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Knowledge on the seaweeds of eastern Sorsogon in the Philippines is uneven. Not only is eastern Sorsogon among the areas of high seaweed diversity but locals there have interacted with seaweeds for ages. Despite seaweeds’ assumed importance to Sorsoganon, ethnobotanical records are missing. In this study, we documented the traditional knowledge on seaweed use and determined the rate of knowledge transmission among the locals of eastern Sorsogon. Vernacular names and modes of preparation were given of the 12 identified species bearing culinary and medicinal importance. Ten species were eaten while three were used therapeutically. Based on ethnobotanical indices, Caulerpa chemnitzia ecad turbinata and Gelidiella acerosa were the most important seaweeds. The least cited was Caulerpa racemosa. Our study demonstrated that most of the seaweed resources in eastern Sorsogon remain largely untapped, as the identified ethnotaxa were only about 5% of the total seaweed species diversity reported for the area. The seaweed knowledge in eastern Sorsogon appeared to be homogenous across age groups with primary sources of knowledge biased towards female relatives (mothers and grandmothers) and to children as inheritors. Cessation of seaweed knowledge may come at a potential cost, as a significant fraction of the population did not transmit their knowledge to others. Our study furthered the interest in providing sophisticated resource management recommendations that consider the relationships of traditional and scientific knowledge of seaweed selection and use in eastern Sorsogon and beyond.

Introduction: Extracted from gamboge resin, gambogic acid (GBA) is a natural product that displays a complex caged xanthone structure and exhibits promising antitumor properties. However, efforts to advance this compound to clinical applications have been thwarted by its limited availability that in turn, restricts its pharmacological optimization.Methods: We report here an efficient method that allows multigram scale isolation of GBA in greater than 97% diastereomeric purity from various sources of commercially available gamboge. The overall process includes: (a) isolation of organic components from the resin; (b) separation of GBA from the organic components via crystallization as its pyridinium salt; and (c) acidification of the salt to isolate the free GBA.Results and Discussion: We found that GBA is susceptible to epimerization at the C2 center that produces epi-gambogic acid (epi-GBA), a common contaminant of all commercial sources of this compound. Mechanistic studies indicate that this epimerization proceeds via an ortho-quinone methide intermediate. Although the observed stereochemical erosion accounts for the chemical fragility of GBA, it does not significantly affect its biological activity especially as it relates to cancer cell cytotoxicity. Specifically, we measured similar levels of cytotoxicity for either pure GBA or an equilibrated mixture of GBA/ epi-GBA in MBA-MB-231 cells with IC50 values at submicromolar concentration and induction of apoptosis after 12 hours of incubation. The results validate the pharmacological promise of gambogic acid and, combined with the multigram-scale isolation, should enable drug design and development studies.

Embaràs i malaltia cardíaca; Resultats de l’embaràs; Transposició de les grans artèries Embarazo y enfermedad cardíaca; Resultados del embarazo; Transposición de las grandes arterias Pregnancy and cardiac disease; Pregnancy outcomes, Transposition of the great arteries Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate. Funding from “Zabawas Foundation” and “De Hoop Foundation” in addition to the support from EURObservational Research Programme (EORP) is greatly acknowledged. Since the start of EORP, the following companies have supported the program: Abbott Vascular Int (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2019), Daiichi Sankyo Europe GmbH (2011–2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc (2014–2016), Menarini Int Op (2009–2012), MSD‐Merck & Co (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2009–2021), and Vifor (2019–2022).

We investigated the effect of the cation-π interaction on the susceptibility of a tryptophan model system toward interaction with singlet oxygen, that is, type II photooxidation. The model system consists of two indole units linked to a lariat crown ether to measure the total rate of removal of singlet oxygen by the indole units in the presence of sodium cations (i.e. indole units subject to a cation-π interaction) and in the absence of this interaction. We found that the cation-π interaction significantly decreases the total rate of removal of singlet oxygen (kT ) for the model system, that is, (kT = 2.4 ± 0.2) × 108 m-1 s-1 without sodium cation vs (kT = 6.9 ± 0.9) × 107 m-1 s-1 upon complexation of sodium cation to the crown ether. Furthermore, we found that the indole moieties undergo type I photooxidation processes with triplet excited methylene blue; this effect is also inhibited by the cation-π interaction. The chemical rate of reaction of the indole groups with singlet oxygen is also slower upon complexation of sodium cation in our model system, although we were unable to obtain an exact ratio due to differences of the chemical reaction rates of the two indole moieties.

Nanoindentation utilizes a hard indenter probe to deform the sample surface in order to measure local properties, such as indentation modulus and hardness. Initially intended for characterization of elastic and elastic-plastic materials, nanoindentation has more recently been utilized for viscoelastic solids as well as hydrated and soft biological materials. An advantage to nanoindentation is the ability to determine the nano- and microscale properties of materials with complex microstructures as well as those of limited sample dimension. Nanoindentation finds utility in the characterization of structural tissues, hydrogels, polymers and composites. Nevertheless, testing complexities such as adhesion and surface detection exist in nanoindentation of compliant viscoelastic solids and hydrated materials. These challenges require appropriate modifications in methodology and use of appropriate contact models to analyze nanoindentation data. A full discussion of protocol adjustments has yet to be assembled into a robust nanoindentation testing framework of soft biomaterials and polymers. We utilize existing nanoindentation literature and testing expertise in our laboratories to (1) address challenges and potential errors when performing indentations on soft or hydrated materials, (2) explore best practices for mitigating experimental error, and (3) develop a nanoindentation framework that serves researchers as a primer for nanoindentation testing of soft/hydrated biomaterials and polymers.

