bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune-mediated dormancy: an equilibrium with cancer
Authors: Teng Michele W L , Swann Jeremy B , Koebel Catherine M , Schreiber Robert D , Smyth Mark J
Published: May 2008

This brief review discusses the role of the immune system in tumor development, covering a history of cancer immunity and a summary of the concept of cancer immunoediting, including its three phases: elimination, equilibrium, and escape. The latter half of this review then focuses specifically on the equilibrium phase, making note of previous work, suggesting that immunity might maintain cancer in a dormant state, and concluding with a description of a tractable mouse model unequivocally demonstrating that immunity can indeed hold preformed cancer in check. These findings form a framework for future studies aimed at validating immune-mediated cancer dormancy in humans with the hopes of devising new, immunotherapeutic strategies to treat established cancer.
Endothelins modulate inflammatory reaction in zymosan-induced arthritis: participation of LTB4, TNF-α, and CXCL-1
Authors: Conte Fernando de Paiva , Barja-Fidalgo Christina , Verri Waldiceu A , Cunha Fernando Queiroz , Rae Giles A , Penido Carmen , Henriques Maria das Graças M O
Published: May 2008

Endothelins (ETs) are involved in inflammatory events, including pain, fever, edema, and cell migration. ET-1 levels are increased in plasma and synovial membrane of rheumatoid arthritis (RA) patients, but the evidence that ETs participate in RA physiopathology is limited. The present study investigated the involvement of ETs in neutrophil accumulation and edema formation in the murine model of zymosan-induced arthritis. Intra-articular (i.a.) administration of selective ETA or ETB receptor antagonists (BQ-123 and BQ-788, respectively; 15 pmol/cavity) prior to i.a. zymosan injection (500 μg/cavity) markedly reduced knee-joint edema formation and neutrophil influx to the synovial cavity 6 h and 24 h after stimulation. Histological analysis showed that ETA or ETB receptor blockade suppressed zymosan-induced neutrophil accumulation in articular tissue at 6 h. Likewise, dual blockade of ETA/ETB with bosentan (10 mg/kg, i.v.) also reduced edema formation and neutrophil counts 6 h after zymosan stimulation. Pretreatment with BQ-123 or BQ-788 (i.a.; 15 pmol/cavity) also decreased zymosan-induced TNF-α production within 6 h, keratinocyte-derived chemokine/CXCL1 production within 24 h, and leukotriene B4 at both time-points. Consistent with the demonstration that ET receptor antagonists inhibit zymosan-induced inflammation, i.a. injection of ET-1 (1–30 pmol/cavity) or sarafotoxin S6c (0.1–30 pmol/cavity) also triggered edema formation and neutrophil accumulation within 6 h. Moreover, knee-joint synovial tissue expressed ETA and ETB receptors. These findings suggest that endogenous ETs contribute to knee-joint inflammation, acting through ETA and ETB receptors and modulating edema formation, neutrophil recruitment, and production of inflammatory mediators.
Out-patient psychotherapy for borderline personality disorder:
Cost-effectiveness of schema-focused therapy v.
transference-focused psychotherapy
Authors: van Asselt Antoinette D. I. , Dirksen Carmen D. , Arntz Arnoud , Giesen-Bloo Josephine H. , van Dyck Richard , Spinhoven Philip , van Tilburg Willem , Kreimers Ismay P. , Nadort Marjon , Severens Johan L.
Published: May 2008

Background

Schema-focused therapy (SFT) and transference-focused psychotherapy (TFP)
for borderline personality disorder were recently compared in a
randomised multicentre trial.

Aims

To assess the societal cost-effectiveness of SFT v. TFP in treating
borderline personality disorder.

Method

Costs were assessed by interview. Health-related quality of life was
measured using EQ-5D. Outcomes were costs per recovered patient (recovery
assessed with the Borderline Personality Disorder Severity Index) and
costs per quality-adjusted life-year (QALY).

Results

Mean 4-year bootstrapped costs were $37826 for SFT and $46 795 for TFP
(95% uncertainty interval for difference −21 775 to 3546); QALYs were
2.15 for SFT and 2.27 for TFP (95% UI −0.51 to 0.28). The percentages of
patients who recovered were 52% and 29% respectively. The SFT
intervention was less costly and more effective than TFP (dominant), for
recovery; it saved $90457 for one QALY loss.

Conclusions

Despite the initial slight disadvantage in QALYs, there is a high
probability that compared with TFP, SFT is a cost-effective treatment for
borderline personality disorder.
First- v. second-generation antipsychotics and
risk for diabetes in schizophrenia: Systematic review and
meta-analysis
Authors: Smith M. , Hopkins D. , Peveler R. C. , Holt R. I. G. , Woodward M. , Ismail K.
Published: May 2008

Background

The increased prevalence of diabetes in schizophrenia is partly
attributed to antipsychotic treatment, in particular second-generation
antipsychotics, but the evidence has not been systematically
reviewed.

Aims

Systematic review and meta-analysis comparing diabetes risk for different
antipsychotics in people with schizophrenia.

