bluuebunny/crossref_metadata_2025 huggingface dataset:
CA IX is an Independent Prognostic Marker in Premenopausal Breast Cancer Patients with One to Three Positive Lymph Nodes and a Putative Marker of Radiation Resistance
Authors: Brennan Donal J. , Jirstrom Karin , Kronblad Åsa , Millikan Robert C. , Landberg Goran , Duffy Michael J. , Rydén Lisa , Gallagher William M. , O'Brien Sallyann L.
Published: November 2006

Purpose: Hypoxia in breast cancer is associated with poor prognosis and down-regulation of the estrogen receptor. Carbonic anhydrase IX (CA IX) is a hypoxia-inducible gene that has been associated with poor outcome in many epithelial cancers. Previous studies of CA IX in breast cancer have been carried out on mixed cohorts of premenopausal and postmenopausal patients with locally advanced disease and varying treatment regimens. We examined the potential prognostic and predictive role of CA IX in premenopausal breast cancer patients.

Experimental Design: Using tissue microarrays, we analyzed CA IX expression in 400 stage II breast cancers from premenopausal women. The patients had previously participated in a randomized control trial comparing 2 years of tamoxifen to no systemic adjuvant treatment. Median follow-up was 13.9 years.

Results: CA IX expression correlated positively with tumor size, grade, hypoxia-inducible factor 1α, Ki-67, cyclin E, and cyclin A2 expression. CA IX expression correlated negatively with cyclin D1, estrogen receptor, and progesterone receptor. CA IX expression was associated with a reduced relapse-free survival (P = 0.032), overall survival (P = 0.022), and breast cancer–specific survival (P = 0.005). Multivariate analysis revealed that CA IX was an independent prognostic marker in untreated patients with one to three positive lymph nodes (hazard ratio, 3.2; 95% confidence interval, 1.15-9.13; P = 0.027).

Conclusion: CA IX is marker of poor prognosis in premenopausal breast cancer patients and it is an independent predictor of survival in patients with one to three positive lymph nodes. As all these patients received locoregional radiation therapy, CA IX may be associated with resistance to radiotherapy.
Synthetic MicroRNA Designed to Target Glioma-Associated Antigen 1 Transcription Factor Inhibits Division and Induces Late Apoptosis in Pancreatic Tumor Cells
Authors: Tsuda Naotake , Ishiyama Satoshi , Li Yufeng , Ioannides Constantin G. , Abbruzzese James L. , Chang David Z.
Published: November 2006

Purpose: To determine whether the synthetic microRNAs (miRNA) could effectively target tumor cells we designed several miRNA complementary to glioma-associated antigen-1 (Gli-1) mRNA and investigated their ability to inhibit tumor cell proliferation. The sonic hedgehog pathway is an early and late mediator of tumorigenesis in epithelial cancers. Activation of sonic hedgehog signaling seems to precede transformation of tissue stem cells to cancerous stem cells, with the Gli-1 transcription factor functioning as a mediator of environmental signals. Inhibiting cancer cell proliferation by targeting the Gli-1 effector pathway is difficult to achieve by chemotherapeutic agents or short interfering RNA.

Experimental Design: We hypothesized that targeting the 3′-untranslated region of Gli-1 mRNA would effectively inhibit tumor cell proliferation. To test this hypothesis, we used synthetic miRNAs of our own design and corresponding duplex/small temporal RNAs by introducing three-nucleotide loops in the 3′-untranslated region Gli-1 sequence of high GU content.

Results: We found that miRNA (Gli-1-miRNA-3548) and its corresponding duplex (Duplex-3548) significantly inhibited proliferation of Gli-1+ ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells. The miRNAs mediated delayed cell division and activation of late apoptosis in MiaPaCa-2 cells. This is the first demonstration of inhibition of pancreatic tumor cell division by designed miRNA.

Conclusions: Gli-1 miRNAs should significantly add to the general understanding of the mechanisms of metastasis and contribute toward the design of better treatments for epithelial cancers.
A Phase I Study of Single Administration of Antibody-Directed Enzyme Prodrug Therapy with the Recombinant Anti–Carcinoembryonic Antigen Antibody-Enzyme Fusion Protein MFECP1 and a Bis-Iodo Phenol Mustard Prodrug
Authors: Mayer Astrid , Francis Roslyn J. , Sharma Surinder K. , Tolner Berend , Springer Caroline J. , Martin Jan , Boxer Geoff M. , Bell James , Green Alan J. , Hartley John A. , Cruickshank Clare , Wren Julie , Chester Kerry A. , Begent Richard H.J.
Published: November 2006

Purpose: Antibody-directed enzyme prodrug therapy is a two-stage treatment whereby a tumor-targeted antibody-enzyme complex localizes in tumor for selective conversion of prodrug. The purpose of this study was to establish optimal variables for single administration of MFECP1, a recombinant antibody-enzyme fusion protein of an anti–carcinoembryonic antigen single-chain Fv antibody and the bacterial enzyme carboxypeptidase G2 followed by a bis-iodo phenol mustard prodrug. MFECP1 is manufactured in mannosylated form to facilitate normal tissue elimination.

