bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin's discovery: New insights on its ninetieth birthday
Authors: Roth Jesse , Qureshi Sana , Whitford Ian , Vranic Mladen , Kahn C. Ronald , Fantus I. George , Dirks John H.
Published: May 2012

2012 marks the 90th year since the purification of insulin and the miraculous rescue from death of youngsters with type 1 diabetes. In this review, we highlight several previously unappreciated or unknown events surrounding the discovery. (i) We remind readers of the essential contributions of each of the four discoverers – Banting, Macleod, Collip, and Best. (ii) Banting and Best (each with his own inner circle) worked not only to accrue credit for himself but also to minimize credit to the other discoverers. (iii) Banting at the time of the insulin research was very likely suffering from post‐traumatic stress disorder (PTSD) that originated during his heroic service as a surgeon in World War I on the Western Front in 1918, including an infected shrapnel wound that threatened amputation of his arm. His war record along with the newly discovered evidence of a suicide threat goes along with his paranoia, combativeness, alcohol excess, and depression, symptoms we associate with PTSD. (iv) Banting's eureka idea, ligation of the pancreatic duct to preserve the islets, while it energized the early research, was unnecessary and was bypassed early. (v) Post discovery, Macleod uncovered many features of insulin action that he summarized in his 1925 Nobel Lecture. Macleod closed by raising the question – what is the mechanism of insulin action in the body? – a challenge that attracted many talented investigators but remained unanswered until the latter third of the 20th century. Copyright © 2012 John Wiley & Sons, Ltd.
Titration of Zr3(μ‐OH) Hydroxy Groups at the Cornerstones of Bulk MOF UiO‐67, [Zr6O4(OH)4(biphenyldicarboxylate)6], and Their Reaction with [AuMe(PMe3)]
Authors: Larabi Cherif , Quadrelli Elsje Alessandra
Published: May 2012

The known MOF UiO‐67 of general formula [Zr6O4(OH)4(bpdc)6] [bpdc = biphenyldicarboxylate, O2C(C6H4)2CO2] has been synthesized on a 3 g scale and characterized by BET, TGA, XRD, IR and 13C NMR spectroscopy, and elemental analyses. The chemical accessibility of the hydroxy ligand Zr3(μ‐OH) was assessed by the addition of D2O: The expected isotopic shift of ν(OH) = 3673 cm–1 to ν(OD) = 2709 cm–1 in the IR spectrum was observed. The OH content in bulk UiO‐67, previously mildly activated at 120 °C under vacuum (10–5 Torr) overnight, was quantitatively determined by three methods: (1) By integration of the IR ν(OH) region and comparison with calibrated spectra of MCM‐41 previously dehydroxylated at 500 °C, which gave a spectroscopically measured OH content in bulk UiO‐67 of 2.2 mmol/g (37 mg OH/g); (2) by extrapolation of the OH content from the measured weight loss between 250 and 400 °C in TGA, which corresponded to 1.6 mmol OH/g (27 mg OH/g); and (3) by chemical titration of UiO‐67 with CH3MgBr and GC determination of the evolved methane, which gave 1.8 mmol OH/g (31 mg OH/g). The three methods, and in particular the latter chemical titration, are in very good to excellent agreement with the nominal OH content based on the molecular formula [Zr6O4(OH)4(bpdc)6] (expected: 1.9 mmol OH/g, 32 mg OH/g; experimental/calculated OH content = 110, 85, and 95 %, respectively, for the three methods). The weak acidity of the OH moiety in UiO‐67 was assessed by IR and 31P NMR monitoring of the physisorption of PMe3 in the UiO‐67 cavities. Inclusion of the organometallic AuI complex [AuMe(PMe3)] in a 1:1 molar ratio with respect to [Zr6O4(OH)4(bpdc)6] was achieved. Some chemisorption at 20 % of the cornerstone hydroxy sites also occurred to yield [Zr6O4(OH)3(bpdc)6(OAuPMe3)].
Effects of anaerobic digestion on digestate nutrient availability and crop growth: A review
Authors: Möller Kurt , Müller Torsten
Published: May 2012

Anaerobic digestion (AD) for biogas production leads to several changes in the composition of the resulting digestates compared to the original feedstock (ammonia content, pH, carbon to nitrogen ratio, etc.), which are relevant for the plant availability of macro‐ and micronutrients after field application. Increased NH4+‐N content in digested slurries compared to undigested slurries does not guarantee improved uptake efficiency of slurry nitrogen and increased savings in fertilizer nitrogen. AD of crop residues and cover crops leads to an increase in the total amounts of mobile organic manures within the farming system, resulting in a higher nitrogen use efficiency and an increased scope for target‐oriented nitrogen application in time and space, when needed by the crop, as an alternative to the site‐bound soil incorporation as green manures. AD of dairy manure appears to reduce the fraction of immediate plant available phosphorus and micronutrients. This does, however, not affect short‐term crop availability under field conditions. More studies are needed to improve current knowledge on sulfur losses during AD and fertilizer value of digestates.
Variant 1 of KIAA0101, overexpressed in hepatocellular carcinoma, prevents doxorubicin-induced apoptosis by inhibiting p53 activation
Authors: Liu Lijuan , Chen Xiaobei , Xie Shuixiang , Zhang Chuanjie , Qiu Zhenpeng , Zhu Fan
Published: May 2012

