bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the PyMOL application to reinforce visual understanding of protein structure
Authors: Rigsby Rachel E. , Parker Alison B.
Published: May 2016

Visualization of chemical concepts can be challenging for many students. This is arguably a critical skill for beginning students of biochemistry to develop, since new information is often presented visually in the form of textbook figures. It is recommended that visual literacy be explicitly taught in the classroom rather than assuming that students will develop this skill on their own.  The activity described here is designed to assist students in their development of understanding of basic representations of protein three‐dimensional structure as well as various types of ligands (small molecules, ions) through the use of the iPad application PyMOL.  It has been used as a laboratory exercise but can also be used in a typical 50‐minute class period with a portion of the activity assigned as homework. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):433–437, 2016.
Targeting change: Assessing a faculty learning community focused on increasing statistics content in life science curricula
Authors: Parker Loran Carleton , Gleichsner Alyssa M. , Adedokun Omolola A. , Forney James
Published: May 2016

Transformation of research in all biological fields necessitates the design, analysis and, interpretation of large data sets. Preparing students with the requisite skills in experimental design, statistical analysis, and interpretation, and mathematical reasoning will require both curricular reform and faculty who are willing and able to integrate mathematical and statistical concepts into their life science courses. A new Faculty Learning Community (FLC) was constituted each year for four years to assist in the transformation of the life sciences curriculum and faculty at a large, Midwestern research university. Participants were interviewed after participation and surveyed before and after participation to assess the impact of the FLC on their attitudes toward teaching, perceived pedagogical skills, and planned teaching practice. Overall, the FLC had a meaningful positive impact on participants' attitudes toward teaching, knowledge about teaching, and perceived pedagogical skills. Interestingly, confidence for viewing the classroom as a site for research about teaching declined. Implications for the creation and development of FLCs for science faculty are discussed. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):517–525, 2016.
Hollow Gold Cages and Their Topological Relationship to Dual Fullerenes
Authors: Trombach Lukas , Rampino Sergio , Wang Lai‐Sheng , Schwerdtfeger Peter
Published: May 2016

Golden fullerenes have recently been identified by photoelectron spectra by Bulusu et al. [S. Bulusu, X. Li, L.‐S. Wang, X. C. Zeng, PNAS 2006, 103, 8326–8330]. These unique triangulations of a sphere are related to fullerene duals having exactly 12 vertices of degree five, and the icosahedral hollow gold cages previously postulated are related to the Goldberg–Coxeter transforms of C20 starting from a triangulated surface (hexagonal lattice, dual of a graphene sheet). This also relates topologically the (chiral) gold nanowires observed to the (chiral) carbon nanotubes. In fact, the Mackay icosahedra well known in gold cluster chemistry are related topologically to the dual halma transforms of the smallest possible fullerene C20. The basic building block here is the (111) fcc sheet of bulk gold which is dual to graphene. Because of this interesting one‐to‐one relationship through Euler's polyhedral formula, there are as many golden fullerene isomers as there are fullerene isomers, with the number of isomers Niso increasing polynomially as
). For the recently observed
,
, and
we present simulated photoelectron spectra including all isomers. We also predict the photoelectron spectrum of
. The stability of the golden fullerenes is discussed in relation with the more compact structures for the neutral and negatively charged Au12 to Au20 and Au32 clusters. As for the compact gold clusters we observe a clear trend in stability of the hollow gold cages towards the (111) fcc sheet. The high stability of the (111) fcc sheet of gold compared to the bulk 3D structure explains the unusual stability of these hollow gold cages.
How do you write and present research well? 12—Design graphs to fit within the journal column width
Authors: Patience Gregory S. , Boffito Daria C. , Patience Paul A.
Published: May 2016

Understanding typography — e.g. font types, typefaces, character height, line weight — can help create an aesthetic graph. Identify all correct approximations for a 0.35 mm thick line.[1,2] (Multiple answers.)

1 pt

1.3 px

0.08 em

0.35 pt

The values in (a), (b), (c) and (d) equal 0.35 mm.
Pb Uptake and Phytostabilization Potential of the Mining Ecotype of Athyrium wardii (Hook.) Grown in Pb‐Contaminated Soil
Authors: Zhao Li , Li Tingxuan , Zhang Xizhou , Chen Guangdeng , Zheng Zicheng , Yu Haiying
Published: May 2016

Phytostabilization has been proposed as a cost‐effective remediation strategy to immobilize metals in heavy metal polluted soils. A pot experiment was conducted to evaluate the Pb uptake characteristics and phytostabilization potential of the mining ecotype (ME) of Athyrium wardii and the corresponding non‐mining ecotype (NME) when exposed to the Pb contaminated soils for 40 days. The ME was more tolerant to Pb than the NME when grown in Pb contaminated soil, and the ME demonstrated a greater Pb accumulation ability in roots (30.6–175.45 mg plant−1) than the NME (0.85–25.59 mg plant−1). The bioaccumulation coefficients of ME ranging from 52.02 to 83.16 were 3.24–8.89 times higher than those of the NME under Pb treatment, and the translocation factors of ME ranging from 0.022 to 0.079 were <1. The ME showed a higher capability in absorbing available Pb in soil than the NME. Furthermore, Pb remediation factors in roots of the ME were 6.93–15.35 times higher than those of the NME, and the plant effective number in roots of the ME ranging from 5.70 to 12.74 were lower than those of the NME. These results indicated that the ME showed a greater Pb uptake and phytostabilization potential than the NME, which enabled it as a worthy candidate for Pb phytostabilization.
Increased incidence of FBXW7 and POLE proofreading domain mutations in young adult colorectal cancers
Authors: Kothari Nishi , Teer Jamie K. , Abbott Andrea M. , Srikumar Thejal , Zhang Yonghong , Yoder Sean J. , Brohl Andrew S. , Kim Richard D. , Reed Damon R. , Shibata David
Published: May 2016

BACKGROUND

The incidence and outcomes of patients with colorectal cancer (CRC) varies by age. Younger patients tend to have sporadic cancers that are not detected by screening and worse survival. To understand whether genetic differences exist between age cohorts, the authors sought to characterize unique genetic alterations in patients with CRC.

