bluuebunny/crossref_metadata_2025 huggingface dataset:
Bulky mediastinal Hodgkin's disease management and prognosis
Authors: Liew K. H. , Easton D. , Horwich A. , Barrett A. , Peckham M. J.
Published: January 2013

Of a total of 235 Stage I and II Hodgkin's disease patients treated between 1970 and 1979, 103 (43·8 per cent) had mediastinal involvement in 45 of whom the disease was bulky and in 58 non‐bulky. This report concentrates on bulky disease patients of whom 45 per cent did not relapse after therapy and 71 per cent are alive. Patients with mediastinal disease were treated with radiotherapy (63), sequential chemo‐radiotherapy (37) or chemotherapy alone (3). In the radiotherapy group the relapse rate for bulky disease was significantly higher (65 per cent) than for non‐bulky disease (44 per cent) (P < 0·05) although there was no significant difference in survival. Neither relapse rate nor survival differed significantly in bulky disease patients treated with radiotherapy compared with combined chemo‐radiotherapy although there was a 20 per cent difference in relapse‐free survival rate in favour of the combined treatment group at five years. Treatments were not allocated randomly and the chemo‐radiotherapy group contained a disproportionate number of patients with adverse features (> 3 node areas involved, limited lung extension) compared with the irradiated group: 11/25 and 2/17 respectively. The number of lymph node areas involved appeared to influence the relapse rate in the radiotherapy group. There was no correlation between mediastinal mass size and number of node areas involved suggesting that these two features may be independent prognostic factors.
Leucocyte migration inhibition and leucocyte adherence inhibition studies, using ferritin as ‘antigen’, in patients with malignant lymphoma
Authors: Bruce Lesley , Grail Ann , Hancock B. W.
Published: January 2013

Isoelectric focusing of ferritin prepared from three spleens involved by Hodgkin's disease demonstrated only minor differences from normal spleen ferritin. The leucocyte migration inhibition (LMI) and leucocyte adherence inhibition (LAI) assays were used to assess sensitization to Hodgkin's disease spleen ferritin and its component acidic and basic isoferritins in patients with malignant lymphoma compared to patients with other malignancies and control subjects. A difference in response to ferritin was demonstrated in both tests with patients with malignant lymphoma compared to controls, and in LMI test compared to patients with other malignancies. There were also significant differences in responses in, (i) patients with malignant lymphoma compared to controls, against acidic and basic isoferritins in both tests, (ii) in lymphoma patients versus patients with other malignancies against acidic isoferritins in both tests, (iii) lymphoma versus other malignancy against basic isoferritins in the LMI test only. However, no significant differences, within each group, between responses with acidic and with basic isoferritins were demonstrated, and there was no correlation between individual patients' responses in the two tests.
Differential cytotoxicity of deoxyguanosine and 8‐aminoguanosine for human leukemic cell lines and normal bone marrow progenitor cells
Authors: De Fouw Nanneke J. , Ma David D. F. , Michalevicz Rita , Gray Douglas A. , Hoffbrand A. Victor
Published: January 2013

The inhibitory effect of deoxyguanosine (GdR) alone or in combination with the purine nucleoside phosphorylase (PNP) inhibitor, 8‐aminoguanosine (AG) was tested on human T, B, cALL and myeloid leukaemia cell lines and on normal human bone marrow haemopoietic progenitor cells. GdR was found to be toxic to T‐leukaemia cells. AG (100μm) alone did not have any inhibitory effect, but when used with GdR (2·5 × 10−5m) a synergistic effect was seen towards T cells. Incubation with GdR and AG resulted in a marked decrease in cell viability (> 90 per cent in three and > 75 per cent in four of 5 T leukaemic cell lines tested at 72 h). This drug combination did not inhibit the growth of non‐T leukaemic cells and was also non‐toxic to normal bone marrow multipotent progenitor cells (CFU‐GEMM) in vitro. Adenosine deaminase (ADA) acts consecutively with PNP in purine degradation. The addition of an ADA inhibitor, deoxycoformycin and deoxyadenosine, however, did not enhance the toxicity of GdR and AG for T cell leukaemia. The possibility of using GdR and AG for in vitro removal of residual T leukaemic blasts with the sparing of normal bone marrow cells, prior to autologous bone marrow transplantation should be further explored.
The effects of interferon on granulopoiesis in vitro
Authors: Müller Marianne R. , Hofmann Victor , Cogoli Marianne , Erni Jana , Arrenbrecht Stefan
Published: January 2013

Colony formation by myeloid progenitor cells (CFU‐c) in agar was inhibited to the same extent by heterogeneous human leucocyte IFN (IFN‐Le) and 2 different cloned IFN‐a2 preparations, but ∼10 times less by cloned IFN‐α1; cluster formation remained unaffected by any of the interferons. An antiproliferative effect is suggested by both lower cell yield and DNA synthesis in IFN containing liquid cultures. Incubation of cells with IFN for 18 h prior to plating with colony stimulating factor (CSF) reduced colony formation, indicating an altered responsiveness of CFU‐c to CSF. In IFN treated cultures no consistent block of morphological differentiation occurred, but granulocyte alkaline phosphatase activity was reduced. Thus, IFN may play a modulatory role on functional markers. Our results indicate that the effects observed with heterogeneous preparations are due to IFN and not to impurities and that various differentiation parameters are unequally affected by IFN.
Enhanced Ii expression after n‐butyrate treatment of a P3HR‐1 Burkitt's lymphoma subline which does not express HLA‐D
Authors: Spiro Robert C. , Sairenji Takeshi , Humphreys Robert E.
Published: January 2013

