Journal articles on the topic 'Perpendicular NML'

The purpose of the present study was to find out what particular stimulus features, in addition to the direction and velocity of motion, specifically activate neurons in the nucleus lentiformis mesencephali (nLM) in pigeons. Visual responses of 60 nLM cells to a variety of computer-generated stimuli were extracellularly recorded and quantitatively analyzed. Ten recording sites were histologically verified to be localized within nLM with cobalt sulfide markings. It was shown that the pigeon nLM cells were specifically sensitive to the leading edge moving at the optimal velocity in the preferred direction through their excitatory receptive fields (ERFs). Generally speaking, nLM cells preferred black edges to white ones. However, this preference cannot be explained by OFF-responses to a light spot. The edge sharpness was also an essential factor influencing the responsive strength, with blurred edges producing little or no visual responses at all. These neurons vigorously responded to black edge orientated perpendicular to, and moved in, the preferred direction; the magnitude of visual responses was reduced with changing orientation. The spatial summation occurred in all neurons tested, characterized by the finding that neuronal firings increased as the leading edge was lengthened until saturation was reached. On the other hand, it appeared that nLM neurons could not detect any differences in the shape and area of stimuli with an identical edge. These data suggested that feature extraction characteristics of nLM neurons may be specialized for detecting optokinetic stimuli, but not for realizing pattern recognition. This seems to be at least one of the reasons why large-field gratings or random-dot patterns have been used to study visual responses of accessory optic neurons and optokinetic nystagmus, because many high-contrast edges in these stimuli can activate a neuron to periodically discharge, or groups of neurons to simultaneously fire to elicit optokinetic reflex.

The synthesis of several new surface-active carbazole derivatives is described. These compounds are intended to have applications as hole-transporting materials in thin-film devices assembled by the Langmuir–Blodgett technique. All of the carbazole-containing surfactants gave stable monolayers at the air–water interface with cross sections of 0.35–0.42 nm2/molecule, characteristic of the carbazole ring system oriented perpendicular to the surface with its long axis parallel to the surface. Conditions for Langmuir–Blodgett deposition of multilayers on titanium-coated polyester film were explored. Further characterization of the carbazole derivatives by cyclic voltammetry and fluorescence decay measurements is also described. Keywords: monolayers, Langmuir–Blodgett films, carbazole, surfactants.

Greater than 33 trillion cubic feet of gas, 68 million barrels of natural gas liquids (NGL), and 192 million barrels of water have been produced from the Middle Devonian Marcellus Shale of the Hamilton Group in the Appalachian Basin. These volumes are from more than 11,700 non-commingled wells. Areas of greatest production and future potential for gas and NGL from the Marcellus Shale are within and near the northeast-trending Rome trough in northern West Virginia and Pennsylvania. Southernmost New York, eastern Ohio, western Virginia, and Maryland also contain petroleum potential and (or) reserves. A confluence of factors enhances gas and NGL reserves and resources in the Marcellus Shale. These include (1) brittleness based on lithofacies composition; (2) thickness and distribution of brittle and organic-rich shale; (3) measured thermal maturity of 1% vitrinite reflectance and greater; (4) at least 2 weight percent total organic carbon; (5) dense and complex fracturing and faulting; (6) presence of evaporite beds in the underlying Silurian Salina Group; (7) potential overpressure; (8) current depths of 1,370 m (4,500 ft) and greater, and (9) predominately horizontal wells with laterals that are oriented to the northwest or southeast, or roughly perpendicular to the direction of maximum horizontal stress, and that cross major fault and fracture sets.

