Demonstration of a narrow energy spread, ∼0.5 GeV electron beam from a two-stage laser wakefield accelerator

Laser wakefield acceleration of electrons holds great promise for producing ultracompact stages of GeV scale, high-quality electron beams for applications such as x-ray free electron lasers and high-energy colliders. Ultrahigh intensity laser pulses can be self-guided by relativistic plasma waves (the wake) over tens of vacuum diffraction lengths, to give >1 GeV energy in centimeter-scale low density plasmas using ionization-induced injection to inject charge into the wake even at low densities. By restricting electron injection to a distinct short region, the injector stage, energetic electron beams (of the order of 100 MeV) with a relatively large energy spread are generated. Some of these electrons are then further accelerated by a second, longer accelerator stage, which increases their energy to ～0.5 GeV while reducing the relative energy spread to <5% FWHM.     

Quantum filtering one bit at a time

In this Letter we consider the purification of a quantum state using the information obtained from a continuous measurement record, where the classical measurement record is digitized to a single bit per measurement after the measurements have been made. Analysis indicates that efficient and reliable state purification is achievable for one- and two-qubit systems. We also consider quantum feedback control based on the discrete one-bit measurement sequences.     

Small-molecule discovery from DNA-encoded chemical libraries

Researchers seeking to improve the efficiency and cost effectiveness of the bioactive small-molecule discovery process have recently embraced selection-based approaches, which in principle offer much higher throughput and simpler infrastructure requirements compared with traditional small-molecule screening methods. Since selection methods benefit greatly from an information-encoding molecule that can be readily amplified and decoded, several academic and industrial groups have turned to DNA as the basis for library encoding and, in some cases, library synthesis. The resulting DNA-encoded synthetic small-molecule libraries, integrated with the high sensitivity of PCR and the recent development of ultra high-throughput DNA sequencing technology, can be evaluated very rapidly for binding or bond formation with a target of interest while consuming minimal quantities of material and requiring only modest investments of time and equipment. In this tutorial review we describe the development of two classes of approaches for encoding chemical structures and reactivity with DNA: DNA-recorded library synthesis, in which encoding and library synthesis take place separately, and DNA-directed library synthesis, in which DNA both encodes and templates library synthesis. We also describe in vitro selection methods used to evaluate DNA-encoded libraries and summarize successful applications of these approaches to the discovery of bioactive small molecules and novel chemical reactivity.     

The Fundamental Infrared Spectrum of the Ammonium Ion in Aqueous Solutions

The infrared absorptions of NH₄ ⁺ of aqueous solutions of NH₄ ⁺ salt solutions were recently considered in some detail and, based on changes in the contour of the water band, the effect of anions of the water absorption were discussed.¹ We find, however, that differences of the contours of absorptions of pure water and of aqueous solutions can easily produce an artifact.     

Novel S-Gal analogs as H MRI reporters for in vivo detection of β-galactosidase

The quantitative assessment of gene expression and related enzyme activity in vivo could be important for the characterization of gene altering diseases and therapy. The development of imaging techniques, based on specific reporter molecules may enable routine non-invasive assessment of enzyme activity and gene expression in vivo. We recently reported the use of commercially available S-Gal^® as a β-galactosidase reporter for ¹H MRI, and the synthesis of several S-Gal^® analogs with enhanced response to β-galactosidase activity. We have now compared these analogs in vitro and have identified the optimal analog, C3-GD, based on strong T₁ and T₂ response to enzyme presence (ΔR₁ and ΔR₂ ~ 1.8 times S-Gal^®). Moreover, application is demonstrated in vivo in human breast tumor xenografts. MRI studies in MCF7-lacZ tumors implanted subcutaneously in athymic nude mice (n = 6), showed significant reduction in T₁ and T₂ values (each ~ 13%) 2 h after intra-tumoral injection of C3-GD, whereas the MCF7 (wild type) tumors showed slight increase. Thus, C3-GD successfully detects β-galactosidase activity in vivo and shows promise as a lacZ gene ¹H MR reporter molecule.     

