bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index
Authors: McDonagh Charlotte F. , Kim Kristine M. , Turcott Eileen , Brown Lindsay L. , Westendorf Lori , Feist Tiffany , Sussman Django , Stone Ivan , Anderson Martha , Miyamoto Jamie , Lyon Robert , Alley Stephen C. , Gerber Hans-Peter , Carter Paul J. 
Published: September 2008

Abstract
An anti-CD70 antibody conjugated to monomethylauristatin F (MMAF) via a valine-citrulline dipeptide containing linker has been shown previously to have potent antitumor activity in renal cell cancer xenograft studies. Here, we generated a panel of humanized anti-CD70 antibody IgG variants and conjugated them to MMAF to study the effect of isotype (IgG1, IgG2, and IgG4) and Fcγ receptor binding on antibody-drug conjugate properties. All IgG variants bound CD70+ 786-O cells with an apparent affinity of ∼1 nmol/L, and drug conjugation did not impair antigen binding. The parent anti-CD70 IgG1 bound to human FcγRI and FcγRIIIA V158 and mouse FcγRIV and this binding was not impaired by drug conjugation. In contrast, binding to these Fcγ receptors was greatly reduced or abolished in the variant, IgG1v1, containing the previously described mutations, E233P:L234V:L235A. All conjugates had potent cytotoxic activity against six different antigen-positive cancer cell lines in vitro with IC50 values of 30 to 540 pmol/L. The IgGv1 conjugate with MMAF displayed improved antitumor activity compared with other conjugates in 786-O and UMRC3 models of renal cell cancer and in the DBTRG05-MG glioblastoma model. All conjugates were tolerated to ≥40 mg/kg in mice. Thus, the IgG1v1 MMAF conjugate has an increased therapeutic index compared with the parent IgG1 conjugate. The improved antitumor activity of the IgG1v1 auristatin conjugates may relate to increased exposure as suggested by pharmacokinetic analysis. The strategy used here for enhancing the therapeutic index of antibody-drug conjugates is independent of the antigen-binding variable domains and potentially applicable to other antibodies. [Mol Cancer Ther 2008;7(9):2913–23]
Critical role of prostate apoptosis response-4 in determining the sensitivity of pancreatic cancer cells to small-molecule inhibitor-induced apoptosis
Authors: Azmi Asfar Sohail , Wang Zhiwei , Burikhanov Ravshan , Rangnekar Vivek M. , Wang Guoping , Chen Jianyong , Wang Shaomeng , Sarkar Fazlul H. , Mohammad Ramzi M. 
Published: September 2008

Abstract
Role of prostate apoptosis response-4 (PAR-4) has been well described in prostate cancer. However, its significance in other cancers has not been fully elucidated. For the current study, we selected four pancreatic cancer cell lines (BxPC-3, Colo-357, L3.6pl, and HPAC) that showed differential endogenous expression of PAR-4. We found that nonpeptidic small-molecule inhibitors (SMI) of Bcl-2 family proteins (apogossypolone and TW-37; 250 nmol/L and 1 μmol/L, respectively) could induce PAR-4-dependent inhibition of cell growth and induction of apoptosis. Sensitivity to apoptosis was directly related to the expression levels of PAR-4 (R = 0.92 and R2 = 0.95). Conversely, small interfering RNA against PAR-4 blocked apoptosis, confirming that PAR-4 is a key player in the apoptotic process. PAR-4 nuclear localization is considered a prerequisite for cells to undergo apoptosis, and we found that the treatment of Colo-357 and L3.6pl cells with 250 nmol/L SMI leads to nuclear localization of PAR-4 as confirmed by 4′,6-diamidino-2-phenylindole staining. In combination studies with gemcitabine, pretreatment with SMI leads to sensitization of Colo-357 cells to the growth-inhibitory and apoptotic action of a therapeutic drug, gemcitabine. In an in vivo setting, the maximum tolerated dose of TW-37 in xenograft of severe combined immunodeficient mice (40 mg/kg for three i.v. injections) led to significant tumor inhibition. Our results suggest that the observed antitumor activity of SMIs is mediated through a novel pathway involving induction of PAR-4. To our knowledge, this is the first study reporting SMI-mediated apoptosis involving PAR-4 in pancreatic cancer. [Mol Cancer Ther 2008;7(9):2884–93]
The Hybrid Story of Balaam (Numbers 22–24): Theology for the Diaspora in the Torah
Authors: Sals Ulrike 
Published: September 2008