Com o objetivo de obter uma equação que, por meio de parâmetros lineares dimensionais das folhas, permitisse a estimativa da área foliar de Ipomoea hederifolia e Ipomoea nil, estudaram-se correlações entre a área foliar real (Sf) e os parâmetros dimensionais do limbo foliar, como o comprimento ao longo da nervura principal (C) e a largura máxima (L), perpendicular à nervura principal. Todas as - equações exponenciais, geométricas ou lineares simples - permitiram boas estimativas da área foliar. Do ponto de vista prático, sugere-se optar pela equação linear simples envolvendo o produto C x L, considerando-se o coeficiente linear igual a zero. Desse modo, a estimativa da área foliar de I. hederifolia pode ser feita pela fórmula Sf = 0,7583 x (C x L), ou seja, 75,83% do produto entre o comprimento ao longo da nervura principal e a largura máxima, ao passo que, para I. nil, a estimativa da área foliar pode ser feita pela fórmula Sf = 0,6122 x (C x L), ou seja, 61,22% do produto entre o comprimento ao longo da nervura principal e a largura máxima da folha.

Micromagnetic study of material thickness dependence of Barium-ferrite nano-dot magnetization dynamics has been performed. The used materials characteristics in this research represent the properties of Barium-ferrite. Barium-ferrite was modeled as a nano-dot with a surface area of 50 50 nm2 and its thickness varies from 5 nm to 100 nm. This nano-dot was simulated using micromagnetic simulator software by solving Landau-Lifshitz-Gilbert equation. According to this study, obtained that the Barium-ferrite nano-dot has excellent thermal stability. Magnetization rate of this nano-dot decreases exponentially with the increase of thickness. The fastest magnetization rate observed in 5 nm of nano-dot thickness, meanwhile 45 nm for the slowest rate. Magnetization reversal mode of this Barium-ferrite nano-dot is dominated by domain wall nucleation and propagation. During the propagation of the domain wall, the exchange interaction becomes the main aspect compared to the other contributed energies.

ResumeUne nacrite est intercalée par deux composés organiques polaires: le diméthylsulfoxide (DMSO) et le n-méthylacétamide (NMA). Les deux solvants ont des moments dipolaires très voisins (4 debyes) mais des constantes diélectriques différentes (49 pour le DMSO et 179 pour le NMA). L'intercalation du NMA est plus rapide que celle du DMSO. Les deux complexes homogènes obtenus sont étudiés par diffraction des rayons X, spectroscopie infrarouge et ATD. L'étude par spectroscopie IR a montré que la nacrite expansée par du DMSO se comporte comme la kaolinite expansée par le même solvant. Dans le cas de la nacrite intercalée par du NMA, trois nouvelles bandes d'absorption dues aux vibrations de valence des OH liés par pont hydrogène avec le groupement C=O et situées respectivement à 3500, 3543 et 3589 cm−1 apparaissent. La fréquence v(N-H) du NMA est intermédiaire entre celles du liquide et d'une solution diluée, indiquant une liaison par pont hydrogène probablement avec les oxygènes de la couche tétraédrique du silicate. La diffraction des rayons X sur des échantillons orientés nous a permis d'obtenir 13 réflexions 00l pour chaque complexe. Une étude quantitative, par transformée de Fourier monodimensionnelle dans la direction perpendiculaire au plan du feuillet, a permis de déterminer le nombre de molécules organiques intercalées (une molécule par Si2Al2O5(OH)4) et leur orientation dans l'espace interlamellaire. L'ATD a montré par ailleurs que le complexe Nac.DMSO est plus stable que le complexe Nac.NMA.

