Microstructure of GaN Grown on (111) Si by MOCVD

Gallium nitride was grown on (111) Si by MOCVD by depositing an AIN buffer at 108O"C and then GaN at 1060 {degrees}C. The 2.2pm layer cracked along {1-100} planes upon cooling to room temperature, but remained adherent. We were able to examine the microstructure of material between cracks with TEM. The character and arrangement of dislocation are much like those of GaN grown on Al{sub 2}O{sub 3}: -2/3 pure edge and - 1/3 mixed (edge + screw), arranged in boundaries around domains of GaN that are slightly disoriented with respect to neighboring material. The 30 nm AIN buffer is continuous, indicating that AIN wets the Si, in contrast to GaN on Al{sub 2}O{sub 3}

Size Distributions of Gold Nanoclusters Studied by Liquid Chromatography

The authors report high pressure liquid chromatography, (HPLC), and transmission electron microscopy, (TEM), studies of the size distributions of nanosize gold clusters dispersed in organic solvents. These metal clusters are synthesized in inverse micelles at room temperature and those investigated range in diameter from 1--10 nm. HPLC is sensitive enough to discern changes in hydrodynamic volume corresponding to only 2 carbon atoms of the passivating agent or metal core size changes of less than 4 {angstrom}. The authors have determined for the first time how the total cluster volume (metal core + passivating organic shell) changes with the size of the passivating agent

Mutational status of K- ras and TP53 genes in primary sarcomas of the heart

We investigated three patients with cardiac angiosarcomas and two with cardiac rhabdomyosarcomas, all for mutations at exons 5, 6, 7 and 8 of the p53 gene and at exon 1 of K- ras. No point mutations were observed in the p53 gene in any of the five cases; however, at exon 1 of K- ras, three patients (60%) presented the same mutation at the first base of codon 13 (G to A transition). Interestingly, this mutation was detected in both rhabdomyosarcoma and angiosarcoma histologic sarcoma types. © 2000 Cancer Research Campaig

Microsatellite alterations and TP53 mutations in plasma DNA of small-cell lung cancer patients: Follow-up study and prognostic significance

Background: Small-cell lung cancer (SCLC), one of the major types of lung cancer, is associated with many different somatic molecular genetic changes. These alterations, observed in tumor DNA, have also been identified in the plasma DNA of patients. We undertook the present study to make a prospective investigation into the correlation between abnormal plasma DNA and patient survival. Patients and methods: Thirty-five patients with SCLC were selected after histological diagnosis. Polymorphic markers (ACTBP2, UT762 and AR) were chosen for their reported high rate of alterations in SCLC and analyzed in tumor tissue, normal blood cells and plasma DNA. Furthermore, we looked for mutations of the TP53 gene in tumor and plasma DNA. Results: In 25 patients (71%) at least one molecular change precisely matching that of the primary tumor was detected in the plasma DNA. No difference in survival was observed between patients with aberrant plasma DNA and patients without plasma DNA alterations. However, patients with microsatellite modifications and TP53 mutations concomitantly, showed a significant difference (P = 0.02) in survival compared with patients bearing only one of these molecular changes. In 15 cases it was possible to find a correlation either between tumor response and disappearance of abnormal plasma DNA, or tumor progression and persistence of plasma DNA alterations. Conclusions: Free plasma DNA with molecular alterations is present to a high degree in plasma DNA of SCLC patients and may have a role as a prognostic facto

Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non–Small Cell Lung Cancer: A Phase Ib Study

Purpose: Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated preclinical activity in non–small cell lung cancer (NSCLC). A multicenter, nonrandomized, open-label phase Ib study was conducted to test safety, MTD, pharmacokinetics, and preliminary antitumor activity of abemaciclib in combination with other therapies for treatment in patients with metastatic NSCLC. Patients and Methods: An initial dose escalation phase was used to determine the MTD of twice-daily oral abemaciclib (150, 200 mg) plus pemetrexed, gemcitabine, or ramucirumab, followed by an expansion phase for each drug combination. Pemetrexed and gemcitabine were administered according to label. The abemaciclib plus ramucirumab study examined two dosing schedules. Results: The three study parts enrolled 86 patients; all received ≥1 dose of combination therapy. Across arms, the most common treatment-emergent adverse events were fatigue, diarrhea, neutropenia, decreased appetite, and nausea. The trial did not identify an abemaciclib MTD for the combination with pemetrexed or gemcitabine but did so for the combination of abemaciclib with days 1 and 8 ramucirumab (8 mg/kg). Plasma sample analysis showed that abemaciclib did not influence the pharmacokinetics of the combination agents and the combination agents did not affect abemaciclib exposure. The disease control rate was 57% for patients treated with abemaciclib–pemetrexed, 25% for abemaciclib–gemcitabine, and 54% for abemaciclib–ramucirumab. Median progression-free survival was 5.55, 1.58, and 4.83 months, respectively. Conclusions: Abemaciclib demonstrated an acceptable safety profile when dosed on a continuous twice-daily schedule in combination with pemetrexed, gemcitabine, or ramucirumab. Abemaciclib exposures remained consistent with those observed in single-agent studies

