bluuebunny/crossref_metadata_2025 huggingface dataset:
Gilbert syndrome redefined: A complex genetic haplotype influences the regulation of glucuronidation
Authors: Ehmer Ursula , Kalthoff Sandra , Fakundiny Bastian , Pabst Brigitte , Freiberg Nicole , Naumann Ronald , Manns Michael P. , Strassburg Christian P.
Published: December 2011

Gilbert syndrome (GS) is characterized by intermittent unconjugated hyperbilirubinemia without structural liver damage, affecting about 10% of the white population. In GS the UGT1A1*28 variant reduces bilirubin conjugation by 70% and is associated with irinotecan and protease inhibitor side effects. The aim of this study was to characterize potential

in vivo

consequences of

UGT1A

gene variability in GS. Three hundred GS patients (UGT1A1*28 homozygous) and 249 healthy blood donors (HBD) were genotyped for

UGT1A

(UGT1A1*28,

UGT1A3
-66 T>C, UGT1A6*3a, UGT1A7*3) and transporter single nucleotide polymorphisms (SNPs) (
SCLO1B1

p.V174A,

SCLO1B1

p.N130D,

ABCC2

p.I1324I,

ABCC2
-24 UTR) using TaqMan-5′-nuclease-assays. A humanized transgenic

UGT1A
-SNP and corresponding wildtype mouse model were established carrying the GS-associated

UGT1A

variant haplotype. UGT1A transcript and protein expression, and transcriptional activation were studied

in vivo
. Homozygous UGT1A1*28 GS individuals were simultaneously homozygous for UGT1A3–66 T>C (91%), UGT1A6*2a (77%), and UGT1A7*3 (77%). Seventy-six percent of GS and only 9% of HBD were homozygous for the variant haplotype spanning four

UGT1A

genes.

SCLO1B1

and

ABCC2

SNPs showed no differences. In transgenic humanized

UGT1A

SNP and wildtype mice this

UGT1A

haplotype led to lower UGT1A messenger RNA (mRNA) expression and UGT1A protein synthesis.

UGT1A

transcriptional activation by dioxin, phenobarbital, and endotoxin was significantly reduced in SNP mice.

Conclusion:

Our data redefine the genetic basis behind GS.

In vivo

data studying the genotype present in 76% of GS individuals suggest that transcription and transcriptional activation of glucuronidation genes responsible for conjugation and detoxification is directly affected, leading to lower responsiveness. This study suggests that GS should be considered a potential risk factor for drug toxicity.
Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease
Authors: Krawczyk Marcin , Lütjohann Dieter , Schirin-Sokhan Ramin , Villarroel Luis , Nervi Flavio , Pimentel Fernando , Lammert Frank , Miquel Juan Francisco
Published: December 2011

In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common

ABCG5/8

variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians).

ABCG5/8

variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts.

Conclusion :

Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol GSD. (Hepatology 2012)
Zinc finger transcription factor 191, directly binding to β-catenin promoter, promotes cell proliferation of hepatocellular carcinoma
Authors: Liu Guoyuan , Jiang Songmin , Wang Chenji , Jiang Wei , Liu Zulong , Liu Chao , Saiyin Hexige , Yang Xianmei , Shen Suqin , Jiang Deke , Zhou Ping , Han Dingding , Hu Xiaohui , Yi Qing , Yu Long
Published: December 2011

Activation of β-catenin, the central effector of the canonical wingless-type (Wnt) pathway, has been implicated in hepatocellular carcinoma (HCC). However, the transcription regulation mechanism of the β-catenin gene in HCC remains unknown. Here we report that human zinc finger protein 191 (ZNF191) is a potential regulator of β-catenin transcription. ZNF191, a Krüppel-like protein, specifically interacts with the TCAT motif, which constitutes the HUMTH01 microsatellite in the tyrosine hydroxylase (
TH
) gene

ex vivo
. We demonstrate that ZNF191 is significantly overexpressed in human HCC specimens and is associated with growth of human HCC cells. Global profiling of gene expression in ZNF191 knockdown human hepatic L02 cells revealed that the important Wnt signal pathway genes β-catenin and cyclin D1 messenger RNAs (mRNAs) are significantly down-regulated. In agreement with transcription level, β-catenin and cyclin D1 proteins are also down-regulated in transient and stable ZNF191 knockdown L02 and hepatoma Hep3B cell lines. Moreover, significant correlation between ZNF191 and β-catenin mRNA expression was detected in human HCCs. Promoter luciferase assay indicated that ZNF191 can increase transcription activity of the full-length β-catenin (CTNNB1) promoter, and nucleotide (nt)-1407/-907 of the CTNNB1 promoter exhibited the maximum transcriptional activity. Electrophoretic mobility shift assay showed that purified ZNF191 protein can directly bind to the CTNNB1 promoter, and the binding region is located at nt-1254/-1224. Finally, we demonstrate that the key binding sequence of ZNF191

in vivo

is ATTAATT.

