bluuebunny/crossref_metadata_2025 huggingface dataset:
On Hausdorff dimension monotonicity of a family of dynamical subsets of Rauzy fractals
Authors: Nowak W. Georg , Scheicher Klaus , Sirvent Víctor F.
Published: October 2014

We consider a family of dynamically defined subsets of Rauzy fractals in the plane. These sets were introduced in the context of the study of symmetries of Rauzy fractals. We prove that their Hausdorff dimensions form an ultimately increasing sequence of numbers converging to 2. These results answer a question stated by the third author in 2012.
Peristaltic transport of a conducting Jeffrey fluid in an inclined asymmetric channel
Authors: Vajravelu K. , Sreenadh S. , Sucharitha G. , Lakshminarayana P.
Published: October 2014

Peristaltic flow of a conducting Jeffrey fluid in an inclined asymmetric channel is investigated. The channel asymmetry is produced by considering a peristaltic wave train on the flexible walls of the channel with different amplitudes and phases. The nonlinear governing equations are solved analytically by a perturbation technique. The expressions for the stream function, axial velocity and the pressure rise per wavelength are determined in terms of the Jeffrey number λ1, the Froude number Fr, the perturbation parameter δ, the angle of inclination θ and the phase difference ϕ. Effects of the physical parameters on the velocity field and the pumping characteristics are discussed. It is observed that the size of the trapping bolus increase with an increase in the magnetic parameter and the volume flow rate. That is, the magnetic parameter and the volume flow rate have strong influence on the trapping bolus phenomenon.
MGAT2 deficiency and vertical sleeve gastrectomy have independent metabolic effects in the mouse
Authors: Mul Joram D. , Begg Denovan P. , Haller April M. , Pressler Josh W. , Sorrell Joyce , Woods Stephen C. , Farese Robert V. , Seeley Randy J. , Sandoval Darleen A.
Published: October 2014

Vertical sleeve gastrectomy (VSG) is currently one of the most effective treatments for obesity. Despite recent developments, the underlying mechanisms that contribute to the metabolic improvements following bariatric surgery remain unresolved. VSG reduces postprandial intestinal triglyceride (TG) production, but whether the effects of VSG on intestinal metabolism are related to metabolic outcomes has yet to be established. The lipid synthesis enzyme acyl CoA:monoacylglycerol acyltransferase-2 ( Mogat2; MGAT2) plays a crucial role in the assimilation of dietary fat in the intestine and in regulation of adiposity stores as well. Given the phenotypic similarities between VSG-operated and MGAT2-deficient animals, we reasoned that this enzyme could also have a key role in mediating the metabolic benefits of VSG. However, VSG reduced body weight and fat mass and improved glucose metabolism similarly in whole body MGAT2-deficient ( Mogat2−/−) mice and wild-type littermates. Furthermore, along with an increase in energy expenditure, surgically naive Mogat2−/−mice had altered macronutrient preference, shifting preference away from fat and toward carbohydrates, and increased locomotor activity. Collectively, these data suggest that the beneficial effects of VSG on body weight and glucose metabolism are independent of MGAT2 activity and rather that they are separate from the effects of MGAT2 deficiency. Because MGAT2 inhibitors are proposed as a pharmacotherapeutic option for obesity, our data suggest that, in addition to increasing energy expenditure, shifting macronutrient preference away from fat could be another important mechanism by which these compounds could contribute to weight loss.
Impact of Direct Soil Moisture and Revised Soil Moisture Index Methods on Hydrologic Predictions in an Arid Climate
Authors: Jajarmizadeh Milad , Harun Sobri bin , Shahid Shamsuddin , Akib Shatirah , Salarpour Mohsen
Published: October 2014

The soil and water assessment tool (SWAT) is a physically based model that is used extensively to simulate hydrologic processes in a wide range of climates around the world. SWAT uses spatial hydrometeorological data to simulate runoff through the computation of a retention curve number. The objective of the present study was to compare the performance of two approaches used for the calculation of curve numbers in SWAT, that is, the Revised Soil Moisture Index (SMI), which is based on previous meteorological conditions, and the Soil Moisture Condition II (SMCII), which is based on soil features for the prediction of flow. The results showed that the sensitive parameters for the SMI method are land-use and land-cover features. However, for the SMCII method, the soil and the channel are the sensitive parameters. The performances of the SMI and SMCII methods were analyzed using various indices. We concluded that the fair performance of the SMI method in an arid region may be due to the inherent characteristics of the method since it relies mostly on previous meteorological conditions and does not account for the soil features of the catchment.
Antiproliferative Effects of Methanolic Extracts ofCryptocarya concinnaHance Roots on Oral Cancer Ca9-22 and CAL 27 Cell Lines Involving Apoptosis, ROS Induction, and Mitochondrial Depolarization
Authors: Huang Hurng-Wern , Chung Yi-An , Chang Hsun-Shuo , Tang Jen-Yang , Chen Ih-Sheng , Chang Hsueh-Wei
Published: October 2014

