. Coherence times for mode 1 at 75 Hz are on the order of 8 min for the 3515-km range and 6 min for 5171-km range. At 28 Hz mode 1 is much more stable, with a magnitude-squared coherence of greater than 0.6 for the 20-min transmission period.