julilili42/papers huggingface dataset:
Fracturing of ductile anisotropic multilayers: influence of material strength
2015-05-19

Abstract. Fractures in rocks deformed under dominant ductile conditions typically form simultaneously with viscous flow. Material strength plays a fundamental role during fracture development in such systems, since fracture propagation can be strongly reduced if the material accommodates most of the deformation by viscous flow. Additionally, the degree and nature of anisotropy can influence the orientation and type of resulting fractures. In this study, four plasticine multilayer models have been deformed under coaxial boundary conditions to investigate the influence of strength and anisotropy on the formation of fracture networks. The experiments were made of different mixtures and had two types of anisotropy: composite and composite-intrinsic. The transition from non-localised deformation to systems where fracture networks control deformation accommodation is determined by the ability of the material to dissipate the external work and relax the elastic strain during loading either by viscous flow or by coeval flow and failure. Tension cracks grow in experiments with composite anisotropy, giving rise to a network of shear fractures when they collapse and coalesce with progressive deformation. The presence of an additional intrinsic anisotropy enhances the direct nucleation of shear fractures, the propagation and final length of which depend on the rigidity of the medium. Material strength increases the fracture maximum displacement (dmax) to fracture length (L) ratio, and the resulting values are significantly higher than those from fractures in elastic–brittle rocks. This can be related to the low propagation rates of fractures in rocks undergoing ductile deformation.
New Type of Hamiltonians Without Ultraviolet Divergence for Quantum Field Theories
2015-05-19

We propose a novel type of Hamiltonians for quantum eld theories. They are mathematically well-dened (and in particular, ultraviolet nite) without any ultraviolet cut-o such as smearing out the particles over a nonzero radius; rather, the particles are assigned radius zero. We describe explicit examples of such Hamiltonians. Their denition, which is best expressed in the particle{position representation of the wave function, involves a novel type of boundary condition on the wave function, which we call an interior{boundary condition. The relevant conguration space is one of a variable number of particles, and the relevant boundary consists of the congurations with two or more particles at the same location. The interior{boundary condition relates the value (or derivative) of the wave function at a boundary point to the value of the wave function at an interior point (here, in a sector of conguration space corresponding to a lesser number of
Update of progression-free survival (PFS) and correlative biomarker analysis from coBRIM: Phase III study of cobimetinib (cobi) plus vemurafenib (vem) in advanced BRAF-mutated melanoma.
2015-05-20

9006 Background: Primary analysis of coBRIM showed significant improvement in PFS and overall response rate (ORR) in BRAFV600 mutation–positive patients (pts) with advanced melanoma treated with vem + cobi (Table). We report an updated median PFS evaluation and a correlative analysis of clinical response with baseline (BL) oncogenic mutations coexisting with BRAFV600 mutations. Methods: Study methods were previously described.1 PFS and ORR were updated (cutoff Jan 16, 2015), median follow-up was ~14 months. BRAFV600 mutation and 528 known activating mutations in 17 oncogenic protein kinases were analyzed using next-generation sequencing (average-read depth > 3000×). Reverse-phase protein array (RPPA) was used to assess oncogenic pathway activation in tumors. Co-mutation data were correlated with PFS and ORR. Results: Updated median PFS was 12.3 mo for vem + cobi vs 7.2 mo for vem + placebo (pbo); PFS hazard ratio was 0.58 [95% CI; 0.46-0.72]. ORR data are presented (Table). In 46 of 423 (11%) pt samples, coexisting BL oncogenic mutations were seen in H-,K-,N-Ras, non-V600 BRAF, or receptor tyrosine kinases (RAS/RAF/RTK), with a median allele frequency of 8%. Co-mutations were not correlated with shorter PFS or lower ORR in pts treated with vem + pbo or vem + cobi, despite the tumors' having higher levels of ERK and MEK activation than those without coexistent mutations (detected by RPPA). Conclusions: Longer follow-up confirms the clinical benefit of vem + cobi in pts with advanced BRAFV600-mutant melanoma. Co-existence of BRAFV600 and BL activating RAS/RAF/RTK mutations do not seem to affect disease progression or rate of response to vem + cobi or vem treatment. Clinical trial information: NCT01689519. May 9, 20141 Jan 16, 2015 Vem + Cobi (n = 247) Vem + Pbo (n = 248) Vem + Cobi (n = 247) Vem + Pbo (n = 248) PFS PFS events, n 79 128 143 180 Median follow-up, mo 7.4 7.0 14.9 13.6 Median, mo (95% CI) 9.9 (9-NR) 6.2 (5.6-7.4) 12.3 (9.5-13.4) 7.2 (5.6-7.5) HR (95% CI) 0.51 (0.39-0.68) 0.58 (0.46-0.72) Response Pts, n 167 111 172 124 ORR, % 68 45 70 50 Complete response, n (%) 25 (10) 11 (4) 39 (16) 26 (11) Partial response, n (%) 142 (58) 100 (40) 133 (54) 98 (40) 1Larkin J et al. N Engl J Med. 2014;371:1867-1876.
A phase I/IIa study of the human anti-CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma (rrMM).
2015-05-20

8574 Background: MOR202 is a HuCAL-derived fully human IgG1 anti-CD38 antibody, with high efficacy in preclinical models of MM. Methods: This is an open-label, dose-escalation study (3 + 3 design) to evaluate the safety and preliminary efficacy of MOR202 in adult patients (pts) with rrMM. We present the data of pts previously treated with ≥ 2 prior therapies including an immunomodulatory drug and a proteasome inhibitor. Pts received 2-hour IV MOR202 every 2 weeks (q2w) (8 dose levels [DLs] from 0.01–16 mg/kg) without dexamethasone (DEX), or 4 or 8 mg/kg (DLs 6 and 7), weekly (q1w) +/- DEX. MOR202 16 mg/kg (DL 8) q1w +/- DEX and combination cohorts with lenalidomide (LEN)/pomalidomide (POM) + DEX are planned, as well as confirmation cohorts. Results: As of December 31st 2014, 38 pts had been treated; 29 and 9 pts in the q2w and q1w DLs, respectively. Median age was 70 (44–80) yrs. The median number of prior treatment lines was 4 (2–10) for all pts. 36 pts (94.7%) developed AEs. The most frequently reported AEs ( > 10%) of any grade were anemia (31.6%), fatigue (28.9%), WBC decreased (21.1%), lymphocyte count decreased (LCD) (21.1%), diarrhea (21.1%), nasopharyngitis (18.4%) and leukopenia (13.2%). Grade ≥ 3 hematologic AEs were LCD (15.8%), WBC decreased (7.9%), leukopenia (5.3%), thrombocytopenia (2.6%) and lymphopenia (2.6%). Infusion-related reactions occurred in 13 pts (34%) receiving MOR202 without DEX, mainly during the first infusion. All were grade 1-2 except for 1 pt grade 3. There have been no treatment-related deaths. PK data demonstrate a significant target-mediated drug disposition effect for most pts treated q2w. In 4/6 pts in the q1w 4 mg/kg cohort MOR202 trough levels show the start of target saturation. Only 1 pt (MOR202 0.15 mg/kg q2w) generated a transient anti-drug antibody response to MOR202. Conclusions: The MTD has not been reached. MOR202 is safe and well tolerated. PK data show the potential for full target occupancy in the majority of pts receiving 8 and 16 mg/kg q1w. These latter DLs of MOR202 will be tested as monotherapy or in combination with DEX, LEN + DEX and POM + DEX in the upcoming cohorts. Efficacy analyses are ongoing. Clinical trial information: NCT01421186.
IMAB362 plus zoledronic acid (ZA) and interleukin-2 (IL-2) in patients (pts) with advanced gastroesophageal cancer (GEC): Clinical activity and safety data from the PILOT phase I trial.
2015-05-20