Caso clinico sobre el uso del Mioinositol y su papel en la resistencia a la insulina y la vitamina D y su influencia a nivel reproductivo en el contexto del Sindrome de Ovario Poliquistico.

Introduction/Background Preoperative assessment of myometrial infiltration in endometrial cancer may help to identify cases that may benefit from extended surgery. The aim of this study is to analyse the diagnostic accuracy of two-dimensional transvaginal ultrasound (2D-TVU) for detecting deep myometrial invasion (MI) and cervical stromal involvement (CSI) of endometrial cancer. Methodology All patients with confirmed endometrial cancer underwent a 2D-TVS before surgery. MI and CSI were assessed by subjective impression and recorded prospectively. At the time of the operation the specimens were sent for frozen section and the decision of performing lymph node dissection (LND) was taken intraoperatively. Final histology after hysterectomy served as gold standard. Results Twenty-two patients were included. The mean age was 64.3 years old (43–84). The histology was endometrioid in 19 patients (86.4%), serous in 2 (9.1%) and Mixed Mullerian Malignant Tumour in 1 (4.5%). Superficial MI ( 50%) in 6 (27.3%). Just in one case the cervix was thought to be affected (4.5%). All patients had hysterectomy and bilateral salpingo-oophorectomy, 10 patients underwent bilateral pelvic LND and 4 para-aortic LND, based on MI on frozen section and histological type. Final histology showed pT1A in 14 patients (63.6%), pT1B in 6 (27.3%) and pT2 in 2 (9%). There was one case of no correlation between frozen section and final histology and the patient had a re-operation for LND. Two patients had pelvic and para-aortic lymph node involvement. Accuracy for diagnosing deep MI with 2D-TVU was 86.4%, and for CSI was 95.5%. Conclusion Ultrasound evaluation by subjective impression seems to be a good method for assessing MI and CSI in endometrial cancer. The use of preoperative ultrasound in combination with frozen section improve diagnostic performance. Disclosure Nothing to disclose.

Brown trout Salmo trutta alevins were maintained at 8 and 11° C at three conditions over a 9 day period from yolk sac exhaustion: fed ad libitum, starved or fed ad libitum after starvation. Whole-body gene expressions for proteins involved in energy metabolism and the two primary proteolytic pathways were assessed. This study is the first to show an over-expression of proteasome and autophagy-related genes in young stages of salmonids, particularly at 11° C.

Background The limited efficacy of neoadjuvant schedules to obtain pCR in breast cancer together with a prompt relapse of triple negative breast cancers has opened up the development of new strategies involving the immune system, which is essential in cancer control. We have elaborated an autologous vaccine with dendritic cells loaded with patients' own tumor antigens. Based on the synergistic effect between immunotherapy and chemotherapy our hypothesis is that the combination of both strategies could improve pCR with an excellent tolerance and could increase DFS and OS. Methods Two centers are enrolling patients from February 2011. Twenty-one patients with stage II-III HER2 negative breast cancer have started on sequential neoadjuvant chemotherapy based on dose dense antracyclines (E 100mg/m2 and C 600 mgr/m2) × 4 cycles plus GM-CSF followed by taxanes (DOC 75–100 mgr/m2) × 4 cycles plus vaccination. Vaccine calendar was started after the 4th EC and alternated with taxane schedule and after chemotherapy up to a maximum of a 2 year-period. SNB biopsy was performed before neoadjuvant chemotherapy. pCR in the breast and the axilla is the main endpoint, measured by Miller&Paine classification. Data were analyzed using SPSS and alpha was set at 0.05 (two-tailed). We have compared these results in the vaccinated cohort (V) with our historic cohort (C) of 19 patients treated in the same way but without the vaccine. Results Both cohorts (V and C) were well balanced for age, histologyc type, differentiation grade, Ki67>15%, tumor size ≤ 5 cm, stage and expression of hormone receptors. All patients except one in the vaccine cohort achieved 8 cycles of chemotherapy. According to grade ¾ toxicities we did not find significant differences except for hand-foot syndrome in the V cohort (19% vs 0%; p = 0.04) and vomiting in the C cohort (0% vs 21%; p = 0.02). Lymphopenia was the most common adverse event (81% in V vs 89.5% in C; p = 0.45). Other toxicities were anemia (0% vs 5.3%; p = 0.28), thrombopenia (0% vs 10% p = 0.12), leukopenia (9.5% vs 15.8% p = 0.55) and neutropenia (14% vs 21%, p = 0.57). Gastrointestinal toxicity was similar in both groups: mucositis (0% vs 5.3%, p = 0.28); gastritis (5% in both cohorts), nausea (19% vs 16%, p = 0.78), diarrhea (5% in both cohorts), constipation (0% vs 15% in C, p = 0.06). Myalgias were seen in 19% in V vs 11% in C (p = 0.45). We did not see any local grade ¾ toxicity related to the intradermal vaccines. Regarding efficacy data, clinical complete response by MRI was shown in 38% in the V as compared to 16% in the C (p = 0.06). Breast-conserving surgery was more common in the V cohort (62% vs 53%, p = 0.55). Total pCR (T plus N) was superior with the addition of the vaccine (24% vs 5% p = 0.014). Moreover in three more patients in the V group we find isolated tumor cells in the breast (Titc). Conclusions The addition of autologous dendritic cell vaccines to neoadjuvant chemotherapy significantly increased the rate of pathological complete responses among patients with HER2-negative breast cancer. Vaccination does not seem to add any toxicity to the schedule. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-16-03.

