bluuebunny/crossref_metadata_2025 huggingface dataset:
Unhomeliness
Authors: Holt Robin
Published: January 2018

Arguing that Smith’s spectator is notable for its bridging skepticism and Kant’s sense of a unified subject, but wanting in its presenting a somewhat cosy, moralized, and self-sustaining sense of self, this chapter brings in the more unsettling views of spectating propounded by William Hazlitt. Hazlitt takes up the ideas propounded by Smith and Kant, but refuses to entertain the idea of there being a certain or sustained sense of self outside of the effort of self presenting. The characters of King Lear, Lady Macbeth and Macbeth are used to illustrate this argument. In this sense the self is constantly being produced through spectating, and hence is always living alongside itself, so to speak, often in uncanny ways. The self is its continual attempt at self presenting. In relation to strategic inquiry, this places the work of strategy centre stage, literally, as that process of inquiry by which any organization is brought into meaningful form.
The transcendental turn
Authors: Zahavi Dan
Published: January 2018

Husserl’s turn from a descriptive phenomenology to a transcendental phenomenology is linked to his methodological employment of the reduction and the epoché. But how should one interpret these notions? Are they crucial to phenomenology, do they enable phenomenology to become metaphysically committed, or are they tools that reveal Husserl’s commitment to a form of methodological solipsism? Chapter 3 offers an interpretation of the reduction and the epoché that makes it clear why Husserl’s transcendental turn does not involve a turning-away from the world, but a suspension of a specific dogmatic attitude towards the world, that for the first time permits a proper understanding of the (constituted) being of the world. Contrary to various existing interpretations, it is consequently argued that whereas Husserl’s descriptive phenomenology was indeed metaphysically neutral, he started to engage with metaphysical questions concerning the mind-dependent character of the world the moment he effectuated his transcendental turn.
Internalism, externalism, and transcendental idealism
Authors: Zahavi Dan
Published: January 2018

Whereas a certain popular (Fregean) interpretation of Husserl’s theory of intentionality makes Husserl into an internalist and methodological solipsist, the aim of Chapter 4 is to show that Husserl’s commitment to transcendental idealism prevents his theory from being either. I first discuss competing interpretations of Husserl’s concept of the noema, and argue that the Fregean interpretation misreads the transcendental character of Husserl’s phenomenology. I next present an interpretation of Husserl’s transcendental idealism that highlights its difference from metaphysical idealism and shows why Husserl’s conception of the mind–world relationship cannot be adequately captured within the internalism–externalism framework. In the final part of the chapter, I discuss how the claim that Husserl is a methodological solipsist fails to engage properly with his account of transcendental intersubjectivity, and how that latter account eventually transforms the very character of the transcendental project.
Explanation in Neurobiology
Authors: Woodward James
Published: January 2018

This chapter employs an interventionist framework to elucidate some issues having to do with explanation in neurobiology. I argue that this framework can be used to distinguish theories and models that are explanatory from those that are merely descriptive. This framework can also be used to characterize a notion of a mechanistic explanation, according to which mechanistic explanations are those that meet interventionist criteria for successful explanation and certain additional constraints as well. However, from an interventionist perspective, although mechanistic theories have a number of virtues, it is a mistake to think that such models are the only legitimate kind of explanation in neuroscience and psychology. In particular, some (but not all) dynamical systems models in neuroscience are explanatory as are many models, such as the Hodgkin-Huxley model, that abstract away from mechanistically relevant low-level detail.
Neural Computation, Multiple Realizability, and the Prospects for Mechanistic Explanation
Authors: Kaplan David M.
Published: January 2018

There is an ongoing philosophical and scientific debate concerning the nature of computational explanation in the neurosciences. Recently, some have cited modeling work involving so-called canonical neural computations—standard computational modules that apply the same fundamental operations across multiple brain areas—as evidence that computational neuroscientists sometimes employ a distinctive explanatory scheme from that of mechanistic explanation. Because these neural computations can rely on diverse circuits and mechanisms, modeling the underlying mechanisms is supposed to be of limited explanatory value. I argue that these conclusions about computational explanations in neuroscience are mistaken, and rest upon a number of confusions about the proper scope of mechanistic explanation and the relevance of multiple realizability considerations. Once these confusions are resolved, the mechanistic character of computational explanations can once again be appreciated.
Ethanol and guanine nucleotide binding proteins: a selective interaction
Authors: Hoffman Paula L. , Tabakoff Boris
Published: January 2018

Guanine nucleotide binding proteins (G proteins) play key roles in signal transduction, including the coupling of hormone and neurotransmitter receptors to adenylate cyclase, ion channels, and polyphosphoinositide metabolism. One member of this family of proteins, Gs, appears to represent a specific site of action of ethanol in the central nervous system. Ethanol is often perceived as a nonspecific drug, and its anesthetic effects may in fact arise from relatively nonspecific interactions with cell membrane lipids. However, recent investigations point to a selective effect of low concentrations of ethanol to promote the activation of Gs, and thus to enhance adenylate cyclase activity. Ethanol seems to have little or no effect on the function of other identified G proteins. After chronic ingestion of ethanol by animals, or chronic exposure of cells in culture to ethanol, the sensitivity of adenylate cyclase to stimulation by guanine nucleotides and agonists that act via Gs is decreased. The mechanism of this change may involve qualitative and/or quantitative alterations in Gs, and seems to vary in different cell types. Studies of human platelets and lymphocytes also reveal differences in adenylate cyclase activity between alcoholics and control subjects.∗∗∗ The differences are consistent with involvement of Gs, and do not appear to reverse upon cessation of alcohol exposure. The results suggest that the platelet and/or lymphocyte adenylate cyclase system may provide a biochemical marker of genetic predisposition to alcoholism.—Hoffman, P. L.; Tabakoff, B. Ethanol and guanine nucleotide binding proteins: a selective interaction. FASEB J. 4: 2612‐2622, 1990.
Immobilization of small molecules and proteins by radio‐derivatized polystyrene
Authors: Varga Janos M. , Fritsch Peter
Published: January 2018