Cryptocarya-derived natural products were reported to have several biological effects such as the antiproliferation of some cancers. The possible antioral cancer effect ofCryptocarya-derived substances was little addressed as yet. In this study, we firstly used the methanolic extracts ofC. concinnaHance roots (MECCrt) to evaluate its potential function in antioral cancer bioactivity. We found that MECCrt significantly reduced cell viability of two oral cancer Ca9-22 and CAL 27 cell lines in dose-responsive manners (P<0.01). The percentages of sub-G1 phase and annexin V-positive of MECCrt-treated Ca9-22 and CAL 27 cell lines significantly accumulated (P<0.01) in a dose-responsive manner as evidenced by flow cytometry. These apoptotic effects were associated with the findings that intracellular ROS generation was induced in MECCrt-treated Ca9-22 and CAL 27 cell lines in dose-responsive and time-dependent manners (P<0.01). In a dose-responsive manner, MECCrt also significantly reduced the mitochondrial membrane potential in these two cell lines (P<0.01–0.05). In conclusion, we demonstrated that MECCrt may have antiproliferative potential against oral cancer cells involving apoptosis, ROS generation, and mitochondria membrane depolarization.
The Influence of Monoamine Oxidase Variants on the Risk of Betel Quid-Associated Oral and Pharyngeal Cancer
Authors: Chen Ping-Ho , Huang Bin , Shieh Tien-Yu , Wang Yan-Hsiung , Chen Yuk-Kwan , Wu Ju-Hui , Huang Jhen-Hao , Chen Chun-Chia , Lee Ka-Wo
Published: October 2014

Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolizedviathe monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found inin vitrostudies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.
Localized Pulsating Solutions of the Generalized Complex Cubic-Quintic Ginzburg-Landau Equation
Authors: Uzunov Ivan M. , Georgiev Zhivko D.
Published: October 2014

We study the dynamics of the localized pulsating solutions of generalized complex cubic-quintic Ginzburg-Landau equation (CCQGLE) in the presence of intrapulse Raman scattering (IRS). We present an approach for identification of periodic attractors of the generalized CCQGLE. Using ansatz of the travelling wave and fixing some relations between the material parameters, we derive the strongly nonlinear Lienard-Van der Pol equation for the amplitude of the nonlinear wave. Next, we apply the Melnikov method to this equation to analyze the possibility of existence of limit cycles. For a set of fixed parameters we show the existence of limit cycle that arises around a closed phase trajectory of the unperturbed system and prove its stability. We apply the Melnikov method also to the equation of Duffing-Van der Pol oscillator used for the investigation of the influence of the IRS on the bandwidth limited amplification. We prove the existence and stability of a limit cycle that arises in a neighborhood of a homoclinic trajectory of the corresponding unperturbed system. The condition of existence of the limit cycle derived here coincides with the relation between the critical value of velocity and the amplitude of the solitary wave solution (Uzunov, 2011).
Removal of Endobronchial Malignant Mass by Cryotherapy Improved Performance Status to Receive Chemotherapy
Authors: Fang Yueh-Fu , Hsieh Meng-Heng , Wang Tsai-Yu , Lin Horng-Chyuan , Yu Chih-Teng , Chou Chun-Liang , Lin Shu-Min , Kuo Chih-Hsi , Chung Fu-Tsai
Published: October 2014

Although malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly a palliative treatment. Clinical data on postcryotherapy MEM patients in a university-affiliated hospital between 2007 and 2011 were evaluated. Survival curve with or without postcryotherapy chemotherapy and performance status (PS) improvement of these subjects were analyzed using the Kaplan-Meier method. There were 59 patients (42 males), with median age of 64 years (range, 51–76, and median performance status of 2 (interquartile range [IQR], 2-3). Postcryotherapy complications included minor bleeding (n=12) and need for multiple procedures (n=10), while outcomes were relief of symptoms (n=51), improved PS (n=45), and ability to receive chemotherapy (n=40). The survival of patients with chemotherapy postcryotherapy was longer than that of patients without such chemotherapy (median, 534 versus 106 days; log-rank test,P=0.007; hazard ratio, 0.25; 95% confidence interval, 0.10–0.69). The survival of patients with PS improvement postcryotherapy was longer than that of patients without PS improvement (median, 406 versus 106 days; log-rank test,P=0.02; hazard ratio, 0.28; 95% confidence interval, 0.10–0.81). Cryotherapy is a feasible treatment for MEM. With better PS after cryotherapy, further chemotherapy becomes possible for patients to improve survival when MEM caused dyspnea and poor PS.
Metastatic Uterine Leiomyosarcoma in the Upper Buccal Gingiva Misdiagnosed as an Epulis
Authors: Cassoni Andrea , Terenzi Valentina , Bartoli Davina , Zadeh Oriana Rajabtork , Battisti Andrea , Pagnoni Mario , Conte Davide , Lembo Alessandro , Bosco Sandro , Alesini Francesco , Valentini Valentino
Published: October 2014