AbstractThe strange character of Numbers 22–24 as a story about foreigners and their attempts to rule YHWH can successfully be read with Homi Bhabha's concept of hybridity and Gayatri Spivak's subaltern. Focusing on the characters' relationships in this text, Balak is the hegemon and Balaam the subaltern, and this constitutes much of their communicational failures. The donkey's episode serves as a lesson for the reader as well as for Balaam who is the hegemon in this case: he learns—as Balak does not—that God is the real worldly and 'wordly' hegemon. This monotheistic message is explained to the Judaean readers/listeners through non-Judean protagonists. Many details point to an origin of the final text in a reception of the deuteronomistic YHWH/Assur/Israel constellation and theology in Persian times.
Moses and Abraham Go Arctic
Authors: Petterson Christina 
Published: September 2008

AbstractThis paper reads the Gospel of John as expounded by Musa W. Dube in her article 'Savior of the World but not of This World: A Post-Colonial Reading of Spatial Construction in John' alongside the religious situation in contemporary Greenland, itself an often ignored example of the dilemmas of colonisation and postcolonialism. Tensions between the Danish Lutheran State Church and anti-Danish members of the indigenous Inuit populations over the place of Christianity in contemporary Inuit identity are analogous to the tension in John's gospel over who can claim to be Israel. In making this comparison, I hope not to exemplify what David Jobling warns us about: "Simple links between biblical and current situations, whether they leave the Bible looking good or bad, convey no lasting benefit." I seek to overcome the theoretical problems inherent in blindly adopting Dube's intertextual methods by employing Jonathan Z. Smith's observations on comparison. This in turn poses another range of problems about identity and method for readers as well as for the text which will be outlined here. Both the New Testament and the contemporary situation reveal the complexity of identities which simple categories of 'coloniser' and 'colonised' do not encompass.
Development of a Zero-Dimensional Mesoscale Thermal Model for Urban Climate
Authors: Silva Humberto R. , Bhardwaj Rahul , Phelan Patrick E. , Golden Jay S. , Grossman-Clarke Susanne 
Published: September 2008

Abstract
A simple energy balance model is created for use in developing mitigation strategies for the urban heat island effect. The model is initially applied to the city of Phoenix, Arizona. There are six primary contributions to the overall energy balance: incident solar radiation, anthropogenic heat input, conduction heat loss, outgoing evapotranspiration, outgoing convection, and outgoing emitted radiation. Meteorological data are input to the model, which then computes an urban characteristic temperature at a calculated time step for a specified time range. The model temperature is shown to have the same periodic behavior as the experimentally measured air temperatures. Predicted temperature changes, caused by increasing the average urban albedo, agree within 0.1°C with comparable maximum surface temperature predictions from the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5). The present model, while maintaining valid energy-balance physics, allows users to quickly and easily predict the relative effects of urban heat island mitigation measures. Representative mitigation strategies, namely changes in average albedo and long-wavelength emissivity are presented here. Increasing the albedo leads to the greater reduction in daytime maximum temperatures; increasing the emissivity leads to a greater reduction in nighttime minimum temperatures.
A Wind Tunnel Study on the Shape, Oscillation, and Internal Circulation of Large Raindrops with Sizes between 2.5 and 7.5 mm
Authors: Szakáll Miklós , Diehl Karoline , Mitra Subir K. , Borrmann Stephan 
Published: September 2008

Abstract
Precipitation prediction using weather radars requires detailed knowledge of the shape parameters of raindrops falling at their terminal velocities in air. Because the raindrops undergo oscillation, the most important shape parameters from the radar prediction point of view are the equilibrium drop shape, the time-averaged axis ratio, and the oscillation frequency. These parameters for individual water drops with equivalent diameter from 2.5 to 7.5 mm were investigated in a vertical wind tunnel using high-speed video imaging. A very good agreement was found between the measured and the theoretically determined raindrop shape calculated by a force balance model. A new method was developed to determine the equivalent drop diameter with the help of the oscillation frequency. The drop size determination by means of the frequency method was found to be three times more precise than by volumetric methods. The time-averaged axis ratio was found to be equal to the equilibrium axis ratio in the investigated raindrop size range. The analysis of the oscillation frequency of the raindrops revealed that the drops undergo multimode oscillations and are oscillating in a transverse mode in addition to an axisymmetric oblate–prolate mode. Experiments are included in which the internal circulation associated with drop oscillation was investigated and compared to theory.
On the Use of Satellite Altimeter Data in Argo Quality Control
Authors: Guinehut Stephanie , Coatanoan Christine , Dhomps Anne-Lise , Le Traon Pierre-Yves , Larnicol Gilles 
Published: September 2008

