bluuebunny/crossref_metadata_2025 huggingface dataset:
Associative Recognition Processes Are Modulated by Modality Relations
Authors: Tibon Roni , Ben-Zvi Shir , Levy Daniel A.
Published: February 2014

Although memory of episodic associations is generally considered to be recollective in nature, it has been suggested that when stimuli are experienced as a unit, familiarity-related processes might contribute to their subsequent associative recognition. Furthermore, intradomain associations are believed to be unitized more readily than interdomain associations. To assess these claims, we tested associative recognition following two types of pair associate learning. In the unimodal task, stimulus pairs were pictures of common objects, whereas in the cross-modal task, stimulus pairs consisted of an object picture and an unrelated environmental sound. At test, participants discriminated intact from recombined pairs while ERPs were recorded. In the unimodal task only, associative recognition was accompanied by a robust frontal deflection reminiscent of a component commonly interpreted as related to familiarity processes. In contrast, ERP correlates of associative recognition observed at more posterior sites, akin to a component that has been related to recollection, were apparent in both tasks. These findings indicate that retrieval of unimodal associations can be supported by familiarity-related processes that are dissociable from recollective processes required for the retrieval of cross-modal associations.
Brain Mechanisms of Successful Recognition through Retrieval of Semantic Context
Authors: Flegal Kristin E. , Marín-Gutiérrez Alejandro , Ragland J. Daniel , Ranganath Charan
Published: February 2014

Episodic memory is associated with the encoding and retrieval of context information and with a subjective sense of reexperiencing past events. The neural correlates of episodic retrieval have been extensively studied using fMRI, leading to the identification of a “general recollection network” including medial temporal, parietal, and prefrontal regions. However, in these studies, it is difficult to disentangle the effects of context retrieval from recollection. In this study, we used fMRI to determine the extent to which the recruitment of regions in the recollection network is contingent on context reinstatement. Participants were scanned during a cued recognition test for target words from encoded sentences. Studied target words were preceded by either a cue word studied in the same sentence (thus congruent with encoding context) or a cue word studied in a different sentence (thus incongruent with encoding context). Converging fMRI results from independently defined ROIs and whole-brain analysis showed regional specificity in the recollection network. Activity in hippocampus and parahippocampal cortex was specifically increased during successful retrieval following congruent context cues, whereas parietal and prefrontal components of the general recollection network were associated with confident retrieval irrespective of contextual congruency. Our findings implicate medial temporal regions in the retrieval of semantic context, contributing to, but dissociable from, recollective experience.
Activity in the Nucleus Accumbens and Amygdala Underlies Individual Differences in Prosocial and Individualistic Economic Choices
Authors: Haruno Masahiko , Kimura Minoru , Frith Christopher D.
Published: February 2014

Much decision-making requires balancing benefits to the self with benefits to the group. There are marked individual differences in this balance such that individualists tend to favor themselves whereas prosocials tend to favor the group. Understanding the mechanisms underlying this difference has important implications for society and its institutions. Using behavioral and fMRI data collected during the performance of the ultimatum game, we show that individual differences in social preferences for resource allocation, so-called “social value orientation,” is linked with activity in the nucleus accumbens and amygdala elicited by inequity, rather than activity in insula, ACC, and dorsolateral pFC. Importantly, the presence of cognitive load made prosocials behave more prosocially and individualists more individualistically, suggesting that social value orientation is driven more by intuition than reflection. In parallel, activity in the nucleus accumbens and amygdala, in response to inequity, tracked this behavioral pattern of prosocials and individualists. In addition, we conducted an impunity game experiment with different participants where they could not punish unfair behavior and found that the inequity-correlated activity seen in prosocials during the ultimatum game disappeared. This result suggests that the accumbens and amygdala activity of prosocials encodes “outcome-oriented emotion” designed to change situations (i.e., achieve equity or punish). Together, our results suggest a pivotal contribution of the nucleus accumbens and amygdala to individual differences in sociality.
Predication Drives Verb Cortical Signatures
Authors: Hernández Mireia , Fairhall Scott L. , Lenci Alessandro , Baroni Marco , Caramazza Alfonso
Published: February 2014

Verbs and nouns are fundamental units of language, but their neural instantiation remains poorly understood. Neuropsychological research has shown that nouns and verbs can be damaged independently of each other, and neuroimaging research has found that several brain regions respond differentially to the two word classes. However, the semantic–lexical properties of verbs and nouns that drive these effects remain unknown. Here we show that the most likely candidate is predication: a core lexical feature involved in binding constituent arguments (boy, candies) into a unified syntactic–semantic structure expressing a proposition (the boy likes the candies). We used functional neuroimaging to test whether the intrinsic “predication-building” function of verbs is what drives the verb–noun distinction in the brain. We first identified verb-preferring regions with a localizer experiment including verbs and nouns. Then, we examined whether these regions are sensitive to transitivity—an index measuring its tendency to select for a direct object. Transitivity is a verb-specific property lying at the core of its predication function. Neural activity in the left posterior middle temporal and inferior frontal gyri correlates with transitivity, indicating sensitivity to predication. This represents the first evidence that grammatical class preference in the brain is driven by a word's function to build predication structures.
Placoneis cocquytiae, a new raphid diatom (Bacillariophyceae) from the Senegal River (Senegal, West Africa)
Authors: Fofana Cheikh Abdoul Kader , Sow El Hadji , Taylor Jonathan , Ector Luc , De Vijver Bart Van
Published: February 2014

