bluuebunny/crossref_metadata_2025 huggingface dataset:
GAUGE INVARIANCE OF THE MUONIUM–ANTIMUONIUM OSCILLATION TIME SCALE AND LIMITS ON RIGHT-HANDED NEUTRINO MASSES
Authors: LIU BOYANG
Published: March 2009

The gauge invariance of the muonium–antimuonium [Formula: see text] oscillation time scale is explicitly demonstrated in the Standard Model modified only by the inclusion of singlet right-handed neutrinos and allowing for general renormalizable interactions. The seesaw mechanism is exploited resulting in three light Majorana neutrinos and three heavy Majorana neutrinos with mass scale MR≫MW. The leading order matrix element contribution to the [Formula: see text] oscillation process is computed in Rξ gauge and shown to be ξ-independent thereby establishing the gauge invariance to this order. Present experimental limits resulting from the non-observation of the oscillation process sets a lower limit on MR roughly of order 600 GeV.
Promoting student-centered active learning in lectures with a personal response system
Authors: Gauci Sally A. , Dantas Arianne M. , Williams David A. , Kemm Robert E.
Published: March 2009

We investigated whether an active learning approach, facilitated by a personal response system, would lead to improved student engagement and learning outcomes in large-group physiology lectures for undergraduate science students. We focused on encouraging students' active learning in lectures, whereas previous studies have made more use of audience response technology during lectures for formative or summative assessment. Students voluntarily answered questions posed during lectures with their personal response system (clickers), with individual answers automatically collated for immediate histogram display. This feedback then dictated the focus of followup discussions in the lecture. Student and instructor attitudes were surveyed through voluntary interviews with student responses correlated with their degree of clicker participation and individual exam results. Active lectures were found to increase both student motivation and engagement. Students who participated in answering questions achieved better results than students who chose not to. Students with the lowest scores in a prerequisite course (previous semester physiology exam marks of < 60%) showed significantly better outcomes from the use of clickers than both middle-achieving (60-75%) and high-achieving (>75%) entry students. Significant improvement was evident in both mid- and end-semester exam results compared with student cohorts from preceding years, although this could also be influenced by many other factors. Increased student engagement and the immediate feedback obtained during lectures were advantages commonly noted by lecturing staff.
In pursuit of a holistic learning environment: the impact of music in the medical physiology classroom
Authors: Modell Harold I. , DeMiero Frank G. , Rose Louise
Published: March 2009

A holistic learning environment is one that nurtures all aspects of students' learning. The environment is safe, supportive, and provides opportunities to help students deal with nonacademic as well as academic factors that impact their learning. Creation of such an environment requires the establishment of a supportive learning community. For a variety of reasons, establishing such a learning community of first-year medical students can be challenging. This communication presents one approach to meeting this challenge in a medical school Human Physiology course. Steps were taken at the beginning of the course to create the community, and activities designed to reinforce these efforts were incorporated into the course as it progressed. Two pilot studies were conducted to test the hypothesis that providing students with a participatory music experience may help to promote a holistic learning environment by helping them restore a sense of balance to their emotional well-being as well as reinforce a sense of community in the classroom. Student response to these activities indicated that these efforts provided emotional support during stressful periods during the quarter, helped promote a feeling of safety within the environment, and reenergized the class during long class sessions. This project illustrates that each instructor, within the confines of his/her own classroom, can make a significant contribution to achieving a holistic learning envrionment for his/her students.
Student interaction characteristics during collaborative group testing
Authors: Giuliodori Mauricio J. , Lujan Heidi L. , DiCarlo Stephen E.
Published: March 2009

We used collaborative testing in a veterinary physiology course (65 students) to answer the following questions: 1) do students with individual correct responses or students with individual incorrect responses change their answers during group testing? and 2) do high-performing students make the decisions, that is, are low-performing students carried by high-performing peers? To address these questions, students first completed the exam in the traditional format as individuals. After completing the exam as individuals, students completed the same exam in groups of two. Finally, the same questions were discussed by the instructor and students (instructor feedback). We found that students with individual incorrect responses changed their answers during group testing more often than students with individual correct responses (odds ratio: 7.58, P < 0.01). Furthermore, student feedback was more beneficial when group members had different individual answers than when they had same individual answers ( P < 0.05). In addition, when group members had different individual answers, more answers were changed to correct responses than to incorrect responses (77% vs. 23%, P < 0.01). It was more important to have the correct answer than to be the high-performing student, because the student with the correct response (being either the high- or low-performing student) generally prevailed (∼ 80% of the time, P = 0.5). Finally, the positive effects of group testing (77% of total effects, P < 0.05) were due to students who changed their individual answer to the correct response after discussion with peers with the correct response and also with the incorrect individual response.
Living history: Clark M. Blatteis
Authors: Quan Ning
Published: March 2009

In 2005, the American Physiological Society (APS) initiated the Living History Project to recognize senior members who have made extraordinary contributions during their career to the advancement of the discipline and profession of physiology. During 2007, the APS Section of Environmental and Exercise Physiology selected Clark M. Blatteis to be profiled in Advances in Physiology Education.
Antibody-Drug Conjugates for the Treatment of Non–Hodgkin's Lymphoma: Target and Linker-Drug Selection
Authors: Polson Andrew G. , Calemine-Fenaux Jill , Chan Pamela , Chang Wesley , Christensen Erin , Clark Suzanna , de Sauvage Frederic J. , Eaton Dan , Elkins Kristi , Elliott J. Michael , Frantz Gretchen , Fuji Reina N. , Gray Alane , Harden Kristin , Ingle Gladys S. , Kljavin Noelyn M. , Koeppen Hartmut , Nelson Christopher , Prabhu Saileta , Raab Helga , Ross Sarajane , Stephan Jean-Philippe , Scales Suzie J. , Spencer Susan D. , Vandlen Richard , Wranik Bernd , Yu Shang-Fan , Zheng Bing , Ebens Allen
Published: March 2009