Conclusion:

ZNF191 can directly bind to the CTNNB1 promoter and activate the expression of β-catenin and its downstream target genes such as cyclin D1 in hepatoma cell lines. This study uncovers a new molecular mechanism of transcription regulation of the β-catenin gene in HCC.
Synergistic inhibition of hepatocellular carcinoma growth by cotargeting chromatin modifying enzymes and poly (ADP-ribose) polymerases
Authors: Zhang Jun-Xiang , Li Da-Qiang , He Aiwu Ruth , Motwani Mona , Vasiliou Vasilis , Eswaran Jeyanthy , Mishra Lopa , Kumar Rakesh
Published: December 2011

Hepatocellular carcinoma (HCC) is a particularly lethal form of cancer, yet effective therapeutic options for advanced HCC are limited. The poly(ADP-ribose) polymerases (PARPs) and histone deacetylases (HDACs) are emerging to be among the most promising targets in cancer therapy, and sensitivity to PARP inhibition depends on homologous recombination (HR) deficiency and inhibition of HDAC activity blocks the HR pathway. Here, we tested the hypothesis that cotargeting both enzymatic activities could synergistically inhibit HCC growth and defined the molecular determinants of sensitivity to both enzyme inhibitors. We discovered that HCC cells have differential sensitivity to the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and PARP inhibitor olaparib, and identified one pair of cell lines, termed SNU-398 and SNU-449, with sensitive versus resistant phenotype to both enzyme inhibitors, respectively. Coadministration of SAHA and olaparib synergistically inhibited the growth of SNU-398 but not SNU-449 cells, which was associated with increased apoptosis and accumulated unrepaired DNA damage. Multiple lines of evidence demonstrate that the hepatic fibrosis/hepatic stellate cell activation may be an important genetic determinant of cellular sensitivity to both enzymatic inhibitors, and coordinate activation or inactivation of the aryl hydrocarbon receptor (AhR) and cyclic adenosine monophosphate (cAMP)-mediated signaling pathways are involved in cell response to SAHA and olaparib treatment.

Conclusion:

These findings suggest that combination therapy with both enzyme inhibitors may be a strategy for therapy of sensitive HCC cells, and identification of these novel molecular determinants may eventually guide the optimal use of PARP and HDAC inhibitors in the clinic.
Development of a risk index for the prediction of chronic post‐surgical pain
Authors: Althaus A. , Hinrichs‐Rocker A. , Chapman R. , Becker O. Arránz , Lefering R. , Simanski C. , Weber F. , Moser K.‐H. , Joppich R. , Trojan S. , Gutzeit N. , Neugebauer E.
Published: December 2011

The incidence of chronic post‐surgical pain (CPSP) after various common operations is 10% to 50%. Identification of patients at risk of developing chronic pain, and the management and prevention of CPSP remains inadequate. The aim of this study was to develop an easily applicable risk index for the detection of high‐risk patients that takes into account the multifactorial aetiology of CPSP. A comprehensive item pool was derived from a systematic literature search. Items that turned out significant in bivariate analyses were then analysed multivariately, using logistic regression analyses. The items that yielded significant predictors in the multivariate analyses were compiled into an index. The cut‐off score for a high risk of developing CPSP with an optimal trade‐off between sensitivity and specificity was identified. The data of 150 patients who underwent different types of surgery were included in the analyses. Six months after surgery, 43.3% of the patients reported CPSP. Five predictors multivariately contributed to the prediction of CPSP: capacity overload, preoperative pain in the operating field, other chronic preoperative pain, post‐surgical acute pain and co‐morbid stress symptoms. These results suggest that several easily assessable preoperative and perioperative patient characteristics can predict a patient's risk of developing CPSP. The risk index may help caregivers to tailor individual pain management and to assist high‐risk patients with pain coping.
Analgesic use in a national community sample of German children and adolescents
Authors: Du Y. , Ellert U. , Zhuang W. , Knopf H.
Published: December 2011

Background

Previous studies suggest that pain management by analgesic medications may be low among children. This study aims to investigate analgesic use and its correlates among children in Germany.

Methods

Analgesic use during a 1‐week period was investigated in a community sample of 14,836 children and adolescents aged between 3 and 17 years in Germany. SPSS complex sample method was used to estimate the prevalence and associated factors of analgesic use among the general child population and among those children with pain in the same child population.

Results

The prevalence of analgesic use was 8.9% among the general child population and 17.5% among children with pain that occurred at least once a week. Paracetamol (acetaminophen), aspirin and ibuprofen were the most frequently used paediatric analgesics, accounting for two‐thirds of all analgesics. The vast majority of painkillers were self‐medicated (67%, bought over the counter or obtained from other sources), used for a short term within 1 week (92%) and taken for the treatment of pain (85%). Use of analgesics was closely associated with girls, older age groups, children with a poor overall health status and children with recurrent pain, irrespective of family immigrant background and socioeconomic status.

