bluuebunny/crossref_metadata_2025_split huggingface dataset:
H3K9me3 Inhibition Improves Memory, Promotes Spine Formation, and Increases BDNF Levels in the Aged Hippocampus
Authors: Snigdha Shikha , Prieto G. Aleph , Petrosyan Arpine , Loertscher Brad M. , Dieskau André P. , Overman Larry E. , Cotman Carl W. 
Published: March 2016

An increasing number of studies show that an altered epigenetic landscape may cause impairments in regulation of learning and memory-related genes within the aged hippocampus, eventually resulting in cognitive deficits in the aged brain. One such epigenetic repressive mark is trimethylation of H3K9 (H3K9me3), which is typically implicated in gene silencing. Here, we identify, for the first time, an essential role for H3K9me3 and its histone methyl transferase (SUV39H1) in mediating hippocampal memory functions. Pharmacological inhibition of SUV39H1 using a novel and selective inhibitor decreased levels of H3K9me3 in the hippocampus of aged mice, and improved performance in the objection location memory and fear conditioning tasks and in a complex spatial environment learning task. The inhibition of SUV39H1 induced an increase in spine density of thin and stubby but not mushroom spines in the hippocampus of aged animals and increased surface GluR1 levels in hippocampal synaptosomes, a key index of spine plasticity. Furthermore, there were changes at BDNF exon I gene promoter, in concert with overall BDNF levels in the hippocampus of drug-treated animals compared with control animals. Together, these data demonstrate that SUV39H1 inhibition and the concomitant H3K9me3 downregulation mediate gene transcription in the hippocampus and reverse age-dependent deficits in hippocampal memory.SIGNIFICANCE STATEMENTCognitive decline is a debilitating condition associated with not only neurodegenerative diseases but also aging in general. However, effective treatments have been slow to emerge so far. In this study, we demonstrate that epigenetic regulation of key synaptic proteins may be an underlying, yet reversible, cause of this decline. Our findings suggest that histone 3 trimethylation is a probable target for pharmacological intervention that can counteract cognitive decline in the aging brain. Finally, we provide support to the hypothesis that, by manipulating the enzyme that regulates H3K9me3 (using a newly developed specific inhibitor of SUV39H1), it is possible to alter the chromatin state of subjects and restore memory and synaptic function in the aging brain.
Reconstitution of Giant Mammalian Synapses in Culture for Molecular Functional and Imaging Studies
Authors: Dimitrov Dimitar , Takagi Hiroshi , Guillaud Laurent , Saitoh Naoto , Eguchi Kohgaku , Takahashi Tomoyuki 
Published: March 2016

Giant presynaptic terminal brain slice preparations have allowed intracellular recording of electrical signals and molecular loading, elucidating cellular and molecular mechanisms underlying neurotransmission and modulation. However, molecular genetic manipulation or optical imaging in these preparations is hampered by factors, such as tissue longevity and background fluorescence. To overcome these difficulties, we developed a giant presynaptic terminal culture preparation, which allows genetic manipulation and enables optical measurements of synaptic vesicle dynamics, simultaneously with presynaptic electrical signal recordings. This giant synapse reconstructed from dissociated mouse brainstem neurons resembles the development of native calyceal giant synapses in several respects. Thus, this novel preparation constitutes a powerful tool for studying molecular mechanisms of neurotransmission, neuromodulation, and neuronal development.SIGNIFICANCE STATEMENTWe have developed a novel culture preparation of giant mammalian synapses. These presynaptic terminals make it possible to perform optical imaging simultaneously with presynaptic electrophysiological recording. We demonstrate that this enables one to dissect endocytic and acidification times of synaptic vesicles. In addition, developmental elimination and functional maturation in this cultured preparation provide a useful model for studying presynaptic development. Because this giant synapse preparation allows molecular genetic manipulations, it constitutes a powerful new tool for studying molecular mechanisms of neurotransmission, neuromodulation, and neuronal development.
When Is Selection Effective?
Authors: Gravel Simon 
Published: March 2016