Evaluacion de la dinamica de nematodos asociados al cultivo de cacao en la amazonia peruana

Determinar el índice fungoso y el efecto residual de los plaguicidas en la población y diversidad de hongos en un suelo ácido y alcalino

Resumen “America se hurga el ombligo” examina el dialogo a distancia que sostienen los autores modernistas y real-maravillosos para formular un algoritmo que racionalice la respuesta americana frente a la dilucion, asimilacion y coaccion de las identidades locales con que nos regala la globalizacion. El ensayo se compone de tres secciones. La primera contiene una descripcion de los aportes modernistas a la construccion de una identidad continental y sus contradicciones; la segunda, los esfuerzos de los autores real-maravillosos por refinar un nuevo perfil del latinoamericano a partir de la propuesta modernista; finalmente, la tercera seccion propone ejemplos de aplicacion del principio rector ofrecido por los autores real-maravillosos. Resumo "A America se hurga el ombligo" examina um dialogo, sustentado a distância, entre os autores modernistas e “real-maravillosos” da primeira metade do seculo XX. Depois de reconstruir essos intercâmbios, o artigo revela um algoritmo com o qual os latino-americanos tem enfrentado a diluicao, assimilacao e cooptacao de identidades regionais provocada pelo processo de globalizacao. O artigo contem tres seccoes. A primeira descreve as contribuicoes dos autores modernistas para a construcao de uma identidade latino-americana pos-colonial e suas contradicoes. A segunda destaca os refinamentos autores “real-maravillosos” tem operado sobre o perfil cultural da America Latina oferecido por contribuicoes dos modernistas. Finalmente, a terceira parte apresenta tres exemplos de aplicacao do principio geral proposto pelos autores real maravilhosos. Abstract “America se hurga el ombligo” examines a dialogue, sustained at a distance, between Modernist and Real-Marvelous authors of the first half of the Twentieth Century. Upon reconstructing these exchanges, the article uncovers an algorithm with which Latin Americans have faced the dilution, assimilation, and cooptation of regional identities brought about by the process of Globalization. The article contains three sections. The first one describes Modernist authors’ contributions to the building of a postcolonial Latin American identity and its contradictions. The second one highlights the refinements Real-Marvelous authors operated upon the novel Latin American cultural profile offered by Modernists’ contributions. Finally, the third part presents three applications of the general principle proposed by the Real Marvelous authors.

Knowledge of genetic diversity in farmers’ selections is essential for planning on-farm conservation and rehabilitation. Using 15 microsatellite loci, we analyzed parentage and population structure in 220 farmer selections of cacao from the Huallaga valley in Peruvian Amazon. A high level of allele richness and heterozygosity were detected in these selections. Coordination analysis showed that these farmer selections are mainly comprised of hybrids derived from Trinitario and Upper Amazon Forastero germplasm. Bayesian clustering analysis assigned 54 selections as Trinitario and 166 as Upper Amazon Forastero hybrids. Parentage analysis identified 15 international clones as probable parents for 96 farmer selections, which corresponded to a fraction of the known hybrid families disseminated in this region in the late 1980s. Combined analysis of demographic and molecular data revealed a significant spatial autocorrelation (r = 0.235; P = 0.006) at short geographical distances (

Secondary ion mass spectrometry analysis of ultra-shallow (sub-200 eV) B implants is complicated by the presence of native oxide on the surface of Si. Knowledge of the type of oxide present on the surface as well as accurate oxide thickness is very important for correct data reduction in extra-low energy depth profiling. Sputter rate (SR) variation approach based on the accurate SR measurement in Si and SiO2 can be successfully applied to B implants done through thermal oxides of various thicknesses. Lowest profiling energy should be used to achieve the least profile distortion in the case of de-channeled B implants: the rule of half of the implant energy used for profiling energy is confirmed. Profiling energy that is equal to the implant energy can be used if implantation is done through native oxide or into the stripped Si. If no thermal oxide is present on the surface, the most consistent result will be obtained when implants are done into the pre-stripped Si thus eliminating uncontrollable and variable native oxide-related issues. Copyright © 2012 John Wiley & Sons, Ltd.