Conclusion

Analgesic use appears to be low among children in Germany, reflecting largely the fact that pain perceived among children under ambulant care may be mild to moderate and does not need analgesic medications. As the majority of paediatric analgesics were self‐medicated, use of analgesics still should be closely monitored particularly among specific subpopulations such as adolescents to avoid potential abuse.
Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury
Authors: Yasui M. , Shiraishi Y. , Ozaki N. , Hayashi K. , Hori K. , Ichiyanagi M. , Sugiura Y.
Published: December 2011

To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)‐expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5–28 in BLG and on days 5–21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone‐regenerating cells during the bone injury healing. Anti‐NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing.
Pharmacological characterization of lysophosphatidic acid‐induced pain with clinically relevant neuropathic pain drugs
Authors: Ogawa K. , Takasu K. , Shinohara S. , Yoneda Y. , Kato A.
Published: December 2011

Lysophosphatidic acid (LPA), an initiator of neuropathic pain, causes allodynia. However, few studies have evaluated the pharmacological profile of LPA‐induced pain. In this study, a LPA‐induced pain model was developed and pharmacologically characterized with clinically relevant drugs used for neuropathic pain, including antiepileptics, non‐steroidal anti‐inflammatory agents, analgesics, local anaesthetics/antiarrhythmics and antidepressants. Gabapentin (1–30 mg/kg, p.o.) significantly reversed LPA‐induced allodynia, but neither indomethacin (30 mg/kg, p.o.) nor morphine (0.3–3 mg/kg, s.c.) did, which indicates that LPA‐induced pain consists mostly of neuropathic rather than inflammatory pain. Both pregabalin (0.3–10 mg/kg, p.o.) and ω‐CgTX MVIIA (0.01–0.03 μg/mouse, i.t.) completely reversed LPA‐induced allodynia in a dose‐dependent manner. Lidocaine (1–30 mg/kg, s.c.), mexiletine (1–30 mg/kg, p.o.) and carbamazepine (10–100 mg/kg, p.o.) significantly ameliorated LPA‐induced allodynia dose dependently. Milnacipran (30 mg/kg, i.p.) produced no significant analgesic effect in LPA‐induced allodynia. In LPA‐injected mice, expression of the α2δ1 subunit of the voltage‐gated calcium channel (VGCC) was increased in the dorsal root ganglion (DRG) and spinal dorsal horn. Furthermore, the VGCC current was potentiated in both the DRG from LPA‐injected mice and LPA (1 μM)‐treated DRG from saline‐injected mice, and the potentiated VGCC current was amended by treatment with gabapentin (100 μM). The LPA‐induced pain model described here mimics aspects of the neuropathic pain state, including the sensitization of VGCC, and may be useful for the early assessment of drug candidates to treat neuropathic pain.
Pt‐Al2O3 interfacial bonding in implantable hermetic feedthroughs: Morphology and orientation
Authors: Lu Hong , Svehla Martin Joseph , Skalsky Mike , Kong Charlie , Sorrell Charles Christopher
Published: December 2011

The present work examines the chemistry, microstructure, and crystallography of a Pt‐Al2O3 joint used in implantable hermetic feedthrough designs in neural prostheses. Pt was joined to Al2O3 by passing Pt pins through green Al2O3 disks and then sintering in air. This created a Pt‐Al2O3 joint that was prepared for the current investigation by gross sectioning and then polishing and sectioning into slices using focused ion beam milling. The slices were examined by scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. Two types of interfaces in the sintered material were identified: Vitreous‐bonded Pt‐glass‐Al2O3 and direct‐bonded Pt‐Al2O3. In the case of the former, glass formation owing to the presence of glass‐forming additives (to enhance densification and suppress grain growth) and consequent wetting of both the Pt and Al2O3 facilitated interfacial bonding. In the case of the latter, the interfacial planes were (002)Pt // (0
$\overline 2$2) [rhombohedral] or (002)Pt // (0
$\overline 2$2 2) [hexagonal]. The lattice mismatch was calculated to be 11% (based on the calculated d spacings) or 15% (based on the literature d spacings). Both of these suggest the establishment of semicoherent interfaces. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Very efficient search for protein alignment—VESPA
Authors: Randić M.
Published: December 2011

A novel approach to the problem of protein alignments is described, which in comparison with existing approaches is visibly more efficient. This approach is based on superposition of amino acid adjacency matrices of a pair of proteins, which have been modified to record the sequential order of amino acids. As a result, one obtains simultaneously all segments of the two proteins which are shifted relative to one another by one or more positions in either directions, without need of a prior exhaustive search for an alignment that included unproductive directions and unknown displacement steps. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012
High‐grade osteosarcoma treated with hemicortical resection and biological reconstruction
Authors: Chen Wei‐Ming , Wu Po‐Kuei , Chen Cheng‐Fong , Chung Lien‐Hsiang , Liu Chien‐Lin , Chen Tain‐Hsiung
Published: December 2011

Background and Objectives

Wide excision with a 2–3 cm safe margin is widely‐accepted in treating high‐grade osteosarcoma. However, a wider margin sacrifices more healthy bone and may jeopardize joint function. We hypothesize that our innovative hemicortical resection for such tumors leads to better joint function without higher recurrence rate.

Methods

Between August 2002 and April 2007, six patients of high‐grade osteosarcoma were treated with hemicortical resection and biological reconstruction.

Results

Five tumors were located around the knee and one was located in the distal tibia. The mean tumor size was 20.5 cm3. The bone defects were reconstructed using recycled autograft in four cases (one by extracorporeal irradiation; three by liquid nitrogen) and structural allograft in two. In an average follow‐up of 52 months (24–96), all patients survived without local recurrence or metastasis. All bone grafts incorporated well without mechanical failure or infection. The average Musculoskeletal Tumor Society score was 97.7%.