During a survey of the freshwater diatom flora of the Senegal River, an unknown Placoneis species was observed that was initially identified as Placoneis gastrum. Detailed morphological analysis using both light and scanning electron microscopy observations revealed sufficient morphological differences to separate this species as Placoneis cocquytiae sp. nov. The new species is characterized by a rather broadly lanceolate to elliptic-lanceolate valve outline with rostrate, protracted, broadly rounded apices. The central area has an irregular shape due to the shortening of several striae. An isolated pore is lacking. The new species is compared with similar Placoneis and Navicula s.l. taxa and a short biogeographical analysis based on confirmed African records is presented. So far, P. cocquytiae is also present in Zambia and Lake Tanganyika.
Descriptions of two new species of Myrmedonota Cameron (Staphylinidae: Aleocharinae) from Mexico with comments on the genus taxonomy and behavior
Authors: MATHIS KAITLYN A. , ELDREDGE K. TARO
Published: February 2014

Two new species of Myrmedonota, M. shimmerale n. sp. and M. xipe n. sp., are described, and the genus is recorded from Mexico for the first time. Dorsal habitus photographs, illustrations of the median lobe and spermatheca are presented for diagnostic purposes. We suggest that Myrmedonota is in fact diverse in the New World and that its taxonomy is already in a state of confusion. New behavioral observations show that: (1) Myrmedonota species will aggregate towards agitated ants, possibly to prey on them; (2) Myrmedonota will form mating swarms, either with no apparent landmark or in the vicinity of ants.
On the Role of SST Forcing in the 2011 and 2012 Extreme U.S. Heat and Drought: A Study in Contrasts
Authors: Wang Hailan , Schubert Siegfried , Koster Randal , Ham Yoo-Geun , Suarez Max
Published: February 2014

This study compares the extreme heat and drought that developed over the United States in 2011 and 2012 with a focus on the role of sea surface temperature (SST) forcing. Experiments with the NASA Goddard Earth Observing System, version 5 (GEOS-5), atmospheric general circulation model show that the winter/spring response over the United States to the Pacific SST is remarkably similar for the two years despite substantial differences in the tropical Pacific SST. As such, the pronounced winter and early spring temperature differences between the two years (warmth confined to the south in 2011 and covering much of the continent in 2012) primarily reflect differences in the contributions from the Atlantic and Indian Oceans, with both acting to cool the east and upper Midwest during 2011, while during 2012 the Indian Ocean reinforced the Pacific-driven, continental-wide warming and the Atlantic played a less important role. During late spring and summer of 2011, the tropical Pacific SST forced a continued warming and drying over the southern United States, though considerably weaker than observed. Nevertheless, the observed 2011 anomalies fall well within the model’s intraensemble spread. In contrast, the observed rapid development of intense heat and drying over the central United States during June and July 2012 falls on the margins of the model’s intraensemble spread, with the response to the SST giving little indication that 2012 would produce record-breaking precipitation deficits and heat. A diagnosis of the 2012 observed circulation anomalies shows that the most extreme heat and drought was tied to the development of a stationary Rossby wave and an associated anomalous upper-tropospheric high maintained by weather transients.
Identification and Attenuation of Barriers to Entrepreneurship
Authors: Moon Zola K. , Farmer Frank L , Miller Wayne P. , Abreo Christina
Published: February 2014

Results are reported from a Latino immigrant entrepreneur needs assessment survey. The research project was conducted to identify barriers to business formation and continuation within the target population. A total of 171 surveys representing more than 200 businesses from 39 communities in 21 counties in western Arkansas were collected. Nearly 42% of respondents cited start-up capital as their biggest barrier with another 15% naming it as the second biggest barrier. Understanding government regulations and tax information rated as the second biggest barrier that Latinos encountered. This barrier is more pronounced in rural areas than in urban areas. Other top concerns include advertising, location, and obtaining licenses and permits. A closer examination of barriers finds nuanced differences between rural and urban entrepreneurs. Outreach programs and materials developed in response to research findings are presented.
Acute, Subchronic, and Developmental Toxicological Properties of Lubricating Oil Base Stocks
Authors: Dalbey Walden E. , McKee Richard H. , Goyak Katy Olsavsky , Biles Robert W. , Murray Jay , White Russell
Published: February 2014

Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.
Comparison of alternate scoring of variables on the performance of the frailty index
Authors: Peña Fernando G , Theou Olga , Wallace Lindsay , Brothers Thomas D , Gill Thomas M , Gahbauer Evelyne A , Kirkland Susan , Mitnitski Arnold , Rockwood Kenneth
Published: February 2014

Background

The frailty index (FI) is used to measure the health status of ageing individuals. An FI is constructed as the proportion of deficits present in an individual out of the total number of age-related health variables considered. The purpose of this study was to systematically assess whether dichotomizing deficits included in an FI affects the information value of the whole index.

