bluuebunny/crossref_metadata_2025 huggingface dataset:
NMR relaxation study of molecular motions between unequal potential wells in solid t
r
a
n
s,t
r
a
n
s-muconodinitrile
Authors: Polak Micha , Ailion David C.
Published: February 2003

We report observations of extremely unusual proton NMR relaxation rates in solid trans,trans-muconodinitrile (TMD, N≡C–CH=CH–CH=CH–C≡N). In particular we measured, over the temperature range 77–423 °K, proton dipolar relaxation times T1D and spin lattice relaxation times T1 (at 24 and 58 MHz). The relaxation pattern is characterized by the following features: (a) very long motional T1 and T1D even at their respective minima, (b) no detectable motional narrowing of the line even at the T1D minimum, (c) unequal slopes at temperatures below and above the minimum of T1 (and T1D) vs 1/T, and (d) significant deviations from the usual linear dependence on resonance frequency of the values of the relaxation times at their respective minima. We extended an earlier NMR theory to the case of spin lattice relaxation due to molecular reorientations between the extremely unequal potential energy wells of TMD. We were able to explain all features of the above data in terms of this theory. By comparing our data to the results of several calculations of intermolecular potential energy which used different interatomic force parameters, we were able to rule out some of these, thereby determining the best choice for the parameters in this crystal. The detailed structure of this potential profile (i.e., relative depths of the wells and energy barriers hindering rotation) was then determined from the T1 and T1D data. We thus have observed and characterized in TMD a low concentration of orientational defects which occur when a molecule occupies a higher energy well. Our observations are probably the first of such extreme NMR relaxation effects due to motions between significantly inequivalent sites.
MCD of the Eu3+ ion in aqueous solution. Analysis of the 5D0,1,2←7F0,1,2 transitions
Authors: Görller-Walrand C. , Godemont J.
Published: February 2003

An electric or magnetic dipole character is assigned to the transitions in the visible region of the Eu3+ absorption spectrum. The theoretical calculation of the sign properties of the corresponding Faraday parameters is supported by the experimental MCD of the aqueous solution. It is shown that the magnetic circular dichroism of all the considered transitions points to a D3h symmetry of the hydrated Eu3+ ion.
Determination of state resolved rotationally inelastic cross sections: LiH(j=1) –Ar
Authors: Wilcomb Bruce E. , Dagdigian Paul J.
Published: February 2003

Laser induced fluorescence is used to determine rotationally inelastic relative integral cross sections for collisions of state-selected Litt with Ar.(AIP)
Absolute rate constant for the reaction of atomic chlorine with hydrogen peroxide vapor over the temperature range 265–400 K
Authors: Michael J.V. , Whytock D.A. , Lee J.H. , Payne W.A. , Stief L.J.
Published: February 2003

Rate constants for the reaction of atomic chlorine with hydrogen peroxide have been measured from 265 to 400 K using the flash photolysis–resonance fluorescence technique. Analytical techniques were developed to measure [H2O2] under reaction conditions. Due to ambiguity in the interpretation of the analytical results, the data combine to give two equally acceptable representations of the temperature dependence: k1= (3.14±0.56) ×10−13 cm3 molecule−1 s−1 independent of temperature or k1= (1.24±0.74) ×10−12 exp(−384±168/T)cm3 molecule−1 s−1. The results are compared to previous work at 298 K and are theoretically discussed in terms of the mechanism of the reaction. Additional experiments on the H+H2O2 reaction at 298 and 359 K are compared with earlier results from this laboratory and give a slightly revised bimolecular rate constant of (4.89±0.70) ×10−12 exp(−2780±280/RT) cm3 molecule−1 s−1.
Decline of the self-focusing of a pulsed high intensity electron beam owing to gas breakdown
Authors: Hotta Hiroshi , Arai Hidehiko
Published: February 2003

The self-focusing of a pulsed high-intensity electron beam in a gas declines in the intermediate pressure region owing to gas breakdown. The degree of the self-focusing of a beam from a Febetron 706 in monatomic gases increases by increasing the breakdown time (tB), which is defined as the time when the plasma conductivity becomes 10 mho/cm. Secondary electrons are consumed appreciably in polyatomic gases after tB through their reactions with ions and neutral molecules. Therefore, in such gases, the amount of the consumption must be estimated to analyze the self-focusing. For the estimation of the consumption, we must remark that the mean energy of secondary electrons is quite different between before and after tB because of the different strength of induced longitudinal electric field. As a result of the numerical analyses, we obtain the equation tB−tN =12/w (α−η) (tN is neutralization time, w is electron drift velocity, α is the first Townsend ionization coefficient, and η is the electron attachment coefficient). Since η is usually negligibly small before tB and tN is also negligibly small above a certain pressure, tB is approximately inversely proportional to wα. The tB in polyatomic gases, however, must be corrected for the consumption described above.
High-order ESR transitions of the weak trigonal Gd3+ ESR center in alkaline-earth-fluoride crystals
Authors: Lee Sook , Yang Chi-Chung
Published: February 2003

The ESR spectra obtained from single crystals of BaF2 and SrF2 containing the weak trigonal Gd3+ ESR center exhibited many weak lines at the low-magnetic-field side of its allowed (ΔM=±1) fine-structure lines. These low-field lines were found to arise from the high-order (ΔM≳±1) ESR transitions of the weak trigonal Gd3+ center.
Studies of the luminescence efficiency of tungstate and molybdate phosphors as a function of temperature and high pressure
Authors: Tyner C. E. , Drickamer H. G.
Published: February 2003