Conclusions

Hemicortical resection for high‐grade osteosarcomas located eccentrically in the long bones may be a reliable technique leading to good joint function by preserving surrounding healthy tissues. The functional outcome was encouraging, although long‐term follow‐up is mandatory to validate. With the advancement of chemotherapy and radiographic three‐dimensional imaging, the safe margin in wide excision of high‐grade osteosarcoma may be narrowed down in light of joint surface preservation. J. Surg. Oncol. 2012; 105:825–829. © 2011 Wiley Periodicals, Inc.
Comparison of radioguided occult lesion localization (ROLL) and wire localization for non‐palpable breast cancers: A meta‐analysis
Authors: Sajid Muhammad S. , Parampalli Umesh , Haider Zishan , Bonomi Ricardo
Published: December 2011

Four randomized trials encompassing 449 patients of non‐palpable breast cancer undergoing with radio‐guided occult lesion localization (ROLL) or wire guided localization (WGL). In the fixed effects model, accurate localization, peri‐procedural complications, and reoperation rate were comparable between two techniques. Risk of having positive resection margins following WGL was higher. Duration of localization and surgical excision was shorter for ROLL. Volume and weight of the excised occult breast lesion was similar in WGL and ROLL groups. J. Surg. Oncol. 2012; 105:852–858. © 2011 Wiley Periodicals, Inc.
Reirradiation to the pelvis for recurrent rectal cancer
Authors: Koom Woong Sub , Choi Yunseon , Shim Su Jung , Cha Jihye , Seong Jinsil , Kim Nam Kyu , Nam Ki Chang , Keum Ki Chang
Published: December 2011

Objectives

This study investigated late toxicity and infield progression‐free survival in patients with locally recurrent rectal cancer (LRRC) who had previously received irradiation to the pelvis.

Methods

Twenty‐two patients were treated by reirradiation to the pelvis between January 2000 and August 2007. All patients received curative surgery with preoperative or postoperative chemoradiotherapy as an initial treatment. Five patients (23%) underwent surgical resection after reirradiation. The median follow‐up duration was 20 months (range, 7–91 months).

Results

Two patients (9%) had grade‐3 acute toxicity and eight patients (36%) had grade‐3 to ‐4 late toxicity. The incidence of grade‐3 to ‐4 late toxicity in the gastrointestinal and urinary system was 18% and 27%, respectively. Recurrent tumor location (axial or anterior) and surgical resection after reirradiation significantly influenced severe late toxicity (P = 0.024 and P = 0.039, respectively). In the 17 patients not undergoing surgery after reirradiation, median infield progression‐free survival was 16 months. Reirradiation doses exceeding 50 Gyαβ10 (equivalent dose in 2 Gy fractions) significantly increased the infield progression‐free survival (P = 0.005).

Conclusions

Tumor location (axial or anterior) and surgery after reirradiation may increase severe late toxicity. In addition, an EQD2 exceeding 50 Gyαβ10 may improve infield control. J. Surg. Oncol. 2012; 105:637–642. © 2011 Wiley Periodicals, Inc.
Far infrared‐assisted extraction followed by MEKC for the simultaneous determination of flavones and phenolic acids in the leaves of Rhododendron mucronulatum Turcz
Authors: Fu Yuejiao , Zhang Luyan , Chen Gang
Published: December 2011

A method based on micellar electrokinetic chromatography with amperometric detection and far infrared‐assisted extraction has been developed for the simultaneous determination of two flavones (rutin and farrerol) and three phenolic acids (syringic acid, vanillic acid, and 4‐hydroxybenzoic acid) in the dried leaves of Rhododendron mucronulatum Turcz., a commonly used traditional Chinese medicine. The effects of some important factors such as the voltage applied on the infrared generator, irradiation time, the concentration of borate and sodium dodecylsulfate (SDS), separation voltage, and detection potential were investigated to acquire the optimum conditions. The detection electrode was a 300‐μm diameter carbon disc electrode. The five analytes could be well separated within 8 min in a 40 cm‐long capillary at a separation voltage of 12 kV in a 50 mM borate buffer (pH 9.2) containing 50 mM SDS. The relationship between peak current and analyte concentration was linear over about three orders of magnitude with the detection limits (S/N=3) ranging from 0.20 to 0.46 μM. The results indicated that far infrared irradiations significantly enhanced the extraction efficiency. The extraction time was substantially reduced to 6 min compared with 3 h for conventional hot solvent extraction.
Comparison of the sequential organ failure assessment score with the King's College Hospital criteria and the model for end-stage liver disease score for the prognosis of acetaminophen-induced acute liver failure#
Authors: Cholongitas Evangelos , Theocharidou Eleni , Vasianopoulou Panayota , Betrosian Alex , Shaw Steve , Patch David , O'Beirne James , Agarwal Banwari , Burroughs Andrew K.
Published: December 2011

