bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk‐stratified Management of Well‐differentiated Thyroid Cancers: A Review of Experience from a Single Institution, 1990–2003
Authors: Chew M. H. , Chan G. , Siddiqui M. M. A. , Tai B. C. , Sivanandan R. , Soo K. C. , Lim D. T. H.
Published: January 2008

Introduction

Controversy persists regarding ideal management strategies in well‐differentiated thyroid cancers (WDTC). This retrospective study reviews the utilization of a modified AMES risk stratification in the management of our institution’s patients.

Methods

A total of 352 patients (median follow‐up of 5.5 years) were reviewed and were risk stratified. Surgical resection was performed, and patients with clinically palpable lymph nodes were subjected to radical neck dissection. Patients were referred for adjuvant therapy if necessary.

Results

Of the 352 patients, 264 (75%) were females and 276 (78%) had papillary thyroid cancer (PTC). For those with lymph nodes (50%), 95% had PTC. In this series, 72% of the patients underwent total thyroidectomy; 5‐year disease‐free survival probability was 100% in low‐risk patients, 92% in intermediate‐risk patients, and 64% in high‐risk patients. The 5‐year overall survival probability was 100% in low‐risk patients, 96% in intermediate‐risk patients, and 69% in high‐risk patients, respectively (both logrank trend p < 0.001).

Conclusions

Management of WDTC requires multimodal treatment and should be based on patient risk classifications. We recommend aggressive surgical resection for all gross disease in high‐risk and intermediate‐risk patients. Adjuvant therapy is recommended in high‐risk patients, but should be individualized for intermediate‐risk patients. Total thyroidectomy may not be necessary in low‐risk patients.
Complications After Esophagectomy for Cancer: 53‐Year Experience with 20,796 Patients
Authors: Liu J. F. , Wang Q. Z. , Ping Y. M. , Zhang Y. D.
Published: January 2008

The incidence of esophageal cancer in Hebei Province in China is the highest in the world. Our experience in the Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University with the management of postoperative complications following esophagectomy was determined. From September 1952 to December 2005, a total of 20,796 patients underwent an intended esophagectomy for cancer in our department. Data for the outcome of these procedures was sourced from reported articles in the Chinese‐language literature. The data were collated to determine the incidence and outcomes of postoperative complications. The incidence of major complications declined over the period of study. The likelihood of anastomotic leakage decreased from 5.0% to 2.3%, and pulmonary complications declined from 3.2% to 1.6%. The surgical mortality rate decreased from 17.1% to 0.6%. The incidence of postoperative complications and deaths following esophagectomy for cancer in our unit has fallen steadily over the past five decades. Improvements in preoperative preparation and postoperative management have contributed to this decrease.
Recent Advances in Neonatal Cardiac Surgery
Authors: el‐Zein Chawki , Ilbawi Michel N.
Published: January 2008

Several major advances in the field of neonatal cardiac surgery have improved the outcome of these severely ill patients. Among the preoperative advances are improvement in the management of patients with single ventricle equivalents, prenatal diagnosis, and interventional procedures. Intraoperative advances include better understanding of the inflammatory process caused by cardiopulmonary bypass and ways to manage it, newer techniques for treating hypoplastic left heart syndrome and aortic valve disease, and primary repair of complex lesions. Postoperative refinements in managing pulmonary hypertension, low cardiac output state, and ventricular assist devices have decreased surgical mortality and morbidity. Although his primary interest has been adult cardiac surgery, Dr. Geha has contributed directly and indirectly to these advances.
Determination of Tertiary‐butylhydroquinone and Its Metabolites in Rat Serum by Liquid Chromatography–Ion Trap Mass Spectrometry
Authors: Huang Wen , Gu Yinchun , Niu Hai
Published: January 2008

A new method applying sensitive and selective liquid chromatography coupled with mass spectrometry (LC/MS/MS) for analyzing tertiary‐butylhydroquinone (TBHQ) and its metabolites in rat serum was validated. Using an extracted ion chromatogram (EIC) of m/z 149, free TBHQ was observed in rat serum after dosing TBHQ at 350 mg/kg to male and female Sprague–Dawley (SD) rats. Four major metabolites of TBHQ were identified—a TBHQ‐sulfate, two TBHQ‐sulfate‐derived substances and a TBHQ‐glucuronide through MSn spectra. Besides its simplicity, the sample treatment allows one to obtain a very good recovery of analysts, namely around 95%. This result suggests that the method described here is useful for the analysis of TBHQ and its metabolites in rat serum. Moreover, the metabolism of TBHQ was investigated using the method. After oral administration, TBHQ appear to be more completely absorbed and bio‐transformed by males than females, which may result in higher acute oral toxicity of TBHQ for males than females.
Oral Nanoparticulate Atorvastatin Calcium is More Efficient and Safe in Comparison to Lipicure® in Treating Hyperlipidemia
Authors: Meena A. K. , Ratnam D. Venkat , Chandraiah G. , Ankola D. D. , Rao P. Rama , Kumar M. N. V. Ravi
Published: January 2008

