Fibroadenomas are the most common breast tumors in women under 30 (refs. 1,2). Exome sequencing of eight fibroadenomas with matching whole-blood samples revealed recurrent somatic mutations solely in ...MED12, which encodes a Mediator complex subunit. Targeted sequencing of an additional 90 fibroadenomas confirmed highly frequent MED12 exon 2 mutations (58/98, 59%) that are probably somatic, with 71% of mutations occurring in codon 44. Using laser capture microdissection, we show that MED12 fibroadenoma mutations are present in stromal but not epithelial mammary cells. Expression profiling of MED12-mutated and wild-type fibroadenomas revealed that MED12 mutations are associated with dysregulated estrogen signaling and extracellular matrix organization. The fibroadenoma MED12 mutation spectrum is nearly identical to that of previously reported MED12 lesions in uterine leiomyoma but not those of other tumors. Benign tumors of the breast and uterus, both of which are key target tissues of estrogen, may thus share a common genetic basis underpinned by highly frequent and specific MED12 mutations.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The accurate computation of Hamiltonian ground, excited and thermal states on quantum computers stands to impact many problems in the physical and computer sciences, from quantum simulation to ...machine learning. Given the challenges posed in constructing large-scale quantum computers, these tasks should be carried out in a resource-efficient way. In this regard, existing techniques based on phase estimation or variational algorithms display potential disadvantages; phase estimation requires deep circuits with ancillae, that are hard to execute reliably without error correction, while variational algorithms, while flexible with respect to circuit depth, entail additional high-dimensional classical optimization. Here, we introduce the quantum imaginary time evolution and quantum Lanczos algorithms, which are analogues of classical algorithms for finding ground and excited states. Compared with their classical counterparts, they require exponentially less space and time per iteration, and can be implemented without deep circuits and ancillae, or high-dimensional optimization. We furthermore discuss quantum imaginary time evolution as a subroutine to generate Gibbs averages through an analogue of minimally entangled typical thermal states. Finally, we demonstrate the potential of these algorithms via an implementation using exact classical emulation as well as through prototype circuits on the Rigetti quantum virtual machine and Aspen-1 quantum processing unit.The quantum imaginary time evolution and Lanczos algorithms offer a resource-efficient way to compute ground or excited states of target Hamiltonians on quantum computers. This offers promise for quantum simulation on near-term noisy devices.
It has been widely accepted worldwide that global warming is by far the greatest threat and challenge in the new millennium. In order to stop global warming and to promote sustainable development, ...renewable energy is a perfect solution to achieve both targets. Presently million hectares of land in Malaysia is occupied with oil palm plantation generating huge quantities of biomass. In this context, biomass from oil palm industries appears to be a very promising alternative as a source of raw materials including renewable energy in Malaysia. Thus, this paper aims to present current scenario of biomass in Malaysia covering issues on availability and sustainability of feedstock as well as current and possible utilization of oil palm biomass. This paper will also discuss feasibility of some biomass conversion technologies and some ongoing projects in Malaysia related to utilization of oil palm biomass as a source of renewable energy. Based on the findings presented, it is definitely clear that Malaysia has position herself in the right path to utilize biomass as a source of renewable energy and this can act as an example to other countries in the world that has huge biomass feedstock.
CMOS platforms operating at the telecommunications wavelength either reside within the highly dissipative two-photon regime in silicon-based optical devices, or possess small nonlinearities. Bandgap ...engineering of non-stoichiometric silicon nitride using state-of-the-art fabrication techniques has led to our development of USRN (ultra-silicon-rich nitride) in the form of Si7 N3 , that possesses a high Kerr nonlinearity (2.8 × 10-13 cm2 W-1 ), an order of magnitude larger than that in stoichiometric silicon nitride. Here we experimentally demonstrate high-gain optical parametric amplification using USRN, which is compositionally tailored such that the 1,550 nm wavelength resides above the two-photon absorption edge, while still possessing large nonlinearities. Optical parametric gain of 42.5 dB, as well as cascaded four-wave mixing with gain down to the third idler is observed and attributed to the high photon efficiency achieved through operating above the two-photon absorption edge, representing one of the largest optical parametric gains to date on a CMOS platform.
The quest for renewable energy has intensified since the escalating price of crude petroleum in the recent years. Renewable energy such as biodiesel has the potential to replace petroleum-derived ...transportation fuel in the future. Biodiesel is defined as the mono-alkyl esters of long-chain fatty acids derived from vegetable oils such palm oil, rapeseed and soybean. Currently, more than 80% of the world biodiesel productions are from rapeseed oil. However, the cost of palm oil which is at least US$ 200 per tonne cheaper than rapeseed oil indicates that palm oil could be a more suitable and attractive candidate as the source of biodiesel compared to other vegetable oils. Although palm oil is known to be a multi-purpose vegetable oil with products ranging from food to biodiesel, there are a lot of issues surrounding palm oil production. Nevertheless, some of these issues reported in the literature were found to be misleading and are thus confusing the public perception on palm oil. Thus, the aim of this paper is to highlight and clarify the negative issues reported in the literature surrounding palm oil production. Apart from that, various policies or/and strategies that will lead to a more sustainable production and development of palm oil industries will also be proposed. Hence, palm oil will be able to become the leading vegetable oil in terms of food and non-food production, especially as the main source of renewable energy, biodiesel.
