Roadmap: proton therapy physics and biology.

The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200 000 patients have been treated with proton beams worldwide and the number of operating proton therapy (PT) facilities will soon reach one hundred. PT has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While PT has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of PT cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effect difference compared to photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because PT treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in PT categorized into four different themes, 'improving efficiency', 'improving planning and delivery', 'improving imaging', and 'improving patient selection'.

SU-D-211-06: The Effect of Motion in RapidArc Lung SBRT Delivery.

PURPOSE: RapidArc is routinely used for stereotactic radiotherapy for lung cancer. While treatment dose is optimized and calculated on a static CT image, the motion of the target in conjunction with the motion of the MLC may Result in a delivered dose deviating from the planed dose. In this study, we investigate the dosimetric consequences of the inter-play effect by simulating dynamic dose delivery on a dynamic CT dataset of real patients. METHODS: The target motion in 20 patients was analyzed and 5 patients with >10 mm motion were chosen for this study. The RapidArc plan for eachpatient is optimized on a free-breathing CT using 2 arcs. Inherent in each plan is data on the associated parameters such as timestamp, MLC leave position, gantry angle and delivered beam MUs for each control point. Simulated dynamic delivery is performed by associating these parameters with each of the breathing phases of the 4D-CT. The starting breathing phase is selected randomly for each of the two arcs. Dose from the derived partial plans associated with each phase of the 4D-CT dose is recalculated in Eclipse. Accumulation of dose is performed using deformable image registration from each phase of the 4D-CT to the exhale phase of the 4D-CT. RESULTS: The coverage of the GTV and PTV shows negligible variations from the interplay effect. But the Homogeneity Index is affected by the motion. The prescription isodose volume is smaller than what was from the treatment plan dose. There were both intra- and inter-fraction effects seen inthe OARs dose in some patients. CONCLUSIONS: We investigated the motioneffect in RapidArc Lung SBRT delivery in 5 patients. Negligible variations were shown for target coverage. However the motion effects were observed in high dose distribution and volume. Some OARs dose distributions were affected by the motion.

Tunneling resonances and coherence in an optical lattice.

The center-of-mass quantization of atoms trapped in a gray optical lattice is observed to manifest itself in the steady-state properties of the atoms. Modulations in the lifetime and macroscopic magnetization as a function of an applied B field are attributed to quantum mechanical tunneling resonances and are shown to exist only under conditions which afford spatial coherence of the trapped atoms over several lattice wells and coherence times that exceed the tunneling period.

A comparative study of third-order nonlinear optical properties of silver phenylacetylide and related compounds via ultrafast optical Kerr effect measurements.

A comparative study of the third-order nonlinear optical properties, via the newly developed heterodyned optical Kerr effect (OHD-OKE) measurements, of silver phenylacetylide and related compounds is reported. [AgC[triple bond]CC(6)H(5)](n) (1) was found to exhibit efficient third-order nonlinear optical susceptibility chi((3)) of 2.4 x 10(-14) esu, and second hyperpolarizability gamma of 9.07 x 10(-32) esu. These results are compared with those of two related silver phenylacetylide compounds, namely, a double salt, (silver phenylacetylide).(silver tert-butylthiolate) [AgC[triple bond]CC(6)H(5).AgS(t-C(4)H(9))](n) complex (2), and a cluster, triphenylphosphine silver phenylacetylide tetramer, [(C(6)H(5))(3)PAgC[triple bond]CC(6)H(5)](4) (3), as well as that of the related organic polymer polyphenylacetylene (4). These four compounds represent different types of phenylacetylide derivatives: 1 is an organometallic polymer, 2 a polymeric double salt, 3 a discrete metal cluster, and 4 an organic polymer. It was found that the third-order optical nonlinear response was enhanced by the incorporation of silver d electrons into the delocalized conjugated organic pi system, and its magnitude is highly dependent upon the extent of the pi delocalization. Specifically, the relative magnitudes of chi((3)) and gamma follow the order silver phenylacetylide polymer (1) > (silver phenylacetylide).(silver tert-butylthiolate) double salt (2) > polyphenylacetylene polymer (4) > tetrameric (triphenylphosphine silver phenylacetylide)(4) cluster (3). The observed trend may be attributed to the decreasing length of pi conjugation. It is interesting to note that the incorporation of Ag(I) into the polymeric framework of polyphenylacetylene enhances the chi((3)) by 25-fold for the same degree of polymerization (n = 7). The signs of chi((3)) and gamma, which are related to the response mechanisms, were found to be solvent dependent.

Synthesis and Structure of [DB24C8)Na][Cd(SCN)3. Formation of a novel linear Cd...Cd...Cd chain with a mer-CdN3S3 coordination confirmation and new coiled [(DB24C8)Na]+ cation.