METHODS

In total, 283 patients who were diagnosed with sporadic CRC between 1998 and 2010 were identified and divided by age into 2 cohorts—ages ≤45 years (the younger cohort) and ≥65 years (the older cohort)—and targeted exome sequencing was performed. The Fisher exact test was used to detect differences in mutation frequencies between the 2 groups. Whole exome sequencing was performed on 21 additional younger patient samples for validation. Findings were confirmed in The Cancer Genome Atlas CRC data set.

RESULTS

In total, 246 samples were included for final analysis (195 from the older cohort and 51 from the younger cohort). Mutations in the FBXW7 gene were more common in the younger cohort (27.5% vs 9.7%; P = .0022) as were mutations in the proofreading domain of polymerase ε catalytic subunit (POLE) (9.8% vs 1%; P = .0048). There were similar mutation rates between cohorts with regard to TP53 (64.7% vs 61.5%), KRAS (43.1% vs 46.2%), and APC (60.8% vs 73.8%). BRAF mutations were numerically more common in the older cohort, although the difference did not reach statistical significance (2% vs 9.7%; P = .082).

CONCLUSIONS

In this retrospective study, a unique genetic profile was identified for younger patients who have CRC compared with patients who are diagnosed at an older age. These findings should be validated in a larger study and could have an impact on future screening and treatment modalities for younger patients with CRC. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2828–2835. © 2016 American Cancer Society
Malignancy‐associated hemophagocytic lymphohistiocytosis in adults: Relation to hemophagocytosis, characteristics, and outcomes
Authors: Tamamyan Gevorg N. , Kantarjian Hagop M. , Ning Jing , Jain Preetesh , Sasaki Koji , McClain Kenneth L. , Allen Carl E. , Pierce Sherry A. , Cortes Jorge E. , Ravandi Farhad , Konopleva Marina Y. , Garcia‐Manero Guillermo , Benton Christopher B. , Chihara Dai , Rytting Michael E. , Wang Sa , Abdelall Waleed , Konoplev Sergej N. , Daver Naval G.
Published: May 2016

BACKGROUND

Malignancy‐associated hemophagocytic lymphohistiocytosis (HLH) in adults is a highly lethal disorder. Knowledge gaps have resulted in under diagnosis or delayed diagnosis.

METHODS

The University of Texas MD Anderson Cancer Center pathology database (1991‐2014) was retrospectively interrogated for the keywords “hemophagocytosis” and/or “lymphohistiocytosis.” Seventy‐seven adult patients were identified. All had an underlying malignancy. Sixteen patients who had insufficient documentation were excluded.

RESULTS

The majority of patients who had pathologic evidence of hemophagocytosis/lymphohistiocytosis had an incomplete workup to confirm or refute HLH using the 2004 HLH criteria (HLH‐2004; n = 8 variables), which is a common problem in adult HLH. Only 13 of 61 patients (21%) met the HLH‐2004 diagnostic criteria based on available retrospective data. To identify potentially missed cases of HLH, the published literature was reviewed, and selected additional variables known to be associated with adult HLH were selected, resulting in extended diagnostic criteria of 18 variables. Thirty‐five patients met the extended criteria, and 33 had follow‐up data available. The median overall survival of the 13 patients who met both the extended criteria and the HLH‐2004 criteria was similar to that of the 20 patients who met the extended criteria but NOT the HLH‐2004 criteria (1.43 vs 1.76 months, respectively; P = .34) indicating a similar underlying, aggressive, systemic process. Twenty‐six patients did not meet either criteria, and 17 had follow‐up data available. The median overall survival of the 17 patients who had pathologic hemophagocytosis or lymphohistiocytosis but met neither criteria was significantly superior to the survival of those who met both the extended criteria and the HLH‐2004 criteria and those who met the extended criteria but not the HLH‐2004 criteria (17.27 vs 1.43 vs 1.76, respectively; P = .002).

CONCLUSIONS

The addition of diagnostic laboratory variables that are more easily and rapidly available in smaller institutions and primary care settings than the HLH‐2004 variables may be a good surrogate to raise early suspicion of malignancy‐associated HLH. Prospective validation is warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2857–2866. © 2016 American Cancer Society
Helping parents live with the hole in their heart: The role of health care providers and institutions in the bereaved parents' grief journeys
Authors: Snaman Jennifer M. , Kaye Erica C. , Torres Carlos , Gibson Deborah V. , Baker Justin N.
Published: May 2016

BACKGROUND

Bereaved parents experience significant psychosocial and health sequelae, suggesting that this population may benefit from the ongoing extension of support and resources throughout the grief journey. The interaction of hospital staff with patients and families at the end of a child's life and after death profoundly affects parental grief, offering a unique opportunity for the medical community to positively impact the bereavement experience. The current study was conducted to explore the role of the health care team and medical institutions in the grief journeys of parents whose child died a cancer‐related death.