KIAA0101 overexpression was detected in numerous malignant solid tumors and involved in tumor progression; however, the correlation between KIAA0101 expression level and human hepatocellular carcinoma (HCC) was controversial. Our data revealed abnormal expression of the KIAA0101 transcript variant 1 (KIAA0101 tv1) at both messenger RNA and protein levels in HCC tissues and cell lines assessed by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), virtual northern blot, western blot, and immunohistochemical analysis, especially in stage 3-4 HCCs. NIH3T3 cells transfected with KIAA0101 tv1 induced colony formation

in vitro

and tumor xenorafts

in vivo

, implying the oncogenic potential of KIAA0101 tv1. Semiquantitative RT-PCR, real-time quantitative RT-PCR, and western blot analysis demonstrated that doxorubicin (Adriamycin, ADR) treatment down-regulated expression of the KIAA0101 tv1, whereas it increased the acetylation of the p53 protein. Additionally, KIAA0101 tv1 prevented cells from apoptosis caused by ADR through suppressing the acetylation of p53 at Lys382. Immunoprecipitation analysis and mammalian two-hybrid assay indicated that KIAA0101 tv1 bound to the transactivation region (1-42 amino acids) of p53 and strongly inhibits its transcriptional activity. Taken together, our data suggest that KIAA0101 tv1 played an important role in the late stage of metastatic HCC and prevented apoptosis after chemotherapeutic drug treatment through inhibiting the transcriptional activity of the p53 gene.

Conclusion:

KIAA0101 tv1 may function as a regulator, promoting cell survival in HCC through regulating the function of p53. Suppression of the KIAA0101 tv1 function is likely to be a promising strategy to develop novel cancer therapeutic drugs.
FINANCIAL MARKETS AND INTERNATIONAL RISK SHARING IN EMERGING MARKET ECONOMIES
Authors: Schmitz Martin
Published: May 2012

In light of rapidly increasing foreign equity liability positions of emerging market economies, we test for a necessary condition of international risk sharing, namely for systematic patterns between idiosyncratic output fluctuations and financial market developments. Panel analysis of 22 emerging market economies shows strong evidence for pro‐cyclicality of capital gains on domestic stock markets both over short‐term and medium‐term horizons. This implies that domestic output fluctuations can be hedged through cross‐border ownership of financial markets. Copyright © 2012 John Wiley & Sons, Ltd.
Amniotic membrane as part of a skin substitute for full‐thickness wounds: An experimental evaluation in a porcine model
Authors: Loeffelbein Denys J. , Baumann Claudia , Stoeckelhuber Mechthild , Hasler Rafael , Mücke Thomas , Steinsträßer Lars , Drecoll Enken , Wolff Klaus‐Dietrich , Kesting Marco R.
Published: May 2012

Background:

We evaluated the use of human amniotic membrane (HAM) as a graft material for the treatment of iatrogenic full‐thickness (FT) skin wounds in a porcine model with a view to reducing donor site morbidity in free flap transfer.

Methods:

Forty experimental FT‐wounds were covered with an autologous split‐thickness skin graft (STSG) alone or in combination with a mono‐ or multilayer HAM or Integra®. Untreated wounds served as controls. Clinical evaluation and biopsy‐sampling for histological and immunohistochemical staining with von‐Willebrand‐factor (vWF) antibody, laminin antibody, Ki‐67 antibody, and smooth muscle actin (αSMA) antibody were performed on days 5, 7, 10, 20, 40, and 60 after surgical intervention.

Results:

Considerable disparities in the estimated criteria were observed between the various treatment groups of the FT‐wounds. The use of HAM was found to have an accelerating impact on re‐epithelialization. The multilayered amnion membrane showed better results than the Integra® and monolayer technique in terms of contraction rate, inflammation, and scarring and seemed useful as a dermal substitute in FT‐wounds giving comparable results to STSG coverage alone.

Conclusions:

This study demonstrates the successful application of HAM as part of a skin substitute in FT‐wounds in minipigs. The results offer promise as a simple and effective technique for the application of multilayer HAM in iatrogenic human skin defects and the acceleration of wound healing. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Halofuginone prevents estrogen‐deficient osteoporosis in mice
Authors: DeSelm Carl J. , Zou Wei , Teitelbaum Steven L.
Published: May 2012

Osteoporosis is characterized by enhanced activity of osteoclasts relative to that of osteoblasts. Thus, the principal means of treating the most common form of osteoporosis, namely that attending menopause, is inhibition of osteoclast formation or function. We have demonstrated that the inflammatory cytokine, IL‐17, mediates estrogen‐deficient osteoporosis, in mice, and that genetic blockade of its function prevents ovariectomy‐induced bone loss. We herein report that the febrifugine derivative, halofuginone, a small molecule drug, reduces abundance of Th‐17 cells in mice and prevents estrogen‐deficient osteoporosis by diminishing bone resorption without impacting osteogenesis. In keeping with IL‐17 mediating its osteoclastogenic effects by promoting RANK ligand expression by osteoblasts, halofuginone does not directly inhibit the bone resorptive cell. Thus, halofuginone, which is presently FDA‐approved for treatment of scleroderma, is a candidate therapeutic for post‐menopausal osteoporosis. J. Cell. Biochem. 113: 3086–3092, 2012. © 2012 Wiley Periodicals, Inc.
An insertion in loop L7 of human eosinophil‐derived neurotoxin is crucial for its antiviral activity
Authors: Sikriwal Deepa , Seth Divya , Parveen Shama , Malik Anu , Broor Shobha , Batra Janendra K.
Published: May 2012