When molded polystyrene (PS) products (e.g., microtiter plates) or latex particles are irradiated with high‐energy (1‐10 Mrads) gamma rays in the presence of nonpolymerizable small molecules such as aromatic amines, some of these molecules incorporate into PS, which leads to the formation of radio‐derivatized PS (RDPS). Two classes of RDPS can be identified regarding their ability for immobilization of biologically important molecules: 1) reactive RDPS that are able to form covalent bonds with molecules such as proteins without the help of cross‐linkers, and 2) functionalized RDPS that can be used for the immobilization of molecules with activators (e.g., carbodiimides) or cross‐linkers. The method can be used for the production of low‐noise supports for binding assays. Most of the RDPS can be produced without impairment of the optical quality of PS, making derivatized microtiter plates suitable for colorimetric assays. The principle can be applied for the preparation of affinity sorbents, e.g., for high‐performance affinity chromatography and for the immobilization of enzymes using latex PS particles.—Varga, J. M.; Fritsch, P. Immobilization of small molecules and proteins by radio‐derivatized polystyrene. FASEB J. 4: 2671‐2677, 1990.
Biomechanical study of olecranon plate fixation in comminuted osteoporotic fracture model: locking compression plates versus dynamic compression plates
Authors: Shakir Irshad , Israel Heidi , Cannada Lisa K. , Bledsoe Gary
Published: January 2018

This cadaveric biomechanical study compared locking compression plates (LCP) to dynamic compression plates (DCP) in a comminuted olecranon fracture using cyclic loading to measure fragment displacement and maximal failure load. Eight paired human cadavers were used. We confirmed all specimens were osteopenic using DEXA. One paired half of the specimens randomly received LCP fixation and the other DCP. Implants were secured to the intact ulna prior to creating an osteotomy. Two vertical osteotomies were created to simulate a fracture gap of 5 mm. The specimens were loaded and placed on the MTS machine. Saw-toothed cyclic loading was applied and force/gap displacement measured. Failure was defined as fracture gap greater than 2 mm or catastrophic failure of the bone/construct. Biomechanical parameters were compared between two groups. The average force for the DCP was 22.12 N compared to 33.40 N (P<0.05) for the LCP. The average gap for the DCP was 7.32 mm compared to 6.40 mm (P<0.05) for the LCP. The force measure was statistically significant at 60, 70, 80, 90, and 100 mm of displacement (P<0.05) for the LCP. This implies that the LCP was able to withstand higher force than the DCP. The gap displacement was statistically significant at 60, 70, 80, 90, and 100 mm of displacement (P<0.05). This implies that the LCP maintained the reduction better than the DCP. No differences in force/gap were noted when comparing gender, right versus left forearm, or osteoporotic versus osteopenic bone. There was no difference when failure occurred between the DCP and LCP groups. Our study found that LCP was able to withstand higher force than DCP, and there was less displacement of the fracture with biomechanical testing in the LCP compared to the DCP. Both could be appropriate surgical techniques for fixation of comminuted olecranon fractures. When treating comminuted and osteopenic fractures, LCP are advantageous. Further studies would be needed to compare these two plates clinically.
Women’s Health Outpatient Care Teams: Focus on Advanced Practice Providers
Authors: SLINKARD PHILIPP MONICA , STONEHOCKER JODY
Published: January 2018

Team-based care in the outpatient women’s health setting has the potential to help alleviate the demand for women’s health care providers and to deliver improved quality of care to the growing population of US women. Although teamwork is necessary in the current health care system, most of the current obstetrics and gynecology and advanced practice provider (APP) workforce were not trained for collaborative practice. Core competencies for building an effective outpatient women’s health care team are explained and current evidence regarding the specific role of APPs in women’s health care is reviewed.
Hepatitis C in Pregnancy in the Era of Direct-acting Antiviral Treatment: Potential Benefits of Universal Screening and Antepartum Therapy
Authors: BERNSTEIN HELENE B. , DUNKELBERG JEFFREY C. , LESLIE KIMBERLY K.
Published: January 2018

Hepatitis C in pregnancy is on the rise, and new direct-acting antiviral agents are available that cure the disease. Published recommendations need to be reviewed and clinically evaluated for the care of pregnant women who are at risk for or have chronic hepatitis C. Available evidence and some of the medical and ethical reasons to consider universal screening and antepartum therapy for hepatitis C during pregnancy are presented. Universal screening and proactive treatment during pregnancy is on the horizon, and these measures should be quickly evaluated for safety and implemented if appropriate.
SHORT-TERM EFFICACY OF CONBERCEPT AND RANIBIZUMAB FOR POLYPOIDAL CHOROIDAL VASCULOPATHY
Authors: Huang Zhen , Ding Qin , Yan Min , Lian Haiyan , Chen Zhongshan , Chen Xiao , Song Yanping
Published: January 2018

Purpose:

To compare the 6-month efficacy of the intravitreal injection of conbercept or ranibizumab for patients with polypoidal choroidal vasculopathy (PCV).