Method

We searched MEDLINE, PsycINFO, EMBASE, International Pharmaceutical
Abstracts, CINAHL and Web of Knowledge until September 2006. Studies were
eligible for inclusion if the design was cross-sectional, case-control,
cohort or a controlled trial in individuals with schizophrenia or related
psychotic disorders, where second-generation antipsychotics (defined as
clozapine, olanzapine, risperidone and quetiapine) were compared with
first-generation antipsychotics and diabetes was an outcome. Data were
pooled using random effects inverse variance weighted meta-analysis.

Results

Of the studies that met the inclusion criteria (n=14), 11 had sufficient
data to include in the meta-analysis. Four of these were retrospective
cohort studies. The relative risk of diabetes in patients with
schizophrenia prescribed one of the second-generation v.
first-generation antipsychotics was 1.32 (95% CI 1.15-1.51). There were
insufficient data to include aripiprazole, ziprasidone and amisulpride in
this analysis.

Conclusions

There is tentative evidence that the second-generation antipsychotics
included in this study are associated with a small increased risk for
diabetes compared with firstgeneration antipsychotics in people with
schizophrenia. Methodological limitations were found in most studies,
leading to heterogeneity and difficulty interpreting data. Regardless of
type of antipsychotic, screening for diabetes in all people with
schizophrenia should be routine.
Changes in male suicides in Scottish prisons: 10-year study
Authors: Bird Sheila M.
Published: May 2008

Background

In 1999 I estimated the expected number of UK prison suicides, taking into account that opioid users' deaths from suicide were 10 times the number expected for their age and gender. Changes have since taken place in Scottish prisons.

Aims

To estimate the expected number of male suicides in Scottish prisons in 1994–2003, having taken age and opioid dependency into account; and to consider the extremes of prisoner age.

Method

The effective number that prisons safeguard in terms of suicide risk was approximated as 10 times the number of opioid-dependent inmates plus other inmates. By applying age-appropriate suicide rates for Scottish males to these effective numbers, expectations for male suicides in Scottish prisons were calculated.

Results

In 1994-98, there were at least 57 male suicides, significantly exceeding the age- and opioid-adjusted expectation of 41. In 1999–2003, the 51 male suicides in prison were consistent with expectation (upper 95% limit: at least 54). During the decade 1994–2003, observed and expected suicides were mismatched at both extremes of age: 40 males aged 15-24 years died by suicidev.24 expected, and 13 males aged 45+ v. 2 expected. Against 4.5 prison suicides expected for males aged 15-24 years during a 2-year period, actual suicides were 3 in 2002 + 2003 and 4 in 2004 + 2005.

Conclusions

Scotland has redressed an excess of male suicides, especially by its youngest prisoners.
Emotional memory in bipolar disorder
Authors: Kauer-Sant'Anna Marcia , Yatham Lakshmi N. , Tramontina Juliana , Weyne Fernanda , Cereser Keila Maria , Gazalle Fernando Kratz , Andreazza Ana Cristina , Santin Aida , Quevedo Joao , Izquierdo Ivan , Kapczinski Flavio
Published: May 2008

Background

Cognitive impairment has been well documented in bipolar disorder.
However, specific aspects of cognition such as emotional memory have not
been examined.

Aims

To investigate episodic emotional memory in bipolar disorder, as
indicated by performance on an amygdala-related cognitive task.

Method

Twenty euthymic patients with bipolar disorder and 20 matched controls
were recruited. Participants were shown a slide show of an emotionally
neutral story, or a closely matched emotionally arousing story. One week
later, participants were assessed on a memory-recall test.

Results

In contrast with the pattern observed in controls, patients with bipolar
disorder had no enhancement of memory for the emotional content of the
story (F=14.7, d.f.=1.36, P < 0.001). The subjective perception of the
emotional impact of the emotional condition was significantly different
from that of the neutral condition in controls but not in people with
bipolar disorder.

Conclusions

Our data suggest that the physiological pattern of enhanced memory
retrieval for emotionally bound information is blunted in bipolar
disorder.
Hippocampal volume and 2-year outcome in
depression
Authors: Kronmüller Klaus-Thomas , Pantel Johannes , Köhler Sebastian , Victor Daniela , Giesel Frederik , Magnotta Vincent A. , Mundt Christoph , Essig Marco , Schröder Johannes
Published: May 2008

Although the hippocampus has been found to be smaller in people with
depression, the clinical relevance of this is unclear. We investigated
hippocampal volume (using high-resolution magnetic resonance imaging) and
2-year outcome in 57 patients with major depression. The left and right
hippocampal volumes of patients with a depression relapse were significantly
smaller than those of healthy controls. Our results support the hypothesis
that the hippocampus is crucial in the outcome of depression.
Morphology of the corpus callosum at different stages of
schizophrenia: Cross-sectional study in first-episode and chronic
illness
Authors: Walterfang Mark , Wood Amanda G. , Reutens David C. , Wood Stephen J. , Chen Jian , Velakoulis Dennis , McGorry Patrick D. , Pantelis Christos
Published: May 2008

Background

The shape of the corpus callosum may differ in schizophrenia, although no
study has compared first-episode with established illness.

Aims

To investigate the size and shape of the corpus callosum in a large
sample of people with first-episode and established schizophrenia.

Method

Callosal size and shape were determined using highresolution magnetic
resonance imaging on 76 patients with first-episode
schizophrenia-spectrum disorders, 86 patients with established
schizophrenia and 55 healthy participants.