Experimental Design: Pharmacokinetic, biodistribution, and tumor localization studies were used to test the hypothesis that MFECP1 localizes in tumor and clears from normal tissue via the liver. Firstly, safety of MFECP1 and a blood concentration of MFECP1 that would avoid systemic prodrug activation were tested. Secondly, dose escalation of prodrug was done. Thirdly, the dose of MFECP1 and timing of prodrug administration were optimized.

Results: MFECP1 was safe and well tolerated, cleared rapidly via the liver, and was less immunogenic than previously used products. Eighty-fold dose escalation from the starting dose of prodrug was carried out before dose-limiting toxicity occurred. Confirmation of the presence of enzyme in tumor and DNA interstrand cross-links indicating prodrug activation were obtained for the optimal dose and time point. A total of 28 of 31 patients was evaluable for response, the best response being a 10% reduction of tumor diameter, and 11 of 28 patients had stable disease.

Conclusions: Optimal conditions for effective therapy were established. A study testing repeat treatment is currently being undertaken.
Anti-Vascular Endothelial Growth Factor Receptor-1 Antagonist Antibody as a Therapeutic Agent for Cancer
Authors: Wu Yan , Zhong Zhaojing , Huber James , Bassi Rajiv , Finnerty Bridget , Corcoran Erik , Li Huiling , Navarro Elizabeth , Balderes Paul , Jimenez Xenia , Koo Henry , Mangalampalli Venkata R.M. , Ludwig Dale L. , Tonra James R. , Hicklin Daniel J.
Published: November 2006

Purpose: Vascular endothelial growth factor receptor-1 (VEGFR-1) plays important roles in promotion of tumor growth by mediating cellular functions in tumor vascular endothelium and cancer cells. Blockade of VEGFR-1 activation has been shown to inhibit pathologic angiogenesis and tumor growth, implicating VEGFR-1 as a potential therapeutic target for the treatment of cancer. We have thus developed a VEGFR-1 antagonist human monoclonal antibody designated as IMC-18F1 and evaluated its antitumor activity in preclinical experimental models to show the therapeutic potential of the antibody for cancer treatment in clinic.

Experimental Design: Human IgG transgenic mice were used for generation of anti-VEGFR-1 antibodies. Anti-VEGFR-1-specific blocking antibodies were identified using solid-phase binding and blocking assays. Inhibitory antitumor cell activity of IMC-18F1 was assessed in cell-based kinase and growth assays. Pharmacokinetic/pharmacodynamic studies were done to determine the association of antibody blood level with antitumor efficacy of the antibody in vivo. Antitumor efficacy of the anti-VEGFR-1 antibodies as monotherapy and in combination with cytotoxic agents was evaluated in human breast cancer xenograft models.

Results: A fully human neutralizing antibody, IMC-18F1, was shown to be a high-affinity (KD = 54 pmol) inhibitor of VEGFR-1 ligand binding (VEGF-A, VEGF-B, and placental growth factor). IMC-18F1 inhibited ligand-induced intracellular activation of VEGFR-1 and mitogen-activated protein kinase signaling and prevented ligand-stimulated in vitro growth of breast cancer cells. In vivo, IMC-18F1 suppressed the growth of human breast tumor xenografts in association with reduced mitogen-activated protein kinase and Akt activation, reduced tumor cell proliferation, and increased tumor cell apoptosis. Pharmacokinetic/pharmacodynamic studies established a plasma elimination half-life of 5 days for IMC-18F1 and a steady-state trough plasma therapeutic threshold of 88 μg/mL. Importantly, inhibition of mouse and human VEGFR-1 with MF1 and IMC-18F1, respectively, enhanced the antitumor efficacy of cytotoxic agents commonly used to treat breast cancer.

Conclusions: Based on preclinical validation studies, IMC-18F1 anti-VEGFR-1 has potential to provide clinical benefit to cancer patients.
Increased Safety with Preserved Antitumoral Efficacy on Hepatocellular Carcinoma with Dual-Regulated Oncolytic Adenovirus
Authors: Zhang Qi , Chen Guihua , Peng Linhui , Wang Xinghua , Yang Yang , Liu Chen , Shi Wenfang , Su Changqing , Wu Hongping , Liu Xinyuan , Wu Mengchao , Qian Qijun
Published: November 2006

Purpose: A dual-regulated adenovirus variant CNHK500, in which human telomerase reverse transcriptase promoter drove the adenovirus 5 (Ad5) E1a gene and hypoxia-response promoter controlled the E1b gene, was engineered. This virus has broad anticancer spectrum and higher specificity compared with mono-regulated adenovirus CNHK300. The objective of the current study is to show its antitumor selectivity and therapeutic potential.

Experimental Design: The antitumor specificity of human telomerase reverse transcriptase and hypoxia response promoters was evaluated in a panel of tumor and normal cells. Under the control of these promoters, the tumor-selective expression of E1a and E1b genes was evaluated. Further in vitro antitumor specificity and potency of this virus were characterized by viral replication and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Subsequently, hepatocellular carcinoma xenografts were established to evaluate CNHK500 antitumor efficacy in vivo by different routes of virus administration and different dosages.

