402 research outputs found
Bent crystal spectrometer for both frequency and wavenumber resolved x-ray scattering at a seeded free-electron laser
We present a cylindrically curved GaAs x-ray spectrometer with energy
resolution and wave-number resolution of
, allowing plasmon scattering at the resolution
limits of the Linac Coherent Light Source (LCLS) x-ray free-electron laser. It
spans scattering wavenumbers of 3.6 to \AA\ in 100 separate bins, with
only 0.34\% wavenumber blurring. The dispersion of 0.418~eV/m agrees
with predictions within 1.3\%. The reflection homogeneity over the entire
wavenumber range was measured and used to normalize the amplitude of scattering
spectra. The proposed spectrometer is superior to a mosaic HAPG spectrometer
when the energy resolution needs to be comparable to the LCLS seeded bandwidth
of 1~eV and a significant range of wavenumbers must be covered in one exposure
The Phase-Contrast Imaging Instrument at the Matter in Extreme Conditions Endstation at LCLS
We describe the Phase-Contrast Imaging instrument at the Matter in Extreme
Conditions (MEC) endstation of the Linac Coherent Light Source. The instrument
can image phenomena with a spatial resolution of a few hundreds of nanometers
and at the same time reveal the atomic structure through X-ray diffraction,
with a temporal resolution better than 100 femtosecond. It was specifically
designed for studies relevant to High-Energy-Density Science and can monitor,
e.g., shock fronts, phase transitions, or void collapses. This versatile
instrument was commissioned last year and is now available to the MEC user
community
Measurement of competing pathways in a shock-induced phase transition in zirconium by femtosecond diffraction
The traditional picture of solid-solid phase transformations assumes an
ordered parent phase transforms into an ordered daughter phase via a single
unique pathway. Zirconium and its prototypical phase transition from hexagonal
close-packed (hcp) to simple hexagonal (hex-3) structure has generated
considerable controversy over several decades regarding which mechanism
mediates the transformation. However, a lack of in situ measurements over the
relevant atomistic timescales has hindered our ability to identify the true
pathway. In this study, we exploit femtosecond X-ray diffraction coupled with
nanosecond laser compression to give unprecedented insights into the
complexities of how materials transform at the lattice level. We observe
single-crystal zirconium changing from hcp to a hex-3 structure via not one but
three competing pathways simultaneously. Concurrently, we also observe a broad
diffuse background underlying the sharp Bragg diffraction during the
transition. We corroborate our observation of the diffuse signal with
multimillion-atom molecular dynamics simulations using a machine-learned
interatomic potential. Our study demonstrates that the traditional mechanistic
view of transitions may fail for even an elemental metal and that the
mechanisms by which materials transform are far more intricate than generally
thought
Short-term calorie restriction ameliorates genomewide, age-related alterations in DNA methylation
DNA methylation plays major roles in many biological processes, including aging, carcinogenesis, and development. Analyses of DNA methylation using next-generation sequencing offer a new way to profile and compare methylomes across the genome in the context of aging. We explored genomewide DNA methylation and the effects of short-term calorie restriction (CR) on the methylome of aged rat kidney. Whole-genome methylation of kidney in young (6 months old), old (25 months old), and OCR (old with 4-week, short-term CR) rats was analyzed by methylated DNA immunoprecipitation and next-generation sequencing (MeDIP-Seq). CpG islands and repetitive regions were hypomethylated, but 5'-UTR, exon, and 3'-UTR hypermethylated in old and OCR rats. The methylation in the promoter and intron regions was decreased in old rats, but increased in OCR rats. Pathway enrichment analysis showed that the hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. Thus, these findings suggest that short-term CR could partially ameliorate age-related methylation changes in promoters in old rats. From the epigenomic data, we propose that the hypermethylation found in the promoter regions of disease-related genes during aging may indicate increases in susceptibility to age-related diseases. Therefore, the CR-induced epigenetic changes that ameliorate age-dependent aberrant methylation may be important to CR's health-and life-prolonging effects.ope
Improving gastric cancer preclinical studies using diverse in vitro and in vivo model systems
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International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made.Abstract
Background
Biomarker-driven targeted therapy, the practice of tailoring patients treatment to the expression/activity levels of disease-specific genes/proteins, remains challenging. For example, while the anti-ERBB2 monoclonal antibody, trastuzumab, was first developed using well-characterized, diverse in vitro breast cancer models (and is now a standard adjuvant therapy for ERBB2-positive breast cancer patients), trastuzumab approval for ERBB2-positive gastric cancer was largely based on preclinical studies of a single cell line, NCI-N87. Ensuing clinical trials revealed only modest patient efficacy, and many ERBB2-positive gastric cancer (GC) patients failed to respond at all (i.e., were inherently recalcitrant), or succumbed to acquired resistance.
Method
To assess mechanisms underlying GC insensitivity to ERBB2 therapies, we established a diverse panel of GC cells, differing in ERBB2 expression levels, for comprehensive in vitro and in vivo characterization. For higher throughput assays of ERBB2 DNA and protein levels, we compared the concordance of various laboratory quantification methods, including those of in vitro and in vivo genetic anomalies (FISH and SISH) and xenograft protein expression (Western blot vs. IHC), of both cell and xenograft (tissue-sectioned) microarrays.