Methods

Secondary analysis of three population-based longitudinal studies of community dwelling individuals: Nova Scotia Health Survey (NSHS, n = 3227 aged 18+), Survey of Health, Ageing and Retirement in Europe (SHARE, n = 37546 aged 50+), and Yale Precipitating Events Project (Yale-PEP, n = 754 aged 70+). For each dataset, we constructed two FIs from baseline data using the deficit accumulation approach. In each dataset, both FIs included the same variables (23 in NSHS, 70 in SHARE, 33 in Yale-PEP). One FI was constructed with only dichotomous values (marking presence or absence of a deficit); in the other FI, as many variables as possible were coded as ordinal (graded severity of a deficit). Participants in each study were followed for different durations (NSHS: 10 years, SHARE: 5 years, Yale PEP: 12 years).

Results

Within each dataset, the difference in mean scores between the ordinal and dichotomous-only FIs ranged from 0 to 1.5 deficits. Their ability to predict mortality was identical; their absolute difference in area under the ROC curve ranged from 0.00 to 0.02, and their absolute difference between Cox Hazard Ratios ranged from 0.001 to 0.009.

Conclusions

Analyses from three diverse datasets suggest that variables included in an FI can be coded either as dichotomous or ordinal, with negligible impact on the performance of the index in predicting mortality.
Estrogen receptor α-coupled Bmi1 regulation pathway in breast cancer and its clinical implications
Authors: Wang Huali , Liu Haijing , Li Xin , Zhao Jing , Zhang Hong , Mao Jingzhuo , Zou Yongxin , Zhang Hong , Zhang Shuang , Hou Wei , Hou Lin , McNutt Michael A , Zhang Bo
Published: February 2014

Background

Bmi1 has been identified as an important regulator in breast cancer, but its relationship with other signaling molecules such as ERα and HER2 is undetermined.

Methods

The expression of Bmi1 and its correlation with ERα, PR, Ki-67, HER2, p16INK4a, cyclin D1 and pRB was evaluated by immunohistochemistry in a collection of 92 cases of breast cancer and statistically analyzed. Stimulation of Bmi1 expression by ERα or 17β-estradiol (E2) was analyzed in cell lines including MCF-7, MDA-MB-231, ERα-restored MDA-MB-231 and ERα-knockdown MCF-7 cells. Luciferase reporter and chromatin immunoprecipitation assays were also performed.

Results

Immunostaining revealed strong correlation of Bmi1 and ERα expression status in breast cancer. Expression of Bmi1 was stimulated by 17β-estradiol in ERα-positive MCF-7 cells but not in ERα-negative MDA-MB-231 cells, while the expression of Bmi1 did not alter expression of ERα. As expected, stimulation of Bmi1 expression could also be achieved in ERα-restored MDA-MB-231 cells, and at the same time depletion of ERα decreased expression of Bmi1. The proximal promoter region of Bmi1 was transcriptionally activated with co-transfection of ERα in luciferase assays, and the interaction of the Bmi1 promoter with ERα was confirmed by chromatin immunoprecipitation. Moreover, in breast cancer tissues activation of the ERα-coupled Bmi1 pathway generally correlated with high levels of cyclin D1, while loss of its activity resulted in aberrant expression of p16INK4a and a high Ki-67 index, which implied a more aggressive phenotype of breast cancer.

Conclusions

Expression of Bmi1 is influenced by ERα, and the activity of the ERα-coupled Bmi1 signature impacts p16INK4a and cyclin D1 status and thus correlates with the tumor molecular subtype and biologic behavior. This demonstrates the important role which is played by ERα-coupled Bmi1 in human breast cancer.
Epidemiology and treatment outcomes of diabetic retinopathy in a diabetic population from Cameroon
Authors: Jingi Ahmadou M , Noubiap Jean Jacques N , Ellong Augustin , Bigna Jean Joel R , Mvogo Côme Ebana
Published: February 2014

Background

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes. It can lead to significant visual loss. The aim of this study was to determine the frequency and clinical profile of diabetic retinopathy, and assess the outcomes of laser photocoagulation therapy in a diabetic population in Cameroon.

Methods

We carried out a prospective cohort study during 24 months in the Department of Ophthalmology of the Douala General Hospital, Cameroon. We included all diabetic patients who were referred from diabetes clinics for ophthalmologic evaluation. Data included type and duration of diabetes, visual acuity, intra-ocular pressure, results of fundoscopy and fluorescein angiography, and outcomes two months after treatment with laser photocoagulation.

Results

We included 407 patients; 88% had type 2 diabetes. Their mean duration of diabetes was 6.4 years (SD=6.6). Forty point three percent (164/407) of patients were found to have DR on fundoscopy. Of the 164 patients with DR, 63.4% (104/164) had non-proliferative and 36.6% (60/164) had proliferative DR. Diabetic maculopathy was found in 14.5% (59/407) of all participants, and 36% (59/164) of patients with DR. There was a strong correlation between the duration of diabetes and retinopathy status (p < 0.001, r = 0.9541). Overall, 17.4% (71/407) of patients were eligible for laser photocoagulation. Of these, 66.2% (47/71) were treated, and 78.7% (37/47) of treated patients came back for control two months later. Among these treated patients an improvement of the retinopathy was noted in 73% (27/37), no change in 16.2% (6/37) and a worsening in 10.8% (4/37). Severe proliferative DR was significantly associated with treatment failure (p < 0.001).

