bluuebunny/crossref_metadata_2025 huggingface dataset:
Ubiquitin COOH-Terminal Hydrolase 1: A Biomarker of Renal Cell Carcinoma Associated with Enhanced Tumor Cell Proliferation and Migration[?Q1: Running head: UCHL1, a Biomarker of RCC. Short title OK?Q1]
Authors: Seliger Barbara , Fedorushchenko Alla , Brenner Walburgis , Ackermann Angelika , Atkins Derek , Hanash Samir , Lichtenfels Rudolf
Published: January 2007

Purpose: Renal cell carcinoma (RCC) accounts for 2% to 3% of all malignancies. It represents one of the most radiation- and chemotherapy-resistant tumors and surgical resections are only effective in organ-defined disease. However, RCC is an immunogenic tumor with response rates to immunotherapies between 10% and 20% of the treated patients. Due to the currently inefficient therapies and the low 5-year survival rates of RCC patients, novel diagnostic, prognostic, and therapeutic markers are urgently needed for this disease.

Experimental Design: Proteome-based approaches were used to identify (a) differentially expressed proteins in RCC compared with normal kidney epithelium and (b) proteins that are able to induce an antibody response in RCC patients. Based on these experiments, a promising candidate was subsequently validated by reverse transcription-PCR, Western blot analyses, and immunohistochemistry. In addition, functional assays were done in generated transfectants.

Results: The ubiquitin COOH-terminal hydrolase L1 (UCHL1) was found to be differentially expressed in both RCC lesions and RCC cell lines and immunoreactive using patients' sera. UCHL1 expression was often down-regulated in primary RCC when compared with normal kidney epithelium but dependent on the RCC subtype, the von Hippel-Lindau phenotype, and the tumor grading. Moreover, the frequency and the level of UCHL1 expression were higher in metastases when compared with primary RCC lesions. Gain-of-function transfectants exhibited a significant higher proliferation and migration rate than UCHL1-negative RCC cells.

Conclusions: UCHL1 expression seems to be associated with the metastatic phenotype of RCC and therefore might serve as potential biomarker for the diagnosis and prognosis of RCC patients.
Increased Dose Density Is Feasible: A Pilot Study of Adjuvant Epirubicin and Cyclophosphamide followed by Paclitaxel, at 10- or 11-Day Intervals with Filgrastim Support in Women with Breast Cancer
Authors: Fornier Monica N. , Seidman Andrew D. , Lake Diana , D'Andrea Gabriella , Bromberg Jacqueline , Robson Mark , Van Poznak Catherine , Panageas Katherine S. , Atienza Marietta , Norton Larry , Hudis Clifford
Published: January 2007

Purpose: Because Cancer and Leukemia Group B 9741 trial showed a benefit for every 14-day administration of chemotherapy compared with every 21-day treatment, we hypothesized that even greater dose density would be more effective. We conducted a pilot trial to assess the feasibility of dose-dense chemotherapy consisting of a standard regime at 10- to 11-day intervals in the adjuvant/neoadjuvant setting. A 2-day window was allowed for scheduling logistics.

Experimental Design: Thirty-nine women with early-stage breast carcinoma were accrued from April 2004 to October 2004. Median age was 47 years (range, 26-67 years). Patients received therapy with 100 mg/m2 epirubicin and 600 mg/m2 cyclophosphamide (EC) q 10 to 11 days for four cycles followed by 175 mg/m2 paclitaxel q 10 to 11 days for four cycles, all with filgrastim support (300 μg s.c. daily) from day 2 to 24 h before the next treatment.

Results: Thirty-five (90%) patients completed all planned therapy. The median intertreatment interval was 10 days (range, 8-28 days). Cycles (80.7%) were delivered at no more than 10- to 11-day intervals. There were five dose reductions of 25% for grade 3 nonhematologic toxicity in five patients. Six (16%) patients developed febrile neutropenia defined as temperature >38°C with absolute neutrophil count <1,000/μL. All febrile neutropenia was during therapy with EC. Other grade 3 toxicities included bone pain, hand and foot syndrome, neuropathy, mucositis, nausea, and vomiting.

Conclusions: Therapy with EC for four cycles followed by paclitaxel for four cycles at 10- to 11-day intervals is feasible. The ∼30% reduction in intertreatment interval compared with every 14-day treatment could increase the efficacy of adjuvant chemotherapy.
Cerebral Blood Flow Autoregulation and Edema Formation During Pregnancy in Anesthetized Rats
Authors: Euser Anna G. , Cipolla Marilyn J.
Published: January 2007