Results
The biomarker assessment methods strongly agreed, as did correlation between RNA and protein expression. However, although ERBB2 genomic anomalies showed good in vitro vs. in vivo correlation, we observed striking differences in protein expression between cultured cells and mouse xenografts (even within the same GC cell type). Via our unique pathway analysis, we delineated a signaling network, in addition to specific pathways/biological processes, emanating from the ERBB2 signaling cascade, as a potential useful target of clinical treatment. Integrated analysis of public data from gastric tumors revealed frequent (10 – 20 %) amplification of the genes NFKBIE, PTK2, and PIK3CA, each of which resides in an ERBB2-derived subpathway network.
Conclusion
Our comprehensive bioinformatics analyses of highly heterogeneous cancer cells, combined with tumor omics profiles, can optimally characterize the expression patterns and activity of specific tumor biomarkers. Subsequent in vitro and in vivo validation, of specific disease biomarkers (using multiple methodologies), can improve prediction of patient stratification according to drug response or nonresponse
Intravenous fluid prescription practices among pediatric residents in Korea
PurposeRecent studies have established the association between hypotonic fluids administration and hospital-acquired hyponatremia in children. The present paper investigated the pattern of current practice in intravenous fluid prescription among Korean pediatric residents, to underscore the need for updated education.MethodsA survey-based analysis was carried out. Pediatric residents at six university hospitals in Korea completed a survey consisting of four questions. Each question proposed a unique scenario in which the respondents had to prescribe either a hypotonic or an isotonic fluid for the patient.ResultsNinety-one responses were collected and analyzed. In three of the four scenarios, a significant majority prescribed the hypotonic fluids (98.9%, 85.7%, and 69.2%, respectively). Notably, 69.2% of the respondents selected the hypotonic fluids for postoperative management. Almost all (96.7%) selected the isotonic fluids for hydration therapy.ConclusionIn the given scenarios, the majority of Korean pediatric residents would prescribe a hypotonic fluid, except for initial hydration. The current state of pediatric fluid management, notably, heightens the risk of hospital-acquired hyponatremia. Updated clinical practice education on intravenous fluid prescription, therefore, is urgently required
Severe ischemic bowel necrosis caused by terlipressin during treatment of hepatorenal syndrome
Terlipressin is a vasopressin analogue that is widely used in the treatment of hepatorenal syndrome or variceal bleeding. Because it acts mainly on splanchnic vessels, terlipressin has a lower incidence of severe ischemic complications than does vasopressin. However, it can still lead to serious complications such as myocardial infarction, skin necrosis, or bowel ischemia. Herein we report a case of severe ischemic bowel necrosis in a 46-year-old cirrhotic patient treated with terlipressin. Although the patient received bowel resection, death occurred due to ongoing hypotension and metabolic acidosis. Attention should be paid to patients complaining of abdominal pain during treatment with terlipressin
Interplay of thermal and non-thermal effects in x-ray-induced ultrafast melting
X-ray laser-induced structural changes in silicon undergoing femtosecond
melting have been investigated by using an x-ray pump-x-ray probe technique.
The experimental results for different initial sample temperatures reveal that
the onset time and the speed of the atomic disordering are independent of the
initial temperature, suggesting that equilibrium atomic motion in the initial
state does not play a pivotal role in the x-ray-induced ultrafast melting. By
comparing the observed time-dependence of the atomic disordering and the
dedicated theoretical simulations, we interpret that the energy transfer from
the excited electrons to ions via electron-ion coupling (thermal effect) as
well as a strong modification of the interatomic potential due to electron
excitations (non-thermal effect) trigger the ultrafast atomic disordering. Our
finding of the interplay of thermal and non-thermal effects in the
x-ray-induced melting demonstrates that accurate modeling of intense x-ray
interactions with matter is essential to ensure a correct interpretation of
experiments using intense x-ray laser pulses
Paroxysmal atrial fibrillation developed during incomplete epidural anesthesia -A case report-
Atrial fibrillation (AF) is the most common sustained tachyarrhythmia, and occurs in organic heart disease such as rheumatic, atherosclerotic and hypertensive heart disease. In recent studies, the sympathetic and parasympathetic nervous systems have been shown to have important roles in initiating paroxysmal AF. We report here a patient who developed paroxysmal AF that might be a result of an imbalance of the sympathetic-parasympathetic systems due to epidural anesthesia, and that was potentiated by pain with inadequate analgesia. A 69-year-old woman was scheduled for operation of a right-sided ankle fracture. Twenty minutes after epidural drug injection, paroxysmal AF occurred. Even after intravenous administration of esmolol and digoxin, AF continued. After transfer to the intensive care unit, her heart rate gradually decreased and AF disappeared. During perioperative anesthetic management, the proper preoperative prevention and intraoperative treatment are needed in AF high-risk patients
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