Results

There were no significant differences in total area across groups.
Reductions in callosal width were seen in the region of the anterior genu
in first-episode disorder (P<0.005). Similar reductions were seen in
the chronic schizophrenia group in the anterior genu, but also in the
posterior genu and isthmus (P = 0.0005).

Conclusions

Reductions in anterior callosal regions connecting frontal cortex are
present at the onset of schizophrenia, and in established illness are
accompanied by changes in other regions of the callosum connecting
cingulate, temporal and parietal cortices.
Influence of 5-HT2Creceptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia
Authors: Yevtushenko Olga O. , Cooper Stephen J. , O'Neill Ryan , Doherty Jennifer K. , Woodside Jayne V. , Reynolds Gavin P.
Published: May 2008

Background

Obesity and metabolic syndrome are significant problems for patients taking antipsychotic drugs. Evidence is emerging of genetic risk factors.

Aims

To investigate the influence of two candidate genes, smoking and drug treatment on obesity and metabolic syndrome in patients with schizophrenia.

Method

Patients (n=134) were assessed for measures of obesity, other factors contributing to metabolic syndrome, and two genetic polymorphisms (5-HT2Creceptor −759C/T and leptin −2548A/G).

Results

Neither genotype nor smoking was significantly associated with measures of obesity. However, both leptin genotype and smoking were significantly associated with metabolic syndrome. Significant interaction occurred between the genetic polymorphisms for effects on obesity, whereby a genotype combination increased risk. Drug treatment showed significant effects on measures of obesity and triglyceride concentrations; risperidone was associated with lower values than olanzapine or clozapine.

Conclusions

The findings suggest interacting genetic risk factors and smoking influence development of metabolic syndrome in patients on antipsychotic drugs.
High-dose and combination antipsychotic prescribing in acute adult wards in the UK: The challenges posed by p.r.n. prescribing
Authors: Paton Carol , Barnes Thomas R. E. , Cavanagh Mary-Rose , Taylor David , Lelliott Paul
Published: May 2008

Background

Clinical guidelines recommend the routine use of a single antipsychotic drug in a standard dose, but prescriptions for high-dose and combined antipsychotics are common in clinical practice.

Aims

To evaluate the effectiveness of a quality improvement programme in reducing the prevalence of high-dose and combined antipsychotic prescribing in acute adult in-patient wards in the UK.

Method

Baseline audit was followed by feedback of benchmarked data and delivery of a range of bespoke change interventions, and then by a further audit 1 year later.

Results

Thirty-two services participated, submitting data for 3942 patients at baseline and 3271 patients at the 1-year audit. There was little change in the prevalence of high-dose (baseline 36%; re-audit 34%) or combined antipsychotic prescribing (baseline 43%; re-audit 39%). As required (‘p.r.n.’) prescriptions were the principal cause of both high-dose and combined antipsychotic prescribing on both occasions.

Conclusions

The quality improvement programme did not have a demonstrable impact on prescribing practice in the majority of services. Future efforts to align practice with clinical guidelines need to specifically target the culture and practice of p.r.n. prescribing.
Hospital care and repetition following self-harm: Multicentre
comparison of self-poisoning and self-injury
Authors: Lilley Rachael , Owens David , Horrocks Judith , House Allan , Noble Rachael , Bergen Helen , Hawton Keith , Casey Deborah , Simkin Sue , Murphy Elizabeth , Cooper Jayne , Kapur Navneet
Published: May 2008

Background

Quantitative research about self-harm largely deals with self-poisoning,
despite the high incidence of self-injury.

Aims

We compared patterns of hospital care and repetition associated with
self-poisoning and self-injury.

Method

Demographic and clinical data were collected in a multicentre,
prospective cohort study, involving 10 498 consecutive episodes of
self-harm at six English teaching hospitals.

Results

Compared with those who self-poisoned, people who cut themselves were
more likely to have self-harmed previously and to have received support
from mental health services, but they were far less likely to be admitted
to the general hospital or receive a psychosocial assessment. Although
only 17% of people repeated self-harm during the 18 months of study,
survival analysis that takes account of all episodes revealed a
repetition rate of 33% in the year following an episode: 47% after
episodes of self-cutting and 31% after self-poisoning (P<0.001). Of
those who repeated, a third switched method of self-harm.

Conclusions

Hospital services offer less to people who have cut themselves, although
they are far more likely to repeat, than to those who have self-poisoned.
Attendance at hospital should result in psychosocial assessment of needs
regardless of method of self-harm.
Cognitive-behavioural therapy and family intervention for
relapse prevention and symptom reduction in psychosis: Randomised controlled
trial
Authors: Garety Philippa A. , Fowler David G. , Freeman Daniel , Bebbington Paul , Dunn Graham , Kuipers Elizabeth
Published: May 2008

Background

Family intervention reduces relapse rates in psychosis.
Cognitive-behavioural therapy (CBT) improves positive symptoms but
effects on relapse rates are not established.

Aims

To test the effectiveness of CBT and family intervention in reducing
relapse, and in improving symptoms and functioning in patients who had
recently relapsed with non-affective psychosis.

Method

A multicentre randomised controlled trial (ISRCTN83557988) with two
pathways: those without carers were allocated to treatment as usual or
CBT plus treatment as usual, those with carers to treatment as usual, CBT
plus treatment as usual or family intervention plus treatment as usual.
The CBT and family intervention were focused on relapse prevention for 20
sessions over 9 months.

