An ultra-stable, high-power cw Nd:YAG laser system, developed for the ground-based gravitational wave detector Advanced LIGO (Laser Interferometer Gravitational-Wave Observatory), was comprehensively ...characterized. Laser power, frequency, beam pointing and beam quality were simultaneously stabilized using different active and passive schemes. The output beam, the performance of the stabilization, and the cross-coupling between different stabilization feedback control loops were characterized and found to fulfill most design requirements. The employed stabilization schemes and the achieved performance are of relevance to many high-precision optical experiments.
Plastic pollution in Ambon Bay Smeets, R; Winkelmann, L; Knoester, R ...
IOP conference series. Earth and environmental science,
07/2023, Volume:
1207, Issue:
1
Journal Article
Peer reviewed
Open access
Abstract
Ambon has problems with plastic pollution, both in the rivers and the bay. Due to faults in the waste system, 60 tons of waste is not collected in Kota Ambon. This waste ends up in illegal ...landfills, the waste is burned or thrown in the water. The plastic pollution in the bay contributes to the global problem of plastic soup. Research was conducted based on question; which recommendations can be given to collect the floating plastics in the rivers around Ambon Market by using the litter traps. To answer the main question, sub-questions are drafted covering the sources of pollution, possible locations, and the possibilities for a trap. The research is conducted using different methods that is interview to local experts, observation, literature research and talks to residents. Most of the plastic found are single-use plastics, like water and food packaging materials. The most feasible location for a litter trap is the end of Batu Merah River due to the abundance of plastic, the depth, and the nearby presence of Speed
Sampah
. The concept litter trap showed that this device could be effective at Batu Merah River. Further research is needed to create a more definitive solution for plastic pollution. Several aspects must be taken into account, such as the circumstances like the rainy season, sedimentation, current, and tide can impact the working of the litter trap and should be considered during the designing process.
A solid-state laser system for the next generation of gravitational wave detectors with an output power of 220 W at the wavelength of 1064 nm is presented. Single-frequency operation of the laser was ...achieved by injection-locking of a high-power ring oscillator to an amplified non-planar ring oscillator (NPRO) following the Pound–Drever–Hall scheme. The high-power stage which features four longitudinally pumped Nd:YAG laser crystals as active media in a ring resonator configuration was designed for reliable long term operation. Using a non-confocal ring cavity to filter the output beam, a pure TEM
00
mode with 168 W output power was obtained.
Flavopiridol, a cyclin-dependent kinase inhibitor, has promising clinical activity when combined with chemotherapy. Preclinical data indicate that flavopiridol enhances oxaliplatin- and fluorouracil ...(5FU)-induced apoptosis in a sequence-dependent manner.
We conducted a phase I trial of flavopiridol + FOLFOX (folinic acid, 5FU, and oxaliplatin) for advanced solid tumors. Flavopiridol was administered every 2 weeks with oxaliplatin before 5FU, based on sequence-dependent growth inhibition. Flavopiridol pharmacokinetics and p53 status were evaluated.
Forty-eight patients were treated on study. With dose escalation of oxaliplatin (85 mg/m(2)) and 5FU (2,400 mg/m(2)), dose-limiting toxicities included hyponatremia, thrombocytopenia, and neutropenia. 5FU was subsequently reduced to allow for dose escalation of flavopiridol. Dose-limiting toxicities with escalation of flavopiridol were nausea, vomiting, and neutropenia. The maximum tolerated dose was 70 mg/m(2) flavopiridol, 85 mg/m(2) oxaliplatin, and 1,800 mg/m(2) 5FU continuous infusion over 48 hours. Clinical activity was noted in platinum-refractory germ cell tumors: 3 of 9 (33%) evaluable patients showed a partial response on imaging and 7 of 10 (70%) had a decline in serum tumor markers. Responses were also observed in pancreatic, gastric, and sweat gland tumors. Flavopiridol pharmacokinetics had significant interpatient variability. At the maximum tolerated dose, tumor samples were p53 mutant (>30% positive cells) for responders and p53 wild-type for nonresponders.
