687 research outputs found
Reverse Biomimetic’ Synthesis of L-Arogenate and its Stabilized Analogues from L-Tyrosine
l-Arogenate (also known as l-pretyrosine) is a primary metabolite on a branch of the shikimate biosynthetic pathway to aromatic amino acids. It plays a key role in the synthesis of plant secondary metabolites including alkaloids and the phenylpropanoids that are the key to carbon fixation. Yet understanding the control of arogenate metabolism has been hampered by its extreme instability and the lack of a versatile synthetic route to arogenate and its analogues. We now report a practical synthesis of l-arogenate in seven steps from O-benzyl l-tyrosine methyl ester in an overall yield of 20%. The synthetic route also delivers the fungal metabolite spiroarogenate, as well as a range of stable saturated and substituted analogues of arogenate. The key step in the synthesis is a carboxylative dearomatization by intramolecular electrophilic capture of tyrosine's phenolic ring using an N-chloroformylimidazolidinone moiety, generating a versatile, functionalizable spirodienone intermediate
Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker - longitudinal relationships with pain and structural changes: data from the Osteoarthritis Initiative
Abstract Introduction Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN). Methods A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume). Results This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume. Conclusion Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression
Multicomponent frailty assessment tools for older people with psychiatric disorders: a systematic review
Objective: To review evidence evaluating the use of multi-component frailty assessment tools in assessing frailty in older adults with psychiatric disorders. Methods: A systematic literature review was conducted to identify all multi-component frailty assessment tools (i.e. a tool that assesses ≥2 indicators of frailty). The items of each frailty assessment tool were compared to DSM-5 diagnostic criteria for psychiatric disorders to assess construct overlap. Studies conducted in community, inpatient and outpatient clinical settings were considered for inclusion. Participants: Adults aged ≥60 years old. Results: 5,639 studies in total were identified following the removal of duplicates; 97 of which were included for review. Of the 48 multi-component frailty assessment tools identified, no tool had been developed for, or validated in, older adult populations with psychiatric disorder. 24/48 frailty assessment tools contained a psychological assessment domain, with 18/48 tools using presence of depressed mood and/or anxiety as a frailty indicator. Common areas of construct overlap in frailty assessment tools and DSM-5 diagnostic criteria included weight loss (29/48) and fatigue (21/48). Conclusions: Significant construct overlap exists between the indicators of frailty as conceptualised in existing frailty assessment tools and DSM-5 diagnostic criteria for common psychiatric disorders, including Major Depressive Episode and Generalised Anxiety Disorder, which has the potential to confound frailty assessment results. Further research is necessary to establish a reliable and valid tool to assess frailty in this population
Mechanical design and development of TES bolometer detector arrays for the Advanced ACTPol experiment
The next generation Advanced ACTPol (AdvACT) experiment is currently underway
and will consist of four Transition Edge Sensor (TES) bolometer arrays, with
three operating together, totaling ~5800 detectors on the sky. Building on
experience gained with the ACTPol detector arrays, AdvACT will utilize various
new technologies, including 150mm detector wafers equipped with multichroic
pixels, allowing for a more densely packed focal plane. Each set of detectors
includes a feedhorn array of stacked silicon wafers which form a spline profile
leading to each pixel. This is then followed by a waveguide interface plate,
detector wafer, back short cavity plate, and backshort cap. Each array is
housed in a custom designed structure manufactured from high purity copper and
then gold plated. In addition to the detector array assembly, the array package
also encloses cryogenic readout electronics. We present the full mechanical
design of the AdvACT high frequency (HF) detector array package along with a
detailed look at the detector array stack assemblies. This experiment will also
make use of extensive hardware and software previously developed for ACT, which
will be modified to incorporate the new AdvACT instruments. Therefore, we
discuss the integration of all AdvACT arrays with pre-existing ACTPol
infrastructure.Comment: 9 pages, 5 figures, SPIE Astronomical Telescopes and Instrumentation
conference proceeding
Teaching Matters: Essays by UMF Faculty
Essays by faculty at the University of Maine at Farmington.https://scholarworks.umf.maine.edu/publications/1086/thumbnail.jp
The Atacama Cosmology Telescope: The polarization-sensitive ACTPol instrument
The Atacama Cosmology Telescope (ACT) is designed to make high angular
resolution measurements of anisotropies in the Cosmic Microwave Background
(CMB) at millimeter wavelengths. We describe ACTPol, an upgraded receiver for
ACT, which uses feedhorn-coupled, polarization-sensitive detector arrays, a 3
degree field of view, 100 mK cryogenics with continuous cooling, and meta
material anti-reflection coatings. ACTPol comprises three arrays with separate
cryogenic optics: two arrays at a central frequency of 148 GHz and one array
operating simultaneously at both 97 GHz and 148 GHz. The combined instrument
sensitivity, angular resolution, and sky coverage are optimized for measuring
angular power spectra, clusters via the thermal Sunyaev-Zel'dovich and kinetic
Sunyaev-Zel'dovich signals, and CMB lensing due to large scale structure. The
receiver was commissioned with its first 148 GHz array in 2013, observed with
both 148 GHz arrays in 2014, and has recently completed its first full season
of operations with the full suite of three arrays. This paper provides an
overview of the design and initial performance of the receiver and related
systems
Improving Photoelectron Counting and Particle Identification in Scintillation Detectors with Bayesian Techniques
Many current and future dark matter and neutrino detectors are designed to
measure scintillation light with a large array of photomultiplier tubes (PMTs).