On Forbidden Pairs Implying Hamilton‐Connectedness

Let X, Y be connected graphs. A graph G is ‐free if G contains a copy of neither X nor Y as an induced subgraph. Pairs of connected graphs such that every 3‐connected ‐free graph is Hamilton connected have been investigated most recently in (Guantao Chen and Ronald J. Gould, Bull. Inst. Combin. Appl., 29 (2000), 25–32.) [8] and (H. Broersma, R. J. Faudree, A. Huck, H. Trommel, and H. J. Veldman, J. Graph Theory, 40(2) (2002), 104–119.) [5]. This paper improves those results. Specifically, it is shown that every 3‐connected ‐free graph is Hamilton connected for and or N_{1, 2, 2} and the proof of this result uses a new closure technique developed by the third and fourth authors. A discussion of restrictions on the nature of the graph Y is also included.     

Event-related fMRI with painful electrical stimulation of the trigeminal nerve

Several functional brain imaging studies of pain using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have shown that painful stimulation causes activation of different brain areas. The aim of the present study was to develop and implement painful stimulation of the trigeminal nerve, which can be applied with event-related paradigms by using MRI. Twelve healthy, right-handed volunteers were examined. Painful electrical stimulation of the first trigeminal branch was performed. In an event-related setting with a 1.5 T clinical scanner with EPI capability, the following fMRI parameters were used: 20 slices, 3 mm thickness, isotropic voxel, 306 measurements with 54 randomized events. Statistical postprocessing was performed with SPM99. Activation of the ipsi- and contralateral secondary somatosensory cortex (SII), and the contralateral insular cortex was observed as well as a contralateral thalamic activation (T=4.45, extension 15 voxels). Six of the 12 volunteers revealed also activation of the cingulate cortex. The investigation demonstrates that painful stimulation of the trigeminal nerve activates the contralateral insular cortex, SII, and thalamus, as well as the ipsilateral SII. In contrast to other studies, the cingulate cortex was only activated inconsistently.     

The feasibility of assessing branched-chain amino acid metabolism in cellular models of prostate cancer with hyperpolarized [1-C]-ketoisocaproate

Recent advancements in the field of hyperpolarized ¹³C magnetic resonance spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis of metabolic pathways. These non-invasive methods have increasingly shown application in impacting disease diagnosis and have further been employed in mechanistic studies of disease onset and progression. Our goals were to investigate branched-chain aminotransferase (BCAT) activity in prostate cancer with a novel molecular probe, hyperpolarized [1-¹³C]-2-ketoisocaproate ([1-¹³C]-KIC), and explore the potential of branched-chain amino acid (BCAA) metabolism to serve as a biomarker. Using traditional spectrophotometric assays, BCAT enzymatic activities were determined in vitro for various sources of prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse and human cell lines). These preliminary studies indicated that low levels of BCAT activity were present in all models of prostate cancer but enzymatic levels are altered significantly in prostate cancer relative to healthy tissue. The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU-145) that exhibited levels of BCAA metabolism comparable to the human disease state. Hyperpolarized [1-¹³C]-KIC was administered to prostate cancer cell lines, and the conversion of [1-¹³C]-KIC to the metabolic product, [1-¹³C]-leucine ([1-¹³C]-Leu), could be monitored via hyperpolarized ¹³C MRS.     

Application of double spin echo spiral chemical shift imaging to rapid metabolic mapping of hyperpolarized [1-¹³C]-pyruvate

Undersampled spiral CSI (spCSI) using a free induction decay (FID) acquisition allows sub-second metabolic imaging of hyperpolarized 13C. Phase correction of the FID acquisition can be difficult, especially with contributions from aliased out-of-phase peaks. This work extends the spCSI sequence by incorporating double spin echo radiofrequency (RF) pulses to eliminate the need for phase correction and obtain high quality spectra in magnitude mode. The sequence also provides an added benefit of attenuating signal from flowing spins, which can otherwise contaminate signal in the organ of interest. The refocusing pulses can potentially lead to a loss of hyperpolarized magnetization in dynamic imaging due to flow of spins through the fringe field of the RF coil, where the refocusing pulses fail to provide complete refocusing. Care must be taken for dynamic imaging to ensure that the spins remain within the B?-homogeneous sensitive volume of the RF coil.