e12062 Background: Prosigna is a standardized test based on the PAM50 gene signature which provides information on intrinsic subtype and risk of recurrence (ROR) score predicting 10y recurrence probability (NanoString Technologies, Inc., Seattle, WA). We evaluated Prosigna’s impact on adjuvant treatment decision beyond immunohistochemistry (IHC) testing. Methods: 125 pre- and postmenopausal EBC patients with ER+, HER2-, pT1-T2 pN0/pN1mi were enrolled (12 centers; 8/2015-11/2016). FFPE specimens were centrally analyzed using Prosigna to classify patients according to the intrinsic tumor subtype and ROR score. The primary endpoint was the impact of the Prosigna test on adjuvant treatment decision. Results: 64% of tumors were classified by PAM50 as Lum A, 35% as Lum B, 0% Basal, 1% HER2-E. The intrinsic subtype concordance between immunohistochemistry (IHC) and Prosigna (n = 119) was 61.3%. In Lum B tumors by IHC the discordance rate was the highest (48% were reclassified as Lum A by Prosigna) as shown in the Table. ROR risk groups were as follows: ROR low (54; 43%), ROR interm. (38; 30%), and ROR high (33; 27%). Prosigna results led to a treatment recommendation change in 49 (39%) patients. In the 76 (61%) cases with the initial recommendation of Hormonal Therapy (HT) alone the final decision changed to chemotherapy (CT)+HT (CHT) in 24 (32%) patients. In the 49 (39%) cases in which the initial recommendation was CHT the final decision changed to HT in 25 (51%) patients. Among the 38 patients with Prosigna intermediate risk, 21 (55%) were allocated to HT. Conclusions: In this prospective decision impact study, Prosigna results led to a 39% change in adjuvant therapy indication. Patients with initial indication of CHT were changed to HT alone in > 50% of cases. Thus, Prosigna results influenced the treatment decisions and reinforced its clinical utility in real-world settings. The intrinsic subtype classification based on IHC didn’t show to be an adequate surrogate for the genomic subtypes as determined by Prosigna. [Table: see text]

BACKGROUND: We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed. METHODS: Twenty-five patients treated with pemetrexed-based regimens were included. Genomic DNA was isolated prior to treatment. The variable number of tandem repeat (VNTR) polymorphisms, the G > C single nucleotide polymorphisms (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3' untranslated region (UTR) polymorphisms were analyzed and correlated with overall response rate (ORR), progression-free survival (PFS), overall-survival (OS) and toxicity. RESULTS: The genotype +6/+6 predicted a higher ORR among active/former smokers compared to +6/-6 genotype (100% vs. 50%; p = 0.085). Overall, the 3R/3R genotype predicted a higher ORR (100%) over the rest VNTR polymorphisms (p = 0.055). The presence of 3R/3R genotype significantly correlated with a superior ORR in patients without EGFR activating mutations (100%) compared to 2R/2R, 2R/3R and 3R/4R genotype (77.8%, 33.3% and 0% respectively; p = 0.017). After a median follow-up of 21 months, a trend towards a better PFS, although not significant, was found among subjects showing 3R/3R polymorphisms (p = 0.089). A significantly superior OS was found in patients showing 3R/3R genotype rather than other VNTR polymorphisms (p = 0.019). No significant correlation with the toxicity was observed. CONCLUSION: In our series, 3R/3R polymorphism correlated with a superior OS. Also, this polymorphism, when associated to wild type EGFR, was related to a higher ORR to pemetrexed. Toxicity was not significantly correlated with a specific TS genotype.

In Colombia, just the same as in the whole World, globalization of the market led to a large increase in importating of diverse devices. In case of devices for aesthetic use, importing a large number of different device types without adequate control of products, increases the risk of appearance of adverse events for their users. On the other hand, there are very few studies of adverse events caused by their use, or risk assessment studies. This paper presents the role of academy in defining the conditions for safety of aesthetic devices and evaluation of medical devices "Class 1", for use in aesthetics. With support of the Colombian government, the Pan American Health Organization PAHO, and the regulating entity INVIMA, we proposed a model of control and regulation of use of devices for aesthetics in order to achieve ease of classification and ensure adequate use of devices for aesthetics, and to minimize the risk for users of the technology. As a result of this model, a tool was developed to facilitate to the regulatory entity the classification and evaluation of devices for aesthetic use "Class 1", which will be implemented by the Colombian government with the support of biomedical engineers having the required knowledge and skills.

Sweat bees (family Halictidae) comprise a numerous and diverse group that are arguably among the most socially labile of all insect taxa. Given the lack of highly variable markers for eusocial species of the family, we developed a suite of dinucleotide and trinucleotide markers for one of its members, the Eurasian Lasioglossum malachurum, and used them to amplify DNA from other halictids. Loci were highly variable in L. malachurum and amplified DNA from many other halictids.

Background Frontline treatment of metastatic castration-resistant prostate cancer (mCRPC) consists of docetaxel-based chemotherapy. The median time to progression (TTP) from chemotherapy initiation is 6 to 8 months. Ketoconazole, a nonspecific cytochrome P17 inhibitor (CYP17i), blocks adrenal androgen synthesis. Low-dose ketoconazole (LDK), (200 mg three times daily [t.d.s]) has shown activity in mCRPC after progression to androgen deprivation. The role of a CYP17i after docetaxel treatment in the maintenance setting has been unexplored. Methods We identified 38 patients with mCRPC who showed progression to luteinizing hormone releasing–hormone agonists (LHRHa) and who were treated with a median of 7 cycles of frontline three-weekly docetaxel (75 mg/m2) plus prednisone (10 mg/d) and LHRHa. Medical charts of 20 patients who showed no progression to docetaxel were reviewed. After the last docetaxel cycle, 10 patients received LDK maintenance treatment plus prednisone (10 mg/d) and LHRHa, whereas 10 patients received LHRHa alone. TTP was the primary endpoint. Results After a follow-up of 27 months, disease in all patients receiving LHRHa alone progressed, whereas 8/10 patients progressed to maintenance therapy. Median TTP from docetaxel initiation was 11.5 months (95% confidence interval [CI], 6.3-16.6) for maintenance therapy and 9.2 months (95% CI, 8.5-9.9) for LHRHa alone (P = .047). The maintenance treatment was well tolerated. Only 1 patient experienced a grade 4 adverse event due to a nonsymptomatic pulmonary embolism. Conclusion This is the first study evaluating a CYP17i for maintenance therapy after docetaxel therapy. We showed a 2-month significant benefit in TTP for patients with mCRPC treated with LDK maintenance therapy after docetaxel, with a favorable toxicity profile. A large prospective randomized study using a CYP17i is warranted.