Atorvastatin calcium (AC) is a second‐generation 3‐hydroxy‐3‐methylglutaryl‐CoA reductase inhibitor approved for clinical use as a lipid lowering agent. AC, the world's best selling drug is associated with poor oral bioavailability and serious adverse effects like rhabdomyolysis on chronic administration. A biodegradable nanoparticulate approach was introduced here with a view to improving the efficacy and safety of AC. Poly lactide‐co‐glycolic acid (PLGA) nanoparticles containing atorvastatin calcium were prepared using two stabilizers i.e. didodecyl dimethyl ammonium bromide (DMAB) and Vitamin E tocopheryl polyethylene glycol 1000 succinate (Vit E‐TPGS) using a co‐solvent approach by emulsion–diffusion–evaporation method. AC loaded PLGA nanoparticles prepared using DMAB and Vit E‐TPGS were found to be 120.0 ± 4.2 nm and 140.0 ± 1.5 nm (z‐average) in size respectively. In vitro release studies at pH 7.4 revealed a zero order release profile for nanoparticles. Efficacy and safety parameters of the prepared nanoparticles against marketed formulation were evaluated in high fat diet fed (hyperlipidemic) rats. It was found that atorvastatin calcium nanoparticles were equally effective in comparison to Lipicure®, at a 66%‐reduced dose in treating the hyperlipidemia characterized by alterations in PTC, LDL‐C, VLDL‐C, HDL‐C, PTG and PGL in the high fat diet fed rats. On the other hand, when evaluated for safety, nanoparticulate formulation showed no/negligible myotoxicity characterized by lower PC, BUN, CK, LDH and AST levels in comparison to the marketed formulation.
Chemical Properties of Epidermal Lipids, Especially Sphingolipids, of the Antarctic Minke Whale
Authors: Yunoki Keita , Ishikawa Hajime , Fukui Yutaka , Ohnishi Masao
Published: January 2008

It is well known that sphingolipids specifically exist in the terrestrial mammal epidermis and correlate with skin barrier functions. However, the lipid properties of the marine mammal epidermis have not been examined in detail. We thus investigated the chemical composition of lipid components, especially sphingolipids, in the black epidermis (outer skin) of Antarctic minke whales (six mature and six immature specimens). Complex lipid fractions mainly contained cerebroside (CE), cholesteryl sulfate and sphingomyelin (SM), as well as two glycerophospholipids. Moreover, in the superficial layer of the black epidermis, CE was richly abundant but phospholipids were scarce. As component fatty acids, the non‐hydroxy monounsaturated very long chain fatty acids (VLFA) within 34 carbons were generally present in CE and SM in the black epidermis. CE also consisted of α‐hydroxy fatty acids with monounsaturation within C34 (17%) and a slight proportion of ω‐hydroxy ones (32:1 and 34:1), the latter being probably derived from acyl‐CE. Component sphingoid bases of both sphingolipids were predominantly 4‐sphingenine (64%), followed by a C16 analogue (21%). When comparing these by different maturities, mature whales showed sphingolipid profiles with higher levels of unsaturated fatty acids and with shorter sphingoid base chains than those of immature ones. Component analysis revealed that CE sugars were 67% glucose and 33% galactose, and α‐hydroxy fatty acids only bound to galactose.
THE CLOSED RANGE PROPERTY FOR BANACH SPACE OPERATORS
Authors: MILLER THOMAS L. , MÜLLER VLADIMIR
Published: January 2008

LetTbe a bounded operator on a complex Banach spaceX. LetVbe an open subset of the complex plane. We give a condition sufficient for the mappingf(z)↦ (T−z)f(z) to have closed range in the Fréchet spaceH(V,X) of analyticX-valued functions onV. Moreover, we show that there is a largest open setUfor which the mapf(z)↦ (T−z)f(z) has closed range inH(V,X) for allV⊆U. Finally, we establish analogous results in the setting of the weak–* topology onH(V, X*).
QUANTUM ANALOGUES OF SCHUBERT VARIETIES IN THE GRASSMANNIAN
Authors: LENAGAN T.H. , RIGAL L.
Published: January 2008

We study quantum Schubert varieties from the point of view of regularity conditions. More precisely, we show that these rings are domains that are maximal orders and are AS-Cohen-Macaulay and we determine which of them are AS-Gorenstein. One key fact that enables us to prove these results is that quantum Schubert varieties are quantum graded algebras with a straightening law that have a unique minimal element in the defining poset. We prove a general result showing when such quantum graded algebras are maximal orders. Finally, we exploit these results to show that quantum determinantal rings are maximal orders.
PROJECTIVE LINEAR GROUPS AS MAXIMAL SYMMETRY GROUPS
Authors: TORSTENSSON ANNA
Published: January 2008

A maximal symmetry group is a group of isomorphisms of a three-dimensional hyperbolic manifold of maximal order in relation to the volume of the manifold. In this paper we determine all maximal symmetry groups of the typesPSL(2,q) andPGL(2,q). Depending on the primepthere are one or two such groups withq=pkandkalways equals 1, 2 or 4.
INFINITE HILBERT CLASS FIELD TOWERS OVER CYCLOTOMIC FIELDS
Authors: SHPARLINSKI IGOR E.
Published: January 2008

We use a result of Y. Furuta to show that for almost all positive integers m, the cyclotomic field $\Q(\exp(2 \pi i/m))$ has an infinite Hilbert p-class field tower with high rank Galois groups at each step, simultaneously for all primes p of size up to about (log logm)1 + o(1). We also use a recent result of B. Schmidt to show that for infinitely many m there is an infinite Hilbert p-class field tower over $\Q(\exp(2 \pi i/m))$ for some p≥m0.3385 + o(1). These results have immediate applications to the divisibility properties of the class number of $\Q(\exp(2 \pi i/m))$.
SOME REMARKS ON TRANSVERSALLY HARMONIC MAPS
Authors: KONDERAK JERZY J. , WOLAK ROBERT
Published: January 2008