Treatment of P3HR‐1 Burkitt's lymphoma cultured cells with 4 mM n‐butyrate for 48 h induced the abundant expression of a 35 000 dalton, microsomal membrane protein which was demonstrated to be the electrophoretically invariant Ii molecule. To prove this point, [35S]methionine‐labelled, microsomal membrane proteins or immunoprecipitates of such detergent‐solubilized proteins were subjected to electrophoresis either in SDS gels or in two‐dimensional, nonequilibrium pH gradient gels. The induced p35 molecule was judged to be Ii by molecular weight and isoelectric characteristics and by immune complex associations. The abundant expression of Ii on butyrate‐treated P3HR‐1 cells mimicked the high level of expression of p35 or Ii on leukemic cells of a subset of patients with hairy cell leukemia. Alpha and beta chains of the HLA‐D complex were absent from the P3HR‐1 cell line and present in the Jijoye parent from which mutant P3HR‐1 was derived. This relatively simple model can lead to the study of inducible synthesis, processing and expression of Ii, with or without HLA‐D alpha and beta chains.
The management of localized, infradiaphragmatic Hodgkin's disease: Experience of a rare clinical presentation at St Bartholomew's Hospital
Authors: Dorreen M. S. , Wrigley P. F. M. , Jones A. E. , Shand W. S. , Stansfeld A. G. , Lister T. A.
Published: January 2013

Between 1969 and 1982, 23 previously untreated patients with Hodgkin's disease (HD) confined to infradiaphragmatic sites were treated at St Bartholomew's Hospital. The distinguishing clinical characteristics of the patient population were a male: female ratio of 20:3. The mean age was 39 years, which was significantly older (P<0·05) than the mean age of patients with supradiaphragmatic HD (32 years) referred during the same period. Sixteen patients underwent formal pathological staging while one additional patient underwent a diagnostic laparotomy without splenectomy. The final pre‐treatment stages were PS IA: 5; PS IIA: 11; CS IIA: 1; PS IIB: 1; CS IIB 5. Splenic involvement correlated closely with the number of nodal sites involved, being detected in 1 / 7 patients with one site only compared with 8/9 with more (P<0·001).

Complete remission (CR) was achieved in 21 (91 per cent) patients: 12/12 following ‘inverted Y’ radiotherapy (RT) and 9/11 following combination chemotherapy. Twenty patients remain alive and 18 continue without recurrence of HD between 15 months and 12 years. All patients who failed to enter CR or who relapsed had presented with three or more sites of involvement or with constitutional (‘B’) symptoms. These results confirm the generally good prognosis of this uncommon presentation of HD and also suggest that prognosis is determined by the bulk of disease rather than its precise anatomical localization, provided that appropriate therapy is administered.
Expression of p35 in hairy leukemic cells from Japanese patients
Authors: Shibuya Atsushi , Matsuo Yoshinobu , Sagawa Kimitaka , Katayama Isao
Published: January 2013

Spiro and coworkers found a 35 000 dalton membrane protein (p35) expressed abundantly in hairy cells of a subset of white, American patients with hairy cell leukemia. They subsequently identified p35 to be the human homologue of murine Ii, an electrophoretically invariant protein associated with Ia molecules. Using related analytical techniques, we have studied leukemic cells of two blood and one splenic samples from three Japanese patients with hairy cell leukemia and have demonstrated abundance of p35 in the splenic and one of the blood samples. The second blood sample was negative for p35 by our method of analysis, but the same hairy cells became positive for p35 at 2 months in culture and negative again at 4 months in culture. All 3 samples of this patient (fresh hairy cells and cultured cells at 2 and 4 months) remained consistently positive for Ia and for light chain‐restricted immunoglobulin. Control cells from one each of acute lymphoblastic leukemia and Burkitt's lymphoma were negative for abundant p35 expression after culture as well as in the fresh state. One can conclude that the Japanese form of hairy cell leukemia, while varying in several distinct clinical and laboratory features from hairy cell leukemia in caucasions, is characterized also by abundant expression of p35 as seen in a subset of white patients. In addition, this expression of p35 is developed by hairy leukemic cells in culture initially but is lost upon longer term culture, in parallel with the level of tartrate‐resistant acid phosphatase reactivity.
Re‐evaluation of high incidence of Hodgkin's disease in Kyushu, Japan
Authors: Tajima Kazuo , Suchi Taizan , Hirose Kaoru , Nakagawa Noriko , Kuroishi Tetsuo , Tominaga Suketami
Published: January 2013

In order to revaluate the high mortality from Hodgkin's disease (HD) in Kyushu, Japan, the chronological changes of the geographical variation of HD were analysed. The age‐adjusted death rates (AADRs) for HD of the three periods 1969–71, 1974–76, and 1979–81 were calculated for each prefecture and 128 cases of HD in 1969–72 were re‐examined to evaluate the difference in the diagnostic criteria of HD among these periods.

