bluuebunny/crossref_metadata_2025_split huggingface dataset:
Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System
Authors: Gao Rong , Godfrey Katherine A. , Sufian Mahir A. , Stock Ann M. 
Published: July 2017

ABSTRACT

Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the “memory” to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the
Escherichia coli
PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that “memory” of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions.

IMPORTANCE
Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal with such complexity. In this study, we examined the molecular “memory” that is generated by previous exposure to stimulus. Under our experimental conditions, activating effects of autoregulated two-component signaling and inhibitory effects of the stress response counterbalanced the transcriptional output to approach response homeostasis whether or not cells had been preexposed to stimulus. Modeling allows prediction of response behavior in different scenarios and demonstrates both the robustness of the system output and its sensitivity to historical parameters such as timing and levels of exposure to stimuli.
Methods, applications, interpretations and challenges of interrupted time series (ITS) data: protocol for a scoping review
Authors: Ewusie Joycelyne E , Blondal Erik , Soobiah Charlene , Beyene Joseph , Thabane Lehana , Straus Sharon E , Hamid Jemila S 
Published: July 2017

ObjectivesInterrupted time series (ITS) design involves collecting data across multiple time points before and after the implementation of an intervention to assess the effect of the intervention on an outcome. ITS designs have become increasingly common in recent times with frequent use in assessing impact of evidence implementation interventions. Several statistical methods are currently available for analysing data from ITS designs; however, there is a lack of guidance on which methods are optimal for different data types and on their implications in interpreting results. Our objective is to conduct a scoping review of existing methods for analysing ITS data, to summarise their characteristics and properties, as well as to examine how the results are reported. We also aim to identify gaps and methodological deficiencies.Methods and analysisWe will search electronic databases from inception until August 2016 (eg, MEDLINE and JSTOR). Two reviewers will independently screen titles, abstracts and full-text articles and complete the data abstraction. The anticipated outcome will be a summarised description of all the methods that have been used in analysing ITS data in health research, how those methods were applied, their strengths and limitations and the transparency of interpretation/reporting of the results. We will provide summary tables of the characteristics of the included studies. We will also describe the similarities and differences of the various methods.Ethics and disseminationEthical approval is not required for this study since we are just considering the methods used in the analysis and there will not be identifiable patient data. Results will be disseminated through open access peer-reviewed publications.
Environmental triggers of COPD symptoms: a case cross-over study
Authors: Sama Susan R , Kriebel David , Gore Rebecca J , DeVries Rebecca , Rosiello Richard 
Published: July 2017

IntroductionThis study investigated the hypothesis that common environmental chemical exposures with known irritant or sensitising properties trigger exacerbations for patients with chronic obstructive pulmonary disease (COPD).MethodsWe conducted a case cross-over study in 168 patients with COPD who were members of a disease management group in central Massachusetts. Participants completed a baseline health survey and several short exposure surveys. Exposure surveys were administered by a nurse when a participant telephoned to report an exacerbation (case periods) and at a maximum of three randomly identified control periods when they were not experiencing an exacerbation. We compared exposures in the week preceding an exacerbation with exposures in normal (non-exacerbation) weeks. The questionnaire assessed short-term (1 week) home, community and workplace activities and exposures that may be associated with COPD exacerbation.ResultsSelf-reported exercise was negatively associated with exacerbation (OR=0.59, 95% CI: 0.35 to 1.00). Among the environmental chemical exposures, car and truck exhaust (OR=4.36, 95% CI: 1.76 to 10.80) and use of scented laundry products (OR=2.69, 95% CI: 1.31 to 5.52) showed strong positive effects. Self-reported respiratory infections were strongly associated with exacerbation (OR=7.90, 95% CI 4.29 to 14.50). Variations in outdoor temperature were associated with COPD exacerbation risk (moderate versus cold temperature OR=1.95, 95% CI 1.09 to 3.49 and warm versus cold OR=0.43, 95% CI: 0.26 to 0.70).ConclusionsThese results suggest that some environmental chemical exposures may play a role in triggering COPD exacerbations. If confirmed, they may provide useful guidance for patients with COPD to better manage their disease.
Non-visualisation of strings after postplacental insertion of Copper-T 380A intrauterine device
Authors: Dewan Rupali , Dewan Abhinav , Singal Sunita , Bharti Rekha , Kaim Mansi 
Published: July 2017