Results

A total of 301 patients and 83 carers participated. Primary outcome data
were available on 96% of the total sample. The CBT and family
intervention had no effects on rates of remission and relapse or on days
in hospital at 12 or 24 months. For secondary outcomes, CBT showed a
beneficial effect on depression at 24 months and there were no effects
for family intervention. In people with carers, CBT significantly
improved delusional distress and social functioning. Therapy did not
change key psychological processes.

Conclusions

Generic CBT for psychosis is not indicated for routine relapse prevention
in people recovering from a recent relapse of psychosis and should
currently be reserved for those with distressing medication-unresponsive
positive symptoms. Any CBT targeted at this acute population requires
development. The lack of effect of family intervention on relapse may be
attributable to the low overall relapse rate in those with carers.
Gender differences in the association of mixed anxiety and
depression with suicide
Authors: Bjerkeset Ottar , Romundstad Pål , Gunnell David
Published: May 2008

The incidence of depression is higher in women than men but the reverse
pattern is seen with suicide. In a cohort of 50 692 Norwegians we found that
suicide risk associated with comorbid anxiety and depression was two-fold
higher in men (OR=7.4, 95% CI 3.1-17.5) than women (OR=2.9, 95% CI
0.8-10.6), although statistical evidence for a difference was weak (P=0.4).
If real, these gender differences could reflect either a more severe symptom
profile in men with self-reported anxiety and depression, perhaps because of
gender differences with regard to the stigma associated with mental illness,
or gender differences in the way men respond to mental illness (e.g.
self-medication/help-seeking).
Association of cannabis use with prodromal symptoms of psychosis
in adolescence
Authors: Miettunen Jouko , Törmänen Sari , Murray Graham K. , Jones Peter B. , Mäki Pirjo , Ebeling Hanna , Moilanen Irma , Taanila Anja , Heinimaa Markus , Joukamaa Matti , Veijola Juha
Published: May 2008

Recent interest has focused on the association between cannabis use and risk
of psychosis. In the largest unselected population-based study on this topic
to date, we examined cannabis use and prodromal symptoms of psychosis at age
15-16 years among 6330 adolescents. Those who had tried cannabis (n=352;
5.6% of the total sample) were more likely to present three or more
prodromal symptoms even after controlling for confounders including previous
behavioural symptoms (OR=2.23; 95% CI 1.70-2.94). A dose-response effect was
seen. We conclude that cannabis use is associated with prodromal symptoms of
psychosis in adolescence.
Neuropsychiatric morbidity in focal epilepsy
Authors: Adams Sophia J. , O'Brien Terence J. , Lloyd John , Kilpatrick Christine J. , Salzberg Michael R. , Velakoulis Dennis
Published: May 2008

Background

Previous work has identified elevated prevalence rates for psychiatric
disorders in individuals with medically refractory focal epilepsy,
particularly temporal lobe epilepsy. Many studies were undertaken before
the advent of video electroencephalogram monitoring (VEM) and magnetic
resonance imaging (MRI).

Aims

To investigate which characteristics of the focal epilepsy syndromes are
associated with the presence of depression or psychosis.

Method

Three hundred and nineteen individuals with focal epilepsy admitted for
VEM were seen over an 11-year period. The lifetime history of depression
and psychosis, epileptic site, laterality and type of lesion were
determined by clinical assessment, VEM and MRI scan.

Results

There was a significant association between the prevalence of depressive
symptoms and non-lesional focal epilepsy. There were no significant
differences in prevalence of neuropsychiatric disorders between the
groups with temporal lobe epilepsy and those with extratemporal lobe
epilepsy.

Conclusions

These findings contrast with previous findings in smaller cohorts. The
association between non-lesional focal epilepsy and depression may be due
to the effects of a more diffuse epileptogenic area.
Communication and psychosis: It's good to talk, but how?
Authors: McCabe Rose , Priebe Stefan
Published: May 2008

Communication between clinicians and patients is at the heart of psychiatric practice and particularly challenging with psychotic patients. It may influence patient outcome indirectly or be therapeutic in its own right. Appropriate conceptual models, evidence on effective interventions and specific training are required to optimise communication in everyday routine practice.
Cognitive-behavioural therapy for severe mental disorders: Back
to the future?
Authors: Scott Jan
Published: May 2008

Like recent medication studies, it appears that when cognitive-behavioural
therapy is tested in pragmatic effectiveness trials involving routine
clinical populations it does not fare as well as in efficacy trials. Given
the multitude of factors that can ‘muddy the waters’ in clinical trials, how
do we best make sense of the findings?
Alternative Route to Metal Halide Free Ionic Liquids
Authors: Takao Koichiro , Ikeda Yasuhisa
Published: June 2008

An alternative synthetic route to metal halide free ionic liquids using trialkyloxonium salt is proposed. Utility of this synthetic route has been demonstrated by preparing 1-ethyl-3-methylimidazolium tetrafluoroborate ionic liquid through the reaction between 1-methylimidazole and triethyloxonium tetrafluoroborate in anhydrous ether.
Inhibition of translation in living eukaryotic cells by an RNA G-quadruplex motif
Authors: Arora Amit , Dutkiewicz Mariola , Scaria Vinod , Hariharan Manoj , Maiti Souvik , Kurreck Jens
Published: May 2008