The human eosinophil granule ribonuclease, eosinophil‐derived neurotoxin (EDN) has been shown to have antiviral activity against respiratory syncytial virus‐B (RSV‐B). Other closely related and more active RNases such as RNase A, onconase, and RNase k6 do not have any antiviral activity. A remarkable unique feature of EDN is a nine‐residue insertion in its carboxy‐terminal loop, L7 which is not present in RNase A, and differs in sequence from the corresponding loop in another eosinophil RNase, eosinophil cationic protein (ECP). ECP has a much lower antiviral activity as compared to EDN. The current study probed the role of loop L7 of EDN in its antiviral activity. Three residues in loop L7, Arg117, Pro120, and Gln122, which diverge between EDN, ECP, and RNase A, were mutated to alanine alone and in combination to generate single, double, and triple mutants. These mutants, despite having RNase activity had decreased antiviral activity towards RSV suggesting the involvement of loop L7 in the interaction of EDN with RSV. It appears that the mutations in loop L7 disrupt the interaction of protein with the viral capsid, thereby inhibiting its entry into the virions. The study demonstrates that besides the RNase activity, loop L7 is another important determinant for the antiviral activity of EDN. J. Cell. Biochem. 113: 3104–3112, 2012. © 2012 Wiley Periodicals, Inc.
Clarification of succinic acid fermentation broth by ultrafiltration in succinic acid bio–refinery
Authors: Wang Caixia , Li Qiang , Tang Huang , Zhou Wei , Yan Daojiang , Xing Jianmin , Wan Yinhua
Published: May 2012

BACKGROUND: Succinic acid is an important precursor chemical for the synthesis of high value‐added products. In this work, ultrafiltration was first investigated to clarify succinic acid fermentation broth by integrating fermentation and separation and removal processes of the product in situ. Four different ultrafiltration membranes (PES 100 kDa, PES 30 kDa, PES 10 kDa and RC 10 kDa) were used in this work.

RESULTS: Results indicate that ultrafiltration is feasible for clarifying succinic acid fermentation broth. Almost all the microorganism cells (99.6%) were removed from the fermentation broth. Proteins were also removed effectively by all the membranes studied. The removal rate was 79.86% for PES 100 kDa, 86.43% for PES 30 kDa, 86.83% for PES 10 kDa, and 80.06% for the RC 10 kDa. After ultrafiltration, a clearer permeate was obtained compared with that from centrifugation.

CONCLUSION: Membranes operating at high flux are always susceptible to rapid fouling. Compared with molecular weight cut‐offs (MWCO), membrane material has a significant influence on the flux. Membrane flux measured in this study shows industrial potential of this technology in treatment of succinic acid fermentation broth. © 2012 Society of Chemical Industry
Tritium labeling of full‐length small interfering RNAs
Authors: Christensen Jesper , Natt François , Hunziker Jürg , Krauser Joel , Andres Hendrik , Swart Piet
Published: May 2012

A simple procedure is described for full‐length single internal [3H]‐radiolabeling of oligonucleotides. Previous labeling strategies have been applied to large molecular weight compounds such as proteins and oligonucleotides, for example, iodination and 111In labeling via covalently bounded chelators. However, a procedure has not yet been reported for single internal radiolabeling of oligonucleotides that preserves the molecular structure (3H replacing a 1H). In following our strategy, the radiolabel can be strategically placed within a stable and predetermined internal position of the siRNA. This placement was accomplished by placing a 5‐bromouridine or 5‐bromo‐2′‐O‐methyluridine phosphoramidite building block into the middle of the antisense strand using standard phosphoramidite chemistry. The deprotected full‐length antisense strand was tritium labeled by bromine/tritium exchange, catalyzed by palladium on charcoal in the predetermined 5‐position of either uridine or 2′‐O‐methyluridine. Internal placement of the building block within the oligonucleotide sequence and label placement at 5‐position decreases the likelihood of the label to be readily cleaved from the oligonucleotide in vivo, and loss of the label by spontaneous tritium/hydrogen exchange. The tritiated single‐stranded and double‐stranded RNAs were also shown to be radio and chemically stable for at least 6 months at −80 °C. This allows more than sufficient time to conduct pharmaceutical formulation and pharmacokinetic studies. Copyright © 2012 John Wiley & Sons, Ltd.
Radiosynthesis and biological evaluation of the M1 muscarinic acetylcholine receptor agonist ligand [11C]AF150(S)
Authors: Buiter Hans J.C. , Leysen Josée E. , Schuit Robert C. , Fisher Abraham , Lammertsma Adriaan A. , Windhorst Albert D.
Published: May 2012

Purpose

M1 muscarinic acetylcholine receptor (M1ACh‐R) agonists are potential therapeutics for cognitive disorders. The aim of this study was to develop an orthosteric agonist positron emission tomography (PET) ligand for the M1ACh‐R that would provide a tool to explore the active G‐protein coupled receptor. To that extend, the radiosynthesis, receptor binding in vitro, and brain uptake of [11C]AF150(S), a selective M1ACh‐R agonist, were investigated.

Procedures

[11C]AF150(S) was synthesized, its binding properties were investigated using autoradiography on rat brain sections, and brain uptake was determined in biodistribution studies ex vivo in rats. Metabolites in brain and blood were measured using high‐performance liquid chromatography.

Results

Yield of the [11C]AF150(S) radiosynthesis was 69 ± 9% with radiochemical purity >99%. The logDoct,7.4 was 0.05. Autoradiography showed binding in M1ACh‐R rich brain areas and selective inhibition by muscarinic agents in conditions promoting agonist binding. Biodistribution studies revealed rapid and high brain uptake, to levels exceeding five times the blood level. In M1ACh‐R rich areas, specific uptake versus cerebellum was apparent, remaining constant over 60 min in spite of rapid decline of radioactivity from the brain and rapid peripheral metabolism. Brain uptake of [11C]AF150(S) may involve facilitated transport.

