bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrrolamide DNA Gyrase Inhibitors: Fragment-Based Nuclear Magnetic Resonance Screening To Identify Antibacterial Agents
Authors: Eakin Ann E. , Green Oluyinka , Hales Neil , Walkup Grant K. , Bist Shanta , Singh Alok , Mullen George , Bryant Joanna , Embrey Kevin , Gao Ning , Breeze Alex , Timms Dave , Andrews Beth , Uria-Nickelsen Maria , Demeritt Julie , Loch James T. , Hull Ken , Blodgett April , Illingworth Ruth N. , Prince Bryan , Boriack-Sjodin P. Ann , Hauck Sheila , MacPherson Lawrence J. , Ni Haihong , Sherer Brian 
Published: December 2011

ABSTRACT

DNA gyrase is an essential enzyme in bacteria, and its inhibition results in the disruption of DNA synthesis and, subsequently, cell death. The pyrrolamides are a novel class of antibacterial agents targeting DNA gyrase. These compounds were identified by a fragment-based lead generation (FBLG) approach using nuclear magnetic resonance (NMR) screening to identify low-molecular-weight compounds that bind to the ATP pocket of DNA gyrase. A pyrrole hit with a binding constant of 1 mM formed the basis of the design and synthesis of a focused library of compounds that resulted in the rapid identification of a lead compound that inhibited DNA gyrase with a 50% inhibitory concentration (IC
50
) of 3 μM. The potency of the lead compound was further optimized by utilizing iterative X-ray crystallography to yield DNA gyrase inhibitors that also displayed antibacterial activity. Spontaneous mutants were isolated in
Staphylococcus aureus
by plating on agar plates containing pyrrolamide 4 at the MIC. The resistant variants displayed 4- to 8-fold-increased MIC values relative to the parent strain. DNA sequencing revealed two independent point mutations in the pyrrolamide binding region of the
gyrB
genes from these variants, supporting the hypothesis that the mode of action of these compounds was inhibition of DNA gyrase. Efficacy of a representative pyrrolamide was demonstrated against
Streptococcus pneumoniae
in a mouse lung infection model. These data demonstrate that the pyrrolamides are a novel class of DNA gyrase inhibitors with the potential to deliver future antibacterial agents targeting multiple clinical indications.
Effect of Food on the Pharmacokinetics of the Integrase Inhibitor Dolutegravir
Authors: Song Ivy , Borland Julie , Chen Shuguang , Patel Parul , Wajima Toshihiro , Peppercorn Amanda , Piscitelli Stephen C. 
Published: December 2011

ABSTRACT

Healthy subjects received dolutegravir at 50 mg in a single-dose crossover study while they were in the fasted state or with low-, moderate-, or high-fat meals. Food increased dolutegravir exposure and reduced the rate of absorption. The area under the concentration-time curve from 0 h to infinity (AUC
0–∞
) increased by 33%, 41%, and 66% when administered with low-, moderate-, or high-fat meals, respectively, compared with fasting. This increase in dolutegravir exposure is not anticipated to impact clinical safety, and therefore dolutegravir can be taken with or without food and without regard to fat content.
Increase in physical activity and cardiometabolic risk profile change during lifestyle intervention in primary healthcare: 1-year follow-up study among individuals at high risk for type 2 diabetes
Authors: Kujala Urho M , Jokelainen Jari , Oksa Heikki , Saaristo Timo , Rautio Nina , Moilanen Leena , Korpi-Hyövälti Eeva , Saltevo Juha , Vanhala Mauno , Niskanen Leo , Peltonen Markku , Tuomilehto Jaakko , Uusitupa Matti , Keinänen-Kiukaannemi Sirkka 
Published: December 2011