10000 Background: Pediatric mature B-cell NHL differ from aggressive B-NHL of adults in terms of biology and treatment outcome. In contrast to adults, rituximab (Rx) is not established in the treatment of pediatric B-NHL has not be determined yet. Even the activity of Rx in pediatric B-NHL is not determined. We conducted a phase II window study to examine the activity of Rx in newly diagnosed pediatric B-NHL. Methods: Eligibility: age < 19 y, CD20 + B-NHL, ≥ 1 measurable lesion/s, informed consent. Exclusion: Lansky performance scale 5, pre-treatment, impaired renal-, heart-, liver-function, hepatitis B, pre-existing disease, pregnancy. Treatment: Rx 375 mg/m2 IV at day 1; concomitant therapy: Rasburicase, steroids only for anaphylaxis, intrathecal (IT) triple drug at days 1, 3 for CNS+ pts only. Begin of chemotherapy at day 5. Response evaluation: product of 2 perpendicular diameters of 1 - 3 index lesions/% blasts in BM/PB within 24 h prior to Rx and at day 5: responder (RP): at least 1 lesion with at least objective effect (decrease of ≥25%) and no progress (increase of ≥25 %) at other sites. Study plan: Simon 2-stage phase II with α and β = 5%. Response rate (RR) for poor activity was set to 45%, for good activity 65%. 33 pts entered the first stage, final evaluation after 79 pts. Results: One hundred thirty-six pts were enrolled from 04/04–08/08. NTC °3/4 toxicities: general condition 16%, fatigue 13%, anaphylaxis (chill/fever/bronchospasm) 6 (1/2/4)%, infection 3%, S-GOT/GPT 10%, acute tumor lysis (ATL) 7%, capillary leakage (0), toxic death (0). Forty-nine pts were not evaluable for response: Withdrawal (anaphylaxis 8, ATL 2, suspected progression, not verified 4, other 2), IT therapy in CNS- pts (8), corticosteroids (3), technical inadequacy of response evaluation (21), no index lesion (1). Of the 87 evaluable pts 37 were RPs (42.5%, 95%-CI 32% - 54%). RR by histology: BL/B-ALL 29/68, DLBCL 6/14, juvenile follicular lymphoma 1/2, PMBCL 1/1, B-NHL nfs 0/2. Fifty pts were non-RPs. Conclusions: Although the RR was lower than requested Rx as single agent is active in pediatric B-NHL. No significant financial relationships to disclose.

The late-type edge-on spiral galaxy NGC 4631 is known for its high star formation rate and extended radio halo with a uniform magnetic field component ordered predominantly perpendicular to the plane of the galaxy in the inner 6 kpc (assuming a distance of 7.5 Mpc, 1′ = 2.2 kpc) (Hummel et al. 1988; Golla, Ph.D., in preparation). The strongest radio continuum source of NGC 4631 is located at the eastern edge of the central region near a giant HII region complex CM67 (Crillon and Monnet 1969). The magnetic field orientation going out from the central region and especially from the region CM67 as well as the prominent north eastern low frequency radio spur (cf. Hummel et al. 1991) indicate a close connection between the synchrotron emission of the radio halo of NGC 4631 and star forming regions/CM67 in the disk (Golla and Hummel, in preparation). Probably cosmic rays from star forming regions in the disk propagate along the magnetic field Unes into the halo.

In 2017, NFL viewers complained when NBC Sports used the “Madden” camera for live play-by-play coverage of two Thursday Night Football games. Their comments indicated that they had a difficult time estimating yardage from the new perspective. Those games were just two recent examples of viewers complaining about changes in the visual presentation of live sports broadcasts—a phenomenon that has been happening with the Madden camera for more than a decade. The sports broadcasters’ inability to adjust its production technique for live football coverage, despite repeated attempts, provides important insights about the nature of mass communication. As sports broadcasters continue to look for new production techniques in a constantly evolving media landscape, these findings could help guide their production practices. Using game footage from four NFL broadcasts, the present study tested for differences in yardage estimations made from the traditional game camera (i.e., a stationary camera perpendicular to the field) and the Madden camera (i.e., a moving camera on wires positioned over the field). Participants (N = 473) were randomly assigned to watch 11 plays from either the traditional game camera angle or the Madden camera angle. No significant differences were found in estimates of yardage gains based on camera angle. Thehigh variance in the findings suggests that distance estimations are complex visual processes that may require specialized training to improve accuracy.

Purpose The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL. Patients and Methods Patients younger than age 19 years with CD20+ B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m2 administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had ≥ 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity. Results From April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n = 16), IT therapy in CNS-negative patients (n = 8), corticosteroid treatment (n = 3), technical inadequacy of response evaluation (n = 21), or no evaluable lesion (n = 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P = .007). Conclusion Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.