Methods:

This is a retrospective case–control study involved 79 PCV eyes of 77 patients. The PCV eyes were treated with an intravitreal injection of either ranibizumab (n = 44) or conbercept (n = 35). Three monthly loading doses were injected and followed by retreatment as needed. The best-corrected visual acuity and angiographic characteristics were evaluated after 6 months.

Results:

The mean logarithm of the minimum angle of resolution best-corrected visual acuity had improved from 0.86 (Snellen equivalent, 20/145) at baseline to 0.70 (Snellen equivalent, 20/100) at 6 months in the conbercept group (P < 0.001), and from 0.74 (Snellen equivalent, 20/110) at baseline to 0.63 (Snellen equivalent, 20/85) at 6 months in the ranibizumab group (P = 0.032), respectively. The central foveal thickness was decreased from 407 ± 146 μm to 230 ± 71 μm in the conbercept group (P < 0.001), and from 394 ± 93 μm to 208 ± 56 μm in the ranibizumab group (P < 0.001). Polyps were completely regressed and in 21 (47.7%) eyes in the conbercept group at 6 months, significant higher than in 10 (28.6%) eyes in the ranibizumab group (P = 0.029).

Conclusion:

Both conbercept and ranibizumab effectively increased the visual acuity and regressed the polyps of PCV eyes. No significant difference was found in the visual acuity improvement of the patients with PCV between the conbercept group and ranibizumab group at 6 months. However, conbercept was superior to ranibizumab monotherapy in the regression of polyps.
A Common Procedure With an Uncommon Pathology: Triamcinolone Acetonide Eyelid Injection
Authors: Wolkow Natalie , Jakobiec Frederick A. , Hatton Mark P.
Published: January 2018

Local corticosteroid injections are frequently employed by ophthalmologists to treat a variety of ocular, periocular, and orbital inflammatory conditions. Triamcinolone acetonide is a slowly dissolving crystalline corticosteroid that is often used for this purpose because of its prolonged anti-inflammatory effect. On occasion, previously injected corticosteroid material persists in tissues longer than anticipated, creating nodules that may masquerade as other disease conditions, or appearing incidentally in excised lesions on histopathologic examination. The histopathologic features of corticosteroid residues are unfamiliar to most ophthalmic pathologists and general pathologists. These features are described herein. Triamcinolone acetonide deposits in the skin appear as pale eosinophilic lakes of acellular frothy material on hematoxylin-eosin staining and are occasionally surrounded by a mild inflammatory reaction.
Apremilast Use in a Case of Cicatricial Ectropion Secondary to Severe Lamellar Ichthyosis
Authors: Abboud Jean-Paul J. , Whittington Alexander , Ahmed Masih , Himebaugh Jesse T. , Wiley Lee A. , Haffar Ahmad , Nguyen John
Published: January 2018

Ichthyosis is a cutaneous disorder characterized by excessive amounts of dry thickened skin surface scales. Ocular manifestations of ichthyosis include cicatricial ectropion, which may cause exposure keratoconjunctivitis and rarely corneal perforation. Topical emollients, anti-inflammatory ointments, and systemic retinoids have been used to control the disease process, while surgical correction with donor graft has been reserved for severe cases involving corneal exposure. The authors report a case of a Caucasian male with lamellar ichthyosis with severe bilateral upper and lower eyelid cicatricial ectropion and corneal ulceration requiring surgical correction. Treatment with apremilast, a novel phosphodiesterase-4 inhibitor, for the treatment of a concomitant plaque psoriasis achieved good control of his skin diseases and minimized the recurrence of eyelid ectropion.
Inpatient Outcomes for Gastrointestinal Bleeding Associated With Percutaneous Coronary Intervention
Authors: Cholankeril George , Hu Menghan , Cholankeril Rosann , Khan Muhammad A. , Gadiparthi Chiran , Yoo Eric R. , Perumpail Ryan B. , Nair Satheesh , Howden Colin W.
Published: January 2018

Goals:

The goal of this study was to evaluate the impact of inpatient outcomes of gastrointestinal bleeding (GIB) related to percutaneous coronary intervention (PCI).

Background:

With all-cause mortality increasing in patients undergoing PCIs, outcomes for GIB associated with PCI may be adversely impacted.

Study:

Using the National Inpatient Sample (2007 to 2012), we performed a nested case-control study assessing inpatient outcomes including incidence and mortality for PCI-related GIB hospitalizations. Multivariate logistic regression analyses were performed to determine significant predictors for GIB incidence and mortality.

Results:

A total of 9332 (1.2%) of PCI hospitalizations were complicated by GIB with the age-adjusted incidence rate increasing 13% from 2007 (11.3 GIB per 1000 PCI) to 2012 (12.8). Patients ≥75 years of age experienced the steepest incline in GIB incidence, which increased 31% during the study period. Compared with non-GIB patients, mean length of stay (9.4 d vs. 3.3 d) and median cost of care ($29,236 vs. $17,913) was significantly higher. Significant demographic risk factors for GIB included older age and comorbid risk factors included gastritis or duodenitis, and Helicobacter pylori infection.

