Precision Test of a Multi-Functional Scan Body for the Scan and Cross-Mount of an Edentulous Arch: A Pilot Case-Control Study.

Objective: The primary goal of this pilot study was to evaluate the three-dimensional comparisons of an intraoral digital scan utilizing a custom multifunctional scan body against the digitized stone models fabricated from a conventional open tray impression of fully edentulous maxilla and mandible in order to test the scan body's precision. The secondary goal of this study was to showcase a method for utilizing the scan body library to generate a fixed fiducial marker for the cross-mount of an edentulous arch. Design: Comparative analysis was performed as a case-control study. Methods: The custom scan body was utilized to generate the positions of the titanium bases from the intraoral models and digitized stone models of three maxillary arches (All-On-6, All-On-5, and All-On-4) and two mandibular All-On-4 arches. The titanium base positions were compared using advanced 3D inspection software. Results: The mean±SD was found to be 30.38±17.78 µm (95% CI: [14.8-45.97 µm]). The mean±SD of the maxilla was 38.73±19.24 µm (95% CI: 16.96-60.5 µm), and the mean±SD of the mandible was 17.85±0.92 µm (95% CI: 16.58-19.12 µm). Conclusion: The study's promising results demonstrated that deviations between the intraoral impressions and the digitized stone models fell within established tolerance ranges. Initial studies showed promising results that the digital workflow could be implemented with similar success as the conventional approach. The usage of the scan body library to generate a fiducial marker successfully demonstrated an efficient method for cross-mounting the edentulous arch.

Structure of human TFIID and mechanism of TBP loading onto promoter DNA.

The general transcription factor IID (TFIID) is a critical component of the eukaryotic transcription preinitiation complex (PIC) and is responsible for recognizing the core promoter DNA and initiating PIC assembly. We used cryo-electron microscopy, chemical cross-linking mass spectrometry, and biochemical reconstitution to determine the complete molecular architecture of TFIID and define the conformational landscape of TFIID in the process of TATA box-binding protein (TBP) loading onto promoter DNA. Our structural analysis revealed five structural states of TFIID in the presence of TFIIA and promoter DNA, showing that the initial binding of TFIID to the downstream promoter positions the upstream DNA and facilitates scanning of TBP for a TATA box and the subsequent engagement of the promoter. Our findings provide a mechanistic model for the specific loading of TBP by TFIID onto the promoter.

SAGA Is a General Cofactor for RNA Polymerase II Transcription.

Prior studies suggested that SAGA and TFIID are alternative factors that promote RNA polymerase II transcription, with about 10% of genes in S. cerevisiae dependent on SAGA. We reassessed the role of SAGA by mapping its genome-wide location and role in global transcription in budding yeast. We find that SAGA maps to the UAS elements of most genes, overlapping with Mediator binding and irrespective of previous designations of SAGA- or TFIID-dominated genes. Disruption of SAGA through mutation or rapid subunit depletion reduces transcription from nearly all genes, measured by newly synthesized RNA. We also find that the acetyltransferase Gcn5 synergizes with Spt3 to promote global transcription and that Spt3 functions to stimulate TBP recruitment at all tested genes. Our data demonstrate that SAGA acts as a general cofactor required for essentially all RNA polymerase II transcription and is not consistent with the previous classification of SAGA- and TFIID-dominated genes.

A systematic methodology review of phase I radiation dose escalation trials.

BACKGROUND AND PURPOSE: The purpose of this review is to evaluate the methodology used in published phase I radiotherapy (RT) dose escalation trials. A specific emphasis was placed on the frequency of reporting late complications as endpoint. MATERIALS AND METHODS: We performed a systematic literature review using a predefined search strategy to identify all phase I trials reporting on external radiotherapy dose escalation in cancer patients. RESULTS: Fifty-three trials (phase I: n = 36, phase I-II: n = 17) fulfilled the inclusion criteria. Of these, 20 used a modified Fibonacci design for the RT dose escalation, but 32 did not specify a design. Late toxicity was variously defined as > 3 months (n = 43) or > 6 months (n = 3) after RT, or not defined (n = 7). In only nine studies the maximum tolerated dose (MTD) was related to late toxicity, while only half the studies reported the minimum follow-up period for dose escalation (n = 26). CONCLUSION: In phase I RT trials, late complications are often not taken into account and there is currently no consensus on the methodology used for radiation dose escalation studies. We therefore propose a decision-tree algorithm which depends on the endpoint selected and whether a validated early surrogate endpoint is available, in order to choose the most appropriate study design.

