Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

Phd by thesis

This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003. In the case of all approved agents the time frame has been extended to include the 251/2 years from 01/1981 to 06/2006 for all diseases worldwide and from 1950 (earliest so far identified) to 06/2006 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a “natural product mimic” or “NM” to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 155 small molecules, 73% are other than “S” (synthetic), with 47% actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the antiinfective area ...

/pdf/natural-products-as-sources-of-new-drugs-over-the-last-25-24stxjn5tu.pdf

Natural Products as Sources of New Drugs over the Last 25 Years

It is difficult to mix solutions in microchannels. Under typical operating conditions, flows in these channels are laminar—the spontaneous fluctuations of velocity that tend to homogenize fluids in turbulent flows are absent, and molecular diffusion across the channels is slow. We present a passive method for mixing streams of steady pressure-driven flows in microchannels at low Reynolds number. Using this method, the length of the channel required for mixing grows only logarithmically with the Pe «clet number, and hydrodynamic dispersion along the channel is reduced relative to that in a simple, smooth channel. This method uses bas-relief structures on the floor of the channel that are easily fabricated with commonly used methods of planar lithography.

https://www.princeton.edu/%7Estonelab/Publications/pdfs/From%20Howard/ScienceNaturePNAS/Science/abe-mixer-science.pdf

Chaotic Mixer for Microchannels

Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.

/pdf/urinary-tract-infections-epidemiology-mechanisms-of-3j8ivu97xb.pdf

Urinary tract infections: epidemiology, mechanisms of infection and treatment options

Sasidharan Swarnalatha Lucky,†,§ Khee Chee Soo,‡ and Yong Zhang*,†,§,∥ †NUS Graduate School for Integrative Sciences & Engineering (NGS), National University of Singapore, Singapore, Singapore 117456 ‡Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore 169610 Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore 117576 College of Chemistry and Life Sciences, Zhejiang Normal University, Zhejiang, P. R. China 321004

Nanoparticles in photodynamic therapy.

The present invention relates to oligosaccharide mixtures whose individual constituents have an identical core structure which is substituted by at least one sugar and in which all positional isomers are represented, and all isomers with respect to the substituent are in the form of α- or β-isomers, to a process for the preparation of said oligosaccharide mixture and to a process for the rapid isolation of a biologically active oligosaccharide.

Process for the preparation of oligosaccharide mixtures

The invention relates to carbohydrate ligands and moieties, respectively, mimicking glycoepitopes comprised by glycosphingolipids of the nervous system, particularly glycoepitopes comprised by glycosphingolipids of the cerebroside, the globoside-, the ganglioside- and the sulfoglucuronyl paragloboside type, which are bound by anti-glycan antibodies associated with neurological diseases. The invention further relates to the use of these carbohydrate ligands/moieties, in diagnosis as well as for the treatment of neurological diseases associated with anti-glycan antibodies. In particular, the invention relates to compounds of formula (I) and (II) and to therapeutically acceptable polymers comprising a multitude of these compounds, including polymers with loading of one compound of formula (I) or (II) or combinations of several compounds of formula (I), and/or (II). The compounds of formula (I) are defined as: formula (I), wherein R I1 is Z or (AA) or (BB) or (CC) or (DD); wherein R I2 is H, SO 3 H, or (EE) or (FF) or (GG) or (HH) or (JJ) or (KK) or (LL), wherein R I3 is H or (MM); wherein R I4 is H or (NN) or (OO), wherein R I5 and R I6 are independently H or (EE); wherein R I7 is H or (EE) or (FF) and compounds of formula (II) are defined as: formula (II), wherein R II1 is Z or (PP), wherein R II2 is Z or (QQ) or (RR) or (SS) or (TT), wherein Z is -N(R a )-A-B-CH 2 -(CH 2 ) q -SH, wherein R a is H, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, CH 2 C 6 H 5 , CH 2 CH 2 C 6 H 5 , OCH 2 C 6 H 5 , or OCH 2 CH 2 C 6 H 5 ; A is C 1 -C 7 -alkylene, C 1 -C 7 -alkoxy, C 1 -C 4 -alkyl–(OCH 2 CH 2 )pO–C 1 -C 4 -alkyl, or C 1 -C 7 -alkoxy-R b , wherein R b is an optionally substituted aryl or an optionally substituted heteroaryl, and wherein p is 0 to 6, preferably p is 1, 2 or 3, and further preferably p is 1; B is NHC(O), S or CH 2 ; q is 0 to 6, preferably q is 1, 2, 3 or 4, and further preferably q is 1 or 2.