We consider transversally harmonic foliated maps between two Riemannian manifolds equipped with Riemannian foliations. We give various characterisations of such maps and we study the relation between the properties ‘harmonic’ and ‘transversally harmonic’ for a given map. We also consider these problems for particular classes of manifolds: manifolds with transversally almost Hermitian foliations and Riemannian flows.
COEFFICIENTS OF THE PROBABILISTIC FUNCTION OF A MONOLITHIC GROUP
Authors: JIMÉNEZ–SERAL PAZ
Published: January 2008

We relate the coefficients of the probabilistic zeta function of a finite monolithic group to those of an almost simple group.
Ist die Epidemie der Adipositas bei Kindern noch aufhaltbar?
Authors: Puder J. J. , Kriemler S.
Published: January 2008

Die kindliche Adipositas beeinflusst das erwachsene Körpergewicht und ist selbst mit mehreren Komorbiditäten assoziiert. Die Prävalenz des Übergewichtes und der Adipositas bei Schweizer Schulkindern hat sich in den letzten 20 Jahren verdrei- bis versechsfacht. Jedes vierte bis fünfte Kind ist übergewichtig oder adipös. Eine Primärprävention ist also absolut essentiell. Das Übergewicht resultiert aus einer positiven Energiebilanz: Änderungen in der Quantität und Qualität der Ernährung, eine Verminderung der körperlichen Aktivität, eine Zunahme des sesshaften Lebensstils inklusive Medienkonsum sowie eine Verminderung der Schlafdauer sind gemäss der heutigen Literatur die wichtigsten Umgebungsfaktoren, die zur Entwicklung der kindlichen Adipositas nach dem Kleinkindesalter führen, wobei auch das intrauterine Milieu und genetische Faktoren eine Rolle spielen. Kinder von übergewichtigen Eltern, Kinder von niedrigem sozio-ökonomischen Status und Migranten sind besonders von der Adipositas-Epidemie betroffen. Randomisierte kontrollierte Studien, die eine mittel- bis langfristige (≥ 1 Jahr) Verminderung des BMI oder der Fettmasse zum Ziel hatten, sind vorwiegend schulbasiert und involvieren teilweise auch die Familie. Leider ergaben diese mehrheitlich nur negative oder bescheidene Resultate. Unserer Meinung nach benötigt eine erfolgreiche und anhaltende Prävention drei Elemente: 1. Eine relativ intensive und anhaltende individuelle Verhaltensänderung, die der multifaktoriellen Ursache der kindlichen Adipositas gerecht wird. 2. Eine gleichzeitige Umgebungsanpassung, die diese Veränderungen mit ermöglicht. 3. Ein Miteinbezug der sozio-ökonomischen und politischen Aspekte.
Sepsis nach einer Pharyngitis
Authors: Schmid I. , Licht A. , Eich G.
Published: January 2008

Wir berichten über eine 36-jährige Patientin, die 4 Tage nach einer Pharyngitis, eine Sepsis mit hohem Fieber und rezidivierendem Erbrechen entwickelte. Das konventionelle Thorax-Röntgenbild zeigte multiple Lungenabszesse und mittels Computertomographie konnte zusätzlich eine Thrombose der Vena communicans zwischen der V. jugularis anterior und der V. jugularis interna nachgewiesen werden. Dieses Krankheitsbild ist unter dem Namen Lemierre-Syndrom bekannt. Der am häufigsten nachgewiesene Erreger ist das Fusobacterium necrophorum, doch auch andere Bakterien der oberen Atemwegsflora sind als Erreger beschrieben worden. Unter adäquater antibiotischer Therapie und supportiven Massnahmen ist die Prognose meist günstig.
A CBS domain-containing pyrophosphatase ofMoorella thermoaceticais regulated by adenine nucleotides
Authors: Jämsen Joonas , Tuominen Heidi , Salminen Anu , Belogurov Georgiy A. , Magretova Natalia N. , Baykov Alexander A. , Lahti Reijo
Published: January 2008

CBS (cystathionine β-synthase) domains are found in proteins from all kingdoms of life, and point mutations in these domains are responsible for a variety of hereditary diseases in humans; however, the functions of CBS domains are not well understood. In the present study, we cloned, expressed in Escherichia coli, and characterized a family II PPase (inorganic pyrophosphatase) from Moorella thermoacetica (mtCBS-PPase) that has a pair of tandem 60-amino-acid CBS domains within its N-terminal domain. Because mtCBS-PPase is a dimer and requires transition metal ions (Co2+ or Mn2+) for activity, it resembles common family II PPases, which lack CBS domains. The mtCBS-PPase, however, has lower activity than common family II PPases, is potently inhibited by ADP and AMP, and is activated up to 1.6-fold by ATP. Inhibition by AMP is competitive, whereas inhibition by ADP and activation by ATP are both of mixed types. The nucleotides are effective at nanomolar (ADP) or micromolar concentrations (AMP and ATP) and appear to compete for the same site on the enzyme. The nucleotide-binding affinities are thus 100–10000-fold higher than for other CBS-domain-containing proteins. Interestingly, genes encoding CBS-PPase occur most frequently in bacteria that have a membrane-bound H+-translocating PPase with a comparable PPi-hydrolysing activity. Our results suggest that soluble nucleotide-regulated PPases act as amplifiers of metabolism in bacteria by enhancing or suppressing ATP production and biosynthetic reactions at high and low [ATP]/([AMP]+[ADP]) ratios respectively.
PCNASUMO and Srs2: a model SUMO substrate–effector pair
Authors: Ulrich H.D.
Published: January 2008