AADRs for HD in Kagoshima Prefecture, which had the highest mortality from HD in Japan in the early period, has decreased drastically and the mortality from HD in Kyushu has not been high in the most recent period.

The main reasons for the decreased mortality from HD in Kyushu may be as follows: (1) HD has been more strictly diagnosed by histopathological criteria in recent years; (2) adult T‐cell leukemia/lymphoma (ATLL) which is prevalent in Kyushu and has similar histopathological features to those of HD may have been diagnosed as HD in the past when the concept of ATLL did not exist. Therefore, it is suggested that the mortality from HD in Kyushu has been essentially the same as for other areas in Japan even in the past.
Differential effect of TPA and n‐butyrate on induction of Ii and EBV antigens in the P3HR‐1 lymphoblastoid cell line
Authors: Sairenji Takeshi , Spiro Robert C. , Humphreys Robert E.
Published: January 2013

The aim of this study was to test whether EBV induction by TPA or n‐butyrate was related directly to hyperexpression of Ii, an electrophoretically invariant, 35 000 dalton, HLA‐DR antigen‐associated glycoprotein which is abundantly detected in EBV freshly transformed cells and is enhanced by EBV superinfection of lymphoblastoid cell lines. P3HR‐1 lymphoblasts were treated with n‐butyrate or TPA in variable doses and durations. The augmented expression of Ii, EBV antigens (EA and VCA), DNA synthesis, and cell growth and viability were monitored. n‐Butyrate induced hyperexpression of Ii at 2 days with a maximal effective dose of 4 mm, induced EBV antigens (EA and VCA) in 36 per cent of the cells at 2 days, inhibited DNA synthesis and cell growth, and was not cytolytic at 48 h when Ii induction was maximal. TPA did not induce hyperexpression of Ii, induced EBV antigens (EA) in 30 per cent of the cells at 4 days, did not inhibit DNA synthesis and cell growth, and was not cytolytic in the time course and doses studied. Ii expression, therefore, did not appear to be an obligatory consequence of EBV antigen induction. Ii induction might be related to an effect of EBV inducers on cellular DNA synthesis, or on control of the cell cycle, or directly upon Ii gene regulation.
Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH‐AARP Diet and Health Study
Authors: Daugherty Sarah E. , Lacey, James V. , Pfeiffer Ruth M. , Park Yikyung , Hoover Robert N. , Silverman Debra T.
Published: January 2013

The incidence of bladder cancer among women is at least one‐third to one‐fourth that observed among men in many countries. Even after accounting for known risk factors, the reason for this gender disparity remains unexplained. We conducted a comprehensive evaluation of reproductive factors and exogenous hormone use with a primary focus on menopausal hormone therapy use and risk of bladder cancer in women in the NIH‐AARP Diet and Health Study. Reproductive and hormonal factors were ascertained on the baseline questionnaire in 1995–1996 among 201,492 females who were followed until December 31, 2006. During follow‐up, 651 cases of bladder cancer were diagnosed. A subset of women provided detailed information on use of MHT in a second questionnaire in 1996–1997. In this analysis, 127,361 females were followed through June 30, 2002 and 198 incident bladder cancer cases were identified. Cox proportional hazard models, adjusted for smoking status, cigarettes per day and body mass index using age as the time metric, were used to obtain hazard ratios (HRs). A reduced risk was observed among parous women (HR=0.76; 95% CI 0.62–0.93) and women who reported late age at menarche (≥15 years) (HR=0.57; 95% CI 0.39–0.84). Women who reported ever using estrogen and progestin therapy had a decreased risk (HR=0.53; 95% CI: 0.34–0.83) compared with women who did not report MHT use. No association was observed for estrogen only users (HR=0.82; 95% CI: 0.58–1.15). Our results suggest a putative role for sex hormones in the etiology of bladder cancer among women.
Carcinoembryonic antigen‐related cell adhesion molecule 1 negatively regulates granulocyte colony‐stimulating factor production by breast tumor‐associated macrophages that mediate tumor angiogenesis
Authors: Samineni Sridhar , Zhang Zhifang , Shively John E.
Published: January 2013

Carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1), a cell adhesion molecule expressed on epithelial cells and activated immune cells, is downregulated in many cancers and plays a role in inhibition of inflammation in part by inhibition of granulocyte colony‐stimulating factor (G‐CSF) production by myeloid cells. As macrophages are associated with a poor prognosis in breast cancer, but play important roles in normal breast, we hypothesized that CEACAM1 downregulation would lead to tumor promotion under inflammatory conditions. Cocultures of proinflammatory M1 macrophages with CEACAM1 negative MCF7 breast cells produced high levels of G‐CSF (10 ng/mL) compared to CEACAM1‐transfected MCF7/4S cells (1 ng/mL) or anti‐inflammatory M2 macrophage cocultures (0.5 or 0.1 ng/mL, MCF7 or MCF7/4S, respectively). The expression of CEACAM1 on M1s was much greater than for M2s and was observed only in cocultures with either MCF7 or MCF7/4S cells. When M1 macrophages were mixed with MCF7 cells and implanted in murine mammary fat pads of nonobese diabetic/severe combined immunodeficient mice, tumor size and blood vessel density were significantly greater than MCF7 or MCF7/4S only tumors which were hardly detected after 8 weeks of growth. In contrast, M1 cells had a much reduced effect on MCF7/4S tumor growth and blood vessel density, indicating that the tumor inhibitory effect of CEACAM1 is most likely related to its anti‐inflammatory action on inflammatory macrophages. These results support our previous finding that CEACAM1 inhibits both G‐CSF production by myeloid cells and G‐CSF‐stimulated tumor angiogenesis.
18F-fluoride PET as a noninvasive imaging biomarker for determining treatment efficacy of bone active agents at the hip: A prospective, randomized, controlled clinical study
Authors: Frost Michelle L , Moore Amelia E , Siddique Musib , Blake Glen M , Laurent Didier , Borah Babul , Schramm Ursula , Valentin Marie-Anne , Pellas Theodore C , Marsden Paul K , Schleyer Paul J , Fogelman Ignac
Published: January 2013