Antibody-drug conjugates (ADC), potent cytotoxic drugs covalently linked to antibodies via chemical linkers, provide a means to increase the effectiveness of chemotherapy by targeting the drug to neoplastic cells while reducing side effects. Here, we systematically examine the potential targets and linker-drug combinations that could provide an optimal ADC for the treatment for non–Hodgkin's lymphoma. We identified seven antigens (CD19, CD20, CD21, CD22, CD72, CD79b, and CD180) for potential treatment of non–Hodgkin's lymphoma with ADCs. ADCs with cleavable linkers mediated in vivo efficacy via all these targets; ADCs with uncleavable linkers were only effective when targeted to CD22 and CD79b. In target-independent safety studies in rats, the uncleavable linker ADCs showed reduced toxicity, presumably due to the reduced release of free drug or other toxic metabolites into the circulation. Thus, our data suggest that ADCs with cleavable linkers work on a broad range of targets, and for specific targets, ADCs with uncleavable linkers provide a promising opportunity to improve the therapeutic window for ADCs in humans. [Cancer Res 2009;69(6):2358–64]
Coordination of Intratumoral Immune Reaction and Human Colorectal Cancer Recurrence
Authors: Camus Matthieu , Tosolini Marie , Mlecnik Bernhard , Pagès Franck , Kirilovsky Amos , Berger Anne , Costes Anne , Bindea Gabriela , Charoentong Pornpimol , Bruneval Patrick , Trajanoski Zlatko , Fridman Wolf-Herman , Galon Jérôme
Published: March 2009

A role for the immune system in controlling the progression of solid tumors has been established in several mouse models. However, the effect of immune responses and tumor escape on patient prognosis in the context of human cancer is poorly understood. Here, we investigate the cellular and molecular parameters that could describe in situ immune responses in human colorectal cancer according to clinical parameters of metastatic lymph node or distant organ invasion (META− or META+ patients). Primary tumor samples of colorectal carcinoma were analyzed by integrating large-scale phenotypic (flow cytometry, 39 patients) and gene expression (real time reverse transcription-PCR, 103 patients) data sets related to immune and protumoral processes. In META− colorectal cancer primary tumors with high densities of T cells, we observed significant positive correlations between markers of innate immune cells [tumor-associated macrophages, dendritic cells, natural killer (NK) cells, and NKT cells] and markers of early-activated T cells. Significant correlations were also observed between markers of cytotoxic and effector memory T-cell subpopulations. These correlation profiles were absent in tumors with low T-cell infiltrates and were altered in META+ tumors with high T-cell infiltrates. We show that the coexpression of genes mediating cytotoxicity (GNLY) and Th1 adaptive immune responses (IRF1) accurately predicted patient survival independently of the metastatic status. High intratumoral mRNA expression of the proangiogenic mediator vascular endothelial growth factor was associated with significantly reduced survival rates in patients expressing high mRNA levels of GNLY. Investigation of the colorectal cancer primary tumor microenvironment allowed us to uncover the association of favorable outcomes with efficient coordination of the intratumoral immune response. [Cancer Res 2009;69(6):2685–93]
Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles
Authors: Chisholm Edward J. , Vassaux Georges , Martin-Duque Pilar , Chevre Raphael , Lambert Olivier , Pitard Bruno , Merron Andrew , Weeks Mark , Burnet Jerome , Peerlinck Inge , Dai Ming-Shen , Alusi Ghassan , Mather Stephen J. , Bolton Katherine , Uchegbu Ijeoma F. , Schatzlein Andreas G. , Baril Patrick
Published: March 2009

The lack of safe and efficient systemic gene delivery vectors has largely reduced the potential of gene therapy in the clinic. Previously, we have reported that polypropylenimine dendrimer PPIG3/DNA nanoparticles are capable of tumor transfection upon systemic administration in tumor-bearing mice. To be safely applicable in the clinic, it is crucial to investigate the colloidal stability of nanoparticles and to monitor the exact biodistribution of gene transfer in the whole body of the live subject. Our biophysical characterization shows that dendrimers, when complexed with DNA, are capable of forming spontaneously in solution a supramolecular assembly that possesses all the features required to diffuse in experimental tumors through the enhanced permeability and retention effect. We show that these nanoparticles are of sizes ranging from 33 to 286 nm depending on the DNA concentration, with a colloidal stable and well-organized fingerprint-like structure in which DNA molecules are condensed with an even periodicity of 2.8 nm. Whole-body nuclear imaging using small-animal nano-single-photon emission computed tomography/computer tomography scanner and the human Na/I symporter (NIS) as reporter gene shows unique and highly specific tumor targeting with no detection of gene transfer in any of the other tissues of tumor-bearing mice. Tumor-selective transgene expression was confirmed by quantitative reverse transcription-PCR at autopsy of scanned animals, whereas genomic PCR showed that the tumor sites are the predominant sites of nanoparticle accumulation. Considering that NIS imaging of transgene expression has been recently validated in humans, our data highlight the potential of these nanoparticles as a new formulation for cancer gene therapy. [Cancer Res 2009;69(6):2655–62]
Inhibition of Constitutively Activated Nuclear Factor-κB Induces Reactive Oxygen Species- and Iron-Dependent Cell Death in Cutaneous T-Cell Lymphoma
Authors: Kiessling Michael K. , Klemke Claus D. , Kamiński Marcin M. , Galani Ioanna E. , Krammer Peter H. , Gülow Karsten
Published: March 2009