METHODS

Eleven bereaved parents participated in 2 focus groups. Responses to each of the 3 main prompts were coded and analyzed independently using semantic content analysis techniques.

RESULTS

Four main concepts were identified within the parental narratives, including the importance of strong and ongoing relationships between providers and bereaved families, the importance of high‐quality communication, the effect of negative experiences between providers and families on parental grief, and the importance of the institution's role in the grief journeys of bereaved parents.

CONCLUSIONS

Bereaved parents consistently identified the critical role played by medical staff and medical institutions throughout the grief journey. Key components of bereavement support identified by parents should serve to guide the actions of providers as well as provide a template for the development of a comprehensive bereavement program within an institution. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2757–2765. © 2016 American Cancer Society.
Ductal carcinoma in situ: How much is too much?
Authors: Gogineni Keerthi
Published: May 2016

In this issue of Cancer, Shiyanbola et al describe changing trends in the treatment of ductal carcinoma in situ. Their findings reinforce the need for research into the natural history of ductal carcinoma in situ that may enable women with low‐risk lesions to undergo less invasive treatment. See also pages 2810–8.
Low‐power and low‐noise complementary metal oxide semiconductor distributed amplifier using the gain‐peaking technique
Authors: Izadi Saadi Rokhsare , Hakimi Ahmad
Published: May 2016

This paper presents an improved topology for ultra‐low‐power complementary metal oxide semiconductor (CMOS) distributed amplifier (DA) based on modified folded cascode gain cells. The proposed CMOS‐DA can be applicable in low‐supply‐voltage applications, because of the use of folded gain cell's structure. The proposed DA decreases power consumption by employing the forward body biasing network, while maintains high gain. By using a gain‐peaking inductor at the gate of the transistor, the proposed DA structure achieved to the gain flatness in high frequencies while the bandwidth is improved as well. In addition, employing RC network at the body terminal improves the noise performance of the proposed DA. The DA architecture consists of three amplification stages. Detailed analysis is provided for the proposed folded cascode DA. According to the post‐layout simulation results of the proposed amplifier using a 0.13‐µm CMOS process, DA achieves power gain of 17.3 ± 0.8 dB in bandwidth of 14.5 GHz, a good input third‐order intercept point (IIP3) of +5.5 dBm. The minimum noise figure is 1.8–5 dB, and input and output return losses are less than −11.5 dB and −10 dB, respectively, and the proposed structure consumes 12 mW from a 0.5 V voltage supply. Copyright © 2016 John Wiley & Sons, Ltd.
Antinociceptive Effect of Racemic Flurbiprofen and Caffeine Co‐Administration in an Arthritic Gout‐Type Pain in Rats
Authors: Liévano‐Reyes Ricardo , Pérez‐Méndez Hermínia Ines , Solís‐Oba Aida , Jaramillo‐Morales Osmar Antonio , Espinosa‐Juárez Josué Vidal , López‐Muñoz Francisco Javier
Published: May 2016

Preclinical Research

Drug combinations are routinely used in the treatment of pain. In drug associations, adjuvants such as caffeine, are employed with different non‐steroidal anti‐inflammatories drugs (NSAIDs), however, at present does not exist studies showing the effect of the combination of racemic flurbiprofen (rac‐Flur) in association with caffeine. The objective of this work was to evaluate the combination of rac‐Flur + caffeine oral in arthritic gout‐type pain in rats. The antinociceptive effects of the rac‐Flur alone and in combination with caffeine were analyzed on a pain‐induced functional impairment model in rat. rac‐Flur induced a dose‐dependent antinociceptive effect and caffeine did not present any effect. The combination of rac‐Flur and caffeine achieve a higher percentage of antinociceptive effect compared with the individual administration of rac‐Flur. The dose‐response curve (DRCs) shows that the combination of rac‐Flur (31.6 mg/kg) + caffeine (17.8 mg/kg) exhibited the maximal antinociceptive efficacy (294.0 ± 21.2 area units), while rac‐Flur alone (31.6 mg/kg) showed 207.2 ± 35.2 au, thus indicating an increase in efficacy (potentiation). Furthermore, the DRCs of the combinations presented a displacement to the left, indicating a change in the potency. Caffeine is able to increase the effect of rac‐Flur in the arthritic gout‐type pain in rats. Drug Dev Res 77 : 192–198, 2016.   © 2016 Wiley Periodicals, Inc.
Experience‐dependent changes in the development of face preferences in infant rhesus monkeys
Authors: Parr Lisa A. , Murphy Lauren , Feczko Eric , Brooks Jenna , Collantes Marie , Heitz Thomas R.
Published: May 2016

It is well known that early experience shapes the development of visual perception for faces in humans. However, the effect of experience on the development of social attention in non‐human primates is unknown. In two studies, we examined the effect of cumulative social experience on developmental changes in attention to the faces of unfamiliar conspecifics or heterospecifics, and mom versus an unfamiliar female. From birth, infant rhesus monkeys preferred to look at conspecific compared to heterospecific faces, but this pattern reversed over time. In contrast, no consistent differences were found for attention to mom's face compared to an unfamiliar female. These results suggest differential roles of social experience in shaping the development of face preferences in infant monkeys. Results have important implications for establishing normative trajectories for the development of face preferences in an animal model of human social behavior.
Plant–fungus competition for nitrogen erases mycorrhizal growth benefits of Andropogon gerardii under limited nitrogen supply
Authors: Püschel David , Janoušková Martina , Hujslová Martina , Slavíková Renata , Gryndlerová Hana , Jansa Jan
Published: May 2016

