Protocols for Thermoluninescence and Optically Stimulated Luminescence Research at DOSAR

The Life Sciences Division (LSD) of Oak Ridge National Laboratory (ORNL) has a long record of radiation dosimetry research at the Dosimetry Applications Research (DOSAR) facility complex. These facilities have been used by a broad segment of the research community to perform a variety of experiments in areas including, but not limited to, radiobiology, radiation dosimeter and instrumentation development and calibration, and materials testing in a variety of radiation environments. Collaborations with the University of Tennessee-Knoxville (UTK) have also led to important contributions in the area of archaeometry, particularly as it relates to the use of radiation dosimetry to date archaeological artifacts. This manual is to serve as the primary instruction and operation manual for dosimetric and archaeometric research at DOSAR involving thermoluminescence (TL) and optically stimulated luminescence (OSL). Its purpose is to (1) provide protocols for common practices associated with the research, (2) outline the relevant organizational structure, (3) identify the Quality Assurance plan, and (4) describe all the procedures, operations, and responsibilities for safe and proper operation of associated equipment. Each person who performs research at DOSAR using TL/OSL equipment is required to read the latest revision of this manual and be familiar with its contents, and to sign and date the manual's master copy indicating that the manual has been read and understood. The TL/OSL Experimenter is also required to sign the manual after each revision to signify that the changes are understood. Each individual is responsible for completely understanding the proper operation of the TL/OSL equipment used and for following the guidance contained within this manual. The instructions, protocols, and operating procedures in this manual do not replace, supersede, or alter the hazard mitigation controls identified in the Research Safety Summary (''Thermoluminescence/Optically Stimulated Luminescence Dosimetry'') for this research, ORNL's Standards-Based Management System or any other official guidelines

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Classification of non-Riemannian doubled-yet-gauged spacetime

Assuming $\mathbf{O}(D,D)$ covariant fields as the `fundamental' variables, Double Field Theory can accommodate novel geometries where a Riemannian metric cannot be defined, even locally. Here we present a complete classification of such non-Riemannian spacetimes in terms of two non-negative integers, $(n,\bar{n})$, $0\leq n+\bar{n}\leq D$. Upon these backgrounds, strings become chiral and anti-chiral over $n$ and $\bar{n}$ directions respectively, while particles and strings are frozen over the $n+\bar{n}$ directions. In particular, we identify $(0,0)$ as Riemannian manifolds, $(1,0)$ as non-relativistic spacetime, $(1,1)$ as Gomis-Ooguri non-relativistic string, $(D{-1},0)$ as ultra-relativistic Carroll geometry, and $(D,0)$ as Siegel's chiral string. Combined with a covariant Kaluza-Klein ansatz which we further spell, $(0,1)$ leads to Newton-Cartan gravity. Alternative to the conventional string compactifications on small manifolds, non-Riemannian spacetime such as $D=10$, $(3,3)$ may open a new scheme of the dimensional reduction from ten to four.Comment: 1+41 pages; v2) Refs added; v3) Published version; v4) Sign error in (2.51) correcte

Using Evidence in a Highly Fragmented Legislature: The Case of Colombia's Health System Reform

This chapter examines how evidence is used in major policy health policy initiatives in a highly contested political context. Through a case study of legislation proposed in the context of Colombia’s ongoing health systems reformed process, it explores how such use is affected by the specific role played by the legislature within a highly fragmented polity. It draws on an analysis of evidence cited in the drafting of relevant laws in the process of health systems reform. Reflecting the role of the legislature in Colombia’s contested political system, evidence cited in legislative debates was unable to forge consensus amongst relevant policy actors over health system reforms. While scientific research was available and at the disposal of legislators, it was unable to provide the common ground on which to overcome embedded policy positions and form the basis of compromise over the direction of health systems reforms

Quantum fields during black hole formation: how good an approximation is the Unruh state?

We study the quantum effects of a test Klein-Gordon field in a Vaidya space-time consisting of a collapsing null shell that forms a Schwazschild black hole, by explicitly obtaining, in a (1 + 1)-dimensional model, the Wightman function, the renormalised stress-energy tensor, and by analysing particle detector rates along stationary orbits in the exterior black hole region, and make a comparison with the folklore that the Unruh state is the state that emerges from black hole formation. In the causal future of the shell, we find a negative ingoing flux at the horizon that agrees precisely with the Unruh state calculation, and is the source of black hole radiation, while in the future null infinity we find that the radiation flux output in the Unruh state is an upper bound for the positive outgoing flux in the collapsing null shell spacetime. This indicates that back-reaction estimates based on Unruh state calculations over-estimate the energy output carried by so-called pre-Hawking radiation. The value of the output predicted by the Unruh state is however approached exponentially fast. Finally, we find that at late times, stationary observers in the exterior black hole region in the collapsing shell spacetime detect the local Hawking temperature, which is also well characterised by the Unruh state, coming from right-movers. Early-time discrepancies between the detector rates for the Unruh state and for the state in the collapsing shell spacetime are explored numerically

Fatal gemcitabine-induced pulmonary toxicity in metastatic gallbladder adenocarcinoma

