Operando Investigation of Silicon Anodes During Electrochemical Cycling in Li-ion Batteries.

Silicon (Si) is recognized as a promising anode material for next-generation anodes due to its high capacity. However, large volume expansion and active particle pulverization during cycling rapidly deteriorate the battery performance. The relationship between Si anode particle size and particle pulverization, and the structure evolution of Si particles during cycling is not well understood.

Identifying the major lactate transporter of Toxoplasma gondii tachyzoites.

Toxoplasma gondii and Plasmodium falciparum parasites both extrude L-lactate, a byproduct of glycolysis. The P. falciparum Formate Nitrite Transporter, PfFNT, mediates L-lactate transport across the plasma membrane of P.

Protein kinase A negatively regulates Ca2+ signalling in Toxoplasma gondii.

The phylum Apicomplexa comprises a group of obligate intracellular parasites that alternate between intracellular replicating stages and actively motile extracellular forms that move through tissue. Parasite cytosolic Ca2+ signalling activates motility, but how this is switched off after invasion is complete to allow for replication to begin is not understood. Here, we show that the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A catalytic subunit 1 (PKAc1) of Toxoplasma is responsible for suppression of Ca2+ signalling upon host cell invasion.

Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.

Apicomplexans are obligate intracellular parasites that scavenge essential nutrients from their hosts via transporter proteins on their plasma membrane. The identities of the transporters that mediate amino acid uptake into apicomplexans are unknown. Here we demonstrate that members of an apicomplexan-specific protein family-the Novel Putative Transporters (NPTs)-play key roles in the uptake of cationic amino acids.

The Malaria Parasite's Lactate Transporter PfFNT Is the Target of Antiplasmodial Compounds Identified in Whole Cell Phenotypic Screens.

In this study the 'Malaria Box' chemical library comprising 400 compounds with antiplasmodial activity was screened for compounds that perturb the internal pH of the malaria parasite, Plasmodium falciparum. Fifteen compounds induced an acidification of the parasite cytosol. Two of these did so by inhibiting the parasite's formate nitrite transporter (PfFNT), which mediates the H+-coupled efflux from the parasite of lactate generated by glycolysis.

Evaluating Immunogenicity Risk Due to Host Cell Protein Impurities in Antibody-Based Biotherapeutics.

A potential risk factor for immunogenicity of a biotherapeutic is the low levels of host cell protein (HCP) impurities that remain in the product following the purification process. During process development, significant attention has been devoted to removing HCPs due to their potential safety risk. Samples from different purification steps of several monoclonal antibodies (mAbs) purified by one type of platform were evaluated for their residual Chinese Hamster Ovary (CHO) cell-derived HCP content.

Andrographidine G, a new flavone glucoside from Andrographis paniculata.

A new flavone glucoside, andrographidine G (1), was isolated from Andrographis paniculata together with 13 known compounds, including flavonoids, diterpenoids, and iridoids. The structure of 1 was established by spectroscopic and spectrometric techniques, including HR-ESI-TOF-MS, 1D and 2D NMR, and chemical methods. The known compounds were identified as andrographidine A (2), (2R)-5-hydroxy-7,8-dimethoxyflavanone-5-O-beta-D-glucopyranoside (3), acanthoside B (4), neoandrographiside (5), andropanoside (6), andrographiside (7), andrographolide (8), 14-deoxy-11,12-didehydroandrographiside (9), 14-deoxy-11,12-didehydroandrographolide (10), procumbide (11), procumboside (12), 6-epi-8-O-acetylharpagide (13), and curvifloruside F (14).

Analysis and characterization of aggregation of a therapeutic Fc-fusion protein.

Protein aggregation was observed in a purification intermediate of a therapeutic Fc-fusion protein stored at -30 °C, even though the protein was stable at 4 and -80 °C. The protein was expressed in Escherichia coli as an inclusion body, refolded, and purified using chromatography columns. To study the nature of this aggregation, a series of experiments were conducted to investigate factors that contributed to the protein instability during freezing.

Uncertainty estimates of purity measurements based on current information: toward a "live validation" of purity methods.

