NMR, Metabonomics and Molecular Profiles: Applications to the Quality Assessment of Foodstuffs

Nuclear Magnetic Resonance (NMR) is a branch of spectroscopy that is based on the fact that many atomic nuclei may be oriented by a strong magnetic field and will absorb radiofrequency radiation at characteristic frequencies. The parameters that can be measured on the resulting spectral lines (line positions, intensities, line widths, multiplicities and transients in time-dependent experi-ments) can be interpreted in terms of molecular structure, conformation, molecular motion and other rate processes. In this way, high resolution (HR) NMR allows performing qualitative and quantitative analysis of samples in solution, in order to determine the structure of molecules in solution and not only. In the past, high-field NMR spectroscopy has mainly concerned with the elucidation of chemical structure in solution, but today is emerging as a powerful exploratory tool for probing biochemical and physical processes. It represents a versatile tool for the analysis of foods. In literature many NMR studies have been reported on different type of food such as wine, olive oil, coffee, fruit juices, milk, meat, egg, starch granules, flour, etc using different NMR techniques. Traditionally, univariate analytical methods have been used to ex-plore spectroscopic data. This method is useful to measure or to se-lect a single descriptive variable from the whole spectrum and , at the end, only this variable is analyzed. This univariate methods ap-proach, applied to HR-NMR data, lead to different problems due especially to the complexity of an NMR spectrum. In fact, the lat-ter is composed of different signals belonging to different mole-cules, but it is also true that the same molecules can be represented by different signals, generally strongly correlated. The univariate methods, in this case, takes in account only one or a few variables, causing a loss of information. Thus, when dealing with complex samples like foodstuff, univariate analysis of spectra data results not enough powerful. Spectra need to be considered in their wholeness and, for analysing them, it must be taken in consideration the whole data matrix: chemometric methods are designed to treat such multivariate data. Multivariate data analysis is used for a number of distinct, differ-ent purposes and the aims can be divided into three main groups: • data description (explorative data structure modelling of any ge-neric n-dimensional data matrix, PCA for example); • regression and prediction (PLS); • classification and prediction of class belongings for new samples (LDA and PLS-DA and ECVA). The aim of this PhD thesis was to verify the possibility of identify-ing and classifying plants or foodstuffs, in different classes, based on the concerted variation in metabolite levels, detected by NMR spectra and using the multivariate data analysis as a tool to inter-pret NMR information. It is important to underline that the results obtained are useful to point out the metabolic consequences of a specific modification on foodstuffs, avoiding the use of a targeted analysis for the different metabolites. The data analysis is performed by applying chemomet-ric multivariate techniques to the NMR dataset of spectra acquired. The research work presented in this thesis is the result of a three years PhD study. This thesis reports the main results obtained from these two main activities: A1) Evaluation of a data pre-processing system in order to mini-mize unwanted sources of variations, due to different instrumental set up, manual spectra processing and to sample preparations arte-facts; A2) Application of multivariate chemiometric models in data analy-sis.

Microfluidic device and interfacial transport: application to biomolecules and nanostructures

The aim of my dissertation is to provide new knowledge and applications of microfluidics in a variety of problems, from materials science, devices, and biomedicine, where the control on the fluid dynamics and the local concentration of the solutions containing the relevant molecules (either materials, precursors, or biomolecules) is crucial. The control of interfacial phenomena occurring in solutions at dierent length scales is compelling in nanotechnology for devising new sensors, molecular electronics devices, memories. Microfluidic devices were fabricated and integrated with organic electronics devices. The transduction involves the species in the solution which infills the transistor channel and confined by the microfluidic device. This device measures what happens on the surface, at few nanometers from the semiconductor channel. Soft-lithography was adopted to fabricate platinum electrodes, starting from platinum carbonyl precursor. I proposed a simple method to assemble these nanostructures in periodic arrays of microstripes, and form conductive electrodes with characteristic dimension of 600 nm. The conductivity of these sub-microwires is compared with the values reported in literature and bulk platinum. The process is suitable for fabricating thin conductive patterns for electronic devices or electrochemical cells, where the periodicity of the conductive pattern is comparable with the diusion length of the molecules in solution. The ordering induced among artificial nanostructures is of particular interest in science. I show that large building blocks, like carbon nanotubes or core-shell nanoparticles, can be ordered and self-organised on a surface in patterns due to capillary forces. The eective probability of inducing order with microfluidic flow is modeled with finite element calculation on the real geometry of the microcapillaries, in soft-lithographic process. The oligomerization of A40 peptide in microconfined environment represents a new investigation of the extensively studied peptide aggregation. The added value of the approach I devised is the precise control on the local concentration of peptides together with the possibility to mimick cellular crowding. Four populations of oligomers where distinguished, with diameters ranging from 15 to 200 nm. These aggregates could not be addresses separately in fluorescence. The statistical analysis on the atomic force microscopy images together with a model of growth reveal new insights on the kinetics of amyloidogenesis as well as allows me to identify the minimum stable nucleus size. This is an important result owing to its implications in the understanding and early diagnosis and therapy of the Alzheimer’s disease