Studies have been made of the luminescence properties of three molybdate and three tungstate phosphors as a function of temperature and pressure. The data include peak energy, half-width, peak shape (skewness), luminescent lifetime, and integrated intensity. The modifications of the high pressure luminescence technique which permit these measurements, especially of the intensities as a function of temperature and pressure, are described. The data are analyzed in terms of a quantum mechanical single configuration coordinate model developed by Struck and Fonger. For most of the compounds studied the changes of intensity and lifetime can be reasonably correlated with the observed changes in peak energy and shape.
NMR study of angular momentum relaxation in fluids. II. Mixtures of CF4 with inert gases
Authors: Wolfe M. , Arndt E. , Jonas J.
Published: February 2003

The effects of density and temperature on the angular momentum correlation time, τJ, in binary fluid mixtures of CF4 with Ar and Ne, respectively, are reported. The 19F spin–lattice relaxation times, T1, were measured at 56.4 MHz for 0.1, 0.25, and 0.6 mole fraction CF4 in Ar and Ne from 273 to 373 °K and pressures up to 2040 atm. The spin-rotation interactions provide the dominant relaxation mechanism for the fluorine nuclei. The experimental τJ data for CF4 infinitely dilute in Ar and Ne in the high density region (ρ≳2ρc) are successfully interpreted in terms of the rough hard sphere model (RHSM) modified for use in binary mixtures. The values of the parameter a12 characterizing the collisional efficiency of angular momentum transfer are obtained for CF4–Ar and CF4–Ne systems. The variation of τJ with mole fraction in these binary mixtures in the dense fluid region was also successfully interpreted in terms of the RHSM indicating that attractive forces are not important in determining the magnitude of the collisional efficiencies aij. At intermediate and low densities, τJ as a function of mole fraction deviates from the RHSM. As in Paper I, these deviations are interpreted in terms of the effect of attractive forces on the radial distribution function at contact.
Importin β-depending Nuclear Import Pathways: Role of the Adapter Proteins in the Docking and Releasing Steps
Authors: Rollenhagen Christiane , Mühlhäusser Petra , Kutay Ulrike , Panté Nelly
Published: February 2003

Nuclear imports of uridine-rich small nuclear ribonucleoprotein (U1 snRNP) and proteins with classical nuclear localization signal (cNLS-protein) are mediated by importin β. However, due to the presence of different import signals, the adapter protein of the imported molecules and importin β is different for each pathway. Although the adapter for cNLS-protein is importin α, the adapter for U1 snRNP is snurportin1 (SPN1). Herein, we show that the use of distinct adapters by importin β results in differences at the docking and releasing step for these two import pathways. Nuclear pore complex (NPC) docking of U1 snRNP but not of cNLS-protein was inhibited by an anti-CAN/Nup214 antibody. Thus, the initial NPC-binding site is different for each pathway. Pull-down assays between immobilized SPN1 and two truncated forms of importin β documented that SPN1 and importin α have different binding sites on importin β. Importin β fragment 1–618, which binds to SPN1 but not to importin α, was able to support the nuclear import of U1 snRNPs. After the translocation through the NPC, both import complexes associated with the nuclear side of the NPC. However, we found that the nature of the importin β-binding domain of the adapters influences the release of the cargo into the nucleoplasm.
Endocytosis of a Glycosylphosphatidylinositol-anchored Protein via Clathrin-coated Vesicles, Sorting by Default in Endosomes, and Exocytosis via RAB11-positive Carriers
Authors: Grünfelder Christoph G. , Engstler Markus , Weise Frank , Schwarz Heinz , Stierhof York-Dieter , Morgan Gareth W. , Field Mark C. , Overath Peter
Published: February 2003

Recently, proteins linked to glycosylphosphatidylinositol (GPI) residues have received considerable attention both for their association with lipid microdomains and for their specific transport between cellular membranes. Basic features of trafficking of GPI-anchored proteins or glycolipids may be explored in flagellated protozoan parasites, which offer the advantage that their surface is dominated by these components. In Trypanosoma brucei, the GPI-anchored variant surface glycoprotein (VSG) is efficiently sorted at multiple intracellular levels, leading to a 50-fold higher membrane concentration at the cell surface compared with the endoplasmic reticulum. We have studied the membrane and VSG flow at an invagination of the plasma membrane, the flagellar pocket, the sole region for endo- and exocytosis in this organism. VSG enters trypanosomes in large clathrin-coated vesicles (135 nm in diameter), which deliver their cargo to endosomes. In the lumen of cisternal endosomes, VSG is concentrated by default, because a distinct class of small clathrin-coated vesicles (50–60 nm in diameter) budding from the cisternae is depleted in VSG. TbRAB11-positive cisternal endosomes, containing VSG, fragment by an unknown process giving rise to intensely TbRAB11- as well as VSG-positive, disk-like carriers (154 nm in diameter, 34 nm in thickness), which are shown to fuse with the flagellar pocket membrane, thereby recycling VSG back to the cell surface.
PDP: protein domain parser
Authors: Alexandrov Nickolai , Shindyalov Ilya
Published: February 2003

Summary: We have developed a program for automatic identification of domains in protein three-dimensional structures. Performance of the program was assessed by three different benchmarks: (i) by comparison with the expert-curated SCOP database of structural domains; (ii) by comparison with a collection of manual domain assignments; and (iii) by comparison with a set of 55 proteins, frequently used as a benchmark for automatic domain assignment. In all these benchmarks PDP identified domains correctly in more than 80% of proteins.