Purpose: To predict precision and other performance characteristics of chromatographic purity methods, which represent the most widely used form of analysis in the biopharmaceutical industry.

Methods: We have conducted a comprehensive survey of purity methods, and show that all performance characteristics fall within narrow measurement ranges. This observation was used to develop a model called Uncertainty Based on Current Information (UBCI), which expresses these performance characteristics as a function of the signal and noise levels, hardware specifications, and software settings.

Use of capillary electrophoresis-sodium dodecyl sulfate to monitor disulfide scrambled forms of an Fc fusion protein during purification process.

Overexpression of recombinant Fc fusion proteins in Escherichia coli frequently results in the production of inclusion bodies that are subsequently used to produce fully functional protein by an in vitro refolding process. During the refolding step, misfolded proteins such as disulfide scrambled forms can be formed, and purification steps are used to remove these product-related impurities to produce highly purified therapeutic proteins. A variety of analytical methods are commonly used to monitor protein variants throughout the purification process.

High-sensitivity detection of biological amines using fast Hadamard transform CE coupled with photolytic optical gating.

Here, we report the first utilization of Hadamard transform CE (HTCE), a high-sensitivity, multiplexed CE technique, with photolytic optical gating sample injection of caged fluorescent labels for the detection of biologically important amines. Previous implementations of HTCE have relied upon photobleaching optical gating sample injection of fluorescent dyes. Photolysis of caged fluorescent labels reduces the fluorescence background, providing marked enhancements in sensitivity compared to photobleaching.

Design, characterization, and utilization of a fast fluorescence derivatization reaction utilizing o-phthaldialdehyde coupled with fluorescent thiols.

We have developed a chemical derivatization scheme for primary amines that couples the fast kinetic properties of o-phthaldialdehyde (OPA) with the photophysical properties of visible, high quantum yield, fluorescent dyes. In this reaction, OPA is used as a cross-linking reagent in the labeling reaction of primary amines in the presence of a fluorescent thiol, 5-((2-(and-3)-S-(acetylmercapto)succinoyl)amino)fluorescein (SAMSA fluorescein), thereby incorporating fluorescein (epsilon = 78 000 M(-1), quantum yield of 0.98) into the isoindole product.

Capillary electrophoresis with a UV light-emitting diode source for chemical monitoring of native and derivatized fluorescent compounds.

We report the utilization of a high power UV light-emitting diode for fluorescence detection (UV-LED-IF) in CE separations. CE-UV-LED-IF allows analysis of a range of environmentally and biologically important compounds, including PAHs and biogenic amines, including neurotransmitters, amino acids, proteins, and peptides, that have been derivatized with UV-excited fluorogenic labels, e.g.

Aspergillus meningitis following spinal anaesthesia for caesarean section in Colombo, Sri Lanka.

We report six cases of Aspergillus meningitis after spinal anaesthesia for caesarean section administered in June and July 2005. Three patients died before a fungal infection was confirmed at the first post-mortem examination in August. Thereafter anti-fungal therapy was successful in saving the lives of the other three patients.

High-speed capillary zone electrophoresis with online photolytic optical injection.

We report an online, optical injection interface for capillary zone electrophoresis (CZE) based upon photophysical activation of a caged, fluorogenic label covalently attached to the target analyte. This injection interface allows online analysis of biomolecular systems with high temporal resolution and high sensitivity. Samples are injected onto the separation capillary by photolysis of a caged-fluorescein label using the 351-364 nm irradiation of an Ar+ laser.

Fast Hadamard transform capillary electrophoresis for on-line, time-resolved chemical monitoring.

We report a new approach for collecting and deconvoluting the data in Hadamard transform capillary electrophoresis, referred to as fast Hadamard transform capillary electrophoresis (fHTCE). Using fHTCE, total analysis times can be reduced by up to 48% per multiplexed separation compared to conventional Hadamard transform capillary electrophoresis (cHTCE) while providing comparable signal-to-noise ratio enhancements. In fHTCE, the sample is injected following a pseudorandom pulsing sequence derived from the first row of a simplex matrix (S-matrix) in contrast to cHTCE, which utilizes a sequence of twice the length.