Melanopsin (Opn4) Requirement for Normal Light-Induced Circadian Phase Shifting

like the latter two groups, mammals lack functional extraocular photoreceptors (28); thus, redundancy in photoreception is confined to the retina. One challenge is to determine the relative contributions of melanopsin, rod/cone opsins, cryptochromes, and other currently uncharacterized photopigments in communicating photic information to the circadian system. Fluorescent lights (Philips F32T8/TL741 Hi-Vision, 4100 K) were used both for light pulses and for overhead lighting in the activity recording room. Light intensity on the cage floor ranged from 20 to 60 W⅐cm Ϫ2 or 70 to 280 lux for light pulses and from 10 to 30 W⅐cm Ϫ2 or 30 to 120 lux for LD and LL conditions, depending on the location of the sensor in the cage. Light was measured in both radiometric (International Light, model IL-1405 Radiometer System) and photometric (Iso-Tech, ILM 350) units of measure to facilitate comparison between traditional photoreception and circadian studies. Mice used for in situ hybridization were sacrificed at the end of the light or dark pulse and their brains were frozen on dry ice. In situ experiments were performed as described in (16). Small sample sizes precluded statistical evaluation of c-fos levels

Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study

Patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) for whom autologous hematopoietic cell transplantation (auto-HCT) had failed experienced frequent and durable responses to nivolumab in the phase 2 CheckMate 205 trial. We present updated results (median follow-up, ~5 years). Patients with R/R cHL who were brentuximab vedotin (BV)–naive (cohort A), received BV after auto-HCT (cohort B), or received BV before and/or after auto-HCT (cohort C) were administered with nivolumab 3 mg/kg IV every 2 weeks until progression or unacceptable toxicity. Patients in cohort C with complete remission (CR) for 1 year could discontinue nivolumab and resume upon relapse. Among 243 patients (cohort A, n = 63; B, n = 80; and C, n = 100), the objective response rate (ORR) was 71.2% (95% confidence interval [CI], 65.1-76.8); the CR rate was 21.4% (95% CI, 16.4-27.1). Median duration of response, CR, and partial remission were 18.2 (95% CI, 14.7-26.1), 30.3, and 13.5 months, respectively. Median progression-free survival was 15.1 months (95% CI, 11.3-18.5). Median overall survival (OS) was not reached; OS at 5 years was 71.4% (95% CI, 64.8-77.1). In cohort C, all 3 patients who discontinued in CR and were subsequently re-treated achieved objective response. No new or unexpected safety signals were identified. This 5-year follow-up of CheckMate 205 demonstrated favorable OS and confirmed efficacy and safety of nivolumab in R/R cHL after auto-HCT failure. Results suggest patients may discontinue treatment after persistent CR and reinitiate upon progression. This trial was registered at www.clinicaltrials.gov as #NCT02181713

SEOM clinical guidelines for the treatment of non‑small cell lung cancer (2018)

Non-small cell lung cancer (NSCLC) accounts for up to 85% of all lung cancers. The last few years have seen the development of a new staging system, diagnostic procedures such as liquid biopsy, treatments like immunotherapy, as well as deeper molecular knowledge; so, more options can be offered to patients with driver mutations. Groups with specific treatments account for around 25% and demonstrate significant increases in overall survival, and in some subgroups, it is important to evaluate each treatment alternative in accordance with scientific evidence, and even more so with immunotherapy. New treatments similarly mean that we must reconsider what should be done in oligometastatic disease where local treatment attains greater valu