AimTo assess the incidence of visible strings of intrauterine contraceptive devices (IUDs) after postplacental insertion following vaginal or caesarean delivery and to establish a management protocol of follow-up visits when strings are not visualised.MethodsThis was a prospective study of a cohort of 348 women who underwent postplacental insertion of Copper-T 380A IUDs following vaginal or caesarean delivery, conducted at a hospital in New Delhi, India. Women were followed up at 6 weeks, 3, 6 and 12 months after IUD insertion and were questioned about IUD expulsion or removal at each visit. The cervix was inspected to visualise the IUD strings. All women whose IUD strings could not be visualised at the cervical os at any given follow-up were identified. We analysed the cumulative incidence of visible strings and of procedures performed to locate the IUD when strings were not visible.ResultsAt 1 year follow-up, the IUD wasin situin 313/348 (89.9%) women. There were eight (2.3%) expulsions and 15 (4.3%) IUD removals. Among women with IUDsin situ, the strings were not visible in 73 (21%) cases. Pelvic ultrasound confirmed intrauterine position of the IUDs in these cases. At 1 year, string visibility was significantly lower after intra-caesarean insertions as compared to vaginal insertions (72.4% vs 98.1%;p<0.05).ConclusionsVisualisation of strings after postplacental vaginal insertion is more common than after intra-caesarean insertion. Pelvic ultrasonography can be used to verify the presence of the device in cases of missing strings.
Evaluation of Project Architecture in Software Development Mixing Waterfall and Agile by Using Process Simulation
Authors: Mitsuyuki Taiga , Hiekata Kazuo , Goto Takuya , Moser Bryan 
Published: July 2017

For software development, especially massive software systems, a waterfall process is used traditionally. A waterfall process can be highly effective on the condition that a master plan is fixed and the possibility of changes and uncertain rework is low. However, in software development projects, many kinds of reworks occur corresponding to uncertain requirement changes and program bugs. In addition, with the advent of cloud-based software platforms and continuous development operations, it is possible to develop a software system while operating the system. To respond to this situation, software development projects often adopt an agile process. Agility may allow conditional response to uncertain rework, yet at the same time it may be difficult to control the achievement of known project targets. Recently, many cases of adopting mixed processes including waterfall and agile have been reported in the massive software development projects. In this paper, we argue that the mixed process architecture should be designed, considering the scale of the targeted software project, the culture of organization, the probability of uncertain requirement changes, and so on. This paper proposes a methodology of evaluating the impact of waterfall, agile, and mixed project architectures by using process simulation. A project architectural approach is evaluated with a simulator which includes a software reliability growth model and uncertain rework driven by requirement change and error propagation. The proposed methodology was applied to a development project for a simple shopping website. The results showed that the proposed methodology allows exploration of partial agile adoption depending on the nature of the system development project, including its scale and chances of change. For example, in this paper, if the scale of the project is small, the positive effect of increasing agility by adopting agile processes is low. On the other hand, if the scale of the project is large, the effect of increasing agility by adopting agile process can increase. Furthermore, it became clear that it is important to not apply an agile process blindly, but instead to design a mixed project architecture considering the number of errors and development schedule targets across the project scope.
Unlocking 4D seismic technology to maximize recovery from the pre-salt Rotliegend gas fields of the Southern North Sea
Authors: Brain Jonathan , Lassaigne Thomas , Darnet Mathieu , Van Loevezijn Peter 
Published: July 2017