Availability: http://123d.ncifcrf.gov/

Contact: nicka@ceres-inc.comshindyal@sdsc.edu

* To whom correspondence should be addressed.
No Yin without its Yang
Authors: Rabey Gordon
Published: February 2003

The pressures on managers today are increasing and what was current yesterday may be quite different from the uncertainties of tomorrow. Top level leadership may be transient and organisational structures are changing but one element of constancy is probably that most people at work continue to report to a direct manager for task assignment, even if not within the traditional hierarchical patterns. Many managers seem not to be fully aware of the latent power of this human resource and of its potential for strengthening their own positions. Makes the point that the effectiveness of managers in achieving results can be improved significantly by building and developing a closer linkage with those people who actually do the work. Gives illustrative examples and suggests a funnel shape organisation.
Learning and development in action learning: the energy investment model
Authors: Edmonstone John
Published: February 2003

In action learning sets participants bring their personal energy and attitudes. These produce identifiable behaviour styles (not types of people). In the energy investment model four behaviour styles of set members are identified, showing participants’ typical feelings and reactions, the support needed and what helpful questions may be.
Forum for organisational learning: combining learning at work, organisational learning and training in new ways
Authors: Simons P.R.J. , Germans J. , Ruijters M.
Published: February 2003

A new initiative has been taken that aims to combine learning at work, training and organisational learning and change. In this “Forum for organisational learning”, scientists, organisational advisors and practitioners cooperate in new ways in order to reach new goals: improving organisational learning, workplace learning and training and especially their alignment. In the Forum organisations meet each other in order to learn from their experiences with individual, team and organisational learning. Each organisation is represented by at least two and preferably three or more representatives, fulfilling different roles. Some, the thinkers, follow a full master program. Others, the do‐ers, follow only part of this program, but work within the organisation focusing on organisational learning and workplace learning. Finally, in each organisation there is a responsible manager who sponsors the internal organisational process. In the program, five paradoxes of learning form the core content: how to combine top‐down and bottom‐up approaches for strategy formation, how to combine learning and working, how to combine individual and organisational ambitions, how to combine structure and empowerment in leading teams and individuals, and how to combine motivational approaches with approaches directed resistance reduction.
Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal
Authors: Narayanan Krishna , Chen Chun-Jen , Maeda Junko , Makino Shinji
Published: February 2003

For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) protein is the first step described in the process of viral RNA packaging. In the murine coronavirus a selective interaction between the viral transmembrane envelope protein M and the viral ribonucleoprotein complex, composed of N protein and viral RNA containing a short
cis
-acting RNA element, the packaging signal, determines the selective RNA packaging into virus particles. In this report we show that expressed coronavirus envelope protein M specifically interacted with coexpressed noncoronavirus RNA transcripts containing the short viral packaging signal in the absence of coronavirus N protein. Furthermore, this M protein-packaging signal interaction led to specific packaging of the packaging signal-containing RNA transcripts into coronavirus-like particles in the absence of N protein. These findings not only highlight a novel RNA packaging mechanism for an enveloped virus, where the specific RNA packaging can occur without the core or N protein, but also point to a new, biologically important general model of precise and selective interaction between transmembrane proteins and specific RNA elements.
Simian-Human Immunodeficiency Virus SHIV89.6-Induced Protection against Intravaginal Challenge with Pathogenic SIVmac239 Is Independent of the Route of Immunization and Is Associated with a Combination of Cytotoxic T-Lymphocyte and Alpha Interferon Responses
Authors: Abel Kristina , Compton Lara , Rourke Tracy , Montefiori David , Lu Ding , Rothaeusler Kristina , Fritts Linda , Bost Kristen , Miller Christopher J.
Published: February 2003

Attenuated primate lentivirus vaccines provide the most consistent protection against challenge with pathogenic simian immunodeficiency virus (SIV). Thus, they provide an excellent model to examine the influence of the route of immunization on challenge outcome and to study vaccine-induced protective anti-SIV immune responses. In the present study, rhesus macaques were immunized with live nonpathogenic simian-human immunodeficiency virus (SHIV) 89.6 either intravenously or mucosally (intranasally or intravaginally) and then challenged intravaginally with pathogenic SIVmac239. The route of immunization did not affect mucosal challenge outcome after a prolonged period of systemic infection with the nonpathogenic vaccine virus. Further, protection from the SIV challenge was associated with the induction of multiple host immune effector mechanisms. A comparison of immune responses in vaccinated-protected and vaccinated-unprotected animals revealed that vaccinated-protected animals had higher frequencies of SIV Gag-specific cytotoxic T lymphocytes and gamma interferon (IFN-γ)-secreting cells during the acute phase postchallenge. Vaccinated-protected animals also had a more pronounced increase in peripheral blood mononuclear cell IFN-α mRNA levels than did the vaccinated-unprotected animals in the first few weeks after challenge. Thus, innate as well as cellular anti-SIV immune responses appeared to contribute to the SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239.
Duplication of U3 Sequences in the Long Terminal Repeat of Mink Cell Focus-Inducing Viruses Generates Redundancies of Transcription Factor Binding Sites Important for the Induction of Thymomas
Authors: DiFronzo Nancy L. , Frieder Marisa , Loiler Scott A. , Pham Quynh N. , Holland Christie A.
Published: February 2003