Spontaneous emission of luminescent material is strongly dependent on the surrounding electromagnetic environment. To enhance the emission rate of a single-photon emitter, we proposed a wire-groove resonant nanocavity around the single-photon emitter. An InGaAs quantum dot embedded in a GaAs nanowire was employed as a site-control single-photon emitter. The nanoscale cavity built by a wire-groove perpendicular to the quantum dot with an extremely narrow width of 10 nm exhibited an extremely small volume of 10 × 40 × 259 nm3. Theoretical analysis showed that the emission rate of the quantum dot was dramatically enhanced by 617x due to the Purcell effect induced by the wire-groove cavity. A fast single-photon emitter with a rate of 50.2 GHz can be obtained that speeds up the data rate of the single-photon emitter. This ultrafast single-photon source would be of great significance in quantum information systems and networks.

SUMMARY The magnetotelluric (MT) impedance tensor has a nil diagonal when one of the axes of the coordinate system coincides with the strike of a 2-D structure. In general, real data are full tensors either because of 3-D effects or measurements not aligned to the geological strike. The usual practice to adapt the field tensor to the 2-D assumption is to rotate to a new system of coordinates. In most cases, there is no single angle of rotation that warranties that the diagonal elements become zeros as in the ideal 2-D case. Even maximizing the off-diagonal elements does not necessarily produce a nil diagonal. Consequently, the 2-D inversions proceed by neglecting whatever there is left in the diagonals. In this work, we explore an alternative that places no constraints on direction but assures a nil diagonal. We use two rotational invariants that compact the four elements of the tensor into only two and reduce in 2-D to the TE and TM impedances. These are obtained readily by solving a quadratic equation. We explore four different scenarios: (1) using the invariants, (2) rotating the tensor perpendicular to the profile, (3) rotating to the average maximum orientation for each station and (4) maximizing the off-diagonal elements of the tensor for each site, frequency to frequency. These approaches were applied to 3-D synthetic and field data. The field data correspond to two marine magnetotelluric surveys in the Gulf of California. In one of them, there is no information on the instrument orientation because the compasses failed. In this case, the rotational invariants come handy to overcome the problem. In the other survey, there was orientation information and the 2-D inversions illustrate the better performance of the invariants relative to the traditional approaches.

For future nanoelectronic devices – such as room-temperature single electron transistors – the site-controlled formation of single Si nanocrystals (NCs) is a crucial prerequisite. Here, we report an approach to fabricate single Si NCs via medium-energy Si+ or Ne+ ion beam mixing of Si into a buried SiO2 layer followed by thermally activated phase separation. Binary collision approximation and kinetic Monte Carlo methods are conducted to gain atomistic insight into the influence of relevant experimental parameters on the Si NC formation process. Energy-filtered transmission electron microscopy is performed to obtain quantitative values on the Si NC size and distribution in dependence of the layer stack geometry, ion fluence and thermal budget. Employing a focused Ne+ beam from a helium ion microscope, we demonstrate site-controlled self-assembly of single Si NCs. Line irradiation with a fluence of 3000 Ne+/nm2 and a line width of 4 nm leads to the formation of a chain of Si NCs, and a single NC with 2.2 nm diameter is subsequently isolated and visualized in a few nanometer thin lamella prepared by a focused ion beam (FIB). The Si NC is centered between the SiO2 layers and perpendicular to the incident Ne+ beam.

This work is a pilot study that introduces an improved method for estimation of a chronological age of a human being using the incremental lines in a dental cementum. Scanning Electron Microscopy (SEM) images of longitudinal sections of the tooth roots were subject to SEM analysis. The protocol allows accurate age estimation even if the SEM images reveal a limited number of distinct incremental lines. Micrographs were analyzed with a calibrated thickness measuring tool, such as ImageJ. The study was based on fifteen freshly extracted teeth from adult males and females of a known age. An average cementum thickness (C) and average incremental line thickness (IL) was calculated for each chosen perpendicular level of the tooth root from the SEM image. The number of the incremental lines (nIL) was calculated from the ratio of the mean C and IL, averaged across all levels. Finally, the estimated age is presented as a mean age from the data measured. The proposed protocol for age estimation represents a highly accurate (95%), repeatable and reliable tool for estimation of the chronological age of an individual, using one single SEM scan. Also, from a single case study, we report that an anomalously thick incremental line occurred at the time position which could be related to a childbirth of that female individual. The method can serve forensic purposes.