Acetaminophen-induced acute liver failure (ALF) is a complex multiorgan illness. An assessment of the prognosis is essential for the accurate identification of patients for whom survival without liver transplantation (LT) is unlikely. The aims of this study were the comparison of prognostic models [King's College Hospital (KCH), Model for End-Stage Liver Disease, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II)] and the identification of independent prognostic indicators of outcome. We evaluated consecutive patients with severe acetaminophen-induced ALF who were admitted to the intensive care unit. At admission, demographic, clinical, and laboratory parameters were recorded. The discriminative ability of each prognostic score at the baseline was evaluated with the area under the receiver operating characteristic curve (AUC). In addition, using a multiple logistic regression, we assessed independent factors associated with outcome. In all, 125 consecutive patients with acetaminophen-induced ALF were evaluated: 67 patients (54%) survived with conservative medical management (group 1), and 58 patients (46%) either died without LT (28%) or underwent LT (18%; group 2). Group 1 patients had significantly lower median APACHE II (10 versus 14) and SOFA scores (9 versus 12) than group 2 patients (P < 0.001). The independent indicators associated with death or LT were a longer prothrombin time (P = 0.007), the inspiratory oxygen concentration (P = 0.005), and the lactate level at 12 hours (P < 0.001). The KCH criteria had the highest specificity (83%) but the lowest sensitivity (47%), and the SOFA score had the best discriminative ability (AUC = 0.79). In conclusion, for patients with acetaminophen-induced ALF, the SOFA score performed better than the other prognostic scores, and this reflected the presence of multiorgan dysfunction. A further evaluation of SOFA with the KCH criteria is warranted. Liver Transpl 18:405–412, 2012. © 2011 AASLD.
VUV‐Induced Photopolymerization of Acrylates
Authors: Scherzer Tom
Published: December 2011

Acrylates and methacrylates are photopolymerized without photoinitiator by exposure to 172 nm radiation. The kinetics of the polymerization is studied using real‐time Fourier‐transform infrared attenuated total reflectance (FTIR‐ATR) spectroscopy. It is shown that layers with a thickness of ≈500 nm can be polymerized very rapidly. The effect of structure, viscosity, functionality, and absorption of the acrylates as well as the influence of temperature and oxygen concentration on the reactivity are studied. A strong conversion gradient is observed in layers up to ≈2 μm thickness, which reflects the intensity gradient within the layer. However, the penetration of the polymerization into the layer exceeds the initial penetration depth of the VUV radiation, which indicates strong bleaching of the acrylates during irradiation.
Role of epigenetic and miR‐22 and miR‐29b alterations in the downregulation of Mat1a and Mthfr genes in early preneoplastic livers in rats induced by 2‐acetylaminofluorene
Authors: Koturbash Igor , Melnyk Stepan , James S. Jill , Beland Frederick A. , Pogribny Igor P.
Published: December 2011

Carcinogenesis is a multistep sequential process of clonal expansion of initiated cells associated with the accumulation of multiple cancer‐specific heritable phenotypes. The acquisition of these heritable cancer‐specific alterations may be triggered by mutational and/or non‐mutational changes in the genome that affect the regulation of gene expression. Currently, cancer‐specific epigenetically mediated changes in gene expression are regarded as driving events in tumorigenesis. In the present study, we investigated the role of gene‐specific expression changes in the mechanism of rat hepatocarcinogenesis induced by the complete hepatocarcinogen 2‐acetylaminofluorene (2‐AAF). The results of the present study demonstrate significant alterations in gene expression, especially of Mat1a and Mthfr genes, during early stages of rat 2‐AAF‐induced liver carcinogenesis. Both of these genes were downregulated in the livers of 2‐AAF‐treated male rats. Inhibition of Mat1a expression was associated with an increase in histone H3 lysine 27 trimethylation and a decrease in histone H3 lysine 18 acetylation at the gene promoter/first exon region. Additionally, we demonstrate for the first time a critical contribution of miR‐22 and miR‐29b microRNAs in the inhibition of Mat1a and Mthfr gene expression during 2‐AAF‐induced rat hepatocarcinogenesis. The downregulation of Mat1a and Mthfr genes was accompanied by marked functional alterations in one‐carbon metabolism. The results of the present study suggest that downregulation of the Mat1a and Mthfr genes may be one of the main driver events that promote liver carcinogenesis by causing a profound accumulation of subsequent epigenetic abnormalities during progression of the carcinogenic process. © 2011 Wiley Periodicals, Inc.
Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T
Authors: Singh Anup , Haris Mohammad , Cai Kejia , Kassey Victor B. , Kogan Feliks , Reddy Damodar , Hariharan Hari , Reddy Ravinder
Published: December 2011

The sensitivity of chemical exchange saturation transfer (CEST) on glycosaminoglycans (GAGs) in human knee cartilage (gagCEST) in vivo was evaluated at 3 and 7 T field strengths. Calculated gagCEST values without accounting for B0 inhomogeneity (∼0.6 ppm) were >20%. After B0 inhomogeneity correction, calculated gagCEST values were negligible at 3 T and ∼6% at 7 T. These results suggest that accurate B0 correction is a prerequisite for observing reliable gagCEST. Results obtained with varying saturation pulse durations and amplitudes as well as the consistency between numerical simulations and our experimental results indicate that the negligible gagCEST observed at 3 T is due to direct saturation effects and fast exchange rate. As GAG loss from cartilage is expected to result in a further reduction in gagCEST, gagCEST method is not expected to be clinically useful at 3 T. At high fields such as 7 T, this method holds promise as a viable clinical technique. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Adiabatic turbo spin echo in human applications at 7 T
Authors: van Kalleveen Irene M. L. , Koning Wouter , Boer Vincent O. , Luijten Peter R. , Zwanenburg Jaco J. M. , Klomp Dennis W. J.
Published: December 2011