Uterine leiomyosarcoma (LMS) is a rare tumor constituting 1% of all uterine malignancies. This sarcoma demonstrates an aggressive growth pattern with an high rate of recurrence with hematologic dissemination; the most common sites are lung, liver, and peritoneal cavity, head and neck district being rarely interested. Only other four cases of metastasis in the oral cavity have been previously described. The treatment of choice is surgery and the use of adjuvant chemotherapy and radiation has limited impact on clinical outcome. In case of metastases, surgical excision can be performed considering extent of disease, number and type of distant lesions, disease free interval from the initial diagnosis to the time of metastases, and expected life span. We illustrate a case of uterine LMS metastasis in the upper buccal gingiva that occurred during chemotherapy in a 63-year-old woman that underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for a diagnosis of LMS staged as pT2bN0 and that developed lung metastases eight months after primary treatment. Surgical excision of the oral mass (previously misdiagnosed as epulis at a dental center) and contemporary reconstruction with pedicled temporalis muscle flap was performed in order to improve quality of life. Even if resection was achieved in free margins, “local” relapse was observed 5 months after surgery.
Plasticity-Mediated Persistence in New and Changing Environments
Authors: Morris Matthew R. J.
Published: October 2014

Baldwin’s synthesis of the Organicist position, first published in 1896 and elaborated in 1902, sought to rescue environmentally induced phenotypes from disrepute by showing their Darwinian significance. Of particular interest to Baldwin was plasticity’s mediating role during environmental change or colonization—plastic individuals were more likely to successfully survive and reproduce in new environments than were nonplastic individuals. Once a population of plastic individuals had become established, plasticity could further mediate the future course of evolution. The evidence for plasticity-mediated persistence (PMP) is reviewed here with a particular focus on evolutionary rescue experiments, studies on invasive success, and the role of learning in survival. Many PMP studies are methodologically limited, showing that preexistent plasticity has utility in new environments (soft PMP) rather than directly demonstrating that plasticity is responsible for persistence (hard PMP). An ideal PMP study would be able to demonstrate that (1) plasticity preexisted environmental change, (2) plasticity was fortuitously beneficial in the new environment, (3) plasticity was responsible for individual persistence in the new environment, and (4) plasticity was responsible for population persistence in succeeding generations. Although PMP is not ubiquitous, Baldwin’s hypotheses have been largely vindicated in theoretical and empirical studies, but much work remains.
Fascia Wrapping Technique: A Modified Method for the Treatment of Cubital Tunnel Syndrome
Authors: Han Hyun Ho , Kang Hae Won , Lee Jun Yong , Jung Sung-No
Published: October 2014

Variations of the anterior transposition of the ulnar nerve for cubital tunnel syndrome include subcutaneous, submuscular, intramuscular, and subfascial methods. We introduce a modification of subfascial transposition, which is designed to facilitate nerve gliding by wrapping the nerve with fascia. Twenty patients with wrapping surgery following the diagnosis of cubital tunnel syndrome were reviewed retrospectively. Preoperative electrodiagnostic studies were performed in all patients and all of them were rechecked postoperatively. The preoperative mean value of motor conduction velocity (MCV) was37.1±6.7 m/s within the elbow segment and this result showed a decrease compared to the result of MCV with53.9±6.9 m/s in the below the elbow-wrist segment with statistical significance (P<0.05). Postoperative mean values of MCV were improved in all of 20 patients to47.6±5.5 m/s (P<0.05). 19 patients of 20 (95%) reported good or excellent clinical outcomes according to a modified Bishop scoring system. The surgical treatment methods for cubital tunnel syndrome have their own advantages and disadvantages, and the preferred method differs depending on the surgeon. The wrapping method of anterior transposition is a newly designed alternative method modified from subfascial transposition. This method could be an alternative option to treat cubital tunnel syndrome.
Spinless Particles in Exponentially Varying Electric and Magnetic Fields
Authors: Sogut Kenan , Havare Ali
Published: October 2014

We investigate the motion of the charged spin-0 particles subjected to the space-dependent electric and magnetic fields. By selecting the external fields oriented parallel and orthogonal to each other, exact solutions of the motion are obtained for the nonrelativistic and the relativistic cases. The quantized energy spectrum is determined by using the solutions obtained for the motion of the particles and dependence of the energy on the strengths of the electric and magnetic fields is discussed. We compared the energy spectrum of the nonrelativistic and the relativistic particles by using the numerical results obtained for the first few quantum levels.
Ergosterol Is the Active Compound of Cultured Mycelium Cordyceps sinensis on Antiliver Fibrosis
Authors: Peng Yuan , Tao Yanyan , Wang Qinglan , Shen Li , Yang Tao , Liu Zulong , Liu Chenghai
Published: October 2014