Aberrant signaling of the nuclear facotr (NF-κB) pathway has been identified as a mediator of survival and apoptosis resistance in leukemias and lymphomas. Here, we report that cell death of cutaneous T-cell lymphoma cell lines induced by inhibition of the NF-κB pathway is independent of caspases or classic death receptors. We found that free intracellular iron and reactive oxygen species (ROS) are the main mediators of this cell death. Antioxidants such as N-Acetyl-l-cysteine and glutathione or the iron chelator desferrioxamine effectively block cell death in cutaneous T-cell lymphoma cell lines or primary T cells from Sézary patients. We show that inhibition of constitutively active NF-κB causes down-regulation of ferritin heavy chain (FHC) that leads to an increase of free intracellular iron, which, in turn, induces massive generation of ROS. Furthermore, direct down-regulation of FHC by siRNA caused a ROS-dependent cell death. Finally, high concentrations of ROS induce cell death of malignant T cells. In contrast, T cells isolated from healthy donors do not display down-regulation of FHC and, therefore, do not show an increase in iron and cell death upon NF-κB inhibition. In addition, in a murine T-cell lymphoma model, we show that inhibition of NF-κB and subsequent down-regulation of FHC significantly delays tumor growth in vivo. Thus, our results promote FHC as a potential target for effective therapy in lymphomas with aberrant NF-κB signaling. [Cancer Res 2009;69(6):2365–74]
Activation of Meiosis-Specific Genes Is Associated with Depolyploidization of Human Tumor Cells following Radiation-Induced Mitotic Catastrophe
Authors: Ianzini Fiorenza , Kosmacek Elizabeth A. , Nelson Elke S. , Napoli Eleonora , Erenpreisa Jekaterina , Kalejs Martins , Mackey Michael A.
Published: March 2009

Cancer is frequently characterized histologically by the appearance of large cells that are either aneuploid or polyploid. Aneuploidy and polyploidy are hallmarks of radiation-induced mitotic catastrophe (MC), a common phenomenon occurring in tumor cells with impaired p53 function following exposure to various cytotoxic and genotoxic agents. MC is characterized by altered expression of mitotic regulators, untimely and abnormal cell division, delayed DNA damage, and changes in morphology. We report here that cells undergoing radiation-induced MC are more plastic with regards to ploidy and that this plasticity allows them to reorganize their genetic material through reduction division to produce smaller cells which are morphologically indistinguishable from control cells. Experiments conducted with the large-scale digital cell analysis system are discussed and show that a small fraction of polyploid cancer cells formed via radiation-induced MC can survive and start a process of depolyploidization that yields various outcomes. Although most multipolar divisions failed and cell fusion occurred, some of these divisions were successful and originated a variety of cell progeny characterized by different ploidy. Among these ploidy phenotypes, a progeny of small mononucleated cells, indistinguishable from the untreated control cells, is often seen. We report here evidence that meiosis-specific genes are expressed in the polyploid cells during depolyploidization. Tumor cells might take advantage of the temporary change from a promitotic to a promeiotic division regimen to facilitate depolyploidization and restore the proliferative state of the tumor cell population. These events might be mechanisms by which tumor progression and resistance to treatment occur in vivo. [Cancer Res 2009;69(6):2296–304]
miR-34b Targets Cyclic AMP–Responsive Element Binding Protein in Acute Myeloid Leukemia
Authors: Pigazzi Martina , Manara Elena , Baron Emma , Basso Giuseppe
Published: March 2009

The cyclic AMP–responsive element binding protein (CREB) is documented to be overexpressed in leukemia, but the underlying mechanism remains unknown. Here, microRNAs (miRNA), which act as negative regulators of gene expression principally through translational repression, are investigated for the mediation of high CREB protein levels. A series of miRNAs that target CREB were identified. Real-time quantitative PCR revealed that miR-34b was expressed significantly less in myeloid cell lines, previously known for high CREB protein levels. Exogenous miR-34b expression was induced, and results revealed a direct interaction with the CREB 3′-untranslated region, with the consequent reduction of the CREB protein levels in vitro. miR-34b restored expression caused cell cycle abnormalities, reduced anchorage-independent growth, and altered CREB target gene expression, suggesting its suppressor potential. Using reverse-phase protein array, CREB target proteins (BCL-2, cyclin A1, cyclin B1, cyclin D, nuclear factor-κB, Janus-activated kinase 1, and signal transducer and activator of transcription 3), as well as many downstream protein kinases and cell survival signaling pathways (AKT/mammalian target of rapamycin and extracellular signal-regulated kinase) usually elicited by CREB, were observed to have decreased. The miR-34b/miR-34c promoter was shown to be methylated in the leukemia cell lines used. This epigenetic regulation should control the observed miR-34b expression levels to maintain the CREB protein overexpressed. In addition, the inverse correlation between miR-34b and CREB expression was found in a cohort of 78 pediatric patients at diagnosis of acute myeloid leukemia, supporting this relationship in vivo. Our results identify a direct miR-34b target gene, provide a possible mechanism for CREB overexpression, and provide new information about myeloid transformation and therapeutic strategies. [Cancer Res 2009;69(6):2471–8
Molecular imaging of Bcr-Abl phosphokinase in a xenograft model
Authors: Wu Ji Yuan , Yang David J. , Angelo Laura S. , Kohanim Saady , Kurzrock Razelle
Published: March 2009