Nonuniform B1 fields in ultrahigh‐field MR imaging cause severe image artifacts, when conventional radiofrequency (RF) pulses are used. Particularly in MR sequences that encompass multiple RF pulses, e.g., turbo spin echo (TSE) sequences, complete signal loss may occur in certain areas. When using a surface coil for transmitting the RF pulses, these problems become even more challenging, as the spatial B1 field variance is substantial. As an alternative to conventional TSE sequences, adiabatic TSE sequences can be applied, which have the benefit that these sequences are insensitive to B1 nonuniformity. In this study, we investigate the potential of using adiabatic TSE at 7 T with surface coil transceivers in human applications. The adiabatic RF pulses were tuned to deal with the constraints in B1 strength and RF power deposition, but remained in the superadiabatic regime. As a consequence, the dynamic range in B1 is compromised, and signal modulation is obtained over the echo train. Multidimensional Bloch simulations over the echo train and phantom measurements were obtained to assess these limitations. Still, using proper k‐space sampling, we demonstrate improved image quality of the adiabatic TSE versus conventional TSE in the brain, the neck (carotid artery) and in the pelvis (prostate) at 7 T. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Breast cancer in a case of Shwachman Diamond syndrome
Authors: Singh Sharon A. , Vlachos Adrianna , Morgenstern Nora J. , Ouansafi Ihsane , Ip Wan , Rommens Johanna M. , Durie Peter , Shimamura Akiko , Lipton Jeffrey M.
Published: December 2011

Shwachman Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome (IBMFS) characterized by neutropenia, exocrine pancreatic dysfunction, and cancer predisposition. Patients are at risk for myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) but, unlike other IBMFS, there have been no reported cases of solid tumors. We report a novel case of a solid tumor in a patient with SDS and biallelic mutations in the Shwachman Bodian Diamond Syndrome gene (SBDS). Whether the development of breast cancer in this patient is due to SDS or an isolated case due to unknown factors requires further study. Pediatr Blood Cancer 2012; 59: 945–946. © 2011 Wiley Periodicals, Inc.
Towards clinical applications of selected reaction monitoring for plasma protein biomarker studies
Authors: Krisp Christoph , Randall Sarah A. , McKay Matthew J. , Molloy Mark P.
Published: December 2011

The widespread clinical adoption of protein biomarkers with diagnostic, prognostic and/or predictive value remains a formidable challenge for the biomedical community. From discovery to validation, the path to biomarkers of clinical relevance abounds with many protein candidates, yet so few concrete examples have been substantiated. In this review, we focus on the recent adoption of selected reaction monitoring (SRM) of plasma proteins in the path to clinical use for a broad range of diseases including cancer, cardiovascular disease, genetic disorders and various metabolic disorders. Recent progress reveals a promising outlook for clinical applications using SRM, which now provides the routine analysis of clinically relevant protein markers at low nanogram per millilitre in plasma.
Systems biology analysis of protein‐drug interactions
Authors: Colinge Jacques , Rix Uwe , Bennett Keiryn L. , Superti‐Furga Giulio
Published: December 2011

Drugs induce global perturbations at the molecular machinery level because their cognate targets are involved in multiple biological functions or because of off‐target effects. The analysis or the prediction of such systems level consequences of drug treatment therefore requires the application of systems biology concepts and methods. In this review, we first summarize the methods of chemical proteomics that can measure unbiased and proteome‐wide drug protein target spectra, which is an obvious necessity to perform a global analysis. We then focus on the introduction of computational methods and tools to relate such target spectra to global models such as pathways and networks of protein‐protein interactions, and to integrate them with existing protein functional annotations. In particular, we discuss how drug treatment can be mapped onto likely affected biological functions, how this can help identifying drug mechanisms of action, and how such mappings can be exploited to predict potential side effects and to suggest new indications for existing compounds.
The current Salmonella‐host interactome
Authors: Schleker Sylvia , Sun Jingchun , Raghavan Balachandran , Srnec Matthew , Müller Nicole , Koepfinger Mary , Murthy Leelavati , Zhao Zhongming , Klein‐Seetharaman Judith
Published: December 2011

Salmonella bacteria cause millions of infections and thousands of deaths every year. This pathogen has an unusually broad host range including humans, animals, and even plants. During infection, Salmonella expresses a variety of virulence factors and effectors that are delivered into the host cell triggering cellular responses through protein‐protein interactions (PPI) with host cell proteins which make the pathogen's invasion and replication possible. To speed up proteomic efforts in elucidating Salmonella‐host interactomes, we carried out a survey of the currently published Salmonella‐host PPI. Such a list can serve as the gold standard for computational models aimed at predicting Salmonella‐host interactomes through integration of large‐scale biological data sources. Manual literature and database search of >2200 journal articles and >100 databases resulted in a gold standard list of currently 62 PPI, including primarily interactions of Salmonella proteins with human and mouse proteins. Only six of these interactions were directly retrievable from PPI databases and 16 were highlighted in databases featuring literature extracts. Thus, the literature survey resulted in the most complete interactome available to date for Salmonella. Pathway analysis using Ingenuity and Broad Gene Set Enrichment Analysis (GSEA) software revealed among general pathways such as MAPK signaling in particular those related to cell death as well as cell morphology, turnover, and interactions, in addition to response to not only Salmonella but also other pathogenic ‐ viral and bacterial ‐ infections. The list of interactions is available at http://www.shiprec.org/indicationslist.htm.
Deficiency of DNA repair nuclease ERCC1‐XPF promotes prostate cancer progression in a tissue recombination model
Authors: Matoka Derek J. , Yao Veronica , Harya Diana S. , Gregg Jennifer L. , Robinson Andria R. , Niedernhofer Laura J. , Parwani Anil V. , Maier Christoph , Bacich Dean J.
Published: December 2011