Considered to play an important role in plant mineral nutrition, arbuscular mycorrhizal (AM) symbiosis is a common relationship between the roots of a great majority of plant species and glomeromycotan fungi. Its effects on the plant host are highly context dependent, with the greatest benefits often observed in phosphorus (P)‐limited environments. Mycorrhizal contribution to plant nitrogen (N) nutrition is probably less important under most conditions. Moreover, inasmuch as both plant and fungi require substantial quantities of N for their growth, competition for N could potentially reduce net mycorrhizal benefits to the plant under conditions of limited N supply. Further compounded by increased belowground carbon (C) drain, the mycorrhizal costs could outweigh the benefits under severe N limitation. Using a field AM fungal community or a laboratory culture of Rhizophagus irregularis as mycorrhizal inoculants, we tested the contribution of mycorrhizal symbiosis to the growth, C allocation, and mineral nutrition of Andropogon gerardii growing in a nutrient‐poor substrate under variable N and P supplies. The plants unambiguously competed with the fungi for N when its supply was low, resulting in no or negative mycorrhizal growth and N‐uptake responses under such conditions. The field AM fungal communities manifested their potential to improve plant P nutrition only upon N fertilization, whereas the R. irregularis slightly yet significantly increased P uptake of its plant host (but not the host's growth) even without N supply. Coincident with increasing levels of root colonization by the AM fungal structures, both inoculants invariably increased nutritional and growth benefits to the host with increasing N supply. This, in turn, resulted in relieving plant P deficiency, which was persistent in non‐mycorrhizal plants across the entire range of nutrient supplies.
Towards a paradigm for open and free sharing of scientific data on global change science in china
Authors: Peng Changhui , Song Xinzhang , Jiang Hong , Zhu Qiuan , Chen Huai , Chen Jing M. , Gong Peng , Jie Chang , Xiang Wenhua , Yu Guirui , Zhou Xiaolu
Published: May 2016

Despite great progress in data sharing that has been made in China in recent decades, cultural, policy, and technological challenges have prevented Chinese researchers from maximizing the availability of their data to the global change science community. To achieve full and open exchange and sharing of scientific data, Chinese research funding agencies need to recognize that preservation of, and access to, digital data are central to their mission, and must support these tasks accordingly. The Chinese government also needs to develop better mechanisms, incentives, and rewards, while scientists need to change their behavior and culture to recognize the need to maximize the usefulness of their data to society as well as to other researchers. The Chinese research community and individual researchers should think globally and act personally to promote a paradigm of open, free, and timely data sharing, and to increase the effectiveness of knowledge development.
Microfluidic free‐flow zone electrophoresis and isotachophoresis using carbon black nano‐composite PDMS sidewall membranes
Authors: Fu Xiaotong , Mavrogiannis Nicholas , Ibo Markela , Crivellari Francesca , Gagnon Zachary R.
Published: May 2016

We present a new type of free‐flow electrophoresis (FFE) device for performing on‐chip microfluidic isotachophoresis and zone electrophoresis. FFE is performed using metal gallium electrodes, which are isolated from a main microfluidic flow channel using thin micron‐scale polydimethylsiloxane/carbon black (PDMS/CB) composite membranes integrated directly into the sidewalls of the microfluidic channel. The thin membrane allows for field penetration and effective electrophoresis, but serves to prevent bubble generation at the electrodes from electrolysis. We experimentally demonstrate the ability to use this platform to perform on‐chip free‐flow electrophoretic separation and isotachophoretic concentration. Due to the small size and simple fabrication procedure, this PDMS/CB platform could be used as a part of an on‐chip upstream sample preparation toolkit for portable microfluidic diagnostic applications.
Genomic profiling and directed ex vivo drug analysis of an unclassifiable myelodysplastic/myeloproliferative neoplasm progressing into acute myeloid leukemia
Authors: Hyrenius‐Wittsten Axel , Sturesson Helena , Bidgoli Mahtab , Jonson Tord , Ehinger Mats , Lilljebjörn Henrik , Scheding Stefan , Andersson Anna K.
Published: May 2016

Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN‐U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, whole exome sequencing and single nucleotide polymorphism arrays were used to characterize the bone marrow and blood samples from a 39‐year‐old woman at MDS/MPN‐U diagnosis and at AML progression, in which routine genetic diagnostics had not identified any genetic alterations. The data revealed the presence of a partial tandem duplication of the MLL gene as the only detectable copy number change and 11 non‐silent somatic mutations, including DNMT3A R882H and NRAS G13D. All somatic lesions were present both at initial MDS/MPN‐U diagnosis and at AML presentation at similar mutant allele frequencies. The patient has since had two extramedullary relapses and is at high risk of a future bone marrow relapse. A directed ex vivo drug sensitivity analysis showed that the patient's AML cells are sensitive to, for example, the MEK inhibitor trametinib and the proteasome inhibitor bortezomib, indicating that she may benefit from treatment with these drugs. © 2016 Wiley Periodicals, Inc.
Impact of socio‐economic position on cancer stage at presentation: Findings from a large hospital‐based study in Germany
Authors: Singer Susanne , Roick Julia , Briest Susanne , Stark Sylvia , Gockel Ines , Boehm Andreas , Papsdorf Kirsten , Meixensberger Jürgen , Müller Tobias , Prietzel Torsten , Schiefke Franziska , Dietel Anja , Bräunlich Jens , Danker Helge
Published: May 2016

