Xenophobia in Seventeenth-Century India

Zowel India als Nederland kennen op het moment scherpe tegenstellingen, in Nederland onder andere tussen autochtonen en allochtonen en in India tussen Hindoes en Moslims. Komen zulke scherp afgebakende groepsgrenzen voort uit de menselijke natuur of uit een bepaalde in het westen uitgevonden manier van denken? Dit boek onderzoekt zes tegenstellingen in centraal India in de zeventiende eeuw, dus voordat het westerse kolonialisme zijn sterkste invloed deed gelden. Het blijkt dat groepstegenstellingen ook in het zeventiende-eeuwse Indiase leven een belangrijke rol speelden. Het ging in het zeventiende-eeuwse India wel om andere tegenstellingen dan vandaag de dag, zoals bijvoorbeeld de vergeten tegenstelling tussen Links- en Rechtshandige kasten. Verder blijkt -- ook anders dan vandaag -- dat de tegenstelling tussen Portugezen en Nederlanders (al of niet in dienst van de VOC) belangrijker was dan die tussen Europeanen en IndiC+rs. De ooit zo grote tegenstelling tussen Indiase Moslims en buitenlandse Moslims werd in de loop van de zeventiende eeuw overvleugeld door de tegenstelling tussen Hindoes en Moslims die vandaag de dag een grote rol speelt. In verband met de politieke gevoeligheid van dit onderzoek, omvat het boek ook een pleidooi tegen het 'erfgoed-denken' en het in verband brengen van de huidige Moslimgemeenschap in India met iedere Moslim die ooit een Hindoetempel heeft verwoest. Dit pleidooi strekt zich uit tot andere situaties waarin het erfgoed-denken hoogtij viert -- denk aan de verheerlijking van de VOC en het slavernij-debat in Nederland. Ironisch genoeg vormen de VOC-archieven wel een van de belangrijkste bronnen voor dit boek. It is tempting to think of precolonial India as a harmonious society, but was it? This study brings evidence from new and unexpected sources to take position in the sensitive debate over that question. From the investigation of six conflicts in the Deccan region it draws conclusions about group behaviour that put modern clashes in context. Some of the conflicts under investigation appear odd today but were very real to the involved, as the antagonism between Left and Right Hand castes was for about a thousand years. Other conflicts continue to the present day: the seventeenth century saw lasting changes in the relationship between Hindus and Muslims as well as the rise of patriotism and early nationalism in both India and Europe. This book carefully brings to life the famous and obscure people who made the era, from the Dutch painter Heda to queen Khadija and from maharaja Shivaji to the English rebel Keigwin.315 p.Wetensch. publicati

Molecular construction of HIV-gp120 discontinuous epitope mimics by assembly of cyclic peptides on an orthogonal alkyne functionalized TAC-scaffold

Mimics of discontinuous epitopes of for example bacterial or viral proteins may have considerable potential for the development of synthetic vaccines, especially if conserved epitopes can be mimicked. However, due to the structural complexity and size of discontinuous epitopes molecular construction of these mimics remains challeging. We present here a convergent route for the assembly of discontinuous epitope mimics by successive azide alkyne cycloaddition on an orthogonal alkyne functionalized scaffold. Here the synthesis of mimics of the HIV gp120 discontinuous epitope that interacts with the CD4 receptor is described. The resulting protein mimics are capable of inhibition of the gp120–CD4 interaction. The route is convergent, robust and should be applicable to other discontinuous epitopes