e15079 Background: IMAB362 is the first-in-class monoclonal antibody against the tight junction molecule claudin 18.2 (CLDN18.2) executing its antitumor activity via 4 highly potent modes of action (antibody-dependent cellular cytotoxicity [ADCC], complement-dependent cytotoxicity, proliferation inhibition, apoptosis). Previous in vitro and in vivo data showed that ZA and IL-2 augmented IMAB362’s antitumor activity by affecting immune-related mechanisms. This exploratory Phase I trial aimed to evaluate IMAB362 plus ZA/IL-2 in pts with CLDN18.2+GEC. Methods: Pts with CLDN18.2+ chemo-refractory GEC received IMAB362 (800 in cycle [cy] 1, followed by 600 mg/m2 in subsequent cy, IV q3w) plus ZA (4 mg, IV, day 1 of cy 1 & 3) in arm 1; IMAB362, ZA plus low IL-2 (1×106 IU, s.c., days 1–3 of cy 1 & 3) in arm 2; IMAB362, ZA plus intermediate IL-2 (3×106 IU s.c., days 1–3 of cy 1 & 3) in arm 3; and IMAB362 alone in arm 4. Primary endpoints are biomarkers to assess immunomodulatory effects of treatments (modulation of immune cell populations, ADCC; data not available at time of this analysis). Here we report data on safety (NCI-CTCAE v4.0, primary endpoint) and antitumor activity (DCR, PFS, OS, secondary endpoint). Results: 28 pts (median age 56 years), most of which had progressed on ≥ 1 chemotherapy, received a median of 2.5 (1–14) IMAB362 cycles. Treatment was well tolerated and safe. 26 pts had ≥ 1 AE, 13 pts had ≥ 1 SAEs. Two SAEs were related to IMAB362 (grade [gr] 3 vomiting, gr 4 hiatus hernia). All but 1 IMAB362-related AEs were gr 1–3; most commonly nausea and vomiting in 16 (2 pts gr 3) and 15 (2 pts gr 3) pts, respectively. Of 20 evaluable pts 11 had disease control (1 pt, unconfirmed partial response; 10 pts, stable disease). Median PFS was 12.7 and median OS was 40 weeks. The safety and activity profiles did not differ between arms. Conclusions: IMAB362 (q3w) can safely be combined with ZA/IL-2. IMAB362’s safety profile is unaltered by ZA/IL-2. Signs of activity were observed with IMAB362 as single agent and in combination with ZA/IL2. Emerging primary endpoint data will show whether adding ZA/IL2 achieves the desired augmentation of IMAB362-mediated immune effects. Clinical trial information: NCT01671774.
Pathological response to neoadjuvant 5-FU, oxaliplatin, and docetaxel (FLOT) versus epirubicin, cisplatin, and 5-FU (ECF) in patients with locally advanced, resectable gastric/esophagogastric junction (EGJ) cancer: Data from the phase II part of the FLOT4 phase III study of the AIO.
2015-05-20