Carbohydrate ligands that bind to antibodies against glycoepitopes of glycosphingolipids

Summary Urinary tract infections (UTIs), which are among the most prevalent bacterial infections worldwide, are mainly attributed to uropathogenic Escherichia coli (UPEC). Because of frequent antibiotic treatment, antimicrobial resistance constitutes an increasing therapeutic problem. Antagonists of the mannose-specific bacterial lectin FimH, a key protein mediating the adhesion of UPEC to human bladder cells, would offer an alternative anti-adhesive treatment strategy. In general, FimH antagonists consist of a mannose moiety and a wide range of lipophilic aglycones. Modifications of the mannose core led to a distinct drop in affinity. A visual inspection of the crystal structure of FimH revealed a previously unexplored cavity surrounded by Ile13, Phe142 and Asp140, which could be reached by functional groups in the equatorial 2-position of the mannose. Here, we describe the synthesis of 2-C-branched mannosides and evaluation of their pharmacodynamic properties. ITC experiments with the selected antagonists revealed a drastic enthalpy loss for all 2-C-branched antagonists, which, however, is partially compensated by an entropy gain. This supports the hypothesis that the target cavity is too small to accommodate 2-C-substituents.

2-C-Branched mannosides as a novel family of FimH antagonists—Synthesis and biological evaluation

A compound of the formula I where denotes the form of its optical isomers (8R, 15R), (8R, 15S), (8S, 15R) and (8S, 15S), and its alkali metal and alkaline earth metal salts. The optical isomers are obtainable by means of a multi-step process and are suitable for protecting cherries from attack by cherry fruit flies.

Optical palmitoylglucopyranoside isomer and process for its preparation

The neuroprotective role of natural polyphenols is well established but phenolics poor water solubility affects their bioavailability and bioactivity. Aiming to overcome this issue, we were encouraged to investigate the 2-deoxyglycosylation of natural or nature inspired neuroprotective molecules, using glycals as easily accessed glycosyl donors. This robust methodology allowed the generation of a set of new resveratrol and caffeic acid ester glycosides, envisioning more effective and bioavailable compounds. Resveratrol 2-deoxyglycosides were more effective at protecting the neuronal cells from peroxide-induced cytotoxicity than resveratrol itself, while the caffeic acid ester glycoside also showed extraordinary neuroprotection activity. Coefficient partition measurements demonstrated the moderate lipophilicity of resveratrol glycosides, which Log D values are typical of a central nervous system (CNS) drug and ideal for blood-brain barrier (BBB) penetration. Passive permeation assessed by the parallel artificial membrane permeability assay (PAMPA) revealed that 2,6-dideoxy- l - arabino -hexopyranosides were more effective than 2-deoxy- d - arabino -hexopyranosides. The lack of toxicity of the neuroprotective glycosides and their promising physicochemical properties revealed the usefulness of sugar coupling towards the modulation of natural product properties and bioactivity.

Beat Ernst

Papers

Process for the preparation of oligosaccharide mixtures

Carbohydrate ligands that bind to antibodies against glycoepitopes of glycosphingolipids

2-C-Branched mannosides as a novel family of FimH antagonists—Synthesis and biological evaluation

Optical palmitoylglucopyranoside isomer and process for its preparation

2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature