bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis
Authors: Chang Katherine , Svabek Catherine , Vazquez-Guillamet Cristina , Sato Bryan , Rasche David , Wilson Strother , Robbins Paul , Ulbrandt Nancy , Suzich JoAnn , Green Jonathan , Patera Andriani C , Blair Wade , Krishnan Subramaniam , Hotchkiss Richard
Published: January 2014

Introduction

A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognized phenomenon of T cell exhaustion is mediated in part by PD-1 effects on T cells. This study tested the ability of anti-PD-1 and anti-PD-L1 antibodies to prevent apoptosis and improve lymphocyte function in septic patients.

Methods

Blood was obtained from 43 septic and 15 non-septic critically-ill patients. Effects of anti-PD-1, anti-PD-L1, or isotype-control antibody on lymphocyte apoptosis and interferon gamma (IFN-γ) and interleukin-2 (IL-2) production were quantitated by flow cytometry.

Results

Lymphocytes from septic patients produced decreased IFN-γ and IL-2 and had increased CD8 T cell expression of PD-1 and decreased PD-L1 expression compared to non-septic patients (P<0.05). Monocytes from septic patients had increased PD-L1 and decreased HLA-DR expression compared to non-septic patients (P<0.01). CD8 T cell expression of PD-1 increased over time in ICU as PD-L1, IFN-γ, and IL2 decreased. In addition, donors with the highest CD8 PD-1 expression together with the lowest CD8 PD-L1 expression also had lower levels of HLA-DR expression in monocytes, and an increased rate of secondary infections, suggestive of a more immune exhausted phenotype. Treatment of cells from septic patients with anti-PD-1 or anti-PD-L1 antibody decreased apoptosis and increased IFN-γ and IL-2 production in septic patients; (P<0.01). The percentage of CD4 T cells that were PD-1 positive correlated with the degree of cellular apoptosis (P<0.01).

Conclusions

In vitro blockade of the PD-1:PD-L1 pathway decreases apoptosis and improves immune cell function in septic patients. The current results together with multiple positive studies of anti-PD-1 and anti-PD-L1 in animal models of bacterial and fungal infections and the relative safety profile of anti-PD-1/anti-PD-L1 in human oncology trials to date strongly support the initiation of clinical trials testing these antibodies in sepsis, a disorder with a high mortality.
DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment
Authors: Mikyšková Romana , Indrová Marie , Vlková Veronika , Bieblová Jana , Šímová Jana , Paračková Zuzana , Pajtasz-Piasecka Elzbieta , Rossowska Joanna , Reiniš Milan
Published: January 2014

MDSCs represent one of the key players mediating immunosuppression. These cells accumulate in the TME, lymphoid organs, and blood during tumor growth. Their mobilization was also reported after CY therapy. DNMTi 5AC has been intensively studied as an antitumor agent. In this study, we examined, using two different murine tumor models, the modulatory effects of 5AC on TU-MDSCs and CY-MDSCs tumor growth and CY therapy. Indeed, the percentage of MDSCs in the TME and spleens of 5AC-treated mice bearing TRAMP-C2 or TC-1/A9 tumors was found decreased. The changes in the MDSC percentage were accompanied by a decrease in the Arg-1 gene expression, both in the TME and spleens. CY treatment of the tumors resulted in additional MDSC accumulation in the TME and spleens. This accumulation was subsequently inhibited by 5AC treatment. A combination of CY with 5AC led to the highest tumor growth inhibition. Furthermore, in vitro cultivation of spleen MDSCs in the presence of 5AC reduced the percentage of MDSCs. This reduction was associated with an increased percentage of CD11c+ and CD86+/MHCII+ cells. The observed modulatory effect on MDSCs correlated with a reduction of the Arg-1 gene expression, VEGF production, and loss of suppressive capacity. Similar, albeit weaker effects were observed when MDSCs from the spleens of tumor-bearing animals were cultivated with 5AC. Our findings indicate that beside the direct antitumor effect, 5AC can reduce the percentage of MDSCs accumulating in the TME and spleens during tumor growth and CY chemotherapy, which can be beneficial for the outcome of cancer therapy.
Morphology Analysis for Effect of the Polymer Cluster Produced from Adamantyl-bearing Trifunctional Monomer on the Stability of Liquid Crystal Alignment
Authors: Mizusaki Masanobu , Nakamura Kimiaki
Published: January 2014

Effect on stability of liquid crystal (LC) alignment due to formation of polymer clusters on alignment films produced from the copolymer of 1,3,5-triacryloyloxyadamantane and 4,4′-diacryloyloxybiphenyl was investigated with morphology analysis. Experimental results revealed that the stability of the LC alignment was increased because the polymer clusters effectively held the LC molecules adjacent to the polymer clusters.
Recent Progress in MMX-Chain Complexes: Unique Electronic States and Characteristics Developed by Introducing Binary Countercations
Authors: Iguchi Hiroaki , Takaishi Shinya , Yamashita Masahiro
Published: January 2014

MMX-Type quasi-one-dimensional iodide-bridged diplatinum complexes (MMX chains) provide various electronic states and attractive physical properties. In this review, we summarize the recent progress in MMX chains consisting of pyrophosphite (pop) ligands. The MMX chains with binary countercations, which have short Pt–I–Pt distance and robust frameworks, form a new electronic state. They show reversible dehydration–rehydration accompanied by the change of electronic states and electrical conductivity. Relatively high electrical conductivity in the MMX chains with binary countercations enables us to investigate the negative differential resistance (NDR) and electrochemical characteristics in the solid state for the first time in MMX chains.
Survey of management of common iliac artery aneurysms by members of the Vascular Society of Great Britain and Ireland
Authors: Williams SK , Campbell WB , Earnshaw JJ
Published: January 2014

Introduction

The aim of this study was to determine whether the current management of common iliac artery aneurysms (CIAAs) by vascular surgeons is in tune with existing guidelines for referral.

Methods

This was a postal survey of members of the Vascular Society of Great Britain and Ireland. The main outcome measures were relative frequency of ruptured CIAA, respondents’ size threshold for surveillance versus intervention, and their management strategies for isolated unilateral CIAAs, bilateral CIAAs and aortoiliac aneurysms.

Results

Two hundred and eighty-four (anonymous) replies were received (48% response rate). Respondents estimated that a ruptured abdominal aortic aneurysm (AAA) was 25 times more common than a ruptured CIAA. Most surgeons (64%) would wait until a CIAA reached 4cm in diameter before considering intervention. This threshold was not affected by other scenarios such as the presence of a bilateral CIAA or a small (4cm) AAA. Eighty per cent of surgeons would treat a non-ruptured CIAA by stenting, where possible. The majority of surgeons felt that ultrasonography surveillance should be commenced when a CIAA exceeds 1.5cm, with a surveillance interval of 1 year but with more frequent surveillance for CIAAs wider than 3cm.

Conclusions

Existing guidelines that recommend referral for possible intervention for non-ruptured CIAAs at a diameter of 3cm are out of tune with current practice. Most surgeons in this survey would wait until the diameter was 4cm.
Assessment of recurrent laryngeal nerve function during thyroid surgery
Authors: Smith J , Douglas J , Smith B , Dougherty T , Ayshford C
Published: January 2014

Introduction

There is disparity in the reported incidence of temporary and permanent recurrent laryngeal nerve (RLN) palsy following thyroidectomy. Much of the disparity is due to the method of assessing vocal cord function. We sought to identify the incidence and natural history of temporary and permanent vocal cord palsy following thyroid surgery. The authors wanted to establish whether intraoperative nerve monitoring and stimulation aids in prognosis when managing vocal cord palsy.

Methods

Prospective data on consecutive thyroid operations were collected. Intraoperative nerve monitoring and stimulation, using an endotracheal tube mounted device, was performed in all cases. Endoscopic examination of the larynx was performed on the first postoperative day and at three weeks.

Results

Data on 102 patients and 123 nerves were collated. Temporary and permanent RLN palsy rates were 6.1% and 1.7%. Most RLN palsies were identified on the first postoperative day with all recognised at the three-week review. No preoperative clinical risk factors were identified. Although dysphonia at the three-week follow-up visit was the only significant predictor of vocal cord palsy, only two-thirds of patients with cord palsies were dysphonic. Intraoperative nerve monitoring and stimulation did not predict outcome in terms of vocal cord function.

Conclusions

Temporary nerve palsy rates were consistent with other series where direct laryngoscopy is used to assess laryngeal function. Direct laryngoscopy is the only reliable measure of cord function, with intraoperative monitoring being neither a reliable predictor of cord function nor a predictor of eventual laryngeal function. The fact that all temporary palsies recovered within four months has implications for staged procedures.
The diagnostic value of fine needle aspiration in parotid lumps
Authors: Pierre SK , Moody AB , Howlett DC
Published: January 2014

Mallon DH, Kostalas M, MacPherson FJ et al. The diagnostic value of fine needle aspiration in parotid lumps. Ann R Coll Surg Engl 2013; 95: 258–262 doi 10.1308/003588413X13511609958370
Pasteurella multocida infected total knee arthroplasty: a case report and review of the literature
Authors: Ferguson KB , Bharadwaj R , MacDonald A , Syme B , Bal AM
Published: January 2014

Pasteurella multocida is a rare cause of prosthetic joint infection. This infection generally follows significant animal contact, usually licks and scratches. We report a case of P multocida infection that was treated with linezolid with salvage of the implant. Linezolid is generally active against Gram-positive organisms only with the exception of Pasteurella, which is Gram-negative. We extensively review the previous reported cases of implant infection with P multocida.
Obesity and recurrent intervertebral disc prolapse after lumbar microdiscectomy
Authors: Quah C , Syme G , Swamy GN , Nanjayan S , Fowler A , Calthorpe D
Published: January 2014

Introduction

The primary aim of this study was to investigate the relationship between obesity and recurrent intervertebral disc prolapse (IDP) following lumbar microdiscectomy.

Methods

A retrospective review of case notes from 2008 to 2012 was conducted for all patients who underwent single level lumbar microdiscectomy performed by a single surgeon. All patients were followed up at two weeks and six weeks following surgery, and given an open appointment for a further six months.

Results

A total of 283 patients were available for analysis: 190 (67%) were in the non-obese group and 93 (32.9%) in the obese group. There was no statistical difference in postoperative infection, dural tear or length of stay between the non-obese and obese groups. Recurrent symptomatic IDP was seen in 27 patients (9.5%) confirmed by magnetic resonance imaging. Nineteen (10.0%) were in the non-obese group and eight (8.6%) in the obese group (p>0.8).

Conclusions

In our study, obesity was not a predictor of recurrent IDP following lumbar microdiscectomy. Our literature review confirmed that this study reports the largest series to date analysing the relationship between obesity and recurrent IDP following lumbar microdiscectomy in the British population.
Surgical resection of hepatic and cardiac neuroendocrine metastases from a caecal primary tumour
Authors: Williamson JML , Anderson J , Spalding DRC
Published: January 2014

A 66-year-old patient had an incidentally detected caecal neuroendocrine tumour that had metastasised to the liver and left atrium. He was asymptomatic with regard to this tumour and did not have carcinoid syndrome. Resection of the primary tumour and the metastatic deposits (with the ablation of one lesion) is thought to be curative.
YAP regulates cell proliferation, migration, and steroidogenesis in adult granulosa cell tumors
Authors: Fu David , Lv Xiangmin , Hua Guohua , He Chunbo , Dong Jixin , Lele Subodh M , Li David Wan-Cheng , Zhai Qiongli , Davis John S , Wang Cheng
Published: January 2014

The Hippo signaling pathway has been implicated as a conserved regulator of organ size in bothDrosophilaand mammals. Yes-associated protein (YAP), the central component of the Hippo signaling cascade, functions as an oncogene in several malignancies. Ovarian granulosa cell tumors (GCT) are characterized by enlargement of the ovary, excess production of estrogen, a high frequency of recurrence, and the potential for malignancy and metastasis. Whether the Hippo pathway plays a role in the pathogenesis of GCT is unknown. This study was conducted to examine the expression of YAP in human adult GCTs and to determine the role of YAP in the proliferation and steroidogenesis of GCT cells. Compared with age-matched normal human ovaries, GCT tissues exhibited higher levels of YAP expression. YAP protein was predominantly expressed in the nucleus of tumor cells, whereas the non-tumor ovarian stromal cells expressed very low levels of YAP. YAP was also expressed in cultured primary human granulosa cells and in KGN and COV434 GCT cell lines. siRNA-mediated knockdown of YAP in KGN cells resulted in a significant reduction in cell proliferation (P<0.001). Conversely, overexpression of wild type YAP or a constitutively activeYAP(YAP1) mutant resulted in a significant increase in KGN cell proliferation and migration. Moreover, YAP knockdown reduced FSH-induced aromatase (CYP19A1) protein expression and estrogen production in KGN cells. These results demonstrate that YAP plays an important role in the regulation of GCT cell proliferation, migration, and steroidogenesis. Targeting the Hippo/YAP pathway may provide a novel therapeutic approach for GCT.
TRIB1 downregulates hepatic lipogenesis and glycogenesis via multiple molecular interactions
Authors: Ishizuka Yuumi , Nakayama Kazuhiro , Ogawa Ayumi , Makishima Saho , Boonvisut Supichaya , Hirao Atsushi , Iwasaki Yusaku , Yada Toshihiko , Yanagisawa Yoshiko , Miyashita Hiroshi , Takahashi Masafumi , Iwamoto Sadahiko , _ _
Published: January 2014

Mammalian tribbles homolog 1 (TRIB1) regulates hepatic lipogenesis and is genetically associated with plasma triglyceride (TG) levels and cholesterol, but the molecular mechanisms remain obscure. We explored these mechanisms in mouse livers transfected with a TRIB1 overexpression, a shRNA template or a control (LacZ) adenovirus vector. The overexpression of TRIB1 reduced, whereas induction of the shRNA template increased, plasma glucose, TG, and cholesterol and simultaneously hepatic TG and glycogen levels. The involvement of TRIB1 in hepatic lipid accumulation was supported by the findings of a human SNP association study. A TRIB1 SNP, rs6982502, was identified in an enhancer sequence, modulated enhancer activity in reporter gene assays, and was significantly (P=9.39×10−7) associated with ultrasonographically diagnosed non-alcoholic fatty liver disease in a population of 5570 individuals. Transcriptome analyses of mouse livers revealed significant modulation of the gene sets involved in glycogenolysis and lipogenesis. Enforced TRIB1 expression abolished CCAAT/enhancer binding protein A (CEBPA), CEBPB, and MLXIPL proteins, whereas knockdown increased the protein level. Levels of TRIB1 expression simultaneously affected MKK4 (MAP2K4), MEK1 (MAP2K1), and ERK1/2 (MAPK1/3) protein levels and the phosphorylation of JNK, but not of ERK1/2. Pull-down and mammalian two-hybrid analyses revealed novel molecular interaction between TRIB1 and a hepatic lipogenic master regulator, MLXIPL. Co-expression of TRIB1 and CEBPA or MLXIPL reduced their protein levels and proteasome inhibitors attenuated the reduction. These data suggested that the modulation of TRIB1 expression affects hepatic lipogenesis and glycogenesis through multiple molecular interactions.
Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats
Authors: Kurtz M , Capobianco E , Careaga V , Martinez N , Mazzucco M B , Maier M , Jawerbaum A
Published: January 2014