Attachment of the SUMO (small ubiquitin-related modifier) to the replication factor PCNA (proliferating-cell nuclear antigen) in the budding yeast has been shown to recruit a helicase, Srs2, to active replication forks, which in turn prevents unscheduled recombination events. In the present review, I will discuss how the interaction between SUMOylated PCNA and Srs2 serves as an example for a mechanism by which SUMO modulates the properties of its targets and mediates the activation of downstream effector proteins.
Regulation of the dual-function transcription factor Sp3 by SUMO
Authors: Valin A. , Gill G.
Published: January 2008

In eukaryotes, gene expression is controlled by a relatively small number of regulators. Post-translational modifications dramatically increase the functional possibilities of those regulators. Modification of many transcription factors and cofactors by SUMO (small ubiquitin-related modifier) correlates, in most cases, with inhibition of transcription. Recent studies suggest a model whereby SUMO conjugation to transcription factors promotes the recruitment of co-repressors through direct protein–protein interaction with the SUMO protein. HDACs (histone deacetylases) are important, but not exclusive, effectors of SUMO-mediated repression. Sp3 (specificity protein 3), a zinc-finger DNA-binding domain transcription factor, has the ability to both activate and repress transcription in a context-dependent manner. SUMOylation regulates the dual nature of Sp3 function. Current data suggest that Sp3 represses transcription in a SUMO-dependent manner but independent of HDACs. Recent studies to identify additional co-repressors associated with SUMO and further investigate regulated activity of Sp3 are providing a deeper understanding of SUMO-dependent mechanisms of transcriptional regulation.
Pc2 and SUMOylation
Authors: Wotton D. , Merrill J.C.
Published: January 2008

Polycomb proteins are key regulators of transcription in metazoan organisms. Recent work has shed light on the nature of the polycomb protein complexes in flies and mammalian cells. Multiple enzymatic activities have been shown to associate with polycomb complexes, including histone methyltransferase, histone deacetylase and ubiquitination activities, which are primarily directed towards the modification of chromatin structure. In addition to these chromatin-based functions, other potential roles for polycomb proteins exist. Here, we present a comparison of vertebrate Pc2 (polycomb 2 protein) homologues, and review the known functions of the mammalian Pc2 focusing on its role as a SUMO (small ubiquitin-related modifier) E3 ligase. Pc2 is an E3 for several SUMO substrates, but still appears to have a more limited repertoire than other SUMO E3s, perhaps due to its association with polycomb complexes. One possibility is that Pc2 represents a relatively specialized polycomb protein, which has additional functions to those associated with other mammalian Pc (polycomb protein) paralogues.
Signalling pathways and the regulation of SUMO modification
Authors: Guo B. , Yang S.-H. , Witty J. , Sharrocks A.D.
Published: January 2008

The modification of proteins by SUMO (small ubiquitin-related modifier) conjugation is becoming increasingly recognized as an important regulatory event. Protein SUMOylation can control a whole range of activities, including subcellular localization, protein–protein interactions and enzymatic activity. However, the SUMOylation process can itself be controlled. In the present review, the mechanisms through which protein SUMOylation is regulated are discussed, with particular emphasis on the impact of signalling pathways. A major point of regulation of the SUMO pathway is through targeting the E3 ligases, and a number of different ways to achieve this have been identified. More generally, the MAPK (mitogen-activated protein kinase) pathways represent one way through which SUMOylation of specific proteins is controlled, by using molecular mechanisms that at least in part also function by modifying the activity of SUMO E3 ligases. Further intricacies in signalling pathway interactions are hinted at through the growing number of examples of cross-talk between different post-translational modifications and SUMO modification.
Small ubiquitin-related modifiers in chains
Authors: Vertegaal A.C.O.
Published: January 2008

Post-translational modification of proteins by SUMOs (small ubiquitin-related modifiers) plays an important role in a wide variety of biological processes. The mammalian SUMO family includes three members, SUMO-1, SUMO-2 and SUMO-3. While target proteins are predominantly conjugated to monomeric SUMO, all three SUMO family members are able to multimerize in vitro. In cells, SUMOs have the potential to multimerize via internal consensus sites for SUMOylation that are present in SUMO-2 and SUMO-3. A SUMO-binding motif in Ubc9 (ubiquitin-conjugating enzyme 9) contributes to SUMO chain formation in vitro and SUMO E3 ligases further enhance SUMO polymerization. SUMO chain formation is reversible; SUMO polymers are disassembled by SUMO proteases both in vitro and in vivo. Despite recent progress, the functional relevance of SUMO polymerization is still unclear and little is known about the identity of the endogenous target proteins that are conjugated to SUMO polymers.
SUMOylation-dependent function of a T-box transcriptional repressor in Caenorhabditis elegans
Authors: Crum T.L. , Okkema P.G.
Published: January 2008