ObjectivesTo investigate the association between increase in physical activity and changes in cardiometabolic risk factors during a lifestyle intervention programme in routine clinical settings.DesignProspective follow-up.Setting400 primary healthcare centres and occupational healthcare outpatient clinics in Finland.ParticipantsIndividuals at high risk for type 2 diabetes identified in the implementation project of the national diabetes prevention programme (FIN-D2D) and participating in baseline and 1-year follow-up visits. Final study group comprised the 1871 non-diabetic participants who responded at follow-up visit to a question on stability versus increase of physical activity.InterventionsLifestyle intervention.Primary outcome measuresCardiometabolic risk factors (body composition, blood pressure and those measured from fasting venous blood samples) measured at baseline and follow-up visits.ResultsOf the participants, 310 (16.6% of all responders) reported at follow-up having clearly increased their physical activity during the past year, while 1380 (73.8%) had been unable to increase their physical activity. Those who increased their activity decreased their weight by 3.6 kg (95% CI 2.9 to 4.3, age and sex adjusted, p<0.001) and waist circumference by 3.6 cm (95% CI 2.9 to 4.3, p<0.001) more than those who did not increase their activity. Similarly, those who increased their physical activity had greater reductions in total cholesterol (group difference in reduction 0.17 mmol/l, 95% CI 0.06 to 0.28, p=0.002), low-density lipoprotein cholesterol (0.16 mmol/l, 95% CI 0.06 to 0.26, p=0.001), low-density lipoprotein/high-density lipoprotein ratio (0.17, 95% CI 0.08 to 0.25, p<0.001) as well as fasting glucose (0.09 mmol/l, 95% CI 0.03 to 0.15, p=0.004) and 2 h glucose levels (0.36 mmol/l, 95% CI 0.17 to 0.55, p=0.023) than those who did not increase their physical activity.ConclusionIncreasing physical activity seems to be an important feature of cardiometabolic risk reduction among individuals at high risk for type 2 diabetes participating in preventive interventions in routine clinical settings.
Suicide by burning in the South Asian origin population in England and Wales a secondary analysis of a national data set
Authors: Tuck Andrew , Bhui Kamaldeep , Nanchahal Kiran , McKenzie Kwame 
Published: December 2011

ObjectivesA descriptive analysis of suicide by burning in England and Wales in the general population and in people of South Asian origin.DesignA cross-sectional secondary analysis of a national data set.SettingA population study of all those who died by suicide in England and Wales between 1993 and 2003 inclusive.ParticipantsAll cases of suicide and undetermined intent identified by the Office for National Statistics for England and Wales. A computer algorithm was used to identify people of the South Asian origin from their names. There were 55 140 suicides in the UK between 1993 and 2003. The ratio of male to female suicides was 3:1. There were 1455 South Asian suicides identified by South Asian Name and Group Recognition Algorithm.Primary and secondary outcome measuresDeath by suicide and undetermined intent, as determined by Coroner's Inquest. ICD9 codes E958.1 and E988.1 and ICD10 codes X76 and Y26.Results1.77% of suicides in the general population and 8.45% of suicides in the South Asian origin population were by burning. The suicide rate by burning was 0.8/100 000 person-years for England and Wales and 2.9/100 000 person-years for the South Asian origin population. The odds of suicide by burning were increased in the South Asian group as a whole (OR 3.06, 95% CI 2.30 to 4.08). Those born in Asia and Africa were at higher risk than those born in the UK (OR 2.69, 95% CI 2.01 to 3.60 and OR 2.10, 95% CI 1.46 to 3.01, respectively). The increased risk was for those aged 25–64 years.ConclusionSuicide by burning remains a significant issue in the South Asian origin working-age population in England and Wales. A prevention strategy could target working-age people of South Asian origin born abroad as they are at the highest risk. More in depth research on the reasons for using this method may help to identify possible prevention strategies.
Age-related cerebral white matter disease (leukoaraiosis): a review
Authors: Grueter Basil E , Schulz Ursula G 
Published: December 2011

Abstract
With the availability of improved brain imaging techniques, the high prevalence and clinical importance of cerebral small vessel disease have been increasingly recognised in recent years. As age is one of the most important risk factors for this condition, its prevalence is set to rise further as populations age. This may lead to an increase in the clinical consequences of white matter disease, namely cognitive decline, decreased mobility and increased stroke risk. Given the impact this will have on individuals and on healthcare systems, knowledge of the risk factors for small vessel disease, its prevention and its treatment is becoming more important. Although a lot of data are now available on the epidemiology, risk factors, clinical consequences and prognosis of leukoaraiosis, some of this information is conflicting. In this review, we summarise the current literature on cerebral small vessel disease, with an emphasis on its clinical aspects.
AN EFFICIENT EIGEN VALUES BASED TECHNIQUE FOR ONLINE IRIS IMAGE COMPRESSION AND IDENTIFICATION
Authors: MISHRA KAMTA NATH , AGRAWAL ANUPAM , SRIVASTAVA PRAKASH C. , TRIPATHI VIVEK , GUPTA VISHAL 
Published: December 2011