The ability of mink cell focus-inducing (MCF) viruses to induce thymomas is determined, in part, by transcriptional enhancers in the U3 region of their long terminal repeats (LTRs). To elucidate sequence motifs important for enhancer function in vivo, we injected newborn mice with MCF 1dr (supF), a weakly pathogenic, molecularly tagged (supF) MCF virus containing only one copy of a sequence that is present as two copies (known as the directly repeated [DR] sequence) in the U3 region of MCF 247 and analyzed LTRs from supF-tagged proviruses in two resulting thymomas. Tagged proviruses integrated upstream and in the reverse transcriptional orientation relative to c
-myc
provided the focus of our studies. These proviruses are thought to contribute to thymoma induction by enhancer-mediated deregulation of c-
myc
expression. The U3 region in a tagged LTR in one thymoma was cloned and sequenced. Relative to MCF 1dr (supF), the cloned U3 region contained an insertion of 140 bp derived predominantly from the DR sequence of the injected virus. The inserted sequence contains predicted binding sites for transcription factors known to regulate the U3 regions of various murine leukemia viruses. Similar constellations of binding sites were duplicated in two proviral LTRs integrated upstream from c-
myc
in a second thymoma. We replaced the U3 sequences in an infectious molecular clone of MCF 247 with the cloned proviral U3 sequences from the first thymoma and generated an infectious chimeric virus, MCF ProEn. When injected into neonatal AKR mice, MCF ProEn was more pathogenic than the parental virus, MCF 1dr (supF), as evidenced by the more rapid onset and higher incidence of thymomas. Molecular analyses of the resultant thymomas indicated that the U3 region of MCF ProEn was genetically stable. These data suggest that the arrangement and/or redundancy of transcription factor binding sites generated by specific U3 sequence duplications are important to the biological events mediated by MCF proviruses integrated near c-
myc
that contribute to transformation.
Identification of Serum Soluble ST2 Receptor as a Novel Heart Failure Biomarker
Authors: Weinberg Ellen O. , Shimpo Masahisa , Hurwitz Shelley , Tominaga Shin-ichi , Rouleau Jean-Lucien , Lee Richard T.
Published: February 2003

Background—

Using genomic technology, we previously identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes. The soluble receptor form of ST2 is secreted and detectable in human serum. This study tested the hypothesis that soluble ST2 levels in the serum of patients with severe chronic heart failure are increased in patients with neurohormonal activation.

Methods and Results—

Serum samples, clinical variables, and neurohormone levels from the PRAISE-2 heart failure trial (NYHA functional class III-IV; end point, mortality or transplantation) were analyzed. ST2 serum measurements were performed with ELISA on samples from 161 patients obtained at trial enrollment and from 139 of the same patients obtained 2 weeks after trial enrollment. Baseline ST2 levels were correlated with baseline B-type natriuretic peptide (BNP) levels (
r
=0.36,
P
<0.0001), baseline proatrial natriuretic peptide (ProANP) levels (
r
=0.36,
P
<0.0001), and baseline norepinephrine levels (
r
=0.39,
P
<0.0001). The change in ST2 was significant as a univariate predictor of subsequent mortality or transplantation (
P
=0.048), as was baseline BNP (
P
<0.0001) and baseline ProANP (
P
<0.0001). In multivariate models including BNP and ProANP, the change in ST2 remained significant as a predictor of mortality or transplantation independent of BNP and ProANP.

Conclusions—

Serum soluble ST2 is a novel biomarker for neurohormonal activation in patients with heart failure. In patients with severe chronic NYHA class III to IV heart failure, the change in ST2 levels is an independent predictor of subsequent mortality or transplantation.
Local Drug Delivery via a Coronary Stent With Programmable Release Pharmacokinetics
Authors: Finkelstein Ariel , McClean Dougal , Kar Saibal , Takizawa Kaname , Varghese Kiron , Baek Namjin , Park Kinam , Fishbein Michael C. , Makkar Raj , Litvack Frank , Eigler Neal L.
Published: February 2003

Background—

Fixed drug release kinetics and vessel wall partitioning may limit the effectiveness of drug-eluting stents. We report preliminary experience using a new coronary stent with programmable pharmacokinetics.

Methods and Results—

A newly designed metallic stent contains honeycombed strut elements with inlaid stacked layers of drug and polymer. In vitro studies evaluated recipes for loading paclitaxel to establish the parameters for controlling drug release. Manipulation of the layers of biodegradable polymer and drug allowed varying of the initial 24-hour burst release of paclitaxel from 69% to 8.6% (
P
<0.0001). Late release of drug could be adjusted dependently or independently of early burst release. A biphasic release profile was created by the addition of blank layers of polymer within the stack. In the 30-day porcine coronary model (n=17 pigs), there was a 70% reduction in late loss (0.3±0.5 versus 1.0±0.5 mm,
P
=0.04), a 28% increase in luminal volume (132±12 versus 103±21 mm
3
,
P
=0.02), and a 50% decrease in histological neointimal area (2.0±0.5 versus 4.0±1.6 mm
2
;
P
<0.001) compared with bare metal controls. Temporal and regional variations in vascular healing were seen histologically.