Results: Human telomerase reverse transcriptase and hypoxia response promoters were activated in a tumor-selective manner or under hypoxia treatment in a broad panel of cells. Selective adenoviral early gene expression, efficient viral replication, and oncolysis were observed in all tested cancer cells with more attenuated replication capacity in normal cells. Significant regression of hepatocellular carcinoma xenografts and prolonged survival were observed by either i.t. or i.v. administration.

Conclusions: CNHK500 greatly reduced side effects in normal cells via dual control of adenoviral essential genes while still preserving potent antitumor efficacy on broad-spectrum cancer cells in vitro and in vivo. It can be used as a powerful therapeutic agent not only for liver cancers but also for other solid tumors.
Does the EGFR and VEGF Expression Predict the Prognosis in Colon Cancer?
Authors: Doger Furuzan Kacar , Meteoglu Ibrahim , Tuncyurek Pars , Okyay Pinar , Cevikel Hakan
Published: November 2006

Background/Aim: Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are frequently encountered with aggressive tumor phenotype and poor prognosis, but the relationship between EGFR/VEGF expression and survival remains unclear. The aim of our study was to further investigate the prognostic value of EGFR and VEGF expression in colon cancer. Materials and Methods: The pathological specimens of 60 colon carcinoma patients were retrospectively evaluated and grouped according to EGFR and VEGF staining intensity and percentage of stained neoplastic cells. A final score was assigned to each case by multiplying percentage and staining score. The patients were stratified into the following categories: negative (score 0), low expression (score 1 or 2), and high expression (score 4). The remaining patient data were filtered out from the institutional cancer database. Results: The mean survival time was 28.93 ± 14.1 (range 2–52) months in the EGFR-negative group, 23.92 ± 14.0 (range 6–46) months in the group with a low EGFR expression, and 17.00 ± 12.8 (range 10–40) months in the group with a high EGFR expression. The median survival time was 27.50 ± 14.7 (range 4–52) months in the VEGF-negative group, 29.33 ± 12.8 (range 6–48) months in the group with a low VGEF expression, and 14.50 ± 14.2 (range 2–40) months in the group with a high VGEF expression. The expression of EGFR and VEGF was not an independent factor that affects survival. Conclusions: The EGFR and VEGF expression rates of colon tumors do not predict the survival. In addition, the EGFR expression in the primary tumor was not predictive of metastatic lymph nodes. The prognostic value of EGFR/VEGF staining may be further questioned.
Cellular Mechanisms of Vestibular Compensation
Authors: Paterson Janet M. , Menzies John R.W. , Bergquist Filip , Dutia Mayank B.
Published: November 2006

Vestibular compensation, the behavioral recovery that takes place after unilateral vestibular deafferentation, is a complex and multifactorial process involving synaptic and neuronal plasticity in the vestibular nuclei, cerebellum and related structures. Recent experimental evidence suggests that changes in the intrinsic properties of the vestibular nucleus neurons, changes in the efficacy of their inhibitory synaptic inputs, activity-dependent rewiring of synaptic connectivity in the vestibular brainstem, and changes in the cerebellar control of the brainstem neurons are involved in the rebalancing of resting activity of the vestibular neurons after deafferentation. In this article, we review recent advances in understanding the cellular and molecular mechanisms of vestibular compensation.
Peripheral Vestibular Responses to Sound
Authors: Curthoys Ian S.
Published: November 2006

As well as activating the cochlea, sound also activates some vestibular receptors and afferents. That is true for both air- and bone-conducted sound and this review briefly summarizes the neural evidence for vestibular activation by sound in mammals and considers the implications of this result. These neural results have been rapidly translated into clinical use and underpin a new clinical test of human vestibular function using sound as the test stimulus.
Prothrombotic Effects of Hyperhomocysteinemia and Hypercholesterolemia in ApoE-Deficient Mice
Authors: Wilson Katina M. , McCaw Ryan B. , Leo Lorie , Arning Erland , Lhoták Šárka , Bottiglieri Teodoro , Austin Richard C. , Lentz Steven R.
Published: November 2006

Objective—

We tested the hypothesis that hyperhomocysteinemia and hypercholesterolemia promote arterial thrombosis in mice.

Methods and Results—

Male apolipoprotein E (
Apoe
)-deficient mice were fed one of four diets: control, hyperhomocysteinemic (HH), high fat (HF), or high fat/hyperhomocysteinemic (HF/HH). Total cholesterol was elevated 2-fold with the HF or HF/HH diets compared with the control or HH diets (
P
<0.001). Plasma total homocysteine (tHcy) was elevated (12 to 15 μmol/L) with the HH or HF/HH diets compared with the control or HF diets (4 to 6 μmol/L;
P
<0.001). Aortic sinus lesion area correlated strongly with total cholesterol (
P
<0.001) but was independent of tHcy. At 12 weeks of age, the time to thrombotic occlusion of the carotid artery after photochemical injury was >50% shorter in mice fed the HF diets, with or without hyperhomocysteinemia, compared with the control diet (
P
<0.05). At 24 weeks of age, carotid artery thrombosis was also accelerated in mice fed the HH diet (
P
<0.05). Endothelium-dependent nitric oxide–mediated relaxation of carotid artery rings was impaired in mice fed the HF, HH, or HF/HH diets compared with the control diet (
P
<0.05).