BACKGROUND

The excision repair cross complementing (ERCC1) gene product plays a vital role in the nucleotide excision repair (NER) and DNA interstrand crosslink repair pathways, which protect the genome from mutations and chromosomal aberrations, respectively. Genetic deletion of Ercc1 in the mouse causes dramatically accelerated aging. We examined the effect of Ercc1 deletion in the development of prostate cancer in a prostate recapitulation model as Ercc1 deficient mice die within four weeks of birth.

METHODS

Prostate tissues from Ercc1−/− mice or wild‐type littermates were combined with embryonic rat urogenital mesenchyme and grown as renal grafts for a total of 8, 16, and 24 weeks before histological, expression and proliferative evaluation.

RESULTS

Invasive adenocarcinoma was observed in Ercc1−/− tissue recombinants but not wild‐type as early as 8 weeks post‐grafting. PIN‐like lesions in Ercc1−/− tissue recombinants had more cytologic and architectural atypia than wild‐type (P = 0.02, P = 0.0065, and P = 0.0003 at the 8, 16, and 24 weeks, respectively), as well as more proliferative cells (P = 0.022 and P = 0.033 at 8 and 16 weeks, respectively). With serial grafting, Ercc1−/− tissue recombinants progressed to a more severe histopathological phenotype more rapidly than wild‐type (P = 0.011).

CONCLUSIONS

Results show that ERCC1 and by implication the NER and/or interstrand crosslink repair mechanisms protect against prostate carcinogenesis and mutations or polymorphisms affecting these DNA repair pathways may predispose prostate epithelial cells to transformation. Prostate 72:1214–1222, 2012. © 2011 Wiley Periodicals, Inc.
Magnetic resonance of a highly symmetric metamaterial at microwave frequency
Authors: Park J. W. , Jin X. R. , Tuong P. V. , Rhee J. Y. , Kim K. W. , Kim D. , Lee Y. P.
Published: December 2011

We studied the highly symmetric magnetic components of a metamaterial with negative permeability in the microwave‐frequency region. Their characteristics are investigated by using numerical simulation and experiment, and a reasonable agreement between the measurements and the numerical simulations was achieved. The simple and highly symmetric structure of the metamaterial not only significantly relaxes the designing condition for the realization of the negative‐index property but also opens up a great possibility for application.
Virtual flow‐net for accountability and forensics of computer and network systems
Authors: Takahashi Daisuke , Xiao Yang , Meng Ke
Published: December 2011

Information/secret leaking cannot always be recorded in digital log files. In other words, in log files, not all information/events are recorded, and it is thus impossible to trace the paths of secret leaking on the basis of log files alone. In this paper, to resolve the difficulty of the lack of information, we utilize user–relationship graphs, or social networks, to compensate for the required information. We also utilize a probabilistic analysis to build virtual links to follow information flows. User–relationship graphs are constructed from several flow‐net data structures over a longer period so that we can avoid missing embedded threats such as hostile codes. We call this approach virtual flow‐net. Copyright © 2011 John Wiley & Sons, Ltd.
Konstruktion und Berechnung von explosionshemmenden Seilnetzfassaden
Authors: Wellershoff Frank , Gebbeken Norbert , Teich Martien , Nehring Gordon
Published: December 2011

Die Bedrohung durch Bombenanschläge ist heute sehr real, und wir hören häufiger von den tragischen Konsequenzen dieser Anschläge. Um die Öffentlichkeit zu schützen, werden derzeit neue Fassadensysteme und Bemessungsmethoden entwickelt, die mit einem vertretbaren finanziellen Aufwand die Schutzfunktion gefährdeter Gebäude wesentlich verbessern. Die Entwicklungsphilosophie umfasst vor allem Fragen der Stand‐ und Reststandsicherheit (Schutz von Leben und Vermeiden von Verletzungen) und Aspekte der Gebrauchstauglichkeit. Aber auch die Minimierung des finanziellen Schadens wird berücksichtigt.

Bei Fassaden mit Spannweiten über 15 m sind Seilnetzsysteme die transparenteste Lösung (maximaler Glasanteil bezogen auf die Fassadenfläche). Seilnetzfassaden werden daher häufig im Eingangsbereich von Bahnhöfen, Flughäfen, Banken oder Hotels gebaut. Für diese Gebäude wird häufig ein erhöhtes Schutzniveau gefordert. Hieraus resultiert der Bedarf an neuen Konstruktionselementen und Bemessungsmethoden für explosionshemmende Seilnetzfassaden. Drei neuentwickelte Konstruktionselemente werden im Folgenden im Detail dargestellt. Die Verbindung zwischen der unmittelbaren Glaslagerung (z. B. Eckklemme) und dem Seil kann mit einem Crashkörper versehen werden, wodurch die Spitzenspannung in der Glasscheibe wesentlich reduziert werden kann. Sollte die Scheibe dennoch brechen, kann durch einen besonderen Glashalter die Resttragfähigkeit der Verglasung verbessert werden. Neu entwickelte Seilendverankerungen verringern die Belastungen auf die Seile und das Gebäude.