Conclusions—

Layered polymer/drug inlay stent technology permits flexible and controllable pharmacokinetic profiles. Programmable, complex chemotherapy using this approach may be feasible for the treatment of cardiovascular disease.
Cardioprotective Effect of Diazoxide Is Mediated by Activation of Sarcolemmal but Not Mitochondrial ATP-Sensitive Potassium Channels in Mice
Authors: Suzuki Masashi , Saito Tomoaki , Sato Toshiaki , Tamagawa Masaji , Miki Takashi , Seino Susumu , Nakaya Haruaki
Published: February 2003

Background—

We recently demonstrated that the sarcolemmal ATP-sensitive potassium (sarcK
ATP
) channel plays a key role in cardioprotection against ischemia/reperfusion injuries in Kir6.2-knockout (KO) mice. In the present study, we evaluated the effects of diazoxide, a mitochondrial ATP-sensitive potassium (mitoK
ATP
) channel opener, on ischemia-induced myocardial stunning in sarcK
ATP
channel-deficient mice.

Methods and Results—

Langendorff-perfused hearts of wild-type (WT) and KO mice were subjected to global ischemia/reperfusion. Diazoxide improved the recovery of contractile function in WT hearts but not in KO hearts. Treatment with HMR1098 (a sarcK
ATP
channel blocker) but not 5-hydroxydecanoate (a mitoK
ATP
channel blocker) abolished the cardioprotective effect of diazoxide in WT hearts. In coronary-perfused WT ventricular muscle preparations, action potential shortening during ischemia was accelerated in the presence of diazoxide.

Conclusions—

Diazoxide enhances action potential shortening during ischemia by activating sarcK
ATP
channels and provides cardioprotection in mouse hearts.
Both B and T lymphocytes may be clonally involved in myelofibrosis with myeloid metaplasia
Authors: Reeder Terra L. , Bailey Richard J. , Dewald Gordon W. , Tefferi Ayalew
Published: February 2003

A combination of magnetic cell sorting (MACS) and fluorescent in situ hybridization (FISH) techniques was used to detect clonal cytogenetic markers in different myeloid and lymphoid cell types of the peripheral blood from 4 patients with myelofibrosis with myeloid metaplasia (MMM) that was associated with either a 13q− or a 20q− karyotypic abnormality. Interphase cytogenetics studies demonstrated abnormal clonal FISH signal patterns in neutrophil, myeloid, erythroid, megakaryocyte, and B- and T-cell preparations in 3 of the 4 patients. In one patient, FISH results were within normal limits in T cells and slightly abnormal in B cells. In general, the percentage of abnormal nuclei was variable in both lymphocyte populations but always higher in B lymphocytes compared with T lymphocytes. The current study provides direct evidence for the clonal involvement of both B and T lymphocytes in MMM. A larger study is needed to clarify the relevance of the observed interpatient heterogeneity in clonal constitution.
Insights into leukocyte adhesion deficiency type 2 from a novel mutation in the GDP-fucose transporter gene
Authors: Hidalgo Andrés , Ma Songhui , Peired Anna J. , Weiss Linnea A. , Cunningham-Rundles Charlotte , Frenette Paul S.
Published: February 2003

Leukocyte adhesion deficiency type 2 (LADII) is characterized by defective selectin ligand formation, recurrent infection, and mental retardation. This rare syndrome has only been described in 2 kindreds of Middle Eastern descent who have differentially responded to exogenous fucose treatment. The molecular defect was recently ascribed to single and distinct missense mutations in a putative Golgi guanosine diphosphate (GDP)–fucose transporter. Here, we describe a patient of Brazilian origin with features of LADII. Sequencing of the GDP-fucose transporter revealed a novel single nucleotide deletion producing a shift in the open-reading frame and severe truncation of the polypeptide. Overexpression of the mutant protein in the patient's fibroblasts did not rescue fucosylation, suggesting that the deletion ablated the activity of the transporter. Administration of oral L-fucose to the patient produced molecular and clinical responses, as measured by the appearance of selectin ligands, normalization of neutrophil counts, and prevention of infectious recurrence. The lower neutrophil counts paralleled improved neutrophil interactions with activated endothelium in cremasteric venules of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, fucose supplementation induced autoimmune neutropenia and the appearance of H antigen on erythrocytes, albeit without evidence of intravascular hemolysis. The robust response to fucose despite a severely truncated transporter suggests alternative means to transport GDP-fucose into the Golgi complex.
TCL1 expression in plasmacytoid dendritic cells (DC2s) and the related CD4+ CD56+ blastic tumors of skin
Authors: Herling Marco , Teitell Michael A. , Shen Rhine R. , Medeiros L. Jeffrey , Jones Dan
Published: February 2003

Initially considered to be of natural killer (NK)–cell origin, CD4+ CD56+ blastic tumors (BTs) of skin have recently been proposed to be of dendritic cell lineage. We have previously described BTs with transformation to myelomonocytic leukemia. Here we report expression of the lymphoid proto-oncogene TCL1 in 10 (83%) of 12 BTs and in lymph node plasmacytoid dendritic cells (DC2s). TCL1 was also expressed in myelomonocytic blasts of 3 transformed BT cases but not in true NK-cell tumors (n = 18), de novo acute myelomonocytic leukemias (1 of 14, 7%), or mature T-cell malignancies (1 of 112, < 1%), with the exception of T-prolymphocytic leukemia (T-PLL). All BT cases were also positive for the DC2-associated marker CD123. These results further support derivation of BTs from DC2s, and demonstrate that TCL1 expression in this tumor is common to the immature blastoid, lymphoid-appearing, and subsequent myelomonocytic phases of this disease.
Cell surface peptidase CD26/DPPIV mediates G-CSF mobilization of mouse progenitor cells
Authors: Christopherson Kent W. , Cooper Scott , Broxmeyer Hal E.
Published: February 2003

