bluuebunny/crossref_metadata_2025_split huggingface dataset:
Farnesylthiosalicylic acid (salirasib) inhibits Rheb in TSC2‐null ELT3 cells: A potential treatment for lymphangioleiomyomatosis
Authors: Makovski Victoria , Haklai Roni , Kloog Yoel 
Published: April 2011

AbstractThe small GTPase proteins, Ras and Rheb, serve as molecular switches regulating cell proliferation, differentiation and apoptosis. Ras also regulates Rheb by inactivating the tuberous sclerosis complex (TSC), which includes products of the TSC1 and TSC2 genes encoding hamartin (TSC1) and tuberin (TSC2), respectively, and acts as a Rheb‐specific GTPase‐activating protein. Loss of function of TSC1 or TSC2 results in an increase in active Rheb.GTP with the consequent translational abnormalities and excessive cell proliferation characteristic of the genetic disorders, tuberous sclerosis and lymphangioleiomyomatosis (LAM). To determine whether inactivation of Rheb, Ras or both might be a potential treatment for LAM, we used TSC2‐null ELT3 cells as a LAM model. The cells were treated with the Ras inhibitor S‐trans,trans‐farnesylthiosalicylic acid (FTS; salirasib), which mimics the C‐terminal S‐farnesyl cysteine common to Ras and Rheb. This C‐terminus is critical for their attachment to cellular membranes and for their biological activities. Untreated, the ELT3 cells expressed significant amounts of Rheb but little Ras.GTP, and this phenotype was reversed by TSC2 reexpression. Treatment with FTS decreased Ras.GTP only slightly in the TSC2‐null cells, but reduced their overactive Rheb as well as their proliferation, migration and tumor growth. Notably, TSC2 reexpression in these ELT3 cells rescued them from the inhibitory effect of FTS. Evidently, therefore, FTS blocks active Rheb in TSC2‐null ELT3 cells and may have therapeutic potential for LAM.
Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer
Authors: Sinha Indu , Null Kevin , Wolter William , Suckow Mark A. , King Tonya , Pinto John T. , Sinha Raghu 
Published: April 2011

AbstractAlternative strategies are needed to control growth of advanced and hormone refractory prostate cancer. In this regard, we investigated the efficacy of methylseleninic acid (MSeA), a penultimate precursor to the highly reactive selenium metabolite, methylselenol, to inhibit growth of invasive and hormone refractory rat (PAIII) and human (PC‐3 and PC‐3M) prostate cancer cells. Our results demonstrate that MSeA inhibits PAIII cell growth in vitro as well as reduces weights of tumors generated by PAIII cells treated ex vivo. A significant reduction in the number of metastatic lung foci by MSeA treatment was also noted in Lobund‐Wistar rats. The PAIII cells along with PC‐3, DU145 and PC‐3M cells undergo apoptosis after MSeA treatments in both normoxia and hypoxia. Treatment of metastatic rat and human prostate cancer cell lines with MSeA decreased hypoxia‐inducible factor‐1α (HIF‐1α) levels in a dose‐dependent manner. Additionally, HIF‐1α transcription activity both in normoxic and hypoxic conditions is reduced after MSeA treatment of prostate cancer cells. Furthermore, VEGF and GLUT1, downstream targets of HIF‐1α, were also reduced in prostate cancer cells after MSeA treatment. Our study illustrates the efficacy of MSeA in controlling growth of hormone refractory prostate cancer by downregulating HIF‐1α, which is possibly occurring through stabilization or increase in prolyl hydroxylase activity.
The novel DNA alkylating agent BO‐1090 suppresses the growth of human oral cavity cancer in xenografted and orthotopic mouse models
Authors: Sanjiv Kumar , Su Tsann‐Long , Suman Sharda , Kakadiya Rajesh , Lai Tsung‐Ching , Wang Hsuan‐Yao , Hsiao Michael , Lee Te‐Chang 
Published: April 2011