In total, 1044 (11%) of GIB patients died during hospitalization with the GIB mortality rate increasing 30% from 2007 (95 deaths per 1000 GIB) to 2012 (123). Older age had the strongest association with inpatient mortality.

Conclusions:

Inpatient incidence and mortality for PCI-related GIB has been increasing particularly with a large increase in incidence among older patients. A multidisciplinary approach focused on risk-stratifying patients may improve preventable causes of GIB.
Liquid Nitrogen Spray Cryotherapy is Associated With Less Postprocedural Pain Than Radiofrequency Ablation in Barrett’s Esophagus
Authors: Solomon Sanjeev S. , Kothari Shivangi , Smallfield George B. , Inamdar Sumant , Stein Peter , Rodriguez Viviana A. , Sima Adam P. , Bittner Krystle , Zfass Alvin M. , Kaul Vivek , Trindade Arvind J.
Published: January 2018

Goals and Background:

Two common endoscopic therapies for eradication of dysplastic Barrett’s esophagus are radiofrequency ablation (RFA) and liquid nitrogen spray cryotherapy (LNC). There is no data comparing postprocedural pain. This study aimed to compare the incidence of postprocedural pain between the 2 ablation modalities.

Methods:

This is a multicenter prospective study in which pain intensity scores and the presence of dysphagia were assessed immediately before and after treatment, 48 hours posttreatment and at 3 weeks posttreatment using validated instruments.

Results:

Of 94 patients, 35 underwent LNC and 59 underwent RFA [36 with focal radiofrequency ablation (RFA-F) and 23 with circumferential radiofrequency ablation (RFA-C)]. Immediately posttreatment, patients in the LNC group reported an average Numeric Pain Scale score that was lower than in the RFA groups [LNC 0.41 vs. RFA-F 1.18 (P=0.026), LNC 0.41 vs. RFA-C 1.38 (P=0.010)]. These differences persisted at 48 hours posttreatment [LNC 0.76 vs. RFA-F 1.77 (P=0.013), LNC 0.76 vs. RFA-C 1.73 (P=0.018)]. The odds of pain after RFA were at least 5 times greater than after LNC [immediately posttreatment odds ratio, 5.26 (95% confidence interval, 1.85-14.29) and 48 h posttreatment odds ratio, 5.56 (95% confidence interval, 2.27-14.29)]. There was no difference in dysphagia after treatment in either group, at any time point (P=0.429).

Conclusion:

LNC was associated with less postprocedural pain when compared with RFA. These results help inform patients and physicians about the expected symptoms after ablative endotherapy.
Obesity and Pancreatic Cancer
Authors: Xu Mu , Jung Xiaoman , Hines O. Joe , Eibl Guido , Chen Yijun
Published: January 2018

Currently, there are no effective preventive strategies for pancreatic cancer. Obesity has been increasingly recognized as a strong but modifiable risk factor of pancreatic cancer. In this article, we aim to review the literature regarding weight loss on prevention of pancreatic cancer. Epidemiological and laboratory studies have shown that obesity is associated with increased incidence of pancreatic cancer and potentially worse cancer outcome. Whereas the underlying pathomechanisms remain unclear, chronic inflammation, insulin resistance, and altered intestinal microbiota are all implicated in the carcinogenic effect of obesity. Weight loss, especially the durable and significant weight loss after bariatric surgery, has been shown to reduce the risks of multiple cancers and may become a good intervention for pancreatic cancer prevention.
A Qualitative Study of Multidisciplinary Providers' Experiences With the Transfer Process for Injured Children and Ideas for Improvement
Authors: Gawel Marcie , Emerson Beth , Giuliano John S. , Rosenberg Alana , Minges Karl E. , Feder Shelli , Violano Pina , Morrell Patricia , Petersen Judy , Christison-Lagay Emily , Auerbach Marc
Published: January 2018

Objective

Most injured children initially present to a community hospital, and many will require transfer to a regional pediatric trauma center. The purpose of this study was 1) to explore multidisciplinary providers' experiences with the process of transferring injured children and 2) to describe proposed ideas for process improvement.

Methods

This qualitative study involved 26 semistructured interviews. Subjects were recruited from 6 community hospital emergency departments and the trauma and transport teams of a level I pediatric trauma center in New Haven, Conn. Participants (n = 34) included interprofessional providers from sending facilities, transport teams, and receiving facilities. Using the constant comparative method, a multidisciplinary team coded transcripts and collectively refined codes to generate recurrent themes across interviews until theoretical saturation was achieved.

Results

Participants reported that the transfer process for injured children is complex, stressful, and necessitates collaboration. The transfer process was perceived to involve numerous interrelated components, including professions, disciplines, and institutions. The 5 themes identified as areas to improve this transfer process included 1) Creation of a unified standard operating procedure that crosses institutions/teams, 2) Enhancing "shared sense making" of all providers, 3) Improving provider confidence, expertise, and skills in caring for pediatric trauma transfer cases, 4) Addressing organization and environmental factors that may impede/delay transfer, and 5) Fostering institutional and personal relationships.

Conclusions

Efforts to improve the transfer process for injured children should be guided by the experiences of and input from multidisciplinary frontline emergency providers.
Premorbid Activity Limitation Stages Are Associated With Posthospitalization Discharge Disposition
Authors: Na Ling , Hennessy Sean , Xie Dawei , Saliba Debra , Pan Qiang , Kwong Pui L. , Kurichi Jibby E. , Bogner Hillary R. , Streim Joel E.
Published: January 2018

Objective

Activity of daily living stages and instrumental activity of daily living stage have demonstrated associations with mortality and health service use among older adults. This cohort study aims to assess the associations of premorbid activity limitation stages with acute hospital discharge disposition among community-dwelling older adults.

Design

Study participants were Medicare beneficiaries aged 65 yrs or older who enrolled in the Medicare Current Beneficiary Survey between 2001 and 2009. Associations of premorbid stages with discharge dispositions were estimated with multinomial logistic regression models adjusted for covariates.

Results

The proportions of elderly Medicare patients discharged to home with self-care, home with services, postacute care facilities, and other dispositions were 59%, 15%, 19%, and 7%, respectively. The following adjusted relative risk ratios and 95% confidence intervals of postacute care facilities versus home with self-care discharge increased with higher premorbid activity limitation stages (except nonfitting stage III): 1.7 (1.5–2.0), 2.4 (2.0–2.9), 2.4 (1.9–3.0), and 2.5 (1.6–4.1) for activity of daily living stages I–IV; a similar pattern was found for instrumental activity of daily living stages. The adjusted relative risk ratios of discharge to home with services also increased with higher premorbid activity limitation stages compared with no limitation.

Conclusions

Routinely assessed activity limitation stages predict posthospitalization discharge disposition among older adults and may be used to anticipate postacute care and services use by elderly Medicare beneficiaries.
Development and implementation of multilocus sequence typing to study the diversity of the yeast Kluyveromyces marxianus in Italian cheeses
Authors: Tittarelli Fabrizia , Varela Javier A. , Gethins Loughlin , Stanton Catherine , Ross R.P. , Suzzi Giovanna , Grazia Luigi , Tofalo Rosanna , Morrissey John P.
Published: January 2018

The yeast Kluyveromyces marxianus possesses advantageous traits like rapid growth, GRAS (generally regarded as safe) status and thermotolerance that make it very suitable for diverse biotechnological applications. Although physiological studies demonstrate wide phenotypic variation within the species, there is only limited information available on the genetic diversity of K. marxianus. The aim of this work was to develop a multilocus sequence typing (MLST) method for K. marxianus to improve strain classification and selection. Analysis of housekeeping genes in a number of sequenced strains led to the selection of five genes, IPP1, TFC1, GPH1, GSY2 and SGA1, with sufficient polymorphic sites to allow MLST analysis. These loci were sequenced in an additional 76 strains and used to develop the MLST. This revealed wide diversity in the species and separation of the culture collection and wild strains into multiple distinct clades. Two subsets of strains that shared sources of origin were subjected to MLST and split decomposition analysis. The latter revealed evidence of recombination, indicating that this yeast undergoes mating in the wild. A public access web-based portal was established to allow expansion of the database and application of MLST to additional K. marxianus strains. This will aid understanding of the genetic diversity of the yeast and facilitate biotechnological exploitation.
HOTAIR ancient sequence suggests regulatory roles both in cis and trans
Authors: Nepal Chirag , Hadzheiv Yavor , Pundhir Sachin , Mydel Piotr , Lenhard Boris , Müeller Ferenc , Andersen Jesper B
Published: January 2018

HOTAIRis a long noncoding RNA transcribed betweenHOXC11andHOXC12in mammals. The proposed function(s) ofHOTAIRlacks consensus as to whether it regulates HoxD cluster genes intransor HoxC cluster genes incis. We have identified a 32-nucleotide long conserved noncoding element (CNE) asHOTAIRancient sequence which has a paralogous copy embedded inHOXD11noncoding transcript. All vertebrates except teleosts have two copies of CNE and the paralogous CNEs exhibit sequence complementarity in the transcribed orientation. Moreover, paralogous CNEs underwent compensatory mutations suggesting they co-evolved and might hybridize. In both human and mouse,HOTAIRCNE exhibits characteristic features of a poised enhancer inHOTAIR-unexpressed stem cells and of an active enhancer inHOTAIR-expressed cells. Tight correlation between the transcriptional activity of the CNE andHOTAIRpromoter suggestsHOTAIRtranscription is crucial for enhancer activity. InHOTAIR-expressed cells,HOTAIRexpression is positively correlated withHOXC11incisand negatively correlated withHOXD11intrans, suggesting a dual modality ofHOTAIRancient sequence.
Replication timing shapes the cancer epigenome and the nature of chromosomal rearrangements
Authors: Du Qian , Bert Saul A. , Armstrong Nicola J. , Caldon C. Elizabeth , Song Jenny Z. , Nair Shalima S. , Gould Cathryn M. , Luu Phuc Loi , Khoury Amanda , Qu Wenjia , Zotenko Elena , Stirzaker Clare , Clark Susan J.
Published: January 2018

Highlights

Replication timing alterations are conserved in cancers of different cell origins

Long-range epigenetic deregulation in cancer involves altered replication timing

Cancer late-replicating loci are hypomethylated and acquire facultative heterochromatin

Replication timing status potentiates cis and trans chromosomal rearrangements

Replication timing is known to facilitate the establishment of epigenome, however, the intimate connection between DNA replication timing and changes to the genome and epigenome in cancer remain uncharted. Here, we perform Repli-Seq and integrated epigenome analysis and show that early-replicating loci are predisposed to hypermethylation and late-replicating loci to hypomethylation, enrichment of H3K27me3 and concomitant loss of H3K9me3. We find that altered replication timing domains correspond to long-range epigenetically deregulated regions in prostate cancer, and a subset of these domains are remarkably conserved across cancers from different tissue origins. Analyses of 214 prostate and 35 breast cancer genomes reveal that late-replicating DNA is prone to cis and early-replicating DNA to trans chromosomal rearrangements. We propose that differences in epigenetic deregulation related to spatial and temporal positioning between early and late replication potentiate the landscape of chromosomal rearrangements in cancer.
Functional repurposing of regulatory element activity during mammalian evolution
Authors: Carelli Francesco N. , Liechti Angélica , Halbert Jean , Warnefors Maria , Kaessmann Henrik
Published: January 2018

The spatiotemporal control of gene expression exerted by promoters and enhancers is central for organismal development, physiology and behaviour. These two types of regulatory elements have long been distinguished from each other based on their function, but recent work highlighted common architectural and functional features. It also suggested that inheritable alterations in the epigenetic and sequence context of regulatory elements might underlie evolutionary changes of their principal activity, which could result in changes in the transcriptional profile of genes under their control or even facilitate the birth of new genes. Here, based on integrated cross-mammalian analyses of DNase hypersensitivity, chromatin modification and transcriptional data, we provide support for this hypothesis by detecting 449 regulatory elements with signatures of activity turnover in sister species from the primate and rodent lineages (termed “P/E” elements). Through the comparison with outgroup species, we defined the directionality of turnover events, which revealed that most instances represent transformations of ancestral enhancers into promoters, leading to the emergence of species-specific transcribed loci or 5’ exons. Notably, P/E elements have distinct GC sequence compositions and stabilizing 5’ splicing (U1) regulatory motif patterns, which may predispose them to functional repurposing during evolution. Moreover, we trace changes in the U1 and polyadenylation signal densities and distributions that accompanied and likely drove the evolutionary activity switches. Overall, our work suggests rather widespread evolutionary remodelling of regulatory element functions. Functional repurposing thus represents a notable mechanism that likely facilitated regulatory innovation and the origination of new genes and exons during mammalian evolution.
Large differences in small RNA composition between human biofluids
Authors: Godoy Paula M. , Bhakta Nirav R. , Barczak Andrea J. , Cakmak Hakan , Fisher Susan , Mackenzie Tippi C. , Patel Tushar , Price Richard W. , Smith James F. , Woodruff Prescott G. , Erle David J.
Published: January 2018

Extracellular miRNAs and other small RNAs are implicated in cellular communication and may be useful as disease biomarkers. We systematically compared small RNAs in 12 human biofluid types using RNA-seq. miRNAs and tRNA-derived RNAs (tDRs) accounted for the majority of mapped reads in all biofluids, but the ratio of miRNA to tDR reads varied from 72 in plasma to 0.004 in bile. miRNA levels were highly correlated across all biofluids but levels of some miRNAs differed markedly between biofluids. tDR populations differed extensively between biofluids. Y RNA fragments were seen in all biofluids and accounted for >10% of reads in blood plasma, serum, and CSF. Reads mapping exclusively to piRNAs were very rare except in seminal plasma. These results demonstrate extensive differences in small RNAs between human biofluids and provide a useful resource for investigating extracellular RNA biology and developing biomarkers.
Elimination of PCR duplicates in RNA-seq and small RNA-seq using unique molecular identifiers
Authors: Fu Yu , Wu Pei-Hsuan , Beane Timothy , Zamore Phillip D. , Weng Zhiping
Published: January 2018

RNA-seq and small RNA-seq are powerful, quantitative tools to study gene regulation and function. Common high-throughput sequencing methods rely on polymerase chain reaction (PCR) to expand the starting material, but not every molecule amplifies equally, causing some to be overrepresented. Unique molecular identifiers (UMIs) can be used to distinguish undesirable PCR duplicates derived from a single molecule and identical but biologically meaningful reads from different molecules. We have incorporated UMIs into RNA-seq and small RNA-seq protocols and developed tools to analyze the resulting data. Our UMIs contain stretches of random nucleotides whose lengths sufficiently capture diverse molecule species in both RNA-seq and small RNA-seq libraries generated from mouse testis. Our approach yields high-quality data while allowing unique tagging of all molecules in high-depth libraries. Using simulated and real datasets, we demonstrate that our methods increase the reproducibility of RNA-seq and small RNA-seq data. Notably, we find that the amount of starting material and sequencing depth, but not the number of PCR cycles, determine PCR duplicate frequency. Finally, we show that computational removal of PCR duplicates based only on their mapping coordinates introduces substantial bias into data analysis.
Molecular control of gene expression byBrucellaBaaR, an IclR-family repressor
Authors: Herrou Julien , Czyż Daniel M. , Fiebig Aretha , Willett Jonathan W. , Kim Youngchang , Wu Ruiying , Babnigg Gyorgy , Crosson Sean
Published: January 2018

TheBrucella abortusgeneral stress response sigma factor, σE1, directly and indirectly regulates the transcription of dozens of genes that influence stress survival and host infection. Characterizing the functions of σE1regulated genes therefore contributes to understanding ofB. abortusphysiology and infection biology. Transcription of the IclR family regulator, Bab2_0215, is indirectly activated by σE1but its function remains undefined. We present a structural and functional characterization of Bab2_0215, which we have namedBrucellaadipic acid activated regulator (BaaR). BaaR adopts a classic IclR-family fold and directly regulates the transcription of two operons with predicted roles in carboxylic acid oxidation. BaaR binds two sites on chromosome II between baaR and a divergently transcribed hydratase/dehydrogenase (acaD2), and represses transcription. We identified three carboxylic acids (adipic acid tetradecanedioic acid, ε-aminocaproic acid) and a lactone (ε-caprolactone) that enhance transcription from thebaaRandacaD2promoters. However, neither the activating acids nor caprolactone enhance transcription by binding directly to BaaR. Induction ofbaaRtranscription by adipic acid requires the genebab2_0213, which encodes a major facilitator superfamily transporter, suggesting that Bab2_0213 transports adipic acid across the inner membrane. We conclude that a set of structurally related organic molecules activate transcription of genes repressed by BaaR. Our study provides molecular-level understanding of a gene expression program regulated downstream of σE1.
Characterization and gas adsorption of a novel three-dimensional metal–organic framework (MOF) generated from a new polydentate fluorene-bridged ligand
Authors: Han Shu-Ying , Niu Xue , Wang Jia , Jin Guo-Xia , Liu Ai , Ma Jian-Ping
Published: January 2018

A polydentate ligand bridged by a fluorene group, namely 9,9-bis(2-hydroxyethyl)-2,7-bis(pyridin-4-yl)fluorene (L), has been prepared under solvothermal conditions in acetonitrile. Crystals of the three-dimensional metal–organic framework (MOF) poly[[[μ3-9,9-bis(2-hydroxyethyl)-2,7-bis(pyridin-4-yl)fluorene-κ3
N:N′:O]bis(methanol-κO)(μ-sulfato-κ2
O:O′)nickel(II)] methanol disolvate], {[Ni(SO4)(C27H24N2O2)(CH3OH)]·2CH3OH}
n
, (I), were obtained by the solvothermal reaction of L and NiSO4 in methanol. The ligand L forms a two-dimensional network in the crystallographic bc plane via two groups of O—H...N hydrogen bonds and neighbouring two-dimensional planes are completely parallel and stack to form a three-dimensional structure. In (I), the NiII ions are linked by sulfate ions through Ni—O bonds to form inorganic chains and these Ni-containing chains are linked into a three-dimensional framework via Ni—O and Ni—N bonds involving the polydentate ligand L. With one of the hydroxy groups of L coordinating to the NiII atom, the torsion angle of the hydroxyethyl group changes from that of the uncoordinated molecule. In addition, the adsorption properties of (I) with carbon dioxide were investigated.
Higher hydrates of lithium chloride, lithium bromide and lithium iodide
Authors: Sohr Julia , Schmidt Horst , Voigt Wolfgang
Published: January 2018

For lithium halides, LiX (X = Cl, Br and I), hydrates with a water content of 1, 2, 3 and 5 moles of water per formula unit are known as phases in aqueous solid–liquid equilibria. The crystal structures of the monohydrates of LiCl and LiBr are known, but no crystal structures have been reported so far for the higher hydrates, apart from LiI·3H2O. In this study, the crystal structures of the di- and trihydrates of lithium chloride, lithium bromide and lithium iodide, and the pentahydrates of lithium chloride and lithium bromide have been determined. In each hydrate, the lithium cation is coordinated octahedrally. The dihydrates crystallize in the NaCl·2H2O or NaI·2H2O type structure. Surprisingly, in the tri- and pentahydrates of LiCl and LiBr, one water molecule per Li+ ion remains uncoordinated. For LiI·3H2O, the LiClO4·3H2O structure type was confirmed and the H-atom positions have been fixed. The hydrogen-bond networks in the various structures are discussed in detail. Contrary to the monohydrates, the structures of the higher hydrates show no disorder.
To the letter vs the spirit
Authors: Heggen Campbell , Sridharan VG , Subramaniam Nava
Published: January 2018

Purpose

The purpose of this paper is to examine why firms governed by the same environmental management standards within an industry exhibit contrasting responses, with some adhering to the letter and others achieving the spirit behind the standards.

Design/methodology/approach

Using Arenaet al.(2010) as an analytical schema to examine the institutional dynamics behind such contrasting responses, the paper analyses archival and interview data relating to firm strategy, control technology and human expertise in two contrasting Australian forestry firms.

Findings

The embedding and decoupling of environmental standards with a firm’s environmental management practices is influenced, first, by the extent to which founder directors and senior management integrate environmental responsibility with the underlying business motives and, second, by the use of organisational beliefs and values systems to institutionalise the integrated strategic rationality throughout the firm. Finally, informed by the institutionalised strategic rationality, the participation and expertise of actors across the organisational hierarchy determine the level to which the design and execution of the eco-control technologies move beyond merely monitoring compliance, and act to facilitate continuous improvement, knowledge integration and organisational learning at the operational level.