The purpose of this study was to determine whether the Bcr-Abl tyrosine kinase can be assessed by γ-imaging using an 111In-labeled anti-phosphotyrosine (APT) antibody, and if the response to treatment with imatinib could be detected using this imaging technique. APT antibody was labeled with 111In using ethylenedicysteine (EC) as a chelator. To determine if 111In-EC-APT could assess a nonreceptor tyrosine kinase, xenografts of the human chronic myelogenous leukemia cell line K562 were used. γ-Scintigraphy of the tumor-bearing mice, before and after imatinib treatment, was obtained 1, 24, and 48 h after they were given 111In-EC-APT (100 μCi/mouse i.v.). 111In-EC-APT is preferentially taken up by Bcr-Abl-bearing tumor cells when compared with 111In-EC-BSA or 111In-EC-IgG1 controls and comparable with the level of uptake of 111In-EC-Bcr-Abl. Imatinib treatment resulted in decreased expression of phospho-Bcr-Abl by Western blot analysis, which correlated with early (4 days after starting imatinib) kinase down-regulation as assessed by imaging using 111In-EC-APT. The optimal time to imaging was 24 and 48 h after injection of 111In-EC-APT. Although tumor regression was insignificant on day 4 after starting imatinib treatment, it was marked by day 14. 111In-EC-APT can assess intracellular phosphokinase activity, and down-regulation of phosphokinase activity predates tumor regression. This technique may therefore be useful in the clinic to detect the presence of phosphokinase activity and for early prediction of response. [Mol Cancer Ther 2009;8(3):703–10]
A selective small-molecule nuclear factor-κB inhibitor from a high-throughput cell-based assay for “activator protein-1 hits”
Authors: Kang Moon-Il , Henrich Curtis J. , Bokesch Heidi R. , Gustafson Kirk R. , McMahon James B. , Baker Alyson R. , Young Matthew R. , Colburn Nancy H.
Published: March 2009

NSC 676914 has been identified as a selective nuclear factor-κB (NF-κB) inhibitor that does not inhibit cell proliferation. This compound was originally identified in a high-throughput cell-based assay for activator protein-1 (AP-1) inhibitors using synthetic compound libraries and the National Cancer Institute natural product repository. NSC 676914 shows activity against NF-κB in luciferase reporter assays at concentrations much less than the IC50 for AP-1. A serum response element reporter used as a specificity control and indicator of cell proliferation was relatively insensitive to the compound. Pretreatment with NSC 676914 is here shown to repress 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced IκB-α phosphorylation and translocation of p65/50 to the nucleus but not the processing of p52 from p100, suggesting the inhibition of NF-κB regulator IKKβ rather than IKKα. Inhibition of NF-κB activation occurred as a consequence of blocking phosphorylation of IKK. Induction of IκB-α phosphorylation by TPA was diminished by pretreatment of NSC 676914 even at 1.1 μmol/L. In contrast, kinases c-Jun-NH2-kinase and extracellular signal-regulated kinases 1 and 2, important for AP-1 activation, showed no significant repression by this compound. Furthermore, a Matrigel invasion assay with breast cancer cell lines and a transformation assay in mouse JB6 cells revealed that TPA-induced invasion and transformation responses were completely repressed by this compound. These results suggest that NSC 676914 could be a novel inhibitor having potential therapeutic activity to target NF-κB for cancer treatment or prevention. [Mol Cancer Ther 2009;8(3):571–81]
Normal Breast Tissue Implanted into Athymic Nude Mice Identifies Biomarkers of the Effects of Human Pregnancy Levels of Estrogen
Authors: Blance Rognvald N. , Sims Andrew H. , Anderson Elizabeth , Howell Anthony , Clarke Robert B.
Published: March 2009

We have generated a novel model system for the study of estrogen intervention in normal breast tissue. Nulliparous human breast tissue was implanted into immunocompromised nude mice and treated with high-dose estrogen to simulate the effects of pregnancy. Treatment of mice with human mid-pregnancy levels of 17β-estradiol for a period of 4 weeks was followed by 4 weeks of withdrawal to mimic involution. Gene expression in the xenograft tissue was then analyzed by real-time reverse transcription-PCR to identify differences between treated and control tissues. Ten genes previously identified as altered by pregnancy in rodent models were found to be differentially expressed in human breast tissue with a ≥1.8-fold up-regulation of CDC42, TGFβ3, DCN, KRT14, LTF, and AREG and a ≥0.7-fold down-regulation of STAT1, CTGF, IGF1, and VAMP1. Immunohistochemical analysis of archival paraffin-embedded adult premenopausal human breast tissue specimens identified a significantly lower level of expression of STAT1 (P < 0.05, Mann-Whitney U test) in parous compared with age-matched nulliparous tissue (median of 24% compared with 42% epithelial cells positive). We conclude that many of the pregnancy-induced breast cancer–protective changes observed in rodent models also occur in human breast tissue following intervention using human pregnancy levels of estrogen and that STAT1 expression is a potential biomarker of parity-induced breast cancer protection in the human breast.
Risk of Cardiovascular Events in a Randomized Placebo-Controlled, Double-Blind Trial of Difluoromethylornithine plus Sulindac for the Prevention of Sporadic Colorectal Adenomas
Authors: Zell Jason A. , Pelot Daniel , Chen Wen-Pin , McLaren Christine E. , Gerner Eugene W. , Meyskens Frank L.
Published: March 2009