Abstract
Satellite altimeter measurements are used to check the quality of the Argo profiling floats time series. The method compares collocated sea level anomalies from altimeter measurements and dynamic height anomalies calculated from Argo temperature and salinity profiles for each Argo float time series. Different kinds of anomalies (sensor drift, bias, spikes, etc.) have been identified on some real-time but also delayed-mode Argo floats. About 4% of the floats should probably not be used until they are carefully checked and reprocessed by the principal investigators (PIs). The method appears to be very complementary to the existing quality control checks performed in real time or delayed mode. It could also be used to quantify the impact of the adjustments made in delayed mode on the pressure, temperature, and salinity fields.
Diabatically Induced Secondary Flows in Tropical Cyclones. Part II: Periodic Forcing
Authors: Willoughby Hugh E. 
Published: September 2008

Abstract
The linearized equation for the time-varying, axially symmetric circumferential component of the vorticity in a hurricane-like vortex closely resembles the classical Sawyer–Eliassen equation for the quasi-steady, diabatically induced secondary-flow streamfunction. The salient difference lies in the coefficients of the second partial derivatives with respect to radius and height. In the Sawyer–Eliassen equation, they are the squares of the buoyancy and isobaric local inertia frequencies; in the circumferential vorticity equation they are the differences between these quantities and the square of the frequency with which the imposed forcing varies. The coefficient of the mixed partial derivative with respect to radius and height is the same in both equations. Thus, for low frequencies the response to periodic forcing is a slowly varying analog to steady Sawyer–Eliassen solutions. For high frequencies, the solutions are radially propagating inertia-buoyancy waves. Since the local inertia frequency, which approximately defines the boundary between quasi-steady and propagating solutions, decreases with radius, quasi-steady solutions in the vortex core transform into radiating ones far from the center. Periodic forcing will always lead to some wave radiation to the storm environment unless the period of the forcing is longer than a half-pendulum day.
Composite Meteorological Forcing of Puerto Rican Springtime Flood Events
Authors: Jury Mark R. , Sanchez David M. 
Published: September 2008

Abstract
The central Antilles Islands experience short periods of heavy rainfall during the spring season (April and May) when trade winds weaken across the Caribbean Sea. Composite analysis of the top 10 flood events in the period 1979–2005 is carried out to understand the meteorological forcing. Cases are selected when mean rainfall over Puerto Rico exceeds 50 mm day−1 and emergency management reports indicate the day is a “declared weather disaster.” In the NCEP–NCAR composite analyses, pulses of moisture shift westward across the tropical Atlantic about 10 days before a flood event. Five days before the composite flood a westerly trough penetrates eastward from the Gulf of Mexico. Northward flow develops over the Caribbean Sea and a southwest-oriented cloud band extends from Colombia toward Puerto Rico. A key feature of the midtropospheric circulation field is the development of anomalous twin rotors east of Florida in the mid- to upper troposphere. The flood events coincide with a change in zonal wind shear from westerly to easterly that is brought about by slow tropical and fast subtropical wave systems.
Histopathology of the Urinary Bladders of Cynomolgus Monkeys Treated with PPAR Agonists
Authors: Hardisty Jerry F. , Anderson Daniel C. , Brodie Scott , Cline J. Mark , Hahn Fletcher F. , Kolenda-Roberts Holly , Lele Subodh M. , Lowenstine Linda J. 
Published: September 2008