Cultured mycelium Cordyceps sinensis (CMCS) is a Chinese herbal medicine, which is widely used for a variety of diseases including liver injury in clinic. The current study aims to investigate the protective effects of CMCS against liver fibrosis and to exploit its active antifibrotic substances in vivo and in vitro. For evaluating the antifibrotic effect of CMCS and ergosterol, male C57BL/6 mice were injected intraperitoneally with carbon tetrachloride (CCl4) and treated with CMCS (120 mg/kg/d) or ergosterol (50 mg/kg/d). Four weeks later, serum liver function, hepatic hydroxyproline (Hyp) content, liver inflammation, collagen deposition, and expression of alpha smooth muscle actin (α‐SMA) in liver tissue were evaluated. Besides, toxicological effects of active compounds of CMCS on hepatocytes and hepatic stellate cells (HSCs) were detected and expressions of permeability of the lysosomal membrane, EdU, F‐actin, and α‐SMA of activated HSCs were analyzed to screen the antifibrotic substance in CMCS in vitro. Our results showed that CMCS could significantly alleviate levels of serum liver functions, attenuate hepatic inflammation, decrease collagen deposition, and relieve levels of α‐SMA in liver, respectively. Ergosterol, the active compound in CMCS that was detected by HPLC, played a dose‐dependent inhibition role on activated HSCs via upregulating expressions of permeability of the lysosomal membrane and downregulating levels of EdU, F‐actin, and α‐SMA on activated HSCs in vitro. Moreover, ergosterol revealed the antifibrotic effect alike in vivo. In conclusion, CMCS is effective in alleviating liver fibrosis induced by CCl4 and ergosterol might be the efficacious antifibrotic substance in CMCS in vivo and in vitro.
Takotsubo’s Cardiomyopathy in a Patient with Kartagener’s Syndrome
Authors: Dominguez Luis W. , Doggette Robert P. , Gonzalez-Ibarra Fernando , Shaik Imam H. , Syed Amer K.
Published: October 2014

A 46-year-old African-American male with past medical history significant for Kartagener’s syndrome, essential hypertension, and HIV presented with acute chest pain. ECG and troponins indicated an acute myocardial infarction. Ventriculography confirmed dyskinesia of the left ventricle, with an EF of 25%. However the coronary catheterization showed nonobstructed coronaries. Ventricular contraction and EF were restored in 4 weeks. To our knowledge, this is the first incidence of Takotsubo’s reported in a young patient with Kartagener’s syndrome. Chronic lung disease may contribute to the development of Takotsubo’s cardiomyopathy, which is a documented yet not fully understood phenomenon.
Multiparametric Monitoring of Early Response to Antiangiogenic Therapy: A Sequential Perfusion CT and PET/CT Study in a Rabbit VX2 Tumor Model
Authors: Kim Jung Im , Lee Hyun-Ju , Kim Young Jae , Kim Kwang Gi , Lee Kyung Won , Lee Jae Ho , Lee Hak Jong , Lee Won Woo
Published: October 2014

Objectives.To perform dual analysis of tumor perfusion and glucose metabolism using perfusion CT and FDG-PET/CT for the purpose of monitoring the early response to bevacizumab therapy in rabbit VX2 tumor models and to assess added value of FDG-PET to perfusion CT.Methods.Twenty-four VX2 carcinoma tumors implanted in bilateral back muscles of 12 rabbits were evaluated. Serial concurrent perfusion CT and FDG-PET/CT were performed before and 3, 7, and 14 days after bevacizumab therapy (treatment group) or saline infusion (control group). Perfusion CT was analyzed to calculate blood flow (BF), blood volume (BV), and permeability surface area product (PS); FDG-PET was analyzed to calculate SUVmax, SUVmean, total lesion glycolysis (TLG), entropy, and homogeneity. The flow-metabolic ratio (FMR) was also calculated and immunohistochemical analysis of microvessel density (MVD) was performed.Results.On day 14, BF and BV in the treatment group were significantly lower than in the control group. There were no significant differences in all FDG-PET-derived parameters between both groups. In the treatment group, FMR prominently decreased after therapy and was positively correlated with MVD.Conclusions.In VX2 tumors, FMR could provide further insight into the early antiangiogenic effect reflecting a mismatch in intratumor blood flow and metabolism.
The Effects of Uygur Herb Hyssopus officinalis L. on the Process of Airway Remodeling in Asthmatic Mice
Authors: Ma Xiaojuan , Ma Xiumin , Ma Zhixing , Sun Zhan , Yu Wenyan , Wang Jing , Li Fengsen , Ding Jianbing
Published: October 2014

It has been proved that Uygur herb Hyssopus offcinalis L. could affect the levels of some cytokines (such as IL‐4, IL‐6, IL‐17, and IFN‐γ) in asthmatic mice. By detection of the expressions of MMP‐9 and TIMP‐1 and the morphological changes, the aim of this research is to reveal the mechanism of Uygur herb Hyssopus offcinalis L. in the process of airway remodeling. It was observed that the expressions of MMP‐9 and TIMP‐1 increased, but the ratio of MMP‐9/TIMP‐1 decreased in airway remodeling group. However, the expression of both MMP‐9 and TIMP‐1 decreased after being treated with dexamethasone and Hyssopus offcinalis L., accompanied by the relieved pathological changes, including collagen deposition, mucus secretion, and smooth muscle proliferation. It is suggested that Uygur herb Hyssopus offcinalis L. could inhibit airway remodeling by correcting imbalance of MMP‐9/TIMP‐1 ratio.
Unusual Case of Simultaneous Presentation of Plasma Cell Myeloma, Chronic Myelogenous Leukemia, and a Jak2 Positive Myeloproliferative Disorder
Authors: Maerki J. , Katava G. , Siegel D. , Silberberg J. , Bhattacharyya P. K.
Published: October 2014