AbstractOral cancer is the fourth‐most common cause of death in males and overall the sixth‐most common cause of cancer death in Taiwan. Surgery, radiotherapy and chemotherapy combined with other therapies are the most common treatments for oral cavity cancer. Although cisplatin, 5‐fluorouracil and docetaxel are commonly used clinically, there is no drug specific for oral cavity cancer. Here, we demonstrated that derivatives of 3a‐aza‐cyclopenta[a]indene, a class of newly synthesized alkylating agents, may be drugs more specific for oral cancer based on its potent in vitro cytotoxicity to oral cancer cells and on in vivo xenografts. Among them, BO‐1090, bis(hydroxymethyl)‐3a‐aza‐cyclopenta[a]indene derivative, targeted DNA for its cytotoxic effects as shown by inhibition of DNA synthesis (bromodeoxyuridine‐based DNA synthesis assay), induction of DNA crosslinking (alkaline gel shift assay), and induction of DNA single‐stranded breaks (Comet assay) and double‐stranded breaks (γ‐H2AX focus formation). Following DNA damage, BO‐1090 induced G1/S‐phase arrest and apoptosis in oral cancer cell lines. The therapeutic potential of BO‐1090 was tested in mice that received a xenograft of oral cavity cancer cell lines (SAS or Cal 27 cells). Intravenous injection of BO‐1090 significantly suppressed tumor growth in comparison to control mice. BO‐1090 also significantly reduced the tumor burden in orthotopic mouse models using SAS cells. There was no significant adverse effect of BO‐1090 treatment with this dosage based on whole blood count, biochemical enzyme profiles in plasma and histopathology of various organs in mouse. Taken together, our current results demonstrate that B0‐1090 may have potential as a treatment for oral cavity cancer.
The toll‐like receptor 2 (TLR2) ‐196 to ‐174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C
Authors: Nischalke Hans‐Dieter , Coenen Martin , Berger Cordula , Aldenhoff Katharina , Müller Tobias , Berg Thomas , Krämer Benjamin , Körner Christian , Odenthal Margarete , Schulze Falko , Grünhage Frank , Nattermann Jacob , Sauerbruch Tilman , Spengler Ulrich 
Published: April 2011

AbstractChronic hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC). HCV proteins core and NS3 can bind to toll‐like receptor 2 (TLR2) and trigger inflammatory responses. Polymorphisms in the TLR2 gene predispose to various forms of malignancy but have not been studied in HCV‐associated HCC. Here, we investigated whether single nucleotide polymorphisms (SNPs), rs4696480, rs5743708, rs5743704 and the ‐196 to ‐174 del/ins polymorphism of the TLR2 gene affect the risk for HCC in chronic hepatitis C. The study involved 189 and 192 HCV genotype 1 infected patients with and without HCC, respectively, as well as 347 healthy controls. TLR2 alleles were determined by hybridization probe assays and allele‐specific short fragment polymerase chain reaction on a LightCycler system. All TLR2 polymorphisms matched the Hardy–Weinberg equilibrium in each study group. Although TLR2 SNPs showed no effect, the frequency of the TLR2 ‐196 to ‐174 del allele was significantly higher in patients with HCV‐associated HCC (22.5%) than in HCV‐infected patients without HCC (15.6%, p = 0.016) and healthy controls (15.3%, p = 0.003). HCV‐infected carriers of a TLR2 ‐196 to ‐174 del allele had significantly higher HCV viral loads than TLR2 ‐196 to ‐174 ins/ins homozygous patients (p = 0.031). Finally, in carriers of the TLR2 ‐196 to ‐174 del allele, stimulation of monocytes resulted in significantly lower TLR2 expression levels and interleukin‐8 (IL‐8) induction than in individuals with the TLR2 ‐196 to ‐174 ins/ins genotype (p < 0.05). Our data suggest the TLR2 ‐196 to ‐174 del allele to affect HCV viral loads and to increase the risk for HCC in HCV genotype1‐infected patients.
MDAnalysis: A toolkit for the analysis of molecular dynamics simulations
Authors: Michaud‐Agrawal Naveen , Denning Elizabeth J. , Woolf Thomas B. , Beckstein Oliver 
Published: April 2011

AbstractMDAnalysis is an object‐oriented library for structural and temporal analysis of molecular dynamics (MD) simulation trajectories and individual protein structures. It is written in the Python language with some performance‐critical code in C. It uses the powerful NumPy package to expose trajectory data as fast and efficient NumPy arrays. It has been tested on systems of millions of particles. Many common file formats of simulation packages including CHARMM, Gromacs, Amber, and NAMD and the Protein Data Bank format can be read and written. Atoms can be selected with a syntax similar to CHARMM's powerful selection commands. MDAnalysis enables both novice and experienced programmers to rapidly write their own analytical tools and access data stored in trajectories in an easily accessible manner that facilitates interactive explorative analysis. MDAnalysis has been tested on and works for most Unix‐based platforms such as Linux and Mac OS X. It is freely available under the GNU General Public License from http://mdanalysis.googlecode.com. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011
Calculation of free energy landscapes: A histogram reweighted metadynamics approach
Authors: Smiatek Jens , Heuer Andreas 
Published: April 2011