Background Small-cell carcinoma (SCC) comprises 1% of primary bladder tumors and approximately 2% of prostate neoplasms. Metastatic disease at diagnosis is common, and survival outcomes are extremely poor. There is controversy about the ideal clinical management of these patients. The neuron-specific enolase (NSE) serum levels have never been studied in patients with small-cell carcinoma of the urinary tract (SCCUT). Patients and Methods We report the clinical outcome of 12 consecutive SCCUT patients treated during the past 10 years. We also study the NSE levels at diagnosis and during treatment. Results Patients with limited disease (LD) experienced a non-significant longer progression-free survival (PFS) and overall survival (OS) compared with extensive disease (ED) subjects. Patients with bladder SCC showed a significantly higher median PFS compared with prostate SCCUT patients (22 vs. 6 months; P = .034), although that difference did not impact on a significant longer OS. NSE levels decreased during chemotherapy administration in all patients with ED and baseline high levels. Conclusions Our patients showed a poor prognosis as described in previous studies. A better outcome for patients with bladder SCC compared with prostate SCC could be suggested. Serum NSE levels should be further evaluated to prove its potential use in early diagnosis and treatment monitoring during chemotherapy.

A strategy for the efficient two-step synthesis of triazole derivatives of oxindoles and spirooxindoles is presented. Using a common set of N-propargylated isatins, a series of mechanistically distinct stereoselective reactions with different combinations of nucleophiles and catalysts provide access to diverse hydroxy-oxindoles, spiroindolones, and spirocyclic oxazoline structures. The resulting N-propargylated oxindoles are then converted to triazoles using copper-catalyzed azide–alkyne cycloaddition (CuAAC) reactions. Overall, this strategy affords a 64-member pilot-scale library of diverse oxindoles and spirooxindoles.

Reaction of various isatins with 5-methoxyoxazoles proceeds regioselectively and with high diastereoselectivity to afford spiro products (III) and (V).

Controlling short channel effects for further scaled CMOS is required to take full advantage of the introduction of high K/metal gate or stress induced carrier mobility enhancement. Ultra‐Shallow junction formation is necessary to minimize the short channel effects. In this paper, we will discuss the challenges for 28 nm Ultra‐Shallow Junction formations in terms of figure of merits of Rs/Xj and junction leakage. We will demonstrate that by adopting and integrating Carborane (CBH, C2B10H12) molecular implant and Phosphorus along with co‐implantation and PTC II (VSEA Process Temperature Control) technology, sub‐32 nm pLDD and nLDD junction targets can be timely achieved using traditional anneals. Those damage engineering solutions can be readily implemented on state‐of‐the‐art 28 nm device manufacturing.

A regio- and stereoselective cyclization between isatins and 5-methoxyoxazoles has been developed using catalytic titanium(IV) chloride (10 or 20 mol %) to afford spiro[3,3'-oxindoleoxazolines] in excellent yield (up to 99%) and diastereoselectivity (dr >99:1). Substitution at the 4-position of the oxazole controls nucleophilic attack to provide either the 2-oxazoline or 3-oxazoline spirocycle with excellent (>99:1) regiocontrol.

The photoinjector test facility at DESY, Zeuthen site (PITZ), was built to develop and optimize photoelectron sources for superconducting linacs for high-brilliance, short-wavelength free-electron laser (FEL) applications like the free-electron laser in Hamburg (FLASH) and the European x-ray free-electron laser (XFEL). In this paper, the detailed characterization of two laser-driven rf guns with different operating conditions is described. One experimental optimization of the beam parameters was performed at an accelerating gradient of about 43 MV/m at the photocathode and the other at about 60 MV/m. In both cases, electron beams with very high phase-space density have been demonstrated at a bunch charge of 1 nC and are compared with corresponding simulations. The rf gun optimized for the lower gradient has surpassed all the FLASH requirements on beam quality and rf parameters (gradient, rf pulse length, repetition rate) and serves as a spare gun for this facility. The rf gun studied with increased accelerating gradient at the cathode produced beams with even higher brightness, yielding the first demonstration of the beam quality required for driving the European XFEL: The geometric mean of the normalized projected rms emittance in the two transverse directions was measured to be 1.26±0.13 mm mrad for a 1-nC electron bunch. When a 10% charge cut is applied excluding electrons from those phase-space regions where the measured phase-space density is below a certain level and which are not expected to contribute to the lasing process, the normalized projected rms emittance is about 0.9 mm mrad.

The study of beam dynamics and the localization of potential sources of instabilities are important tasks in the design of modern, high-intensity particle accelerators. In the case of synchrotrons and storage rings, coupling impedance data are needed to characterize the parasitic interaction of critical components with the beam. In this article we demonstrate the application of numerical field simulations to the computation of transverse kicker coupling impedances. Based on the 3D simulation results, a parametrized model is developed to incorporate the impedance of an arbitrary pulse-forming network attached to the kicker. Detailed comparisons of numerical results with twin-wire and direct measurements are discussed at the example of the Spallation Neutron Source extraction kicker.