Xenophobia in Seventeenth-Century India

Zowel India als Nederland kennen op het moment scherpe tegenstellingen, in Nederland onder andere tussen autochtonen en allochtonen en in India tussen Hindoes en Moslims. Komen zulke scherp afgebakende groepsgrenzen voort uit de menselijke natuur of uit een bepaalde in het westen uitgevonden manier van denken? Dit boek onderzoekt zes tegenstellingen in centraal India in de zeventiende eeuw, dus voordat het westerse kolonialisme zijn sterkste invloed deed gelden. Het blijkt dat groepstegenstellingen ook in het zeventiende-eeuwse Indiase leven een belangrijke rol speelden. Het ging in het zeventiende-eeuwse India wel om andere tegenstellingen dan vandaag de dag, zoals bijvoorbeeld de vergeten tegenstelling tussen Links- en Rechtshandige kasten. Verder blijkt -- ook anders dan vandaag -- dat de tegenstelling tussen Portugezen en Nederlanders (al of niet in dienst van de VOC) belangrijker was dan die tussen Europeanen en IndiC+rs. De ooit zo grote tegenstelling tussen Indiase Moslims en buitenlandse Moslims werd in de loop van de zeventiende eeuw overvleugeld door de tegenstelling tussen Hindoes en Moslims die vandaag de dag een grote rol speelt. In verband met de politieke gevoeligheid van dit onderzoek, omvat het boek ook een pleidooi tegen het 'erfgoed-denken' en het in verband brengen van de huidige Moslimgemeenschap in India met iedere Moslim die ooit een Hindoetempel heeft verwoest. Dit pleidooi strekt zich uit tot andere situaties waarin het erfgoed-denken hoogtij viert -- denk aan de verheerlijking van de VOC en het slavernij-debat in Nederland. Ironisch genoeg vormen de VOC-archieven wel een van de belangrijkste bronnen voor dit boek. It is tempting to think of precolonial India as a harmonious society, but was it? This study brings evidence from new and unexpected sources to take position in the sensitive debate over that question. From the investigation of six conflicts in the Deccan region it draws conclusions about group behaviour that put modern clashes in context. Some of the conflicts under investigation appear odd today but were very real to the involved, as the antagonism between Left and Right Hand castes was for about a thousand years. Other conflicts continue to the present day: the seventeenth century saw lasting changes in the relationship between Hindus and Muslims as well as the rise of patriotism and early nationalism in both India and Europe. This book carefully brings to life the famous and obscure people who made the era, from the Dutch painter Heda to queen Khadija and from maharaja Shivaji to the English rebel Keigwin.315 p.Wetensch. publicati

Xenophobia in seventeenth-century India

=========ABSTRACT=========It is tempting to think of precolonial India as a harmonious society, but was it? This study brings evidence from new and unexpected sources to take position in the sensitive debate over that question. From the investigation of six conflicts in the Deccan region it draws conclusions about group behaviour that put modern clashes in context. Some of the conflicts under investigation appear odd today but were very real to the involved, as the antagonism between Left and Right Hand castes was for about a thousand years. Other conflicts continue to the present day: the seventeenth century saw lasting changes in the relationship between Hindus and Muslims as well as the rise of patriotism and early nationalism in both India and Europe. This book carefully brings to life the famous and obscure people who made the era, from the Dutch painter Heda to queen Khadija and from maharaja Shivaji to the English rebel Keigwin=========NOTES=========First Leiden University Press edition, 2009. Entirely revised from the author’s dissertation Xenophobia and Consciousness in Seventeenth-Century India: Six Cases from the Deccan, 12-Mar-2008.LEI Universiteit LeidenAsian Studie

Клінічні особливості генетично детермінованих гіпобета-ліпопротеїнемії та гіпохолестеролемії

Familial hypobetalipoproteinemia (FHBL) is an autosomal dominant disorder of lipid metabolism characterized by extremely low plasma levels of apolipoprotein B, total cholesterol and low-density lipoprotein cholesterol. Heterozygotes for FHBL are often asymptomatic. Clinical features of homozygous FHBL can include acanthocytosis, deficiencies in fat-soluble vitamins secondary to malabsorption, atypical retinitis pigmentosa and neuromuscular abnormalities

A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds

Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7–28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS

A new perspective on fungal metabolites:Identification of bioactive compounds from fungi using zebrafish embryogenesis as read-out