We explored the relationship between socio‐economic characteristics and cancer stage at presentation. Patients admitted to a university hospital for diagnosis and treatment of cancer provided data on their education, vocational training, income, employment, job, health insurance and postcode. Tumor stage was classified according to the Union International Contre le Cancer (UICC). To analyze disparities in the likelihood of late‐stage (UICC III/IV vs. I/II) diagnoses, logistic regression models adjusting for age and gender were used. Out of 1,012 patients, 572 (59%) had late‐stage cancer. Separately tested, increased odds of advanced disease were associated with post‐compulsory education compared to college degrees, with apprenticeship and no vocational training, with unemployment, disability pension, jobs with a low hierarchy level, blue collar jobs and with low income. Health insurance and community size were not related with late‐stage cancer. Jointly modelled, there was evidence for an independent effect of unemployment (odds ratio (OR) 1.7, CI 1.0–2.8), disability pension (OR 1.8, CI 1.0–3.2) and very low income (OR 2.6, CI 1.1–6.1) on the likelihood of advanced disease stage. It is of great concern that these socio‐economic gradients occur even in systems with equal access to health care.
Pluripotent stem cells: An in vitro model for nanotoxicity assessments
Authors: Handral Harish K. , Tong Huei Jinn , Islam Intekhab , Sriram Gopu , Rosa Vinicus , Cao Tong
Published: May 2016

The advent of technology has led to an established range of engineered nanoparticles that are used in diverse applications, such as cell–cell interactions, cell–material interactions, medical therapies and the target modulation of cellular processes. The exponential increase in the utilization of nanomaterials and the growing number of associated criticisms has highlighted the potential risks of nanomaterials to human health and the ecosystem. The existing in vivo and in vitro platforms show limitations, with fluctuations being observed in the results of toxicity assessments. Pluripotent stem cells (PSCs) are viable source of cells that are capable of developing into specialized cells of the human body. PSCs can be efficiently used to screen new biomaterials/drugs and are potential candidates for studying impairments of biophysical morphology at both the cellular and tissue levels during interactions with nanomaterials and for diagnosing toxicity. Three‐dimensional in vitro models obtained using PSC‐derived cells would provide a realistic, patient‐specific platform for toxicity assessments and in drug screening applications. The current review focuses on PSCs as an alternative in vitro platform for assessing the hazardous effects of nanomaterials on health systems and highlights the importance of PSC‐derived in vitro platforms. Copyright © 2016 John Wiley & Sons, Ltd.
Raman spectroscopic analysis of Lactobacillus rhamnosus GG in response to dehydration reveals DNA conformation changes
Authors: Myintzu Hlaing Mya , Wood Bayden , McNaughton Don , Ying DanYan , Augustin Mary Ann
Published: May 2016

Dehydration of bacterial cells elicits cellular stress responses in bacteria. Microencapsulation has been used to protect cells against the environmental stress. In this study, Confocal Raman Spectroscopy was used to examine DNA changes in the chemical composition of non‐encapsulated and microencapsulated Lactobacillus rhamnosus GG and the reversibility of these changes upon freeze drying and rehydration. The viability of cells upon freeze drying was also enumerated using culture methods and membrane integrity was measured using BacLight Live/Dead staining. Raman analyses show changes in the spectral features associated with various biochemical compounds, which are interpreted as the result of detrimental freeze drying effects on the bacterial cells. Specifically, analyses based on Principal Components Analysis (PCA) of Raman spectra, confirm that microencapsulation protects cells from environmental stress. The results also reveal a B‐ to A‐like DNA conformation change in dormant cells that provided insights into the extent of reversibility of this transition upon rehydration. The extent of this reversibility is less in non‐encapsulated than in microencapsulated cells. These findings indicate the potential application of Raman spectroscopy in rapid sensing of microbial dehydration stress responses.

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Sodium chloride's effect on self‐assembly of diphenylalanine bilayer
Authors: Kwon Junpyo , Lee Myeongsang , Na Sungsoo
Published: May 2016

Understanding self‐assembling peptides becomes essential in nanotechnology, thereby providing a bottom‐up method for fabrication of nanostructures. Diphenylalanine constitutes an outstanding building block that can be assembled into various nanostructures, including two‐dimensional bilayers or nanotubes, exhibiting superb mechanical properties. It is known that the effect of the ions is critical in conformational and chemical interactions of bilayers or membranes. In this study, we analyzed the effect of sodium chloride on diphenylalanine bilayer using coarse‐grained molecular dynamics simulations, and calculated the bending Young's modulus and the torsional modulus by applying normal modal analysis using an elastic network model. The results showed that sodium chloride dramatically increases the assembling efficiency and stability, thereby promising to allow the precise design and control of the fabrication process and properties of bio‐inspired materials. © 2016 Wiley Periodicals, Inc.
Determination of Urine Albumin by New Simple High‐Performance Liquid Chromatography Method
Authors: Klapkova Eva , Fortova Magdalena , Prusa Richard , Moravcova Libuse , Kotaska Karel
Published: May 2016

Background

A simple high‐performance liquid chromatography (HPLC) method was developed for the determination of albumin in patients' urine samples without coeluting proteins and was compared with the immunoturbidimetric determination of albumin. Urine albumin is important biomarker in diabetic patients, but part of it is immuno‐nonreactive.

