409 research outputs found
The aggregation of cytochrome C may be linked to its flexibility during refolding
Large-scale expression of biopharmaceutical proteins in cellular hosts results in production of large insoluble mass aggregates. In order to generate functional product, these aggregates require further processing through refolding with denaturant, a process in itself that can result in aggregation. Using a model folding protein, cytochrome C, we show how an increase in final denaturant concentration decreases the propensity of the protein to aggregate during refolding. Using polarised fluorescence anisotropy, we show how reduced levels of aggregation can be achieved by increasing the period of time the protein remains flexible during refolding, mediated through dilution ratios. This highlights the relationship between the flexibility of a protein and its propensity to aggregate. We attribute this behaviour to the preferential urea-residue interaction, over self-association between molecules
Analogue peptides for the immunotherapy of human acute myeloid leukemia
Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies
An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model
Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine residues. Examination of pathogenic properties revealed that the virus (m5MR) carrying mutations in E (N154A) and NS1 (N130A and N207A) was fully attenuated with no disease signs in infected mice, inducing high levels of humoral and cell-mediated immune responses, and protecting mice from subsequent lethal virus challenge. Furthermore, passive transfer of sera from m5MR-infected mice into naïve animals resulted in complete protection from lethal challenge. The immune sera from m5MR-infected animals neutralized both African and Asian lineage viruses equally well, suggesting that m5MR virus could be developed as a potentially broad live virus vaccine candidate
Semi-analytic results for quasi-normal frequencies
The last decade has seen considerable interest in the quasi-normal
frequencies [QNFs] of black holes (and even wormholes), both asymptotically
flat and with cosmological horizons. There is wide agreement that the QNFs are
often of the form omega_n = (offset) + i n (gap), though some authors have
encountered situations where this behaviour seems to fail. To get a better
understanding of the general situation we consider a semi-analytic model based
on a piecewise Eckart (Poeschl-Teller) potential, allowing for different
heights and different rates of exponential falloff in the two asymptotic
directions. This model is sufficiently general to capture and display key
features of the black hole QNFs while simultaneously being analytically
tractable, at least for asymptotically large imaginary parts of the QNFs. We
shall derive an appropriate "quantization condition" for the asymptotic QNFs,
and extract as much analytic information as possible. In particular, we shall
explicitly verify that the (offset)+ i n (gap) behaviour is common but not
universal, with this behaviour failing unless the ratio of rates of exponential
falloff on the two sides of the potential is a rational number. (This is
"common but not universal" in the sense that the rational numbers are dense in
the reals.) We argue that this behaviour is likely to persist for black holes
with cosmological horizons.Comment: V1: 28 pages, no figures. V2: 3 references added, no physics changes.
V3: 29 pages, 9 references added, no physics changes; V4: reformatted, now 27
pages. Some clarifications, comparison with results obtained by monodromy
techniques. This version accepted for publication in JHEP. V5: Minor typos
fixed. Compatible with published versio
An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) and Non-Structural Protein 1 (NS1) Confers Complete Protection against Lethal Challenge in a Mouse Model
Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine residues. Examination of pathogenic properties revealed that the virus (m5MR) carrying mutations in E (N154A) and NS1 (N130A and N207A) was fully attenuated with no disease signs in infected mice, inducing high levels of humoral and cell-mediated immune responses, and protecting mice from subsequent lethal virus challenge. Furthermore, passive transfer of sera from m5MR-infected mice into naïve animals resulted in complete protection from lethal challenge. The immune sera from m5MR-infected animals neutralized both African and Asian lineage viruses equally well, suggesting that m5MR virus could be developed as a potentially broad live virus vaccine candidate
Logarithmic perturbation theory for quasinormal modes
Logarithmic perturbation theory (LPT) is developed and applied to quasinormal
modes (QNMs) in open systems. QNMs often do not form a complete set, so LPT is
especially convenient because summation over a complete set of unperturbed
states is not required. Attention is paid to potentials with exponential tails,
and the example of a Poschl-Teller potential is briefly discussed. A numerical
method is developed that handles the exponentially large wavefunctions which
appear in dealing with QNMs.Comment: 24 pages, 4 Postscript figures, uses ioplppt.sty and epsfig.st
Contamination Control and Assay Results for the Majorana Demonstrator Ultra Clean Components
The MAJORANA DEMONSTRATOR is a neutrinoless double beta decay experiment
utilizing enriched Ge-76 detectors in 2 separate modules inside of a common
solid shield at the Sanford Underground Research Facility. The DEMONSTRATOR has
utilized world leading assay sensitivities to develop clean materials and
processes for producing ultra-pure copper and plastic components. This
experiment is now operating, and initial data provide new insights into the
success of cleaning and processing. Post production copper assays after the
completion of Module 1 showed an increase in U and Th contamination in finished
parts compared to starting bulk material. A revised cleaning method and
additional round of surface contamination studies prior to Module 2
construction have provided evidence that more rigorous process control can
reduce surface contamination. This article describes the assay results and
discuss further studies to take advantage of assay capabilities for the purpose
of maintaining ultra clean fabrication and process design.Comment: Proceedings of Low Radioactivity Techniques (LRT May 2017, Seoul
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