AbstractWe present an efficient method for the calculation of free energy landscapes. Our approach involves a history‐dependent bias potential, which is evaluated on a grid. The corresponding free energy landscape is constructed via a histogram reweighting procedure a posteriori. Because of the presence of the bias potential, it can be also used to accelerate rare events. In addition, the calculated free energy landscape is not restricted to the actual choice of collective variables and can in principle be extended to auxiliary variables of interest without further numerical effort. The applicability is shown for several examples. We present numerical results for the alanine dipeptide and the Met‐Enkephalin in explicit solution to illustrate our approach. Furthermore, we derive an empirical formula that allows the prediction of the computational cost for the ordinary metadynamics variant in comparison with our approach, which is validated by a dimensionless representation. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Intra‐ and interobserver variability of 2D and 3D transvaginal sonography in the diagnosis of benign versus malignant adnexal masses
Authors: Pascual Maria A. , Graupera Betlem , Hereter Lourdes , Rotili Anna , Rodriguez Ignacio , Alcázar Juan Luis 
Published: April 2011

AbstractPurpose.The purpose of this study was to investigate the intraobserver and interobserver agreements in the diagnosis of malignant versus benign adnexal masses using two‐dimensional ultrasonography (2D US) and three‐dimensional ultrasonography (3D US).Methods.Two experienced sonographers performed a retrospective review of digitally stored 2D images and 3D data from a sample of 41 consecutive patients with a diagnosis of adnexal mass. Each observer independently, and blinded to each other, evaluated the 2D static images of each adnexal mass and then the 3D volumes 1 week later. The observers were required to classify the adnexal lesion as benign or malignant according to pattern recognition analysis. Intraobserver and interobserver agreement were assessed by calculating the kappa index (κ).Results.Intraobserver agreement between 2D US and 3D US for the observer A was 1.00 and for the observer B was 0.69. Interobserver agreement was 0.69 for 2D US and 1.00 for 3D US (p > 0.05)Conclusions.Although 3D US in the diagnosis of adnexal masses appeared more reproducible than 2D US, the difference was not statistically significant. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011;
Periovulatory follicular volume and vascularization determined by 3D and power Doppler sonography as pregnancy predictors in intrauterine insemination cycles
Authors: Engels Virginia , Sanfrutos Luis , Perez‐Medina Tirso , Alvarez Pilar , Zapardiel Ignacio , Godoy‐Tundidor Sonia , Salazar Francisco J. , Troyano Juan , Bajo‐Arenas Jose M. 
Published: April 2011

AbstractPurpose.To evaluate the relationship between volume and vascularization of the periovulatory follicle and subfollicular area measured by three‐dimensional power Doppler ultrasound (US), and ovulation and pregnancy in patients undergoing intrauterine insemination (IUI).Methods.We studied 79 consecutive cycles of IUI on hCG administration day. We measured the periovulatory follicle and subfollicular area by means of three‐dimensional power Doppler US. The stored volumes were processed with the VOCAL image processing software to calculate the volume of the follicle and the following vascular indices: vascularization index (VI), flow index (FI), and vascularization flow index (VFI).Results.The follicular volume was higher in anovulatory cycles (7.7 ± 3.7 cubic centimeters (CC) versus 4.1 ± 2.0 CC; p < 0.001). There was no difference between the follicular volumes in cycles with or without subsequent pregnancy. The vascular indices of the follicle did not differ significantly between ovulatory and anovulatory cycles, and between cycles that did and did not achieve pregnancy. Periovulatory subfollicular VI and VFI were lower in women who became pregnant (VI: 2.9 ± 2.3% versus 5.6 ± 4.6%; p < 0.05, and VFI: 1.1 ± 0.8 versus 2.2 ± 2.2; p < 0.01).Conclusions.High values of follicular volume were associated with anovulatory cycles. Subfollicular VI and VFI might be used as markers of follicular quality and pregnancy predictors. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound 2011;
Thrombus in transit within a patent foramen ovale: An argument for consideration of prophylactic closure?
Authors: Chow Vincent , Wang William , Wilson Michael , Yiannikas John 
Published: April 2011