Guanine-rich sequences can adopt intramolecular four-stranded structures, called G-quadruplexes. These motifs have been intensively investigated on the DNA level, but their overall biological relevance remains elusive. Only recently has research concerning the function of G-quadruplexes in RNAs commenced. Here, we demonstrate for the first time, that an RNA G-quadruplex structure inhibits translation in vivo in eukaryotic cells. We investigated the function of a highly conserved, thermodynamically stable RNA G-quadruplex in the 5′-UTR of the mRNA of the human Zic-1 zinc-finger protein. Using dual luciferase reporter assay, we demonstrate that the Zic-1 RNA G-quadruplex represses protein synthesis inside eukaryotic cells. Quantitative RT-PCR assays confirmed that the reduction of protein synthesis is due to regulation of the translation process and not a consequence of reduced transcription. Western blot analysis revealed that expression of Zic-1 is strongly reduced by a 73 nucleotides-long fragment of the UTR containing the G-quadruplex motif. These structures might add to the more recently discovered elements in untranslated regions of mRNAs that regulate their translation.
Dynamic guide–target interactions contribute to sequential 2′-O-methylation by a unique archaeal dual guide box C/D sRNP
Authors: Singh Sanjay K. , Gurha Priyatansh , Gupta Ramesh
Published: May 2008

Assembly and guide–target interaction of an archaeal box C/D-guide sRNP was investigated under various conditions by analyzing the lead (II)-induced cleavage of the guide RNA. Guide and target RNAs derived from Haloferax volcanii pre-tRNATrp were used with recombinant Methanocaldococcus jannaschii core proteins in the reactions. Core protein L7Ae binds differentially to C/D and C′/D′ motifs of the guide RNA, and interchanging the two motifs relative to the termini of the guide RNA did not affect L7Ae binding or sRNA function. L7Ae binding to the guide RNA exposes its D′-guide sequence first followed by the D guide. These exposures are reduced when aNop5p and aFib proteins are added. The exposed guide sequences did not pair with the target sequences in the presence of L7Ae alone. The D-guide sequence could pair with the target in the presence of L7Ae and aNop5p, suggesting a role of aNop5p in target recruitment and rearrangement of sRNA structure. aFib binding further stabilizes this pairing. After box C/D-guided modification, target–guide pairing at the D-guide sequence is disrupted, suggesting that each round of methylation may require some conformational change or reassembly of the RNP. Asymmetric RNPs containing only one L7Ae at either of the two box motifs can be assembled, but a functional RNP requires L7Ae at the box C/D motif. This arrangement resembles the asymmetric eukaryal snoRNP. Observations of initial D-guide–target pairing and the functional requirement for L7Ae at the box C/D motif are consistent with our previous report of the sequential 2′-O-methylations of the target RNA.
Initiating translation with D-amino acids
Authors: Goto Yuki , Murakami Hiroshi , Suga Hiroaki
Published: May 2008

Here we report experimental evidence that the translation initiation apparatus accepts D-amino acids (Daa), as opposed to only L-methionine, as initiators. Nineteen Daa, as the stereoisomers to their natural L-amino acids, were charged onto initiator tRNAfMetCAU using flexizyme technology and tested for initiation in a reconstituted Escherichia coli translation system lacking methionine, i.e., the initiator was reprogrammed from methionine to Daa. Remarkably, all Daa could initiate translation while the efficiency of initiation depends upon the type of side chain. The peptide product initiated with Daa was generally in a nonformylated form, indicating that methionyl-tRNA formyltransferase poorly formylated the corresponding Daa-tRNAfMetCAU. Although the inefficient formylation of Daa-tRNAfMetCAU resulted in modest expression of the corresponding peptide, preacetylation of Daa-tRNAfMetCAU dramatically increased expression level, implying that the formylation efficiency is one of the critical determinants of initiation efficiency with Daa. Our findings provide not only the experimental evidence that translation initiation tolerates Daa, but also a new means for the mRNA-directed synthesis of peptides capped with Daa or acyl-Daa at the N terminus.
C. elegans La-related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis
Authors: Nykamp Keith , Lee Myon-Hee , Kimble Judith
Published: May 2008

RNA regulators are critical for animal development, especially in the germ line where gene expression is often modulated by changes in mRNA stability, translation, and localization. In this paper, we focus on Caenorhabditis elegans LARP-1, a representative of one La-related protein (Larp) family found broadly among eukaryotes. LARP-1 possesses a signature La motif, which is an ancient RNA-binding domain, plus a second conserved motif, typical of LARP-1 homologs and therefore dubbed the LARP1 domain. LARP-1 appears to bind RNA in vitro via both the La motif and the LARP1 domain. larp-1 null mutants have an oogenesis defect reminiscent of hyperactive Ras-MAPK signaling; this defect is suppressed or enhanced by down- or up-regulating the Ras-MAPK pathway, respectively. Consistent with a role in down-regulating the Ras-MAPK pathway, larp-1 null mutants have higher than normal levels of selected pathway mRNAs and proteins. LARP-1 protein colocalizes with P bodies, which function in RNA degradation. We suggest that LARP-1 functions in P bodies to attenuate the abundance of conserved Ras-MAPK mRNAs. We also propose that the cluster of LARP-1 homologs may function generally to control the expression of key developmental regulators.
A novel noncoding RNA processed by Drosha is restricted to nucleus in mouse
Authors: Ganesan Gayatri , Rao Satyanarayana M.R.
Published: May 2008