Conclusion

[11C]AF150(S) was successfully synthesized, showed M1ACh‐R agonist binding properties, and high brain uptake. It provides an interesting lead for the development of an M1ACh‐R agonist PET ligand meant to explore the active receptor state. Copyright © 2012 John Wiley & Sons, Ltd.
Correlation of volume transfer coefficient Ktrans with histopathologic grades of gliomas
Authors: Zhang Na , Zhang Lijuan , Qiu Bensheng , Meng Li , Wang Xiaoyi , Hou Bob L.
Published: May 2012

Purpose:

To evaluate the roles of dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and optimum tracer kinetic parameters in the noninvasive grading of the glial brain tumors with histopathological grades (I–IV).

Materials and Methods:

Twenty‐eight patients with histopathologically graded gliomas were imaged. Images with five flip angles were acquired before injection of gadolinium‐DTPA and were processed to calculate the T1 value of each region of interest (ROI). All the DCE‐MRI data acquired during the injection were processed based on the MRI signal and pharmacokinetic models to establish concentration–time curves in the ROIs drawn within the tumors, contralateral normal areas, and area of the individual artery input functions (iAIF) of each patient. A nonlinear least‐square‐fitting method was used to obtain tracer kinetic parameters. Kruskal–Wallis H‐test and Mann–Whitney U‐test were applied to these parameters in different histopathological grade groups for statistical differences (P < 0.05).

Results:

Volume transfer coefficient (Ktrans) and extravascular extracellular space volume fraction (Ve) calculated using iAIFs can be used not only to distinguish the low (ie, I and II) from the high (ie, III and IV) grade gliomas (P() < 0.001 and PVe < 0.001), but also grade II from III (P() = 0.016 and PVe = 0.033).

Conclusion:

Ktrans is the most sensitive and specific parameter in noninvasive grading, distinguishing the high (III and IV) from the low (I and II) grade and high grade III from low grade II gliomas. J. Magn. Reson. Imaging 2012;36:355–363. © 2012 Wiley Periodicals, Inc.
Reproducibility of single‐subject fMRI language mapping with AMPLE normalization
Authors: Voyvodic James T.
Published: May 2012

Purpose:

To evaluate the reproducibility of presurgical functional MRI (fMRI) language mapping based on test–retest scans, comparing traditional activation t‐maps to relative activation maps normalized by activation mapping as percentage of local excitation (AMPLE).

Materials and Methods:

Language fMRI scans were performed by 12 healthy volunteer subjects undergoing a standard clinical presurgical mapping protocol in multiple independent scan sessions. Objective relative AMPLE activation maps were generated automatically by normalizing statistical t‐value maps to the local peak activation amplitude within each functional brain region. The spatial distribution of activation was quantified and compared across mapping algorithms, subjects, scanners, and pulse sequences.

Results:

The spatial distribution of traditional blood oxygen level‐dependent (BOLD) t‐value statistical activation maps was highly variable in test–retest scans of single subjects, whereas AMPLE normalized maps were highly reproducible in terms of the location, hemispheric laterality, and spatial extent of relative activation. AMPLE map reproducibility was good regardless of scanner, field strength, or pulse sequence used, but reproducibility was best for scans acquired on the same scanner using the same pulse sequence.

Conclusion:

Reproducibility of the spatial pattern of BOLD activation makes relative amplitude fMRI mapping a useful normalization tool for clinical imaging of language function, where reproducibility and quantitative measurements are critical concerns. J. Magn. Reson. Imaging 2012;36:569–580. © 2012 Wiley Periodicals, Inc.
Microtubule and male sterility in a gene‐cytoplasmic male sterile line of non‐heading Chinese cabbage
Authors: Zhang Jingyi , Zhang Changwei , Cheng Yan , Qi Li , Wang Shumin , Hou Xilin
Published: May 2012

BACKGROUND: Microtubules are the basic components of the cytoskeleton in eukaryotic cells and are made up of 13 parallel protofilaments, each composed of α‐ and β‐tubulin unit molecules aligned along the longitudinal axis of the microtubule.

RESULTS: α‐Tubulin gene TUBA2 from non‐heading Chinese cabbage (Brassica campestris ssp. chinensis Makino) was expressed at the highest level in stamens and at lower levels in other organs. In addition, it was expressed at a much lower level in the cytoplasmic male sterile (CMS) line than in the maintainer line. Furthermore, at the microsporocyte stage of development in the CMS line the microtubule bundles were knitted together in random organisation, which differed significantly from the radiate microtubule bundles running circumferentially around the nucleus in the maintainer line. Also, large vacuoles appeared within the cytoplasm in the CMS line with no dyed microtubules.

