Experimental Demonstration of Double Emittance Exchange toward Arbitrary Longitudinal Beam Phase-Space Manipulations.

Many of the most significant advances in accelerator science have been due to improvements in our ability to manipulate beam phase space. Despite steady progress in beam phase-space manipulation over the last several decades, future accelerator applications continue to outpace the ability to manipulate the phase space. This situation is especially pronounced for longitudinal beam phase-space manipulation, and is now getting increased attention. Herein, we report the first experimental demonstration of the double emittance exchange concept, which allows for the control of the longitudinal phase space using relatively simple transverse manipulation techniques. The double emittance exchange beamline enables extensive longitudinal manipulation, including tunable bunch compression, time-energy correlation control, and nonlinearity correction, in a remarkably flexible manner. The demonstration of this new method opens the door for arbitrary longitudinal beam manipulations capable of responding to the ever increasing demands of future accelerator applications.

Turn-key constrained parameter space exploration for particle accelerators using Bayesian active learning.

Particle accelerators are invaluable discovery engines in the chemical, biological and physical sciences. Characterization of the accelerated beam response to accelerator input parameters is often the first step when conducting accelerator-based experiments. Currently used techniques for characterization, such as grid-like parameter sampling scans, become impractical when extended to higher dimensional input spaces, when complicated measurement constraints are present, or prior information known about the beam response is scarce. Here in this work, we describe an adaptation of the popular Bayesian optimization algorithm, which enables a turn-key exploration of input parameter spaces. Our algorithm replaces  the need for parameter scans while minimizing prior information needed about the measurement's behavior and associated measurement constraints. We experimentally demonstrate that our algorithm autonomously conducts an adaptive, multi-parameter exploration of input parameter space, potentially orders of magnitude faster than conventional grid-like parameter scans, while making highly constrained, single-shot beam phase-space measurements and accounts for costs associated with changing input parameters. In addition to applications in accelerator-based scientific experiments, this algorithm addresses challenges shared by many scientific disciplines, and is thus applicable to autonomously conducting experiments over a broad range of research topics.

Transition Radiation in Photonic Topological Crystals: Quasiresonant Excitation of Robust Edge States by a Moving Charge.

We demonstrate, theoretically and experimentally, that a traveling electric charge passing from one photonic crystal into another generates edge waves-electromagnetic modes with frequencies inside the common photonic band gap localized at the interface-via a process of transition edge-wave radiation (TER). A simple and intuitive expression for the TER spectral density is derived and then applied to a specific structure: two interfacing photonic topological insulators with opposite spin-Chern indices. We show that TER breaks the time-reversal symmetry and enables valley- and spin-polarized generation of topologically protected edge waves propagating in one or both directions along the interface. Experimental measurements at the Argonne Wakefield Accelerator Facility are consistent with the excitation and localization of the edge waves. The concept of TER paves the way for novel particle accelerators and detectors.

Generation of High-Power, Reversed-Cherenkov Wakefield Radiation in a Metamaterial Structure.

We present the first demonstration of high-power, reversed-Cherenkov wakefield radiation by electron bunches passing through a metamaterial structure. The structure supports a fundamental transverse magnetic mode with a negative group velocity leading to reversed-Cherenkov radiation, which was clearly verified in the experiments. Single 45 nC electron bunches of 65 MeV traversing the structure generated up to 25 MW in 2 ns pulses at 11.4 GHz, in excellent agreement with theory. Two bunches of 85 nC with appropriate temporal spacing generated up to 80 MW by coherent wakefield superposition, the highest rf power that metamaterial structures ever experienced without damage. These results demonstrate the unique features of metamaterial structures that are very attractive for future high-gradient wakefield accelerators, including two-beam and collinear accelerators. Advantages include the high shunt impedance for high-power generation and high-gradient acceleration, the simple and rugged structure, and a large parameter space for optimization.

Changes in treatment of hyperglycemia in a hypertensive type 2 diabetes population as renal function declines.