Originality/value

This paper responds to institutional theorists’ call for a holistic explanation that considers the interactions among several intra-organisational factors to explain the dynamics behind why some firms decouple while others do not, even though the firms exist in the same social and regulatory context.
Blame game or dialogue? Financial, professional and democratic accountabilities in a complex health care setting
Authors: Pellinen Jukka , Mättö Toni , Sippola Kari , Rautiainen Antti
Published: January 2018

Purpose

The purpose of this paper is to investigate how the complexity of the network governance setting affects accountability practices. The authors pay particular attention to the organizational characteristics that may enable a common understanding of multiple accountability relationships, or lead to problems in reconciling competing forms of accountability, thereby appearing as blame game-type behavior.

Design/methodology/approach

The authors conducted a case study with 31 semi-structured interviews in a Finnish health care organization (FHC) that offers basic public health care services. The organization represents a co-operative arrangement with the main city and three smaller municipalities. The FHC has faced difficulties in balancing budget constraints with the provision of statutory care to citizens. This case is analyzed with the help of theories relating to accountability, the blame game, and dialogue.

Findings

The authors found that in the FHC operating under austerity constraints, attempts to reconcile financial, professional, and democratic accountability were made but, instead of dialogue and consensus, the different stakeholder groups resorted to defensive tactics in order to protect their resources, position, or sense of professional obligation. The authors suggest that in a context of network governance, accompanied by an increasing emphasis on financial accountability, organizational practices are susceptible to conflicting accountabilities and behavior characterized in this paper as a blame game.

Originality/value

The study contributes to the empirical studies on accountability in the new public governance context by analyzing the complex accountability relations between stakeholder groups with different agendas. The authors suggest organizational characteristics that may exacerbate conflicts between different stakeholder groups and prevent constructive dialogue. Furthermore, the study analyzes the composition of democratic accountability within the studied organization.
E-service usage and satisfaction in Botswana
Authors: Jaiyeoba Olumide Olasimbo , Chimbise Totwana Tito , Roberts-Lombard Mornay
Published: January 2018

Purpose

The purpose of this paper is to establish the level of usage of e-services (websites and e-mail) by Botswana Public Officers Medical Aid Scheme (BPOMAS) and PULA Medical Aid (PULA) customers; the level of satisfaction; perceived value; and benefits derived from the website and e-mail services.

Design/methodology/approach

In total, 200 BPOMAS members and 100 PULA members were sampled. Systematic sampling technique was used to select the participants. A questionnaire mainly guided by the E-S-QUAL and E-RecS-QUAL scales was designed to gain an in-depth understanding of customers’ perceptions and experiences of e-service quality.

Findings

It was established that there is a positive and significant relationship between the usage of e-services and benefits derived from e-services and between the usage of e-services and satisfaction. In addition, a nexus of relationship was observed between perceived value of the e-services and satisfaction.

Research limitations/implications

The management of healthcare services in Botswana needs to understand customers’ value perceptions of e-services and e-service quality in order to establish where to make the most of their efforts.

Practical implications

The managers of healthcare insurance providers should consider stepping up e-service usage and satisfaction levels, supported by client-centred training programmes, to assist clinicians deliver care to the expectation of patients.

Originality/value

There is an acute lack of research in the Botswana context, particularly into the link between e-service usage and satisfaction in the health insurance industry. This paper contributes to the extant literature by elucidating the nexus of relationship between e-service usage and satisfaction in Botswana.
Integrated FAHP-FPROMETHEE for thermal insulation of masonry buildings
Authors: Seddiki Mohammed , Anouche Karima , Bennadji Amar
Published: January 2018

Purpose

The need for the thermal insulation of masonry buildings in Algeria is no longer debated. This paper aims to propose an integrated fuzzy multi-criteria decision aid method for the thermal insulation of masonry buildings to rank the thermal insulation solutions.

Design/methodology/approach

The proposed method combines the fuzzy analytical hierarchy process with the fuzzy preference ranking organization method for enrichment evaluation.

Findings

A case study using the proposed method is detailed in this paper. The building users’ preferences obtained by the fuzzy analytical hierarchy process had a higher level of consistency and accuracy. The case study demonstrates how in a highly uncertain field such as thermal insulation of masonry buildings, the fuzzy preference ranking organization method for enrichment evaluation can prevent the loss of valuable evaluation data and overcome difficulty in integrating linguistic assessments of the thermal insulation alternatives.

Originality/value

The proposed method extends current knowledge by using the fuzzy analytical hierarchy process to consider uncertainties regarding the building users’ preferences, and the fuzzy preference ranking organization method for enrichment evaluation to get a complete ranking of the thermal insulation solutions taking into account the uncertainties related to the alternatives’ evaluations.
An efficient iterative algorithm for the natural convection equations based on finite element method
Authors: Wang Lei , Li Jian , Huang Pengzhan
Published: January 2018

Purpose

This paper aims to propose a new highly efficient iterative method based on classical Oseen iteration for the natural convection equations.

Design/methodology/approach

First, the authors solve the problem by the Oseen iterative scheme based on finite element method, then use the error correction strategy to control the error arising.

Findings

The new iterative method not only retains the advantage of the Oseen scheme but also saves computational time and iterative step for solving the considered problem.

Originality/value

In this work, the authors introduce a new iterative method to solve the natural convection equations. The new algorithm consists of the Oseen scheme and the error correction which can control the errors from the iterative step arising for solving the nonlinear problem. Comparing with the classical iterative method, the new scheme requires less iterations and is also capable of solving the natural convection problem at higher Rayleigh number.