Eclampsia is considered a form of hypertensive encephalopathy in which an acute elevation in blood pressure causes autoregulatory breakthrough, blood–brain barrier disruption, and edema formation. We hypothesized that pregnancy predisposes the brain to eclampsia by lowering the pressure of autoregulatory breakthrough and enhancing cerebral edema formation. Because NO production is increased in pregnancy, we also investigated the role of NO in modulating autoregulation. Cerebral blood flow autoregulation was determined by phenylephrine infusion and laser Doppler flowmetry. Four groups were studied: untreated nonpregnant (n=7) and late-pregnant (days 19 to 21; n=8) Sprague–Dawley rats and nonpregnant (n=8) and late-pregnant (n=8) animals treated with an NO synthase inhibitor (N
G
-nitro-
l
-arginine methyl ester; 0.5 to 0.7 g/L). Brain water content and blood–brain barrier permeability to sodium fluorescein were determined after breakthrough. Pregnancy caused no change in autoregulation or the pressure of breakthrough. However, treatment with the NO synthase inhibitor significantly increased the pressure of autoregulatory breakthrough (nonpregnant: 183.6±3.0 mm Hg versus 212.0±2.8 mm Hg,
P
<0.05; late-pregnant: 180.8±3.2 mm Hg versus 209.3±4.7 mm Hg,
P
<0.05). After autoregulatory breakthrough, only late-pregnant animals showed a significant increase in cerebral edema formation, which was attenuated by NO synthase inhibition. There was no difference in blood–brain barrier permeability between nonpregnant and late-pregnant animals in response to acute hypertension, suggesting that pregnancy may predispose the brain to eclampsia by increasing cerebral edema through increased hydraulic conductivity.
Tumor Necrosis Factor-α Induces Endothelial Dysfunction in Lepr
db
Mice
Authors: Gao Xue , Belmadani Souad , Picchi Andrea , Xu Xiangbin , Potter Barry J. , Tewari-Singh Neera , Capobianco Stefano , Chilian William M. , Zhang Cuihua
Published: January 2007

Background—

We hypothesized that the inflammatory cytokine tumor necrosis factor-α (TNF) produces endothelial dysfunction in type 2 diabetes.

Methods and Results—

In m Lepr
db
control mice, sodium nitroprusside and acetylcholine induced dose-dependent vasodilation, and dilation to acetylcholine was blocked by the NO synthase inhibitor
N
G
-monomethyl-
l
-arginine. In type 2 diabetic (Lepr
db
) mice, acetylcholine- or flow-induced dilation was blunted compared with m Lepr
db
, but sodium nitroprusside produced comparable dilation. In Lepr
db
mice null for TNF (db
TNF
−
/db
TNF
−
), dilation to acetylcholine or flow was greater than in diabetic Lepr
db
mice and comparable to that in controls. Plasma concentration of TNF was significantly increased in Lepr
db
versus m Lepr
db
mice. Real-time polymerase chain reaction and Western blotting showed that mRNA and protein expression of TNF and nuclear factor-κB were higher in Lepr
db
mice than in controls. Administration of anti-TNF or soluble receptor of advanced glycation end products attenuated nuclear factor-κB and TNF expression in the Lepr
db
mice. Immunostaining results show that TNF in mouse heart is localized predominantly in vascular smooth muscle cells rather than in endothelial cells and macrophages. Superoxide generation was elevated in vessels from Lepr
db
mice versus controls. Administration of the superoxide scavenger TEMPOL, NAD(P)H oxidase inhibitor (apocynin), or anti-TNF restored endothelium-dependent dilation in Lepr
db
mice. NAD(P)H oxidase activity, protein expression of nitrotyrosine, and hydrogen peroxide production were increased in Lepr
db
mice (compared with controls), but these variables were restored to control levels by anti-TNF.

Conclusion—

Advanced glycation end products/receptor of advanced glycation end products and nuclear factor-κB signaling play pivotal roles in TNF expression through an increase in circulating and/or local vascular TNF production in the Lepr
db
mouse with type 2 diabetes. Increases in TNF expression induce activation of NAD(P)H oxidase and production of reactive oxidative species, leading to endothelial dysfunction in type 2 diabetes.
IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells
Authors: Acacia de Sa Pinheiro Ana , Morrot Alexandre , Chakravarty Sumana , Overstreet Michael , Bream Jay H , Irusta Pablo M , Zavala Fidel
Published: January 2007

IL-4 has distinct effects on the differentiation and functional properties of CD8+ T cells. In vivo studies have shown that it is critical for the development of protective memory responses against tumors and infections by Leishmania and Plasmodium parasites. The intracellular signaling events mediated by IL-4/IL-4 receptor (IL-4R) interactions on CD4+ T cells have been studied extensively; however, the nature of IL-4-induced signaling on CD8+ T cells has not been characterized. Using naïve, activated, as well as differentiated CD8+ T cells, we show that IL-4 has a strong in vivo and in vitro antiapoptotic effect on activated and resting CD8+ T cells. We demonstrate that IL-4 induces the phosphorylation of the IL-4R, which is followed by the activation of at least two distinct intracellular signaling cascades: the Jak1/STAT6 and the insulin receptor substrate/PI-3K/protein kinase B pathways. We also found that IL-4 induces the Jak3-mediated phosphorylation and nuclear migration of STAT1, STAT3, and STAT5 in naïve, activated, as well as differentiated, IFN-γ-producing CD8+ T cells. The induction of this broad signaling activity in CD8+ T cells coincides with a transcriptional activity of suppressors of cytokine signaling genes, which are decreased significantly in comparison with CD4+ T cells. To our knowledge, this report constitutes the first comprehensive analysis of the signaling events that shape CD8+ T cell responses to IL-4.
Aβ1-42 stimulates actin polymerization in hippocampal neurons through Rac1 and Cdc42 Rho GTPases
Authors: Mendoza-Naranjo Ariadna , Gonzalez-Billault Christian , Maccioni Ricardo B.
Published: January 2007