Peroxisome proliferator-activated receptors (PPAR) are involved in the pathogenesis of insulin resistance, diabetes, hyperlipidemias, and related complications. Consequently, a mechanistic understanding of PPAR subtypes and their activation provides promising therapeutic targets for the management of type 2 diabetes mellitus and the metabolic syndrome. Available data from rodent carcinogenicity studies, however, demonstrate that PPAR agonists can be tumorigenic in one or more species of rodents at multiple sites. Sufficient data are not yet available to explain the mode(s) of action for most of these tumor types. There has been information presented by FDA that indicates there are urothelial changes in the monkey (and possibly the dog) in addition to the rat. Outstanding questions exist regarding potency, species differences, safety margins, and other issues. In 2005, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) PPAR Agonist Project Committee was established to advance research on the modes of action and potential human relevance of emerging rodent tumor data. Additionally, the HESI PPAR Agonist Project Committee authorized a Pathology Working Group (PWG) to examine the urinary bladder from cynomolgus monkeys. The focus of this PWG was to establish consistent diagnostic criteria for urothelial changes and to assess the potential relationship of these changes to treatment. Specific diagnostic criteria and nomenclature were recommended for the diagnosis of urothelial granules, vacuolation, hypertrophy, and hyperplasia in studies conducted with PPARγ and dual α/γ agonists in cynomolgus monkeys, which will assist investigators performing toxicity studies to provide data in a consistent manner between studies and laboratories. In this review of selected tissues, treatment with PPAR agonists was not associated with urothelial hypertrophy or hyperplasia, but there was an increased incidence in the size and frequency of vacuoles within the superficial urothelial and adjacent intermediate cell layers.
Magnetic Resonance Imaging Appearance of a Repaired Capsulolabral Complex after Arthroscopic Bankart Repair
Authors: Yoo Jae Chul , Lee Yong Seuk , Tae Suk Kee , Park Jung Ho , Park Jong Woong , Ha Hae Chan 
Published: September 2008

Background Revision Bankart operations frequently show capsulolabral buttress loss and recurrent soft tissue Bankart lesion. Capsulolabral augmentation is designed to increase glenohumeral stability by 2 separate mechanisms: deepening the glenoid concavity and reducing capsular laxity. This is accomplished by shifting the capsule to buttress the glenoid labrum. Hypothesis A retained capsulolabral buttress may show loss of height and slope at a certain period after surgery, regardless of stability. Thus, the authors wanted to confirm the importance of an intraoperative establishment of capsulolabral buttress in terms of stability. Study Design Case-control study; Level of evidence, 3. Methods Arthroscopically repaired Bankart lesions in 21 consecutive shoulders that showed no frank dislocation were evaluated using axial and oblique coronal T2-weighted magnetic resonance imaging at 3 timepoints (preoperative period, average postoperative week 6 and a nearly full range of motion recovery, and postoperative month 6 with a return to daily activity). The authors measured 2 parameters (height and slope) on axial (mainly capsulolabral containment) and oblique coronal images (mainly inferior glenohumeral ligament) at the anteroinferior portion of the glenoid (5 mm above the most inferior anchor). In addition, they compared the above-mentioned parameters at postoperative month 6 by magnetic resonance imaging in 21 controls and in 21 patients whose instability recurred after surgery (not included in the prospective study). Results There was a significant increase between the preoperative period and postoperative week 6 in all 4 parameters ( P < .0001). There was also a significant increase between the preoperative period and postoperative month 6 in all 4 parameters ( P < .0001). However, no statistically significant difference was observed between postoperative week 6 and postoperative month 6 in all 4 parameters ( P > .1). Furthermore, significant differences were observed between normal controls and patients with recurrent instability ( P < .001) and between the authors’ cases and patients with recurrent instability not in the study (P < .001). However, no difference was observed between their cases and normal shoulders ( P > .1). Conclusion After suture anchor Bankart repair, initial capsulolabral buttress property was maintained at 6 months postoperatively. Furthermore, the buttress was more prominent in stable and normal shoulders than in recurrent instability shoulders. Therefore, the authors believe that the establishment of a capsulolabral buttress is meaningful during Bankart repair.
Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2
Authors: Foot Natalie J. , Dalton Hazel E. , Shearwin-Whyatt Linda M. , Dorstyn Loretta , Tan Seong-Seng , Yang Baoli , Kumar Sharad 
Published: September 2008