Abstract The mean serum half life of rituximab reported in the current approved package insert (February 2007) is 76.3 and 205.8 hours following the first and fourth infusions, respectively. This results is based on data from 14 Non-Hodgkin’s Lymphoma (NHL) patients treated with a dose of 375 mg/m2 weekly × 4 analyzed using non-compartmental analysis (NCA). The aims of the current analysis were: to develop a population pharmacokinetic (POP PK) model using a large NHL patient population to investigate possible mechanisms that may explain the observed increase in half-life with time such as a B-cell/tumor burden mediated clearance to identify covariates as potential predictors of PK variability. The population PK analysis was performed using NONMEM V based on 3739 rituximab serum concentration samples from 298 patients who received rituximab as a single agent or in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy from six clinical studies. Tested covariates evaluated included body surface area (BSA), gender, age, race, WHO status, baseline CD19+ counts, sum of the tumor perpendicular diameters (SPD) of tumor and CHOP therapy. A non-parametric bootstrap procedure was used to estimate the precision of model parameters, and the model performance was assessed using visual predictive check. Rituximab concentration data were best described by a two-compartment model with time-varying clearance. Total clearance comprised of two terms, a non-specific clearance pathway (CL1), which remains unchanged throughout treatment, and a specific clearance pathway (CL2, B cells/tumor burden mediated), which decreased at a first-order decay rate from its initial value following the first infusion. The typical population estimates of rituximab nonspecific clearance (CL1), specific clearance (CL2), and central compartment volume of distribution (V1) were 0.14 L/day, 0.59 L/day, and 2.7 L, respectively. Age, gender, race, and WHO performance status had no effect on the PK of rituximab. Covariate analysis revealed that patients with higher CD19 counts or SPD of tumor burden at baseline had a higher rituximab CL2, while V1 varied by body surface area (BSA) and CHOP chemotherapy. However, unexplained inter-individual variability remained high for CL2 following correction for CD19/SPD. Changes from typical V1 values contributed by extreme BSA (1.53 to 2.32 m2) and concurrent CHOP therapy, were relatively minor (27.1% and 19.0%) and explained 27.3% and 5.75% of the inter-individual variability in V1, respectively. Dose adjustment for the tested covariates is not expected to result in a meaningful reduction in rituximab PK variability. Retrospective analysis of rituximab PK using non linear mixed effect modeling confirmed that rituximab elimination decreased following multiple infusions. The median of individual estimates of rituximab terminal half-life was 22 days (range, 6.1 to 52 days), which is typical for immunoglobulin isotype IgG in human and is longer than that reported for humanized anti-CD20 clinical candidates, IMMU106 and of atumumab of 12.0 and 14.3 days, respectively.

Mechanical properties of six different binary ionic porphyrin crystals with variable morphologies were measured and correlated with their structural properties. These solids were formed from stoichiometric combinations of negatively charged tectons, meso-tetra(4-sulfonatophenyl)porphyrin (TSPP), Cu(II) meso-tetra(4-sulfonatophenyl)porphyrin (CuTSPP), Ni(II) meso-tetra (4-sulfonatophenyl)porphyrin (NiTSPP), and four different cationic tectons, namely, meso-tetra (4-pyridyl)porphyrin (TPyP), tetra([Formula: see text]-methyl-4-pyridyl)porphyrin (TMPyP), Cu(II) meso-tetra([Formula: see text]-methyl-4-pyridyl)porphyrin (CuTMPyP), Ni(II) meso-tetra([Formula: see text]-methyl-4-pyridyl)porphyrin (NiTMPyP), and tetra(4-aminophenyl)porphyrin (TAPP). Crystal structures were determined from single crystal and powder X-ray diffraction patterns. Scanning electron and atomic force microscopes (SEM and AFM) provided topographical information. The common arrangement of the porphyrin tectons within the crystals is consistent with alternating face-to-face molecular arrangement forming coherent columns along the fast-growing long axis which are held together by electrostatic and [Formula: see text]–[Formula: see text] interactions as well as hydrogen bonding. In acquiring the indentation data of the porphyrin crystals using AFM, stress was applied perpendicular to the direction where ionic and [Formula: see text]–[Formula: see text] bonds dominate the packing. At indent loads [Formula: see text]50 nN/nm2, all the porphyrin structures deformed elastically. Young’s modulus ([Formula: see text] values for the different crystals range from 6 to 28 GPa. In a broader perspective, this study highlights the extraordinary mechanical behavior of porphyrin assemblies formed by ionic self-assembly. Judicious selection of charged porphyrin synthons can yield crystalline materials with mechanical properties that combine the elastic characteristics of ‘soft’ polymers with the stiffness of composite materials. Such high-performance materials are excellent candidates for deformable optoelectronic devices.