Background. Multiple articles discuss the rare incidence and potential causes of second hematologic disorders arising after treatment of Chronic Myelogenous Leukemia (CML), leading to the theory of imatinib, the current treatment regimen for CML, as a possible trigger for the development of secondary neoplasms. Our case eliminates the possibility of imatinib as the sole cause since our patient received a diagnosis of simultaneous plasma cell myeloma, CML, and a Jak2 mutation positive myeloproliferative disorder (MPD) arising de novo, prior to any treatment. We will further investigate into alternative theories as potential causes for multiple hematopathologic disorders.Case Report. There are currently no reported cases with the diagnosis of simultaneous plasma cell myeloma, chronic myelogenous leukemia, and Jak2 positive myeloproliferative disorder. We present a case of a 77-year-old male who was discovered to have these three concurring hematopathologic diagnoses. Our review of the literature includes a look at potential associations linking the three coexisting hematologic entities.Conclusion. The mechanism resulting in simultaneous malignancies is most likely multifactorial and potentially includes factors specific to the host, continuous stimulation of the immune system, previous chemotherapy or radiation, a potential common pluripotent stem cell, or, lastly, preexisting myeloma which may increase the susceptibility of additional malignancies.
Loss‐Averse Retailer’s Optimal Ordering Policies for Perishable Products with Customer Returns
Authors: Chen Xu , Zhou Qian
Published: October 2014

We investigate the loss‐averse retailer’s ordering policies for perishable product with customer returns. With the introduction of the segmental loss utility function, we depict the retailer’s loss aversion decision bias and establish the loss‐averse retailer’s ordering policy model. We derive that the loss‐averse retailer’s optimal order quantity with customer returns exists and is unique. By comparison, we obtain that both the risk‐neutral and the loss‐averse retailer’s optimal order quantities depend on the inventory holding cost and the marginal shortage cost. Through the sensitivity analysis, we also discuss the effect of loss‐averse coefficient and the ratio of return on the loss‐averse retailer’s optimal order quantity with customer returns.
Functional Stability of Plasminogen Activator Inhibitor-1
Authors: Yasar Yildiz Songul , Kuru Pinar , Toksoy Oner Ebru , Agirbasli Mehmet
Published: October 2014

Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT) and myocardial infarction (MI). The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.
Nutritional Assessment and Antioxidant Activities of Different Varieties ofVigna radiata
Authors: Ullah Riaz , Ullah Zain , Al-Deyab Salem S. , Adnan Muhammad , Tariq Akash
Published: October 2014

Three cultivars ofVigna radiata, namely, NM-92, NM-98, and NM-06, were analyzed for their proximate composition. The samples were also tested by HPLC for amino acid content. The data showed that all the varieties had same moisture level. The maximum ash content (4.29%) was present in NM-92, and crude fat (2.26%) was highest in NM-98 while NM-06 contained maximum amount of crude protein. About eighteen types of amino acids were detected in each of the three varieties. Acidic amino acids, that is, aspartic and glutamic acids, were in considerable amount ranged from 13 to 23% followed by leucine, isoleucine, alanine, valine, lysine, phenyl alanine, serine, and arginine which fell in the range of 3–8% of total protein. The maximum amount (13.00 and 22.80%) of aspartic and glutamic acids was present in NM-98. Similarly arginine (6.83%) and serine (5.45%) were also in highest amount in this variety. Leucine (7.46%) was maximum in NM-92 variety. NM-06 contained almost all the amino acids in lesser quantity except for few like threonine, proline, glycine, and alanine. It was concluded from the present study that varieties were of different nutritional value and HPLC was a sensitive method for amino acids determination. Antioxidant activities of all three varieties were also assayed and showed significant results.
Associated Use Attainment Response between Multiple Aquatic Assemblage Indicators for Evaluating Catchment, Habitat, Water Quality, and Contaminants
Authors: Simon Thomas P. , Morris Charles C.
Published: October 2014

Use attainability analysis (UAA) at a watershed scale typically relies on the assumption that indicator organisms are responding similarly to the same environmental stressor. Factors explaining variance in fish, crayfish, and macroinvertebrate assemblage structure and function were investigated with emphasis on catchment and reach scale land use, habitat, contaminants, and water quality variables. Habitat quality scores ranged from 25 to 85 (average 61.36±10.08). The substrate score, instream cover, riffle-run score, and channel score were primary factors contributing to declining habitat quality. Factor analysis found that four factors explained 69% of the contributed variance in fish assemblage, two factors accounted for 56% of variance in macroinvertebrate assemblages, and two factors explained 49% of the variance in crayfish assemblages. Overall drivers of assemblage structure were associated with broad scale issues of wastewater treatment, groundwater, and land use. Our results show that fish, macroinvertebrate, and crayfish assemblages respond to similar broad scale stimulus; however, the specific constituents responsible for the stress may vary with the magnitude of the cumulative stress, which may be expressed by each organismal group differently. Our data suggest that varying organismal groups can respond independently and stress reflected in one assemblage may not necessarily be observed in another since each organismal group is measuring different aspects of the environment.
Bilateral Lung Transplantation in a Patient with Humoral Immune Deficiency: A Case Report with Review of the Literature
Authors: Farmer Jocelyn R. , Sokol Caroline L. , Bonilla Francisco A. , Murali Mandakolathur R. , Kradin Richard L. , Astor Todd L. , Walter Jolan E.
Published: October 2014