Scaling of source/drain extension junctions continues to be a major focus for sub 45 nm planar CMOS process development. Device scalability, drive current, and leakage performance are determined by junction depth, activation, and residual disorder. These requirements have driven ion implants into the deep sub-keV regime and integration of millisecond anneals for activation. In this paper, we introduce the formation of extension junctions using thermally stable boron containing molecular implant which alleviates productivity concerns with sub-keV implantation and runs on a standard high current implanter. In combination with advanced millisecond sub-melt laser anneal, p-n junctions with high activation and negligible dopant profile movement are produced. Limiting diffusion and maximizing activation with optimized dopant concentration, effect of different amorphization schemes, and the use of diffusion modifiers such as carbon will also be discussed in the context of millisecond laser anneals. In addition, the role of implantation in minimizing residual disorder after laser anneals and its relevance to junction leakage is discussed.

The computation of wake fields excited by ultrashort electrons bunches in accelerator components with geometrical discontinuities is a challenging problem, as an accurate resolution for both the small bunch and the large model geometry are needed. Several computational codes (PBCI,ROCOCO,CST PARTICLE STUDIOtrade) have been developed to deal with this type of problems. Wake field simulations of the RF electron gun of the Photoinjector Test Facility at DESY Zeuthen (PITZ) are performed with different specialized codes. Here we present a comparison of the wake potentials calculated numerically obtained from the different codes. Several structures of the photoinjector are considered.

Summary Driven by science, engineering and daily practice in sediment management a big variety of technologies for treatment and disposal is available. Main fields for further development with respect to sediment management is to find the way to compare different complex scenarios of treatment and disposal (assessment) and to build up the markets for treatment of sediments. The SedNet mission makes obvious that sustainability is only achievable on a new spatial and time scale. Since the present structures for decision-making are mostly local or regional acting administrations, however their actions have often consequences on a bigger scale, the river basin scale. Additionally, to build up a sustainable sediment management long-termeffects over the time span of a generation or more have to be considered. According to the aim of a sustainable sediment management we recommend assessment on a river basin scale considering a sustainable time scale of one generation! A sustainable river basin model has to integrate social, environmental and economic aspects, but so far a model offering this is only vague: In a river basin the members of the society are the driving force, economy can be seen as the sum of activities and the environment is part of the “capital stock” that is available for development and activities of the society. Some parts of this “capital” is not renewable. Consequently, in a broader view of economy, neglecting environmental effects bears the risk of a loss of capital stocks, consequently decreasing the economy and social welfare on the long term. What are the consequences of this new river basin view? The people are the driving part in the system. In general, people can only react rationally with respect to economy and environment, if they are informed. Knowledge is the basis for understanding processes and mutual interaction and at least informed people will understand and accept rational decisions based on assessment procedures. Besides information of the public an assessment procedure is the second column for decision making. The outcome of such an assessment is a ranking of treatment alternatives offered for a sediment problem. Such an assessment should not base on a single tool e.g. a cost calculation or LCA, because no tool covers all fields necessary to be considered (economy, environment, society). It must be recommended that a combination of tools (Costs, LCA, cost-benefit evaluation, risk assessment studies) should become routine before decisionmaking. European standards for assessing treatment and disposal alternatives should consider the present know-how about long-term effects (e.g. the life-cycle of sediments and products and effects on mobility and bio-availability of pollutants with time) and the differences between the results of biological and chemical methods applied for the same sediments. Thinking about assessment standards leads to the necessity of harmonizing those standards Europewide in order to avoid transport of sediments across boarders between regions and countries in Europe applying different standards. Looking at sustainability some benefits like the reduction of space consumption, climate or re-use of secondary material substituting primary resources are complicated to be evaluated. We will come closer to sustainability the more we have an overall or comprehensive model considering economic factors as well as the environment. The example of the European Guideline for Trading Emission Certificates (2003/87/EC) can be seen as a general approach how to combine economy and ecology in a way accepted from the society. So we recommend to conduct research in fields that provide us with parameters or better tools to evaluate goods like “the landscape”, “space consumption”, etc. useful to improve decision making. Accordingly, an integration of broader economic know-how into the assessment procedures is needed in order to evaluate benefits outside common budgets on to consider “hidden costs” and superior issues like source control or resource demands, which are not covered by the responsibility and budget of water and sediment management authorities today.