Abstract
The Southern North Sea is a mature gas basin, producing mainly from faulted Permian Rotliegend sandstones. Identifying infill well opportunities in un-depleted or partially depleted blocks in these fields is challenging, particularly if the sealing capacity of faults within a field is uncertain. Time-lapse (4D) seismic monitoring provides an opportunity to identify depleted reservoir blocks by measuring differences in travel time across the producing interval between seismic surveys acquired before and after gas production. 4D seismic field tests were initially performed by Nederlandse Aardolie Maatschappij (NAM) and Shell in 2001. However, the observed travel-time differences proved to be smaller than predicted and any possible signals were too noisy to confidently detect depletion. Since then, advances in seismic acquisition and processing technology have improved the accuracy of 4D measurements and enabled the effective mapping of 4D related gas depletion signals. 4D seismic has now been deployed over a number of fields in the Southern North Sea, and a portfolio of infill opportunities has been identified. In 2015, the first 4D targeted infill well was successfully drilled into a block with limited depletion. This technology represents a breakthrough for operators seeking to maximize hydrocarbon recovery and extend field life in the Rotliegend play of the Southern North Sea.
TP53INP1 Downregulation Activates a p73-Dependent DUSP10/ERK Signaling Pathway to Promote Metastasis of Hepatocellular Carcinoma
Authors: Ng Kai-Yu , Chan Lok-Hei , Chai Stella , Tong Man , Guan Xin-Yuan , Lee Nikki P , Yuan Yunfei , Xie Dan , Lee Terence K , Dusetti Nelson J , Carrier Alice , Ma Stephanie 
Published: July 2017

Abstract
Identifying critical factors involved in the metastatic progression of hepatocellular carcinoma (HCC) may offer important therapeutic opportunities. Here, we report that the proapoptotic stress response factor TP53INP1 is often selectively downregulated in advanced stage IV and metastatic human HCC tumors. Mechanistic investigations revealed that TP53INP1 downregulation in early-stage HCC cells promoted metastasis via DUSP10 phosphatase-mediated activation of the ERK pathway. The DUSP10 promoter included putative binding sites for p73 directly implicated in modulation by TP53INP1. Overall, our findings show how TP53INP1 plays a critical role in limiting the progression of early-stage HCC, with implications for developing new therapeutic strategies to attack metastatic HCC. Cancer Res; 77(17); 4602–12. ©2017 AACR.
Combining Local Immunotoxins Targeting Mesothelin with CTLA-4 Blockade Synergistically Eradicates Murine Cancer by Promoting Anticancer Immunity
Authors: Leshem Yasmin , O'Brien James , Liu Xiufen , Bera Tapan K. , Terabe Masaki , Berzofsky Jay A. , Bossenmaier Birgit , Niederfellner Gerhard , Tai Chin-Hsien , Reiter Yoram , Pastan Ira 
Published: July 2017

Abstract
Immune checkpoint blockade using antibodies to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) benefits a limited number of cancer patients. SS1P and LMB-100 are immunotoxins that target mesothelin. We observed delayed responses to SS1P in patients with mesothelioma suggesting that antitumor immunity was induced. Our goal was to stimulate antitumor immunity by combining SS1P or LMB-100 with anti–CTLA-4. We constructed a BALB/c breast cancer cell line expressing human mesothelin (66C14-M), which was implanted in one or two locations. SS1P or LMB-100 was injected directly into established tumors and anti–CTLA-4 administered i.p. In mice with two tumors, one tumor was injected with immunotoxin and the other was not. The complete regression rate was 86% for the injected tumors and 53% for the uninjetced tumors. No complete regressions occurred when drugs were given separately. In regressing tumors, dying and dead tumor cells were intermingled with PMNs and surrounded by a collar of admixed eosinophils and mononuclear cells. Tumor regression was associated with increased numbers of tumor-infiltrating CD8+ cells and blocked by administration of antibodies to CD8. Surviving mice were protected from tumor rechallenge by 66C14 cells not expressing mesothelin, indicating the development of antitumor immunity. The antitumor effect was abolished when a mutant noncytotoxic variant was used instead of LMB-100, showing that the antitumor response is not mediated by recognition of a foreign bacterial protein. Our findings support developing a therapy composed of immunotoxins and checkpoint inhibitors for patients. Cancer Immunol Res; 5(8); 685–94. ©2017 AACR.
ДОСЛІДЖЕННЯ АНАТОМІЧНОЇ БУДОВИ ПІДЗЕМНИХ ОРГАНІВ РОДОВИКА ЛІКАРСЬКОГО (SANGUISORBA OFFICINALIS L. )
Authors: Kudrya V. V. , Marchyshyn S. M. , Sira L. M. , Rudenko V. P. , Dakhym I. S. 
Published: July 2017

Мета роботи. Родовик лікарський (Sanguisorba о№ сіпаіів L.) - багаторічна трав’яниста рослина, підземні органи якої здавна використовують у медицині як в'яжучий і кровоспинний засіб. Офіційною медициною використовуються препарати родовика лікарського з кореневища з коренями. У наукових джерелах недостатньо інформації про фармакогностичне вивчення підземних органів родовика лікарського, тому метою нашої роботи було вивчити анатомічну будову, встановити і зіставити діагностичні ознаки кореневищ і коренів, зібраних восени на першому і другому роках вегетації даного виду.Матеріали і методи. Виготовлення мікропрепаратів проводили за загальноприйнятими методами. Використовували мікроскоп МС 10 (окуляри Х5, Х10, 15, об’єктиви Х10, Х40). Мікрофотографії зроблені фотокамерою Sаmsung PL50.Результати й обговорення. Кореневище. Підземна частина родовика лікарського представлена багаторічним епігеогенним кореневищем з придатковими коренями. Кореневище поступово дерев’яніє, стає пухким, порожнистим у центрі. Анатомічна будова кореневища безпучкова. Молоді однорічні кореневища вкриті темно-бурим, поздовжньо зморшкуватим корком. У особин другого року вегетації клітини корка ущільнюються, починають злущуватись. Первинна кора однорічних кореневищ представлена шарами крупноклітинної паренхіми. Ксилема і флоема паренхіматизовані, пронизані розширеними радіальними серцевинними променями. В клітинах накопичуються прості і складні крохмальні зерна, часто зустрічаються друзи. Помітно виділяється щільне кільце камбію. Провідна система представлена судинами. Механічні волокна розташовані відокремлено, невеликими ділянками поблизу судин або утворюють суцільне кільце поряд з камбієм. Серцевина з міжклітинниками, паренхімні клітини з крохмальними зернами і друзами кальцій оксалату. Корені мають вторинну будову. Корок шаруватий, кільця з коричневим або жовтуватим вмістом чергуються з кільцями світлішими або безбарвними. Зона камбію багатошарова, темніша, добре помітна. Ксилема промениста. Трахеїди пористі. Серцевинних променів багато. У клітинах наявні дрібні прості овальні та округлі крохмальні зерна, друзи та поодинокі призматичні або багатогранні кристали кальцію оксалату. У дворічних коренів зовнішній шар корка товстий, темно-коричневий, з тріщинами; чітко виділяються річні кільця ксилеми, серцевинних променів багато, волокна лубу чисельні, здерев’янілі.Висновки. Досліджено анатомічну будову підземних органів родовика лікарського, зібраних на першому і другому роках вегетації. Виявлено мікроскопічні діагностичні ознаки кореневищ і коренів.
Left Ventricular Assist Device Malfunctions
Authors: Kormos Robert L. , McCall Michael , Althouse Andrew , Lagazzi Luigi , Schaub Richard , Kormos Michael A. , Zaldonis Jared A. , Sciortino Christopher , Lockard Kathleen , Kuntz Nicole , Dunn Elizabeth , Teuteberg Jeffrey J. 
Published: July 2017

Background:
Reports of left ventricular assist device (LVAD) malfunction have focused on pump thrombosis. However, the device consists of the pump, driveline, and peripherals, all of which are potentially subject to failure.