AbstractMany ion channels and transporters are regulated by ubiquitination mediated by the Nedd4 family of HECT-type ubiquitin ligases (E3s). These E3s commonly interact with substrates via their WW domains that bind to specific motifs in target proteins. However, not all potential targets of these E3s contain WW-binding motifs. Therefore, accessory proteins may mediate the interaction between Nedd4 family members and their targets. Here we report that the divalent metal ion transporter DMT1, the primary nonheme iron transporter in mammals, is regulated by ubiquitination mediated by the Nedd4 family member WWP2. DMT1 interacts with 2 WW domain-interacting proteins, Ndfip1 and Ndfip2, previously proposed to have roles in protein trafficking. This promotes DMT1 ubiquitination and degradation by WWP2. Consistent with these observations, Ndfip1−/− mice show increased DMT1 activity and a concomitant increase in hepatic iron deposition, indicating an essential function of Ndfip1 in iron homeostasis. This novel mechanism of regulating iron homeostasis suggests that Ndfips and WWP2 may contribute to diseases involving aberrant iron transport.
Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial
Authors: Kearon Clive , Julian Jim A. , Kovacs Michael J. , Anderson David R. , Wells Philip , MacKinnon Betsy , Weitz Jeffrey I. , Crowther Mark A. , Dolan Sean , Turpie Alexander G. , Geerts William , Solymoss Susan , van Nguyen Paul , Demers Christine , Kahn Susan R. , Kassis Jeannine , Rodger Marc , Hambleton Julie , Gent Michael , Ginsberg Jeffrey S. 
Published: September 2008

Abstract
We sought to determine whether thrombophilic defects increase recurrent venous thromboembolism (VTE) during warfarin therapy. Six hundred sixty-one patients with unprovoked VTE who were randomized to extended low-intensity (international normalized ratio [INR], 1.5-1.9) or conventional-intensity (INR, 2.0-3.0) anticoagulant therapy were tested for thrombophilia and followed for a mean of 2.3 years. One or more thrombophilic defects were present in 42% of patients. The overall rate of recurrent VTE was 0.9% per patient-year. Recurrent VTE was not increased in the presence of factor V Leiden (hazard ratio [HR], 0.7; 95% CI, 0.2-2.6); the 20210G>A prothrombin gene mutation (HR, 0); antithrombin deficiency (HR, 0); elevated factor VIII (HR, 0.7; 95% CI, 0.1-5.4); elevated factor XI (HR, 0.7; 95% CI, 0.1-5.0), or elevated homocysteine (HR, 0.7; 95% CI, 0.1-5.3), but showed a trend to an increase with an antiphospholipid antibody (HR, 2.9; 95% CI, 0.8-10.5). Compared with patients with no thrombophilic defects, the rate of recurrence was not increased in the presence of one (HR, 0.7; 95% CI, 0.2-2.3) or more than one (HR, 0.7; 95% CI, 0.2-3.4) defect. We conclude that single or multiple thrombophilic defects are not associated with a higher risk of recurrent VTE during warfarin therapy.
Multidimensional protein fractionation using ProteomeLab PF 2D™ for profiling amyotrophic lateral sclerosis immunity: A preliminary report
Authors: Schlautman Joshua D , Rozek Wojciech , Stetler Robert , Mosley R Lee , Gendelman Howard E , Ciborowski Pawel 
Published: September 2008

Abstract

Background
The ProteomeLab™ PF 2D platform is a relatively new approach to global protein profiling. Herein, it was used for investigation of plasma proteome changes in amyotrophic lateral sclerosis (ALS) patients before and during immunization with glatiramer acetate (GA) in a clinical trial.

Results
The experimental design included immunoaffinity depletion of 12 most abundant proteins from plasma samples with the ProteomeLab™ IgY-12 LC10 column kit as first dimension separation, also referred to as immuno-partitioning. Second and third dimension separations of the enriched proteome were performed on the PF 2D platform utilizing 2D isoelectric focusing and RP-HPLC with the resulting fractions collected for analysis. 1D gel electrophoresis was added as a fourth dimension when sufficient protein was available. Protein identification from collected fractions was performed using nano-LC-MS/MS approach. Analysis of differences in the resulting two-dimensional maps of fractions obtained from the PF 2D and the ability to identify proteins from these fractions allowed sensitivity threshold measurements. Masked proteins in the PF 2D fractions are discussed.

Conclusion
We offer some insight into the strengths and limitations of this emerging proteomic platform.