4016 Background: Pathological response can be a potent surrogate factor for efficacy of neoadjuvant chemotherapy. Data from our phase II/III study comparing perioperative FLOT with ECF(X) in resectable stages were analyzed for pathological response upon request of the German Cancer Aid in order to further sponsor the trial. Methods: In the FLOT4, 714 patients (pts) are stratified and randomized to either 3+3 perioperative cycles of ECF/ECX (epirubicin 50 mg/m2, d1; cisplatin 60 mg/m2, d1; 5-FU 200 mg/m2 (or capecitabine 1250 mg/m2 p.o) d1-d21, qd21) or 4+4 cycles of perioperative FLOT (docetaxel 50mg/m2, d1; 5-FU 2600 mg/m2, d1; leucovorin 200 mg/m2, d1; oxaliplatin 85 mg/m2, d1, qd14). Central pathology (by AT) is performed according to Becker classification. Results: Samples of 157 pts of the phase-II part of the study were analyzed. Median age was 63 yrs; 79.6% of pts were male. The primaries were gastric in 43.3%, EGJ in 56.1% and not evaluable in 0.6% of pts. In the most relevant categories complete (CR) and subtotal (SR) histopathological response, FLOT was superior to ECF with CR 12.8% vs. 5.1% and SR 16.7% vs. 10.1%, respectively, with statistical significance for CR+SR (FLOT, 29.5% vs. ECF, 15.2%, p = .036). Also, significantly more pts in the ECF-arm had no pathological regression or even did not reach surgery (ECF, 41.8% vs. FLOT, 24.4%; p = .027). See also Table. Conclusions: Perioperative FLOT shows more pathological remissions (CR + SR) than ECF/ECX in patients with resectable gastric cancer. Clinical trial information: NCT01216644.
THE ORIGIN AND PALEOECOLOGY OF CLYPEASTEROID ASSEMBLAGES FROM DIFFERENT SHELF SETTINGS OF THE MIOCENE OF SARDINIA, ITALY
2015-05-20

Abstract Clypeasteroid echinoids can be common in both siliciclastic and carbonate sedimentary sequences of the Miocene of the Mediterranean and Paratethys areas where they frequently form highly fossiliferous deposits. Two echinoid assemblages dominated by clypeasteroids from the early-middle Miocene of Logudoro region (Northern Sardinia) are compared using a detailed sedimentological and taphonomic analysis along with functional morphological considerations. The assemblages differ widely with respect to taxonomic composition, sedimentological features, and taphonomic signatures, such as the orientation and degree of abrasion, encrustation, and bioerosion. The first assemblage (Ardara) is characterized by a low-diversity echinoid fauna, consisting exclusively of the two clypeasteroid genera, Amphiope and different morphotypes of Clypeaster. This deposit represents a proximal tempestite originating in a high-energy, shallow-water, shoreface setting. Higher diversity characterizes the second assemblage (It...
Excited-State Dynamics of Diindenoperylene in Liquid Solution and in Solid Films
2015-05-20

The excited-state dynamics of diindenoperylene (DIP) are investigated in dilute solution and in a solid film at room temperature using picosecond photoluminescence and femtosecond transient absorption measurements. In solution, DIP undergoes a rapid (0.89 ns) internal conversion back to its ground state, with no detectable formation of triplet or other long-lived states. In the solid state, multiple emissive species are formed. The time-resolved photoluminescence signal is dominated by an intrinsic exciton that decays on a time scale of 166 ps. Emission from lower energy excimer-like species then persists for >10 ns. Transient absorption experiments indicate that the majority of the excited-state population relaxes to the ground state on the 166 ps time scale, but a smaller fraction (<10%) survives in longer-lived trap or defect states. The rapid internal conversion leads to transient heating that results in a derivative line shape in the transient absorption signal at longer delays. DIP does not appear to support long-lived singlet exciton states or singlet fission. The implications of these results for the function of DIP in organic solar cells are discussed.
AN ICHTHYOSAUR CARCASS-FALL COMMUNITY FROM THE POSIDONIA SHALE (TOARCIAN) OF GERMANY
2015-05-20

The possibility that large marine reptiles and other Mesozoic vertebrates produced nekton-fall communities similar to those of modern cetaceans is presently receiving increased attention in the literature. The author describes a rare ichthyosaur carcass-fall community from the Posidonia Shale (lower Toarcian) of Germany, which provides insights into the role played by large marine vertebrates in determining regional benthic ecology during this period. It is demonstrated here that, while more important than previously thought, there is little evidence to suggest that ichthyosaur carcasses played a substantial role in structuring the benthic ecology of the European Toarcian epeiric sea. In general, within the shallow waters of the Posidonia Shale, conditions conducive to the creation of carcass-fall communities were rare, and when present, resulted in localized magnification of background taxa and higher local biodiversity, rather than a unique community of epibiont organisms. The community which developed is ecologically similar to modern whale-fall communities, but differs in important ways, particularly with regard to the presence/absence of the chemosynthetic faunas which are most intensively described in the literature.
Short QT and atrial fibrillation: A KCNQ1 mutation–specific disease. Late follow-up in three unrelated children
2015-05-20