Humoral immune deficiencies have been associated with noninfectious disease complications including autoimmune cytopenias and pulmonary disease. Herein we present a patient who underwent splenectomy for autoimmune cytopenias and subsequently was diagnosed with humoral immune deficiency in the context of recurrent infections. Immunoglobulin analysis prior to initiation of intravenous immunoglobulin (IVIG) therapy was notable for low age-matched serum levels of IgA (11 mg/dL), IgG2 (14 mg/L), and IgG4 (5 mg/L) with a preserved total level of IgG. Flow cytometry was remarkable for B cell maturation arrest at the IgM+/IgD+ stage. Selective screening for known primary immune deficiency-causing genetic defects was negative. The disease course was uniquely complicated by the development of pulmonary arteriovenous malformations (AVMs), ultimately requiring bilateral lung transplantation in 2012. This is a patient with humoral immune deficiency that became apparent only after splenectomy, which argues for routine immunologic evaluation prior to vaccination and splenectomy. Lung transplantation is a rare therapeutic endpoint and to our knowledge has never before been described in a patient with humoral immune deficiency for the indication of pulmonary AVMs.
Copper Signaling Axis as a Target for Prostate Cancer Therapeutics
Authors: Safi Rachid , Nelson Erik R. , Chitneni Satish K. , Franz Katherine J. , George Daniel J. , Zalutsky Michael R. , McDonnell Donald P.
Published: October 2014

Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for prostate cancer cell function as we observed only modest effects of chelation strategies on the growth of these cells in vitro. With the goal of exploiting prostate cancer cell proclivity for copper uptake, we developed a “conditional lethal” screen to identify compounds whose cytotoxic actions were manifested in a copper-dependent manner. Emerging from this screen was a series of dithiocarbamates, which, when complexed with copper, induced reactive oxygen species–dependent apoptosis of malignant, but not normal, prostate cells. One of the dithiocarbamates identified, disulfiram (DSF), is an FDA-approved drug that has previously yielded disappointing results in clinical trials in patients with recurrent prostate cancer. Similarly, in our studies, DSF alone had a minimal effect on the growth of prostate cancer tumors when propagated as xenografts. However, when DSF was coadministered with copper, a very dramatic inhibition of tumor growth in models of hormone-sensitive and of castrate-resistant disease was observed. Furthermore, we determined that prostate cancer cells express high levels of CTR1, the primary copper transporter, and additional chaperones that are required to maintain intracellular copper homeostasis. The expression levels of most of these proteins are increased further upon treatment of androgen receptor (AR)–positive prostate cancer cell lines with androgens. Not surprisingly, robust CTR1-dependent uptake of copper into prostate cancer cells was observed, an activity that was accentuated by activation of AR. Given these data linking AR to intracellular copper uptake, we believe that dithiocarbamate/copper complexes are likely to be effective for the treatment of patients with prostate cancer whose disease is resistant to classical androgen ablation therapies. Cancer Res; 74(20); 5819–31. ©2014 AACR.
Oxidative Stress–Related Genetic Variants, Pro- and Antioxidant Intake and Status, and Advanced Prostate Cancer Risk
Authors: Geybels Milan S. , van den Brandt Piet A. , van Schooten Frederik J. , Verhage Bas A.J.
Published: October 2014

Background: Increased oxidative stress has been linked to prostate cancer. We investigated oxidative stress–related genetic variants in relation to advanced prostate cancer risk and examined potential interactions with pro- and antioxidant exposures.

Methods: A case-cohort analysis was conducted in the prospective Netherlands Cohort Study, which included 58,279 men ages 55 to 69 years. Cohort members completed a baseline questionnaire and provided toenail clippings, which were used to isolate DNA. Advanced prostate cancer cases were identified during 17.3 years of follow-up. The analysis included 14 genetic variants and 11 exposures. Cox regression models were used for analysis and FDR Q-values were calculated.

Results: Complete genotyping data were available for 952 cases and 1,798 subcohort members. CAT rs1001179 was associated with stage III/IV and stage IV prostate cancer risk, with HRs per minor allele of 1.16 [95% confidence intervals (CI), 1.01–1.33; P = 0.032] and 1.25 (95% CI, 1.07–1.46; P = 0.006), respectively. We tested 151 gene–environment interactions in relation to both stage III/IV and IV prostate cancer risk. Seven interactions were statistically significant after adjusting for multiple testing (FDR Q-value <0.20); for stage III/IV prostate cancer, these involved intake of β-carotene (GPX1 rs17650792, hOGG1 rs1052133) and heme iron (GPX1 rs1800668 and rs3448), and for stage IV prostate cancer, these involved intake of catechin (SOD2 rs4880) and heme iron (hOGG1 rs1052133, SOD1 rs10432782).

Conclusion: This study of advanced prostate cancer risk showed a marginal association with a CAT polymorphism and seven novel gene–environment interactions in the oxidative stress pathway.