Flavopiridol with FOLFOX is a safe and tolerable regimen. Promising clinical activity was seen across tumor types. Encouraging results in the platinum-refractory germ cell tumor population has prompted a phase II trial that is currently open for accrual.
The Laser Interferometer Gravitational Wave Observatory (LIGO) consists of two widely separated 4 km laser interferometers designed to detect gravitational waves from distant astrophysical sources in ...the frequency range from 10 Hz to 10 kHz. The first observation run of the Advanced LIGO detectors started in September 2015 and ended in January 2016. A strain sensitivity of better than 10 super(-23)/radicalHz was achieved around 100 Hz. Understanding both the fundamental and the technical noise sources was critical for increasing the astrophysical strain sensitivity. The average distance at which coalescing binary black hole systems with individual masses of 30Mmiddot could be detected above a signal-to-noise ratio (SNR) of 8 was 1.3 Gpc, and the range for binary neutron star inspirals was about 75 Mpc. With respect to the initial detectors, the observable volume of the Universe increased by a factor 69 and 43, respectively. These improvements helped Advanced LIGO to detect the gravitational wave signal from the binary black hole coalescence, known as GW150914.
Programmed death 1 (PD-1) is an immune checkpoint that provides inhibitory signals to the immune system in order to modulate the activity of T cells in peripheral tissues and maintain self-tolerance ...in the setting of infection and inflammation. In cancer, the immune checkpoints are exploited so that the tumor cells are able to evade the immune system. Immune checkpoint inhibitors are a type of cancer immunotherapy that targets pathways such as PD-1 in order to reinvigorate and enhance the immune response against tumor cells. The US Food and Drug Administration (FDA) has approved 2 PD-1 inhibitors, nivolumab and pembrolizumab, and several others are under investigation. Although PD-1 inhibitors have demonstrated activity in many different types of malignancies, FDA approval has been granted only in melanoma and in non-small cell lung cancer (NSCLC). Identifying biomarkers that can predict response to PD-1 inhibitors is critical to maximizing the benefit of these agents. Future directions for PD-1 inhibitors include investigation of combination therapies, use in malignancies other than melanoma and NSCLC, and refinement of biomarkers.
This paper tests for the importance of non-pecuniary costs of unemployment using a longitudinal data-set on life-satisfaction of working-age men in Germany. We show that unemployment has a large ...detrimental effect on satisfaction after individual specific fixed effects are controlled for. The non-pecuniary effect is much larger than the effect that stems from the associated loss of income.
Purpose
Phosphatidylinositol-3-kinase I (PI3K) inhibition sensitizes a wide range of cancer cell lines to platinum/taxane-based chemotherapy. This phase I study combines buparlisib, a pan-class 1A ...PI3K inhibitor, with two schedules of carboplatin and paclitaxel for patients with advanced solid tumors (ClinicalTrials.gov, NCT01297452).
Methods
There were two regimens: Group 1 received carboplatin AUC 5 and paclitaxel 175 mg/m
2
, on day 1 of a 21-day cycle with pegfilgrastim support; Group 2 received carboplatin AUC 5 (day 1) and paclitaxel 80 mg/m
2
(days 1, 8, and 15) on a 28-day cycle without growth factor support. In both groups, three dose levels of buparlisib were explored: 50, 80, and 100 mg/day. Primary endpoint was to identify recommended phase II doses of buparlisib in both groups.
Results
Thirty subjects enrolled, 16 in Group 1 and 14 in Group 2. The DLTs were elevated alkaline phosphatase (
n
= 1) and uncomplicated neutropenia (
n
= 2). The median numbers of cycles were 5 (Group 1) and 6 (Group 2). The MTDs for buparlisib were 100 mg/day in Group 1 and 80 mg/day in Group 2. Among 25 patients with measurable disease, the confirmed objective response rate was 20 % (one complete response, four partial responses). Among three patients with known loss of PTEN expression, all derived clinical benefit from treatment.
Conclusion
The addition of buparlisib to carboplatin + paclitaxel was well tolerated, and preliminary activity was notable against tumors with loss of PTEN expression.