T-box transcription factors are crucial developmental regulators, and they have not previously been associated with SUMOylation. In Caenorhabditis elegans, the Tbx2 subfamily member TBX-2 (T-box protein 2) is required for anterior pharyngeal muscle development. TBX-2 interacts with SUMOylation pathway enzymes, and loss of these enzymes phenocopies tbx-2 mutants. We hypothesize that TBX-2 functions as a SUMOylation-dependent transcriptional repressor. TBX-2 contains two consensus SUMOylation sites conserved in many T-box transcriptional repressors, and we suggest that the function of these T-box factors may similarly involve SUMOylation.
Immunostimulatory activity of Toll-like receptor 8 agonists towards human leucocytes: basic mechanisms and translational opportunities
Authors: Philbin V.J. , Levy O.
Published: January 2008

TLR8 (Toll-like receptor 8) is activated by ssRNAs (single-stranded RNAs) and synthetic imidazoquinoline compounds that resemble purines and have immunostimulatory activity. TLR8 agonists are particularly effective at inducing Th1-polarizing responses from human monocytes and myeloid dendritic cells, with the magnitude of response substantially exceeding that induced by agonists of other TLRs. Mechanisms underlying the remarkable efficacy of TLR8 agonists may include: (i) particularly robust activation of intracellular signalling cascades culminating in nuclear translocation of NF-κB (nuclear factor κB), (ii) activation of BTK (Bruton's tyrosine kinase), and (iii) the ability of some imidazoquinolines to induce TLR-independent effects via antagonism of adenosine receptors. The strong agonist activities of TLR8 agonists also extend to human neonatal leucocytes, which usually display impaired Th1-polarizing responses to many diverse stimuli including agonists of other TLRs. Their strong Th1-polarizing properties render TLR8 agonists attractive targets of biopharmaceutical development as agents that may induce protective immune responses in diverse populations, including newborns.
Toll-like receptor (TLR)-based networks regulate neutrophilic inflammation in respiratory disease
Authors: Sabroe I. , Whyte M.K.B.
Published: January 2008

The neutrophil is a crucial early defence against microbial infection, but neutrophilic inflammation can result in devastating acute and chronic inflammatory diseases. In the lungs, the neutrophil is a principal part of the pathology of the acute respiratory distress syndrome, and its activation may also be of substantial importance in chronic obstructive pulmonary disease and some forms of asthma. Induction of neutrophil recruitment in response to microbial attack requires activation of TLR (Toll-like receptor)-based signalling pathways and the concerted actions of multiple cell types, including sentinel cells such as monocytes and macrophages acting together with tissue cell types such as the epithelium or smooth-muscle cell. The present review describes some of these networks and the resulting potential for their targeting in respiratory disease.
Peptidoglycan recognition inDrosophila
Authors: Aggrawal K. , Silverman N.
Published: January 2008

Drosophila rely primarily on innate immune responses to effectively combat a wide array of microbial pathogens. The hallmark of the Drosophila humoral immune response is the rapid production of AMPs (antimicrobial peptides) by the fat body, the insect homologue of the mammalian liver. Production of these AMPs is controlled at the level of transcription by two NF-κB (nuclear factor κB) signalling pathways. The Toll pathway is activated by fungal and many Gram-positive bacterial microbes, whereas the IMD (immune deficiency) pathway responds to Gram-negative bacteria and certain Gram-positive bacilli. In the present review, we discuss the mechanisms involved in bacterial recognition, in particular the differential recognition of various types of bacterial PGN (peptidoglycan) by different members of the PGRP (PGN recognition protein) family of receptors.
Targeting intracellular mediators of pattern-recognition receptor signalling to adjuvant vaccination
Authors: Wales J. , Andreakos E. , Feldmann M. , Foxwell B.
Published: January 2008

PRR (pattern-recognition receptor) signalling is involved early in the immune response and therefore would be attractive to target during vaccination. The use of PRR ligands has shown some success; however, toxicity and non-specificity are issues with this strategy. The targeting of PRR intracellular signalling networks would allow for greater specificity and reduced systemic toxicity. The present review examines the successes seen with overexpression or repression of PRR signalling molecules.
Zymocin, a composite chitinase and tRNase killer toxin from yeast
Authors: Jablonowski D. , Schaffrath R.
Published: January 2008

Growth inhibition of Saccharomyces cerevisiae by the plasmid-encoded trimeric (αβγ) zymocin toxin from dairy yeast, Kluyveromyces lactis, depends on a multistep response pathway in budding yeast. Following early processes that mediate cell-surface contact by the chitinase α-subunit of zymocin, later steps enable import of the γ-toxin tRNase subunit and cleavage of target tRNAs that carry modified U34 (wobble uridine) bases. With the emergence of zymocin-like toxins, continued zymocin research is expected to yield new insights into the evolution of yeast pathosystems and their lethal modes of action.
Prediction of protein stability upon point mutations
Authors: Gromiha M.M.
Published: January 2008

Prediction of protein stability upon amino acid substitution is a challenging problem and it will be helpful for designing stable mutants. We have developed a thermodynamic database for proteins and mutants (ProTherm), which has more than 20000 thermodynamic data along with sequence and structure information, experimental conditions and literature information. It is freely accessible at http://gibk26.bse.kyutech.ac.jp/jouhou/protherm/protherm.html. Utilizing the database, we have analysed the relationship between amino acid properties and protein stability and developed different methods, such as average assignment method, distance and torsion potentials and decision tree models to discriminate the stabilizing and destabilizing mutants, and to predict the stability change upon mutation. Our method could distinguish the stabilizing and destabilizing mutants with an accuracy of 82 and 85% respectively from amino acid sequence and protein three-dimensional structure. We obtained the correlation of 0.70 and 0.87, between the experimental and predicted stability changes upon mutations, from sequence and structure respectively. Furthermore, we have developed different web servers for discrimination and prediction and they are freely accessible at http://bioinformatics.myweb.hinet.net/iptree.htm and http://cupsat.tu-bs.de/.
Enhancement of oligomeric stability by covalent linkage and its application to the human p53tet domain: thermodynamics and biological implications
Authors: Poon G.M.K.
Published: January 2008