CONCLUSION: TUBA2 was very important to pollen development, which might be closely related to male sterility. Large vacuoles might replace the nuclei close to the cell walls and lead to a lack of microtubules when the cells abort. Abnormalities and defects in the organisation and composition of microtubules in the male sterile line highlighted the complex interaction between microtubules and cytoplasmic male sterility. Copyright © 2012 Society of Chemical Industry
Lipids and human milk
Authors: Kim Jongsoo , Friel James
Published: May 2012

To support the growth and development of the breast‐fed infant, human milk provides the dietary essential fatty acids, linoleic acid (LA; 18:2n‐6), α‐linolenic acid (ALA, 18:3n‐3), as well as longer‐chain polyunsaturated fatty acids including arachidonic acid (20:4n‐6) and docosahexanoic (DHA 22:6n‐3). The linoleic acid, alpha‐linolenic acid, DHA and arachidonic acid concentration of pasteurized and unpasteurized human milk remains stable during the first month of storage at –20°C and –80°C. However after the first month, a slow decrease in concentration progresses until the end of 6 months of storage at both temperatures. The levels of n‐6 and n‐3 fatty acids, particularly linoleic acid, alpha‐linolenic acid and DHA, in human milk vary widely within and among different populations, and are readily changed by maternal dietary intake of the respective fatty acid. The present paper reviews recent understanding from key researchers of maternal diet and human milk fat composition and form our work the effect of milk fat composition on storage conditions. It is important to understand that maternal diet can affect human milk fat composition and subsequently infant development and growth.
Outcomes after living donor liver transplantation for acute liver failure in Japan: Results of a nationwide survey
Authors: Yamashiki Noriyo , Sugawara Yasuhiko , Tamura Sumihito , Nakayama Nobuaki , Oketani Makoto , Umeshita Koji , Uemoto Shinji , Mochida Satoshi , Tsubouchi Hirohito , Kokudo Norihiro
Published: May 2012

Nationwide surveys of acute liver failure (ALF) are conducted annually in Japan, and 20% of patients with ALF undergo liver transplantation (LT). We extracted data for 212 patients who underwent LT for ALF from the nationwide survey database of the Intractable Liver Diseases Study Group of Japan. After the exclusion of 3 patients who underwent deceased donor LT, 209 recipients of living donor liver transplantation (LDLT) were analyzed. ALF patients were placed into 3 subgroups according to the time from the onset of the disease to the occurrence of encephalopathy: patients who presented with encephalopathy within 10 days of the disease's onset were classified as having acute ALF, patients who presented within 11 to 56 days were classified as having subacute ALF, and patients who presented within 9 to 24 weeks were classified as having late-onset hepatic failure (LOHF). Long-term follow-up data were obtained from the registry of the Japanese Liver Transplantation Society. The 2 data sets were merged, and descriptive and survival data were analyzed. A Cox regression analysis was performed to define factors predicting overall mortality, short-term mortality (≤90 days after LT), and long-term mortality (>90 days after LT). One hundred ninety of the analyzed patients (91%) were adults (age ≥ 18 years); 70 patients (34%) were diagnosed with acute ALF, 124 (59%) were diagnosed with subacute ALF, and 15 (7%) were diagnosed with LOHF. Hepatitis B virus was the most common cause of acute ALF (61%), whereas autoimmune hepatitis (14%) and drug allergy–induced hepatitis (14%) were more frequent in patients with subacute ALF or LOHF. The cumulative patient survival rates 1, 5, and 10 years after LT were 79%, 74%, and 73%, respectively. Patient age was associated with short- and long-term mortality after LT, whereas ABO incompatibility affected short-term mortality, and donor age affected long-term mortality. In conclusion, the long-term outcomes of LDLT for ALF in this study were excellent, regardless of the etiology or classification. The majority of the donors were living donors. Increasing the deceased donor pool might be an urgent necessity. Liver Transpl, 2012. © 2012 AASLD.
Existence of solutions for degenerate elliptic equations with singular potential on conical singular manifolds
Authors: Chen Hua , Wei Yawei , Zhou Bin
Published: May 2012

In this work, we study the Dirichlet problem for a class of degenerate elliptic equations with singular potential on conical singular manifolds. By using the cone Sobolev inequality and Hardy inequality, the existence of nontrivial solutions has been proved.
Radial positive definite functions and spectral theory of the Schrödinger operators with point interactions
Authors: Goloshchapova N. , Malamud M. , Zastavnyi V.
Published: May 2012

We complete the classical Schoenberg representation theorem for radial positive definite functions. We apply this result to study spectral properties of self‐adjoint realizations of two‐ and three‐dimensional Schrödinger operators with point interactions on a finite set. In particular, we prove that any realization has purely absolute continuous nonnegative spectrum.
Artificial Leaves via Reproduction of Hierarchical Structures by a Fast Molding and Curing Process
Authors: Park Sungjune , van Rijn Patrick , Böker Alexander
Published: May 2012

In this work, we have developed a practical approach for the replication of hierarchical structures on a native leaf surface via a fast two‐step molding process combining both the fast curability to prevent shrinkage of cells and the strong resistance to chemical compounds for further applications. The negative replica of the leaf was produced from perfluoropolyether (PFPE) by precise molding followed by a fast curing with UV. A liquid ceramic precursor material (polyvinylsilazane, PVSZ) was used to fabricate the positive leaf structure through the same process as applied for the negative imprint of the surface yielding a highly detailed replica of the native leaf surface structure. Static water contact angle measurements show that the biomimetic surfaces exhibit a wettability similar to the native leaves.
A Narrative Review of Evidence‐Based Recommendations for the Physical Examination of the Lumbar Spine, Sacroiliac and Hip Joint Complex
Authors: Wong C. K. , Johnson E. K.
Published: May 2012