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect ofin vivoactivation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4(LTB4, PPARα ligand) or 15deoxyΔ12,14prostaglandin J2(15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4and partially restored by 15dPGJ2in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.
Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue
Authors: Gajdosechova Lucia , Krskova Katarina , Segarra Ana Belen , Spolcova Andrea , Suski Maciej , Olszanecki Rafal , Zorad Stefan
Published: January 2014

The metabolic action of oxytocin has recently been intensively studied to assess the ability of the peptide to regulate energy homeostasis. Despite the obvious weight-reducing effect of oxytocin observed in experimental studies, plasma oxytocin levels were found to be unchanged or even elevated in human obesity. The aim of our study was to evaluate the changes in the oxytocin system in Zucker rats, an animal model closely mirroring morbid obesity in humans. Plasma oxytocin levels were measured in obese Zucker rats and lean controls by enzyme immunoassay after plasma extraction. The expression of oxytocin and oxytocin receptor (OXTR) was assessed at the mRNA and protein levels by quantitative real-time PCR and immunoblotting respectively. Plasma and tissue activity of oxytocinase, the main enzyme involved in oxytocin degradation, were measured by fluorometric assay using an arylamide derivate as the substrate. Obese Zucker rats displayed a marked reduction in plasma oxytocin levels. Elevated liver and adipose tissue oxytocinase activity was noticed in obese Zucker rats. Hypothalamic oxytocin gene expression was not altered by the obese phenotype. OXTR mRNA and protein levels were upregulated in the adipose tissue of obese animals in contrast to the reduced OXTR protein levels in skeletal muscle. Our results show that obesity is associated with reduced plasma oxytocin due to increased peptide degradation by liver and adipose tissue rather than changes in hormone synthesis. This study highlights the importance of the oxytocin system in the pathogenesis of obesity and suggests oxytocinase inhibition as a candidate approach in the therapy of obesity.
Combining sitagliptin/metformin with a functional fiber delays diabetes progression in Zucker rats
Authors: Reimer Raylene A , Grover Gary J , Koetzner Lee , Gahler Roland J , Lyon Michael R , Wood Simon
Published: January 2014

Our primary objective was to determine whether administering the viscous and fermentable polysaccharide PolyGlycopleX (PGX) with metformin (MET) or sitagliptin/metformin (S/MET) reduces hyperglycemia in Zucker diabetic fatty (ZDF) rats more so than monotherapy of each. Glucose tolerance, adiposity, satiety hormones and mechanisms related to dipeptidyl peptidase 4 activity, gut microbiota and, hepatic and pancreatic histology were examined. Male ZDF rats (9–10 weeks of age) were randomized to: i) cellulose/vehicle (control, C); ii) PGX (5% wt/wt)/vehicle (PGX); iii) cellulose/metformin (200 mg/kg) (MET); iv) cellulose/S/MET (10 mg/kg+200 mg/kg) (S/MET); v) PGX (5%)+MET (200 mg/kg) (PGX+MET); vi) cellulose/sitagliptin/MET (5%)+(10 mg/kg+200 mg/kg) (PGX+S/MET) for 6 weeks. PGX+MET and PGX+S/MET reduced glycemia compared with C and singular treatments (P=0.001). Weekly fasted and fed blood glucose levels were lower in PGX+MET and PGX+S/MET compared with all other groups at weeks 4, 5, and 6 (P=0.001). HbA1c was lower in PGX+S/MET than C, MET, S/MET, and PGX at week 6 (P=0.001). Fat mass was lower and GLP1 was higher in PGX+S/MET compared with all other groups (P=0.001). β-cell mass was highest and islet degeneration lowest in PGX+S/MET. Hepatic lipidosis was significantly lower in PGX+S/MET compared with PGX or S/MET alone. When combined with PGX, both MET and S/MET markedly reduce glycemia; however, PGX+S/MET appears advantageous over PGX+MET in terms of increased β-cell mass and reduced adiposity. Both combination treatments attenuated diabetes in the obese Zucker rat.
Cardiac Angiosarcoma: A Case with Bilateral Pleural and Pericardial Effusion
Authors: Oc Mehmet , Farsak Bora , Arun Oguzhan , Oc Bahar , Simsek Murat , Yıldırım Serkan
Published: January 2014

Cardiac sarcomas are rare malignant tumors. Angiosarcoma is the most common cardiac sarcoma and is present in up to 33% of cases. Angiosarcomas have a poor prognosis, with a short survival expectancy. We report a case of a right atrial angiosarcoma treated by partial tumor resection followed by chemotherapy.
An Expression QTL of Closely Linked Candidate Genes Affects pH of Meat in Chickens
Authors: Nadaf Javad , Berri Cecile , Dunn Ian , Godet Estelle , Le Bihan-Duval Elisabeth , De Koning Dirk Jan
Published: January 2014

Genetical genomics has been suggested as a powerful approach to study the genotype–phenotype gap. However, the relatively low power of these experiments (usually related to the high cost) has hindered fulfillment of its promise, especially for loci (QTL) of moderate effects.One strategy with which to overcome the issue is to use a targeted approach. It has two clear advantages: (i) it reduces the problem to a simple comparison between different genotypic groups at the QTL and (ii) it is a good starting point from which to investigate downstream effects of the QTL. In this study, from 698 F2 birds used for QTL mapping, gene expression profiles of 24 birds with divergent homozygous QTL genotypes were investigated. The targeted QTL was on chromosome 1 and affected initial pH of breast muscle. The biological mechanisms controlling this trait can be similar to those affecting malignant hyperthermia or muscle fatigue in humans. The gene expression study identified 10 strong local signals that were markedly more significant compared to any genes on the rest of the genome. The differentially expressed genes all mapped to a region <1 Mb, suggesting a remarkable reduction of the QTL interval. These results, combined with analysis of downstream effect of the QTL using gene network analysis, suggest that the QTL is controlling pH by governing oxidative stress. The results were reproducible with use of as few as four microarrays on pooled samples (with lower significance level). The results demonstrate that this cost-effective approach is promising for characterization of QTL.
Detecting Structure of Haplotypes and Local Ancestry
Authors: Guan Yongtao
Published: January 2014

We present a two-layer hidden Markov model to detect the structure of haplotypes for unrelated individuals. This allows us to model two scales of linkage disequilibrium (one within a group of haplotypes and one between groups), thereby taking advantage of rich haplotype information to infer local ancestry of admixed individuals. Our method outperforms competing state-of-the-art methods, particularly for regions of small ancestral track lengths. Applying our method to Mexican samples in HapMap3, we found two regions on chromosomes 6 and 8 that show significant departure of local ancestry from the genome-wide average. A software package implementing the methods described in this article is freely available at http://bcm.edu/cnrc/mcmcmc.
Learning from confidential reporting
Authors: Soane Alastair
Published: January 2014

Cross (confidential reporting on structural safety) is a UK scheme that collects, analyses and publishes personal reports about failures and the safety of structures so that engineers can learn from the experiences of others. Names of authors are confidential and identifying features from event descriptions are removed. When a trend is detected, action is taken to influence changes in culture and, when possible, in standards or legislation. Reported subjects have covered design, construction, use, demolition and regulation issues associated with buildings, specialist structures and bridges. Examples are given on fixings, temporary stage structures, snow load collapses, tall asymmetric structures, and false and misleading documentation. Data from identified trends have been passed to code committees, government departments, institutions or others who have influence on best practice. The information is also on a database on the site www.structural-safety.org .
Structural unsafety revealed by failure databases
Authors: Terwel Karel , Boot Wouter , Nelisse Mirjam
Published: January 2014

After several major structural incidents in the Netherlands, such as the collapse of five balconies in Maastricht in 2001 resulting in two fatalities, various initiatives have been started to improve structural safety. Research studies were initiated on the characteristics, causes and consequences of structural incidents. In this paper the results of three of these research studies are compared. Each study uses different data sources: a confidential reporting system called ABC registration, Dutch arbitration awards on functional and structural failures and a study of structural incidents mentioned in a newspaper for the building industry, called Cobouw. A comparison of the results shows variations due to the type of sources used. However, general patterns have been derived from the three studies. The cause of structural failure on average was approximately 35% in the design phase, approximately 30% in the construction phase and approximately 10% in the use and maintenance phase. This paper shows that contrasting and combining results of different sources has improved the overview of structural incidents and has provided an insight into trends.
Failure case databases related to risk in civil engineering
Authors: Breysse Denys , Ndiaye Amadou
Published: January 2014

Risk management in construction has only recently become a topic of interest for French engineers and researchers. In 2003, MRGenCi, the first French national organisation for risk management in civil engineering, was founded by the first author. It now brings together more than 20 partners (including authorities, builders, consultants, academics and insurers). The understanding of failure analysis has developed progressively among the community of experts and engineers. It is now important to open a new perspective by showing the value of a shared failure database. A first prototype database has been promoted by the authors, which now contains more than 960 failure cases. For many reasons this prototype database cannot yet be considered as a research tool, but merely as a demonstration tool to show what can be done, once organisational problems are identified and solved. It can also be used (among other purposes) for teaching, both using specific failure cases and at a more synthetic level. Information contained in the database is useful for incorporation in a range of courses, on topics such as geotechnics, materials science, tunnelling, bridges and reinforced concrete. It also has direct application for teaching risk management in civil engineering.
Durability aspects of HVFA-based recycled aggregate concrete
Authors: Saravanakumar Palaniraj , Dhinakaran Govindasamy
Published: January 2014

The utilisation of recycled coarse aggregate obtained from demolished concrete has gained momentum in recent years due to its contribution towards sustainability by minimising the use of artificially produced materials and eliminating environmental problems due to dumped waste materials. The present research exploited the possibility of producing high-volume fly ash (HVFA)-based recycled aggregate (RA) high-strength concrete. It was found that 50% of desired strength could be achieved even with 50% replacement of cement with fly ash and 50% of natural aggregate (NA) with RA. An attempt was thus made to study the effects of RA and HVFA on durability characteristics. The parameters considered were resistance to chloride ion penetration, acid attack, sulfate attack and sorption. It was found that replacement of NA with RA and cement with fly ash in higher volumes showed a way of considering economy and environmental effects as criteria, given a little bit of compromise towards strength and durability criteria but still falling well within an acceptable limit.
Flexural performance of functionally graded RC cross-section with steel and PP fibres
Authors: Naghibdehi Mahan Ghasemi , Mastali Mohammad , Sharbatdar Mohammad Kazem , Naghibdehi Maysam Ghasemi
Published: January 2014