Background The course and sequelae of Kawasaki disease (KD), an acute, self-limited pediatric vasculitis, vary widely among patients. Autopsy evidence of chronic cardiovascular inflammation years after KD resolution suggests a need to monitor and address this potential underlying cause of late cardiovascular morbidity and mortality. Objectives A unique high resolution, multi-analytics systems biology approach was employed to yield insights into individual patient disease biology driving their clinical course of disease. In particular, comprehensive and longitudinal molecular profiling aims to more fully characterize biological processes contributing to the development of post-acute coronary aneurysms, to identify biomarkers to monitor them and to suggest therapies to mitigate these serious sequelae in KD. Methods We applied an individual patient-oriented, high-resolution integrated analytics approach to eight KD subjects with and without coronary aneurysm. A longitudinal analysis across acute, subacute and convalescent stages was performed with a combination of whole blood gene transcript profiling and plasma analysis via shotgun proteomics, ELISA, and plasma protein glycomics to analyze longitudinal samples from eight KD subjects with different clinical outcomes. Results Subject samples clustered into two molecular profiles corresponding to the acute or the subacute and convalescent stage of KD. The individual subjects9 molecular profile trajectories across these stages of KD showed significant differences between patients which corresponded to their clinical course. Notably, subjects who developed post-acute stage giant aneurysms showed molecular profiles indicative of unresolved inflammation. This persistent inflammation was characterized by markers of acute phase response, cardiovascular injury, a pro-coagulant state, increased cell adhesion/migration, and increased activation of granulocytes. Conclusions Personalized high-resolution, integrated analytics provided a comprehensive view of the clinical state of individual patients and the trajectory of their disease. Novel biomarkers of tissue-level inflammation and potential new molecular targets for therapeutic intervention were identified. Acknowledgements We thank Dr. K. Frank Austen and Dr. Jan Hillson for helpful discussions of this work. This work supported in part by grants from the National Institutes of Health, Heart, Lung, and Blood Institute to JCB (U54 HL108460 and HL69413). R.S. acknowledges funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 260600 (“GlycoHIT”). H.Stockmann acknowledges the support of the EU FP7 program HighGlycan, Grant No. 278535 and S.A. acknowledges Science Foundation Ireland ((08/SRC/B1393, Alimentary Glycoscience Research Cluster (AGRC). Disclosure of Interest L. Ling Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, D. Bulik Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, J. Duffner Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, C. Shimizu: None declared, H. Sarvaiya Shareholder of: Momenta Pharmaceuticals, B. Kapoor: None declared, J. Brown Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, L. Markowitz Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, E. Arevalo Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, B. Schultes Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, I. Capila Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, R. Saldova: None declared, H. Stockmann: None declared, S. Albrecht: None declared, C. McManus: None declared, P. Rudd: None declared, G. Kaudinya Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, A. Manning Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, A. Tremoulet: None declared, C. Bosques Shareholder of: Momenta Pharmaceuticals, Employee of: Momenta Pharmaceuticals, J. Burns: None declared

Nonmelt laser annealing (NLA) is used to form heavily-doped, ultra-shallow regions in boron implanted crystalline silicon. Results are compared to samples receiving a conventional 1050degC spike anneal. A high-dose non-amorphizing boron implant of 1015 ions/cm2 at 500 eV is used. The implant is laser annealed with between one and 1000 20 ns long pulses or a 1050degC spike anneal. NLA alone produces junction depths from 21 to 25 nm with sheet resistances around 800 W/sq, while spike annealing results in 40 nm junctions at ~ 2400 W/sq. Hall effect measurements produce mobilities around 30 cm2/V-s. Plan-view TEM shows damage from the implant is completely removed after 100 pulses. Thus, nonmelt laser annealing alone can be used to produce shallower junctions with lower resistivity than conventional RTA offering junction characteristics suitable for the 2007 65 nm ITRS technology node

Purpose This study aimed to review the clinical features, therapeutic management and natural course of patients with small-cell carcinoma of the urinary tract (SCCUT), based on our own clinical experience. Material and methods From March 2002 to February 2012 twelve patients were diagnosed with SCCUT and started treatment at the Clinica Universidad de Navarra, Pamplona (Spain). Results The primary tumor site was prostate in 6/12 (50%), urinary bladder in 5/12 (41.7%) and kidney in 1/12 (8.3%) of the cases. Overall, 5 patients (41.7%) had limited disease (LD) and 7 (58.3%) had extensive disease (ED) at the time of diagnosis. Neuron-Specific Enolase (NSE) serum levels were determined in 5 patients at onset. In all of them, levels over the upper-limit were observed. Detailed treatment information was available in 10 patients, 5 with LD and 5 with ED. LD patients were treated in a multimodality fashion. After a median follow-up of 26 months, median progression-free survival (PFS) for patients with LD was 22 months (range 7–40). Median overall survival (OS) was 26 months (range 11–40). Patients showing ED mostly received palliative chemotherapy. The overall response rate for chemotherapy in this cohort was 75%; 2/4 achieved a complete response, 1/4 a partial response and 1/4 showed disease stabilization. After a median follow-up of 12 months, the median PFS was 11 months (range 3–14). The median OS was 14 months (range 12–38) for the ED cohort. However, the differences observed in PFS and OS between LD and ED cohorts did not achieve statistical significance. In addition, patients with bladder SCCUT showed a statistically significant longer PFS (22 months) compared to patients with a prostatic origin (6 months). Conclusions Despite its chemosensitivity, SCCUT showed an aggressive clinical course and poor prognosis in our series. Bladder origin SCCUT may have a better prognosis than those from prostate origin. NSE serum levels may help to achieve an early diagnosis and to provide a proper systemic treatment up-front. Disclosure All authors have declared no conflicts of interest.