The functional imaging technique of 18F-fluoride positron emission tomography (18F-PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if 18F-PET can be used as an early biomarker of treatment efficacy at the hip. Twenty-seven treatment-naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n = 13) or calcium and vitamin D only (control group, n = 14). Subjects in the TPT group were treated with 20 µg/day teriparatide for 12 weeks. 18F-PET scans of the proximal femur, pelvis, and lumbar spine were performed at baseline and 12 weeks. The plasma clearance of 18F-fluoride to bone, Ki, a validated measurement of bone formation, was measured at four regions of the hip, lumbar spine, and pelvis. A significant increase in Ki was observed at all regions of interest (ROIs), including the total hip (+27%, p = 0.002), femoral neck (+25%, p = 0.040), hip trabecular ROI (+21%, p = 0.017), and hip cortical ROI (+51%, p = 0.001) in the TPT group. Significant increases in Ki in response to TPT were also observed at the lumbar spine (+18%, p = 0.001) and pelvis (+42%, p = 0.001). No significant changes in Kiwere observed for the control group. Changes in BMD and bone turnover markers were consistent with previous trials of teriparatide. In conclusion, this is the first study to our knowledge to demonstrate that 18F-PET can be used as an imaging biomarker for determining treatment efficacy at the hip as early as 12 weeks after initiation of therapy.
The regulation of runt-related transcription factor 2 by fibroblast growth factor-2 and connexin43 requires the inositol polyphosphate/protein kinase Cδ cascade
Authors: Niger Corinne , Luciotti Maria A , Buo Atum M , Hebert Carla , Ma Vy , Stains Joseph P
Published: January 2013

Connexin43 (Cx43) plays a critical role in osteoblast function and bone mass accrual, yet the identity of the second messengers communicated by Cx43 gap junctions, the targets of these second messengers and how they regulate osteoblast function remain largely unknown. We have shown that alterations of Cx43 expression in osteoblasts can impact the responsiveness to fibroblast growth factor-2 (FGF2), by modulating the transcriptional activity of runt-related transcription factor 2 (Runx2). In this study, we examined the contribution of the phospholipase Cγ1/inositol polyphosphate/protein kinase C delta (PKCδ) cascade to the Cx43-dependent transcriptional response of MC3T3 osteoblasts to FGF2. Knockdown of expression and/or inhibition of function of phospholipase Cγ1, inositol polyphosphate multikinase, which generates inositol 1,3,4,5-tetrakisphosphate (InsP4) and InsP5, and inositol hexakisphosphate kinase 1/2, which generates inositol pyrophosphates, prevented the ability of Cx43 to potentiate FGF2-induced signaling through Runx2. Conversely, overexpression of phospholipase Cγ1 and inositol hexakisphosphate kinase 1/2 enhanced FGF2 activation of Runx2 and the effect of Cx43 overexpression on this response. Disruption of these pathways blocked the nuclear accumulation of PKCδ and the FGF2-dependent interaction of PKCδ and Runx2, reducing Runx2 transcriptional activity. These data reveal that FGF2-signaling involves the inositol polyphosphate cascade, including inositol hexakisphosphate kinase (IP6K), and demonstrate that IP6K regulates Runx2 and osteoblast gene expression. Additionally, these data implicate the water-soluble inositol polyphosphates as mediators of the Cx43-dependent amplification of the osteoblast response to FGF2, and suggest that these low molecular weight second messengers may be biologically relevant mediators of osteoblast function that are communicated by Cx43-gap junctions.
Effective fragment potential method in Q‐CHEM: A guide for users and developers
Authors: Ghosh Debashree , Kosenkov Dmytro , Vanovschi Vitalii , Flick Joanna , Kaliman Ilya , Shao Yihan , Gilbert Andrew T.B. , Krylov Anna I. , Slipchenko Lyudmila V.
Published: January 2013

A detailed description of the implementation of the effective fragment potential (EFP) method in the Q‐CHEM electronic structure package is presented. The Q‐CHEM implementation interfaces EFP with standard quantum mechanical (QM) methods such as Hartree–Fock, density functional theory, perturbation theory, and coupled‐cluster methods, as well as with methods for electronically excited and open‐shell species, for example, configuration interaction, time‐dependent density functional theory, and equation‐of‐motion coupled‐cluster models. In addition to the QM/EFP functionality, a “fragment‐only” feature is also available (when the system is described by effective fragments only). To aid further developments of the EFP methodology, a detailed description of the C++ classes and EFP module's workflow is presented. The EFP input structure and EFP job options are described. To assist setting up and performing EFP calculations, a collection of Perl service scripts is provided. The precomputed EFP parameters for standard fragments such as common solvents are stored in Q‐CHEM's auxiliary library; they can be easily invoked, similar to specifying standard basis sets. The instructions for generating user‐defined EFP parameters are given. Fragments positions can be specified by their center of mass coordinates and Euler angles. The interface with the IQMOL and WEBMO software is also described. © 2013 Wiley Periodicals, Inc.
Microbes – friends and foes of sugarcane
Authors: Mehnaz Samina
Published: January 2013