Transkulturelle Handlungsstrategien und Vertrauensbildung im internationalen Tourismus : eine Untersuchung von Tauchbasenbetreibern in Ägypten

Der Tauchtourismus übernimmt innerhalb des gesamten internationalen Tourismus in Ägypten eine wichtige Rolle. Besonders in Krisenzeiten sind es die Taucher, die aufgrund der einzigartigen Tauchgebiete weiterhin in das Land kommen und somit einen wesentlichen Beitrag zum Erhalt der Arbeitsplätze und der Infrastruktur beitragen. Doch der Konkurrenzkampf zwischen den Tauchbasen, das derzeit schlechte Image Ägyptens und die Attraktivität weltweiter Tauchdestinationen, zwingt die Betreiber von Tauchbasen dazu, sich einer wandelnden Gästestruktur und deren Reisegewohnheiten anzupassen. In der vorliegenden Untersuchung wird am Beispiel der Tauchbasenbetreiber in Ägypten untersucht, wie kulturelles Handeln eine Rolle bei der Bildung von Vertrauen zwischen einem Anbieter einer touristischen Dienstleistung und dem Kunden einnehmen kann. Als Ausgangspunkt dient dazu das Modell der „Transkulturalität als Praxis“ nach PÜTZ (2004), welches um den Aspekt der internationalen Kooperationsbeziehungen erweitert wird. Es besagt, dass im wirtschaftlichen Handeln zwischen den Akteuren das kulturelle Verständnis eine entscheidende Rolle bei der Bildung von Vertrauen einnimmt. Durch die Fähigkeit, einen kulturellen Blickwinkel in das alltägliche Handeln einzubeziehen, kann ein Unternehmer den Wettbewerbsvorsprung zu seinen Mitkonkurrenten ausbauen.rnrnIm Mittelpunkt des Forschungsinteresses stand dabei die Frage inwieweit die Basenbetreiber über die ihnen zur Verfügung stehenden Möglichkeiten kulturgebundenen Handelns Vertrauen zu den Tauchern generieren. Geschieht die Anwendung aus eigener Initiative heraus oder nur unter dem Konkurrenzdruck? Die Ergebnisse der Studie belegen, dass das Arbeiten im Umfeld kultureller Unterschiede den Blick der Basenbetreiber für die Notwendigkeit einer starken Vertrauensbeziehung zum Kunden von Anfang an geprägt hat. Das Handeln aller Interviewteilnehmer orientiert sich zuerst unbewusst an zahlreichen branchenüblichen Handlungsweisen und Symbolen, stößt aber ab einem bestimmten Punkt an seine Grenzen. Aufgrund von bewusstem kulturellen Handeln ist jedoch die Möglichkeit gegeben, diese Grenzen zu überwinden und individuelle und situationsspezifische Arten der Kundengewinnung in das Handeln einzubeziehen.