Conclusions—

Hyperhomocysteinemia and hypercholesterolemia, alone or in combination, produce endothelial dysfunction and increased susceptibility to thrombosis in Apoe-deficient mice.
Statin Treatment Upregulates Vascular Neuronal Nitric Oxide Synthase Through Akt/NF-κB Pathway
Authors: Nakata Sei , Tsutsui Masato , Shimokawa Hiroaki , Yamashita Takahiro , Tanimoto Akihide , Tasaki Hiromi , Ozumi Kiyoshi , Sabanai Ken , Morishita Tsuyoshi , Suda Osamu , Hirano Hideyasu , Sasaguri Yasuyuki , Nakashima Yasuhide , Yanagihara Nobuyuki
Published: November 2006

Objective—

Three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are known to enhance vascular expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS). In this study, we examined whether statins also upregulate vascular expression of neuronal NOS (nNOS).

Methods and Results—

In cultured rat aortic smooth muscle cells, treatment with atorvastatin significantly increased nNOS expression, associated with activation of Akt and NF-κB. Inhibition of Akt by dominant-negative Akt suppressed atorvastatin-induced nNOS expression as well as Akt and NF-κB activation. Inhibition of NF-κB by dominant-negative IκB also attenuated atorvastatin-induced nNOS expression and NF-κB activation, but not Akt activation. We further examined whether atorvastatin also enhances nNOS expression in isolated mouse aorta, and if so, how much nNOS-derived NO accounts for atorvastatin-induced NOx production. In isolated aortas of wild-type mice, atorvastatin significantly increased all three NOS isoform expression and NOx production. In isolated aortas of doubly i/eNOS
−/−
, n/eNOS
−/−
, and n/iNOS
−/−
mice, which express only nNOS, iNOS, and eNOS, respectively, atorvastatin-induced NOx production was approximately 25%, 25%, and 50% to that of wild-type mice, respectively, suggesting that nNOS accounts for 25% of the atorvastatin-mediated NOx production.

Conclusions—

These results indicate that atorvastatin upregulates vascular nNOS through Akt/NF-κB pathway, demonstrating a novel nNOS-mediated vascular effect of the statin.
A Novel Signal Transduction Cascade Involving Direct Physical Interaction of the Renin/Prorenin Receptor With the Transcription Factor Promyelocytic Zinc Finger Protein
Authors: Schefe Jan H. , Menk Mario , Reinemund Jana , Effertz Karin , Hobbs Robin M. , Pandolfi Pier Paolo , Ruiz Patricia , Unger Thomas , Funke-Kaiser Heiko
Published: November 2006

A human renin/prorenin receptor (RER) has recently been cloned. To gain insight into the molecular function of the RER, we studied its signal transduction mechanisms. Initially, we found a ubiquitous and intracellular expression pattern of the human RER. Consistently, we observed several transcriptional start sites and a high promoter activity of the human RER. We could identify the transcription factor promyelocytic zinc finger (PLZF) protein as a direct protein interaction partner of the C-terminal domain of the RER by yeast 2-hybrid screening and coimmunoprecipitation. Coimmunoprecipitation experiments also indicated homodimerization of the RER. On activation of the RER by renin, PLZF is translocated into the nucleus and represses transcription of the RER itself, thereby creating a very short negative feedback loop, but activates transcription of the p85α subunit of the phosphatidylinositol-3 kinase (PI3K-p85α). Small interfering RNA against the RER abolished these effects. A PLZF
cis
-element in the RER promoter was identified by site-directed mutagenesis and electrophoretic mobility-shift assay. Renin stimulation caused a 6-fold recruitment of PLZF to this promoter region as shown by chromatin immunoprecipitation. Moreover, renin stimulation of rat H9c2 cardiomyoblasts induced an increase of cell number and a decrease of apoptosis. These effects were partly abolished by PI3K inhibition and completely abrogated by small interfering RNA against PLZF. Finally, experiments in PLZF knockout mice confirmed the role of PLZF as an upstream regulator of RER and PI3K-p85α. Our data demonstrate the existence of a novel signal transduction pathway involving the ligand renin, RER, and the transcription factor PLZF, which is of physiological and putative pathophysiological relevance.
Transcriptional Silencing of the Death Gene BNIP3 by Cooperative Action of NF-κB and Histone Deacetylase 1 in Ventricular Myocytes
Authors: Shaw James , Zhang Tong , Rzeszutek Marek , Yurkova Natalia , Baetz Delphine , Davie James R. , Kirshenbaum Lorrie A.
Published: November 2006