The energy resolution and particle identification capabilities of these
detectors depend in part on the ability to accurately identify individual
photoelectrons in PMT waveforms despite large variability in pulse amplitudes
and pulse pileup. We describe a Bayesian technique that can identify the times
of individual photoelectrons in a sampled PMT waveform without deconvolution,
even when pileup is present. To demonstrate the technique, we apply it to the
general problem of particle identification in single-phase liquid argon dark
matter detectors. Using the output of the Bayesian photoelectron counting
algorithm described in this paper, we construct several test statistics for
rejection of backgrounds for dark matter searches in argon. Compared to simpler
methods based on either observed charge or peak finding, the photoelectron
counting technique improves both energy resolution and particle identification
of low energy events in calibration data from the DEAP-1 detector and
simulation of the larger MiniCLEAN dark matter detector.Comment: 16 pages, 16 figure
In-situ characterization of the Hamamatsu R5912-HQE photomultiplier tubes used in the DEAP-3600 experiment
The Hamamatsu R5912-HQE photomultiplier-tube (PMT) is a novel high-quantum
efficiency PMT. It is currently used in the DEAP-3600 dark matter detector and
is of significant interest for future dark matter and neutrino experiments
where high signal yields are needed.
We report on the methods developed for in-situ characterization and
monitoring of DEAP's 255 R5912-HQE PMTs. This includes a detailed discussion of
typical measured single-photoelectron charge distributions, correlated noise
(afterpulsing), dark noise, double, and late pulsing characteristics. The
characterization is performed during the detector commissioning phase using
laser light injected through a light diffusing sphere and during normal
detector operation using LED light injected through optical fibres
Early pre-radiographic structural pathology precedes the onset of accelerated knee osteoarthritis.
BACKGROUND: Accelerated knee osteoarthritis (AKOA) is characterized by more pain, impaired physical function, and greater likelihood to receive a joint replacement compared to individuals who develop the typical gradual onset of disease. Prognostic tools are needed to determine which structural pathologies precede the development of AKOA compared to individuals without AKOA. Therefore, the purpose of this manuscript was to determine which pre-radiographic structural features precede the development of AKOA. METHODS: The sample comprised participants in the Osteoarthritis Initiative (OAI) who had at least one radiographically normal knee at baseline (Kellgren-Lawrence [KL] grade 3) and No AKOA. The index visit was the study visit when participants met criteria for AKOA or a matched timepoint for those who did not develop AKOA. Magnetic resonance (MR) images were assessed for 12 structural features at the OAI baseline, and 1 and 2 years prior to the index visit. Separate logistic regression models (i.e. OAI baseline, 1 and 2 years prior) were used to determine which pre-radiographic structural features were more likely to antedate the development of AKOA compared to individuals not developing AKOA. RESULTS: At the OAI baseline visit, degenerative cruciate ligaments (Odds Ratio [OR] = 2.2, 95% Confidence Interval [CI] = 1.3,3.5), infrapatellar fat pad signal intensity alteration (OR = 2.0, 95%CI = 1.2,3.2), medial/lateral meniscal pathology (OR = 2.1/2.4, 95%CI = 1.3,3.4/1.5,3.8), and greater quantitative knee effusion-synovitis (OR = 2.2, 95%CI = 1.4,3.4) were more likely to antedate the development of AKOA when compared to those that did not develop AKOA. These results were similar at one and two years prior to disease onset. Additionally, medial meniscus extrusion at one year prior to disease onset (OR = 3.5, 95%CI = 2.1,6.0) increased the likelihood of developing AKOA. CONCLUSIONS: Early ligamentous degeneration, effusion/synovitis, and meniscal pathology precede the onset of AKOA and may be prognostic biomarkers
- …