The formation of oligomeric proteins proceeds at a major cost of reducing the translational and rotational entropy for their subunits in order to form the stabilizing interactions found in the oligomeric state. Unlike site-directed mutations, covalent linkage of subunits represents a generically applicable strategy for enhancing oligomeric stability by reducing the entropic driving force for dissociation. Although this can be realized by introducing de novo disulfide cross-links between subunits, issues with irreversible aggregation limit the utility of this approach. In contrast, tandem linkage of subunits in a single polypeptide chain offers a universal method of pre-paying the entropic cost of oligomer formation. In the present paper, thermodynamic, structural and experimental aspects of designing and characterizing tandem-linked oligomers are discussed with reference to engineering a stabilized tetramer of the oligomerization domain of the human p53 tumour-suppressor protein by tandem dimerization.
Cross-linked enzyme aggregates (CLEA®s): stable and recyclable biocatalysts
Authors: Sheldon R.A.
Published: January 2008

The key to obtaining an optimum performance of an enzyme is often a question of devising an effective method for its immobilization. In the present review, we describe a novel, versatile and effective methodology for enzyme immobilization as CLEAs (cross-linked enzyme aggregates). The method is exquisitely simple (involving precipitation of the enzyme from aqueous buffer followed by cross-linking of the resulting physical aggregates of enzyme molecules) and amenable to rapid optimization. We have shown it to be applicable to a wide variety of enzymes, including, in addition to a wide variety of hydrolases, lyases, e.g. nitrile hydratases and oxynitrilases, and oxidoreductases such as laccase and galactose oxidase. CLEAs are stable, recyclable catalysts exhibiting high catalyst productivities. Because the methodology is essentially a combination of purification and immobilization into one step, the enzyme does not need to be of high purity. The technique is also applicable to the preparation of combi-CLEAs, containing two or more enzymes, for use in one-pot, multistep syntheses, e.g. an oxynitrilase/nitrilase combi-CLEA for the one-pot conversion of benzaldehyde into (S)-mandelic acid, in high yield and enantiomeric purity.
Cation and strong co-solute effects on protein kinetic stability
Authors: Broering J.M. , Bommarius A.S.
Published: January 2008

Degradation of proteins is important for the operating life of biocatalysts and the shelf life of protein pharmaceuticals. We have previously found that the deactivating effects of salts on proteins can be correlated to an indicator of ion hydration, the B-viscosity coefficient of the anion in solution. Here, we test the influence of cations on protein kinetic stability by observing deactivation of mRFP (monomeric red fluorescent protein) in ammonium, caesium and chloride salt solutions, and we find that mRFP deactivation does not depend on cation hydration. We also measure mRFP deactivation in solutions containing denaturants (guanidinium chloride or urea) or stabilizing co-solutes (glycerol or sucrose) frequently encountered in many protein formulations to test whether hydration of these co-solutes can be used to indicate their relative effects on protein kinetic stability. We find that mRFP deactivation in solutions containing kosmotropic salts or stabilizers reaches a limiting rate and that hydration of denaturants is not an indicator of their denaturing strength.
Control of protein translation by phosphorylation of the mRNA 5′-cap-binding complex
Authors: Pierrat O.A. , Mikitova V. , Bush M.S. , Browning K.S. , Doonan J.H.
Published: January 2008

Initiation of mRNA translation is a key regulatory step in the control of gene expression. Microarray analysis indicates that total mRNA levels do not always reflect protein levels, since mRNA association with polyribosomes is necessary for protein synthesis. Phosphorylation of translation initiation factors offers a cost-effective and rapid way to adapt to physiological and environmental changes, and there is increasing evidence that many of these factors are subject to multiple regulatory phosphorylation events. The present article focuses on the nature of reversible phosphorylation and the function of the 5′-cap-binding complex in plants.
Impairment of the antioxidant properties of serum albumin in patients with diabetes: protective effects of metformin
Authors: Faure Patrice , Wiernsperger Nicolas , Polge Camille , Favier Alain , Halimi Serge
Published: January 2008

Free radical production is increased during diabetes. Serum albumin is a major antioxidant agent, and structural modification of albumin induced by glucose or free radicals impairs its antioxidant properties. Therefore the aim of the present study was to compare the antioxidant capacities and structural changes in albumin in patients with T2DM (Type 2 diabetes mellitus) treated with MET (metformin) or SU (sulfonylureas) and in healthy control subjects. Structural changes in albumin were studied by fluorescence quenching in the presence of acrylamide. Albumin thiols and fructosamines, reflecting oxidized and glycation-induced changes in serum albumin respectively, were assessed. Structural changes in albumin were demonstrated by a significant decrease in fluorescence quenching in patients with T2DM, with patients treated with MET exhibiting a significant difference in the conformation of albumin compared with patients treated with SU. Oxidation, resulting in a significant decrease in thiol groups and plasma total antioxidant capacity, and glycation, associated with a significant increase in fructosamines, were both found when comparing healthy control subjects with patients with T2DM. When patients treated with MET were compared with those treated with SU, oxidative stress and glycation were found to be significantly lower in MET-treated patients. In conclusion, patients with T2DM have a decrease in the antioxidant properties of serum albumin which may aggravate oxidative stress and, thus, contribute to vascular and metabolic morbidities. Moreover, a significant protection of albumin was found in patients with T2DM treated with MET.
New Global Fractal Formalism Describes Paths to Turbulence
Authors: Levi Barbara G.
Published: January 2008