Earlier we identified a survival role for NF-κB in ventricular myocytes, however, the underlying mechanism was undefined. In this report we provide new mechanistic evidence that the hypoxia-inducible death factor BNIP3 is transcriptionally silenced by NF-κB through a mechanism that involves the cooperative actions of HDAC1. Activation of the NF-κB signaling pathway in ventricular myocytes suppressed basal and hypoxia-inducible BNIP3 gene activity. Basal Bnip3 gene expression was increased in cells derived from p65
−/−
deficient mice. The histone deacetylase (HDAC) inhibitor Trichostatin A (TSA 10 nM) suppressed the inhibitory actions of NF-κB on Bnip3 gene transcription. Basal and hypoxia- induced Bnip3 transcription was repressed by wild type but not a catalytically inactive mutant of HDAC1. Immunoprecipitation assays verified interaction of HDAC1 with wild type p65 NF-κB and mutations of p65 defective for transactivation in ventricular myocytes. Deletion analysis revealed canonical NF-κB elements within the Bnip3 promoter to be important for repression of Bnip3 gene expression by HDAC1. Further, the ability of HDAC1 to repress Bnip3 gene transcription was lost in cells derived from p65
−/−
deficient mice but was restored by repletion of p65 NF-κB into p65
−/−
cells. Mutations of p65 NF-κB defective for DNA binding but not for transactivation abrogated the inhibitory actions of HDAC1 on the Bnip3 gene transcription. Together, our findings provide new mechanistic insight into the cytoprotective actions conferred by NF-κB that extend to the active transcriptional repression of the death factor Bnip3 through a mechanism that is mutually dependent on HDAC-1.
Granulocyte-Colony–Stimulating Factor Mobilizes Bone Marrow Stem Cells in Patients With Subacute Ischemic Stroke
Authors: Sprigg Nikola , Bath Philip M. , Zhao Lian , Willmot Mark R. , Gray Laura J. , Walker Marion F. , Dennis Martin S. , Russell Nigel
Published: November 2006

Background and Purpose—

Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony–stimulating factor (G-CSF) after stroke and its effect on circulating CD34+ stem cells.

Methods—

We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 μg/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34+ stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment.

Results—

Thirty-six patients, whose mean±SD age was 76±8 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 μg/kg) increased CD34+ count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve,
P
=0.005). A dose-dependent rise in white cell count (
P
<0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days.

Conclusions—

G-CSF is effective at mobilizing bone marrow CD34+ stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined.
Collecting the Desert in the Carolingian West
Authors: Coon Lynda
Published: November 2006

The Egyptian desert summoned for its early medieval progeny memories of a past age of superhuman askêsis that posed a challenge to Carolingian attempts at Benedictine hegemony. In response, the architects of ninth-century monastic reform labored to present their votaries with a carefully controlled memory of the Egyptian past, and they did so through a propagandistic aesthetic of literary, visual, and ritual "bricolage." Jaś Elsner defines this aesthetic of bricolage as an artistic form based on symbolic ownership of the past through the display of ancient spolia on contemporary monuments (e.g., the sculptured reliefs collected from past, imperial regimes and exhibited as spolia on the Arch of Constantine) or the layering of present-day texts with past literary forms (e.g., Christian typological exegesis of Hebrew Scripture). Similarly, for the Carolingians, who also ventured into the artistic realm of bricolage, collecting, embodying, and displaying were methods of exerting control over the past.
The Franciscan Hermit: Seeker, Prisoner, Refugee
Authors: Roest Bert
Published: November 2006

This article claims that the initial religious aspirations of the Friars Minor were heavily indebted to eremitical ideals, and that these ideals were never totally forgotten, notwithstanding the quick transformation of the Franciscan movement into an order of professional priests and theologians. The article sketches first of all the eremitical roots of the early Franciscan life. Then it covers the representation of early Franciscan hermitages and the eremitical life in the Vitae of Francis, pointing out specific parallels with Athanasius's Life of Antony. Subsequently, it analyses Francis's conception of the eremitical life according to his Regula pro eremitoriis data. It closes with a review of the ways in which eremitical traditions were retained, both as formative elements in the Franciscan handbooks of religious instruction, and as statements of protest and escape from dominant developments within the Order.
Ex vita patrum formatur vita fratrum: The Appropriation of the Desert Fathers in the Augustinian Monasticism of the Later Middle Ages
Authors: Saak Eric
Published: November 2006

This article traces the role of the desert fathers in the creation of the late medieval Augustinian Myth. It argues that the major problem facing members of the Order of Hermits of Saint Augustine (OESA) was how to appropriate the tradition of the desert fathers and that of Augustine's monasticism for the tradition of the Order. In this light, special attention is given to the Pseudo-Augustinian Sermones ad fratres in eremo and the central importance of John Cassian and Paul of Thebes. Of particular importance are the works of Jordan of Quedlinburg, which shaped the identity of the OESA from the mid-fourteenth to the early sixteenth century. The desert fathers provided the model of the eremitical life, and thus Jordan "mythified" the desert fathers as he had Augustine himself. This was not an issue of historical identification, but of mythic creation in an attempt to provide the foundation of the late medieval OESA.
Bringing Home the Homeless: Landscape and History in Egyptian Hagiography
Authors: van der Vliet Jacques
Published: November 2006

This essay evaluates Egyptian hagiography as a historical source by defining its function in the construction of a Christian landscape. To this purpose, it discusses the Bohairic Martyrdom of Saint James the Persian, shifting attitudes towards the burial of monastic saints, Coptic stories about temple conversions, and contending Christian and Muslim traditions concerning the Holy Family in Egypt.
Time Scales of Land Surface Hydrology
Authors: Wang Aihui , Zeng Xubin , Shen Samuel S. P. , Zeng Qing-Cun , Dickinson Robert E.
Published: November 2006