Methods

Albumin was determined by high‐performance liquid chromatography (HPLC), UV detection at 280 nm, Zorbax 300SB‐C3 column. Immunoturbidimetric analysis was performed using commercial kit on automatic biochemistry analyzer COBAS INTEGRA® 400, Roche Diagnostics GmbH, Manheim, Germany.

Results

The HLPC method was fully validated. No significant interference with other proteins (transferrin, α‐1‐acid glycoprotein, α‐1‐antichymotrypsin, antitrypsin, hemopexin) was found. The results from 301 urine samples were compared with immunochemical determination. We found a statistically significant difference between these methods (P = 0.0001, Mann–Whitney test).

Conclusion

New simple HPLC method was developed for the determination of urine albumin without coeluting proteins. Our data indicate that the HPLC method is highly specific and more sensitive than immunoturbidimetry.
Design, Synthesis, and Biological Evaluation of Some Cyclohepta[b]Thiophene and Substituted Pentahydrocycloheptathieno[2,3‐d]Pyrimidine Derivatives
Authors: Elmongy Elshaymaa I. , Khedr Mohammed A. , Taleb Nageh A. , Awad Hanem M. , Abbas Safinaz E.‐S.
Published: May 2016

This investigation describes the design of a series of cycloheptathieno[2,3‐d]pyrimidines along with their synthetic strategy. The target compounds were screened for their PARP‐1 inhibitory activity. The modeling study declared that most of the docked compounds showed the same interactions as 3‐aminobenzamide, where Gly 894, His 862, Tyr 896, Arg 878, and Ser 864 were the main residues involved in hydrogen bond formation. Compounds eliciting the top ranked docking results were screened for their PARP‐1 inhibitory activity giving promising results, and three representative compounds were tested for their cytotoxic activity using Doxorubicin as a reference standard. The target compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 including cyclohepta[b]thiophene and pentahydrocycloheptathieno[2,3‐d]pyrimidine cores were designed, prepared, and tested for their PARP‐1 inhibitory activity. Compounds 16 (R: ―NHC(S)NH2) and 11 (R: ―CS) were the most potent ones.
β‐Lactam Preparation via Staudinger Reaction with Activated Dimethylsulfoxide
Authors: Zarei Maaroof
Published: May 2016

An efficient synthesis of β‐lactams has been expediently accomplished. These β‐lactams were synthesized by the Staudinger reaction of several substituted imines with various carboxylic acids using activated DMSO at ambient temperature. The imines and substituted acetic acids contain alkyl, aryl, hetero aryl, polycyclic, and 3‐electron‐withdrawing group underwent [2 + 2] ketene‐imine cycloaddition reaction smoothly to obtain the desired β‐lactams in good to excellent yields. This method is cheap, simple, convenient, and efficient, and the products are easily isolated.
Directional deep brain stimulation of the subthalamic nucleus: A pilot study using a novel neurostimulation device
Authors: Steigerwald Frank , Müller Lorenz , Johannes Silvia , Matthies Cordula , Volkmann Jens
Published: May 2016

Introduction

A novel neurostimulation system allows steering current in horizontal directions by combining segmented leads and multiple independent current control. The aim of this study was to evaluate directional DBS effects on parkinsonian motor features and adverse effects of subthalamic neurostimulation.

Methods

Seven PD patients implanted with the novel directional DBS system for bilateral subthalamic DBS underwent an extended monopolar review session during the first postoperative week, in which current thresholds were determined for rigidity control and stimulation‐induced adverse effects using either directional or ring‐mode settings.

Results

Effect or adverse effect thresholds were modified by directional settings for each of the 14 STN leads. Magnitude of change varied markedly between leads, as did orientation of optimal horizontal current steering.

Conclusion

Directional current steering through chronically implanted segmented electrodes is feasible, alters adverse effect and efficacy thresholds in a highly individual manner, and expands the therapeutic window in a monopolar review as compared to ring‐mode DBS. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
Appendectomy in mid and later life and risk of Parkinson's disease: A population‐based study
Authors: Marras Connie , Lang Anthony E. , Austin Peter C. , Lau Cindy , Urbach David R.
Published: May 2016

Introduction

Pathogenic movement of alpha‐synuclein from the gut to the brain in PD has been proposed. The appendix has a relatively high density of alpha‐synuclein deposition in neurologically healthy individuals. We investigated the incidence of PD after appendectomy.

Methods

Using cause‐specific hazards regression models, we compared persons over 35 years of age who had undergone appendectomy with two groups of age‐ and sex‐matched individuals having had: (1) a cholecystectomy and (2) neither procedure. Subsequent diagnoses of PD were identified.

Results

Among 42,999 individuals undergoing appendectomy, no difference in risk of PD was identified compared to cholecystectomy (hazard ratio = 1.004; 95% confidence interval: 0.740–1.364). Compared with no procedure, individuals with appendectomy had a higher incidence of PD within 5 years, but no significant difference in risk thereafter.