A number of psychiatric and neurodegenerative disorders, such as Alzheimer's disease, are characterized by abnormalities in the neuronal cytoskeleton. Here, we find that the enhancement in actin polymerization induced by fibrillar amyloid-beta peptide (Aβ) is associated with increased activity of Rac1/Cdc42 Rho GTPases. Rac1 upregulation involves the participation of Tiam1, a Rac guanine-nucleotide exchange factor, where Aβ exposure leads to Tiam1 activation by a Ca2+-dependent mechanism. These results point to Rho GTPases as one of the targets in Aβ-induced neurodegeneration in Alzheimer's disease pathology, with a role in mediating changes in the actin cytoskeletal dynamics.
Sleep Arrangements and Behavior of Bed-Sharing Families in the Home Setting
Authors: Baddock Sally A. , Galland Barbara C. , Taylor Barry J. , Bolton David P.G.
Published: January 2007

OBJECTIVES. We aimed to provide a quantitative analysis of the sleep arrangements and behaviors of bed-sharing families to further understand the risks and benefits as well as the effects of infant age and room temperature on bed-sharing behaviors.

METHODS. Forty infants who regularly bed shared with ≥1 parent ≥5 hours per night were recruited. Overnight video of the family and physiological monitoring of the infant was conducted in infants' homes. Infant sleep position, potential for exposure to expired air, head covering and uncovering, breastfeeding, movements, family sleep arrangements, responses to the infant, and interactions were logged.

RESULTS. All infants slept with their mother. Fathers were included in 18 studies and siblings in 4. Infants usually slept beside the mother, separated from the father/siblings (if present), facing the mother, with head at mothers’ breast level, touching, or with mother cradling. Median overnight breastfeeding duration was 40.5 minutes. Mothers commonly faced their infant, but infants were rarely in a position that potentially exposed them to maternal expired air. Fathers were seldom in contact with the infant during sleep. Of the 102 head-covering episodes observed in 22 infants, 80% were because of changes in adult sleep position. Sixty-eight percent of head uncovering was facilitated by the mother; half of these events were prompted by the infant. A 1°C increase in room temperature decreased infant head covering by 0.2 hours.

CONCLUSIONS. The mother-infant relationship is of prime importance during bed sharing, whether the father is present or not. The focus around breastfeeding often dictates the sleep position of the infant and mother, though room temperature may also influence this. In colder rooms infants tend to spend more time with their face covered by bedding. Frequent maternal interactions rely on the ability of the mother to arouse with little stimulation. Mothers, perhaps impaired by alcohol, smoking, or overtiredness, may not be able to respond appropriately.
Cost-Effectiveness of Routine Childhood Vaccination for Hepatitis A in the United States
Authors: Rein David B. , Hicks Katherine A. , Wirth Kathleen E. , Billah Kaafee , Finelli Lyn , Fiore Anthony E. , Hoerger Thomas J. , Bell Beth P. , Armstrong Gregory L.
Published: January 2007

OBJECTIVES. Economic analysis is an important component in formulating national policy. We evaluated the economic impact of hepatitis A vaccination of all US children ages 12 to 23 months as compared with no vaccination and with current implementation of the preexisting (issued in 1999), regional policy.

METHODS. We developed a Markov model of hepatitis A that followed a single cohort from birth in 2005 through death or age 95 years. From the societal perspective, the model compared the outcomes that resulted from routine vaccination at age 1 year to 2 scenarios: no hepatitis A vaccination and hepatitis A vaccination at levels observed in 2003 under the preexisting policy. We evaluated the economic impact of vaccination nationwide, in areas where vaccination was already recommended, and in areas where no previous recommendation existed.

RESULTS. Without childhood vaccination, the ∼4 million children in the 2005 birth cohort would be expected over their lifetimes to have 199000 hepatitis A virus infections, including 74000 cases of acute hepatitis A and 82 deaths, resulting in $134 million in hepatitis A–related medical costs and productivity losses. Compared with no vaccination, routine vaccination at age 1 year would prevent 172000 infections, at a cost of $28000 per quality-adjusted life year saved. Compared with maintaining the levels of hepatitis A vaccination under the preexisting regional policy, routine vaccination at age 1 year would prevent an additional 112000 infections, at a cost of $45000 per quality-adjusted life year saved.

CONCLUSIONS. The cost-effectiveness of nationwide hepatitis A vaccination compared with no vaccination, and the incremental cost-effectiveness of this recommendation compared with preexisting recommendations, is similar to that of other accepted public health interventions. In October 2005, the Advisory Committee on Immunization Practices recommended extending hepatitis A immunization to all US children ages 12 to 23 months.
The Joint Research Program “CPR Precipitation” — Breakthroughs in the Understanding of Kinetic Pathways for the Early Stages of Phase Separation
Authors: Martin G.
Published: December 2006

The CNRS joint research program, “CPR Precipitation”, has been carefully prepared by the industrial initiators. Very significant results were obtained: they are summarized in the following and presented in this meeting. As for the future, the CPR has catalyzed the formation of a community of promising scientific interest: it would be of common benefit to stabilize this community by an appropriate further support.
Reconciling the Classical Nucleation Theory and Atomic Scale Observations and Modeling
Authors: Martin G.
Published: December 2006

Here the author recalls the classical assumptions and the resulting expressions to be used in Cluster Dynamics stricto sensu and then, he shows how to establish a precise formal link between Classical Nucleation Theory (CNT) and Cluster Dynamics (CD).
Synthesis and characterization of novel polyurethanes based on 2,6‐bis(4‐hydroxybenzylidene) cyclohexanone hard segments
Authors: Raghu A. V. , Anita G. , Barigaddi Y. M. , Gadaginamath G. S. , Aminabhavi T. M.
Published: January 2007