Sugarcane is an important cash crop for many countries because it is a major source of several products including sugar and bioethanol. To obtain maximum yields there is a need to apply large quantities of chemical fertilizers.Worldwide yields are also severely affected by more than sixty diseases, mostly caused by fungi but viruses, phytoplasmas, nematodes and other pests can also damage this crop. For most of these diseases, chemical control is not available and breeders are struggling with the development of pest resistant varieties. Many members of the grass family Poaceae establish associations with beneficial microbes which promote their growth by direct and indirect mechanisms. They can be used as means to reduce the need for chemical fertilizer and to minimize the impacts of pathogen invasion. This review highlights the diversity of the microbes associated with sugarcane and the role of beneficial microbes for growth promotion and biocontrol. More extensive use of beneficial microbes will help the sugarcane grower not only to reduce the use of chemical fertilizers but also minimize the disease. In this paper, a brief description of both the non‐pathogenic and pathogenic microbes associated with sugarcane is provided. Future prospects for the expanded use of beneficial microbes for sugarcane are also discussed and detailed herein.
Characterization of myxobacterial A‐motility: insights from microcinematographic observations
Authors: Koch Matthias K. , Hoiczyk Egbert
Published: January 2013

Myxococcus xanthus, a predatory soil bacterium, has long been used as a model organism to study bacterial gliding motility. Research has revealed that two fundamentally distinct motor systems power gliding in this bacterium: repeated extensions and retractions of pili mediate social or (S‐) motility, whereas the motor powering adventurous or (A‐) motility has not yet been identified with certainty. Several different hypotheses to explain A‐motility have been suggested and differ with respect to the involved motor structures as well as the mechanics of motility. As some of the more recent models invoke helically arranged structures and processes that require rotations of the cell, we decided to re‐examine myxobacterial motility using microcinematographic techniques. This re‐examination was also prompted by the lack of direct experimental data on the rotation of M. xanthus during gliding. Microcinematographic observations of deformed cells and cells containing large stationary intracellular structures reveal clearly that M. xanthus gliding does not require cell rotation.
An interesting two‐phase solvent system and its use in preparative isolation of aconitines from aconite roots by counter‐current chromatography
Authors: Han Quan‐Bin , Tang Wai‐Lun , Dong Cai‐Xia , Xu Hong‐Xi , Jiang Zhi‐Hong
Published: January 2013

Two‐phase solvent system plays crucial role in successful separation of organic compounds using counter‐current chromatography (CCC). An interesting two‐phase solvent system, composed of chloroform/ethyl acetate/methanol/water, is reported here, in which both phases contain sufficient organic solvents to balance their dissolving capacities. Adjusting the solvent system to get satisfactory partition coefficients (K values) for target compounds becomes relatively simple. This solvent system succeeded in sample preparation of aconitine (8.07 mg, 93.69%), hypaconitine (7.74 mg, 93.17%), mesaconitine (1.95 mg, 94.52%) from raw aconite roots (102.24 mg, crude extract), benzoylmesaconine (34.79 mg, 98.67%) from processed aconite roots (400.01 mg, crude extract), and yunaconitine (253.59 mg, 98.65%) from a crude extract of Aconitum forrestii (326.69 mg, crude extract).
Resource selection by Indiana bats during the maternity season
Authors: Womack Kathryn M. , Amelon Sybill K. , Thompson Frank R.
Published: January 2013

Little information exists on resource selection by foraging Indiana bats (Myotis sodalis) during the maternity season. Existing studies are based on modest sample sizes because of the rarity of this endangered species and the difficulty of radio‐tracking bats. Our objectives were to determine resource selection by foraging Indiana bats during the maternity season and to compare resource use between pregnant and lactating individuals. We used an information theoretic approach with discrete choice modeling based on telemetry data to evaluate our hypotheses that land cover, percent canopy cover, distance to water, and prescribed fire affected the relative probability a point was used by a foraging Indiana bat. We fit models for individual bats and a population‐level model based on all individuals with a random factor to account for differences in sample size among individuals. We radio‐tracked 29 individuals and found variation in resource selection among individuals. However, among individuals with the same supported covariates, the magnitude and direction of the covariates were similar. Eighteen bats selected areas with greater canopy closure and 5 of 6 bats that had areas burned by low‐intensity prescribed fire in their home range selected burned areas. Resource selection was related to land cover for 13 individuals; they selected forest and shrubland over agricultural land, which composed >50% of the landscape within 10 km. We found no support for our hypothesis that resource selection was related to individual reproductive condition or Julian date in our population‐level model indicating habitat selection was not determined by reproductive status or date within the maternity season. Land use or forest management that greatly reduces canopy cover may have a negative impact on Indiana bat use. Maintaining forest cover in agricultural landscapes is likely critical to persistence of maternity colonies in these landscapes. Sites managed with low severity prescribed fire may be selected by some individuals because of reduced understory vegetation. © 2013 The Wildlife Society.
Invasive bullfrog larvae lack developmental plasticity to changing hydroperiod
Authors: Cook Megan T. , Heppell Selina S. , Garcia Tiffany S.
Published: January 2013