Conclusion

In our study, appendectomy in mid or late life does not appear to be associated with a reduced risk of PD. © 2016 International Parkinson and Movement Disorder Society
A pilot study to measure dynamic elasticity of the bladder during urodynamics
Authors: Colhoun Andrew F. , Klausner Adam P. , Nagle Anna S. , Carroll Ashley W. , Barbee Robert W. , Ratz Paul H. , Speich John E.
Published: May 2016

AIMS

Previous studies using isolated strips of human detrusor muscle identified adjustable preload tension, a novel mechanism that acutely regulates detrusor wall tension. The purpose of this investigation was to develop a method to identify a correlate measure of adjustable preload tension during urodynamics.

METHODS

Patients reporting urgency most or all of the time based on ICIq‐OAB survey scores were prospectively enrolled in an extended repeat fill‐and‐empty urodynamics study designed to identify a correlate of adjustable preload tension which we now call “dynamic elasticity.” Cystometric capacity was determined during initial fill. Repeat fills to defined percentages of capacity with passive emptying (via syringe aspiration) were performed to strain soften the bladder. A complete fill with active voiding was included to determine whether human bladder exhibits reversible strain softening.

RESULTS

Five patients completed the extended urodynamics study. Intravesical pressure (pves) decreased with subsequent fills and was significantly lower during Fill 3 compared to Fill 1 (P = 0.008), demonstrating strain softening. Active voiding after Fill 3 caused strain softening reversal, with pves in Fill 4 returning to the baseline measured during Fill 1 (P = 0.29). Dynamic elasticity, the urodynamic correlate of adjustable preload tension, was calculated as the amount of strain softening (or its reversal) per %capacity (Δaverage pves between fills/Δ%capacity). Dynamic elasticity was lost via repeat passive filling and emptying (strain softening) and regained after active voiding regulated the process (strain softening reversal).

CONCLUSIONS

Improved understanding of dynamic elasticity in the human bladder could lead to both improved sub‐typing and novel treatments of overactive bladder. Neurourol. Urodynam. 36:1086–1090, 2017. © 2016 Wiley Periodicals, Inc.
Outcome of TVT operations in women with low maximum urethral closure pressure
Authors: Moe Kjartan , Schiøtz Hjalmar A. , Kulseng‐Hanssen Sigurd
Published: May 2016

Aims

(i) To establish whether low maximal urethral closure pressure (MUCP) is associated with a poorer prognosis after TVT‐surgery, and if so to establish an MUCP cut‐off value for poor outcome. (ii) To characterize the population with a low MUCP.

Methods

Retrospective analysis of data from 6,646 women with stress/mixed urinary incontinence included in the Norwegian Female Incontinence Registry. Postoperative subjective (degree of satisfaction), objective (leakage on stress test) and composite cure according to preoperative MUCP were analyzed in unadjusted and adjusted analysis. Preoperative variables were compared between women having a low or normal MUCP. Non‐parametric tests were used on continuous variables and χ2 tests on categorical variables. Logistic regression was used for the adjusted analysis. Level of significance: P < 0.05.

Results

An analysis of centiles of preoperative MUCP showed that a cut‐off at 20 cm H2O did best identify women at risk of not being cured. In unadjusted analysis MUCP ≤20 cm H2O (n = 422) was associated with objective (OR: 2.48), subjective (OR: 1.60), and composite failure (OR: 1.95) compared to MUCP >20 cm H2O. In adjusted analysis MUCP ≤20 cm H2O was associated with neither objective, subjective, nor composite failure. Women with MUCP <20 cm H2O were preoperatively significantly older, had larger leakage on stress and 24 h pad test, lower mean voided volume and maximum flow rate and higher stress and urge indices.

Conclusions

Women with MUCP ≤20 cm H2O have similar objective, subjective, and composite outcomes after TVT‐surgery compared to women with MUCP >20 cm H2O after adjusting for preoperative variables. Neurourol. Urodynam. 36:1320–1324, 2017. © 2016 Wiley Periodicals, Inc.
Sling mobilization in the management of urinary retention after mid‐urethral sling surgery
Authors: Moksnes Liv Rimstad , Svenningsen Rune , Schiøtz Hjalmar A. , Moe Kjartan , Staff Anne C. , Kulseng‐Hanssen Sigurd
Published: May 2016

Objective

To compare intermittent catheterization, sling mobilization, and sling transection for treatment of urinary retention after mid‐urethral sling surgery.

Methods

Data registered in the Norwegian Female Incontinence Registry from 1998 to 2013 were analyzed in this cohort study to compare subjective and objective outcomes after intermittent catheterization, sling mobilization, and sling transection as management of postoperative urinary retention after mid urethral sling surgery. Subjective outcomes were degree of symptom bother and the percentage of women stating “very satisfied” at the postoperative follow‐up. The objective outcome was leakage at a cough‐jump pad stress test.

Results

Intervention due to urinary retention was performed in 585 of 18,772 women (3.1%). Women who had their sling mobilized or had intermittent catheterization, scored better on all postoperative outcomes than those who had their sling transected (P < 0.001). Sling transection was more often needed after intermittent catheterization than after mobilization (P = 0.023). No outcome differences were found between intermittent catheterization only and sling mobilization only. Intention to treat analysis showed that women who underwent sling mobilization as the primary procedure significantly more often had a negative stress test (P = 0.033) and were more often “very satisfied” with the treatment (P = 0.006) than those who were primarily catheterized.