Therapy resistant neonatal seizures, linear vesicular rash, and unusually early neuroradiological changes: incontinentia pigmenti : A case report, literature review and insight into pathogenesis

CASE PRESENTATION: A substance abusing G2P1 mother spontaneously delivered at term an appropriate for gestational age girl. Neonatal seizures appeared at 21 hours and empiric anticonvulsive and antimicrobial treatment was started. At 25 hours, first vesicles appeared. While routine evaluations remained normal, a head CT revealed multifocal ischemic injuries, and a later MRI showed multifocal petechiae and diffusion abnormalities in the corticospinal tracts. The clinical diagnosis of incontinentia pigmenti (stage 1) was secured by histopathology. Follow-up at 13 months showed global developmental delay. DISCUSSION: We discuss the unusually early bilateral, fronto-occipital corticomedullar ischemias (CT day 3). On the MR imaging (day 7) extensive symmetric cerebral corticomedullar destruction and diffusion sequences with corticospinal tracts abnormalities are seen, which then evolve (day 26) to extensive symmetric cerebral destruction. We review the literature, genetics, suspected pathophysiology and possible neonatal manifestation. CONCLUSION: Incontinentia pigmenti is rare and, therefore, diagnosis is frequently delayed. Nevertheless, in the setting of therapy refractory seizures, excluded infections, and linear vesicular rash, a high index of suspicion is needed. This is the first report of simultaneous corticomedullar involvement as early as the third day of life.

Writing center handbooks and travel guidebooks : redesigning instructional texts for multicultural, multilingual, and multinational contexts

In an increasingly interconnected world characterized by the accelerating interplay of cultural, linguistic, and national difference, the ability to negotiate that difference in an equitable and ethical manner is a crucial skill for both individuals and larger social groups. This dissertation, Writing Center Handbooks and Travel Guidebooks: Redesigning Instructional Texts for Multicultural, Multilingual, and Multinational Contexts, considers how instructional texts that ostensibly support the negotiation of difference (i.e., accepting and learning from difference) actually promote the management of difference (i.e., rejecting, assimilating, and erasing difference). As a corrective to this focus on managing difference, chapter two constructs a theoretical framework that facilitates the redesign of handbooks, guidebooks, and similar instructional texts. This framework centers on reflexive design practices and is informed by literacy theory (Gee; New London Group; Street), social learning theory (Wenger), globalization theory (Nederveen Pieterse), and composition theory (Canagarajah; Horner and Trimbur; Lu; Matsuda; Pratt). By implementing reflexive design practices in the redesign of instructional texts, this dissertation argues that instructional texts can promote the negotiation of difference and a multicultural/multilingual sensibility that accounts for twenty-first century linguistic and cultural realities. Informed by the theoretical framework of chapter two, chapters three and four conduct a rhetorical analysis of two forms of instructional text that are representative of the larger genre: writing center coach handbooks and travel guidebooks to Hong Kong. This rhetorical analysis reveals how both forms of text employ rhetorical strategies that uphold dominant monolingual and monocultural assumptions. Alternative rhetorical strategies are then proposed that can be used to redesign these two forms of instructional texts in a manner that aligns with multicultural and multilingual assumptions. These chapters draw on the work of scholars in Writing Center Studies (Boquet and Lerner; Carino; DiPardo; Grimm; North; Severino) and Technical Communication (Barton and Barton; Dilger; Johnson; Kimball; Slack), respectively. Chapter five explores how the redesign of coach handbooks and travel guidebooks proposed in this dissertation can be conceptualized as a political act. Ultimately, this dissertation argues that instructional texts are powerful heuristic tools that can enact social change if they are redesigned to foster the negotiation of difference and to promote multicultural/multilingual world views.

Variation in hepatic regulation of metabolism during the dry period and in early lactation in dairy cows