Abstract
Deleterious alleles can reach high frequency in small populations because of random fluctuations in allele frequency. This may lead, over time, to reduced average fitness. In this sense, selection is more “effective” in larger populations. Recent studies have considered whether the different demographic histories across human populations have resulted in differences in the number, distribution, and severity of deleterious variants, leading to an animated debate. This article first seeks to clarify some terms of the debate by identifying differences in definitions and assumptions used in recent studies. We argue that variants of Morton, Crow, and Muller’s “total mutational damage” provide the soundest and most practical basis for such comparisons. Using simulations, analytical calculations, and 1000 Genomes Project data, we provide an intuitive and quantitative explanation for the observed similarity in genetic load across populations. We show that recent demography has likely modulated the effect of selection and still affects it, but the net result of the accumulated differences is small. Direct observation of differential efficacy of selection for specific allele classes is nevertheless possible with contemporary data sets. By contrast, identifying average genome-wide differences in the efficacy of selection across populations will require many modeling assumptions and is unlikely to provide much biological insight about human populations.
Dynamic Secure Interconnection for Security Enhancement in Cloud Computing
Authors: He Liwen , Huang Feiyi , Zhang Jie , Liu Bin , Chen Chunling , Zhang Zonghua , Yang Yang , Lu Weifeng 
Published: March 2016

Cloud computing brings efficiency improvement on resource utilization nd other benefits such as on-demand service provisioning, location independence and biquitous access, elastic resource pooling, pay as usage pricing mode, etc. However, t also introduces new security issues because the data management and ownership re separated, and the management is operated on a virtualized platform. In this paper, novel dynamic secure interconnection (DSI) mechanism is proposed to isolate he cloud computing system into a couple of dynamic virtual trust zones with different ecurity policies implemented for different customers so as to enhance security. xperimental results are presented to demonstrate the feasibility and effectiveness of he DSI mechanism.
Patient-Reported Outcomes and Early Discontinuation in Aromatase Inhibitor-Treated Postmenopausal Women With Early Stage Breast Cancer
Authors: Kadakia Kunal C. , Snyder Claire F. , Kidwell Kelley M. , Seewald Nicholas J. , Flockhart David A. , Skaar Todd C. , Desta Zereunesay , Rae James M. , Otte Julie L. , Carpenter Janet S. , Storniolo Anna M. , Hayes Daniel F. , Stearns Vered , Henry N. Lynn 
Published: March 2016

Abstract

Background.
Early discontinuation of aromatase inhibitors (AIs) is common and leads to poor outcomes but is challenging to predict. In the Exemestane and Letrozole Pharmacogenetics trial, a high rate of early discontinuation due to intolerance was observed. We hypothesized that early changes in patient-reported outcomes (PROs) predict AI discontinuation and that biochemical factors are associated with changes in PROs.

Patients and Methods.
Postmenopausal women with early-stage breast cancer enrolled in a prospective randomized trial of exemestane versus letrozole completed questionnaires at baseline and serially over 24 months to assess overall quality of life (EuroQOL Visual Analog Scale [VAS]); mood; and multiple symptoms, including a musculoskeletal symptom cluster. A joint mixed-effects/survival model was used to estimate the effect of the change in PROs on AI discontinuation. Associations between biochemical factors and change in PROs were examined.

Results.
A total of 490 patients were analyzed. Worsening of EuroQOL VAS and the musculoskeletal cluster were associated with the highest risk for early discontinuation (hazard ratio [HR], 2.77 [95% confidence interval (CI), 2.72–2.81; p = .015]; HR, 4.39 [95% CI, 2.40–8.02; p &lt; .0001], respectively). Pharmacokinetics and estrogen metabolism were not consistently associated with change in PRO measures. No clinically significant differences in any PRO between AIs were observed.

Conclusion.
Changes in PROs early during AI therapy were associated with treatment discontinuation. Identification of these changes could be used to target interventions in patients at high risk for early discontinuation.
The Impact of Mismatch Repair Status in Colorectal Cancer on the Decision to Treat With Adjuvant Chemotherapy: An Australian Population-Based Multicenter Study
Authors: He Emily Y. , Hawkins Nicholas J. , Mak Gabriel , Roncolato Felicia , Goldstein David , Liauw Winston , Clingan Philip , Chin Melvin , Ward Robyn L. 
Published: March 2016

Abstract

Background.
Testing for mismatch repair (MMR) status in colorectal cancer (CRC) may provide useful prognostic and predictive information. We evaluated the impact of such testing on real-world practice regarding adjuvant chemotherapy for patients with resected CRC.

