Commissioning of a 1.6 m long 16mm period superconducting undulator at the Australian Synchrotron

A 1.6 m long 16 mm period superconducting undulator (SCU16) has been installed and commissioned at the Australian Synchrotron. The SCU16, developed by Bilfinger Noell GmbH, is based on the SCU20 currently operating at at KIT. The SCU16 is conduction cooled with a maximum on axis field of 1.084 T and a fixed effective vacuum gap of 5.5 mm. The design and performance of the longest superconducting undulator at a light source will be presented

A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.

c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables METN375S to interact with HER2 in a ligand-independent fashion. The resultant METN375S/HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis. Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing METN375S. These results establish METN375S as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies

A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.

c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables METN375S to interact with HER2 in a ligand-independent fashion. The resultant METN375S/HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis. Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing METN375S. These results establish METN375S as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A study of coherent synchrotron radiation: intensity enhancement of the far-IR spectrum by exciting single bunch instabilities

The storage ring at the Australian Synchrotron Light Source (ASLS) is an intense source of radiation that is used in applications such as spectroscopy and imaging. The source of the radiation comes from individual electrons that are grouped in bunches and confined in the storage ring. The observed radiation is usually temporally incoherent and the radiation power scales linearly with the number of electrons, N. If all the electrons have a longitudinal distribution of σz, the degree of temporal coherence of the emitted radiation increases and the power of the radiation will scale as N2 for radiated wavelengths, λ, that are longer than 2πσz. Using this property of coherent synchrotron radiation (CSR), the intensity of the observed radiation at wavelengths longer than λ can be increased by a factor of N above that of the incoherent radiation. With typical values of N around 10^9, the potential enhancement of the radiation power is significant. This property of CSR is used to enhance the radiation in the Far-IR (Footnote: Far Infrared.) spectrum between the wavelengths of 0.3 mm (1 THz) and 3 mm (100 GHz). This region of the radiation spectrum is used by the Far-IR beamline at the ASLS for absorption spectroscopy. The increase in the radiation power will benefit the beamline by increasing the signal-to-noise ratio of the beamline's detector, thereby enabling the measurement of spectra for weakly absorbing materials and providing the capacity to measure spectra at longer wavelengths. To generate CSR, the bunch length in the storage ring is shortened by reducing the momentum compaction factor, αc, using the negative dispersion technique. When αc is reduced by a factor of 100, the storage ring becomes sensitive to perturbations introduced by the accelerator subsystems (e.g., RF system, magnet power supplies and stray electromagnetic fields). An investigation of the various accelerator subsystems showed that the strongest perturbation is at the mains AC frequency of 50 Hz and is caused by currents conducted through the metallic elements of the storage ring. These perturbations limit the shortest achievable bunch length to 1 ps at an electron energy of 3 GeV. A bunch length of 1 ps is not short enough to enhance the radiation power at wavelengths less than 0.3 mm (1 THz). A reduction in the electron beam energy is required to achieve shorter bunch lengths. An alternative method for generating CSR is to excite a longitudinal single bunch instability. The instability that modulates the charge density can be utilised to create periodic bursts of CSR. The onset of the instability creates quasi-periodic bursts of CSR. For CSR to be used as a source of IR radiation, the frequency and the intensity of the bursts of radiation must be constant. Any fluctuation in the frequency or intensity reduces the signal-to-noise ratio (SNR) of any measurements using the CSR. In this thesis a method is developed for optimising the SNR using a microwave diode detector. A microwave diode detector with a fast response time of 1 ns is used to characterise the temporal profile of the CSR bursts. The measurements show a temporal profile with growth and damping rates of 20 kHz which far exceed the natural damping rate expected for the storage ring. Moreover, the results show small oscillations that are believed to be the result of the filamentation of the electron bunch. The observed features of the growth rate, decay rate and small oscillations closely resemble the behaviour seen in numerical simulations by Venturini and Warnock, which show a CSR driven microbunching instability. This model provides a framework for describing the process leading to bursts of CSR. The microwave diode detector is also used to measure the temporal profile's dependence on N. The data collected was used to calculate the change in the SNR to find the optimal working current where the SNR is maximised. The results show that the SNR depends on the burst frequency; in particular when a harmonic of the burst frequency is the same as the characteristic longitudinal oscillation frequency (synchrotron frequency). Measurements were also conducted on the beamline, and the results agree with the observations made using the diode detector. These observations were used to define a low alpha lattice configuration to generate CSR. The CSR created from this configuration was used to measure the absorption spectrum of a sample of N2O with a spectral resolution of 0.025 cm(-1) (750 MHz). For these measurements a Bruker IFS125HR spectrometer was utilised on the IR beamline. This is a challenging measurement as the scan takes 15 minutes to complete, during which the intensity of the source must remain constant. Any fluctuation in the intensity will introduce noise into the spectrum. The results of 20 scans show good agreement between our measurements and previously documented absorption lines for N2O. The outcome shows that the quasi-periodic bursts of CSR can be used to extend the utility of the IR beamline into the Far-IR spectrum. In summary we have used a diode detector to characterise the burst of CSR at the onset of the microwave instability. We have shown that the measurements with a microwave diode detector are in agreement with numerical simulations carried out for this form of instability. A method has also been developed to create a low alpha operational mode that generates bursts of CSR optimised for the IR beamline