CMOS‐compatible nonlinear optics platforms with negligible nonlinear losses and high nonlinearity are of great merit. Silicon, silicon nitride and Hydex glass have made significant headway in ...nonlinear optical signal processing, though none of these platforms possesses the highly sought after combination of high nonlinearity and negligible nonlinear losses. In this manuscript, we present a nonlinear optics platform based on silicon‐rich nitride, deposited at a low temperature of 250°C compatible with back‐end CMOS processing. The silicon‐rich nitride is designed and engineered in composition to have a bandgap of 2.05 eV, such that the two‐photon absorption edge is well below 1.55 μm. The designed and developed waveguides have a nonlinear parameter of 550 W−1/m, 500 times larger than that in silicon nitride waveguides, while at the same time not possessing two‐photon and free‐carrier losses. Using 500‐fs pulses, we generate supercontinuum exceeding 0.6 of an octave.
We present a nonlinear optics platform based on silicon rich nitride, deposited at 250°C and compatible with back‐end CMOS processing. The silicon rich nitride is engineered to have a band gap of 2.05 eV, such that the two photon absorption edge is well below 1.55 μm. Developed waveguides have a nonlinear parameter of 550W−1/m and negligible nonlinear losses. Using 500 fs pulses, we generate supercontinuum exceeding 0.6 of an octave.
Background
The aim of this study was to compare the efficacy and safety of micropulse and continuous wave diode transscleral cyclophotocoagulation in refractory glaucoma.
Design
Randomized, ...comparative, exploratory study in a tertiary hospital setting.
Participants
Patients with refractory, end‐stage glaucoma.
Methods
Forty‐eight patients were randomized to either treatment. The intraocular pressure, visual acuity, number of medicines and repeat treatment were monitored for 18 months. Complications that include visual acuity decline, prolonged anterior chamber inflammation, phthisis bulbi, scleral thinning and ocular pain were noted.
Main Outcome Measure
Intraocular pressure between 6 and 21 mmHg and at least a 30% reduction with or without anti‐glaucoma medications after 18 months.
Results
A successful primary outcome was achieved in 75% of patients who underwent micropulse cyclophotocoagulation and 29% of patients who received continuous wave cyclophotocoagulation after 12 months (P < 0.01). At 18 months, successful outcome was 52% and 30% (P = 0.13), respectively. The mean intraocular pressure was reduced by 45% in both groups (P = 0.70) from a baseline of 36.5 mmHg and 35.0 mmHg (P = 0.50) after 17.5 ± 1.6 months (range 16–19) follow up. No significant difference in retreatment rates or number of intraocular pressure lowering medications was noted. The ocular complication rate was higher in continuous wave treated eyes (P = 0.01).
Conclusion
Diode transscleral cyclophotocoagulation in both micropulse and continuous modes was effective in lowering intraocular pressure. The micropulse mode provided a more consistent and predictable effect in lowering intraocular pressure with minimal ocular complications.
Disposal of waste palm cooking oil (WPCO) via an environmental-friendly route is of major importance in the quest for sustainable development. In this study, WPCO was utilized instead of refined ...vegetable oils as the source of triglycerides for biodiesel production. WPCO contains several impurities, such as water and free fatty acids, which limit its application in catalytic transesterification processes. Consequently, a catalyst-free process using supercritical methanol was employed to investigate the potential of WPCO as an economical feedstock for biodiesel production. The parameters that influence the reaction, including reaction time, temperature and the molar ratio of alcohol to oil, were investigated. For comparison purposes, refined palm oil (RPO) was also subjected to supercritical methanol reaction and it was found that both processes produced comparable optimum yields of 80% at their respective optimum conditions. Hence, it can be concluded that WPCO has high potential as an economical and practical future source of biodiesel.
Summary
Background
Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral ...cutaneous melanoma (NAM) in Asians are not well understood.
Objectives
To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma.
Methods
We performed comprehensive genomic profiling of 409 cancer‐associated genes, using next‐generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs.
Results
Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild‐type (triple‐WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell‐cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell‐cycle aberrations were independent prognostic factors of melanoma‐specific survival.
Conclusions
This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians.
What's already known about this topic?
Mutation frequencies of driver genes vary between melanoma subtypes.
Acral melanoma is the most common subtype of melanoma in Asians.
KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype
What does this study add?
NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment.
Melanomas with cell‐cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration.
What is the translational message?
Cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival.
These observations should be explored further for future drug development.
Linked Comment: Johansson. Br J Dermatol 2020; 182:1085.
Plain language summary available online
In this research, the negative effective mass behavior of elastic/mechanical metamaterials is exhibited by a cantilever-in-mass structure as a proposed design for creating frequency stopping band ...gaps, based on local resonance of the internal structure. The mass-in-mass unit cell model is transformed into a cantilever-in-mass model using the Bernoulli-Euler beam theory. An analytical model of the cantilever-in-mass structure is derived and the effects of geometrical dimensions and material parameters to create frequency band gaps are examined. A two-dimensional finite element model is created to validate the analytical results, and excellent agreement is achieved. The analytical model establishes an easily tunable metamaterial design to realize wave attenuation based on locally resonant frequency. To demonstrate feasibility for 3D printing, the analytical model is employed to design and fabricate 3D printable mechanical metamaterial. A three-dimensional numerical experiment is performed using COMSOL Multiphysics to validate the wave attenuation performance. Results show that the cantilever-in-mass metamaterial is capable of mitigating stress waves at the desired resonance frequency. Our study successfully presents the use of one constituent material to create a 3D printed cantilever-in-mass metamaterial with negative effective mass density for stress wave mitigation purposes.
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