AbstractRecurrent pulmonary embolism (PE) in prothrombotic patients with patent foramen ovale (PFO) is not considered a setting for elective PFO closure. We describe a 35‐year‐old woman with known PFO, recurrent PE on warfarin, and Klippel‐Trenaunay syndrome—a condition with predisposition for thromboembolism—who suffered concurrent saddle PE and devastating stroke with further impending paradoxical embolus across the PFO. Optimal management in patients with biatrial thromboembolus caught in transit across PFO is challenging. Patients with recurrent PE, prothrombotic states, and PFO should be considered for PFO closure. Prompt diagnosis of impending paradoxical embolus with echocardiography and consideration of surgical removal and PFO closure are critical. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound 40:115–118, 2012
Angiosarcoma of the ovary arising in a mucinous cystadenoma
Authors: Aragon Lorenzo , Terreros Daniel , Ho Hoi , Greenberg Harvey , Kupesic Plavsic Sanja 
Published: April 2011

AbstractWe report the case of a 39‐year‐old woman who presented with a pelvic mass extending into the upper abdomen. Transabdominal sonography revealed a complex left adnexal mass. Color Doppler imaging and spectral Doppler analysis showed increased vascularity with low impedance blood flow signals, suggestive of neovascularization. The patient underwent a laparotomy and a 56‐kg predominantly cystic tumor was removed from the left adnexal region. The patient died 3 months later with pulmonary metastases and massive pulmonary hemorrhage. Postmortem resampling of the ovarian tumor initially diagnosed as mucinous cystadenoma showed nodular areas of malignant pleomorphic cells consistent with angiosarcoma. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011;
Myopericytoma of the neck: Sonographic appearance and sonographically guided needle biopsy
Authors: Rho Byung Hak , Lee Sang Kwon , Kwon Sun Young 
Published: April 2011

AbstractWe report the imaging and pathologic findings of a case of myopericytoma of the neck in a 70‐year‐old woman, which was diagnosed by ultrasound‐guided core‐needle biopsy. The mass demonstrated homogeneous intense enhancement on contrast‐enhanced CT and was markedly hypervascular on power Doppler sonography. The histopathological findings of the core biopsy were consistent with myopericytoma. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011;
An efficient one‐pot synthesis of pyridazinones and phthalazinones using HY‐zeolite
Authors: Zare Leila , Mahmoodi Nosratollah , Yahyazadeh Asieh , Mamaghani Manouchehr , Tabatabaeian Khalil 
Published: April 2011

AbstractThe first one‐pot synthesis of pyridazinones and phthalazinones from arenes, cyclic anhydrides, and ArNHNH2 in the presence of efficient recyclable heterogeneous catalyst, HY‐zeolite, in high yield and short reaction time is reported. J. Heterocyclic Chem., (2011).
The dissociation constants of diprotonated chalcogenobispyridines: Transmission of electronic effects across chalcogen bridges
Authors: Angus‐Dunne Sarah J. , Dunne Simon J. 
Published: April 2011

AbstractThe dissociation constants of the diprotonated chalcogenobispyridines have been determined using potentiometric titrations to establish a method for the measurement of the ability of a bridging ligand to relay electronic effects. The relationship between pKa and structure of the chalcogenobispyridines results from a balance between inductive, mesomeric, and steric effects. Delocalization of cationic charge onto the bridgehead increases the apparent electronegativity of the bridging atom, thereby relaying a strong base‐weakening effect to the site of first deprotonation. Such delocalization was found to be a function of both the substitution site (4‐X > 2‐X ≫ 3‐X) and orbital overlap requirements (S > O ≈ Se > Te). J. Heterocyclic Chem., (2011).
Synthesis and antibacterial activity of novel series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline
Authors: Joshi Ratnadeep S. , Mandhane Priyanka G. , Khan Wajid , Gill Charansingh H. 
Published: April 2011

AbstractA new series of 2‐(p‐tolyloxy)‐3‐(5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)quinoline were synthesized from oxidative cyclization of N′‐((2‐(p‐tolyloxy)quinoline‐3‐yl)methylene)isonicotinohydrazide in DMSO/I2 at reflux condition for 3–4 h. The structures of the new compounds were confirmed by elemental analyses as well as IR, 1H‐NMR, and mass spectral data. All the synthesized compounds were screened for their antibacterial activities against various bacterial strains. Several of these compounds showed potential antibacterial activity. J. Heterocyclic Chem., (2011).
Synthesis and in vitro antibacterial assessment of novel chromones featuring 1,2,4‐oxadiazole
Authors: Diwakar Santosh D. , Joshi Ratnadeep S. , Gill Charansing H. 
Published: April 2011