Many studies have been conducted on the behaviour of reinforced concrete (RC) to determine the effects of different fibre types on the mechanical properties of concrete. Tests such as flexural and shear tests are used to evaluate the behaviour of RC. Most previous studies have focused on reinforcement of the entire cross-section with one fibre type, but the use of double-type reinforcement is growing and the lower cost of polypropylene (PP) fibres can be a significant factor in the use of double-type reinforcement. Therefore, in this work, experimental tests and numerical simulations were carried out to study reinforcement of the cross-section with steel fibres, PP fibres or both, in two separate layers. Beams were reinforced using 0·5%, 1% and 2% fibre volume fractions of steel and PP fibres. The beams with a reinforced cross-section with one or two fibre types were evaluated under flexural loading. The results showed that reinforcement of the entire cross-section with steel fibres led to a higher load-carrying capacity than reinforcement of the cross-section with two fibre types in two separate layers.
Pesticides in the River Ravi and its Tributaries Between its Stretches from Shahdara to Balloki Headworks, Punjab‐Pakistan
Authors: Akhtar Mobeen , Mahboob Shahid , Sultana Salma , Sultana Tayyaba
Published: January 2014

The present study investigated the presence and potent source of pesticides and specific pesticide bearing effluent release points on the River Ravi, between the Shahdara and Balloki Headworks. Pakistan has banned the use of organochlorine and nitrogen containing pesticides, yet no attention has been paid to the continuous monitoring and assessment of these banned pesticides to make sure that they are not being used in practice. Levels of selected organochlorine and nitrogen containing pesticide residues were assessed in water collected from 18 sampling sites on the River Ravi and its tributaries using a gas chromatograph equipped with an electron capture detector (GC‐ECD). All water samples were found to be contaminated with varying concentrations of pesticide residues. However, levels of pesticides were below the tolerance limits suggested in national and international standards. Pesticide concentrations in the water of river sites ranged from 0.034 to 0.045μg/L for DDT, 0.033 to 0.046μg/L for DDE, 0.108 to 0.123μg/L for endosulfan and 0.028 to 0.040μg/L for carbofuran. In tributaries, pesticide concentrations ranged from 0.0468 to 0.0685μg/L for DDT, 0.0390 to 0.0637μg/L for DDE, 0.111 to 0.147μg/L for endosulfan and 0.0396 to 0.0631μg/L for carbofuran. The results show pesticide concentrations in river water in the order: endosulfan > DDE > DDT > carbofuran. Pesticide concentrations in tributary waters decreased in the order: endosulfan > DDT> DDE > carbofuran. After Degh Fall and After Hudiara Nulla Fall river sampling sites were severely contaminated while, among the tributaries, Degh Fall and Hudiara Drain were severely contaminated with DDT, DDE, endosulfan and carbofuran. Constant monitoring programs should to be initiated to reform the present situation.
Disseminated tuberculosis in an immunocompetent patient
Authors: Ranganath Sangeetha , Wilson Benjamin , Narasimhan Aarthi , Midturi John
Published: January 2014

A 53-year-old immigrant male patient presented with left scrotal swelling with a draining ulcer on the left hemiscrotum. Patient had intentional weight loss, fever and night sweats, cough, headaches, confusion and difficulty with ambulation. Imaging studies revealed innumerable pulmonary nodules, leptomeningeal enhancement of the brain and bilateral epididymo-orchitis. Acid fast bacilli (AFB) smear was positive from the surgical specimen of bilateral epididymis and left testes. Cerebrospinal fluid (CSF) analysis revealed neutrophilic predominant pleocytosis with low glucose and elevated protein. Polymerase chain reaction (PCR) test performed on the CSF and AFB smear of epididymis was positive for Mycobacterium tuberculosis. Though the CSF and sputum AFB smears were negative, cultures subsequently grew mycobacterium tuberculosis. Patient was diagnosed with disseminated tuberculosis. Human deficiency virus test was negative. Patient was successfully treated with anti-tuberculosis therapy. Steroid was used as adjuvant therapy due to presence of tuberculous meningitis.
A Journey from the Pool of Chiral Synthetic Building Blocks to Cell-Penetrating Peptides, to a Novel Type of Enzyme – and back
Authors: Seebach Dieter
Published: January 2014

The roles of polyhydroxy-butyrates/alkanoates (PHB/PHA) in biology, for the preparation of chiral building blocks, and as a source of inspiration for the discovery of ?- and ?-peptides are discussed. The syntheses and structures of ?-peptides are outlined. The prerequisites
for mimicking peptide/protein interactions with ?-peptides and two examples are presented. Single terminal ?-amino-acid residues can lead to stabilization of peptides (cf. NTS(8-13)) in plasma. Cell-penetrating ?-L-, ?-D-, mixed ?-L/D- and ?-oligoarginines
(OAs) and -oligoprolines, as well as the mechanism(s) of internalization are compared. Recent studies show that infected erythrocytes, parasitic organisms and mycobacteria are entered by OA-derivatives, which have been employed as transporters of the antibiotic fosmidomycin. While ?-peptides
are generally enzymatically stable (for days in mammals), a microorganism (S. xenopeptidilytica) with an Ntn enzyme (3-2W4 BapA) was discovered that cleaves only ?-peptides, and that was applied in preparations of (enantiopure) ?-amino acids and ?-peptides.
Bioinorganic Chemistry of Silver: Its Interactions with Amino Acids and Peptides
Authors: Fromm Katharina M.
Published: January 2014