This paper intends to investigate the time scales of land surface hydrology and enhance the understanding of the hydrological cycle between the atmosphere, vegetation, and soil. A three-layer model for land surface hydrology is developed to study the temporal variation and vertical structure of water reservoirs in the vegetation–soil system in response to precipitation forcing. The model is an extension of the existing one-layer bucket model. A new time scale is derived, and it better represents the response time scale of soil moisture in the root zone than the previously derived inherent time scale (i.e., the ratio of the field capacity to the potential evaporation). It is found that different water reservoirs of the vegetation–soil system have different time scales. Precipitation forcing is mainly concentrated on short time scales with small low-frequency components, but it can cause long time-scale disturbances in the soil moisture of root zone. This time scale increases with soil depth, but it can be reduced significantly under wetter conditions. Although the time scale of total water content in the vertical column in the three-layer model is similar to that of the one-layer bucket model, the time scale of evapotranspiration is very different. This suggests the need to consider the vertical structure in land surface hydrology reservoirs and in climate study.
On the Uncertainties of Flash Flood Guidance: Toward Probabilistic Forecasting of Flash Floods
Authors: Ntelekos Alexandros A. , Georgakakos Konstantine P. , Krajewski Witold F.
Published: November 2006

Quantifying uncertainty associated with flash flood warning or forecast systems is required to enable informed decision making by those responsible for operation and management of natural hazard protection systems. The current system used by the U.S. National Weather Service (NWS) to issue flash-flood warnings and watches over the Unites States is a purely deterministic system. The authors propose a simple approach to augment the Flash Flood Guidance System (FFGS) with uncertainty propagation components. The authors briefly discuss the main components of the system, propose changes to improve it, and allow accounting for several sources of uncertainty. They illustrate their discussion with examples of uncertainty quantification procedures for several small basins of the Illinois River basin in Oklahoma. As the current FFGS is tightly coupled with two technologies, that is, threshold-runoff mapping and the Sacramento Soil Moisture Accounting Hydrologic Model, the authors discuss both as sources of uncertainty. To quantify and propagate those sources of uncertainty throughout the system, they develop a simple version of the Sacramento model and use Monte Carlo simulation to study several uncertainty scenarios. The results point out the significance of the stream characteristics such as top width and the hydraulic depth on the overall uncertainty of the Flash Flood Guidance System. They also show that the overall flash flood guidance uncertainty is higher under drier initial soil moisture conditions. The results presented herein, although limited, are a necessary first step toward the development of probabilistic operational flash flood guidance forecast-response systems.
Soil Moisture Memory in AGCM Simulations: Analysis of Global Land–Atmosphere Coupling Experiment (GLACE) Data
Authors: Seneviratne Sonia I. , Koster Randal D. , Guo Zhichang , Dirmeyer Paul A. , Kowalczyk Eva , Lawrence David , Liu Ping , Mocko David , Lu Cheng-Hsuan , Oleson Keith W. , Verseghy Diana
Published: November 2006

Soil moisture memory is a key aspect of land–atmosphere interaction and has major implications for seasonal forecasting. Because of a severe lack of soil moisture observations on most continents, existing analyses of global-scale soil moisture memory have relied previously on atmospheric general circulation model (AGCM) experiments, with derived conclusions that are probably model dependent. The present study is the first survey examining and contrasting global-scale (near) monthly soil moisture memory characteristics across a broad range of AGCMs. The investigated simulations, performed with eight different AGCMs, were generated as part of the Global Land–Atmosphere Coupling Experiment.

Overall, the AGCMs present relatively similar global patterns of soil moisture memory. Outliers are generally characterized by anomalous water-holding capacity or biases in radiation forcing. Water-holding capacity is highly variable among the analyzed AGCMs and is the main factor responsible for intermodel differences in soil moisture memory. Therefore, further studies on this topic should focus on the accurate characterization of this parameter for present AGCMs. Despite the range in the AGCMs’ behavior, the average soil moisture memory characteristics of the models appear realistic when compared to available in situ soil moisture observations. An analysis of the processes controlling soil moisture memory in the AGCMs demonstrates that it is mostly controlled by two effects: evaporation’s sensitivity to soil moisture, which increases with decreasing soil moisture content, and runoff’s sensitivity to soil moisture, which increases with increasing soil moisture content. Soil moisture memory is highest in regions of medium soil moisture content, where both effects are small.
The Impact of Direct Aerosol Radiative Forcing on Surface Insolation and Spring Snowmelt in the Southern Sierra Nevada
Authors: Kim Jinwon , Gu Yu , Liou K. N.
Published: November 2006