The purpose of this study was to investigate variations in hepatic regulation of metabolism during the dry period, after parturition, and in early lactation in dairy cows. For this evaluation, cows were divided into 2 groups based on the plasma concentration of beta-hydroxybutyric acid (BHBA) in wk 4 postpartum (PP; group HB, BHBA >0.75 mmol/L; group LB, BHBA <0.75 mmol/L, respectively). Liver biopsies were obtained from 28 cows at drying off (mean 59 +/- 8 d antepartum), on d 1, and in wk 4 and 14 PP. Blood samples were collected every 2 wk during this entire period. Liver samples were analyzed for mRNA abundance of genes related to carbohydrate metabolism (pyruvate carboxylase, PC; phosphoenolpyruvate carboxykinase, PEPCK; citrate synthase, CS), fatty acid biosynthesis (ATP citrate lyase, ACLY) and oxidation (acyl-CoA synthetase long-chain, ACSL; carnitine palmitoyltransferase 1A, CPT 1A; carnitine palmitoyltransferase 2, CPT 2; acyl-coenzyme A dehydrogenase very long chain, ACADVL), cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 1, HMGCS1), ketogenesis (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2, HMGCS2), and of genes encoding the transcription factors peroxisome proliferator-activated receptor alpha (PPARalpha), peroxisome proliferator-activated receptor gamma (PPARgamma), and sterol regulatory element binding factor 1 (SREBF1). Blood plasma was assayed for concentrations of glucose, BHBA, nonesterified fatty acids, cholesterol, triglycerides, insulin, insulin-like growth factor-I, and thyroid hormones. In both groups, plasma parameters followed a pattern usually observed in dairy cows. However, changes were moderate and the energy balance in cows turned positive in wk 7 PP for both groups. Additionally, the energy balance and milk yield were similar for both groups after parturition onwards. Significant group effects were found at drying off, when plasma concentrations of triglycerides were higher in LB than in HB, and in wk 4 PP, when plasma concentrations of glucose and IGF-I were lower in HB than in LB. Similarly, moderate changes in mRNA expression of hepatic genes between the different time points were observed, although HB cows showed more adaptive performance than LB cows based on changes in mRNA expression of PEPCKc, PEPCKm, CS, CPT 1A, CPT 2, and PPARalpha. Part of the variation measured in this study was explained by parity. Significant Spearman rank correlation coefficients between the variables were not similar at each time point and were not similar between the groups at each time point, suggesting that metabolic regulation differs between cows. In conclusion, metabolic regulation in dairy cows is a dynamic system, and differs obviously between cows at different metabolic stages related to parturition.

Risk factors for death and unwanted early slaughter in Swiss veal calves kept at a specific animal welfare standard

Calf losses (CL, mortality and unwanted early slaughter) in veal production are of great economic importance and an indicator of welfare. The objective of the present study was to evaluate CL and the causes of death on farms with a specific animal welfare standard (SAW) which exceeds the Swiss statutory regulations. Risk factors for CL were identified based on information about management, housing, feeding, and medication. In total, 74 production cohorts (2783 calves) of 15 farms were investigated. CL was 3.6%, the main causes of death were digestive disorders (52%), followed by respiratory diseases (28%). Factors significantly associated with an increased risk for CL were a higher number of individual daily doses of antibiotics (DDA), insufficient wind deflection in winter, and male gender. For administration of antibiotics to all calves of the cohort, a DDA of 14-21 was associated with a decreased risk for CL compared to a DDA of 7-13 days.

The "Image" of the Pharaoh in Judahite and Israelite Society According to the Glyptic Evidence

Among the many thousand scarabs, scaraboids and other stamp-seal amulets unearthed in Iron Age contexts in Cis- and Transjordan, there are many such seals showing royal Egyptian imagery on their bases. Focusing mainly on Pharaonic motifs, the paper aims to catalogue the principal iconemes, to trace their development throughout the Iron Ages and to extrapolate their significance vis-à-vis the contemporary glyptic assemblages. As will be shown, the royal imagery of the Egyptian king underwent considerable changes during pre-monarchic and monarchic times in Israel/Judah. This allows – to some extent – deducing the perception of the ‘image’ of the Egyptian king in this part of the Southern Levant at the close of the second and during the first centuries of the first millennium BCE. While the local seal production not only vividly copied earlier and contemporary Egyptian prototypes, it also developed idiosyncratic ‘Pharaonic’ motifs that were produced for the local market. On the other hand, imported Egyptian glyptic goods – such as scarabs and other amulet types – reveal further facets of the consumer behavior. They, too, shed light upon the ideological and religious preferences of the local population and illuminate the development of the vernacular attitude towards the Pharaonic symbols of power – including their obvious political and sacred connotations.

Using Acceptance and Commitment Therapy during Methadone Dose Reduction: Rationale, Treatment Description, and a Case Report.