Four novel polyurethanes (PUs) containing 2,6‐bis(4‐hydroxybenzylidene) cyclohexanone hard segments with four diisocyanate, namely, 4,4′‐diphenylmethane diisocyanate, toluene 2,4‐diisocyanate, isophorone diisocyanate, and hexamethylene diisocyanate, were prepared. Structural elucidation and thermal characterization of these PUs were done by Fourier transform infrared, UV, and fluorescence spectroscopy, 1H‐NMR, 13C‐NMR, and differential thermal analysis/thermogravimetric analysis. All of the PUs contained domains of semicrystalline and amorphous structures as indicated by X‐ray diffraction. PUs were soluble in polar aprotic solvents such as N‐methyl‐2‐pyrrolidone, dimethylformamide, and dimethyl sulfoxide. Acoustic properties were calculated from the group contribution method. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Effect of flow history on poly(vinylidine fluoride) crystalline phase transformation
Authors: Sobhani Hadi , Razavi‐Nouri Mohammad , Yousefi Ali Akbar
Published: January 2007

This study was devoted to the effect of extensional flow during film extrusion on the formation of the β‐crystalline phase and on the piezoelectric properties of the extruded poly(vinylidine fluoride) (PVDF) films after cold drawing. The PVDF films were extruded at different draw ratios with two different dies, a conventional slit die and a two‐channel die, of which the latter was capable of applying high extensional flow to the PVDF melt. The PVDF films prepared with the two‐channel die were drawn at different temperatures, strain rates, and strains. The optimum stretching conditions for the achievement of the maximum β‐phase content were determined as follows: temperature = 90°C, strain = 500%, and strain rate = 0.083 s−1. The samples prepared from the dies were then drawn under optimum stretching conditions, and their β‐phase content and piezoelectric strain coefficient (d33) values were compared at equal draw ratios. Measured by the Fourier transform infrared technique, a maximum of 82% β‐phase content was obtained for the samples prepared with the two‐channel die, which was 7% higher than that of the samples prepared by the slit die. The d33 value of the two‐channel die was 35 pC/N, which was also 5 pC/N higher than that of the samples prepared with the slit die. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Solution Structure of Domain 6 from a Self‐Splicing Group II Intron Ribozyme: A Mg2+ Binding Site is Located Close to the Stacked Branch Adenosine
Authors: Erat Michèle C. , Zerbe Oliver , Fox Thomas , Sigel Roland K. O.
Published: January 2007

Group II intron self‐splicing is essential for the correct expression of organellar genes in plants, fungi, and yeast, as well as of bacterial genes. Self‐excision of these autocatalytic introns from the primary RNA transcript is achieved in a two‐step mechanism that is apparently analogous to that of the eukaryotic spliceosome. The 2′‐OH of a conserved adenosine (the branch point) located within domain 6 (D6) acts as the nucleophile in the first step of splicing. Despite the biological importance of group II introns, little is known about their structural organization and usage of metal ions in catalysis. Here we report the first solution structure of a catalytically active D6 construct encompassing the branch point and the neighboring helical regions from the mitochondrial yeast intron ai5γ. The branch adenosine is the single unpaired nucleotide, and, in contrast to the spliceosomal branch site, resides within the helix, being partially stacked between two flanking GU wobble pairs. We identified a novel prominent Mg2+ binding site in the major groove of the branch site. Importantly, Mg2+ addition does not impair the stacking of the branch adenosine, rather it strengthens the interaction with the flanking uridines, as shown by NMR and fluorescence studies. This means that domain 6 presents the branch adenosine in a stacked fashion to the core of group II introns upon folding to the active conformation.
A Valuable, Inexpensive CuI/N‐Heterocyclic Carbene Catalyst for the Selective Diboration of Styrene
Authors: Lillo Vanesa , Fructos Manuel R. , Ramírez Jesús , Braga Ataualpa A. C. , Maseras Feliu , Díaz‐Requejo M. Mar , Pérez Pedro J. , Fernández Elena
Published: December 2006

The complexes [Cu(NHC)(NCMe)]BF4 (NHC=N‐heterocyclic ligand), with bis(catecholato)diboron (B2(cat)2) as the boron source, efficiently catalyze the diboration of styrene with very high degrees of conversion. With the appropriate NHC ligand, the reaction proceeds quantitatively toward the diborated derivative PhCH(Bcat)CH2(Bcat). The [styrene]/[B2(cat)2] ratio also has a strong effect on the selectivity: the use of an excess of styrene allows modification of the selectivity toward the formation solely of the monoborated derivative, PhCH2CH2(Bcat). DFT calculations suggest that no oxidative addition processes take place at copper, but that intermediates containing coordinated σ‐bonds are involved in the catalytic cycle.
Is there a role for platinum chemotherapy in the treatment of patients with hormone‐refractory prostate cancer?
Authors: Oh William K. , Tay Miah‐Hiang , Huang Jiaoti
Published: December 2006