Die neuen Bemessungsmethoden ermöglichen eine schnelle numerische Analyse von Seilnetzfassaden unter definierten Druckwellen und ermöglichen so eine schnelle und effiziente Dimensionierung der neu entwickelten Seilendverankerungen.

Design and calculation of cable net facades under impulsive blast loads. Nowadays the threat of terrorist bomb attacks on buildings is very real, and we frequently hear about tragic consequences of such attacks. To protect the public against such horrible acts, the engineering community has embarked on developing technologies and concepts that can economically provide life safety measures to vulnerable structures. The design philosophy is primarily to save lives and prevent injuries, and secondarily to protect buildings, functions, and assets. The design criteria take a balanced approach to safety, considering cost effectiveness and acknowledging acceptance to some risks.

For cable net facades with point supported glazing new design methods and solutions are developed. These methods include new tools for the numerical evaluation of facades under impulsive blast loads. New design solutions include appropriate connections to the supporting structure (cable end support) which are able to dissipate a significant part of the blast wave energy and positively influence the structural post‐failure behaviour.
Gelatinisation properties of native and annealed potato starches
Authors: Alvani Kamran , Qi Xin , Tester Richard F.
Published: December 2011

The relationship between the gelatinisation parameters of native and annealed starches extracted from ten different potato varieties grown at the same site at the same time was studied. The objective was to identify how native gelatinisation temperatures and enthalpies impacted on annealed starch gelatinisation parameters. Prior to ANN, the initial onset (To), peak (Tp) and conclusion (Tc) gelatinisation temperatures ranged from 58.71 to 62.45, 62.52 to 66.05 and 68.67 to 72.27°C, respectively, which increased to 66.15 to 69.12, 70.22 to 72.30 and 76.21 to 77.44°C, respectively, post ANN. Overall, the greater the initial gelatinisation temperatures the smaller the increment (ΔGT) post ANN. Comparable enthalpy values pre‐ and post‐ANN were 15.13 to 18.37 and 15.76 to 18.37 J/g, respectively. These data indicate that the more ‘perfect’ the crystallites were before ANN the less they could be enhanced by the ANN process and that against a constant background of α‐glucan structure, the pattern (rate) of starch deposition might be the primary differentiator of starch architecture across the varieties.
Cyclodextrin and methacrylic acid octyl phenols poly(ethylene oxide) ester‐induced synergistic effect in a novel poly(AM‐co‐A‐β‐CD‐co‐AE) polymer
Authors: Zou Changjun , Tang Quanwu , Tan Naidi , Xiao Pufu , Hu Xuze
Published: December 2011

Owing to superior properties such as temperature resistance and salt tolerance etc., modified polyacrylamide (PAM) as one of the main injected polymers has been widely investigated to enhance oil production in reservoirs. Herein, a novel poly(AM‐co‐A‐β‐CD‐co‐AE) polymer was synthesized by utilizing β‐CD and AE to copolymerize with AM and characterized by FT‐IR and SEM. Furthermore, the temperature resistance and salt tolerance of poly(AM‐co‐A‐β‐CD‐co‐AE) polymer were explored. The results showed that the presence of the poly(AM‐co‐A‐β‐CD‐co‐AE) polymer better achieved temperature resistance and salt tolerance properties than is the case with PAM, which has potential application for enhancing oil recovery in the high‐temperature and high‐mineralization oilfield. On the other hand, the inhibition performance of poly(AM‐co‐A‐β‐CD‐co‐AE) polymer as a corrosion inhibitor was evaluated by SEM and electrochemical techniques. SEM observations of the carbon steel surface confirmed the protective role of the corrosion inhibitor. The results of potentiodynamic polarization and EIS measurements on the corrosion inhibition of carbon steel samples in 0.5 M sulfuric acid solutions revealed that the highest inhibition efficiency of it over 90% was obtained, indicating poly(AM‐co‐A‐β‐CD‐co‐AE) polymer acts as a more efficient corrosion inhibitor for carbon steel.
Mechanical characterizations of topology‐insensitive rivet bonding using the sidewall bond principle
Authors: Kang S. , Lee E. , Kim H. C. , Chun K.
Published: December 2011

Our goal was to develop a topology‐insensitive rivet bonding method using the sidewall bond principle for MEMS devices and evaluate its mechanical characteristics. The proposed bonding method is comprised of two fundamental structures with a sidewall bond between them. The first is a male wafer having a relatively thick solder as a donor, and the second is a female wafer as an acceptor with a structure similar to a through‐via. The two wafers are bonded laterally by the reflow phenomena of the solder and the excess volume of the donor with the acceptor then generating a rivet. In this study, these structural features were investigated. The rivet bonding led to an enhancement in the bonding strength due to the plastic hardening behavior of the rivet, serving as a cushion for the stress. This was parametrically studied and experimentally verified. © 2011 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.