Conclusions

Sling mobilization is a more successful treatment than intermittent catheterization or transection for urinary retention after mid‐urethral sling surgery.

Clinical Trial Registration

Clinical trial registration was not applicable because this study is based on an analysis of anonymous data from The Norwegian Female Incontinence Registry. Neurourol. Urodynam. 36:1091–1096, 2017. © 2016 Wiley Periodicals, Inc.
Anisotropic swelling of hydrogel nanowires based on poly(vinylpyrrolidone) fabricated by single‐particle nanofabrication technique
Authors: Tsukuda Satoshi , Omichi Masaaki , Sugimoto Masaki , Idesaki Akira , Padalkar Vikas S. , Seki Shu
Published: May 2016

We report a hydrogel nanowire based on poly(vinylpyrrolidone) (PVP) and N,N'‐methylenebis(acrylamide) (MBA), which have anisotropic swelling ratio for radius and length direction. The PVP/MBA nanowires were fabricated by single particle nanofabrication technique, which is a technique for the fabrication of polymeric nanowires using the single ion event, that cause the crosslinking reaction of polymer chains within the ion tracks along the ion paths; furthermore the size (length and radius) of the nanowires was controlled by changing the film thickness and amount of MBA crosslinker. The swelling behaviors in air and water were observed using atomic force microscopy. The PVP/MBA nanowires exhibited anisotropic swelling along the length and radius in aqueous environments, because the hydrogel nanowires consisted of crosslinked networks with inhomogeneous crosslinking points, which reflected the initial energy distribution from incident an ion within the ion track. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 1950–1956
Structural propensities of kinase family proteins from a Potts model of residue co‐variation
Authors: Haldane Allan , Flynn William F. , He Peng , Vijayan R.S.K. , Levy Ronald M.
Published: May 2016

Understanding the conformational propensities of proteins is key to solving many problems in structural biology and biophysics. The co‐variation of pairs of mutations contained in multiple sequence alignments of protein families can be used to build a Potts Hamiltonian model of the sequence patterns which accurately predicts structural contacts. This observation paves the way to develop deeper connections between evolutionary fitness landscapes of entire protein families and the corresponding free energy landscapes which determine the conformational propensities of individual proteins. Using statistical energies determined from the Potts model and an alignment of 2896 PDB structures, we predict the propensity for particular kinase family proteins to assume a “DFG‐out” conformation implicated in the susceptibility of some kinases to type‐II inhibitors, and validate the predictions by comparison with the observed structural propensities of the corresponding proteins and experimental binding affinity data. We decompose the statistical energies to investigate which interactions contribute the most to the conformational preference for particular sequences and the corresponding proteins. We find that interactions involving the activation loop and the C‐helix and HRD motif are primarily responsible for stabilizing the DFG‐in state. This work illustrates how structural free energy landscapes and fitness landscapes of proteins can be used in an integrated way, and in the context of kinase family proteins, can potentially impact therapeutic design strategies.
Strategic Alliances of Entrepreneurial Firms: Value Enhancing Then Value Destroying
Authors: Moghaddam Kaveh , Bosse Douglas A. , Provance Mike
Published: May 2016

Research summary

Based on the RBV and dynamic capabilities, this study explains the relationship between alliance formation and the private (pre‐IPO) entrepreneurial firm's market performance. Findings show that while alliance formation positively and significantly affects the market performance of venture‐backed firms in the software industry, forming a comparatively large number of alliances hurts these firms' market valuations.

Managerial summary

Entrepreneurial firms are better off entering a select number of strategic alliances and focusing on enhancing the outcomes of those select alliances as well as developing a dynamic alliance management capability. Such firms benefit most from establishing a moderate number of alliances rather than depending on a small number of alliances or becoming overwhelmed with a great number of alliances. Copyright © 2016 Strategic Management Society.
Mastering Dendrimer Self‐Assembly for Efficient siRNA Delivery: From Conceptual Design to In Vivo Efficient Gene Silencing
Authors: Chen Chao , Posocco Paola , Liu Xiaoxuan , Cheng Qiang , Laurini Erik , Zhou Jiehua , Liu Cheng , Wang Yang , Tang Jingjie , Col Valentina Dal , Yu Tianzhu , Giorgio Suzanne , Fermeglia Maurizio , Qu Fanqi , Liang Zicai , Rossi John J. , Liu Minghua , Rocchi Palma , Pricl Sabrina , Peng Ling
Published: May 2016

Self‐assembly is a fundamental concept and a powerful approach in molecular science. However, creating functional materials with the desired properties through self‐assembly remains challenging. In this work, through a combination of experimental and computational approaches, the self‐assembly of small amphiphilic dendrons into nanosized supramolecular dendrimer micelles with a degree of structural definition similar to traditional covalent high‐generation dendrimers is reported. It is demonstrated that, with the optimal balance of hydrophobicity and hydrophilicity, one of the self‐assembled nanomicellar systems, totally devoid of toxic side effects, is able to deliver small interfering RNA and achieve effective gene silencing both in cells – including the highly refractory human hematopoietic CD34+ stem cells – and in vivo, thus paving the way for future biomedical implementation. This work presents a case study of the concept of generating functional supramolecular dendrimers via self‐assembly. The ability of carefully designed and gauged building blocks to assemble into supramolecular structures opens new perspectives on the design of self‐assembling nanosystems for complex and functional applications.