A study of coherent synchrotron radiation: intensity enhancement of the far-IR spectrum by exciting single bunch instabilities

The storage ring at the Australian Synchrotron Light Source (ASLS) is an intense source of radiation that is used in applications such as spectroscopy and imaging. The source of the radiation comes from individual electrons that are grouped in bunches and confined in the storage ring. The observed radiation is usually temporally incoherent and the radiation power scales linearly with the number of electrons, N. If all the electrons have a longitudinal distribution of σz, the degree of temporal coherence of the emitted radiation increases and the power of the radiation will scale as N2 for radiated wavelengths, λ, that are longer than 2πσz. Using this property of coherent synchrotron radiation (CSR), the intensity of the observed radiation at wavelengths longer than λ can be increased by a factor of N above that of the incoherent radiation. With typical values of N around 10^9, the potential enhancement of the radiation power is significant. This property of CSR is used to enhance the radiation in the Far-IR (Footnote: Far Infrared.) spectrum between the wavelengths of 0.3 mm (1 THz) and 3 mm (100 GHz). This region of the radiation spectrum is used by the Far-IR beamline at the ASLS for absorption spectroscopy. The increase in the radiation power will benefit the beamline by increasing the signal-to-noise ratio of the beamline's detector, thereby enabling the measurement of spectra for weakly absorbing materials and providing the capacity to measure spectra at longer wavelengths. To generate CSR, the bunch length in the storage ring is shortened by reducing the momentum compaction factor, αc, using the negative dispersion technique. When αc is reduced by a factor of 100, the storage ring becomes sensitive to perturbations introduced by the accelerator subsystems (e.g., RF system, magnet power supplies and stray electromagnetic fields). An investigation of the various accelerator subsystems showed that the strongest perturbation is at the mains AC frequency of 50 Hz and is caused by currents conducted through the metallic elements of the storage ring. These perturbations limit the shortest achievable bunch length to 1 ps at an electron energy of 3 GeV. A bunch length of 1 ps is not short enough to enhance the radiation power at wavelengths less than 0.3 mm (1 THz). A reduction in the electron beam energy is required to achieve shorter bunch lengths. An alternative method for generating CSR is to excite a longitudinal single bunch instability. The instability that modulates the charge density can be utilised to create periodic bursts of CSR. The onset of the instability creates quasi-periodic bursts of CSR. For CSR to be used as a source of IR radiation, the frequency and the intensity of the bursts of radiation must be constant. Any fluctuation in the frequency or intensity reduces the signal-to-noise ratio (SNR) of any measurements using the CSR. In this thesis a method is developed for optimising the SNR using a microwave diode detector. A microwave diode detector with a fast response time of 1 ns is used to characterise the temporal profile of the CSR bursts. The measurements show a temporal profile with growth and damping rates of 20 kHz which far exceed the natural damping rate expected for the storage ring. Moreover, the results show small oscillations that are believed to be the result of the filamentation of the electron bunch. The observed features of the growth rate, decay rate and small oscillations closely resemble the behaviour seen in numerical simulations by Venturini and Warnock, which show a CSR driven microbunching instability. This model provides a framework for describing the process leading to bursts of CSR. The microwave diode detector is also used to measure the temporal profile's dependence on N. The data collected was used to calculate the change in the SNR to find the optimal working current where the SNR is maximised. The results show that the SNR depends on the burst frequency; in particular when a harmonic of the burst frequency is the same as the characteristic longitudinal oscillation frequency (synchrotron frequency). Measurements were also conducted on the beamline, and the results agree with the observations made using the diode detector. These observations were used to define a low alpha lattice configuration to generate CSR. The CSR created from this configuration was used to measure the absorption spectrum of a sample of N2O with a spectral resolution of 0.025 cm(-1) (750 MHz). For these measurements a Bruker IFS125HR spectrometer was utilised on the IR beamline. This is a challenging measurement as the scan takes 15 minutes to complete, during which the intensity of the source must remain constant. Any fluctuation in the intensity will introduce noise into the spectrum. The results of 20 scans show good agreement between our measurements and previously documented absorption lines for N2O. The outcome shows that the quasi-periodic bursts of CSR can be used to extend the utility of the IR beamline into the Far-IR spectrum. In summary we have used a diode detector to characterise the burst of CSR at the onset of the microwave instability. We have shown that the measurements with a microwave diode detector are in agreement with numerical simulations carried out for this form of instability. A method has also been developed to create a low alpha operational mode that generates bursts of CSR optimised for the IR beamline