Determining the mechanisms responsible for the success of invasive species is critical for developing effective management strategies. Artificially draining managed wetlands to maintain natural ephemeral conditions is a common practice in the Pacific Northwest and is assumed to kill invasive American bullfrog (Lithobates catesbeianus) larvae, which typically overwinter in permanent wetlands before metamorphosis. Bullfrogs in the Willamette Valley, Oregon, however, have invaded ephemeral wetland sites with confirmed metamorphosis within 4 months after hatching at 1 site. We hypothesized that plasticity in growth and development rates in response to hydroperiod facilitated bullfrog invasion in Oregon. We tested this hypothesis by quantifying larval bullfrog development and growth in response to 3 hydroperiod conditions in a mesocosm setting. We tested clutches collected from both ephemeral (n = 3) and permanent (n = 3) wetlands. We found no differences in development or growth due to hydroperiod treatments (body length, P = 0.48; mass, P = 0.27), but we found differences in growth among clutches (P ≤ 0.001). These differences likely represent natural variation in growth rates because clutches collected from the same wetland type did not respond with similar growth and geographic barriers between collection sites did not account for the differences. These results indicate a lack of plasticity to hydroperiod and suggest that artificial hydroperiod manipulation in the Pacific Northwest will not induce rapid metamorphosis by invasive bullfrog larvae, although some genotypes may be capable of rapid growth and metamorphosis. © 2013 The Wildlife Society.
The administration of anesthetic in the thyroid pericapsular region increases the possibility of side effects during percutaneous laser photocoagulation of thyroid nodules
Authors: Gambelunghe Giovanni , Bini Vittorio , Monacelli Massimo , Avenia Nicola , D'Ajello Michele , Colella Renato , De Feo Pierpaolo
Published: January 2013

Background and Objective

Nodular thyroid disease is very frequent in iodine‐deficient areas affecting at least 50% of the population. Percutaneous laser ablation (LA) represents an effective method and an alternative to conventional surgery. Since the first description of the LA methodology for thyroid nodules, various studies have suggested some modifications to increase the percentage of volume reduction of the nodules. One of these alternatives involves the injection of anesthetic in the pericapsular thyroid space with detachment of the capsule itself from the surrounding tissue. The aim of this study was to retrospectively evaluate whether using local anesthetic during LA is more effective in reducing volume size of treated nodules, and whether it causes fewer side effects than using no local anesthesia.

Study Design

A retrospective analysis was conducted on 100 LA procedures performed on 100 patients between January 2009 and December 2011. The patients were divided into two groups: Group A (n = 50) received Lidocaine around the capsule of the thyroid nodule and Group B (n = 50) did not receive any local anesthetic treatment. Before treatment, the median volume size of the nodules of the two groups was similar.

Results and Conclusions

The results of our study demonstrate that the injection of local anesthetic does not help reduce nodule volume and that side effects (fever and pain) increase about threefold in the early hours following LA treatment. Thus, we do not recommend local anesthesia before LA of thyroid nodules. Lasers Surg. Med. 45: 34–37, 2013. © 2013 Wiley Periodicals, Inc.
A prospective study to assess in vivo optical coherence tomography imaging for early detection of chemotherapy‐induced oral mucositis
Authors: Calantog Alden , Hallajian Lucy , Nabelsi Tasneem , Mansour Stephanie , Le Anh , Epstein Joel , Wilder‐Smith Petra
Published: January 2013

Background and Objective

Oral mucositis (OM) is a common and severe complication of many cancer therapies. Currently, prediction and early detection are not possible and objective monitoring remains problematic. Goal of this prospective study is to assess non‐invasive imaging using optical coherence tomography (OCT) for early detection and evaluation of chemotherapy‐induced OM in 48 patients, 12 of whom developed clinical mucositis.

Study Design/Materials and Methods

In 48 patients receiving neoadjuvant chemotherapy for primary breast cancer, oral mucosal health was assessed clinically, and imaged using non‐invasive OCT. Images were evaluated for mucositis using an imaging‐based scoring system ranging from 0 to 6. Conventional clinical assessment using the OM assessment scale (OMAS) was used as the gold standard. Patients were evaluated on Days 0–11 after commencement of chemotherapy. OCT images were visually scored by three blinded investigators.

Results

The following events were identified from OCT images (1) change in epithelial thickness and subepithelial tissue integrity (beginning on Day 2), (2) loss of surface keratinized layer continuity (beginning on Day 4), (3) loss of epithelial integrity (beginning on Day 4). Imaging data gave higher scores compared to clinical scores early in treatment, suggesting that the imaging‐based diagnostic scoring was more sensitive to early mucositic change than the clinical scoring system. Once mucositis was established, imaging and clinical scores converged.