Short QT syndrome (SQTS) is an inherited, rare, potentially lethal disease characterized by ventricular repolarization alterations, predisposing individuals to atrial fibrillation (AF), syncope, and high incidence of sudden cardiac death (SCD), often during the first years of life.1,2 SQTS was first described in a family in which some members showed an abnormally short QT interval and 1 of them suffered from AF. An additional patient had a short QT interval, recurrent ventricular arrhythmias, and, ultimately, SCD.
Panitumumab in combination with gemcitabine/cisplatin (GemCis) for patients with advanced kRAS WT biliary tract cancer: A randomized phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
2015-05-20

4082 Background: Biliary tract cancer encompasses a group of genetically heterogeneous tumors. Panitumumab is a human EGFR inhibitor and has shown anti-tumor activity in RAS WT colorectal cancer. Methods: Pts with advanced KRAS wild type biliary tract or gallbladder adenocarcinoma were 2:1 randomized to receive Cis (25mg/m2) followed by Gem (1000mg/m2) on days 1 and 8 of a 21-day cycle, plus Panitumumab (6mg/kg) in arm A until disease progression. Primary endpoint was the progression-free survival rate at 6 months. For genetic profiling, massive parallel multigene sequencing was done by using a custom designed cholangiocarcioma multigene panel on an IonTorrent Proton. Mutations (21 genes) as well as amplifications and deletions (19 genes) were identified by panel tailored bioinformatic algorithms. Results: 93 pts were enrolled (63 per arm A and 30 arm B). Pts characteristics (panitumumab vs. control): median age 61.5 vs. 58.5 years; 59% vs. 50% male; intrahepatic, extrahepatic, gall bladder (%): 63, 16, 17 vs. 71, 11, 11; ECOG PS 0, 1, 2 (%): 64, 33, 2 vs. 45, 55; prior resection (%): 46 both arms. The most common grade 3-4 non-haematological adverse event (AE) was skin toxicity (39% vs 0%). Distribution of other grade 3-4 haematological and non-haematological AEs were not significantly different between both arms. 6-months PFS rate was not significantly different (55% vs 73%), mPFS was 6.7 vs. 8.2 mo, HR (95% CI, Gem/Cis ref.): 0.73 (0.43 – 1.24), p = 0.24; mOS was 12.8 vs. 21.4 mo, HR (95% CI, Gem/Cis ref.): 0.74 (0.39 – 1.4), p = 0.35; response rate (in evaluable pts): panitumumab (28/63 [45%] vs. control 11/28 [39%]. The most frequent genetic variations were detectable in p53 (34%), IDH1/2 (19%) and SMAD4 (11%) with up to 9 events per patient. The prognostic and predictive role of the variants is currently under investigation and will be presented. Conclusions: Panitumumab in combination with chemotherapy does not improve response rate, PFS and OS in patients with advanced bilary tract cancer. Further investigations of chemotherapy in combination with anti-EGFR antibodies are not warranted. Clinical trial information: NCT01320254.
Perioperative chemotherapy and cytoreductive surgery with versus without HIPEC in gastric cancer with limited peritoneal metastases: A randomized phase III study (GASTRIPEC).
2015-05-20