Non‐specific low back pain is a frequent complaint in primary care, but the differential diagnosis for low back pain can be complex. Despite advances in diagnostic imaging, a specific pathoanatomical source of low back pain can remain elusive in up to 85% of individuals. Best practice guidelines recommend that clinicians conduct a focused physical examination to help to identify patients with non‐specific low back pain and an evidence‐based course of clinical management. The use of sensitive and specific clinical methods to assess the lumbar spine, sacroiliac and hip joints is critical for effective physical examination. Psychosocial factors also play an important role in the evaluation of individuals with low back pain, but are not included in this narrative review of physical examination methods. Physical examination of the lumbar spine, sacroiliac and hip joints is presented, organized around patient position for efficient and effective clinical assessment. Copyright © 2012 John Wiley & Sons, Ltd.
Mit Hochdurchsatz auf der Suche nach neuen Katalysatoren
Authors: Klemm Sebastian , Fink Nicole , Mayrhofer Karl
Published: May 2012

Die Umwandlung von CO2 in Energieträger wie Methanol ist eine moderne Dream Reaction — also eine der Reaktionen, die einfach und mit billigen Edukten in einem Schritt, unter milden Bedingungen und in hohen Ausbeuten hochwertige Produkte erzeugen. Mikroelektrochemisches Screening gekoppelt mit Online‐Produktanalyse soll helfen, Katalysatoren für die CO2‐Reduktion zu finden.
Simulationen auswerten
Authors: Brehm Martin
Published: May 2012

Travis ist ein freies Programmpaket, das Molekulardynamik‐ und Monte‐Carlo‐Trajektorien analysiert und visualisiert.
Die deutsche Rohstoffstrategie — eine Zwischenbilanz
Authors: Gäckle Thomas
Published: May 2012

Seit letztem Herbst gibt es eine deutsche Rohstoffstrategie. Sie setzt an mehreren Stellen an, um die Versorgungssicherheit mit metallischen und mineralischen Rohstoffen zu verbessern.
Zwischen Wissenschaft und Verwaltung
Authors: Häckel Marko
Published: May 2012

Universitäten und Forschungsinstitute stehen unter dem Druck, ihre Verwaltungen weiter zu professionalisieren, um ihren Aufgaben in Forschung und Lehre gerecht zu werden. Daraus hat sich ein neues Berufsfeld entwickelt: Forschungsmanagement.
Recherchieren, organisieren, verhandeln
Authors: Gottardi Elvira
Published: May 2012

Eine Tätigkeit im Wissenschaftsmanagement ist nur wenigen Chemiestudenten präsent, wenn sie an Berufseinstieg und Karriere denken. Das war bei Elvira Gottardi nicht anders. Heute unterstützt sie als wissenschaftliche Referentin den Präsidenten der Leibniz‐Gemeinschaft dabei, Strategien zu entwerfen.
Effectiveness of percutaneous posterior tibial nerve stimulation for overactive bladder: A systematic review and meta‐analysis
Authors: Burton C. , Sajja A. , Latthe P.M.
Published: May 2012

Aim

To evaluate the effectiveness of posterior percutaneous tibial nerve stimulation (PTNS) in treating overactive bladder (OAB) symptoms by systematic review of the literature.

Methods

Systematic literature search was carried out (up to April 2011) using relevant search terms in Medline, EMBASE, CINAHL, CENTRAL, National Library for Health, MetaRegister of controlled trials, LILACS, and Google Scholar. Relevant randomized controlled trials (RCTs) and prospective studies were selected and then analyzed by two‐independent reviewers. Meta‐analysis was performed with random effects model using STATA 8 for non‐randomized prospective studies and with Review Manager 5.1 for RCTs.

Results

The studies report variable initial success rates (37–82%) for treating OAB symptoms with PTNS. Four randomized trials compared PTNS with Sham treatment showing a significant difference favoring PTNS [RR 7.02 95% confidence interval (CI) 1.69–29.17]. Two randomized trials compared PTNS with antimuscarinic medication with no significant difference in the change in bladder diary parameters between the treatments. Ten prospective non‐randomized studies were included. The definitions of success were varied. The pooled subjective success rate was 61.4% (95% CI 57.5–71.8) and objective success rate was 60.6% (95% CI 49.2–74.7).

Conclusion

There is evidence of significant improvement in OAB symptoms using PTNS which is comparable to the effect of antimuscarinics but with a better side effect profile. The studies included in the review only considered short‐term outcomes after initial treatment. In order to recommend PTNS as a practical treatment option, long‐term data and health economic analysis are needed. Neurourol. Urodynam. 31:1206–1216, 2012. © 2012 Wiley Periodicals, Inc.
Uniformly stable rectangular elements for fourth order elliptic singular perturbation problems
Authors: Wang Li , WU Yongke , Xie Xiaoping
Published: May 2012

In this article, we consider rectangular finite element methods for fourth order elliptic singular perturbation problems. We show that the non‐ C0 rectangular Morley element is uniformly convergent in the energy norm with respect to the perturbation parameter. We also propose a C0 extended high order rectangular Morley element and prove the uniform convergence. Finally, we do some numerical experiments to confirm the theoretical results. © 2012 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2013
Violence in the Central Iberian Peninsula during the Bronze Age: A Possible Prehistoric Homicide
Authors: JiméNez‐Brobeil S. A. , Roca M. G. , Laffranchi Z. , NáJera T. , Molina F.
Published: May 2012

One of the most interesting sites of the Bronze Age in the central area of the Iberian Peninsula is La Motilla del Azuer (Daimiel, Ciudad Real), dated between 2200 and 1350 bc. The main objective of this study was to investigate interpersonal violence in this site and to report an uncommon case of violent death. No traumatic injury was detected in any child, and men and women significantly differed in the frequency of traumas. More traumatisms were found in men from the earlier stages of occupation, including a young man with at least three blunt force traumas and 26 sharp force traumas. The archaeological findings and trauma patterns in the skeletons of the 65 individuals studied suggest a relatively intense level of exposure to violence for adult men in the earlier stages of occupation of this settlement. Copyright © 2012 John Wiley & Sons, Ltd.
Estimation of the Original Number of Individuals Using Multiple Skeletal Elements
Authors: Nikita E.
Published: May 2012