Conclusion

Using OCT imaging and a novel scoring system, earlier, more sensitive detection of mucositis was possible than using OMAS. Specific imaging‐based changes were a consistent predictor of clinical mucositis. Lasers Surg. Med. 45: 22–27, 2013. © 2013 Wiley Periodicals, Inc.
Tunable Thermoresponsive Pyrrolidone‐Based Polymers from Pyroglutamic Acid, a Bio‐Derived Resource
Authors: Bhat Rajani , Pietrangelo Agostino
Published: January 2013

A series of pyrrolidone‐based polymers is prepared from pyroglutamic acid, a bio‐derived resource. Polymers bearing simple alkoxy substituents (e.g., methoxy, ethoxy, and butoxy) are soluble in common organic solvents and possess glass transition temperatures that are dependent on the length of the alkoxy residue. Replacing these substituents with an ether moiety (CH3OCH2CH2O—) affords a highly sensitive and reversible thermoresponsive polymer with a lower critical solution temperature (LCST) of 42 °C in water. Copolymers composed of repeat units bearing both the ether and simple alkoxy residues are found to exhibit LCSTs that are highly dependent on the nature of the hydrophobic alkoxy residue suggesting that the LCSTs of these polymers can be successfully tuned by simply tailoring the copolymer structure.
Conjugated Polymer Chains Confined in Vertical Nanocylinders of a Block‐Copolymer Film: Preparation, Characterization, and Optoelectronic Function
Authors: Dong Ban Xuan , Honmou Yoshihiro , Komiyama Hideaki , Furumaki Shu , Iyoda Tomokazu , Vacha Martin
Published: January 2013

Hybrid materials composed of phase‐separated block copolymer films and conjugated polymers of the phenylenevinylene family (PPV) are prepared. The PPV chains are embedded in vertical cylinders of nanometer diameter in the block‐copolymer films. The cylinders span continuously the whole film thickness of 70 nm. Incorporation of the PPV chains into the one‐dimensional cylinders leads to modified photoluminescence spectra and to large absorption anisotropy. The hybrid films show electroluminescence from the PPV chains in a simple light‐emitting device at minute doping concentrations, and also exhibit a factor of 19 increase in electron transport efficiency along the single PPV chains.
Exploring the Impact of Alliance Portfolio Management Design on Alliance Portfolio Performance
Authors: Neyens Inge , Faems Dries
Published: January 2013

As firms engage in an increasing number of alliances, they face the challenge of managing such an alliance portfolio. Although existing studies on alliance portfolio management (APM) mainly focus on (i) alliance experience and (ii) APM best practices, they remain silent on how firms structurally design their APM system. On the basis of the survey data of 103 companies that engaged in technology alliances between 2006 and 2008, we identify four first‐order (APM formalization, APM hierarchy, APM specialization, and APM participation) and two second‐order (mechanistic APM and organic APM) dimensions that explain how firms design the management of their technology alliance portfolios. In addition, we find that adopting an organic approach toward designing APM significantly increases alliance portfolio performance, suggesting that particular APM designs might contribute to building alliance management capabilities. Copyright © 2013 John Wiley & Sons, Ltd.
Pain response measured with arterial spin labeling
Authors: Maleki Nasim , Brawn Jennifer , Barmettler Gabi , Borsook David , Becerra Lino
Published: January 2013

The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level‐dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is another imaging approach in which the magnetically labeled arterial water is used as an endogenous tracer that allows for direct measurement of cerebral blood flow. In this study, we assessed the pain response in the brain using a pulsed‐continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised. Copyright © 2013 John Wiley & Sons, Ltd.
Modeling impure clusters in a cluster randomized controlled trial
Authors: Brown Roger L.
Published: January 2013

Cluster randomized controlled trials (CRCT) can be susceptible to a wide range of methodological problems. Many of these problems are not commonly recognized by researchers. This article is focused on one potential problem, the issue of impure clustering (multiple patient membership) within the CRCT structures and how it can lead to possible misunderstanding and bias in the results of the trial. A solution to this problem is presented using a multiple membership random effects model (MMREM). A simulated example of a three‐level CRCT is presented and modeled with and without multiple patient membership data. Results indicate underestimation of higher level variances, and overestimation of lower‐level variances, while also indicating underestimation of level predictors where the multiple membership occurs. © 2013 Wiley Periodicals, Inc. Res Nurs Health 36:216–223, 2013
Structural and dynamics characterization of norovirus protease
Authors: Takahashi Daisuke , Hiromasa Yasuaki , Kim Yunjeong , Anbanandam Asokan , Yao Xiaolan , Chang Kyeong‐Ok , Prakash Om
Published: January 2013

Norovirus protease is an essential enzyme for proteolytic maturation of norovirus nonstructural proteins and has been implicated as a potential target for antiviral drug development. Although X‐ray structural studies of the protease give us wealth of structural information including interactions of the protease with its substrate and dimeric overall structure, the role of protein dynamics in the substrate recognition and the biological relevance of the protease dimer remain unclear. Here we determined the solution NMR structure of the 3C‐like protease from Norwalk virus (NV 3CLpro), a prototype strain of norovirus, and analyzed its backbone dynamics and hydrodynamic behavior in solution. 15N spin relaxation and analytical ultracentrifugation analyses demonstrate that NV 3CLpro is predominantly a monomer in solution. Solution structure of NV 3CLpro shows significant structural variation in C‐terminal domain compared with crystal structures and among lower energy structure ensembles. Also, 15N spin relaxation and Carr–Purcell–Meiboom–Gill (CPMG)‐based relaxation dispersion analyses reveal the dynamic properties of residues in the C‐terminal domain over a wide range of timescales. In particular, the long loop spanning residues T123–G133 show fast motion (ps‐ns), and the residues in the bII–cII region forming the large hydrophobic pocket (S2 site) undergo conformational exchanges on slower timescales (μs–ms), suggesting their important role in substrate recognition.
pH‐selective mutagenesis of protein–protein interfaces: In silico design of therapeutic antibodies with prolonged half‐life
Authors: Spassov Velin Z. , Yan Lisa
Published: January 2013