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.

Many crystalline materials are not perfectly ordered, but are disordered to a smaller or larger extent. The properties of such materials are often related to the nature of the disorder. In diffraction experiments, disorder is observable as diffuse scattering. In routine X-ray structure determinations, only Bragg reflections are considered, leading to average crystal structure models. Methods to derive the average structure from the Bragg reflections are very well established, whereas diffuse scattering is rarely accounted for and mostly ignored. Our attempts at modelling the disordered structure of crystalline sodium fluorosilicate will be presented. Although the average crystal structure is known [1], there is some uncertainty about the true space group [2]. Na2SiF6assumes a crystalline morphology that resembles that of ice and is therefore known as an ice–analog material [3]. In the average crystal structure (in space group P321), the asymmetric unit contains two ordered sodium cations (both sitting on a two-fold axis) and two disordered SiF62-anions (one sitting on a 3-fold axis and the other on a 32 site). Each anion can occupy two alternative sites in the unit cell, related by a non-crystallographic mirror plane at z = ¼. The occupation is mutually exclusive for both anions. Diffuse scattering can be observed as planes perpendicular to l in the hnl and nkl precession images where these diffuse planes can be found at integer l. For l odd, the diffuse scattering is more intense. Also there are diffuse clouds of intensity around certain Bragg peaks. In the hkn planes, diffuse streaks are visible parallel to a*, b*, and a* - b*, while some Bragg peaks have diffuse clouds of intensity around them. The pattern of streaks and clouds evolves when going to higher order planes. In the figure below, the hk1 precession image is illustrated. The observed diffuse scattering features will be interpreted in terms of structural models obtained by Monte Carlo simulations.

Most important aspect of nanotechnology applications in the information ultrahigh storage is the miniaturization of data carrier elements of the storage media with emphasis on the long-term stability. Proposed two-dimensional ultrahigh-density X-ray optical memory, named X-ROM, with long-term stability is an information carrier basically destined for digital data archiving. X-ROM is a semiconductor wafer, in which the high-reflectivity nanosized X-ray mirrors are embedded. Data are encoded due to certain positions of the mirrors. Ultrahigh-density data recording procedure can e.g., be performed via mask-less zone-plate-array lithography (ZPAL), spatial-phase-locked electron-beam lithography (SPLEBL), or focused ion-beam lithography (FIB). X-ROM manufactured by nanolithography technique is a write-once memory useful for terabit-scale memory applications, if the surface area of the smallest recording pits is less than 100 nm2. In this case the X-ROM surface-storage capacity of a square centimetre becomes by two orders of magnitude higher than the volumetric data density really achieved for three-dimensional optical data storage medium. Digital data read-out procedure from proposed X-ROM can e.g., be performed via glancing-angle incident X-ray micro beam (GIX) using the well-developed X-ray reflectometry technique. In presented theoretical paper the crystal-analyser operating like an image magnifier is added to the set-up of X-ROM data handling system for the purpose analogous to case of application the higher numerical aperture objective in optical data read-out system. We also propose the set-up of the X-ROM read-out system based on more the one incident X-ray micro beam. Presented scheme of two-beam data handling system, which operates on two mutually perpendicular well-collimated monochromatic incident X-ray micro beams, essentially increases the reliability of the digital information read-out procedure. According the graphs of characteristic functions presented in paper, one may choose optimally the incident radiation wavelength, as well as the angle of incidence of X-ray micro beams, appropriate for proposed digital data read-out procedure.