To understand the regional impact of the atmospheric aerosols on the surface energy and water cycle in the southern Sierra Nevada characterized by extreme variations in terrain elevation, the authors examine the aerosol radiative forcing on surface insolation and snowmelt for the spring of 1998 in a regional climate model experiment. With a prescribed aerosol optical thickness of 0.2, it is found that direct aerosol radiative forcing influences spring snowmelt primarily by reducing surface insolation and that these forcings on surface insolation and snowmelt vary strongly following terrain elevation. The direct aerosol radiative forcing on surface insolation is negative in all elevations. It is nearly uniform in the regions below 2000 m and decreases with increasing elevation in the region above 2000 m. This elevation dependency in the direct aerosol radiative forcing on surface insolation is related to the fact that the amount of cloud water and the frequency of cloud formation are nearly uniform in the lower elevation region, but increase with increasing elevation in the higher elevation region. This also suggests that clouds can effectively mask the direct aerosol radiative forcing on surface insolation. The direct aerosol radiative forcing on snowmelt is notable only in the regions above 2000 m and is primarily via the reduction in the surface insolation by aerosols. The effect of this forcing on low-level air temperature is as large as −0.3°C, but its impact on snowmelt is small because the sensible heat flux change is much smaller than the insolation change. The direct aerosol radiative forcing on snowmelt is significant only when low-level temperature is near the freezing point, between −3° and 5°C. When low-level temperature is outside this range, the direct aerosol radiative forcing on surface insolation has only a weak influence on snowmelt. The elevation dependency of the direct aerosol radiative forcing on snowmelt is related with this low-level temperature effect as the occurrence of the favored temperature range is most frequent in high elevation regions.
Catch Characteristics of Precipitation Gauges in High-Latitude Regions with High Winds
Authors: Sugiura Konosuke , Ohata Tetsuo , Yang Daqing
Published: November 2006

Intercomparison of solid precipitation measurement at Barrow, Alaska, has been carried out to examine the catch characteristics of various precipitation gauges in high-latitude regions with high winds and to evaluate the applicability of the WMO precipitation correction procedures. Five manual precipitation gauges (Canadian Nipher, Hellmann, Russian Tretyakov, U.S. 8-in., and Wyoming gauges) and a double fence intercomparison reference (DFIR) as an international reference standard have been installed. The data collected in the last three winters indicates that the amount of solid precipitation is characteristically low, and the zero-catch frequency of the nonshielded gauges is considerably high, 60%–80% of precipitation occurrences. The zero catch in high-latitude high-wind regions becomes a significant fraction of the total precipitation. At low wind speeds, the catch characteristics of the gauges are roughly similar to the DFIR, although it is noteworthy that the daily catch ratios decreased more rapidly with increasing wind speed compared to the WMO correction equations. The dependency of the daily catch ratios on air temperature was confirmed, and the rapid decrease in the daily catch ratios is due to small snow particles caused by the cold climate. The daily catch ratio of the Wyoming gauge clearly shows wind-induced losses. In addition, the daily catch ratios are considerably scattered under strong wind conditions due to the influence of blowing snow. This result suggests that it is not appropriate to extrapolate the WMO correction equations for the shielded gauges in high-latitude regions for high wind speed of over 6 m s−1.
Response of Water Vapor and CO2 Fluxes in Semiarid Lands to Seasonal and Intermittent Precipitation Pulses
Authors: Ivans Sasha , Hipps Lawrence , Leffler A. Joshua , Ivans Carolyn Y.
Published: November 2006

Precipitation pulses are important in controlling ecological processes in semiarid ecosystems. The effects of seasonal and intermittent precipitation events on net water vapor and CO2 fluxes were determined for crested wheatgrass (Agropyron desertorum), juniper (Juniperus osteosperma), and sagebrush (Artemisia tridentata) ecosystems using eddy covariance measurements. The measurements were made at Rush Valley, Utah, in the northern Great Basin of the United States. Data were evaluated during the growing seasons of 2002 and 2003. Each of these communities responds to precipitation pulses in all seasons, but these responses vary among season and ecosystem, and differ for water vapor and CO2. The degree and direction of response (i.e., net uptake or efflux) depended upon the timing and amount of precipitation. In early spring, both evapotranspiration (ET) and CO2 fluxes responded only slightly to precipitation pulses because soils were already moist from snowmelt and spring rains. As soils dried later in the spring, ET response to rainfall increased. The summer season was very warm and dry in both years, and both water and CO2 fluxes were generally reduced as compared to fluxes in the spring. Water vapor fluxes increased during and immediately after periodic summer rain events at all sites, especially at juniper, followed by the sagebrush and crested wheatgrass sites. Net CO2 exchange changed significantly at the juniper and sagebrush sites but changed very little at the crested wheatgrass site due to senescence of this grass. However, in the wetter summer of 2003, the grass species maintained physiological activity and responded to rain events. In the fall of both years, responses of ET and CO2 fluxes to precipitation were very similar for all three communities, with only small changes, presumably due to significantly lower temperatures in the fall. This research documents the importance of the temporal distribution of rainfall on patterns of ET and CO2 fluxes and suggests that soil moisture and stand-level leaf area index (LAI) are critical factors governing ET and CO2 responses to precipitation in these communities.
Advanced Applications of Structural Equation Modeling in Counseling Psychology Research
Authors: Martens Matthew P. , Haase Richard F.
Published: November 2006

Structural equation modeling (SEM) is a data-analytic technique that allows researchers to test complex theoretical models. Most published applications of SEM involve analyses of cross-sectional recursive (i.e., unidirectional) models, but it is possible for researchers to test more complex designs that involve variables observed at multiple points in time or variables implicated in reciprocal feedback loops (i.e., bidirectional models). Given SEM’s popularity among counseling psychology researchers, this article aims to introduce three SEM designs not often seen in the counseling psychology literature: cross-lagged panel analyses, latent growth curve modeling, and nonrecursive mediated model analysis. For each design, the authors provide a brief rationale regarding its purpose, procedures for specifying a model to test the design, and a worked illustration.
Scale Development Research
Authors: Worthington Roger L. , Whittaker Tiffany A.
Published: November 2006