Silver and its compounds have been used for centuries for e.g. water storage, burn wounds or as eye ointment. Almost forgotten after the discovery of antibiotics, silver chemistry has had a revival over the past years as a means to combat multi-resistant bacteria. Although the details
of its mechanism of action are still unknown, silver seems to be efficient as it interacts with many biomolecular targets in a cell. In our group, we contribute to the elucidation of this mechanism of action by investigating the interactions of silver ions with amino acids and peptides as
well as the formation of nanoparticles related to the mechanism of biomineralization of silver.
The Search for Relay Stations. Long-distance Electron Transfer in Peptides
Authors: Giese Bernd , Kracht Sonja , Cordes Meike
Published: January 2014

Nature uses peptide aggregates as soft materials for electron transfer over long distances. These reactions occur in a multistep hopping reaction with various functional groups as relay stations that are located in the side chain and in the backbone of the peptides.
Adaptive Peptide Design
Authors: Schneider Gisbert , Lin Yen-Chu , Koch Christian P. , Pillong Max , Perna Anna M. , Reutlinger Michael , Hiss Jan A.
Published: January 2014

Computer algorithms help in the identification and optimization of peptides with desired structure and function. We provide an overview of the current focus of our research group in this field, highlighting innovative methods for peptide representation and de novo peptide generation.
Our evolutionary molecular design cycle contains structure–activity relationship modeling by machine-learning methods, virtual peptide generation, activity prediction, peptide syntheses, as well as biophysical and biochemical activity determination. Such interplay between computer-assisted
peptide generation and scoring with real laboratory experiments enables rapid feedback throughout the design cycle so that adaptive optimization can take place. Selected practical applications are reviewed including the design of new immunomodulatory MHC-I binding peptides and antimicrobial
peptides.
Self-assembled Structures from Amphiphilic Peptides
Authors: Sigg Severin J. , Schuster Thomas B. , Meier Wolfgang P.
Published: January 2014

Nanotechnology and its applications are strongly influenced by structures self-assembled from a variety of different materials. This review covers nanostructures, including micelles, rod-like micelles, fibers and peptide beads, self-assembled from de novo designed amphiphilic peptides.
The latter are promising candidates for the development of nanoscale carrier systems because they are completely composed of amino acids. In addition to designing primary sequences, secondary structure and external parameters are also discussed with respect to their impact on self-assembly.
Moreover, the assembly process itself is examined. Potential applications range from gene and drug delivery devices to diagnostics, thereby highlighting the versatility of the system.
Design and Applications of Protein Epitope Mimetics
Authors: Robinson John A.
Published: January 2014

Macromolecular structures represent an interesting starting point for the design and synthesis of small-molecule mimetics of surface epitopes that mediate protein–protein and protein–nucleic acid interactions. The resulting protein epitope mimetics (PEMs) provide a source
of new biologically active molecules that are useful as biomolecular probes in chemical biology, as well as novel drug or vaccine candidates. This is illustrated here through studies on PEMs as synthetic vaccine candidates targeting the malaria parasite and the human immunodeficiency virus
type-1 (HIV-1). In addition, various folded PEMs with ?-hairpin structures have been designed that target protein–protein and protein–nucleic acid interactions, as well as others that interact with cellular receptors such as CXCR4 and the bacterial outer membrane protein LptD.
In this last example, the PEMs possess a novel antibiotic activity that has so far not been observed with traditional small synthetic molecules or natural products.
Towards a Photochemical Synthesis of Peptides
Authors: Bochet Christian G.
Published: January 2014

The laboratory preparation of peptides, once a challenge, is now a standard operation that can be automatised. However, the need for particular protecting groups requiring relatively harsh conditions for their removal (strong acids or bases) and reactive coupling agents can be problematic
in specific cases (e.g. in a cell or in a microfluidic device). In this account, we describe our efforts towards a fully photochemical approach to peptide synthesis, where both the coupling and the deprotection steps use light instead of reagents. In order to selectively promote one of the two steps at a time, monochromatic light is used.
Towards Intracellular Delivery of Peptides
Authors: Marzinzik Andreas L. , Vorherr Thomas E.
Published: January 2014

In view of our more comprehensive understanding with respect to intracellular pathways and their regulation, a vast number of interesting drug targets appear to be in a space that can be addressed neither by small molecules nor by biologics. Especially, interference with intracellular
protein–protein interactions, if successful, seems to offer considerable opportunities to expand the application of peptides as therapeutics, in particular in the field of oncology. This review focuses on requirements for the development of peptide therapeutics aiming at intracellular
targets. In addition, an outlook for developments in this field based on recent examples for peptides active in cellular assays, highlighting key requirement to assess permeability, is provided.
Directed Evolution of Bicyclic Peptides for Therapeutic Application
Authors: Diderich Philippe , Heinis Christian
Published: January 2014