TPS4132 Background: Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) can improve prognosis of patients with peritoneal metastases (PM) in colorectal cancer. In gastric cancer (GC) patients with PM this concept is under debate. Perioperative chemotherapy has been shown to improve survival in gastric cancer. In patients with limited PM systemic chemotherapy, a palliative gastrectomy and CRS may prolong survival compared to chemotherapy alone (Sun) in selected patients. It is unclear whether HIPEC has an additional benefit in this setting. The GASTRIPEC trial (NCT02158988) will clarify the role of HIPEC. Methods: It is an open label, multicenter randomized phase III trial. 180 patients with histological proven GC or GE-junction and PM will be included. All patients will receive 3 cycles of pre- and postoperative chemotherapy, dependent on the HER 2 status (Her 2 + ve: cisplatin, capecitabine, trastuzumab (CCT); HER 2 –ve: epirubicin, oxaliplatin, capecitabine (EOX). All patients will receive gastrectomy and peritonectomy. Patients randomized into group B will be treated with additional intraoperative HIPEC with Mitomycin C and Cisplatin for 60 minutes at 41-43°C. Main inclusion criteria: Histological proven PM in GC including adenocarcinoma of the GE-junction, no evidence of distant metastases in CT scan chest and abdomen other than PM (exception of Krukenberg tumors), estimation of peritoneal cancer index via staging laparoscopy or laparotomy, possibility of 80% tumor reduction at CRS, Karnofsky lndex > 70%, written informed consent. We hypothesize a hazard ratio for overall survival as the primary endpoint of 0.65 (9 months in None-HIPEC versus 13.8 months in HIPEC arm). With an alpha error of 0.05 and a power of 80 percent 180 patients need to be enrolled. Secondary endpoints are 30 days complication-rate, time to progression, quality of life, toxicity, adverse events. 18 patients are included since March 2014. Conclusion: The GASTRIPEC trial may help to clarify the role of HIPEC in addition to systemic chemotherapy, gastrectomy and CRS in GC patients with limited PM. Clinical trial information: NCT02158988.
Overall survival in COMBI-d, a randomized, double-blinded, phase III study comparing the combination of dabrafenib and trametinib with dabrafenib and placebo as first-line therapy in patients (pts) with unresectable or metastatic BRAF V600E/Kmutation-positive cutaneous melanoma.
2015-05-20

102 Background: This phase III study (NCT01584648) of dabrafenib (D) + trametinib (T) compared with D + placebo (P) demonstrated superior progression-free survival (PFS) for D+T compared with D+P (HR = 0.75 ; 95% CI: 0.57–0.99; p = 0.035) in pts with BRAF V600E/K mutant, metastatic melanoma at the primary analysis (N Engl J Med 2014;371:1877). The interim overall survival (OS) favored D+T (40 deaths on D+T vs 55 on D+P), but did not cross the pre-planned stopping boundary for efficacy. Median time on study at the primary analysis was 9 months (0–16 months). Rates of adverse events (AEs) were similar for both arms. More pts had AEs leading to dose modifications with D+T vs D+P, and fewer hyperproliferative skin AEs were reported with D+T. The study was continued after the primary analysis to evaluate OS without crossover from D+P to D+T. Methods: Pts were randomized 1:1 to receive D (150mg twice daily) + T (2mg once daily) or D+P as first-line therapy. Eligible pts were age 18 or older, ECOG performance status ≤ 1, and had histologically confirmed unresectable stage IIIC or IV, BRAF V600E/K mutant cutaneous melanoma. The primary endpoint was investigator-assessed PFS; secondary endpoints were OS, overall response rate (ORR), duration of response (DoR), and safety. The final statistical OS comparison was to be initiated when 220 events were reported. Results: From May 2012 to January 2013, 423 pts were randomized (211 to D+T, 212 to D+P). The 220th death was reported on Jan 12, 2015; analysis is expected to be completed in Mar 2015. Estimated median time on study at data cut off is 20 months (0-31 months). Conclusions: The statistical analysis will evaluate the superiority of D+T vs D+P for OS. A 2-year OS landmark analysis, updated PFS, ORR, DoR, and safety will be presented. Clinical trial information: NCT01584648.
Survival of SLNB-positive melanoma patients with and without complete lymph node dissection: A multicenter, randomized DECOG trial.
2015-05-20

LBA9002 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Saturday, May 30, 2015, and in the Annual Meeting Proceedings online supplement to the June 20, 2015, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.