This paper introduces an efficient Eigen values based technique for online iris image compression and identification of a human including the case of identical twins. The iris image is extracted after removing the pupil, eye brow, skin and other noise disturbances from an actual image. The extracted iris image is divided into different blocks of size of 16 × 16. Now, Eigen values are calculated for each block and these Eigen values are stored in the smart card memory for further identification. Therefore, when checking if two iris images are identical or not, all we need is to compare the stored Eigen values with online calculated Eigen values. If two iris images have the same Eigen values, this means that both iris images belong to the same person. In our research, we have concluded that iris images of different persons have different Eigen values, including the case of identical twins. We conducted experiments on CASIA and Multimedia University iris image databases and we found that our Eigen Values Based Iris Image Identification Technique is giving 99.99% accuracy for the same image of identical twins and individuals. The implementation leads us to believe that our method is giving the best matching result in the case of identical twins and individuals. It is an efficient, secure and economically feasible approach for online personal identification.
The data cyclotron query processing scheme
Authors: Goncalves Romulo , Kersten Martin 
Published: December 2011

A grand challenge of distributed query processing is to devise a self-organizing architecture which exploits all hardware resources optimally to manage the database hot set, minimize query response time, and maximize throughput without single point global coordination. The Data Cyclotron architecture [Goncalves and Kersten 2010] addresses this challenge using turbulent data movement through a storage ring built from distributed main memory and capitalizing on the functionality offered by modern remote-DMA network facilities. Queries assigned to individual nodes interact with the storage ring by picking up data fragments, which are continuously flowing around, that is, the hot set.

The storage ring is steered by the
Level Of Interest
(
LOI
) attached to each data fragment, which represents the cumulative query interest as it passes around the ring multiple times. A fragment with
LOI
below a given threshold, inversely proportional to the ring load, is pulled out to free up resources. This threshold is dynamically adjusted in a fully distributed manner based on ring characteristics and locally observed query behavior. It optimizes resource utilization by keeping the average data access latency low. The approach is illustrated using an extensive and validated simulation study. The results underpin the fragment hot set management robustness in turbulent workload scenarios.

A fully functional prototype of the proposed architecture has been implemented using modest extensions to MonetDB and runs within a multirack cluster equipped with Infiniband. Extensive experimentation using both microbenchmarks and high-volume workloads based on TPC-H demonstrates its feasibility.
The Data Cyclotron architecture and experiments open a new vista for modern distributed database architectures with a plethora of new research challenges.
Selective Tumor Hypoxia Targeting by Hypoxia-Activated Prodrug TH-302 Inhibits Tumor Growth in Preclinical Models of Cancer
Authors: Sun Jessica D. , Liu Qian , Wang Jingli , Ahluwalia Dharmendra , Ferraro Damien , Wang Yan , Duan Jian-Xin , Ammons W. Steve , Curd John G. , Matteucci Mark D. , Hart Charles P. 
Published: December 2011

Abstract
Purpose: Tumor hypoxia underlies treatment failure and yields a more aggressive, invasive, and metastatic cancer phenotype. TH-302 is a 2-nitroimidazole triggered hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM). The purpose of this study is to characterize the antitumor activity of TH-302 and investigate its selective targeting of the hypoxic cells in human tumor xenograft models.
Experimental Design: Antitumor efficacy was assessed by tumor growth kinetics or by clonogenic survival of isolated cells after tumor excision. Hypoxic fractions (HF) were determined by immunohistochemistry and morphometrics of pimonidazole staining. Tumor hypoxia levels were manipulated by exposing animals to different oxygen concentration breathing conditions. The localization and kinetics of TH-302 induced DNA damage was determined by γH2AX immunohistochemistry.
Results: TH-302 antitumor activity was dose-dependent and correlated with total drug exposure. Correlation was found between antitumor activity and tumor HF across 11 xenograft models. Tumor-bearing animals breathing 95% O2 exhibited attenuated TH-302 efficacy, with whereas those breathing 10% O2 exhibited enhanced TH-302 efficacy, both compared with air (21% O2) breathing. TH-302 treatment resulted in a reduction in the volume of the HF 48 hours after dosing and a corresponding increase in the necrotic fraction. TH-302 induced DNA damage as measured by γH2AX was initially only present in the hypoxic regions and then radiated to the entire tumor in a time-dependent manner, consistent with TH-302 having a “bystander effect.”
Conclusions: The results show that TH-302 has broad antitumor activity and selectively targets hypoxic tumor tissues. Clin Cancer Res; 18(3); 758–70. ©2011 AACR.
Visuo-haptic Neuronal Convergence Demonstrated with an Inversely Effective Pattern of BOLD Activation
Authors: Kim Sunah , Stevenson Ryan A. , James Thomas W. 
Published: December 2011