CXC ligand 12 (CXCL12; also known as stromal cell–derived factor 1α/SDF-1α) chemoattracts hematopoietic stem and progenitor cells (HSCs/HPCs) and is thought to play a crucial role in the mobilization of HSCs/HPCs from the bone marrow. CD26 (dipeptidylpeptidase IV [DPPIV]) is a membrane-bound extracellular peptidase that cleaves dipeptides from the N-terminus of polypeptide chains. CD26 has the ability to cleave CXCL12 at its position-2 proline. We found by flow cytometry that CD26 is expressed on a subpopulation of normal Sca-1+c-kit+lin— hematopoietic cells isolated from mouse bone marrow, as well as Sca-1+c-kit—lin— cells, and that these cells possess CD26 peptidase activity. To test the functional role of CD26 in CXCL12-mediated normal HSC/HPC migration, chemotaxis assays were performed. The CD26 truncated CXCL12(3-68) showed an inability to induce the migration of sorted Sca-1+c-kit+lin— or Sca-1+c-kit—lin— mouse marrow cells compared with the normal CXCL12. In addition, CXCL12(3-68) acts as an antagonist, resulting in the reduction of migratory response to normal CXCL12. Treatment of Sca-1+c-kit+lin— mouse marrow cells, and myeloid progenitors within this population, or Sca-1+c-kit—lin— cells with a specific CD26 inhibitor, enhanced the migratory response of these cells to CXCL12. Finally, to test for potential in vivo relevance of these in vitro observations, mice were treated with CD26 inhibitors during granulocyte colony-stimulating factor (G-CSF)–induced mobilization. This treatment resulted in a reduction in the number of progenitor cells in the periphery as compared with the G-CSF regimen alone. This suggests that a mechanism of action of G-CSF mobilization involves CD26.
X‐ray powder diffraction structural characterization of iron(III) chloro‐ and bromo‐complexes of triphenylphosphine oxide
Authors: Jorík V. , Ondrejkovicová I. , von Dreele R. B. , Ehrenberg H.
Published: February 2003

Iron (III) complexes of the composition [FeX2(OPPh3)4][FeX4], where X is Cl or Br were synthesised by several methods. It was found that each particular synthesis has yielded solids with slightly different powder patterns and also their comparison to those of calculated from single crystal data showed remarkable differences. A series of constrained Rietveld refinements has been performed on the title complexes to explain these differences. In a course of Rietveld refinement it was found that preferred orientation is not the only factor affecting the shape of the pattern and atoms parameters were included into refinement too. The results of Rietveld refinement allowed to conclude that the structures of compounds prepared by different methods are identical. In addition, it was shown that also in the case of rather complicated structure like the title complexes the powder diffraction method can lead to reasonable results.
Cover Picture: Eur. J. Org. Chem. 5/2003
Authors: Vries Johannes G. de , Vries André H.M. de
Published: February 2003

The cover picture shows a graphical depiction of an array of homogeneous catalysis experiments that were performed in an automated synthesizer. Using modern high‐throughput screening techniques has tremendously accelerated both the discovery of a catalyst for a desired transformation as well as the development of the process that can be implemented into the plant. The background of the picture shows a reactor in one of the plants of DSM Pharmaceutical Chemicals. Details are discussed in the Microreview by J. G. de Vries and A. H. M. de Vries on p. 799 ff.
Regular canonical covers
Authors: Ciliberto Ciro , Pardini Rita , Tovena Francesca
Published: February 2003

We construct three sequences of regular surfaces of general type with unbounded numerical invariants whose canonical map is 2–to–1 onto a canonically embedded surface. Only sporadic examples of surfaces with these properties were previously known.
On weighted inequalities for martingale transform operators
Authors: Martínez Teresa
Published: February 2003

For 1 < p < ∞, the almost surely finiteness of $ E \left(v ^{- {p^{\prime} \over p}} \vert {\cal F}_{1} \right) $ is a necessary and sufficient condition in order to have almost surely convergence of the sequences {E(f|ℱn)} with f ∈ Lp(v dP). This condition is also equivalent to have weighted inequalities from Lp(v dP) into Lp(u dP) for some weight u for Doob's maximal function, square function and generalized Burkholder martingale transforms. Similarly, E(u|ℱ1) < ∞ turns out to be necessary and sufficient for the above weighted inequalities to hold for some v.
Subnanosecond fluorescence quenching of dye molecules in solution
Authors: Yu W. , Pellegrino F. , Grant M. , Alfano R. R.
Published: February 2003

Subnanosecond fluorescence kinetics of malachite green and erythrosin were measured. The fluorescence lifetime of malachite green depends on the viscosity of the solution as η2/3. The fluorescence lifetime of erythrosin decreases linearly as the concentration of water increases in a water–acetone mixture. The fluorescence quenching of malachite green and erythrosin is attributed to environmental effects on the nonradiative internal conversion and intersystem crossing rates, respectively.
Catastrophe and propagation in chemical reactions
Authors: Feinn D. , Ortoleva P.
Published: February 2003