Nonsteroidal anti-inflammatory drugs (NSAID) have been associated with adverse cardiovascular (CV) outcomes in cancer prevention and other clinical trials. A recent meta-analysis suggested that baseline CV risk is associated with NSAID-associated adverse CV events. We evaluated the effect of baseline CV risk on adverse CV events in a phase III trial of difluoromethylornithine (DFMO) plus the NSAID sulindac versus placebo in preventing colorectal adenomas. Trial data were analyzed to determine baseline CV risk. CV toxicity outcomes were then assessed overall and excluding high CV-risk patients. Baseline CV risk scores were evenly distributed within our overall trial population of 184 placebo (low risk, 27%; moderate risk, 34%; high risk, 39%) and 191 DFMO/sulindac (low risk, 30%; moderate risk, 29%; high risk, 41%) patients. In patients with a high baseline CV risk, the number of adverse CV events was greater among DFMO/sulindac (n = 9) than among placebo (n = 3) patients. Excluding patients with a high baseline CV risk, the numbers of adverse CV events were similar in the DFMO/sulindac (n = 7) and placebo (n = 6) arms. A high CV risk score at baseline may confer an increased risk of CV events associated with treatment with DFMO/sulindac, and a low baseline score may not increase this risk. These results have implications for future NSAID-based cancer prevention clinical trials.
Identification of an Association between Robinow Syndrome and Moyamoya
Authors: Qaiser Rabia , Scott R. Michael , Smith Edward R.
Published: March 2009

Introduction: Our group, along with others, has previously reported associations between moyamoya syndrome and a number of genetic disorders, including Down syndrome, Seckel dwarfism, sickle cell disease, and neurofibromatosis type I. Here we present the first reported case of a patient with the concomitant diagnosis of moyamoya and Robinow syndrome – a rare genetic disorder characterized by fetal-like faces, mesomelic shortening of the forearms, and developmental delay. The clinical, radiographic, and surgical findings are described, as well as the importance of this association. Methods: Case report. Results: A 13-year-old girl with Robinow syndrome presented with multiple transient ischemic attacks consisting of speech arrest and generalized weakness. Evaluation revealed probable bilateral moyamoya syndrome. Initially, she was treated conservatively due to the rarity of her symptoms and relatively unremarkable angiographic findings. However, she ultimately had progression of her disease both clinically and radiographically, leading to surgical management. She underwent staged bilateral pial synangiosis without complication and has done well subsequently. Conclusion: The potential difficulty of detecting symptoms related to cerebral ischemia in the Robinow’s population – where cognitive impairment may obscure initial neurologic symptoms – can result in delayed diagnosis and treatment. Given the excellent outcomes of moyamoya patients when treated prior to the development of fixed neurologic deficits, case reports such as this and identifying syndromic associations serve to highlight conditions that may result in improved patient outcomes through earlier diagnosis and treatment. The clinical and radiographic features of moyamoya syndrome associated with Robinow syndrome seem comparable to those of primary moyamoya disease. The presence of moyamoya syndrome should be considered in the evaluation of patients with Robinow syndrome who present with transient ischemic attack-like symptoms.
L2-L3 Flexion-Distraction Injury Treated by Posterior Fusion Using Ultra-High Molecular Weight Polyethylene Tape in a 7-Year-Old Boy
Authors: Tofuku Katsuhiro , Koga Hiroaki , Kawabata Naoya , Yone Kazunori , Komiya Setsuro
Published: March 2009

A 7-year-old boy was sitting in the back seat of a car wearing a lap seatbelt when the car was involved in a head-on collision with another vehicle. Radiographs revealed mild scoliosis, anterior column compression of L3 and enlargement of both the intervertebral foramen and interspinous distance between L2 and L3. Computed tomography revealed bilateral L2-L3 facet joint disruption with fracture of the L2 spinous process. Magnetic resonance imaging revealed rupture of the posterior ligamentous complex. An open reduction and posterior fusion with autologous bone graft using 5-mm-wide ultra-high molecular weight polyethylene tape sublaminar wiring was performed. Three months after surgery, bony fusion of L2-L3 was observed. At 6 months after surgery, the patient was asymptomatic and had resumed previous activities.
Predictive Value of the Phosphorylation of Signal Transducers and Activators of Transcription in the Outcome of Interferon Therapy for Chronic Hepatitis C
Authors: Miyaaki Hisamitsu , Ichikawa Tatsuki , Nakao Kazuhiko , Takeshita Shigeyuki , Shibata Hidetaka , Ozawa Eisuke , Akiyama Motohisa , Miuma Satoshi , Eguchi Katsumi
Published: March 2009