Patients and Methods.
A total of 175 patients with stage II and III mismatch repair-deficient (MMRD) CRC were identified from an Australian population-based study of incident CRCs. Their treatment decisions were compared with those for a cohort of 773 stage-matched patients with mismatch repair-proficient (MMRP) CRCs. The effect of MMR status, age, and pathologic characteristics on treatment decisions was determined using multiple regression analysis.

Results.
Overall, 32% of patients in stage II and 71% of patients in stage III received adjuvant chemotherapy. Among the stage II patients, those with MMRD cancer were less likely to receive chemotherapy than were MMRP cases (15% vs. 38%; p &lt; .0001). In this group, the treatment decision was influenced by age, tumor location, and T stage. MMR status influenced the treatment decision such that its impact diminished with increasing patient age. Among patients with stage III tumors, no difference was found in the chemotherapy rates between the MMRD and MMRP cases. In this group, age was the only significant predictor of the treatment decision.

Conclusion.
The findings of this study suggest that knowledge of the MMR status of sporadic CRC influences treatment decisions for stage II patients, in an era when clear recommendations as to how these findings should influence practice are lacking.
LESS COMMON PATTERNS WITH INTENSIFIERS ‘TOO’ AND ‘VERY IN THE CORPUS OF INUGURAL ADDRESSES OF US PRESIDENTS
Authors: Prihantoro Prihantoro 
Published: March 2016

AbstractThis paper studies “very” and “too”, two intensifiers used in the corpus of inaugural address of all US presidents, from Washington to Obama. My aims here is to identify uncommon pattern with “too” and “very”, and the semantic prosodies as well. I downloaded the data and processed it as a corpus by using a corpus tookit called AntConc (Anthony, 2006). I used the query “very” and “too” to obtain concordances. A shared feature of these intensifiers is they mostly modify adjectives as shown by frequency. Although less significant in terms of frequency, some common patterns are discovered, such as “very + N” and “very + AdjSuperlative + N” construction, which are attested in COCA. One that is against prescriptive grammar is <a + too + Adj + N”, where the suggested construction is usually “too + Adj + a + N”. As for the semantic prosody, I found some data attested in COCA, where “too” can be used to intensify positive evaluation, which is contrary to Azar (2002) and some other grammar books. As for very, it is more flexible that the prosodies might either be positive or negative. The result of COCA and BNC has shown that these structures are uncommon. I argue that these structures are used under the markedness frame, to make listeners focus on issues that the speakers wanted to empahasize.Keywords: very, too, intensifiers, semantic prosody, inaugural address, corpus AbstrakArtikel ini menyelidiki "very" dan "too", dua pengintensif yang ditemukan dalam korpus pidato pelantikan semua presiden AS, dari Washington sampai Obama. Tujuan artikel ini adalah untuk mengidentifikasi pola tidak biasa dengan kata "very" dan "too", dan prosodi semantiknya. Saya mengunduh data pidato dan diproses sebagai korpus dengan menggunakan perangkat korpus yang disebut AntConc (Anthony, 2006). Saya menggunakan query "very" dan "too" untuk mendapatkan konkordansi. Fitur yang ditemukan dari kedua pengintensif ini adalah keduanya kebanyakan memodifikasi kata sifat seperti yang ditunjukkan oleh frekuensi. Meskipun kurang signifikan dalam hal frekuensi, beberapa pola umum ditemukan, seperti konstruksi "very+ N" dan "too+ AdjSuperlatif + N", yang dibuktikan dalam COCA. Salah satu fitur yang bersebrangan dengan tata bahasa preskriptif adalah pola “a + too+ Adj + N ", sementara konstruksi yang biasa dipakai adalah " too+ Adj + a + N ". Adapun secara prosodi semantik, saya menemukan beberapa data yang dibuktikan di COCA, di mana "too" dapat juga digunakan untuk mengintensifkan penilaian positif, yang bertentangan dengan Azar (2002) dan beberapa buku tata bahasa lainnya. Sementara itu, kata “very” lebih fleksibel di mana prosodinya bisa positif atau negatif. Hasil COCA dan BNC menunjukkan bahwa struktur ini jarang ditemukan. Saya berpendapat bahwa struktur ini digunakan di bawah bingkai markedness, untuk membuat pendengar berfokus pada isu-isu yang ingin ditekankan penutur.Kata kunci: very, too, pengintensif, prosodi semantik, pidato pelantikan, korpus
NegotiatingWa(Harmony): A Qualitative Study About the Challenges Japanese Women Who Live in New Zealand Have in Maintaining Their Birth Traditions
Authors: Doering Keiko , Patterson Jean , Griffiths Christine 
Published: March 2016