Multiple time scales, common in known chemical instability systems, lead to quasi-steady state ’’behavior’’ surfaces in the phase space of chemical concentrations. A result of catastrophe theory is used to classify the types of topological features, the ’’elementary catastrophes,’’ that these surfaces may take on. By using a multiple time scale scheme we predict the wave form and velocity of a variety of propagating phenomena that can occur because of the various types of catastrophes such as the cuspoids and umbilics. Since the state of chemical equilibrium is unique, we show that the presence of catastrophes on the behavior surface is strictly due to nonequilibrium processes on a short time scale. An important implication of this work is that the topological analysis of multiple time scale systems unfolds the richness of the potential for the variety of propagating phenomena in reacting diffusing systems.
Capillary waves and the mean field theory of interfaces
Authors: Davis H. Ted
Published: February 2003

The relationship of the usual mean field molecular theory of planar interfaces to the capillary wave theory of interfaces is investigated. It is shown that the good agreement between the planar mean field theories and computer simulation of a liquid–vapor interface results from the smallness of the interfacial area chosen for simulation. For an interface of finite thickness, capillary waves lead, through a geometric effect, to a mean square dispersion that is larger than the sum of the intrinsic dispersion of a planar interface and the capillary wave dispersion of a surface. It is shown that the maximum wave vector introduced in capillary wave theory as an arbitrary cutoff parameter is predicted naturally by mean field theory. The implication of capillary wave theory on the possibility of ultralow tensions for fluids far from a critical point is discussed.
LTR_STRUC: a novel search and identification program for LTR retrotransposons
Authors: McCarthy Eugene M. , McDonald John F.
Published: February 2003

Motivation: Long terminal repeat (LTR) retrotransposons constitute a substantial fraction of most eukaryotic genomes and are believed to have a significant impact on genome structure and function. Conventional methods used to search for LTR retrotransposons in genome databases are labor intensive. We present an efficient, reliable and automated method to identify and analyze members of this important class of transposable elements.

Results: We have developed a new data-mining program, LTR_STRUC (LTR retrotransposon structure program) which identifies and automatically analyzes LTR retrotransposons in genome databases by searching for structural features characteristic of such elements. LTR_STRUC has significant advantages over conventional search methods in the case of LTR retrotransposon families having low sequence homology to known queries or families with atypical structure (e.g. non-autonomous elements lacking canonical retroviral ORFs) and is thus a discovery tool that complements established methods. LTR_STRUC finds LTR retrotransposons using an algorithm that encompasses a number of tasks that would otherwise have to be initiated individually by the user. For each LTR retrotransposon found, LTR_STRUC automatically generates an analysis of a variety of structural features of biological interest.

Availability: The LTR_STRUC program is currently available as a console application free of charge to academic users from the authors.
Transforming the company: the differing learning practices of successful and unsuccessful companies
Authors: Coulson‐Thomas Colin
Published: February 2003

Successful and unsuccessful companies adopt very different ways of managing change, competing and winning. Examining outcomes achieved enables the differing attitudes, approaches, behaviours and priorities of winners and losers to the integration of learning and working, partnering with consultants and business schools, operating in the international business environment and creating international learning networks to be compared. Learning, training and development activities and interventions should address the root causes of “losing” ways and focus upon, enable and support winning attitudes and approaches. Success is directly related to the number of critical success factors that are put in place. Hence, the payoff from activities that address them can be considerable.
How training can add real value to the business: part 1
Authors: Hale Richard
Published: February 2003

This is the first of two ground‐breaking articles set to challenge the training community with a call to action written by Dr Richard Hale, a leading proponent of action learning. Here he argues that the time has come to shatter the myths that have emerged based upon the propositions of Donald Kirkpatrick some 43 years ago. Learning should be seen as the responsibility of the learner not the trainer. Proving learning should be integral to the process of learning not based on before and after statistics. This is based on Richard Hale’s own learning from action with international organisations through the International Management Centres Association.
Improved chemical additives in MW fluids
Authors: Jones A.M.
Published: February 2003

The metalworking (MW) fluid industry accounts for approximately 5 per cent of the total world market for lubricants. MW fluids rely upon good formulation expertise and effective chemical additives. It is becoming increasingly apparent that in order to provide chemical additives that meet the increasing demands of the MW fluids market, additive suppliers have to provide increasing amounts of information regarding the performance and environmental impact of their additives.
A Single Amino Acid Substitution in Herpes Simplex Virus Type 1 VP16 Inhibits Binding to the Virion Host Shutoff Protein and Is Incompatible with Virus Growth
Authors: Knez J. , Bilan P. T. , Capone J. P.
Published: February 2003

