Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival ...(PFS) are clinically meaningful end points.
These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy.
Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n=90; PF, n=76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months 95% confidence interval (CI): 31–not reached versus 24 months (95% CI: 13–42) for PF hazard ratio (HR) for death: 0.62; 95% CI: 0.41–0.94; P=0.024. Median PFS for TPF was 21 months (95% CI: 12–59) versus 11 months (95% CI: 8–14) for PF (HR: 0.66; 95% CI: 0.45–0.97; P=0.032). Among operable patients (TPF, n=67; PF, n=56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37–0.95; P=0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P=0.030).
In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.
MS/MS and associated database search algorithms are essential proteomic tools for identifying peptides. Due to their widespread use, it is now time to perform a systematic analysis of the various ...algorithms currently in use. Using blood specimens used in the HUPO Plasma Proteome Project, we have evaluated five search algorithms with respect to their sensitivity and specificity, and have also accurately benchmarked them based on specified false‐positive (FP) rates. Spectrum Mill and SEQUEST performed well in terms of sensitivity, but were inferior to MASCOT, X!Tandem, and Sonar in terms of specificity. Overall, MASCOT, a probabilistic search algorithm, correctly identified most peptides based on a specified FP rate. The rescoring algorithm, PeptideProphet, enhanced the overall performance of the SEQUEST algorithm, as well as provided predictable FP error rates. Ideally, score thresholds should be calculated for each peptide spectrum or minimally, derived from a reversed‐sequence search as demonstrated in this study based on a validated data set. The availability of open‐source search algorithms, such as X!Tandem, makes it feasible to further improve the validation process (manual or automatic) on the basis of “consensus scoring”, i.e., the use of multiple (at least two) search algorithms to reduce the number of FPs.∁
The packaging of the eukaryotic genome into chromatin is likely to have a profound influence on transcription from the underlying genes. We have previously shown that the disassembly of promoter ...nucleosomes is obligatory for activation of the yeast
PHO5 and
PHO8 genes. Here, we show that the
PHO5 promoter nucleosomes are reassembled concomitant with transcriptional repression and displacement of the TATA binding protein and RNA polymerase II (RNA Pol II). We identify the histone H3-H4 chaperone Spt6 as the factor that mediates nucleosome reassembly onto the
PHO5,
PHO8,
ADH2,
ADY2, and
SUC2 promoters during transcriptional repression. Furthermore, promoter nucleosome reassembly is essential for transcriptional repression. In the absence of Spt6-mediated nucleosome reassembly, the activators Pho4 and Pho2 are displaced from the
PHO5 promoter in repressing conditions, yet transcription is sustained. As such, these studies demonstrate that activators are not required for transcription in the absence of competing chromatin reassembly.
Nucleosome loss from a promoter region has recently been described as a potential mechanism for transcriptional regulation. We investigated whether H3/H4 histone chaperones mediate the loss of ...nucleosomes from the promoter of the yeast
PHO5 gene during transcriptional activation. We found that antisilencing function 1 (Asf1p) mediates nucleosome disassembly from the
PHO5 promoter in vivo. We show that nucleosome disassembly also occurs at a second promoter, that of the
PHO8 gene, during activation, and we demonstrate that this is also mediated by Asf1p. Furthermore, we show that nucleosome disassembly is essential for
PHO5 and
PHO8 activation. Contrary to the current dogma, we demonstrate that nucleosome disassembly is not required to enable binding of the Pho4p activator to its
PHO5 UASp2 site in vivo. Finally, we show that nucleosomes are reassembled over the
PHO5 promoter during repression. As such, nucleosome disassembly and reassembly are important mechanisms for transcriptional activation and repression, respectively.
We present measurements of bulk properties of the matter produced in Au+Au collisions at $\sqrt{s}$$_ {NN}$= 7.7, 11.5, 19.6, 27, and 39 GeV using identified hadrons (π±, K±, p, and $\bar{p}$) from ...the STAR experiment in the Beam Energy Scan (BES) Program at the Relativistic Heavy Ion Collider (RHIC). Midrapidity (| y | < 0.1) results for multiplicity densities dN / dy, average transverse momenta $\langle$pT$\rangle$, and particle ratios are presented. The chemical and kinetic freeze-out dynamics at these energies are discussed and presented as a function of collision centrality and energy. These results constitute the systematic measurements of bulk properties of matter formed in heavy-ion collisions over a broad range of energy (or baryon chemical potential) at RHIC.
Nonmonotonic variation with collision energy (sqrts_{NN}) of the moments of the net-baryon number distribution in heavy-ion collisions, related to the correlation length and the susceptibilities of ...the system, is suggested as a signature for the quantum chromodynamics critical point. We report the first evidence of a nonmonotonic variation in the kurtosis times variance of the net-proton number (proxy for net-baryon number) distribution as a function of sqrts_{NN} with 3.1 σ significance for head-on (central) gold-on-gold (Au+Au) collisions measured solenoidal tracker at Relativistic Heavy Ion Collider. Data in noncentral Au+Au collisions and models of heavy-ion collisions without a critical point show a monotonic variation as a function of sqrts_{NN}.
The Breit-Wheeler process which produces matter and antimatter from photon collisions is experimentally investigated through the observation of 6085 exclusive electron-positron pairs in ...ultraperipheral Au + Au collisions at √sNN = 200 GeV . The measurements reveal a large fourth-order angular modulation of cos 4 Δ ϕ = ( 16.8 ± 2.5 ) % and smooth invariant mass distribution absent of vector mesons ( ϕ , ω , and ρ ) at the experimental limit of ≤ 0.2 % of the observed yields. The differential cross section as a function of e+ e− pair transverse momentum P⊥ peaks at low value with √⟨P⊥2 ⟩ = 38.1 ± 0.9 MeV and displays a significant centrality dependence. These features are consistent with QED calculations for the collision of linearly polarized photons quantized from the extremely strong electromagnetic fields generated by the highly charged Au nuclei at ultrarelativistic speed. The experimental results have implications for vacuum birefringence and for mapping the magnetic field which is important for emergent QCD phenomena.
BACKGROUND AND AIMS: Seed physiological dormancy (PD) limits the use and conservation of some of Queensland's (Qld) native forb species. It was hypothesised that optimum dormancy-alleviating ...treatments would reflect environmental conditions that seeds experience in situ, and this premise was tested for PD seeds of four species native to south-west Qld. METHODS: High temperatures and increased rainfall during summer are characteristic of this semi-arid tropical environment. Ex situ treatments were designed to mimic conditions that seeds dispersed in spring experience during the summer months before germinating in cooler autumn temperatures. Seeds received between 4 and 20 weeks of a dry after-ripening (DAR), warm stratification or dry/wet cycling treatment (DAR interspersed with short periods of warm stratification), in darkness, before being transferred to germination test conditions. In addition, natural dormancy alleviation of one of the Goodeniaceae species was investigated in situ. KEY RESULTS: Dry/wet cycling resulted in higher levels of germination of Actinobole uliginosum (Asteraceae), Goodenia cycloptera and Velleia glabrata (Goodeniaceae) when compared with constant DAR or stratification, while Goodenia fascicularis (Goodeniaceae) responded better to short durations of warm stratification. Long durations of DAR partially alleviated PD of A. uliginosum; however, stratification induced and maintained dormancy of this species. Modifications to the dry/wet cycling treatment and germination test conditions based on data collected in situ enabled germination of G. cycloptera and V. glabrata to be further improved. CONCLUSIONS: Treatments designed using temperature, relative humidity and rainfall data for the period between natural seed dispersal and germination can successfully alleviate PD. Differences between the four species in conditions that resulted in maximum germination indicate that, in addition to responding to broad-scale climate patterns, species may be adapted to particular microsites and/or seasonal conditions.
Blood serum is a complex body fluid that contains various proteins ranging in concentration over at least 9 orders of magnitude. Using a combination of mass spectrometry technologies with ...improvements in sample preparation, we have performed a proteomic analysis with submilliliter quantities of serum and increased the measurable concentration range for proteins in blood serum beyond previous reports. We have detected 490 proteins in serum by on-line reversed-phase microcapillary liquid chromatography coupled with ion trap mass spectrometry. To perform this analysis, immunoglobulins were removed from serum using protein A/G, and the remaining proteins were digested with trypsin. Resulting peptides were separated by strong cation exchange chromatography into distinct fractions prior to analysis. This separation resulted in a 3-5-fold increase in the number of proteins detected in an individual serum sample. With this increase in the number of proteins identified we have detected some lower abundance serum proteins (ng/ml range) including human growth hormone, interleukin-12, and prostate-specific antigen. We also used SEQUEST to compare different protein databases with and without filtering. This comparison is plotted to allow for a quick visual assessment of different databases as a subjective measure of analytical quality. With this study, we have performed the most extensive analysis of serum proteins to date and laid the foundation for future refinements in the identification of novel protein biomarkers of disease.
Collisions between prolate uranium nuclei are used to study how particle production and azimuthal anisotropies depend on initial geometry in heavy-ion collisions. We report the two- and four-particle ...cumulants, v_{2}{2} and v_{2}{4}, for charged hadrons from U+U collisions at sqrts_{NN}=193 GeV and Au+Au collisions at sqrts_{NN}=200 GeV. Nearly fully overlapping collisions are selected based on the energy deposited by spectators in zero degree calorimeters (ZDCs). Within this sample, the observed dependence of v_{2}{2} on multiplicity demonstrates that ZDC information combined with multiplicity can preferentially select different overlap configurations in U+U collisions. We also show that v_{2} vs multiplicity can be better described by models, such as gluon saturation or quark participant models, that eliminate the dependence of the multiplicity on the number of binary nucleon-nucleon collisions.
PDF