Cultural birth customs play an important role in maintaining women’s psychological well-being throughout childbearing. The goals of this study were (a) to explore how Japanese women living in New Zealand keep or perform their birth traditions, (b) to educate caregivers about the importance of these traditions to Japanese women, and (c) to provide an environment within which Japanese women feel able to express and negotiate their cultural practices.Following ethical approval from the Otago Polytechnic Research Ethics Committee (ETHICS 470), 13 Japanese women, who had given birth in New Zealand within the previous 3 years, were interviewed individually, or in a focus group. Transcripts of the interviews were analyzed using thematic analysis. The women were all born in Japan, had moved to New Zealand in their 20s, and lived in New Zealand for a period between 2 and 19 years.The women valued their birth traditions and tried to practice these throughout their pregnancy and following birth. This was not always possible within the New Zealand maternity and cultural setting where there was a lack of support or understanding from family and care providers. There was also limited access to shrines where they could perform the rituals. This caused some of the women to experience cultural conflicts.The desire to maintain harmony with others and the environment is embedded in Japanese culture, and this made it difficult for the women in this study to express their need to fulfill these practices and rituals.Although this study focused on Japanese women’s attitudes and cultural practices, it highlights the importance of being able to maintain a woman’s cultural links, particularly around childbirth. It is essential for caregivers to understand that each woman brings her own cultural understandings and traditions to her birth experience and that the support to practice birth rituals contributes to her peace of mind and well-being.
Identificação e mitigação de riscos em projetos de desenvolvimento distribuído de software
Authors: Coelho Pedro Henrique Veras , Fenner Germano , Lima Alberto Sampaio 
Published: March 2016

Os mercados estão cada vez mais globalizados, gerando impactos em diversas áreas e provocando o surgimento de novas formas de competição e cooperação que ultrapassam os limites das fronteiras dos países. Nesse contexto, a área de desenvolvimento de software também foi afetada, impulsionando muitas organizações a experimentarem o desenvolvimento de software em instalações localizadas em vários países. Surgiu assim o desenvolvimento distribuído de software (DDS). O DDS apresenta diversos fatores de risco como a dispersão geográfica e problemas de comunicação. Embora existam diversas dificuldades enfrentadas pelas organizações que adotam o DDS, foi verificado que com medidas de mitigação dos riscos, as vantagens do DDS se sobrepõem as dificuldades e seu uso possibilita a redução de custos e aumento da competitividade das organizações. Foi realizada uma pesquisa bibliográfica e um estudo de caso, onde foram identificados os riscos mais comuns do DDS e as formas de tratá-los.
Management of Pipkin Type-III Femoral Head Fracture and Ipsilateral Open Floating Knee with Extensor Apparatus Injury
Authors: Singaravadivelu V. , Bassetty Keerthy Chandra , Balakrishnan T.M. , Lankaram J.J. 
Published: March 2016

Case:
A twenty-eight-year-old man presented with a Pipkin type-III femoral head fracture and open floating knee injury. Initially debridement was performed, during which the extensor apparatus could not be salvaged. The top priority in management of the floating knee was achievement of adequate soft-tissue coverage followed by skeletal stabilization as staged procedures. Because the femoral head was split, dislocated, comminuted, and deemed nonreconstructible, arthroplasty was considered the best option. The extensor mechanism damage was addressed by reconstruction using an iliotibial tract flap.

Conclusion:
This case report is presented for its uniqueness, the management protocol, and the difficulties encountered during the multistage treatment.
The Pratt Pouch Provides a Three-Fold Access Increase to Antiretroviral Medication for Births outside Health Facilities in Southern Zambia
Authors: Dahinten Alexander P. , Malkin Robert A. 
Published: March 2016

Introduction:
Modern day antiretroviral therapy allows HIV+ pregnant women to lower the likelihood of viral transmission to their infants before, during, and after birth from 20-45% to less than 5%. In developing countries, where non-facility births may outnumber facility births, infant access to safe antiretroviral medication during the critical first three days after birth is often limited. A single-dose, polyethylene pouch (“Pratt Pouch”) addresses this challenge by allowing the medication to be distributed to mothers during antenatal care.