Impact: Oxidative stress–related genes and exposures may have a joint effect on advanced prostate cancer. Cancer Epidemiol Biomarkers Prev; 24(1); 178–86. ©2014 AACR.
Modernizing the Diagnostic and Decision-Making Pathway for Prostate Cancer
Authors: Polascik Thomas J. , Passoni Niccolo' M. , Villers Arnauld , Choyke Peter L.
Published: October 2014

PSA has led to a drastic increase in the detection of prostate cancer, rendering this biomarker the gateway for the diagnostic pathway of prostatic neoplasms. However, the increase in incidence has not been mirrored by a similar reduction in mortality. Widespread PSA testing has facilitated the overdiagnosis and overtreatment of indolent disease. To reduce this phenomenon and avoid negative repercussions on the quality of life of men undergoing unnecessary therapies, the diagnostic pathway of prostate cancer needs to be improved. Multiparametric MRI (mp-MRI) can enhance the sensitivity and specificity of PSA, as well as the shortcomings of random biopsy sampling. This novel imaging technique has been proven to identify larger and more aggressive cancer foci, which should be targeted for treatment. New technological developments now allow for fusion of mp-MRI images with real-time ultrasound, opening the way to lesion-targeted biopsies. Furthermore, mp-MRI and targeted biopsies can also improve active surveillance protocols and permit more conservative focal therapy strategies. By implementing targeted biopsies, the diagnostic pathway will focus on clinically significant disease, consequently reducing overdiagnosis and overtreatment. Before this novel protocol becomes the new gold standard, mp-MRI acquisition and interpretation need to be standardized and targeted-biopsy strategies need to be further validated prior to abandoning random-sampling ones. Several multidisciplinary consortiums are already working on the standardization of prostate MRI, and there are ongoing prospective trials on targeted biopsies and MRI. Soon, imaging of prostatic lesions and selected biopsies will modify the diagnostic evaluation of prostate cancer, reducing overtreatment and therapy-derived complications that negatively affect quality of life. Clin Cancer Res; 20(24); 6254–7. ©2014 AACR.
Are We Nearing an Era of Chemotherapy-Free Management of Indolent Lymphoma?
Authors: Bachy Emmanuel , Salles Gilles
Published: October 2014

Indolent B-cell lymphomas are heterogeneous, comprising three grades of follicular lymphoma, small lymphocytic lymphoma, Waldenstöm macroglobulinemia, marginal zone lymphoma, and most recently, possibly low proliferative mantle cell lymphoma. These lymphomas are characterized by a high responsiveness to chemotherapy or immunochemotherapy; however, in most cases, conventional therapy might not offer a cure. Furthermore, the patient's age at diagnosis, at time to first or subsequent relapses, as well as potential comorbidities often preclude the use of chemotherapy. Recent progress has been made in our understanding of dysregulated pathways and immunologic antitumor responses in indolent lymphoma. Major therapeutic advances have been achieved in the development of nonchemotherapeutic agents, making “chemo-free” treatment a near-future reality. In this article, we highlight these promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs, with mAbs directed against other surface antigens such as CD22, with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling. However, the cost of such therapies and potential, albeit manageable, toxicity should be considered. Phase III trials will confirm the benefit of these new treatment strategies that do not require a chemotherapeutic drug and help us identify their exact place in the therapeutic armamentarium for indolent lymphoma. Here we focus on follicular lymphoma, which is the most frequent subtype of indolent lymphoma and for which an increasing body of evidence has emerged that supports the dawn of a new era of chemotherapy-free treatment.

See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”

Clin Cancer Res; 20(20); 5226–39. ©2014 AACR.
Putting the Clinical and Biological Heterogeneity of Non-Hodgkin Lymphoma into Context
Authors: O'Connor Owen A. , Tobinai Kensei
Published: October 2014

The lymphomas represent one of the most heterogeneous groups of malignancies in all of cancer medicine. Whether one attempts to understand these diseases in the context of their complicated ontogeny, unique biologic features, or clinical presentation, this heterogeneity has been a mixed blessing. On the one hand, it has created an ever-changing way to classify these diseases, as classification schemes have been compelled to reflect the rapidly emerging information that seems to split the disease into smaller and smaller subtypes. On the other hand, the biologic and clinical dissection of these diseases has allowed for the identification of unique biologic features—features that have led to novel targets and generated a plethora of new drugs. Virtually every subtype of non-Hodgkin lymphoma has benefited from these efforts to understand the biology of the different subtypes. This paradigm has led to new clinical trials that tailor novel drug regimens to specific biologic disease subtypes. As a prelude to this CCR Focus section, we attempt to put this evolving heterogeneity into context, bridging historical and modern-day views of classification of these diseases. Then, some of the world's leading lymphoma researchers share their perspectives on how to formulate new concepts of care in this era of biologic discovery. Over a relatively short time, the advances in lymphoma research have been nothing short of stunning. There now seems to be little doubt that these recent breakthroughs will redound favorably on the majority of patients diagnosed with a lymphoproliferative malignancy.