Conclusions

The frequency of DR may be high among diabetic patients in Cameroon. There was a good uptake of laser photocoagulation therapy among patients affected by DR in our setting, with good treatment outcomes. Interventions to prevent diabetes and increase the precocity of diagnosis and treatment of DR should be scaled up.
Treatment fidelity of brief motivational interviewing and health education in a randomized clinical trial to promote dental attendance of low-income mothers and children: Community-Based Intergenerational Oral Health Study “Baby Smiles”
Authors: Weinstein Philip , Milgrom Peter , Riedy Christine A , Mancl Lloyd A , Garson Gayle , Huebner Colleen E , Smolen Darlene , Sutherland Marilynn , Nykamp Ann
Published: February 2014

Background

Fidelity assessments are integral to intervention research but few published trials report these processes in detail. We included plans for fidelity monitoring in the design of a community-based intervention trial.

Methods

The study design was a randomized clinical trial of an intervention provided to low-income women to increase utilization of dental care during pregnancy (mother) or the postpartum (child) period. Group assignment followed a 2 × 2 factorial design in which participants were randomly assigned to receive either brief Motivational Interviewing (MI) or Health Education (HE) during pregnancy (prenatal) and then randomly reassigned to one of these groups for the postpartum intervention. The study setting was four county health departments in rural Oregon State, USA. Counseling was standardized using a step-by-step manual. Counselors were trained to criteria prior to delivering the intervention and fidelity monitoring continued throughout the implementation period based on audio recordings of counselor-participant sessions. The Yale Adherence and Competence Scale (YACS), modified for this study, was used to code the audio recordings of the counselors’ delivery of both the MI and HE interventions. Using Interclass Correlation Coefficients totaling the occurrences of specific MI counseling behaviors, ICC for prenatal was .93, for postpartum the ICC was .75. Participants provided a second source of fidelity data. As a second source of fidelity data, the participants completed the Feedback Questionnaire that included ratings of their satisfaction with the counselors at the completion of the prenatal and post-partum interventions.

Results

Coding indicated counselor adherence to MI protocol and variation among counselors in the use of MI skills in the MI condition. Almost no MI behaviors were found in the HE condition. Differences in the length of time to deliver intervention were found; as expected, the HE intervention took less time. There were no differences between the overall participants’ satisfaction ratings of the HE and MI sessions by individual counselor or overall (p > .05).

Conclusions

Trial design, protocol specification, training, and continuous supervision led to a high degree of treatment fidelity for the counseling interventions in this randomized clinical trial and will increase confidence in the interpretation of the trial findings.

Trial registration

ClinicalTrials.gov: NCT01120041
RETRACTED ARTICLE: Emodin enhances osteogenesis and inhibits adipogenesis
Authors: Yang Feng , Yuan Pu-wei , Hao Yang-Quan , Lu Zheng-Mao
Published: February 2014

Background

It has been suggested that the formation of osteoblasts in bone marrow is closely associated with adipogenesis, and the balance between osteogenesis and adipogenesis differentiation of MSCs (mesenchymal stem cells) is disrupted in osteoporosis. In order to improve the treatment of osteoporosis, available agents with roles of regulating the balance is highly desirable. Emodin is a natural anthraquinone derivative extracted from Chinese herbs, which have been used to treat bone diseases for thousands of years. However, the underlying molecular mechanisms of emodin in modulating osteogenesis and adipogenesis remain poorly understood.

Methods

The molecular mechanisms of emodin on the processes of osteogenesis and adipogenesis in ovariectomized mouse and BMSCs (bone marrow mesenchymal stem cells) have been studied. We have analyzed the effects of emodin in vivo and in vitro. Female ICR mice were assigned to three groups: sham group, ovariectomy group, emodin group. Efficacy was evaluated by H&E, immunohistochemical assay and Micro-CT. In vitro, we analyze the effect of emodin—at concentrations between 0.1 μM and 10 μM-on the processes of inducing osteogenesis and inhibiting adipogenesis in BMSCs by ALP, Oil red O staining, real time RT-PCR and western blot.

Results

As our experiment shows that emodin could increase the number of osteoblast, BMD (bone mineral density), BV/TV (trabecular bone volume fraction), Tb.N (trabecular number) and Conn.D (connectivity density) of OVX (ovariectomized) mice and decrease the bone marrow fat tissue and adipocytes. The genes and proteins expression of osteogenesis markers, such as Runx2, osterix, collagen type I, osteocalcin, or ALP were up-regulated. While, the genes and proteins involved in adipogenesis, PPARγ, C/EBPα and ap2 were down-regulated.

Conclusion

It proves that emodin inhibits adipocyte differentiation and enhances osteoblast differentiation from BMSCs.
Musculoskeletal disorder risk factors among nursing professionals in low resource settings: a cross-sectional study in Uganda
Authors: Munabi Ian G , Buwembo William , Kitara David L , Ochieng Joseph , Mwaka Erisa S
Published: February 2014

Background

Musculoskeletal disorders (MSD) constitute one of the main occupational hazards among health care workers. However, few epidemiological studies on work related MSD among nursing professionals have been carried out in Africa. The purpose of this study was to assess the work related musculoskeletal disorders and associated risk factors among nursing professionals in Uganda.