There is a constant need for new therapeutic compounds. Fungi have proven to be an excellent, but underexplored source for biologically active compounds with therapeutic potential. Here, we combine mycology, embryology and chemistry by testing secondary metabolites from more than 10,000 species of fungi for biological activity using developing zebrafish (Danio rerio) embryos. Zebrafish development is an excellent model for high-throughput screening. Development is rapid, multiple cell types are assessed simultaneously and embryos are available in high numbers. We found that 1,526 fungal strains produced secondary metabolites with biological activity in the zebrafish bioassay. The active compounds from 39 selected fungi were purified by liquid-liquid extraction and preparative HPLC. 34 compounds were identified by a combination of chemical analyses, including LCMS, UV-Vis spectroscopy/ spectrophotometry, high resolution mass spectrometry and NMR. Our results demonstrate that fungi express a wide variety of biologically active compounds, consisting of both known therapeutic compounds as well as relatively unexplored compounds. Understanding their biological activity in zebrafish may provide insight into underlying biological processes as well as mode of action. Together, this information may provide the first step towards lead compound development for therapeutic drug development

Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer

Paclitaxel is an important chemotherapeutic agent for breast cancer. Paclitaxel has high affinity for the P-glycoprotein (P-gp) (drug efflux pump) in the gastrointestinal tract causing low and variable oral bioavailability. Previously, we demonstrated that oral paclitaxel plus the P-gp inhibitor ciclosporin (CsA) is safe and results in adequate exposure to paclitaxel. This study evaluates the activity, toxicity and pharmacokinetics of paclitaxel combined with CsA in breast cancer patients. Patients with measurable metastatic breast cancer were given oral paclitaxel 90 mg m−2 combined with CsA 10 mg kg−1 (30 min prior to each paclitaxel administration) twice on one day, each week. Twenty-nine patients with a median age of 50 years were entered. All patients had received prior treatments, 25 had received prior anthracycline-containing chemotherapy and 19 had three or more metastatic sites. Total number of weekly administrations was 442 (median: 15/patient) and dose intensity of 97 mg m−2 week−1. Most patients needed treatment delay and 17 patients needed dose reductions. In intention to treat analysis, the overall response rate was 52%, the median time to progression was 6.5 months and overall survival was 16 months. The pharmacokinetics revealed moderate inter- and low intrapatient variability. Weekly oral paclitaxel, combined with CsA, is active in patients with advanced breast cancer

Paclitaxel in self-micro emulsifying formulations: oral bioavailability study in mice

The anticancer drug paclitaxel is formulated for i.v. administration in a mixture of Cremophor EL and ethanol. Its oral bioavailability is very low due to the action of P-glycoprotein in the gut wall and CYP450 in gut wall and liver. However, proof-of-concept studies using the i.v. formulation diluted in drinking water have demonstrated the feasibility of the oral route as an alternative when given in combination with inhibitors of P-glycoprotein and CYP450. Because of the unacceptable pharmaceutical properties of the drinking solution, a better formulation for oral application is needed. We have evaluated the suitability of various self-micro emulsifying oily formulations (SMEOF’s) of paclitaxel for oral application using wild-type and P-glycoprotein knockout mice and cyclosporin A (CsA) as P-glycoprotein and CYP450 inhibitor. The oral bioavailability of paclitaxel in all SMEOF’s without concomitant CsA was low in wild-type mice, showing that this vehicle does not enhance intestinal uptake by itself. Paclitaxel (10 mg/kg) in SMEOF#3 given with CsA resulted in plasma levels that were comparable to the Cremophor EL-ethanol containing drinking solution plus CsA. Whereas the AUC increased linearly with the oral paclitaxel dose in P-glycoprotein knockout mice, it increased less than proportional in wild-type mice given with CsA. In both strains more unchanged paclitaxel was recovered in the feces at higher doses. This observation most likely reflects more profound precipitation of paclitaxel within the gastro-intestinal tract at higher doses. The resulting absolute reduction in absorption of paclitaxel from the gut was possibly concealed by partial saturation of first-pass metabolism when P-glycoprotein was absent. In conclusion, SMEOF’s maybe a useful vehicle for oral delivery of paclitaxel in combination with CsA, although the physical stability within the gastro-intestinal tract remains a critical issue, especially when applied at higher dose levels