Docetaxel chemotherapy is the current standard of care for metastatic hormone‐refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin and carboplatin, have moderate single‐agent activity in HRPC. Next‐generation platinum drugs, including satraplatin and oxaliplatin, may have additional activity in the management of HRPC. Furthermore, neuroendocrine differentiation may play a role in disease progression, providing a rationale for platinum‐based chemotherapy in the management of HRPC. The authors reviewed the MEDLINE database for reports related to platinum‐based chemotherapy in patients with advanced prostate cancer and evaluated studies that reviewed the role of neuroendocrine differentiation in the progression of HRPC. Older studies from the 1970s and 1980s suggested a lack of activity of cisplatin and carboplatin; however, those studies were flawed at least in part by their methods of response assessment. More recent Phase II studies of carboplatin suggested a moderate level of clinical and palliative activity when it was used as a single agent. However, when carboplatin was combined with a taxane and estramustine, high response rates were observed in several recent clinical trials. In addition, a randomized trial suggested that satraplatin plus prednisone improved progression‐free survival compared with prednisone alone. For patients who progressed after docetaxel, no standard options existed in the literature that was reviewed. Several preliminary reports suggested that carboplatin and oxaliplatin may have activity as second‐line chemotherapy. Platinum chemotherapy drugs historically have been considered inactive in HRPC, although a review of the data suggested otherwise. Carboplatin, in particular, induced very high response rates when it was combined with estramustine and a taxane, but it also appeared to have activity in patients who progressed after docetaxel. Satraplatin plus prednisone is being investigated in a large Phase III trial as second‐line chemotherapy for HRPC. Targeting neuroendocrine cells may provide a new therapeutic approach to HRPC. Cancer 2007;109:477–486. © 2006 American Cancer Society.
Influence of plasma volume status on blood pressure in patients on maintenance hemodialysis
Authors: Ibrahim Salwa , Taweel Ahmed
Published: December 2006

Background.

Hypervolemia is considered a major pathogenic factor for hypertension in patients receiving hemodialysis (HD). We examined the effect of intradialytic changes in body weight and plasma volume on blood pressure (BP) in a cohort of chronic HD patients.

Patients and Methods.

One hundred chronic, stable HD patients were the subjects of the present study. They were divided into 2 groups according to their pre‐dialysis BP. Each group was examined for potential significant correlations of intradialytic changes in body weight and plasma volume with pre‐ and post‐dialysis blood pressure values. The intradialytic decrease in plasma volume was calculated from pre‐dialysis and post‐dialysis total plasma protein concentrations and was expressed as a percentage of the plasma volume at the beginning of the hemodialysis session.

Results.

In group A (hypertensive group, n=43), post‐dialysis systolic and diastolic blood pressure (SBP and DBP) were significantly lower than pre‐dialysis values (p < 0.05). The mean intradialytic reduction in body weight was 2.97±1.33 kg, and the mean intradialytic decrease in plasma volume was 13.6%±8.23%. There was no significant correlation between intradialytic change in either SBP or DBP and intradialytic change in body weight or plasma volume. In group B (normotensive group, n=57), post‐dialysis SBP and DBP were significantly lower than pre‐dialysis levels (p < 0.05). The mean intradialytic reduction in body weight was 2.64±1.07 kg, and the mean intradialytic decrease in plasma volume was 13.4%±7.73%. A positive significant correlation was recorded between intradialytic change in SBP and change in body weight in normotensive group. Multiple regression analysis revealed that for the study patients as a whole, pre‐dialysis SBP, intradialytic change in SBP, pre‐dialysis DBP, and post‐dialysis SBP were not significantly correlated with intradialytic changes in plasma volume and body weight.

Conclusions.

Our findings clearly indicate that intradialytic change in plasma volume does not influence either pre‐dialysis or post‐dialysis blood pressure. From our results, we conclude that assessment of intradialytic change in plasma volume is not useful for evaluating the hydration status of HD patients in clinical practice.
Can knowledge of developmental processes illuminate the evolution of parental care?
Authors: Michel George F. , Tyler Amber N.
Published: December 2006

There are two levels of investigation for elucidating the evolution of parental behavior. The macro level focuses on how parental behavior can evolve as an aspect of reproduction. The micro level focuses on how species variations in parental behavior evolve. Recently, modern evolutionary biology has turned to developmental biology as a source for information about how trait variability (the substrate upon which natural selection and other evolutionary mechanisms can operate) can emerge during development (called “evo‐devo”). Application of this evo‐devo approach to the phenomenon of parental behavior requires identification of those mechanisms that produce variations in developmental pathways leading to parental behavior. It is these variations that provide the phenotypes for the potential evolution of different parental behavior systems. Variations in rodent maternal behavior affect the development of the HPA and HPG axes in their offspring. These mechanisms are examined to reveal how such developmental variations could underlie the evolution of biparental behavior. Knowledge of the developmental mechanisms responsible for species variations in mammalian parental behavior systems may provide insight into those mechanisms that may have been involved in the evolution of parental behavior itself. © 2006 Wiley Periodicals, Inc. Dev Psychobiol 49: 33–44, 2007.
Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome
Authors: Green Maia L. , Singh Amar V. , Zhang Yihzi , Nemeth Kimberly A. , Sulik Kathleen K. , Knudsen Thomas B.
Published: January 2007

Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol‐induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2× 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter‐exposure to PK11195 (4 mg/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain‐specific and/or PK11195‐dependent. Mapping ethanol‐responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down‐regulation of ribosomal proteins and proteasome, and up‐regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up‐regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near‐significant up‐regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. Developmental Dynamics 236:613–631, 2007. © 2007 Wiley‐Liss, Inc.
FOXP3: Not just for regulatory T cells anymore
Authors: Ziegler Steven F.
Published: December 2006

The forkhead family transcription factor FOXP3 has been shown to be critical for the development and function of CD4+CD25+ regulatory T cells. Recently, FOXP3 expression has been shown to be induced upon activation of human CD4+ T cells. A new report in this issue of the European Journal of Immunology shows that expression of FOXP3 in activated T cell leads to hyporesponsiveness, but not necessarily to acquisition of suppressor function. This finding suggests a new role for FOXP3 in human CD4+ T cells: down‐modulating responses to TCR‐mediated stimulation.