Methods

This was a cross-sectional study of MSD among 880 nursing professionals from five selected hospitals in Uganda. Data was collected using a questionnaire adapted from the Dutch Musculoskeletal and Nordic Musculoskeletal questionnaires. Descriptive (mean, standard deviation and percentages) and inferential (Chi square test and logistic regression analysis) statistics were used to analyse data. Alpha level was set at p < 0.05.

Results

A total of 741 completed questionnaires were analysed (response rate 85.4%). The average age of the respondents was 35.4 (SD 10.7) years and a majority were female (85.7%). The average working hours per week was 43.7 (SD 18.9 hours). The 12-month period-prevalence of MSD at anybody site was 80.8%. The most common site of MSD was the lower back (61.9%). Significant risk factors for reported MSD included often working in a slightly bent posture (adjOR 2.25, 95% CI 1.20-4.26), often working in a slightly twisted posture for long (adjOR 1.97, 95% CI 1.03-3.77), mental exhaustion (adjOR 2.05, 95% CI 1.17-3.5), being absent from the work station for more than 6 months due to illness or an accident (adjO|R, 4.35, 95% CI 1.44-13.08) and feeling rested after a break (adjOR 2.09, 95% CI 1.16-3.76).

Conclusions

Musculoskeletal disorders affect more than 80% of nursing professionals in Uganda with the most commonly, affected site being the lower back. Significant risk factors for MSD include; being absent from the work station for more than 6 months due to illness or an accident, working in awkward postures, pushing/pulling of heavy loads and mental exhaustion. There is a need for greater advocacy, better working conditions and adoption of strategies to reduce occupational injuries.
CD8+T cell–specific induction of NKG2D receptor by doxorubicin plus interleukin-12 and its contribution to CD8+T cell accumulation in tumors
Authors: Hu Jiemiao , Zhu Shiguo , Xia Xueqing , Zhang Liangfang , Kleinerman Eugenie S , Li Shulin
Published: February 2014

Background

Increased infiltration of CD8+T cells into tumors has a positive impact on survival. Our previous study showed that doxorubicin (Dox) plus interleukin-12 (IL-12) boosted the accumulation of CD8+T cells in tumors and had a greater antitumor effect than did either agent alone. The purpose of this study was to determine the impact of NKG2D expression on CD8+T cell infiltration and antitumor efficacy.

Methods

Tumor-bearing mice were administered Dox, IL-12 plasmid DNA, or both via intraperitoneal injection or intramuscular electroporation. The induction of NKG2D on CD8+T cells and other lymphocytes was analyzed via flow cytometry, and NKG2D-positive CD8+T cell–specific localization in tumors was determined by using immunofluorescence staining in various types of immune cell–depleted mice.

Results

The combination of Dox plus IL-12 specifically increased expression of NKG2D in CD8+T cells but not in other types of immune cells, including NK cells, which naturally express NKG2D. This induced NKG2D expression in CD8+T cells was associated with increased accumulation of CD8+T cells in murine tumors. Administration of NKG2D-blocking antibody or CD8+T cell–depletion antibody abrogated the NKG2D+CD8+T cell detection in tumors, whereas administration of NK cell–depletion antibody had no effect. Increased NKG2D expression in CD8+T cells was associated with increased antitumor efficacy in vivo.

Conclusion

We conclude that Dox plus IL-12 induces NKG2D in CD8+T cells in vivo and boosts NKG2D+CD8+T-dependent antitumor immune surveillance. This discovery reveals a novel mechanism for how chemoimmunotherapy synergistically promotes T cell–mediated antitumor immune surveillance.
cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells
Authors: Cho Eun-Ah , Kim Eui-Jun , Kwak Sahng-June , Juhnn Yong-Sung
Published: February 2014

Background

The ataxia–telangiectasia mutated (ATM) protein kinase plays a central role in coordinating the cellular response to radiation-induced DNA damage. cAMP signaling regulates various cellular responses including metabolism and gene expression. This study aimed to investigate the mechanism through which cAMP signaling regulates ATM activation and cellular responses to ionizing radiation in lung cancer cells.

Methods

Lung cancer cells were transfected with constitutively active stimulatory G protein (GαsQL), and irradiated with γ-rays. The phosphorylation of ATM and protein phosphatase 2A was analyzed by western blotting, and apoptosis was assessed by western blotting, flow cytometry, and TUNNEL staining. The promoter activity of NF-κB was determined by dual luciferase reporter assay. BALB/c mice were treated with forskolin to assess the effect in the lung tissue.

Results

Transient expression of GαsQL significantly inhibited radiation-induced ATM phosphorylation in H1299 human lung cancer cells. Treatment with okadaic acid or knock down of PP2A B56δ subunit abolished the inhibitory effect of Gαs on radiation-induced ATM phosphorylation. Expression of GαsQL increased phosphorylation of the B56δ and PP2A activity, and inhibition of PKA blocked Gαs-induced PP2A activation. GαsQL enhanced radiation-induced cleavage of caspase-3 and PARP and increased the number of early apoptotic cells. The radiation-induced apoptosis was increased by inhibition of NF-κB using PDTC or inhibition of ATM using KU55933 or siRNA against ATM. Pretreatment of BALB/c mice with forskolin stimulated phosphorylation of PP2A B56δ, inhibited the activation of ATM and NF-κB, and augmented radiation-induced apoptosis in the lung tissue. GαsQL expression decreased the nuclear levels of the p50 and p65 subunits and NF-κB-dependent activity after γ-ray irradiation in H1299 cells. Pretreatment with prostaglandin E2 or isoproterenol increased B56δ phosphorylation, decreased radiation-induced ATM phosphorylation and increased apoptosis.