Many naturally occurring cyclic peptides or derivatives thereof are used as therapeutics such as the human hormones vasopressin and oxytocin or the antibiotics vancomycin and daptomycin. The success of cyclic peptide therapeutics is based on their ability to bind with high affinity,
their good target selectivity and their low toxicity. As nature provides cyclic peptides to only a small number of disease targets, strategies have been developed to generate cyclic peptide ligands with tailored specificity de novo. Our laboratory is specialized on the directed evolution
of bicyclic peptide ligands by phage display. In this article, we review our recent work to in vitro evolve bicyclic peptide antagonists, the binding and pharmacokinetic properties of bicyclic peptides, as well as efforts to generate bicyclic peptides for therapeutic application.
Design and Synthesis of 16-Membered Cyclopeptides Active Against Vancomycin-resistant Enterococci (VRE)
Authors: Zhu Jieping
Published: January 2014

The design, synthesis and antibiotic activities of the modified carboxylate binding pocket (D-O-E ring) of vancomycin (1) are summarized in this short account. The preliminary structure–activity relationship (SAR) studies indicated that both the structure of the 16-membered
macrocycle including the absolute configuration of the modified AA4 unit and the presence of a hydrophobic chain were important for anti-VRE activities of these series of synthetic analogues. Compounds 9c and 9d in which the central amino acid (AA4) of vancomycin was replaced
by (2R,3R)-?-hydroxy-?-amino acid and (2R,3R)-?,?-diamino acid, respectively, were found to be useful templates in searching for active compounds against both vancomycin-sensitive and -resistant strains. Two of these compounds (16d and
16n) having an elongated peptide chain at the C-terminal were found to be active against a broad spectrum of both vancomycin-sensitive (Staphylococcus aureus) and -resistant strains (E. faecium, E. faecalis).
Non-destructive Localization and Identification of Active Pharmaceutical Compounds by Raman Chemical Imaging
Authors: Brodard Pierre , Roth Samuel , Vorlet Olivier
Published: January 2014

Raman spectroscopy is a powerful and non-destructive technique for chemical and structural identification. Based on inelastic scattering of laser light by molecular vibrations, the analysis can be localized on a microscopic area when combined with a microscope. Thus, by moving the sample
under the microscope objective and recording a Raman spectrum at each point, a map of the intensity of specific Raman bands can be generated, effectively creating a chemical image of the sample at the microscale. Here, we present an application of this technique for identifying and localizing active pharmaceutical ingredients in a polymer matrix.
Evaluations of friends-with-benefits relationship scenarios: Is there evidence of a sexual double standard?
Authors: Weaver Angela D. , Claybourn Marvin , MacKeigan Kelly L.
Published: January 2014

More than half of university students report having had a friends-with-benefits relationship (FWBR), i.e., recurring sexual activity between friends who do not define their relationship as romantic, yet little is known about how people in FWBRs are judged by others. For instance, is there a sexual double standard whereby women are judged more negatively than men? In the present study, 404 university students read one of four randomly assigned scenarios describing an FWBR (scenarios varied on character gender and FWBR experience) and then completed measures of their judgment of the main character, their predictions about the relationship depicted, their beliefs about whether the character should keep the relationship secret, and their perception of how the character would be judged by peers. Two respondent-level variables (respondent gender; respondent FWBR experience) were also examined as predictors. Half of the participants (52.5%) had themselves experienced an FWBR, with a majority evaluating these experiences positively. Male respondents rated scenario characters more positively and made more positive relationship predictions than did female respondents. Respondents who had personal experience of their own FWBR rated characters more positively and made more positive relationship predictions than those who had never experienced an FWBR. There was no evidence of a sexual double standard in character judgments. However, relationship predictions and estimates of others' judgments were more negative when the character was female and there was a greater perceived need for secrecy. Thus, the current research did not support the existence of a sexual double standard for FWBRs, but may have suggested the perception of one.
Protective effect of Oroxylum indicum on acetaminophen induced liver injury in rat
Authors: Bharali Manuj Kr. , Konya Hage , Chetry Luk Bahadur
Published: January 2014

Acetaminophen (APAP) is a common antipyretic drug and leads to liver failure at over dose. In this study, the hepatoprotective effect of Aqueous Methanolic Bark Extract of Oroxylum indicum (L.)Vent. (AMBEOI) has been evaluated in rat model. Rats were treated with 1000 mgkg?1 body weight of APAP alone or with AMBEOI (10, 50 and 100 mgkg?1). Serum Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Lipid peroxidation (LPO) in liver tissues were estimated 24 hrs after APAP and AMBEOI treatment. AMBEOI administration effectively reduced serum level of ALT and AST released from liver cells when compared to APAP treated group. AMBEOI also inhibited production of LPO in the liver tissues of APAP treated rats. Histopathological examination of liver samples revealed reduced necrotic areas in AMBEOI treated APAP group compared to APAP alone treated group. Together, this study confirmed the hepatoprotective activities of AMBEOI in APAP induced liver damage in rat.DOI: http://dx.doi.org/10.3329/icpj.v3i2.17511 International Current Pharmaceutical Journal, January 2014, 3(2): 223-227