The authors conducted a content analysis on new scale development articles appearing in the Journal of Counseling Psychology during 10 years (1995 to 2004). The authors analyze and discuss characteristics of the exploratory and confirmatory factor analysis procedures in these scale development studies with respect to sample characteristics, factorability, extraction methods, rotation methods, item deletion or retention, factor retention, and model fit indexes. The authors uncovered a variety of specific practices that were at variance with the current literature on factor analysis or structural equation modeling. They make recommendations for best practices in scale development research in counseling psychology using exploratory and confirmatory factor analysis.
Color-Blind Ideology and the Cultural Appropriation of Hip-Hop
Authors: Rodriquez Jason
Published: November 2006

This article examines how white youths culturally appropriate hip-hop by adhering to the demands of color-blind ideology. Using ethnographic methods and interviews of members in a local hip-hop scene, I argue that colorblind ideology provides whites with the discursive resources to justify their presence in the scene, and more important, to appropriate hip-hop by removing the racially coded meanings embedded in the music and replacing them with color-blind ones. This research contributes to the existing scholarship on racial ideology by analyzing how it is put into action by individuals in a specific local context in which race is salient. Furthermore, it extends our understanding of how color-blind ideology operates in practice, enabling whites with the discursive resources and racial power to culturally appropriate hip-hop, however unintentionally, for their own purposes.
Criticism as Deviance and Social Control in Alcoholics Anonymous
Authors: Hoffmann Heath C.
Published: November 2006

Emile Durkheim recognized many years ago that all groups—even a “society of saints”—produce deviants. Group members must then come to terms with how to respond to and control those who violate the group's moral order. The Alcoholics Anonymous (AA) meeting offers an interesting context to explore this process. AA members, by their own admission, are far from being “saints,” some admitting to adultery, theft, and assault during their active alcoholism. In this article, the author describes the moral order of AA that functions to prevent and create deviant behavior, focusing on AA members’ use of criticism as both a method of social control and a violation of AA's normative system. This seeming contradiction is explained by showing that criticism is a social control strategy available primarily to high-status members, used primarily against lower-status members.
Minority Group, Majority Space
Authors: Cutler Marianne
Published: November 2006

Based on an ethnographic study of young-adult Jews in a Southern community, this article examines strategies for the protection of self when minority groups navigate terrain that is perceived to be hostile. Although few of the participants of this study had experienced any explicitly anti-Jewish behavior directly, almost all experienced a feeling of unease living in an environment in which a public Christian identity was normative. This unease was grounded in the historical persecution of Jews (and the never-again credo with which many post-Holocaust generation Jews have been raised) and in direct experience with their neighbors' and coworkers' ignorance about Judaism and Jewish life. Study participants used a variety of emotion-work strategies, including compartmentalizing their Jewish identities, distancing themselves emotionally from coworkers, and using humor to deflect potential identity-based insults to sustain a sense of safety.
Gender, Self-Employment, and Earnings
Authors: Budig Michelle J.
Published: November 2006

Using data from the 1979 to 1998 waves of the National Longitudinal Survey of Youth, the author explores how gender, family, and class alter the impact of self-employment on earnings. Fixed-effect regression results show that while self-employment positively influences men’s earnings, not all women similarly benefit. Professionals receive the same self-employment earnings premium, regardless of gender. However, self-employment in nonprofessional occupations negatively affects women’s earnings, with wives and mothers incurring the greatest penalties. The high concentration of nonprofessional self-employed women in child care accounts for much of these penalties. Results are robust despite inclusion of controls for human capital and labor supply, job characteristics, occupational and industrial gender segregation, and demographic characteristics. The compensating differentials argument, that women with greater family responsibilities trade earnings for the family-friendly aspects of self-employment, is discussed in light of these findings. While this argument may explain women’s returns to nonprofessional self-employment, it is less persuasive for interpreting women’s returns to professional self-employment.
Bereavement in Cognitively Impaired Older Adults: Case Series and Clinical Considerations
Authors: Grief Cindy J. , Myran David D.
Published: November 2006

The intersection of bereavement and cognitive impairment presents unique clinical challenges that have been overlooked in the literature. Cognitive impairment can interfere with normal ways of coping in the aftermath of loss. Elderly persons with cognitive impairment may have difficulty processing their loss and may even forget that their loved one has died, repeatedly asking other family members when the deceased is coming to visit. This can prove devastating for such individuals and their families, who are forced to keep reexperiencing their grief. This article examines the phenomenology of bereavement-related distress in older adults with cognitive impairment and dementia through a case series gathered from a large geriatric facility. The dilemmas in caring for bereaved elderly with cognitive difficulties and their families are highlighted, drawing attention to a vulnerable population. The purpose of this undertaking is to present a novel classification of a clinically relevant but overlooked issue as well as provide strategies for management and suggestions for future research.