Objective: Signal transducers and activators of transcription (STATs) play a critical role in antiviral defense. To better understand pegylated interferon (IFN)-α and ribavirin combination therapy resistance, we examined the STAT expression in the liver. Methods: We immunostained Phospho-STAT1 (P-STAT1) and Phospho-STAT3 (P-STAT3) in 59 hepatitis C virus (HCV)-infected liver tissues and compared the expression of these STATs proteins and the clinicopathological factors. Results: The number of P-STAT1 observed correlated significantly with the body mass index (BMI; p = 0.03) and homeostatic model assessment (p = 0.007). The number of P-STAT3 observed correlated significantly with the ALT level (p = 0.002) and platelet count (p = 0.002). The number of P-STAT1 nuclei in the sustained virological response (SVR) group was significantly larger than in the non-SVR group (p = 0.003). On multivariance analysis, the number of P-STAT1 nuclei (p = 0.004) and age (p = 0.016) were significant predictors of SVR. Conclusions: P-STAT1 in the liver tissue prior to IFN therapy correlated with an increased BMI and increased insulin resistance, and might be a useful predictor of HCV clearance by IFN therapy. On the other hand, P-STAT3 might play a critical role in the hepatocellular response against inflammatory damage.
Reduced Antigenicity of Naturally Occurring Hepatitis B Surface Antigen Variants with Substitutions at the Amino Acid Residue 126
Authors: Qiu Song , Zhang Jiming , Tian Yongjun , Yang Yinke , Huang Hanju , Yang Dongliang , Lu Mengji , Xu Yang
Published: March 2009

Background: Substitutions at amino acid residue 126 of hepatitis B surface antigen (HBsAg) occur frequently in hepatitis B virus (HBV) isolates from patients with chronic HBV infection. These substitutions occur naturally, but their significance for viral persistence is unclear and requires further investigation. Methods: We amplified coding regions of HBsAg by PCR using sera from 1 patient chronically infected with HBV. Three representative clones of HBsAg with amino acid residues 126Ile (I), 126Thr (T) and 126Ser (S) were selected from sequenced clones. HBsAg 126Ala (A) mutants of subtype C/adr and D/adw were generated by site-directed mutagenesis. The HBsAg expression vectors were constructed and transiently transfected into HepG2 cells. The binding reactivity of HBsAg to anti-HBs antibodies was tested by chemiluminescent microparticle immunoassay and by immunofluorescence staining with polyclonal and monoclonal anti-HBs antibodies. Results: Diverse HBsAg variants with substitutions at amino acid residue 126 co-existed in a chronically infected HBV patient. HBsAg with the substitution 126S showed a significantly low antigenicity, while the binding reactivity to anti-HBs of other HBsAg with 126I, 126T and 126A were comparable. Conclusion: HBsAg with the 126S substitution has a reduced antigenicity, which may contribute to immune escape in chronic HBV infection.
Serum Transaminase Elevations during Pegylated Interferon Treatment of Chronic HCV Hepatitis Probably Induced by Polyethylene Glycol
Authors: Caroleo B. , Gallelli L. , Staltari O. , De Sarro G. , Guadagnino V.
Published: March 2009

Objective: We report elevated serum alanine aminotransferase (ALT) levels during pegylated interferon (PEG-IFN)-α-2a in a patient with chronic HCV without other clinical manifestations. Case Summary: A 38-year-old man presented for HCV infection evaluation. Serum aspartate aminotransferase (AST) and ALT levels were 43 and 116 U/l, respectively; RT-PCR blood analysis revealed HCV-RNA infection. PEG-IFN-α-2b plus ribavirin treatment induced both a rapid virologic response and a normalization of transaminase plasma levels. During follow-up, an increase in transaminase and HCV-RNA values prompted us to start a new antiviral treatment with PEG-IFN-α-2a plus ribavirin. Four months later, after the follow-up, a new blood test documented both a HCV-RNA titer <50 U/ml and an increase in ALT and AST plasma levels. Immunostaining of the liver biopsy showed an accumulation of PEG-IFN-α-2a. PEG-IFN-α-2a elimination and the addition of recombinant IFN-α-2a induced normalization of the plasma transaminase levels in about 2 months. Conclusion: We postulate PEG-IFN-α-2a treatment because both the molecular weight and the distribution volume of the PEG-IFN may accumulate in the liver resulting in an increase of plasma transaminase levels. In contrast, during PEG-IFN-α-2b treatment, we did not document any increase in plasma transaminase values probably because of the lower molecular weight of the PEG.
Molecular Genetic Diversity of Hepatitis B Virus in Kenya
Authors: Mwangi Joseph , Nganga Zipporah , Songok Elijah , Kinyua Joyceline , Lagat Nancy , Muriuki Joseph , Lihana Raphael , Khamadi Samoel , Osman Saida , Lwembe Raphael , Kiptoo Michael , Mwau Matilu , Chirchir Ruth , Mpoke Solomon , Nyamongo Jack , Okoth Fred , Yamada Rika , Kageyama Seiji , Ichimura Hiroshi
Published: March 2009

Eight genotypes of hepatitis B virus (A-H) and subgenotypes have been recognized worldwide. However, there is limited information on prevalent genotypes in many countries in Africa. This study was undertaken to determine the hepatitis B virus (HBV) genotypes in Kenya. Seropositive HBV blood samples from a blood donor setting were used in the study. HBV genotypes were determined in 52 nucleic acid-positive samples using specific primer in a nested PCR and sequencing employed in the HBV genotyping. This study shows presence of HBV variants with genotypes A (88%), E (8%) and D (4%). In conclusion, we found that HBV genotype A is the most predominant genotype in Kenya with both subgenotype A1 and A2 present. Genotype D and E are also present in our population. This demonstrates that there could be a high genetic diversity of HBV in Kenya.
Sposensor: A Whole-Bacterial Biosensor That Uses Immobilized Bacillus subtilis Spores and a One-Step Incubation/Detection Process
Authors: Fantino Jean-Raphaël , Barras Frédéric , Denizot François
Published: March 2009