One motivation for the intensive study of nonlinear physical systems is the hope that, despite their complex structures, they might possess universal features shared by entire classes of similar nonlinear processes. This hope was strikingly realized several years ago when Mitchell Feigenbaum (then at Los Alamos, now at Cornell) discovered that a few universal ratios—independent of any dynamical details—characterized all systems whose periods doubled repeatedly as they approached turbulence (PHYSICS TODAY, March 1981, page 17). At the point of infinite period doubling, the orbits of Feigenbaum's system showed a complex behavior in which one could discern a scale-invariant, or fractal, structure. Recently a team of theorists has developed a method for describing a new global structure of these fractal objects. The predictions generated by this formalism agree quite well with experimental measurements performed at the University of Chicago on a fluid as it approached turbulence by two distinct paths.
General Streaming of Galaxies Seen Out to 100 Mpc
Authors: Andersen Per H.
Published: January 2008

It is a canon of cosmology that on a large scale the universe is homogeneous and isotropic. If you peer out far enough, it should look about the same in all directions. During the last several months, astrophysicists have been wrestling with the serious implications of observations indicating that locally the expansion of the universe may not be uniform in every direction, even when we look out as far as a hundred million parsecs. Last January at a NATO workshop in Hawaii, an international group of seven astrophysicists claimed to have found observational evidence for a bulk streaming motion of the galaxies throughout our extended neighborhood—out to much larger distances than expected.
Soviets Assess Cause of Chernobyl Accident
Authors: Levi Barbara Goss
Published: January 2008

Some—but by no means all—of the Chernobyl story can now be told. Soviet scientists have assembled enough information from interviews, plant records and computer simulations to describe the chronology of events leading to a severe accident that destroyed a nuclear reactor at Chernobyl on 26 April and spread radiation over much of Europe. A Soviet delegation of 28 specialists headed by V. A. Legasov (Kurchatov Institute) presented a very frank report on the accident's causes and consequences to an experts' meeting sponsored by the International Atomic Energy Agency in Vienna on 25–29 August. Their report places heavy blame on the reactor staff for committing numerous violations of operating rules, one of which left the reactor operating at a power level where the consequences of further violations were greatly exacerbated.
Effect of nanoscale confinement on the β−α phase transition in Ag2Se
Authors: Leon Vincent , Ren Yang , Saboungi Marie-Louise
Published: January 2008

The confinement of silver selenide was investigated using mesoporous silica. Results from x-ray diffraction and electron microscopy show that the confined material still exhibits a β−α transition similar to the one that takes place in the bulk crystalline state but with a transition temperature that depends significantly on the confinement conditions. Decreasing the pore size leads to an increase of the transition temperature, opposite to the behavior of the melting point observed in several metallic and organic materials. In the free particles, on the other hand, no size dependence is observed with particle sizes down to 4 nm.
Reports on Subfields of Physics: Atomic, Molecular and Optical Physics
Authors: Schechter Bruce
Published: January 2008

Atomic, molecular and optical physics encompasses a broad range of theoretical and experimental research on matter at the atomic and molecular level and on light. In the United States it is pursued by over 300 small groups in university, national and industrial laboratories. Advances in this branch of physics not only add to our understanding of the basic laws of physics but lead to new instruments and techniques vital to other areas of science, to industry and to national programs. In their report the Panel on Atomic, Molecular and Optical physics has proposed a program of research initiatives intended to support scientific innovation and to provide an environment for rapid scientific advance. But the panel is quick to point out that in attempting to predict the most promising avenues for scientific advancement one is likely to miss whole new boulevards. The panel admits that had it met ten years ago it would have failed to mention or would have seriously underestimated many important developments: laser cooling of atoms and ions, low-energy highly charged ions, transient molecular states, Rydberg atoms, molecular clusters, four-wave mixing, phase conjugation, ultrasensitive detection. “Nevertheless,” writes the panel, “we believe that the program of research initiatives represents a realistic basis for scientific advance in the near future.” The research initiatives include:
Foreign Physics Graduate Students in the United States
Authors: McDermott Mark N. , Thomas Edward W.
Published: January 2008

The proportion of foreign citizens among first-year physics graduate students in the US has now reached 42%. up from 17% in 1971. This dramatic increase has drawn attention to a wide range of issues, including the following:

▸ The very small number of US-born students who seek higher degrees in physics. Fewer than 800 US citizens a year, from a population of over 230 million, complete PhDs in physics.