Conclusions

cAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-κB in lung cancer cells.
Combination therapy with ampicillin and azithromycin in an experimental pneumococcal pneumonia is bactericidal and effective in down regulating inflammation in mice
Authors: Majhi Arnab , Kundu Kiran , Adhikary Rana , Banerjee Madhubanti , Mahanti Sayantika , Basu Anirban , Bishayi Biswadev
Published: February 2014

Objectives

Emergence of multidrug resistance among Streptococcus pneumoniae (SP), has limited the available options used to treat infections caused by this organism. The objective of this study was to compare the role of monotherapy and combination therapy with ampicillin (AMP) and azithromycin (AZM) in eradicating bacterial burden and down regulating lung inflammation in a murine experimental pneumococcal infection model.

Methods

Balb/C mice were infected with 106 CFU of SP. Treatments with intravenous ampicillin (200 mg/kg) and azithromycin (50 mg/kg) either alone or in combination was initiated 18 h post infection, animals were sacrificed from 0 – 6 h after initiation of treatment. AMP and AZM were quantified in serum by microbiological assay. Levels of TNF-α, IFN-γ IL-6, and IL-10 in serum and in lungs, along with myeloperoxidase, inflammatory cell count in broncho alveolar lavage fluid, COX-2 and histopathological changes in lungs were estimated.

Results

Combination therapy down regulated lung inflammation and accelerated bacterial clearance. This approach also significantly decreased TNF-α, IFN-γ, IL-6 and increased IL-10 level in serum and lungs along with decreased myeloperoxidase, pulmonary vascular permeability, inflammatory cell numbers and COX-2 levels in lungs.

Conclusions

Combinatorial therapy resulted in comparable bactericidal activity against the multi-drug resistant isolate and may represent an alternative dosing strategy, which may help to alleviate problems with pneumococcal pneumonia.
A review of research on salivary biomarkers for oral cancer detection
Authors: Cheng Yi‐Shing Lisa , Rees Terry , Wright John
Published: February 2014

Using saliva for disease diagnostics and health surveillance is a promising approach as collecting saliva is relatively easy and non‐invasive. Over the past two decades, using salivary biomarkers specifically for early cancer detection has attracted much research interest, especially for cancers occurring in the oral cavity and oropharynx, for which the five‐year survival rate (62%) is still one of the lowest among all major human cancers. More than 90% of oral cancers are oral squamous cell carcinoma (OSCC) and the standard method for detection is through a comprehensive clinical examination by oral healthcare professionals. Despite the fact that the oral cavity is easily accessible, most OSCCs are not diagnosed until an advanced stage, which is believed to be the major reason for the low survival rate, and points to the urgent need for clinical diagnostic aids for early detection of OSCC. Thus, much research effort has been dedicated to investigating potential salivary biomarkers for OSCC, and more than 100 such biomarkers have been reported in the literature. However, some important issues and challenges have emerged that require solutions and further research in order to find reliable OSCC salivary biomarkers for clinical use. This review article provides an up‐to‐date list of potential OSCC salivary biomarkers reported as of the fall of 2013, and discusses those emerging issues. By raising the awareness of these issues on the part of both researchers and clinicians, it is hoped that reliable, specific and sensitive salivary biomarkers may be found soon—and not only biomarkers for early OSCC detection but also for detecting other types of cancers or even for monitoring non‐cancerous disease activity.
Vitamin D deficiency and risk of acute lung injury in severe sepsis and severe trauma: a case-control study
Authors: Barnett Nicolas , Zhao Zhiguo , Koyama Tatsuki , Janz David R , Wang Chen-Yu , May Addison K , Bernard Gordon R , Ware Lorraine B
Published: February 2014

Background

The aim of this study was to determine the association between 25-hydroxyvitamin D (25-OHD) levels at the onset of critical illness and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with sepsis or trauma.

Methods

We performed two nested case-control studies of 478 patients with sepsis and trauma with or without ALI/ARDS admitted to the medical, surgical and trauma ICUs of a tertiary-care center. Cases consisted of patients with either sepsis or trauma and ALI/ARDS; controls consisted of equivalent numbers of matched patients with either sepsis or trauma alone. We measured serum 25-OHD levels the morning after ICU admission and used multivariable regression to assess the relationship between 25-OHD and diagnosis of ALI/ARDS during the first four ICU days, controlling for age, gender, diabetes, smoking status and season.

Results

25-OHD levels did not differ between cases with ALI/ARDS and controls in either the sepsis or trauma cohorts. Using a conditional logistic regression model, sepsis patients during the winter season with higher 25-OHD levels were more likely to develop acute lung injury (odds ratio 1.68, 95% confidence interval of 1.05 to 2.69, P = 0.03). This association did not hold for the trauma cohort in either season. Sepsis and trauma patients had a lower risk of hospital mortality at higher 25-OHD levels but neither relationship reached significance. Higher one-year mortality after trauma was associated with lower 25-OHD levels (HR 0.50, CI 0.35,0.72 P = 0.001).