BACKGROUND: Cardiovascular complications associated with expensive noninsulin agents for type 2 diabetes are the focus of concern in light of the risk of kidney dysfunction with aging. Head-to-head comparisons are unavailable to guide the choice of new drugs for hyperglycemia in patients with type 2 diabetes, decreased estimated glomerular filtration rate (eGFR) and increased cardiovascular risk. A first approach would be to document current medication choices. METHODS: All prescriptions for 10 151 patients (5623 males/4528 females) with both type 2 diabetes and hypertension seen two or more times during a 5-year period (2007-12) at Joslin Diabetes Center were evaluated. {mean age 64 years [interquartile range (IQR) 64-65)], body mass index 31 kg/m2 (IQR 30-32) and mean eGFR 78 mL/min/1.73 m2 (IQR 78, 78)}. RESULTS: Insulin was used in >60% of patients, metformin in 50% and sulfonylurea derivatives in 25%. Dipeptidyl peptidase 4 (DPP4) and acarbose class drugs were prescribed in 10% of patients, GLP-1 in 8% and other classes [including thiazolidinediones (TZD)] in <5%. Patients were grouped into four drug Categories none, 447 (4%); insulin only, 3836 (38%); other than insulin, 2910 (29%) and insulin combinations, 2955 (29%). Common combinations included insulin/metformin [n = 2493 (25%)], insulin/sulfonylureas [706 (7%)], metformin/sulfonylureas [2017 (20%)], metformin/GLP1 [949 ( 9%)], metformin/DPP4 [895 (9%)] and metformin/TZD [500 (5%)]. Insulin use increased to 70% from 35% as eGFR dropped to <30 mL/min/1.73 m2; use of insulin combined with other drugs dropped to 12% from 31% and the use of other drugs alone without insulin dropped similarly to 12% from 30%. CONCLUSIONS: Reduced renal function was associated with increased use of insulin and decreased use of other anti-diabetic agents in a statistically significant progression. BMI and gender did not influence medication choice.

In Situ Observation of Dark Current Emission in a High Gradient rf Photocathode Gun.

Undesirable electron field emission (also known as dark current) in high gradient rf photocathode guns deteriorates the quality of the photoemission current and limits the operational gradient. To improve the understanding of dark current emission, a high-resolution (∼100 µm) dark current imaging experiment has been performed in an L-band photocathode gun operating at ∼100 MV/m of surface gradient. Scattered strong emission areas with high current have been observed on the cathode. The field enhancement factor ß of selected regions on the cathode has been measured. The postexaminations with scanning electron microscopy and white light interferometry reveal the origins of ∼75% strong emission areas overlap with the spots where rf breakdown has occurred.

Renal Function Alters Antihypertensive Regimens in Type 2 Diabetic Patients.

To determine the prevalence of multidrug antihypertensive therapy (MDAT), records were evaluated for patients with both type 2 diabetes and hypertension during a 5-year period at Joslin Diabetes Center. Hypertension control was defined as requiring multiple drugs if three or more antihypertensive drugs were used, one of which must be a diuretic (unless patient is receiving dialysis), or use of four or more antihypertensive drugs, one of which a diuretic (unless patient is receiving dialysis) was established. The objective was to determine the prevalence of multidrug requirement for hypertensive therapy in relationship to four levels of renal function estimated by the Modification of Diet in Renal Disease formula for glomerular filtration rate (GFR). Among 10,151 patients, mean estimated GFR was 80 mL/min. Using standard (ASN) classification for renal function, we noted the following breakdown of MDAT use: Estimated GFR Drugs, Mean No. ≥3 Drugs, No. (%) ≥4 Drugs, No. (%) <30 3.1 379 (67) 214 (38) 30-60 2.7 1233 (55) 538 (24) 60-90 2.0 1279 (33) 458 (12) >90 1.5 600 (17) 185 (5) Prevalence of multidrug antihypertensive therapy is markedly increased in the presence of reduced renal function.

Observation of Wakefield Suppression in a Photonic-Band-Gap Accelerator Structure.