Noncoding RNAs constitute a huge repertoire of gene regulatory molecules. Our previous, fine-resolution characterization of a mouse meiotic recombination hotspot from chromosome 8 resulted in identification of 2.4-kb unspliced and polyadenylated noncodingmrhlRNA. The gene is expressed in multiple tissues and is also present in rat but absent in humans. Here we report that themrhlRNA gets processed to a small 80-nucleotide (nt) RNA species and is mediated by the Drosha complex. We also observe that the 80-nt Drosha product could be processed further to a 22-nt small RNA by Dicer in an in vitro reaction. However, this 22-nt product was not detected in vivo. The 80-nt as well as the 2.4-kb full-length RNA are nuclear-localized, showing distinct punctate nuclear signal. The colocalization of the noncoding RNA with Drosha and Nucleolin suggests the nucleolus as the site of processing of the 2.4-kb primary transcript. Additional foci of the processed 80-nt RNA were also observed outside the nucleolus, suggesting its role in some specific chromatin domain(s). Thus, this study reports a novel noncodingmrhlRNA that is processed and restricted within the cell nucleus.
Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs
Authors: Rong Liwei , Livingstone Mark , Sukarieh Rami , Petroulakis Emmanuel , Gingras Anne-Claude , Crosby Katherine , Smith Bradley , Polakiewicz Roberto D. , Pelletier Jerry , Ferraiuolo Maria A. , Sonenberg Nahum
Published: May 2008

Eukaryotic initiation factor (eIF) 4E, the mRNA 5′-cap-binding protein, mediates the association of eIF4F with the mRNA 5′-cap structure to stimulate cap-dependent translation initiation in the cytoplasm. The assembly of eIF4E into the eIF4F complex is negatively regulated through a family of repressor proteins, called the eIF4E-binding proteins (4E-BPs). eIF4E is also present in the nucleus, where it is thought to stimulate nuclear-cytoplasmic transport of certain mRNAs. eIF4E is transported to the nucleus via its interaction with 4E-T (4E-transporter), but it is unclear how it is retained in the nucleus. Here we show that a sizable fraction (∼30%) of 4E-BP1 is localized to the nucleus, where it binds eIF4E. In mouse embryo fibroblasts (MEFs) subjected to serum starvation and/or rapamycin treatment, nuclear 4E-BPs sequester eIF4E in the nucleus. A dramatic loss of nuclear 4E-BP1 occurs in c-Ha-Ras–expressing MEFs, which fail to show starvation-induced nuclear accumulation of eIF4E. Therefore, 4E-BP1 is a regulator of eIF4E cellular localization.
RNA structure-based ribosome recruitment: Lessons from the Dicistroviridae intergenic region IRESes
Authors: Pfingsten Jennifer S. , Kieft Jeffrey S.
Published: May 2008

In eukaryotes, the canonical process of initiating protein synthesis on an mRNA depends on many large protein factors and the modified nucleotide cap on the 5′ end of the mRNA. However, certain RNA sequences can bypass the need for these proteins and cap, using an RNA structure-based mechanism called internal initiation of translation. These RNAs are called internal ribosome entry sites (IRESes), and the cap-independent initiation pathway they support is critical for successful infection by many viruses of medical and economic importance. In this review, we briefly describe and compare mechanistic and structural groups of viral IRES RNAs, focusing on those IRESes that are capable of direct ribosome recruitment using specific RNA structures. We then discuss in greater detail some recent advances in our understanding of the intergenic region IRESes of the Dicistroviridae, which use the most streamlined ribosome-recruitment mechanism yet discovered. By combining these findings with knowledge of canonical translation and the behavior of other IRESes, mechanistic models of this RNA structure-based process are emerging.
Evaluation of the ARTAFIT Method for Fitting Time-Series Input Processes for Simulation
Authors: Biller Bahar , Nelson Barry L.
Published: May 2008

Time-series input processes occur naturally in the stochastic simulation of many service, communications, and manufacturing systems, and there are a variety of time-series input models available to match a given collection of properties, typically a marginal distribution and an autocorrelation structure specified via the use of one or more time lags. The focus of this paper is the situation in which the collection of properties are not “given,” but data are available from which a time-series input model is to be estimated. The input model we consider is the very flexible autoregressive-to-anything (ARTA) model of Cario and Nelson [Cario, M. C., B. L. Nelson. 1996. Autoregressive to anything: Time-series input processes for simulation. Oper. Res. Lett. 19 51–58]. Recently, we developed a statistically valid algorithm (ARTAFIT) for fitting this model to stationary univariate time-series data using marginal distributions from the Johnson translation system. In this paper, we perform a comprehensive numerical study to assess the performance of our algorithm relative to the two most commonly used approaches: (a) fitting the marginal distribution but ignoring the autocorrelation structure, and (b) fitting separately the marginal distribution as in (a) and the autocorrelation structure using the sample autocorrelation function. We find that ARTAFIT, which fits the marginal distribution and the autocorrelation structure jointly, outperforms both (a) and (b), and we demonstrate the importance of taking dependencies into account while developing input models for stochastic simulation.
Top-k ϕ Correlation Computation
Authors: Xiong Hui , Zhou Wenjun , Brodie Mark , Ma Sheng
Published: May 2008