The current report presents simple equations for the estimation of the original number of individuals that have been preserved in a sample of commingled remains and compares the estimates obtained by them to those obtained from the application of the joint hypergeometric estimator, elaborate computer simulations and documented collections. The equations that perform better under different preservation scenarios are the ones that take into consideration that the various bone types have different post mortem survival probabilities. Copyright © 2012 John Wiley & Sons, Ltd.
Qualitative improvement and quantitative assessment of N‐terminomics
Authors: Guryča Vilém , Lamerz Jens , Ducret Axel , Cutler Paul
Published: May 2012

Proteolysis represents one of the most tightly controlled physiological processes, as proteases create events that will typically commit pathways in an irreversible manner. Despite their implication in nearly all biological systems, our understanding of the role of proteases in disease pathology is often limited. Several approaches to studying proteolytic activity as it relates to biology, pathophysiology, and drug therapy have been published, including the recently described terminal amine isotopic labeling of substrates (TAILS) strategy by Kleifeld and colleagues. Here, we investigate TAILS as a methodology based on targeted enrichment and mass spectrometric detection of endogenous N‐terminal peptides from clinically relevant biological samples and its potential to provide quantitative information on proteolysis and elucidation of the protease cleavage sites. While optimizing the most current protocol, by switching to a streamlined one‐tube format and simplifying the reagents’ removal steps, we demonstrate the advantages over previously published methods and provide solutions to some of the technical challenges presented in the Kleifeld publication. We also identify some of the current and unresolved limitations. We use human plasma as a model system to provide data, which illustrates some of the key analytical parameters of the modified TAILS procedure, including specificity, sensitivity, quantitative precision, and accuracy.
Advancing the sensitivity of selected reaction monitoring‐based targeted quantitative proteomics
Authors: Shi Tujin , Su Dian , Liu Tao , Tang Keqi , Camp David G. , Qian Wei‐Jun , Smith Richard D.
Published: May 2012

Selected reaction monitoring (SRM) – also known as multiple reaction monitoring (MRM) – has emerged as a promising high‐throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for, e.g. detecting low‐abundance biomarkers likely present at the low ng/mL to pg/mL range in human blood plasma or serum, or extremely low‐abundance signaling proteins in cells or tissues. Herein, we review recent advances in methods and technologies, including front‐end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides including posttranslational modifications, as well as advances in MS instrumentation which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low‐abundance proteins at low‐ to sub‐ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed.
Mass spectrometry‐based absolute protein quantification: PSAQ™ strategy makes use of “noncanonical” proteotypic peptides
Authors: Jaquinod Michel , Trauchessec Mathieu , Huillet Céline , Louwagie Mathilde , Lebert Dorothée , Picard Guillaume , Adrait Annie , Dupuis Alain , Garin Jérôme , Brun Virginie , Bruley Christophe
Published: May 2012

Absolute quantification of proteins using isotope dilution mass spectrometry requires the selection of proteotypic peptides. When choosing these peptides, a certain number of rules must be respected. Several of these were established to safeguard against quantification errors resulting from the isotopically labeled standard peptides not behaving in the same way as the peptides to be quantified. Of all absolute quantification methods using isotope dilution, Protein Standard for Absolute Quantification (PSAQTM) offers the maximal protein sequence coverage. In the present study, we show that the PSAQ method presents a previously unreported advantage for protein quantification as it makes use of Met/Cys‐containing peptides and peptides‐containing miscleavages in addition to proteotypic peptides. By increasing the total number of peptides that can be considered, robustness of quantification is improved, paving the way for a facilitated quantification of low abundant and/or low‐molecular‐weight proteins.
Multiplexed quantification of estrogen receptor and HER2/Neu in tissue and cell lysates by peptide immunoaffinity enrichment mass spectrometry
Authors: Schoenherr Regine M. , Whiteaker Jeffrey R. , Zhao Lei , Ivey Richard G. , Trute Mary , Kennedy Jacob , Voytovich Uliana J. , Yan Ping , Lin Chenwei , Paulovich Amanda G.
Published: May 2012

Access to a wider range of quantitative protein assays would significantly impact the number and use of tissue markers in guiding disease treatment. Quantitative mass spectrometry‐based peptide and protein assays, such as immuno‐SRM assays, have seen tremendous growth in recent years in application to protein quantification in biological fluids such as plasma or urine. Here, we extend the capability of the technique by demonstrating the application of a multiplexed immuno‐SRM assay for quantification of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) levels in cell line lysates and human surgical specimens. The performance of the assay was characterized using peptide response curves, with linear ranges covering approximately four orders of magnitude and limits of detection in the low fmol/mg lysate range. Reproducibility was acceptable with median coefficients of variation of approximately 10%. We applied the assay to measurements of ER and HER2 in well‐characterized cell line lysates with good discernment based on ER/HER2 status. Finally, the proteins were measured in surgically resected breast cancers, and the results showed good correlation with ER/HER2 status determined by clinical assays. This is the first implementation of the peptide‐based immuno‐SRM assay technology in cell lysates and human surgical specimens.
The basicity of substituted N,N‐dimethylanilines in solution and in the gas phase
Authors: Kaljurand Ivari , Lilleorg Roman , Murumaa Algis , Mishima Masaaki , Burk Peeter , Koppel Ivar , Koppel Ilmar A. , Leito Ivo
Published: May 2012