We report experimental observation of higher order mode (HOM) wakefield suppression in a room-temperature traveling-wave photonic-band-gap (PBG) accelerating structure at 11.700 GHz. It has been long recognized that PBG structures have the potential for reducing long-range wakefields in accelerators. The first ever demonstration of acceleration in a room-temperature PBG structure was conducted in 2005. Since then, the importance of PBG accelerator research has been recognized by many institutions. However, the full experimental characterization of the wakefield spectrum and demonstration of wakefield suppression when the accelerating structure is excited by an electron beam has not been performed to date. We conducted an experiment at the Argonne Wakefield Accelerator test facility and observed wakefields excited by a single high charge electron bunch when it passes through a PBG accelerator structure. Excellent HOM suppression properties of the PBG accelerator were demonstrated in the beam test.

Observation of Field-Emission Dependence on Stored Energy.

Field emission from a solid metal surface has been continuously studied for a century over macroscopic to atomic scales. It is general knowledge that, other than the surface properties, the emitted current is governed solely by the applied electric field. A pin cathode has been used to study the dependence of field emission on stored energy in an L-band rf gun. The stored energy was changed by adjusting the axial position (distance between the cathode base and the gun back surface) of the cathode while the applied electric field on the cathode tip is kept constant. A very strong correlation of the field-emission current with the stored energy has been observed. While eliminating all possible interfering sources, an enhancement of the current by a factor of 5 was obtained as the stored energy was increased by a factor of 3. It implies that under certain circumstances a localized field emission may be significantly altered by the global parameters in a system.

Proteolytic-based method for the identification of human growth hormone.

Human growth hormone (HGH) is a relatively small protein consisting of 191 amino acids and has an average mass of 22,125 amu. The forensic analysis of proteins such as HGH must meet the analytical sufficiency requirements for the laboratory and consists of a binary approach. A suspected sample is analyzed as the whole protein for retention time and mass determination using high performance liquid chromatography equipped with a photodiode array and liquid chromatography mass spectrometry. Further fragmentation of the protein using a proteolytic enzyme adds another dimension to the specificity of the analysis. Porcine trypsin digests proteins in a very predictable manner and yields peptide fragments of the original protein that can be used as a means for fingerprinting the larger biomolecule. In silico, or theoretical, digestion of HGH by trypsin yields 21 peptides ranging in size from 1 to 23 amino acids in length. The larger fragments containing higher numbers of amino acids give more specificity to identifying a protein based on a fragment produced by the digestion of trypsin. Herein, the analysis of HGH using a proteolytic approach is presented that meets the Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG) recommendations for the identification of unknown substances.

Identification and phenotypic characterization of Sphingomonas wittichii strain RW1 by peptide mass fingerprinting using matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Mass spectrometry is a potentially attractive means of monitoring the survival and efficacy of bioaugmentation agents, such as the dioxin-mineralizing bacterium Sphingomonas wittichii strain RW1. The biotransformation activity of RW1 phenotypes is determined primarily by the presence and concentration of the dioxin dioxygenase, an enzyme initiating the degradation of both dibenzo-p-dioxin and dibenzofuran (DF). We explored the possibility of identifying and characterizing putative cultures of RW1 by peptide mass fingerprinting (PMF) targeting this characteristic phenotypic biomarker. The proteome from cells of RW1--grown on various media in the presence and absence of DF--was partially purified, tryptically digested, and analyzed using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Mascot online database queries allowed statistically significant identification of RW1 in disrupted, digested cells (P < 0.01 to 0.05) and in digested whole-cell extracts (P < 0.00001 to 0.05) containing hundreds of proteins, as determined by two-dimensional gel electrophoresis. Up to 14 peptide ions of the alpha subunit of the dioxin dioxygenase (43% protein coverage) were detected in individual samples. A minimum of 10(7) DF-grown cells was required to identify dioxin degradation-enabled phenotypes. The technique hinges on the detection of multiple characteristic peptides of a biomarker that can reveal at once the identity and phenotypic properties of the microbial host expressing the protein. The results demonstrate the power of PMF of minimally processed microbial cultures as a sensitive and specific technique for the positive identification and phenotypic characterization of certain microorganisms used in biotechnology and bioremediation.