AbstractIn search for a new antibacterial agent with improved antimicrobial spectrum and potency, we designed and synthesized a series of novel 3‐((Z)‐2‐(5‐methyl‐1,2,4‐oxadiazol‐3‐yl)‐2‐(4‐nitrophenyl)vinyl)‐4H‐chromen‐4‐ones 7a, 7b, 7c, 7d, 7e, 7f, 7g, 7h by convergent synthesis approach. All the synthesized compounds were assayed for their in vitro antibacterial activities against gram‐negative and gram‐positive bacteria. The preliminary structure‐activity relationship to elucidate the essential structure requirements for the antimicrobial activity has been described. J. Heterocyclic Chem., (2011).
Women in grassroots leadership: Barriers and biases experienced in a membership organization dominated by men
Authors: Kaufman Eric K. , Grace Pat E. 
Published: April 2011

AbstractAmong governing boards traditionally dominated by men, the presence of women is becoming more common. However, these women may face prejudices and discrimination that prevent them from feeling and ultimately being successful. This qualitative study focused on the experiences of women who participated in a grassroots organization's leadership training program. Interviewees revealed that they believed gender‐related obstacles were preventing them from being effective leaders. Four significant themes emerged: persisting stereotypes and bias, separation and isolation, desire for change, and potential for added value. In response, the authors recommend organizations and practitioners engage in more intentional and complete implementation of path‐goal theory throughout the leadership development process.
The effect of personality on virtual communications in warfare
Authors: Nimon Harry I. , Graham George J. 
Published: April 2011

AbstractIndividuals and corporations worldwide are increasing their use of computer‐mediated‐communications (CMC) systems and processes. Such endeavors are shortening lines of communications, yet simultaneously distancing understanding. Winston Churchill once opined that the British and the Americans are two great peoples separated by a common language. Some relate aspects of culture as the source of Churchill's quote. Separating factors may be more engrained than was previously believed or theorized. The authors examined a high‐stress setting in which the trappings of culture disappear leaving only the basic emotional and cognitive survival aspects of personality: the environment of military combat. The study examined the relationship of an individual's ability to function efficiently using virtual communications and processes while under extreme stress. Observing the results of the study's individual‐environment relations raise the question of whether personality is a factor in virtual team efficiency.
Leadership in extreme contexts: A groupthink analysis of the May 1996 Mount Everest disaster
Authors: Burnette Jeni L. , Pollack Jeffrey M. , Forsyth Donelson R. 
Published: April 2011

AbstractGroupthink, as traditionally conceived, is a failure in group decision making that occurs in highly cohesive groups. In the current case study, we propose an alternative potential form of groupthink in which the group's cohesiveness results from the shared pursuit of a collective goal rather than from strong interpersonal bonds between members. Our model, recognizing the multifaceted nature of cohesion, assumes that a group whose members are united in pursuit of a valued collective goal while guided by a directive leader may experience breakdowns in the decision process. Specifically, drawing on reviews of personal accounts, media descriptions, online interviews, and past empirical papers, we propose that the May 1996 Mount Everest disaster can be understood in part from a groupthink perspective. Applications for the proposed model are discussed, along with implications for leaders seeking to improve organizational decision‐making practices.
The role of technology in transforming higher education
Authors: Davidson Phillip 
Published: April 2011

AbstractMore than 100 years ago, John Dewey, a major influence in American education, argued for the need to “stimulate the spirit of inquiry into actual fact” (Dewey, 2002, p. 118). The debate among politicians and educators about the structure, purpose, and goals of education and inquiry continues. Yet the world has changed, largely because of widely accessible and versatile technologies. We are unclear how Dewey's spirit of inquiry will grow, die, or reinvent itself through boundaryless tools of inquiry such as the Internet, but the technology is here and will not disappear while educators debate best methods.Twenty‐first‐century society demands new ways to learn and understand, and these new ways of learning require new ways of teaching (McPheeters, 2009/2010). For many students, especially the younger generations, technology intertwines with almost all daily activities, including social contact. Many educators lag behind the technological curve and express frustration at the challenge to shift their educational paradigms toward increasingly technological means of communication and interaction, or entertain “virtual realities” as legitimate educational forums.The purpose of this symposium is to examine the role of technology in transforming higher education.
The goal is to seek best methods of using technology more effectively to educate learners for the 21st century. The shifts in society's focus and the characteristics of learners going into the future are also critical, and part of this discussion.