Conclusions

Serum 25-OHD measured early after admission to intensive care is not associated with the development of acute lung injury, hospital or one-year mortality in critically ill patients with sepsis although lower 25-OHD levels were associated with higher one-year mortality in patients with severe trauma.
Relative labor supply in intermarriage
Authors: Nottmeyer Olga
Published: February 2014

Spouse’s relative labor supply and the degree of specialization in intermarriage might differ from that in immigrant and native marriage for several reasons. Intermarried couples may specialize less due to smaller comparative advantages resulting from positive assortative mating by education, and due to different bargaining positions within the household. The empirical analysis relies on panel data using a two limit Random Effects Tobit framework to identify determinants of a gender-neutral specialization index. Results indicate that for immigrants intermarriage is indeed related to less specialization, as is similar education levels of spouses, while children and being Muslim or Islamic are associated with greater specialization. For natives, on the other hand, the likelihood to specialize increases with intermarriage. This might result from differences in bargaining strength or be due to adaptation to immigrants’ gender roles.

JEL classification

J1, J12.
Dose-escalation of human anti-interferon-α receptor monoclonal antibody MEDI-546 in subjects with systemic sclerosis: a phase 1, multicenter, open label study
Authors: Goldberg Avram , Geppert Thomas , Schiopu Elena , Frech Tracy , Hsu Vivien , Simms Robert W , Peng Stanford L , Yao Yihong , Elgeioushi Nairouz , Chang Linda , Wang Bing , Yoo Stephen
Published: February 2014

Introduction

Type I interferons (IFNs) are implicated in the pathogenesis of systemic sclerosis (SSc). MEDI-546 is an investigational human monoclonal antibody directed against the type I IFN receptor. This Phase 1 study evaluated the safety/tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of single and multiple intravenous doses of MEDI-546 in adults with SSc.

Methods

Subjects (≥18 years) with SSc were enrolled in an open-label, dose-escalation study to receive single (0.1, 0.3, 1.0, 3.0, 10.0, or 20.0 mg/kg), or 4 weekly intravenous doses (0.3, 1.0, or 5.0 mg/kg/week) of MEDI-546. Subjects were followed for 12 weeks. Safety assessments included adverse events (AEs), laboratory results, and viral monitoring. Blood samples were collected from all subjects for determination of PK, presence of anti-drug antibodies (ADAs), and expression of type I IFN-inducible genes.

Results

Of 34 subjects (mean age 47.4 years), 32 completed treatment and 33 completed the study. Overall, 148 treatment-emergent AEs (TEAEs) were reported (68.9% mild, 27.7% moderate). TEAEs included one grade 1 infusion reaction (5.0 mg/kg/week multiple dose). Of 4 treatment-emergent serious AEs (skin ulcer, osteomyelitis, vertigo, and chronic myelogenous leukemia (CML)), only CML (1.0 mg/kg/week multiple dose) was considered possibly treatment-related. MEDI-546 exhibited non-linear PK at lower doses. ADAs were detected in 5 subjects; no apparent impact on PK was observed. Peak inhibition of the type I IFN signature in whole blood was achieved within 1 day and in skin after 7 days.

Conclusion

The safety/tolerability, PK, and PD profiles observed in this study support further clinical development of MEDI-546.

Trial Registration

ClinicalTrials.gov NCT00930683
Programming of the Hypothalamic-Pituitary-Adrenal Axis by Neonatal Intermittent Hypoxia: Effects on Adult Male ACTH and Corticosterone Responses Are Stress Specific
Authors: Chintamaneni Kathan , Bruder Eric D. , Raff Hershel
Published: February 2014

Intermittent hypoxia (IH) is an animal model of apnea-induced hypoxia, a common stressor in the premature neonate. Neonatal stressors may have long-term programming effects in the adult. We hypothesized that neonatal exposure to IH leads to significant changes in basal and stress-induced hypothalamic-pituitary-adrenal (HPA) axis function in the adult male rat. Rat pups were exposed to normoxia (control) or 6 approximately 30-second cycles of IH (5% or 10% inspired O2) daily on postnatal days 2–6. At approximately 100 days of age, we assessed the diurnal rhythm of plasma corticosterone and stress-induced plasma ACTH and corticosterone responses, as well as mRNA expression of pertinent genes within the HPA axis. Basal diurnal rhythm of plasma corticosterone concentrations in the adult rat were not affected by prior exposure to neonatal IH. Adults exposed to 10% IH as neonates exhibited an augmented peak ACTH response and a prolonged corticosterone response to restraint stress; however, HPA axis responses to insulin-induced hypoglycemia were not augmented in adults exposed to neonatal IH. Pituitary Pomc, Crhr1, Nr3c1, Nr3c2, Avpr1b, and Hif1a mRNA expression was decreased in adults exposed to neonatal 10% IH. Expression of pertinent hypothalamic and adrenal mRNAs was not affected by neonatal IH. We conclude that exposure to neonatal 10% IH programs the adult HPA axis to hyperrespond to acute stimuli in a stressor-specific manner.
Thyroid Function Within the Normal Range and the Risk of Depression: A Population-Based Cohort Study
Authors: Medici Marco , Direk Nese , Visser W. Edward , Korevaar Tim I. M. , Hofman Albert , Visser Theo J. , Tiemeier Henning , Peeters Robin P.
Published: February 2014

Context:

Overt hypo- and hyperthyroidism are associated with an increased risk of depression. Little is known about the effects of variation in thyroid function within the normal range on the risk of depression.