Many clients who undergo methadone maintenance (MM) treatment for heroin and other opiate dependence prefer abstinence from methadone. Attempts at methadone detoxification are often unsuccessful, however, due to distressing physical as well as psychological symptoms. Outcomes from a MM client who voluntarily participated in an Acceptance and Commitment Therapy (ACT) - based methadone detoxification program are presented. The program consisted of a 1-month stabilization and 5-month gradual methadone dose reduction period, combined with weekly individual ACT sessions. Urine samples were collected twice weekly to assess for use of illicit drugs. The participant successfully completed the program and had favorable drug use outcomes during the course of treatment, and at the one-month and one-year follow-ups. Innovative behavior therapies, such as ACT, that focus on acceptance of the inevitable distress associated with opiate withdrawal may improve methadone detoxification outcomes.

Intentional and unintentional non-adherence to medications following an acute coronary syndrome: A longitudinal study

Objective Non-adherence to medication is common among coronary heart disease patients. Non-adherence to medication may be either intentional or unintentional. In this analysis we provide estimates of intentional and unintentional non-adherence in the year following an acute coronary syndrome (ACS). Method In this descriptive prospective observational study of patients with confirmed ACS medication adherence measures were derived from responses to the Medication Adherence Report Scale at approximately 2 weeks (n = 223), 6 months (n = 139) and 12 months (n = 136) following discharge from acute treatment for ACS. Results Total medication non-adherence was 20%, 54% and 53% at each of these time points respectively. The corresponding figures for intentional non-adherence were 8%, 15% and 15% and 15%, 52% and 53% for unintentional non-adherence. There were significant increases in the levels of medication non-adherence between the immediate discharge period (2 weeks) and 6 months that appeared to stabilize between 6 and 12 months after acute treatment for ACS. Conclusion Unintentional non-adherence to medications may be the primary form of non-adherence in the year following ACS. Interventions delivered early in the post-discharge period may prevent the relatively high levels of non-adherence that appear to become established by 6 months following an ACS.

A Comparative Analysis of Bronchial Stricture After Lung Transplantation in Recipients With and Without Early Acute Rejection

BACKGROUND: Risk factors and outcomes of bronchial stricture after lung transplantation are not well defined. An association between acute rejection and development of stricture has been suggested in small case series. We evaluated this relationship using a large national registry. METHODS: All lung transplantations between April 1994 and December 2008 per the United Network for Organ Sharing (UNOS) database were analyzed. Generalized linear models were used to determine the association between early rejection and development of stricture after adjusting for potential confounders. The association of stricture with postoperative lung function and overall survival was also evaluated. RESULTS: Nine thousand three hundred thirty-five patients were included for analysis. The incidence of stricture was 11.5% (1,077/9,335), with no significant change in incidence during the study period (P=0.13). Early rejection was associated with a significantly greater incidence of stricture (adjusted odds ratio [AOR], 1.40; 95% confidence interval [CI], 1.22-1.61; p<0.0001). Male sex, restrictive lung disease, and pretransplantation requirement for hospitalization were also associated with stricture. Those who experienced stricture had a lower postoperative peak percent predicted forced expiratory volume at 1 second (FEV1) (median 74% versus 86% for bilateral transplants only; p<0.0001), shorter unadjusted survival (median 6.09 versus 6.82 years; p<0.001) and increased risk of death after adjusting for potential confounders (adjusted hazard ratio 1.13; 95% CI, 1.03-1.23; p=0.007). CONCLUSIONS: Early rejection is associated with an increased incidence of stricture. Recipients with stricture demonstrate worse postoperative lung function and survival. Prospective studies may be warranted to further assess causality and the potential for coordinated rejection and stricture surveillance strategies to improve postoperative outcomes.

Ancient DNA, a Neolithic legging from the Swiss Alps and the early history of goat

Ancient DNA from a Neolithic legging (1st half of the 3rd millennium BC) found at Lenk, Schnidejoch (2750 m a.sl.) in the Swiss Alps has demonstrated, that modern distribution of genetic variation does not reflect past spatio-temporal signatures. The legging was made from the skin of a domestic goat (Capra hircus), belonging to the caprine haplogroup B1, which is marginal in Europe today, but represents a third highly diverse goat haplogroup entering Europe already in the Neolithic. Population expansion of lineage B therefore happened more than 4500 years ago, but their members were at some point almost completely replaced by goats of today's common A and C haplogroups.