Abstract
We investigated the neural substrates involved in visuo-haptic neuronal convergence using an additive-factors design in combination with fMRI. Stimuli were explored under three sensory modality conditions: viewing the object through a mirror without touching (V), touching the object with eyes closed (H), or simultaneously viewing and touching the object (VH). This modality factor was crossed with a task difficulty factor, which had two levels. On the basis of an idea similar to the principle of inverse effectiveness, we predicted that increasing difficulty would increase the relative level of multisensory gain in brain regions where visual and haptic sensory inputs converged. An ROI analysis focused on the lateral occipital tactile–visual area found evidence of inverse effectiveness in the left lateral occipital tactile–visual area, but not in the right. A whole-brain analysis also found evidence for the same pattern in the anterior aspect of the intraparietal sulcus, the premotor cortex, and the posterior insula, all in the left hemisphere. In conclusion, this study is the first to demonstrate visuo-haptic neuronal convergence based on an inversely effective pattern of brain activation.
Closing the Gates to Consciousness: Distractors Activate a Central Inhibition Process
Authors: Niedeggen Michael , Michael Lars , Hesselmann Guido 
Published: December 2011

AbstractThe paradigm of distractor-induced blindness has previously been used to track the transition from unconscious to conscious visual processing. In a variation of this paradigm used in this study, participants (n = 13) had to detect an orientation change of tilted bars (target) embedded in a dynamic random pattern; the onset of the target was signaled by the presentation of a color cue. Occasional orientation changes preceding the cue served as distractors and severely impaired the target's detection. ERPs showed that a frontal negativity was cumulatively activated by the distractors, and early sensory components were not affected. In a control condition, the target was defined by a coherent motion of the bars. Orientation changes preceding the motion target did not affect its detection, and the frontal suppression process was not observed. However, we obtained a significant reduction of the sensory components. The data support the notion that distractors that share the target's features trigger a cumulative inhibition process preventing the conscious representation of the inhibited features. Explorative source modeling suggests that this process originates in the pFC. A top–down modulation of sensory processing could not be observed.
Isotopic Signal of Earlier Summer Monsoon Onset in the Bay of Bengal
Authors: Yang Xiaoxin , Yao Tandong , Yang Wulin , Xu Baiqing , He You , Qu Dongmei 
Published: December 2011

AbstractThe onset of the Asian summer monsoon is noticeably controversial, spatially and temporally. The stable oxygen isotope δ18O in precipitation has long been used to trace water vapor source, particularly to capture the summer monsoon precipitation signal. The abrupt decrease of precipitation δ18O in the Asian summer monsoon region closely corresponds to the summer monsoon onset. Two stations have therefore been set up at Guangzhou and Lulang in the East Asian summer monsoon domain to clarify the summer monsoon onset dates. Event-based precipitation δ18O during 2007/08 is much lower at Lulang than at Guangzhou and is attributable mainly to the altitude effect offset by different isotopic compositions in marine moisture sources. The earlier appearance of low δ18Owt at Lulang than at Guangzhou confirms the earlier summer monsoon onset in the Bay of Bengal. Isotopically identified summer monsoon evolutions from precipitation δ18O at both stations are verifiable with NCEP–NCAR reanalysis data, indicating that precipitation δ18O offers an alternative approach to studying the summer monsoon circulation from precipitation δ18O.
Knowledge Production in Urban Governance Systems through Qualitative Geographical Information Systems (GIS)
Authors: Pfeffer Karin , Martinez Javier , Baud Isa , Sridharan N. 
Published: December 2011