We report herein a novel coordination solid, [(DB24C8)Na][Cd(SCN)3] (6) (DB24C8 denotes dibenzo-24-crown-8), which exhibits a new type of [Cd(SCN)3-]infinity chain with two unusual stereochemical characteristics: (1) a mer-CdN3S3 coordination and (2) a linear Cd chain with a Cd...Cd...Cd angle of 180 degrees. In addition, the [(DB24C8)Na]+ monocation adopts a new structural type-a coiled structure-for the combination of crown ether DB24C8 and alkali metal Na+. The title compound crystallizes in a monoclinic unit cell of C2/c space group symmetry with lattice parameters a = 16.110(8) A, b = 20.380(5) A, c = 11.01(1) A, beta = 119.87(3) degrees, and Z = 4. The arrangement of the [Cd(SCN)3-](infinity) chains in the crystal lattice in the title compound is approximately hexagonal, creating triangular channels which are filled with [(DB24C8)Na]+ monocations. It was previously reasoned by us that the coiled [(DB24C8)Na]+ monocation, which lacks inversion or mirror symmetries, should enhance the tendency for the formation of the noncentrosymmetric space group of the title crystal, making it a potential second-order nonlinear optical crystal. Interestingly, however, the title compound crystallizes in a centrosymmetric space group (C2/c) and gives rise to no second harmonic generation (SHG). Previously known [Cd(SCN)3-](infinity) chains adopt fac-CdN3S3 coordination and a zigzag Cd chain configuration with a Cd...Cd...Cd angle of 165 degrees. The zigzag chains can align in either parallel or antiparallel fashion, resulting in efficient or no SHG effects, respectively. The linear Cd.Cd.Cd chain configuration observed in the title compound, on the other hand, makes it indistinguishable between parallel and antiparallel alignments. It is concluded that, to ensure the formation of noncentrosymmetric space groups, it is necessary to employ optically pure chiral cations as spacers and/or controllers. Furthermore, to enhance the nonlinear optical responses, [Cd(SCN)3-]infinity chains with fac-CdN3S3 coordination and parallel alignments of the zigzag Cd chains should be used.

Wide spectral range nonlinear optical crystals of one-dimensional coordination solids [Et4N][Cd(SCN)3] and [Et4N][Cd(SeCN)3] and the general design criteria for [R4N][Cd(XCN)3] (Where R = Alkyl and X = S, Se, Te) as NLO crystals.

We report herein two new nonlinear optical (NLO) crystals, [Et4N][Cd(XCN)3], where X = S (1) and Se (2), that are transparent from 220 to 3300 nm, covering the entire near-ultraviolet, the visible, and the near-infrared spectral regions and giving rise to a very wide and continuous optical window, which is useful for many frequency conversion applications. Both 1 and 2 exhibit highly efficient second harmonic generation (SHG) as measured via the Kurtz-Perry method. The corresponding [Me4N]+ salts, [Me4N][Cd(XCN)3 where X = S (3) and Se (4), show no SHG effects. All four structures adopt noncentrosymmetric space groups (Cmc2(1) for 1 and 2 and Pna2(1) for 3 and presumably 4) and are based on one-dimensional anionic [Cd(XCN)3-] infinity zigzag chains. However, a detailed analysis of the structures of [R4N][Cd(XCN)3], where R = Et, Me and X = S, Se revealed that the difference in the second-order nonlinear responses of the Et4N+ salts (1 and 2) and the Me4N+ salts (3 and 4) is attributable to the relative alignment of the [Cd(XCN)3-] infinity zigzag chains, being parallel in the crystals of 1 and 2 but antiparallel in the crystals of 3 and 4. Also reported, for the first time, are the synthesis and crystal structure of [Et4N][Cd(SeCN)3] (2). Compound 2 crystallizes in an orthorhombic unit cell of Cmc21 space group symmetry with lattice parameters of 9.938(1) A, 16.868(2) A, 11.054(1) A, and Z = 4. Other issues related to the molecular and crystal engineering of this class of NLO materials are also discussed.

Clusters of clusters: self-organization and self-similarity in the intermediate stages of cluster growth of Au-Ag supraclusters.

A systematic structural investigation of a new series of high-nuclearity Au-Ag clusters containing 25, 37, 38, and 46 metal atoms led to the description of these clusters as "clusters of clusters" based on vertex-sharing icosahedra as building blocks. Based on the observed structures, a growth sequence is proposed here for the formation of these secondary clusters (clusters of clusters) from a single 13-atom icosahedron to a 127-atom icosahedron of icosahedra via successive additions of vertex-sharing icosahedral units. This cluster-of-clusters growth mechanism parallels the atom-by-atom growth pathway for the primary clusters from a single atom to a 13-atom icosahedron. It is hypothesized that the formation of these clusters of clusters is a manifestation of the spontaneous self-organization and self-similarity processes often observed in nature. It is conceivable that the concept of cluster of clusters may be important in the intermediate stages of some cluster growth as exemplified by the polyicosahedral growth of Au-Ag supraclusters.

Core dimensions in the 3Fe cluster of Desulfovibrio gigas ferredoxin II by extended X-ray absorption fine structure spectroscopy.

We have obtained the iron K-edge extended X-ray adsorption fine structure spectra of the 3Fe ferredoxin II of Desulfovibrio gigas in the oxidized and reduced states. For both states, interpretation of the EXAFS data suggests that the Fe-S first shell coordination distance is near 2.25 A, in agreement with crystallographic studies of model compounds and proteins containing 2Fe-2S and 4Fe-4S centers, as well as with a recent crystallographic study of Azotobacter vinelandii ferredoxin I (Ghosh, D., Furey, W., Jr., O'Donnell, S., and Stout, C. D. (1981) J. Biol. Chem. 256, 4185-4192). The apparent Fe-Fe distance we obtain for the desulfovibrio protein (2.7 A) also agrees with similar distances seen in other Fe-S centers, except with the 3Fe cluster in the Azotobacter vinelandii ferredoxin I structure, for which an Fe-Fe distance of 4.2 A was reported. We conclude that either the two 3Fe ferredoxins have substantially different core dimensions, a possibility apparently unique to 3Fe centers among known Fe-S systems in proteins, or that one (or more) of the structural studies is in substantial error.