See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”

Clin Cancer Res; 20(20); 5173–81. ©2014 AACR.
New Paradigms in Mantle Cell Lymphoma: Is It Time to Risk-Stratify Treatment Based on the Proliferative Signature?
Authors: Dreyling Martin , Ferrero Simone , Vogt Niklas , Klapper Wolfram
Published: October 2014

The elucidation of crucial biologic pathways of cell survival and proliferation has led to the development of highly effective drugs, some of which have markedly improved mantle cell lymphoma (MCL) therapeutic opportunities in the past 10 years. Moreover, an undeniable clinical heterogeneity in treatment response and disease behavior has become apparent in this neoplasm. Thus, the need for biologic markers stratifying patients with MCL in risk classes deserving different treatment approaches has recently been fervently expressed. Among several newly discovered biomarkers, the dismal predictive value of a high proliferative signature has been broadly recognized in large studies of patients with MCL. Different techniques have been used to assess tumor cell proliferation, including mitotic index, immunostaining with Ki-67 antibody, and gene expression profiling. Ki-67 proliferative index, in particular, has been extensively investigated, and its negative impact on relapse incidence and overall survival has been validated in large prospective clinical trials. However, one important pitfall limiting its widespread use in clinical practice is the reported interobserver variability, due to the previous lack of a standardized approach for quantification among different laboratories. In the present review, we describe some of the major techniques to assess cell proliferation in MCL, focusing in particular on the Ki-67 index and its need for a standardized approach to be used in multicenter clinical trials. The value of MCL biologic prognostic scores (as MIPI-b) is discussed, along with our proposal on how to integrate these scores in the planning of future trials investigating a tailored therapeutic approach for patients with MCL.

See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.”

Clin Cancer Res; 20(20); 5194–206. ©2014 AACR.
PLEKHA5 as a Biomarker and Potential Mediator of Melanoma Brain Metastasis
Authors: Jilaveanu Lucia B. , Parisi Fabio , Barr Meaghan L. , Zito Christopher R. , Cruz-Munoz William , Kerbel Robert S. , Rimm David L. , Bosenberg Marcus W. , Halaban Ruth , Kluger Yuval , Kluger Harriet M.
Published: October 2014

Purpose: Approximately 40% of patients with metastatic melanoma develop brain metastases. Our purpose was to identify genes aberrantly expressed in melanoma that might be associated with propensity for brain homing.

Experimental Design: We studied gene expression profiles in a cell line model of brain metastasis (cerebrotropic A375Br cells vs. parental A375P cells) and compared them with profiles of patients who developed early brain metastases and who did not. A tissue microarray containing 169 metastatic melanoma cases with variable time to brain metastasis was constructed to further study marker expression by quantitative immunofluorescence. An in vitro model of the blood brain barrier (BBB) was generated to evaluate potential mediators of brain metastases.

Results: PLEKHA5 was differentially expressed in both the A375 cell line model and patient samples subjected to gene expression profiling. At the protein level, by quantitative immunofluorescence, PLEKHA5 was associated with decreased brain metastasis-free survival. PLEKHA5 overexpression was not associated with other metastatic sites. Knockdown of PLEKHA5 decreases the viability of A375Br cells, inhibits BBB transmigration and invasion in vitro. Similar results were found with YUMUL cells, cultured from a patient with overwhelming brain metastases. PLEKHA5 knockdown did not affect the viability of A375P cells.

Conclusions: PLEKHA5 expression in melanoma tumors was associated with early development of brain metastases. Inhibition of PLEKHA5 might decrease passage across the BBB and decrease proliferation and survival of melanoma cells both in the brain and in extracerebral sites. Clin Cancer Res; 21(9); 2138–47. ©2014 AACR.

See related commentary by Eisele et al., p. 1978
In Vivo Quantification of Hypoxic and Metabolic Status of NSCLC Tumors Using [18F]HX4 and [18F]FDG-PET/CT Imaging
Authors: Zegers Catharina M.L. , van Elmpt Wouter , Reymen Bart , Even Aniek J.G. , Troost Esther G.C. , Öllers Michel C. , Hoebers Frank J.P. , Houben Ruud M.A. , Eriksson Jonas , Windhorst Albert D. , Mottaghy Felix M. , De Ruysscher Dirk , Lambin Philippe
Published: October 2014

Purpose: Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non–small cell lung cancer (NSCLC). PET imaging is a noninvasive technique that is frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using 2[18F]fluoro-2-deoxy-d-glucose (FDG)-PET and hypoxia using HX4-PET imaging.

Experimental Design: FDG- and HX4-PET/CT images of 25 patients with NSCLC were coregistered. At a global tumor level, HX4 and FDG parameters were extracted from the gross tumor volume (GTV). The HX4 high-fraction (HX4-HF) and HX4 high-volume (HX4-HV) were defined using a tumor-to-blood ratio > 1.4. For FDG high-fraction (FDG-HF) and FDG high-volume (FDG-HV), a standardized uptake value (SUV) > 50% of SUVmax was used. We evaluated the spatial correlation between HX4 and FDG uptake within the tumor, to quantify the (mis)match between volumes with a high FDG and high HX4 uptake.

Results: At a tumor level, significant correlations were observed between FDG and HX4 parameters. For the primary GTV, the HX4-HF was three times smaller compared with the FDG-HF. In 53% of the primary lesions, less than 1 cm3 of the HX4-HV was outside the FDG–HV; for 37%, this volume was 1.9 to 12 cm3. Remarkably, a distinct uptake pattern was observed in 11%, with large hypoxic volumes localized outside the FDG-HV.

Conclusion: Hypoxic tumor volumes are smaller than metabolic active volumes. Approximately half of the lesions showed a good spatial correlation between the PET tracers. In the other cases, a (partial) mismatch was observed. The addition of HX4-PET imaging has the potential to individualize patient treatment. Clin Cancer Res; 20(24); 6389–97. ©2014 AACR.