Structure-system correlation identifies a gene regulatory Mediator submodule.

A combination of crystallography, biochemistry, and gene expression analysis identifies the coactivator subcomplex Med8C/18/20 as a functionally distinct submodule of the Mediator head module. Med8C forms a conserved alpha-helix that tethers Med18/20 to the Mediator. Deletion of Med8C in vivo results in dissociation of Med18/20 from Mediator and in loss of transcription activity of extracts. Deletion of med8C, med18, or med20 causes similar changes in the yeast transcriptome, establishing Med8C/18/20 as a predominantly positive, gene-specific submodule required for low transcription levels of nonactivated genes, including conjugation genes. The presented structure-based system perturbation is superior to gene deletion analysis of gene regulation.

Quantitative comparison of tissue oxygen and motexafin lutetium uptake by ex vivo and noninvasive in vivo techniques in patients with intraperitoneal carcinomatosis.

Near-infrared diffuse reflectance spectroscopy (DRS) has been used to noninvasively monitor optical properties during photodynamic therapy (PDT). This technique has been extensively validated in tissue phantoms; however, validation in patients has been limited. This pilot study compares blood oxygenation and photosensitizer tissue uptake measured by multiwavelength DRS with ex vivo assays of the hypoxia marker, 2-(2-nitroimida-zol-1[H]-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5), and the photosensitizer (motexafin lutetium, MLu) from tissues at the same tumor site of three tumors in two patients with intra-abdominal cancers. Similar in vivo and ex vivo measurements of MLu concentration are carried out in murine radiation-induced fibrosarcoma (RIF) tumors (n=9). The selection of optimal DRS wavelength range and source-detector separations is discussed and implemented, and the association between in vivo and ex vivo measurements is examined. The results demonstrate a negative correlation between blood oxygen saturation (StO(2)) and EF5 binding, consistent with published relationships between EF5 binding and electrode measured pO(2), and between electrode measured pO(2) and StO(2). A tight correspondence is observed between in vivo DRS and ex vivo measured MLu concentration in the RIF tumors; similar data are positively correlated in the human intraperitoneal tumors. These results further demonstrate the potential of in vivo DRS measurements in clinical PDT.

Two-dimensional/three dimensional Hybrid Interstitial Diffuse Optical Tomography of Human Prostate during Photodynamic Therapy: Phantom and Clinical Results.

We have developed an efficient Levenberg-Marquardt iterative algorithm utilizing a three-dimensional field measurements coupled to a two-dimensional optical property reconstruction scheme. This technique takes advantage of accurate estimation of light distribution in 3D forward calculation and reduced problem size and less computation time in 2D inversion. Important advances in terms of improving algorithm efficiency and accuracy include use of an iterative general minimum residual method (GMRES) for computing the field solutions, application of the dual mesh scheme and adjoint method for Jacobian construction, and implementation of normalization scheme to reduce the absorption-scattering cross talk. The synthetic measurement data were calculated for a cubic phantom containing a single absorption anomaly and a single scattering anomaly. The model had a background of µa=0.03mm-1 and µs'=1.4mm-1. The absorption and scattering anomalies have the µa = 0.06 mm-1 and µs' = 2.0 mm-1. Five sources and 72 detectors are used per slice. A typical human prostate is composed of 6 slices. The reconstruction images successfully recover the both anomalies with good localization. Experiment data from tissue simulated phantom are also presented. The clinical DOT imaging was performed before photodynamic therapy based on the protocol. The preliminary results showed the reconstructed prostate µa varied between 0.025 and 0.07 mm-1 and µs' ranged from 1.1 to 2 mm-1. These results show that this new 2D-3D hybrid algorithm consistently outperform the 2D-2D or 3D-3D counterparts.