See accompanying article http://dx.doi.org/10.1002/eji.200636435
A Novel Direct Conversion of Primary Amides to Their Corresponding Methyl Esters
Authors: Li Liang‐Chun , Ren Jie , Liao Tou‐Gen , Jiang Ju‐Xing , Zhu Hua‐Jie
Published: December 2006

A novel method was used to directly convert aliphatic and aromatic primary amides into their corresponding methyl esters in high yields (up to 99 %) under mild reaction conditions. Possible mechanisms were studied at the B3LYP/6‐31++G(d,p) level of theory. Formation of the ester proceeded through a rearrangement of the –OMe and –NH2 groups in the RC(O)NHS(O)OMe intermediate in a H+‐catalyzed six‐membered ring transition state structure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Evaluation of the SEDD model for predicting sediment yield at the Sicilian experimental SPA2 basin
Authors: Stefano Costanza Di , Ferro Vito
Published: December 2006

In this paper a spatially distributed model of the hillslope sediment delivery processes, named the sediment delivery distributed (SEDD) model, is initially reviewed; the model takes into account the sediment delivery processes due to both the hillslope sediment transport and the effects of slope curvature.

Then the rainfall and sediment yield events measured at the experimental SPA2 basin, in Sicily, are used both to calibrate the SEDD model and to verify the predictive capability of the distributed sediment delivery approach at event scale.

For the SPA2 basin discretized into morphological units and stream tubes, the SEDD model is calibrated at event scale using the measurements carried out at the outlet of the experimental basin in the period December 2000–January 2001. The model calibration is used to determine a relationship useful for estimating the unique coefficient βe of the model by rainfall erosivity factor Re at event scale.

To test the predictive capability of the βe = f(Re) relationship, 20 events measured in the period September 2002–December 2005 are used; the comparison between measured sediment yield values and calculated ones for all monitored events shows that the sediment delivery distributed approach has a good predictive ability at event scale.

The analysis also shows that estimating βe by the relationship βe = f(Re) gives a better agreement between measured and calculated sediment yields than obtained with the median value βe,m of all 27 calculated βe values.

Finally the analysis at annual scale, for the period 2000–2005, allows the estimation of the median value βa,m representative of the annual behaviour. This analysis shows that the sediment delivery distributed approach also has a good predictive ability at annual scale. Copyright © 2006 John Wiley & Sons, Ltd.
I want to be an independent consultant: Considerations before taking the plunge
Authors: Viola Judah J.
Published: December 2006

The author reflects on his hopes and fears as he considers an independent consulting career.
The evaluation consultant's life cycle: Theory, practice, and implications for learning
Authors: Barrington Gail V.
Published: December 2006

This chapter examines the stages of growth of six independent consultants, the critical incidents that led to stage change, and training requirements to support this development.
Entrepreneurial consulting: Some structural and personal learnings
Authors: Lyons Morgan , Harrington Maura J.
Published: December 2006

This chapter offers firsthand experiences in optimizing the organizational and personal dimensions of evaluation research in an independent, entrepreneurial consulting environment.
Nurturing professional growth: A peer review model for independent evaluators
Authors: Bond Sally L. , Ray Marilyn L.
Published: December 2006

This chapter describes a peer review model for facilitating professional growth developed within the context of the American Evaluation Association's Independent Consulting Topical Interest Group.
Synthesis and characterization of a novel series of metallothiocarbohydrazone polymers and their adducts
Authors: Seleem H. S. , El‐Shetary B. A. , Shebl M.
Published: January 2007

A novel linear polymeric pentadentate (O2N2S‐sites) ligand (H3L) bearing both soft and hard donors was prepared by the reaction of a bifunctional carbonyl compound, 4,6‐diacetylresorcinol, with a bifunctional hydrazide compound, thiocarbohydrazide. Mono‐ and binuclear CuII and NiII complexes/each monomeric unit of the polymeric ligand were obtained depending on the pH of the reaction medium and the metal ion. Adducts with 1,10‐phenanthroline (Phen) and 2,2′‐bipyridyl (Bpy) were obtained. Anomalous dimeric CoII/CoIII complexes of the polymeric ligand were obtained in which two molecules of the linear polymeric ligand trapped two cobalt ions (CoII and CoIII) in each monomeric unit. These structures are very interesting in that they contain CoII/CoIII, side by side, as high‐spin square planar coordinated CoII ions and low‐spin (diamagnetic) octahedral coordinated CoIII ions. The suggested structures of the complexes have been elucidated on the basis of elemental and thermal analyses, conductance, and magnetic susceptibility measurements as well as spectral studies (electronic, IR, and ESR spectra). © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:100–107, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20239
Roscovitine‐activated HIP2 kinase induces phosphorylation of wt p53 at Ser‐46 in human MCF‐7 breast cancer cells
Authors: Węsierska‐Gądek Józefa , Schmitz M. Lienhard , Ranftler Carmen
Published: January 2007

Human MCF‐7 breast cancer cells are relatively resistant to conventional chemotherapy due to the lack of caspase‐3 activity. We reported recently that roscovitine (ROSC), a potent cyclin‐dependent kinase 2 inhibitor, arrests human MCF‐7 breast cancer cells in the G2phase of the cell cycle and concomitantly induces apoptosis. Exposure of MCF‐7 cells to ROSC also strongly activates the wt p53 tumor suppressor protein in a time‐ and dose‐dependent manner. The p53 level increased despite upregulation of Hdm‐2 protein and was attributable to the site‐specific phosphorylation at Ser‐46. The p53 protein phosphorylated at serine 46 causes the up‐regulation of the p53AIP1 protein, a component of mitochondria. In the present study we identified the pathway mediating ROSC‐induced p53 activation. Exposure of MCF‐7 cells to ROSC activated homeodomain‐intereacting protein kinase‐2 (HIPK2). The overexpression of wild‐type but not kinase inactive HIPK2 increased the basal and ROSC‐induced level of p53 phosphorylation at Ser‐46 and strongly enhanced the rate of apoptosis in cells exposed to ROSC. We show that HIPK2 is activated by ROSC and mediates ROSC‐induced P‐Ser‐46‐p53, thereby stabilizing wt p53 and increasing the efficacy of drug‐induced apoptosis in MCF‐7 cells. These results identify HIPK2 as a component of the ROSC‐induced signaling pathway leading to the stabilization and activation of wt p53 protein. J. Cell. Biochem. 100: 865–874, 2007. © 2007 Wiley‐Liss, Inc.
Direct evaluation via forced oscillation method of the electronic state density of sizable clusters
Authors: Conte R. , Arrighini G. P. , Guidotti C.
Published: December 2006

Metal clusters described in the framework of a simple tight binding model have been studied. Application of a dynamical approach (FOM), jointly with efficient storage of the sparse Hamiltonian matrix involved, is shown to allow direct evaluation of the electronic state density of sizable cubic‐symmetry aggregates. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 584–593, 2007
A theoretical investigation of the excited states of OCLO radical, cation, and anion using the CASSCF/CASPT2 method
Authors: Wei Zi‐Zhang , Li Bu‐Tong , Zhang Hong‐Xing , Sun Chia‐Chung , Han Ke‐Li
Published: December 2006

Using the complete active space self‐consistent field method with a large atomic natural orbital basis set, 10, 13, and 9 electronic states of the OClO radical, OClO+ cation, and OClO− anion were calculated, respectively. Taking the further correlation effects into account, the second‐order perturbation (CASPT2) calculations were carried out for the energetic calibration. The photoelectron spectroscopy of the OClO radical and OClO− anion were extensively studied in the both case of the adiabatic and vertical ionization energies. The calculated results presented the relatively complete assignment of the photoelectron bands of the experiments for OClO and its anion. Furthermore, the Rydberg states of the OClO radical were investigated by using multiconfigurational CASPT2 (MS‐CASPT2) theory under the basis set of large atomic natural orbital functions augmented with an adapted 1s1p1d Rydberg functions that have specially been built for this study. Sixteen Rydberg states were obtained and the results were consistent with the experimental results. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 467–477, 2007
Support vector machine based training of multilayer feedforward neural networks as optimized by particle swarm algorithm: Application in QSAR studies of bioactivity of organic compounds
Authors: Lin Wei‐Qi , Jiang Jian‐Hui , Zhou Yan‐Ping , Wu Hai‐Long , Shen Guo‐Li , Yu Ru‐Qin
Published: December 2006

Multilayer feedforward neural networks (MLFNNs) are important modeling techniques widely used in QSAR studies for their ability to represent nonlinear relationships between descriptors and activity. However, the problems of overfitting and premature convergence to local optima still pose great challenges in the practice of MLFNNs. To circumvent these problems, a support vector machine (SVM) based training algorithm for MLFNNs has been developed with the incorporation of particle swarm optimization (PSO). The introduction of the SVM based training mechanism imparts the developed algorithm with inherent capacity for combating the overfitting problem. Moreover, with the implementation of PSO for searching the optimal network weights, the SVM based learning algorithm shows relatively high efficiency in converging to the optima. The proposed algorithm has been evaluated using the Hansch data set. Application to QSAR studies of the activity of COX‐2 inhibitors is also demonstrated. The results reveal that this technique provides superior performance to backpropagation (BP) and PSO training neural networks. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 519–527, 2007
Gradient tabu search
Authors: Stepanenko Svetlana , Engels Bernd
Published: December 2006

This paper presents a modification of the tabu search called gradient tabu search (GTS). It uses analytical gradients for a fast minimization to the next local minimum and analytical diagonal elements of the Hessian to escape local minima. For an efficient blocking of already visited areas tabu regions and tabu directions are introduced into the tabu list (TL). Trials with various well‐known test functions indicate that the GTS is a very promising approach to determine local and global minima of differentiable functions. Possible application areas could be optimization routines for force field parameters or conformational searches for large molecules. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 601–611, 2007
Transition of care for hospitalized elderly patients—Development of a discharge checklist for hospitalists
Authors: Halasyamani L. , Kripalani S. , Coleman E. , Schnipper J. , van Walraven C. , Nagamine J. , Torcson P. , Bookwalter T. , Budnitz T. , Manning D.
Published: December 2006

BACKGROUND

Discharge from the hospital is a critical transition point in a patient's care. Incomplete handoffs at discharge can lead to adverse events for patients and result in avoidable rehospitalization. Care transitions are especially important for elderly patients and other high‐risk patients who have multiple comorbidities. Standardizing the elements of the discharge process may help to address the gaps in quality and safety that occur when patients transition from the hospital to an outpatient setting.

METHODS

The Society of Hospital Medicine's Hospital Quality and Patient Safety committee assembled a panel of care transition researchers, process improvement experts, and hospitalists to review the literature and develop a checklist of processes and elements required for ideal discharge of adult patients. The discharge checklist was presented at the Society of Hospital Medicine's Annual Meeting in April 2005, where it was reviewed and revised by more than 120 practicing hospitalists and hospital‐based nurses, case managers, and pharmacists. The final checklist was endorsed by the Society of Hospital Medicine.

RESULTS

The finalized checklist is a comprehensive list of the processes and elements considered necessary for optimal patient handoff at hospital discharge. This checklist focused on medication safety, patient education, and follow‐up plans.

CONCLUSIONS

The development of content and process standards for discharge is the first step in improving the handoff of care from the inpatient to the posthospital setting. Refining this checklist for patients with specific diagnoses, in specific age categories, and with specific discharge destinations may further improve information transfer and ultimately affect patient outcomes. Journal of Hospital Medicine 2006;1:354–360. © 2006 Society of Hospital Medicine.
Mitogen‐associated protein kinase‐ and protein kinase A‐dependent regulation of rhodopsin promoter expression in zebrafish rod photoreceptor cells
Authors: Yu Chuan‐Jiang , Gao Yan , Willis Callie L. , Li Ping , Tiano Joseph P. , Nakamura Paul A. , Hyde David R. , Li Lei
Published: December 2006

Mitogen‐associated protein kinase (MAPK)‐ and protein kinase A (PKA)‐dependent signal transductions play important roles in the regulation of gene expression. Both MAPK and PKA pathways can be activated by light exposure. In this study, we investigated the effect of light on MAPK and PKA signal transduction and their roles in the regulation of rhodopsin promoter expression by using transgenic zebrafish [Tg(rhod::GFP)]. The Tg(rhod::GFP) fish express short half‐life GFP that is under the transcriptional control of the zebrafish rhodopsin promoter and can therefore be used for in vivo studies of rhodopsin gene transcription in live cells. Blue light plays a role in the regulation of rhodopsin promoter expression via an MAPK‐mediated signal transduction cascade. Blue light excites cryptochromes (CRY), which activate the downstream PKC‐dependent MAPK signal pathway. White light, on the other hand, regulates rhodopsin promoter expression via a G‐protein‐coupled cAMP‐dependent PKA pathway. White light promotes dopamine release in the retina, which activates dopamine receptors and the downstream PKA pathway. Blocking MAPK signaling diminishes the blue light‐induced increases in rhodopsin promoter expression, but this treatment has no effect on white light‐mediated rhodopsin promoter expression. Conversely, blocking the PKA pathway diminishes the white light‐induced rhodopsin promoter expression but does not affect rhodopsin promoter expression regulated by blue light. Together, the data suggest that MAPK and PKA regulate rhodopsin transcription through parallel signal transduction pathways. © 2006 Wiley‐Liss, Inc.
Quantification of glucose diffusion in arterial tissues by using optical coherence tomography
Authors: Larin K V , Ghosn M G , Ivers S N , Tellez A , Granada J F
Published: December 2006

Several investigations suggest that the early stages of atherosclerosis are modulated by the selective permeability of the vascular tissue to pro-inflammatory molecules of different molecular weights. Up to date, a few experiments have been performed to study the permeability of arterial tissue to different molecules. This is primarily due to an absence of an experimental technique capable of depth-resolved, accurate and sensitive assessment of arterial permeability. In this paper, we report our pilot results on nondestructive quantification of glucose diffusion in animal arteriesin vitroby using optical coherence tomography (OCT) technique. Permeability of glucose in animal's aorta was estimated to be 1.43±0.24×10-5cm/sec from five independent experiments. Obtained results suggest capability of OCT technique for highly sensitive, accurate, and nondestructive monitoring and quantification of agents' diffusion in vascular tissues.
Investigation of mechanism of binding of molecular probe eosin to human serum albumin by Raman spectroscopy method
Authors: Vlasova I M , Polyansky D V , Saletsky A M
Published: December 2006

The mechanism of binding of molecular probe eosin to molecules of human serum albumin was studied by the Raman spectroscopy method. The position of binding center on human serum albumin molecule for eosin is determined. The amino acid residues of albumin molecule, participating in binding of eosin at different pH values of solution, are established.
High-average-power diode-side-pumped double Q-switched Nd:YAG laser
Authors: Hajiesmaeilbaigi F , Razzaghi H , Mahdizadeh M , Moghaddam M R A
Published: December 2006

We have designed a high-average-power diode-side-pumped Nd:YAG laser acousto-optically Q-switched at a pulse repetition rate range of 5-20 kHz. Double synchronized Q-switches were used for increasing the hold-off current and obtained more than 200 W average output power at 10 kHz and 110 ns pulse duration with more than 80% Q-switching efficiency and 20% optical-optical efficiency and instability of laser was 1%. The effects of various configurations of resonator on hold-off current of the laser have been experimentally studied.