Plans for an Australian XFEL Using a CLIC X-band Linac

Preliminary plans are presented for a sub-Angstrom wavelength XFEL at the Australian Synchrotron light source site. The design is based around a 6 GeV x-band linac from the CLIC Project. One of the motivations for the design is to have an XFEL co-located on the site with existing storage ring based synchrotron light source. The desire and ability of the Australian photon science community to win beamtime on existing XFELs has lead to this design study to plan for a future machine in Australia. The technology choice is also driven by the Australian participation in the CLIC Collaboration and the local HEP community

X-band Technology for FEL Sources

As is widely recognized, fourth generation Light Sources are based on FELs driven by Linacs. Soft and hard X-ray FEL facilities are presently operational at several laboratories, SLAC (LCLS), Spring-8 (SACLA), Elettra-Sincrotrone Trieste (FERMI), DESY (FLASH), or are in the construction phase, PSI (SwissFEL), PAL (PAL-XFEL), DESY (European X-FEL), SLAC (LCLS II), or are newly proposed in many laboratories. Most of the above mentioned facilities use NC S-band (3 GHz) or C-band (6 GHz) linacs for generating a multi-GeV low emittance beam. The use of the C-band increases the linac operating gradients, with an overall reduction of the machine length and cost. These advantages, however, can be further enhanced by using X-band (12 GHz) linacs that operate with gradients twice that given by C-band technology. With the low bunch charge option, currently considered for future X-ray FELs, X-band technology offers a low cost and compact solution for generating multi-GeV, low emittance bunches. The paper reports the ongoing activities in the framework of a collaboration among several laboratories for the development and validation of X-band technology for FEL based photon sources

The X-Band FEL Collaboration

The X-band FEL collaboration is currently designing an X-ray free-electron laser based on X-band acceleration technology. Due to the higher accelerating gradients achievable with X-band technology, a X-band normal conducting linac can be shorter and therefore potentially cost efficient than what is achievable with lower frequency structures. This cost reduction of future FEL facilities addresses the growing demand of the user community for coherent X-rays. The X-band FEL collaboration consists of 12 institutes and universities that jointly work on the preparation of design reports for the specific FEL projects. In this paper, we report on the on-going activities, the basic parameter choice, and the integrated simulation results. We also outline the interest of the X-band FEL collaboration to use the electron linac CALIFES at CERN to test FEL concepts and technologies relevant for the X-band FEL collaboration