▸ The balance between theorists and experimenters in physics. Half of the growing number of new foreign-student PhDs are theorists, yet for every physicist hired to do theoretical work, three are hired to do experimental work. What will happen when large numbers of theorists graduate in the next five years?
Beyond the Ivory Tower
Authors: Schechter Bruce M.
Published: January 2008

The industrial research laboratory was arguably Thomas Alva Edison's greatest invention. With more ideas than time to pursue them, Edison built a laboratory in Menlo Park, New Jersey, and staffed it with the brightest young men he could find. They were, for the most part, self-taught like himself: He had little patience with universities, having once defined an academic scientist as “a man who would boil his watch while holding onto an egg.” But if he was nothing else, Edison was an experimenter. From time to time he hired an academic scientist. The results were mixed. He said of one:

He knows a lot but he doesn't stick to the job. I set him at work developing details of a plan. But when he happens to note some phenomenon new to him, though easily seen to be of no importance in this apparatus, he gets sidetracked, follows it up and loses time. We can't be spending time that way! We have got to keep working up things of commercial value—that is what this laboratory is for. We can't be like the old German professor who as long as he can get his black bread and beer is content to spend his whole life studying the fuzz on a bee!
Diffraction Gratings at the Mount Wilson Observatory
Authors: Babcock Horace W.
Published: January 2008

The past century has seen major advances in diffraction gratings, motivated by pressure for new and better data in two rather distinct fields: laboratory spectroscopy—aimed at understanding atomic structure and testing quantum theory—and astrophysical spectroscopy—aimed at understanding objects ranging from the Sun and stars to faint sources at the limit of detection. In this historical account I trace some of the hard-won gains in the technology of the ruling machines that produce the gratings, and I touch on the role that larger and higher-quality gratings have played in scientific advances. I focus on the work at the Mount Wilson Observatory, where I directed the diffraction-grating laboratory from 1948 to 1963, but I do so with full recognition of the important contributions made at numerous other laboratories, especially those at The Johns Hopkins University, the Massachusetts Institute of Technology and the Bausch & Lomb Optical Company.
Retarded, or Casimir, Long-Range Potentials
Authors: Spruch Larry
Published: January 2008

Only someone with a short-range view could fail to be aware of the great importance of long-range interactions. Indeed, from the late 18th century, when Coulomb discovered that the electrostatic interaction has the same 1/r2 force law that Newton had found for the gravitational interaction, until perhaps the 1930s, when the strong and weak interactions began to be understood, long-range interactions largely were the subject of physics. By long-range interactions I mean not only those for which the potential behaves as 1/r for all r but those whose potentials behave asymptotically as some power of 1/r. These originate in 1/r potentials and include, for example, the van der Waals 1/r6 interaction (as calculated nonrelativistically) between two spherically symmetric atoms at a large separation r, and multipole interactions between charge distributions. Long-range potentials therefore not only play a vital role in astrophysics via Newton's law of gravitation and a significant role in nuclear physics via Coulomb's law, but determine almost all of atomic, molecular and condensed-matter physics.
Popular and Unpopular Ideas in Particle Physics
Authors: Perl Martin L.
Published: January 2008

I finished writing this article while the 23rd International Conference on High-Energy Physics was taking place in Berkeley. California. It was a wellorganized conference with a variety of theoretical talks, comprehensive plenary lectures and many reports on new experiments. Yet the atmosphere of the conference could be summed up in one word: waiting. The participants knew that no major experimental or theoretical advance in particle physics was to be announced at this conference. They listened to the experimental and theoretical results, but they were prepared to wait until the next conference for a breakthrough.
Hideki Yukawa and the Meson Theory
Authors: Brown Laurie M.
Published: January 2008

A little over 50 years ago, Hideki Yukawa, a young Japanese theoretical physicist at the University of Osaka, proposed a fundamental theory of nuclear forces involving the exchange of massive charged particles between neutrons and protons. He called the exchanged particles “heavy quanta” to distinguish them from the light quanta of the electromagnetic field, but now they are known as pions, the lightest members of a large family of particles called mesons. These days, the meson theory seems to be a straightforward application of quantum field theory to the nuclear forces, but it could not have appeared so 50 years ago. Otherwise it would not have been invented by an obscure, unpublished Japanese physicist who had never even traveled abroad, but instead by one of the many Western physicists, some of them of great reputation, who were working on the theory of nuclear forces. Furthermore, Yukawa's paper was totally neglected for more than two years, although it was written in lucid English and published in a respected journal of rather wide circulation. The meson theory has turned out to be an important paradigm for the theory of elementary particles, as seminal as Ernest O. Lawrence's cyclotron has been for its experimental practice. In this article I will trace the intellectual trail Yukawa followed to arrive at his theory, using unpublished documents that have recently been discovered among Yukawa's papers at Kyoto University. (These documents have been organized and cataloged in the Yukawa Hall Archival Library, and I am grateful to Rokuo Kawabe and Michiji Konuma for translations and comments.)
New Technology for Science: Where Will it Come From?
Authors: Branscomb Lewis M.
Published: January 2008

This is a watershed time in the relationship of American science and engineering to the nation's future, for many circumstances have changed since basic US science policy was set in the 1950s. More than ever, the cornerstone of our science policy must be a national commitment to excellence in both science and engineering.
Josephson Computer Technology
Authors: Hayakawa Hisao
Published: January 2008

In 1962 Brian Josephson predicted that a current of superconducting electron pairs could tunnel through an insulating junction between two superconductors while maintaining the phase coherence of the pairs’ wavefunctions on the two sides of the junction; the effect was soon experimentally verified. Such Josephson junctions can switch rapidly to the resistive state and have very low power dissipation, properties that suggest the application of Josephson junctions to computers. IBM started investigating superconducting computers, using Josephson junctions for memories and logic circuits, in 1964. Juri Matisoo and his colleagues at IBM demonstrated a logic circuit with subnanosecond operation in 1966. At the time, this switching speed was very attractive, for it indicated that Josephson devices could be competitive with semiconductor devices.