Methods:
Prospectively collected data were reviewed for all LVAD device malfunctions (DMs) occurring in rotary LVADs implanted at a single center between April 2004 and May 2016. Durable LVADs included 108 Heartmate II (HM II) and 105 HeartWare VAD (HVAD). DM data were categorized according to device type and into categories related to the component that failed: (1) controller, (2) peripheral components, and (3) implantable blood pump or its integral electric driveline. Pump-related events were analyzed as pump-specific (suspected or confirmed thrombosis) or nonpump-specific (driveline failure). DM rates were reported as events per 1000 patient-days, and Cox proportional hazard models were used for time-to-event analyses. Cumulative rates of malfunction were examined for the main components of each type of LVAD.

Results:

Types of DM included controller failure (30%), battery failure (19%), or patient cable failure (14%), whereas only 13% were because of pump failure. DMs were more common in the HM II device (3.73 per 1000 patient-days versus 3.06 per 1000 patient-days for the HVAD,
P
<0.01). A higher rate of pump-specific malfunctions was discovered in those implanted with an HM II versus an HVAD (0.55 versus 0.39, respectively;
P
<0.01) and peripheral malfunctions (2.32 versus 1.78 for the HM II and HVAD, respectively;
P
<0.01); no difference occurred in the incidence of controller DM between the 2 LVADs. Patients with HVAD were 90% free of a pump-specific malfunction at 3 years compared with 56% for the HM II (log-rank
P
<0.003). Only 74% of the patients with HM II were free of pump thrombosis at 3 years compared with 90% of the patients with HVAD. Freedom from failure of the integrated driveline was 79% at 3 years for the HM II but 100% for the HVAD (log-rank
P
<0.02).

Conclusions:
Device malfunction is much broader than pump failure alone and occurs for different components at different rates based on the type of LVAD.
Implications of American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Guidelines on Statin Underutilization for Prevention of Cardiovascular Disease in Diabetes Mellitus Among Several US Networks of Community Health Centers
Authors: Akhabue Ehimare , Rittner Sarah S. , Carroll Joseph E. , Crawford Phillip M. , Dant Lydia , Laws Reesa , Leo Michael C. , Puro Jon , Persell Stephen D. 
Published: July 2017

Background

Little is known about statin underutilization among diabetes mellitus patients cared for in community health centers, which tend to serve socioeconomically disadvantaged populations. Implications of the American College of Cardiology/American Heart Association (
ACC
/
AHA
) guidelines on preexisting gaps in statin treatment in this population are unclear.

Methods and Results

We included 32 440 adults (45% male, 63% nonwhite, 29% uninsured/Medicaid) aged 40 to 75 years with diabetes mellitus who received care within 16 community health center groups in 11 states in the Community Health Applied Research Network during 2013. Statin prescribing was analyzed as a function of concordance with the National Cholesterol Education Program Adult Treatment Panel 2001 and
ACC
/
AHA
2013 guidelines. More patients’ treatments were concordant with the
ACC
/
AHA
(52.8%) versus the National Cholesterol Education Program Adult Treatment Panel (36.2%) guideline. Female sex was associated with lower concordance for both (odds ratio [
OR
] 0.90,
CI
0.85‐0.94; and
OR
0.84,
CI
0.80‐0.88, respectively). Being insured, an Asian/Pacific Islander, or primarily Spanish speaking were associated with greater concordance for both guidelines: 35.5% (11 526/32 440) were concordant with neither guideline, the majority (79.7%) having no statin prescribed; 28.2% (9168/32 440) were concordant with
ACC
/
AHA
but not the National Cholesterol Education Program Adult Treatment Panel. 8.7% of these patients had a low‐density lipoprotein cholesterol >160 mg/dL despite having a moderate‐ or high‐intensity statin prescribed. And 11.6% (3772/32 440) were concordant with the National Cholesterol Education Program Adult Treatment Panel but not with
ACC
/
AHA
. Most of these patients had a low‐density lipoprotein cholesterol between 70 and 99 mg/dL with no or a low‐intensity statin prescribed.

Conclusions
Opportunities exist to improve cholesterol management in diabetes mellitus patients in community health centers. Addressing care gaps could improve cardiovascular disease prevention in this high‐risk population.