Recently, there has been considerable interest in efficiently computing strongly correlated pairs in large databases. Most previous studies require the specification of a minimum correlation threshold to perform the computation. However, it may be difficult for users to provide an appropriate threshold in practice because different data sets typically have different characteristics. To this end, in this paper, we propose an alternative task: finding the top-k strongly correlated pairs. Consequently, we identify a two-dimensional monotone property of an upper bound of ϕ correlation coefficient and develop an efficient algorithm, called TOP-COP, to exploit this property to effectively prune many pairs even without computing their correlation coefficients. Our experimental results show that TOP-COP can be an order of magnitude faster than alternative approaches for mining the top-k strongly correlated pairs. Finally, we show that the performance of the TOP-COP algorithm is tightly related to the degree of data dispersion. Indeed, the higher the degree of data dispersion, the larger the computational savings achieved by the TOP-COP algorithm.
Efficient Simulation Budget Allocation for Selecting an Optimal Subset
Authors: Chen Chun-Hung , He Donghai , Fu Michael , Lee Loo Hay
Published: May 2008

We consider a class of the subset selection problem in ranking and selection. The objective is to identify the top m out of k designs based on simulated output. Traditional procedures are conservative and inefficient. Using the optimal computing budget allocation framework, we formulate the problem as that of maximizing the probability of correctly selecting all of the top-m designs subject to a constraint on the total number of samples available. For an approximation of this correct selection probability, we derive an asymptotically optimal allocation and propose an easy-to-implement heuristic sequential allocation procedure. Numerical experiments indicate that the resulting allocations are superior to other methods in the literature that we tested, and the relative efficiency increases for larger problems. In addition, preliminary numerical results indicate that the proposed new procedure has the potential to enhance computational efficiency for simulation optimization.
An Empirical Test of Gain-Loss Separability in Prospect Theory
Authors: Wu George , Markle Alex B.
Published: May 2008

We investigate a basic premise of prospect theory: that the valuation of gains and losses is separable. In prospect theory, gain-loss separability implies that a mixed gamble is valued by summing the valuations of the gain and loss portions of that gamble. Two experimental studies demonstrate a systematic violation of the double-matching axiom, an axiom that is necessary for gain-loss separability. We document a reversal between preferences for mixed gambles and the associated gain and loss gambles—mixed gamble A is preferred to mixed gamble B, but the gain and loss portions of B are preferred to the gain and loss portions of A. The observed choice patterns are consistent with a process in which individuals are less sensitive to probability differences when choosing among mixed gambles than when choosing among either gain or loss gambles.
Interactive Coordination of Objective Decompositions in Multiobjective Programming
Authors: Engau Alexander , Wiecek Margaret M.
Published: May 2008

To remedy challenges resulting from a high number of objectives in multiobjective programming and multicriteria decision making, this paper chooses to decompose the vector objective function and characterizes the relationships between solutions for the original problem and the collection of decomposed subproblems. In particular, it is shown how solutions that are found using this decomposition approach relate to solutions found by traditional scalarization techniques. For the selection of a final solution, two interactive coordination methods are proposed that allow to find any solution for the original problem by merely solving the smaller-sized subproblems, while integrating both preferences of the decision maker and trade-off information obtained from a sensitivity analysis. A theoretical foundation for the procedures is established, and their application is illustrated for portfolio optimization and a design selection problem.
Learning and Knowledge Depreciation in Professional Services
Authors: Boone Tonya , Ganeshan Ram , Hicks Robert L.
Published: May 2008

Organizational knowledge is a critical source of competitive advantage for professional service firms. Learning from experience and sustaining past knowledge are critical to the success of such knowledge-driven firms. We use learning curve theory to evaluate learning and depreciation in professional services. Our results, based on seven years of project data collected from an architectural engineering (A/E) firm, show that (a) professional services exhibit learning curves, (b) there is virtually no depreciation of knowledge and, (c) the rate of learning accelerates with experience.
The Influence of Situational Learning Orientation, Autonomy, and Voice on Error Making: The Case of Resident Physicians
Authors: Stern Zvi , Katz-Navon Tal , Naveh Eitan
Published: May 2008

Every organization is confronted by employee errors. Situational learning orientation may mitigate an employee's tendency to err. A situational learning orientation refers to the extent to which employees share the perception that there is an emphasis on improvement and on actively searching for additional knowledge and feedback in their department. The present study suggests that situational learning orientation interacts with two other organizational factors—autonomy and voice—as it influences employee errors, using the example of resident physicians' medical treatment errors. Senior nurses tallied the number of errors made by 123 residents from 25 departments over a three-month period. Results demonstrated that encouraging employee autonomy and voice fosters the benefits of learning by decreasing the number of treatment errors. Specifically, when the situational learning orientation was high, the number of errors decreased at an increasing rate as the perceived autonomy increased. When the learning orientation was low, there was a u-shaped relationship between autonomy and number of errors. In addition, only when the situational learning orientation was high did a higher employee voice lead to fewer treatment errors.
Learning, Knowledge Transfer, and Technology Implementation Performance: A Study of Time-to-Build in the Global Semiconductor Industry
Authors: Salomon Robert , Martin Xavier
Published: May 2008