Basicities of a number of ring‐substituted N,N‐dimethylanilines (DMA) and some related bases in water, acetonitrile, and THF and in the gas phase have been experimentally determined. Gas‐phase basicities of DMAs and related bases were calculated at DFT B3LYP 6‐311+G** and G3(MP2) levels. Structure–Basicity relationships in these four media were discussed. By comparison of gas‐phase basicity shifts induced by stepwise substitution, starting from ammonia and ending at triphenylamine, it was observed that solvent effects of water and acetonitrile exceed the structural effects on intrinsic basicity. It was shown that the influence of substituents in the phenyl ring on DMA basicity is reduced by two to three times when going from the gas phase into the abovementioned condensed media. In the gas phase, 4‐NO, 4‐NO2, 4‐CN, 4‐COMe, and 4‐CHO substituted DMAs protonate on substituent, whereas in solvents, only 4‐NO‐DMA probably protonates on substituent. The sensitivity of DMA basicity toward substitution in the phenyl ring was compared with the related family of phenylphosphazene bases, and it was found that the substituent effect is stronger in DMAs by 1.35 times in acetonitrile, 1.45 times in the gas phase, 2.0 times in THF, and 2.6 times in water. Copyright © 2012 John Wiley & Sons, Ltd.
Further evidence of impaired position sense in knee osteoarthritis
Authors: Marks R
Published: May 2012

The knee joint position sense of a control group of healthy women was compared with that of women diagnosed as having severe osteoarthritis (OA) of the knee. Movements monitored were multi‐joint when weightbearing on one leg. All subjects completed two angle rematching tests on two separate test occasions, and the criterion and reproduction angles which lay in the range of 15–45° knee flexion were recorded photographically on each occasion. The results showed that the OA group performed the rematching tests with less accuracy than the controls (p<0.05). Additionally, the OA group displayed significantly higher average flexion error magnitudes than the controls. These results suggest that joint position sense is less accurate and may be systematically distorted during multi‐joint movements of the affected legs of a high proportion of women with severe knee OA. They further suggest that to improve their functional performance, patients with knee OA probably require a carefully constructed sensorimotor rehabilitation programme in which pain, effusion and fatigue are minimised.
Sequential four‐state folding/unfolding of goat α‐lactalbumin and its N‐terminal variants
Authors: Tomoyori Katsuaki , Nakamura Takashi , Makabe Koki , Maki Kosuke , Saeki Kimiko , Kuwajima Kunihiro
Published: May 2012

Equilibria and kinetics of folding/unfolding of α‐lactalbumin and its two N‐terminal variants were studied by circular dichroism spectroscopy. The two variants were wild‐type recombinant and Glu1‐deletion (E1M) variants expressed in Escherichia coli. The presence of an extra methionine at the N terminus in recombinant α‐lactalbumin destabilized the protein by 2 kcal/mol, while the stability was recovered in the E1M variant in which Glu1 was replaced by Met1. Kinetic folding/unfolding reactions of the proteins, induced by stopped‐flow concentration jumps of guanidine hydrochloride, indicated the presence of a burst‐phase in refolding, and gave chevron plots with significant curvatures in both the folding and unfolding limbs. The folding‐limb curvature was interpreted in terms of accumulation of the burst‐phase intermediate. However, there was no burst phase observed in the unfolding kinetics to interpret the unfolding‐limb curvature. We thus assumed a sequential four‐state mechanism, in which the folding from the burst‐phase intermediate takes place via two transition states separated by a high‐energy intermediate. We estimated changes in the free energies of the burst‐phase intermediate and two transition states, caused by the N‐terminal variations and also by the presence of stabilizing calcium ions. The Φ values at the N terminus and at the Ca2+‐binding site thus obtained increased successively during folding, demonstrating the validity of the sequential mechanism. The stability and the folding behavior of the E1M variant were essentially identical to those of the authentic protein, allowing us to use this variant as a pseudo‐wild‐type α‐lactalbumin in future studies. Proteins 2012; © 2012 Wiley Periodicals, Inc.
Atmospheric water‐vapour profiling from passive microwave sounders over ocean and land. Part I: Methodology for the Megha‐Tropiques mission
Authors: Aires Filipe , Bernardo Frédéric , Prigent Catherine
Published: May 2012

A water‐vapour retrieval algorithm has been developed that uses satellite observations in the microwave region. It is based on neural‐network modelling and includes a dedicated calibration scheme for the satellite observations. The water vapour is retrieved for clear and cloudy scenes, over both ocean and land surfaces. Precipitation cases are excluded. The atmospheric relative humidity profile is retrieved on six atmospheric layers, together with the total column water vapour. By‐products are also retrieved by the algorithm, including surface temperature and microwave emissivities over the continents and surface wind speed over the ocean. A first version of a retrieval chain has been produced for the French–Indian Megha‐Tropiques mission launched on 12 October 2011. The algorithm has been further developed for the instruments AMSR‐E/HSB (resp. AMSU‐A/MHS) on board the AQUA (resp. MetOp) platform, in order to test it on existing satellite observations. In this article, the principles of the inversion method are presented and the theoretical retrieval uncertainties are assessed using direct tests on simulated data as well as estimations using the traditional information‐content analysis. Results of the retrieval algorithm will be evaluated in a companion article for AQUA and MetOp observations using comparisons with European Centre for Medium‐Range Weather Forecasts (ECMWF) analysis and radiosonde measurements. Copyright © 2012 Royal Meteorological Society