Background 5-HT3 antagonists are one of the more effective antiemetic preventions in patients who are receiving platinum-based chemotherapy. Some of these 5-HT3 antagonist are available for oral use, however the therapeutic formulations with more bioavailability and middle course which have been traditionally administrated by the intravenous route, have a limited use in the hospital environment. Up to now, no study has examined the pharmacokinetics of these drugs when administered subcutaneously. We have compared pharmacokinetics of palonosetron in the two different routes, SC and IV. Methods Patients under platinum-based chemotherapy were randomized to receive before the first cycle of chemotherapy, palonosetron by the SC or the IV route. In the second cycle, the drug was administrated by the other route. The main endpoint was Area Under the Curve between 0-24 hours (AUC 0–24h). Blood samples were drawn at 10, 15, 30, 45, 60, 90 min and 2, 3, 4, 8, 12, 24 h after palonosetron. Drug levels were determined by HPLC with fluorescence detection after liquid extraction of the samples, with a quantitation limit of 0.1 ng/ml. Results We included 26 patients, from October 2009 to May 2010. We found no statistically differences in the Area Under Curve at 24 hours after the drug administration (AUC 0-24) between both routes. Maximum concentration (Cmax) reached after its administration was significantly lower via the SC route than by IV. The time to reach the Cmax (Tmax) by the SC route was superior than the IV route. The elimination of unmetabolized drug in urine (Ae 24h) was similar in both routes, in the first 24 hours, about 20% of the administered dose. The prevention of early and late emesis was equivalent with both alternatives. Conclusions Palonosetron SC administration showed similar AUC0-24h to that of the IV route, with the same exposure to the drug, and good control in the prevention of early and late emesis, which can benefit the management of outpatient treatments. i.v. (mean ± SD) s.c. (mean ±SD) p-value AUC 0-24h (ngxh/ml) 14,10 ± 6,73 12,68 ± 9,70 0,160 Cmax (ng/ml) 11,88 ± 7,38 1,91 ± 1,09 Tmax (h) 0,04 ± 0,04 0,26 ± 0,13 Ae24h (%) 19,48 ± 9,99 22,24 ± 8,50 0,660 Disclosure All authors have declared no conflicts of interest.

For many reasons it is advantageous to collect urine separately and collection systems, so called "no-mix-toilets" exist. Therefore, this work deals with some methods to make use of this urine to produce value added products: IBDU and ammonia water. It could be shown that urea can be converted to IBDU only after concentrating urine. With air stripping and absorption ammonificated urine can be treated very effectively and a solution of 10% w/w of ammonia can be obtained.

The alpha-factor tridecapeptide initiates mating in Saccharomyces cerevisiae upon interaction with Ste2p, its cognate G-protein coupled receptor (GPCR). This interaction is being used as a paradigm for understanding the structure and mechanism of activation of GPCRs by medium-sized peptides. In this article, the use of fragments of Ste2p to study its structure is reviewed. Methods of synthesis of peptides corresponding to both extramembranous and transmembrane domains of Ste2p are evaluated and problems that are encountered during synthesis and purification are described. The results from conformational analyses of the peptide fragments using fluorescence spectroscopy, CD, infrared spectroscopy, and NMR spectroscopy in organic-aqueous mixtures and in the presence of detergent micelles and lipid bilayers are critically reviewed. The data obtained to date provide biophysical evidence for the structure of different domains of Ste2p and indicate that peptides corresponding to these domains have unique biophysical tendencies. The studies carried out on Ste2p fragments indicate that valuable information concerning the structure of the intact receptor can be obtained by studying peptide fragments corresponding to domains of these polytopic integral membrane proteins.

The effect of the pre-anneal conditions on the final defect microstructure after flash annealing of Ge implanted Si is investigated using transmission electron microscopy. (100) Si wafers were implanted with 30keV Ge+ implant at a dose of 1 t 1015/cm2 followed by a 500eV B implant at a dose of 1 t 1015/cm2. The germanium implant produces an amorphous layer 480A thick and the boron implant is completely contained within the amorphous layer. The wafer was subsequently subjected to an impulse anneal at ramp rates between 50dC/sec and 400dC/sec to temperatures between 700 and 900dC followed by a flash anneal to temperatures between 1100dC and 1300dC. The flash anneal occurred over a microsecond time scale so the ramp rates and the cooling rates are estimated to be 106dC/sec. It was found that the ramp rate and temperature of the impulse pre-anneal has a remarkable effect on the final microstructure and sheet resistance of the implant. For the 760dC pre-anneal impulse temperature, followed by a 1300dC flash, decreasing the ramp rate of the impulse anneal from 400dC/sec to 50dC/sec increases the end of range defect density by 270% while the sheet resistance increased from 613 to 704 ohms/square. As the impulse temperature is increased the effects of the impulse ramp rate appear to decrease. The changes in the electrical and microstructural properties of the Si imply that the relatively low temperature impulse conditions play an increasingly important role as the high temperature flash anneals become shorter.

We investigate the dynamics of a lattice soliton on a monatomic chain in the presence of damping and external forces. We consider Stokes and hydrodynamical damping. In the quasi-continuum limit the discrete system leads to a damped and forced Boussinesq equation. By using a multiple-scale perturbation expansion up to second order in the framework of the quasi-continuum approach we derive a general expression for the first-order velocity correction which improves previous results. We compare the soliton position and shape predicted by the theory with simulations carried out on the level of the monatomic chain system as well as on the level of the quasi-continuum limit system. For this purpose we restrict ourselves to specific examples, namely potentials with cubic and quartic anharmonicities as well as the truncated Morse potential, without taking into account external forces. For both types of damping we find a good agreement with the numerical simulations both for the soliton position and for the tail which appears at the rear of the soliton. Moreover we clarify why the quasi-continuum approximation is better in the hydrodynamical damping case than in the Stokes damping case.