Organizational growth and performance hinge upon the effective deployment of productive knowledge in new facilities. However, getting those facilities fully operational can be difficult and time consuming. Interestingly, we understand little about what determines the performance of that process. In this paper we help fill this gap by analyzing multiple determinants of time-to-build—i.e., the time it takes a firm to build and ramp up operations at a new manufacturing facility. Theoretically, we develop predictions regarding the effects of competitive, firm, and technology characteristics on time-to-build. Empirically, we test our predictions on a sample of plant construction projects in the memory segment of the global semiconductor industry. We find that competition from rivals with superior technology is associated with shorter time-to-build, at least up to a point. Firm and industry experience are associated with shorter time-to-build. International projects, and those that push the technological frontier, take longer. Findings from this study enrich the literatures on corporate growth, international expansion, and technology strategy. We discuss implications for research and practice.
Performance Implications of Peer Monitoring
Authors: Loughry Misty L. , Tosi Henry L.
Published: May 2008

Peer monitoring, which occurs when individuals notice and respond to their peers' behavior or performance results, is an informal organizational control that has not been extensively studied. Agency theory suggests that peer monitoring should be associated with higher performance because it allows workers whose interests are aligned with those of the organization to encourage their peers to perform well and deters inappropriate behavior by increasing the chances that it would be detected.

This paper considers two research questions. The first is, “What is peer monitoring?” We found two types of peer monitoring. Direct peer monitoring occurs when workers notice their peers' behavior or results and respond in a forthright way, such as correcting coworkers who make mistakes. Indirect peer monitoring occurs when workers gossip about or avoid poorly performing peers. The second research question is, “Is peer monitoring associated with higher work-unit performance?” We examined the effects of both types of peer monitoring on the performance of 67 theme park work units. We considered supervisory monitoring, task interdependence, and cohesiveness as moderators.

We measured performance as the degree to which the work unit is free of employee behavior problems and found a positive main effect of direct peer monitoring. The effect was stronger when supervisory monitoring was low or task interdependence was high. Indirect peer monitoring did not have a main effect on work-unit performance, but when supervisory monitoring or cohesiveness was high, indirect peer monitoring was associated with lower performance. We discuss these results and suggest areas for future research.
Hoping for A to Z While Rewarding Only A: Complex Organizations and Multiple Goals
Authors: Ethiraj Sendil K. , Levinthal Daniel
Published: May 2008

This paper explores the trade-offs inherent in the pursuit and fulfillment of multiple performance goals in complex organizations. We examine two related research questions: (1) What are the organizational implications of pursuing multiple performance goals? (2) Are local and myopic (as opposed to global) goal prioritization strategies effective in dealing with multiple goals? We employ a series of computational experiments to examine these questions. Our results from these experiments both formalize the intuition behind existing wisdom and provide new insights. We show that imposing a multitude of weakly correlated performance measures on even simple organizations (i.e., an organization comprised of independent employees) leads to a performance freeze in that actors are not able to identify choices that enhance organizational performance across the full array of goals. This problem increases as the degree of interdependence of organizational action increases. We also find that goal myopia, spatial differentiation of performance goals, and temporal differentiation of performance goals help rescue organizations from this status quo trap. In addition to highlighting a new class of organizational problems, we argue that in a world of boundedly rational actors, incomplete guides to action in the sense of providing only a subset of underlying goals prove more effective at directing and coordinating behavior than more complete representations of underlying objectives. Management, in the form of the articulation of a subset of goals, provides a degree of clarity and focus in a complex world.
Treatment Alternatives for Overweight and Obesity: The Role of Online Interventions
Authors: Baulch Jacqueline , Chester Andrea , Brennan Leah
Published: May 2008

This review examines the application of online interventions to the treatment of obesity. The unprecedented prevalence rates of overweight and obesity worldwide are indicative of the need to develop efficacious treatment alternatives. While research suggests that diet, physical activity and behaviour therapy are core components of effective obesity treatment programs, their ability to penetrate large portions of the population is limited. The empirically verified effectiveness of online interventions for disorders such as depression and social phobia, coupled with unparalleled rates of internet access, suggest that online interventions for overweight and obesity are a feasible and logical treatment modality. A limited number of randomised controlled trials reviewed in this article have evaluated the efficacy of this treatment alternative. Results are promising and encourage further use, development and empirical research in this area.
Experiential Avoidance in Civilian War Survivors With Current Versus Recovered Posttraumatic Stress Disorder: A Pilot Study
Authors: Morina Nexhmedin , Stangier Ulrich , Risch Anne Katrin
Published: May 2008

The present study investigated the role of experiential avoidance in posttraumatic stress disorder (PTSD) following war-related stress. Eighty-four civilian war survivors were assigned to one of three PTSD groups — current PTSD, recovered PTSD and non-PTSD. Groups were subsequently compared in regard to experiential avoidance. Results indicated significantly higher rates of experiential avoidance and psychological distress in the current PTSD group as compared with the recovered PTSD and non-PTSD groups. The recovered PTSD and non-PTSD groups did not significantly differ.