A generic whole-cell bacterial sensor called sposensor was developed with immobilized sporesfrom engineered Bacillus subtilis. Sposensor contains two different types of spores: reporting spores that contain a reporter gene fused to a promoter responding to a compound to be detected, and control spores use to monitor cell germination and viability. A one-step incubation/detection process was developed to meet the constraints of on-site analysis. Spores were directly incubated with culture medium containing the compound to be detected. β-Galactosidase was chosen as a reporter protein in both cases and its activity followed by a colorimetric assay. Results showed that sposensor was efficient in detecting two different compounds, a metal (Zn2+) and a peptidic antibiotic (bacitracin). Owing to the stability and robustness of spores, sposensor is a very efficient and easy tool to manipulate for analyzing the presence of toxic compounds in natural settings.
A Model Fit Statistic for Generalized Partial Credit Model
Authors: Liang Tie , Wells Craig S.
Published: March 2009

Investigating the fit of a parametric model is an important part of the measurement process when implementing item response theory (IRT), but research examining it is limited. A general nonparametric approach for detecting model misfit, introduced by J. Douglas and A. S. Cohen (2001), has exhibited promising results for the two-parameter logistic model and Samejima s graded response model. This study extends this approach to test the fit of generalized partial credit model (GPCM). The empirical Type I error rate and power of the proposed method are assessed for various test lengths, sample sizes, and type of assessment. Overall, the proposed fit statistic performed well under the studied conditions in that the Type I error rate was not inflated and the power was acceptable, especially for moderate to large sample sizes. A further advantage of the nonparametric approach is that it provides a convenient graphical display of possible misfit.
Marking Territory
Authors: Walsh Lynda
Published: March 2009

This article reports the results of a study analyzing the interaction of administrative genres and stakeholder beliefs in the Mexican Wolf Blue Range Reintroduction Project (MWBRRP) in New Mexico and Arizona. The author examines this interaction through an analysis of a set of 944 recorded public comments (with administrative responses) concerning the project's federally mandated Five-Year Review. To reconstruct stakeholder beliefs from this data set, the author uses filter theory, a method that works inductively from interpretive decisions made in the face of competing beliefs to produce a ranking of those beliefs' impact on the decision process, called a “filter.” Results suggest that incompatibilities in stakeholder filters, combined with inappropriate generic choices, foreclosed on a possible rhetorical space for cooperation in the MWBRRP. However, some compatibility in stakeholder filters indicates common ground on which administration should focus future cooperative efforts.
Serving `The Guest': Günther Anders at the Grand Seaside Hotel
Authors: Bunzel Dirk , Parker Martin
Published: March 2009

Drawing on data collected during 14 months of ethnographic research in an Australian Coastal Hotel, the paper describes the management of service encounters. Hotel staff used meetings and training sessions to simulate service scenarios, hypothesizing `customer wants and needs'. In order to do this they constructed the image of an ideal `Guest', an image that was collectively evoked in order to shape the conduct of service encounters. We claim that these imaginary service encounters mean that the `creators' of this imaginary object become increasingly subjected to its demands. The object, `The Guest', attempts to dominate its creators. The traditional demarcation between subject and object is blurred, and perhaps reversed. Drawing on the neglected work of Günther Anders, the paper inquires into the status of this object and addresses the process of its production and consumption. It demonstrates how subjects and an (imaginary) object become entangled.
Review: Male obesity and reproductive potential
Authors: Ghiyath Shayeb A. , Bhattacharya Siladitya
Published: March 2009

The prevalence of overweight and obesity is increasing worldwide. There is an established association between female obesity and infertility but a similar link is yet to be proven in men. Herein we review publications, identified via keyword electronic database searches (1980—2008), which considered the influence of adiposity on male reproductive potential. It would appear that obesity has a detrimental effect on semen quality and that there are several potential mechanisms underlying this phenomenon. Br J Diabetes Vasc Dis 2009;9: 7—12
Fatness, faltering metabolism and fecundity: an expanding challenge in reproductive medicine
Authors: Nelson Scott M , Sattar Naveed
Published: March 2009

Increasing adiposity worldwide is having a negative impact on health with a rise in metabolic disorders and co-morbid conditions including reduced reproductive capacity in men and women. Furthermore, maternal adiposity and hyperglycaemia are strongly associated with adverse outcomes for both mother and baby, with the potential for long-term impact on the offspring. Introduction of a spectrum of public health strategies covering the entire reproductive lifespan are required to minimise the clinical burden of obesity-related disease. Br J Diabetes Vasc Dis, 2009; 9:36—37
Gestational diabetes: causes and consequences
Authors: Lindsay Robert S
Published: March 2009

Diabetes during pregnancy carries important implications for mother and child. Recent evidence has clarified the relationship of maternal glycaemia to neonatal outcomes and demonstrated that appropriate detection and treatment can improve outcomes. This review examines normal physiological changes of glucose metabolism in pregnancy and the association of gestational diabetes with complications both at time of delivery (macrosomia, hypoglycaemia, jaundice, polycythaemia, respiratory distress syndrome, and hypocalcaemia) and later disease associations for both mother and child. Finally recent evidence that at least some of these adverse effects can be reduced is examined. Br J Diabetes Vasc Dis 2009; 9: 27—31
Subcutaneous interferon beta-1a has a positive effect on cognitive performance in mildly disabled patients with relapsing—remitting multiple sclerosis: 2-year results from the COGIMUS study
Authors: Patti Francesco , Pia Amato Maria , Bastianello Stefano , Caniatti Luisa , Di Monte Elisabetta , Lijoi Fausto , Goretti Benedetta , Messina Silvia , Picconi Orietta , Tola Maria Rosalia , Trojano Maria ,   COGIMUS Study Group
Published: March 2009