Understanding the effects of mutation on pH‐dependent protein binding affinity is important in protein design, especially in the area of protein therapeutics. We propose a novel method for fast in silico mutagenesis of protein–protein complexes to calculate the effect of mutation as a function of pH. The free energy differences between the wild type and mutants are evaluated from a molecular mechanics model, combined with calculations of the equilibria of proton binding. The predicted pH‐dependent energy profiles demonstrate excellent agreement with experimentally measured pH‐dependency of the effect of mutations on the dissociation constants for the complex of turkey ovomucoid third domain (OMTKY3) and proteinase B. The virtual scanning mutagenesis identifies all hotspots responsible for pH‐dependent binding of immunoglobulin G (IgG) to neonatal Fc receptor (FcRn) and the results support the current understanding of the salvage mechanism of the antibody by FcRn based on pH‐selective binding. The method can be used to select mutations that change the pH‐dependent binding profiles of proteins and guide the time consuming and expensive protein engineering experiments. As an application of this method, we propose a computational strategy to search for mutations that can alter the pH‐dependent binding behavior of IgG to FcRn with the aim of improving the half‐life of therapeutic antibodies in the target organism. © Proteins 2013. © 2012 Wiley Periodicals, Inc.
Crystal structure of the ω‐aminotransferase from Paracoccus denitrificans and its phylogenetic relationship with other class III amino‐ transferases that have biotechnological potential
Authors: Rausch Christian , Lerchner Alexandra , Schiefner André , Skerra Arne
Published: January 2013

Apart from their crucial role in metabolism, pyridoxal 5′‐phosphate (PLP)‐dependent aminotransferases (ATs) constitute a class of enzymes with increasing application in industrial biotechnology. To provide better insight into the structure‐function relationships of ATs with biotechnological potential we performed a fundamental bioinformatics analysis of 330 representative sequences of pro‐ and eukaryotic Class III ATs using a structure‐guided approach. The calculated phylogenetic maximum likelihood tree revealed six distinct clades of which the first segregates with a very high bootstrap value of 92%. Most enzymes in this first clade have been functionally well characterized, whereas knowledge about the natural functions and substrates of enzymes in the other branches is sparse. Notably, in those clades 2‐6 members of the peculiar class of ω‐ATs prevail, many of which have proven useful for the preparation of chiral amines or artificial amino acids. One representative is the ω‐AT from Paracoccus denitrificans (PD ω‐AT) which catalyzes, for example, the transamination in a novel biocatalytic process for the production of L‐homoalanine from L‐threonine. To gain structural insight into this important enzyme, its X‐ray analysis was carried out at a resolution of 2.6 Å, including the covalently bound PLP as well as 5‐aminopentanoate as a putative amino donor substrate. On the basis of this crystal structure in conjunction with our phylogenetic analysis, we have identified a generic set of active site residues of ω‐ATs that are associated with a strong preference for aromatic substrates, thus guiding the discovery of novel promising enzymes for the biotechnological production of corresponding chiral amines. © Proteins 2013. © 2012 Wiley Periodicals, Inc.
Effects of protonation state of Asp181 and position of active site water molecules on the conformation of PTP1B
Authors: Özcan Ahmet , Olmez Elif Ozkirimli , Alakent Burak
Published: January 2013

In protein tyrosine phosphatase 1B (PTP1B), the flexible WPD loop adopts a closed conformation (WPDclosed) in the active state of PTP1B, bringing the catalytic Asp181 close to the active site pocket, while WPD loop is in an open conformation (WPDopen) in the inactive state. Previous studies showed that Asp181 may be protonated at physiological pH, and ordered water molecules exist in the active site. In the current study, molecular dynamics simulations are employed at different Asp181 protonation states and initial positions of active site water molecules, and compared with the existing crystallographic data of PTP1B. In WPDclosed conformation, the active site is found to maintain its conformation only in the protonated state of Asp181 in both free and liganded states, while Asp181 is likely to be deprotonated in WPDopen conformation. When the active site water molecule network that is a part of the free WPDclosed crystal structure is disrupted, intermediate WPD loop conformations, similar to that in the PTPRR crystal structure, are sampled in the MD simulations. In liganded PTP1B, one active site water molecule is found to be important for facilitating the orientation of Cys215 and the phosphate ion, thus may play a role in the reaction. In conclusion, conformational stability of WPD loop, and possibly catalytic activity of PTP1B, is significantly affected by the protonation state of Asp181 and position of active site water molecules, showing that these aspects should be taken into consideration both in MD simulations and inhibitor design. © Proteins 2013. © 2012 Wiley Periodicals, Inc.