Gemcitabine is a chemotherapy agent that may cause unpredictable side effects. In this report, we describe a fatal gemcitabine-induced pulmonary toxicity in a patient with gallbladder metastatic adenocarcinoma. A 72-year-old patient was submitted to an elective laparoscopic cholecystectomy, and a tubular adenocarcinoma in the gallbladder was incidentally diagnosed. CT scan and ultrasound before the surgery did not show any tumor. After the surgery a Pet scan was positive for a hot-spot in the left colon. The colonic lesion was conveniently removed and the histology evaluation confirmed the diagnosis of adenocarcinoma tubular. The patient was then submitted to three sections of 1,600 mg/m2 of gemcitabine with intervals of 1 week. Three weeks later he developed severe respiratory distress. A helicoidal CT scan showed diffuse and severe interstitial pneumonitis, and lung biopsy confirmed accelerated usual interstitial pneumonia consistent with drug-induced toxicity. The patient presented unfavorable evolution with progressive worsening of respiratory function, hypotension, and renal failure. He died 1 month later in spite of methylprednisolone pulse therapy, large spectrum antimicrobial therapy, and full support of respiratory, hemodynamic and renal systems. Gemcitabine-induced pulmonary toxicity is usually a dramatic condition. Physicians should suspect pulmonary toxicity in patients with respiratory distress after gemcitabine chemotherapy, mainly in elderly patients

Hepatitis C infection: eligibility for antiviral therapies

peer reviewedBackground Current treatments of chronic hepatitis C virus (HCV) are effective, but expensive and susceptible to induce significant side effects. Objectives To evaluate the proportion of HCV patients who are eligible for a treatment. Methods In a database comprising 1726 viraemic HCV patients, the files of 299 patients who presented to the same hepatologist for an initial appointment between 1996 and 2003 were reviewed. Results Patients' characteristics were age 43.1 +/- 15.6 years, 53% male and 92% Caucasian. The main risk factors were transfusion (43%) and drug use (22%). Genotypes were mostly genotype 1 (66%), genotype 3 (12%) and genotype 2 (10%). These characteristics were not different from those of the whole series of 1726 patients. A total of 176 patients (59%) were not treated, the reasons for non-treatment being medical contraindications (34%), non-compliance (25%) and normal transaminases (24%). In addition, 17% of patients declined therapy despite being considered as eligible, mainly due to fear of adverse events. Medical contraindications were psychiatric (27%), age (22%), end-stage liver disease (15%), willingness for pregnancy (13%), cardiac contraindication (7%) and others (16%). Only 123 patients (41%) were treated. A sustained viral response was observed in 41%. The treatment was interrupted in 16% for adverse events. Conclusions The majority of HCV patients are not eligible for treatment. This implies that, with current therapies, only 17% of patients referred for chronic HCV become sustained responders. Some modifications of guidelines could extend the rate of treatment (patients with normal transaminases), but an important barrier remains the patients' and the doctors' fear of adverse events

Relatively higher norms of blood flow velocity of major intracranial arteries in North-West Iran

<p>Abstract</p> <p>Background</p> <p>Transcranial Doppler (TCD) is a noninvasive, less expensive and harmless hemodynamic study of main intracranial arteries. The aim of this study was to assess normal population values of cerebral blood flow velocity and its variation over age and gender in a given population.</p> <p>Findings</p> <p>Eighty healthy volunteers including 40 people with an age range of 25-40 years (group1) and 40 persons with an age range of 41-55 years (group2) were studied. In each group 20 males and 20 females were enrolled. Peak systolic, end diastolic and mean velocities of nine main intracranial arteries were determined using TCD. Mean age of the studied volunteers was 31.6 ± 4.50 years in group one and 47.2 ± 4.3 years in group two. Mean age among males was 40 years and among females it was 39. Mean blood flow velocity in middle, anterior and posterior cerebral arteries, vertebral and basilar arteries was 60 ± 8, 52 ± 9, 42 ± 6, 39 ± 8 and 48 ± 8 cm/sec respectively. Cerebral blood flow velocities among females were relatively higher than males. Cerebral blood flow velocity of left side was relatively higher than right side.</p> <p>Conclusion</p> <p>Compared to previous studies, cerebral blood flow velocity in this population was relatively higher.</p

Accreting Millisecond X-Ray Pulsars

Accreting Millisecond X-Ray Pulsars (AMXPs) are astrophysical laboratories without parallel in the study of extreme physics. In this chapter we review the past fifteen years of discoveries in the field. We summarize the observations of the fifteen known AMXPs, with a particular emphasis on the multi-wavelength observations that have been carried out since the discovery of the first AMXP in 1998. We review accretion torque theory, the pulse formation process, and how AMXP observations have changed our view on the interaction of plasma and magnetic fields in strong gravity. We also explain how the AMXPs have deepened our understanding of the thermonuclear burst process, in particular the phenomenon of burst oscillations. We conclude with a discussion of the open problems that remain to be addressed in the future.Comment: Review to appear in "Timing neutron stars: pulsations, oscillations and explosions", T. Belloni, M. Mendez, C.M. Zhang Eds., ASSL, Springer; [revision with literature updated, several typos removed, 1 new AMXP added