The effect of interferon (IFN) beta-1a (44 and 22 μg subcutaneously [sc] three times weekly [tiw]) on cognition in mildly disabled patients with relapsing—remitting multiple sclerosis (McDonald criteria; Expanded Disability Status Scale ≤4.0) was assessed by validated neuropsychological testing at baseline and at regular intervals for up to 2 years in this ongoing open-label, 3-year study. Year-2 data were available for 356 patients (22 μg, n = 175; 44 μg, n = 181). The proportion of patients with impaired cognitive function was stable during the study: 21.4% at baseline and 21.6% at 2 years. At 2 years, the proportion of patients with ≥3 impaired cognitive tests was significantly lower in the 44 μg treatment group (17.0%) compared with the 22 μg group (26.5%; p = 0.034), although there was already a trend towards a higher proportion of patients with cognitive impairment in the 22 μg group at baseline. Factors associated with impairment in ≥ three cognitive tests after 2 years were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.00—1.09), verbal intelligence quotient (OR: 0.95; 95% CI: 0.92—0.98), and having ≥ three impaired cognitive tests at baseline (OR: 11.60; 95% CI: 5.94—22.64). These interim results show that IFN beta-1a sc tiw may have beneficial effects on cognitive function as early as 2 years after treatment initiation, but the final 3-year data of the study are required to confirm these results.
Synthesis of nanostructured titanium nitride films by PLD through reactive processing
Authors: Krishnan R. , Ramaseshan R. , Mathews T. , Nithya R. , Dash S. , Tyagi A. K. , Raj Baldev
Published: March 2009

High quality TiN films were synthesised from elemental metallic target using reactive and plasma assisted pulsed laser deposition (RPLD and PAPLD) techniques. In these processes, a high pure titanium target is ablated using a nanosecond pulsed Nd:YAG laser operating at 1064 nm wavelength at different nitrogen pressures. In RPLD process, the titanium plume reacts directly with the nitrogen gas at pressures less than 0·07 mbar to yield TiN films. In PAPLD process, additional nitrogen plasma was generated and confined by a DC coil positioned between target and substrate. Resultant films were characterised for phase, composition and morphology using glancing incidence X-ray diffraction, Auger Electron Spectroscopy (AES), Rutherford back-scattering and Atomic Force Microscope (AFM). Reactive pulsed laser deposition grown TiN films were found to contain traces of unreacted titanium. The crystallite size is estimated to be 15 and 50 nm respectively by using X-ray diffraction and AFM. Rutherford backscattering investigations helped the authors in arriving at the stoichiometry and AES analysis revealed the formation of TiN with low oxygen contamination.
Descriptive Zulu Placenames of San Origin
Authors: Raper Peter E
Published: March 2009

AbstractAlthough the meanings of Zulu placenames are important as part of the culture of the Zulu people, these meanings are frequently uncertain, and various interpretations of a name are sometimes encountered. The reason is that many names, particularly those of natural features such as watercourses and mountains, are ancient, in the present KwaZulu-Natal frequently being of Bushman (or San) origin, but subsequently adapted into the Zulu phonological and orthographic systems. Such names would tend to be primarily descriptive of the color, shape or other characteristic of the named feature, or to designate the feature itself. In some instances the meanings have been preserved as part of the oral tradition, in others recourse may be had to toponymic configurations, sometimes revealing Bushman (or San) words fossilized in the placename but otherwise not in the Zulu vocabulary or lexicon.
Increased Competition and Reduced Popularity: US Given Name Trends of the Twentieth and Early Twenty-First Centuries
Authors: Tucker D Kenneth
Published: March 2009

AbstractIn this paper, I identify changes in the naming of children in the US from 1880 to 2006. I identify the frequencies of the most popular given names in this period, and provide graphs of the male and female populations by names ranked in order of popularity, together with graphs showing the cumulative percentage populations for name rank for both the twentieth century and the first six years of the current century. It seems that parents are increasingly and deliberately avoiding selecting known popular names for their children, resulting in a decline in the absolute population share of these names. The irony of this is that there is hot competition within the top echelon, which comprises the population previously held by the single most popular given name.
A Note on the Names of Selected Characters and Villains in Dick Tracy
Authors: Nuessel Frank
Published: March 2009

AbstractThis article provides a brief history of the comic strip Dick Tracy (1931) and its creator, author, and illustrator Chester Gould (1900-1985). Gould was very inventive and creative in naming the characters that populated his strip. He provided distinctive names to the rogues that populated his strip. Their names reflected physical, psychological, or behavioral traits that emphasized deviance as a way to distinguish them from honest, hardworking citizens. In the 1930s and 1940s, the villains in Dick Tracy were distinctive and unique because of their idiosyncratic traits. The main characters also had unique names that represented positive traits. Minorities likewise had names that were stereotypic in nature. The comic strip regained its popularity in 1990 with the release of the very successful Disney movie "Dick Tracy".