Methods:
The Pratt Pouch was introduced as part of a one year clinical feasibility study in two districts in Southern Province, Zambia. Participating nurses, community health workers, and pharmacists were trained before implementation. Success in achieving improved antiretroviral medication access was assessed via pre intervention and post intervention survey responses by HIV+ mothers.

Results:
Access to medication for HIV-exposed infants born outside of a health facility increased from 35% (17/51) before the introduction of the pouch to 94% (15/16) after (p<0.05). A non-significant increase in homebirth rates from 33% (pre intervention cohort) to 50% (post intervention cohort) was observed (p>0.05). Results remained below the national average homebirth rate of 52%. Users reported minimal spillage and a high level of satisfaction with the Pratt Pouch.

Conclusion:
The Pratt Pouch enhances access to infant antiretroviral medication in a rural, non-facility birth setting. Wide scale implementation could have a substantial global impact on HIV transmission rates from mother to child.
Initial Results of an Acetabular Center Axis Registration Technique in Navigated Hip Arthroplasty with Deformed Acetabular Rims
Authors: Wada Hiroshi , Mishima Hajime , Yoshizawa Tomohiro , Sugaya Hisashi , Nishino Tomofumi , Yamazaki Masashi 
Published: March 2016

BackgroundIn cementless total hip arthroplasty, imageless computer-assisted navigation is usually used to register the anterior pelvic plane (APP). The accuracy of this method is influenced by the subcutaneous tissues overlying the registration landmarks. On the other hand, the acetabular center axis (ACA) is determined from the acetabular rim. Precise registration of the ACA is possible because of direct palpation using a pointer. Imageless navigation using the ACA usually targets patients with normal acetabular morphology. The aim of this study was to investigate the accuracy of imageless navigation using the ACA instead of the APP in patients with normal or deformed acetabular rims.MethodsThe intraoperative cup position was compared with that obtained from the postoperative computed tomography (CT) images in 18 cases.ResultsThe inclination angle derived from the navigation system was 3.4 ± 5.3 degrees smaller and the anteversion angle was 1.4 ± 3.1 degrees larger than those derived from the CT images.ConclusionThe inclination cup angle of the navigation system was significantly inferior to the true value, particularly in cases with large anterior osteophytes.
Facile fabrication, microstructure, and corrosion resistance of high-strength, high-hardness pure bulk aluminum
Authors: Yin Bing , Jin Kongjie , Yang Jun , Tang Huaguo , Qiao Zhuhui 
Published: March 2016

AbstractHigh-strength pure bulk aluminum was fabricated by mechanical alloying and press forming, and its electrochemical properties and corrosion behavior in 0.5 M NaCl solution were investigated by means of potentiodynamic polarization and electrochemical impedance spectroscopy. Microstructural characterizations revealed that in addition to a Vickers hardness of 144 HV, the refined grain (0.2–1 μm) enhanced tensile and yield strengths to 560 and 520 MPa, respectively. Electrochemical data demonstrated that pure Al exhibited higher corrosion resistance than its alloys AA5083 and AA2024. Ultrafine, compact structure and homogeneous composition ensured a dense film formation during passivation. Moreover, the defect-free passive film protects the substrate by providing a high barrier against the aggressive chloride ions.
Anticancer activity of midostaurin in hormone refractory human prostate cancer DU145 cells
Authors: Sun Jin-Jun , Kan Shi-Feng , Sun Guan-Xing 
Published: March 2016

<p class="Abstract">We tried a new method of prostate cancer treatment by inducing<em> in vitro</em> differentiation which resulted in reduction of cancer cells growth. A protein kinase inhibitor, midostaurin's ability to trigger the human prostate cancer cell line, DU145 to segregate into nerve cells was studied. Midostaurin (100 nM) suppressed the growth of DU145 cells but without change in the number of dead cells. Midostaurin started to extend neurites on DU145 cells after 24 hours and differentiated into nerve cells by 72 hours. The microtubule was stabilized by tau protein and its mRNA expression showed time-dependent increase in midostaurin-treated DU145 cells. At the same time, the amount of acetylcholinesterase was also increased. The midostaurin-treated DU145 cells showed 40% less activity than control in the colony forming assay. The results suggests that midostaurin can induce differentiation of DU145 cells into nerve cells.</p><p> </p>