Urban governance offers opportunities for more inclusive urban management, incorporating tacit knowledge and citizens’ preferences. The question is how to elicit such knowledge and preferences so that they are both inclusive as well as efficient. Field visits to Indian cities have shown that a lot of effort is put into the implementation of E-governance tools and setting up Geographic Information Systems (GIS), focusing on administrative interaction with citizens. Little attention is paid to how GIS could be included in strategic governance processes. The main question here is how a combination of GIS-based qualitative and quantitative approaches can make local embedded knowledge visible for inclusive urban governance. Therefore workshops were held in four Indian cities (Mysore, Hubli–Dharward, Kalyan and Mira–Bhayandar) with participants from local government departments and elected councillors to elicit and discuss local knowledge on urban inequalities. GIS maps were used as an input to the process and for visualizing outcomes. The workshops show that using GIS throughout the process provides an understanding of the local context, enriches knowledge obtained from local databases, and therefore supports multiple forms of knowledge. However, the outcome depends greatly on the nature of input maps, the situated knowledge of workshop participants and map literacy.
Unemployment in multiple sclerosis: the contribution of personality and disease
Authors: Strober Lauren B , Christodoulou Christopher , Benedict Ralph HB , Westervelt Holly J , Melville Patricia , Scherl William F , Weinstock-Guttman Bianca , Rizvi Syed , Goodman Andrew D , Krupp Lauren B 
Published: December 2011

Background: Multiple sclerosis (MS) is the leading cause of neurological disability among young and middle-aged adults. One of the most devastating consequences of MS in this relatively young population group is unemployment. Although certain demographic and disease factors have been associated with employment, few studies have examined the contribution of person-specific factors, such as personality. Objective: The goal of this study was to determine the extent to which personality, demographics, and clinical measures contribute to unemployment in MS. Method: A total of 101 individuals with MS who were enrolled in a clinical trial on cognition underwent a brief neuropsychological battery and completed questionnaires related to vocation, mood, fatigue, and personality. Neurological impairment was measured with the Expanded Disability Status Scale (EDSS). Results: Employment status was related with disease duration, MS subtype, level of neurological impairment, fatigue, performance on measures assessing information processing speed (Symbol Digit Modalities Test (SDMT)), learning and memory (Selective Reminding Test), and the personality characteristic of persistence. Based on a forward logistic regression analysis, EDSS, SDMT, and persistence were the strongest predictors of employment status. Conclusions: These findings underscore the importance of personality on outcomes in MS and point to the need for more clinical attention and research in this area.
Predictive nature of IgM anti-α-glucose serum biomarker for relapse activity and EDSS progression in CIS patients: a BENEFIT study analysis
Authors: Freedman MS , Metzig C , Kappos L , Polman CH , Edan G , Hartung H-P , Miller DH , Montalban X , Yarden J , Spector L , Fire E , Dotan N , Schwenke S , Lanius V , Sandbrink R , Pohl C 
Published: December 2011

Background: Higher serum levels of at least one of a panel of four α-glucose IgM antibodies (gMS-Classifier1) in clinically isolated syndrome (CIS) patients are associated with imminent early relapse within 2 years. Objective: The objective of this study was to determine the prognostic value of gMS-Classifier1 in a large study cohort of CIS patients. Methods: The BEtaseron® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) 5-year study was designed to evaluate the impact of early versus delayed interferon-β-1b (IFNβ-1b; Betaseron®) treatment in patients with a first event suggestive of multiple sclerosis (MS). Patients ( n = 258, 61% of total) with a minimum of 2 ml baseline serum were eligible for the biomarker study. gMS-Classifier1 antibodies’ panel (anti-GAGA2, anti-GAGA3, anti-GAGA4 and anti-GAGA6) levels were measured blinded to clinical data. Subjects were classified as either ‘positive’ or ‘negative’ according to a classification rule. Results: gMS-Classifier1 was not predictive for the time to clinically definite MS or time to MS according to the revised McDonald’s criteria, but did significantly predict an increased risk for confirmed disability progression (log-rank test: p = 0.012). Conclusions: We could not confirm previous results that gMS-Classifier1 can predict early conversion to MS in CIS. However, raised titres of these antibodies may predict early disability progression in this patient population.