Objective:

The objective of the study was to examine the association between normal-range thyroid function and the risk of depression.

Design, Setting, and Participants:

This was a cohort study in 1503 Dutch men and women, aged 70.6 (7.3) (mean [SD]) years. At baseline, serum TSH, thyroperoxidase antibody levels, and depressive symptoms [Center for Epidemiologic Studies Depression Scale (CES-D)] were assessed. A CES-D of 16 or greater is indicative of a depressive disorder. During follow-up (mean 8.0 y), participants were continuously monitored for the occurrence of incident depressive syndromes (n = 156).

Results:

Cross-sectionally, persons in the lowest TSH tertile (0.3–1.0 mU/L) had more depressive symptoms [CES-D score (mean): 7.95 vs 6.63, P = .014] as well as an increased risk of a CES-D of 16 or greater [10.7% vs 5.0%, odds ratio (95% confidence interval) 2.22 (1.18–4.17)], compared with persons in the highest normal range TSH tertile (1.6–4.0 mU/L). In the prospective analyses, persons in the lowest TSH tertile who were depression free at baseline had a higher risk of incident depressive syndromes [12.3% vs 7.6%, odds ratio (95% confidence interval) 1.85 (1.10–3.11)]. Thyroid autoimmunity (thyroperoxidase antibody positivity) was not associated with CES-D scores or incident depressive syndromes.

Conclusions:

Elderly persons with low-normal TSH levels have more concurrent depressive symptoms as well as a substantially increased risk of developing a depressive syndrome in the subsequent years. This study identifies low-normal TSH as an important risk factor for depression in the elderly.
Stability of tautological bundles on the Hilbert scheme of two points on a surface
Authors: Wandel Malte
Published: February 2014

Let (X, H) be a polarized smooth projective surface satisfyingH1(Χ, OΧ) = 0, and letƑbe either a rank 1 torsion-free sheaf or a rank 2μH-stable vector bundle onΧ. Assume thatc1(Ƒ) ≠ 0. This article shows that the rank 2—respectively, rank 4—tautological sheafƑ[2]associated withƑon the Hilbert squareΧ[2]isμ-stable with respect to a certain polarization.
Simple normal crossing Fano varieties and log Fano manifolds
Authors: Fujita Kento
Published: February 2014

A projective log variety (X, D) is called a log Fano manifold if X is smooth and if D is a reduced simple normal crossing divisor on Χ with − (KΧ + D) ample. The n-dimensional log Fano manifolds (X, D) with nonzero D are classified in this article when the log Fano index r of (X, D) satisfies either r ≥ n/2 with ρ(X) ≥ 2 or r ≥ n − 2. This result is a partial generalization of the classification of logarithmic Fano 3-folds by Maeda.
Optimization-Based Approaches for Maximizing Aggregate Recommendation Diversity
Authors: Adomavicius Gediminas , Kwon YoungOk
Published: February 2014

Recommender systems are being used to help users find relevant items from a large set of alternatives in many online applications. Most existing recommendation techniques have focused on improving recommendation accuracy; however, diversity of recommendations has also been increasingly recognized in research literature as an important aspect of recommendation quality. This paper proposes several optimization-based approaches for improving aggregate diversity of top-N recommendations, including a greedy maximization heuristic, a graph-theoretic approach based on maximum flow or maximum bipartite matching computations, and an integer programming approach. The proposed approaches are evaluated using real-world movie rating data sets and demonstrate substantial improvements in both diversity and accuracy as compared to the recommendation reranking approaches, which have been introduced in prior literature for the purposes of diversity improvement and were used for baseline comparisons in our study. The paper also discusses the computational complexity and the scalability of the proposed approaches, as well as the potential directions for future work.
Infinite Horizon Strategies for Replenishment Systems with a General Pool of Suppliers
Authors: Federgruen Awi , Yang Nan
Published: February 2014

We consider a general infinite horizon inventory control model that combines demand and supply risks and the firm's ability to mitigate the supply risks by diversifying its procurement orders among a set of N potential suppliers. Supply risks arise because only a random percentage of any given replenishment order is delivered as useable units. The suppliers are characterized by the price they charge and the distribution of their yield factor. Assuming unsatisfied demand is backlogged, the firm incurs, as in standard inventory models, three types of costs: (i) procurement costs, (ii) inventory carrying costs for units carried over from one period to the next, and (iii) backlogging costs. We establish the existence of an optimal stationary policy, under both the long-run discounted and average cost criteria, and characterize its structure. Assuming each period's inventory level distribution can be approximated as a normal, we develop an efficient solution method identifying additional structural properties. Finally, we identify a simple class of heuristic policies that come close to being optimal.