In addition to its well-established role in the activation of herpes simplex virus immediate-early gene transcription, VP16 interacts with and downregulates the function of the virion host shutoff protein (vhs), thereby attenuating vhs-mediated destruction of viral mRNAs and translational arrest at late times of infection. We have carried out two-hybrid analysis in vivo and protein-protein interaction assays in vitro to identify determinants in VP16 necessary for interaction with vhs. The minimal amino-terminal subfragment of VP16 capable of binding to vhs encompassed residues 1 to 345. Alteration of a single leucine at position 344 to alanine (L344A) in the context of the amino-terminal fragment of VP16 containing residues 1 to 404 was sufficient to abolish interaction with vhs in vitro and in vivo. Leu344 could be replaced with hydrophobic amino acids (Ile, Phe, Met, or Val) but not by Asn, Lys, or Pro, indicating that hydrophobicity is an important property of binding to vhs. VP16 harboring a loss-of-function mutation at L344 was not compromised in its ability to interact with host cell factor (HCF-1) or to activate transcription of viral immediate-early genes in transient-transfection assays. Virus complementation assays using the VP16-null virus 8MA and the VP16/vhs double-mutant virus 8MAΔSma showed that VP16(L344A) was able to complement the growth of 8MAΔSma but not 8MA. Thus, a single point mutation in VP16 uncouples binding to vhs from other functions of VP16 required for virus growth and indicates that direct physical association between VP16 and vhs is necessary to sustain a productive infection.
Envelopment of Human Cytomegalovirus Occurs by Budding into Golgi-Derived Vacuole Compartments Positive for gB, Rab 3, Trans-Golgi Network 46, and Mannosidase II
Authors: Homman-Loudiyi M. , Hultenby K. , Britt W. , Söderberg-Nauclér C.
Published: February 2003

Although considerable progress has been made towards characterizing virus assembly processes, assignment of the site of tegumentation and envelopment for human cytomegalovirus (HCMV) is still not clear. In this study, we examined the envelopment of HCMV particles in human lung fibroblasts (HF) HL 411 and HL 19, human umbilical vein endothelial cells, human pulmonary arterial endothelial cells, and arterial smooth muscle cells at different time points after infection by electron microscopy (EM), immunohistochemistry, and confocal microscopy analysis. Double-immunofluorescence labeling experiments demonstrated colocalization of the HCMV glycoprotein B (gB) with the Golgi resident enzyme mannosidase II, the Golgi marker TGN (trans-Golgi network) 46, and the secretory vacuole marker Rab 3 in all cell types investigated. Final envelopment of tegumented capsids was observed at 5 days postinfection by EM, when tegumented capsids budded into subcellular compartments located in the cytoplasm, in close proximity to the Golgi apparatus. Immunogold labeling and EM analysis confirmed staining of the budding compartment with HCMV gB, Rab 3, and mannosidase II in HL 411 cells. However, the markers Rab 1, Rab 2, Rab 7, Lamp 1 (late endosomes and lysosomes), and Lamp 2 (lysosomes) neither showed specific staining of the budding compartment in the immunogold labeling experiments nor colocalized with gB in the immunofluorescent colocalization experiments in any cell type studied. Together, these results suggest that the final envelopment of HCMV particles takes place mainly into a Golgi-derived secretory vacuole destined for the plasma membrane, which may release new infectious virus particles by fusion with the plasma membrane.
An Essential Role of the Enhancer for Murine Cytomegalovirus In Vivo Growth and Pathogenesis
Authors: Ghazal Peter , Messerle Martin , Osborn Kent , Angulo Ana
Published: February 2003

The transcription of cytomegalovirus (CMV) immediate-early (IE) genes is regulated by a large and complex enhancer containing an array of binding sites for a variety of cellular transcription factors. Previously, using bacterial artificial chromosome recombinants of the virus genome, it was reported that the enhancer region of murine CMV (MCMV) is dispensable but performs a key function for viral multiplication (A. Angulo, M. Messerle, U. H. Koszinowski, and P. Ghazal, J. Virol.
72:
8502-8509, 1998). In the present study, we defined, through the reconstitution of infectious enhancerless MCMVs, the growth requirement for the enhancer in tissue culture and explored its significance for steering a productive infection in vivo. A comparison of
cis
and
trans
complementation systems for infection of enhancerless virus in permissive fibroblasts revealed a multiplicity-dependent growth phenotype that is severely compromised in the rate of infectious-virus multiplication. The in vivo impact of viruses that have an amputated enhancer was investigated in an extremely sensitive model of MCMV infection, the SCID mouse. Histological examination of spleens, livers, lungs, and salivary glands from animals infected with enhancer-deficient MCMV demonstrated an absence of tissue damage associated with CMV infection. The lack of pathogenic lesions correlated with a defect in replication competence. Enhancerless viruses were not detectable in major target organs harvested from SCID mice. The pathogenesis and growth defect reverted upon restoration of the enhancer. Markedly, while SCID mice infected with 5 PFU of parental MCMV died within 50 days postinfection, all mice infected with enhancerless virus survived for the duration of the experiment (1 year) after infection with 5 × 10
5
PFU. Together, these results clarify the importance of the enhancer for MCMV growth in cell culture and underscore the in vivo significance of this region for MCMV virulence and pathogenesis.
The Function of Nuclear Architecture: A Genetic Approach
Authors: Taddei Angela , Hediger Florence , Neumann Frank R. , Gasser Susan M.
Published: February 2003

▪ Abstract  Eukaryotic genomes are distributed on linear chromosomes that are grouped together in the nucleus, an organelle separated from the cytoplasm by a characteristic double membrane studded with large proteinaceous pores. The chromatin within chromosomes has an as yet poorly characterized higher-order structure, but in addition to this, chromosomes and specific subchromosomal domains are nonrandomly positioned in nuclei. This review examines functional implications of the long-range organization of the genome in interphase nuclei. A rigorous test of the physiological importance of nuclear architecture is achieved by introducing mutations that compromise both structure and function. Focussing on such genetic approaches, we address general concepts of interphase nuclear order, the role of the nuclear envelope (NE) and lamins, and finally the importance of spatial organization for DNA replication and heritable gene expression.