e20046 Background: Clinical studies of liso-cel show low incidences of severe CRS and NEs. Pts with high tumor burden and inflammation are at higher risk of CRS and NEs (Borrega, Hemasphere 2019). Here, we characterize the presenting symptoms, timing, and management of CRS and NEs in pts with R/R LBCL treated with liso-cel in TRANSCEND NHL 001 (NCT02631044). A deeper understanding of CRS/NEs after liso-cel treatment may help clinicians identify and manage these toxicities. Methods: Pts with R/R LBCL and ≥2 lines of therapy received liso-cel after lymphodepletion (LD) with fludarabine and cyclophosphamide. Bridging therapy was allowed for pts with PET-positive disease before LD (Abramson, ASH 2019 #241). Investigators were educated on prospectively identifying liso-cel–related NEs and CRS, which were collected and graded per NCI CTCAE v4.03 (NEs) or 2014 Lee criteria (CRS). Timing and severity of individual CRS/NE symptoms and interventions were also collected. Results: The analysis included 269 pts (median age, 63 y): 38% had sum of perpendicular diameters ≥50 cm2 or lactate dehydrogenase ≥500 U/L, and 59% received bridging therapy. CRS and NEs had delayed onset (median, 5 and 9 d, respectively) and a low incidence of grade (Gr) ≥3 events (CRS 2%; NE 10%). CRS occurred before NEs in most pts and was Gr 1/2 at onset in all but 2 pts (Table). The most common CRS symptoms were pyrexia (40%), hypotension (20%), and tachycardia (18%). Overall, 20% of pts received tocilizumab and/or corticosteroids for CRS (10% tocilizumab only; 2% corticosteroids only; 8% both); 3% received vasopressors. The most common NE symptoms were confusional state (11%), tremor (9%), and aphasia (8%); most were low grade. A total of 17% of pts received tocilizumab and/or corticosteroids for NEs (13% corticosteroids only; < 1% tocilizumab only; 3% both); < 1% received vasopressors. Overall, 4% of pts were admitted to the ICU for CRS and/or NEs. Additional analyses on timing of intervention and type/severity of initial symptoms will be presented. Conclusions: In pts with high-risk, aggressive R/R LBCL, liso-cel treatment was associated with a low incidence of severe CRS/NEs, late onset of mostly low-grade events at presentation, and low use of tocilizumab/corticosteroids. Clinical trial information: NCT02631044 . [Table: see text]

Abstract Abstract 59 Introduction: CD22 is a lineage marker expressed in most B-cell lymphomas. DCDT2980S is an ADC consisting of an anti-CD22 monoclonal antibody conjugated to monomethyl auristatin E (MMAE), a potent microtubule disrupting agent linked to the antibody via a protease-cleavable peptide linker. DCDT2980S exhibits potent anti-tumor activity in murine xenograft models of B-cell lymphoma and is being evaluated in a Phase I study to assess the safety, tolerability, pharmacokinetics (PK), and biologic activity in patients (pts) with relapsed/refractory B-cell NHL. Methods: Pts receive DCDT2980S intravenously every 21 days at dose levels 0.1 to 3.2 mg/kg until disease progression or unacceptable toxicity. Intrapatient dose escalation based on tolerability at higher doses is permitted. Following determination of the recommended Phase II dose (RP2D) based on protocol-defined dose-limiting toxicities (DLTs) occurring within 21 days of dosing, additional pts with indolent and aggressive B-cell NHL are being enrolled to further evaluate safety and efficacy based on Cheson response criteria. Here we report the RP2D and preliminary safety and efficacy results. Results: To date, 35 pts (57% male), median age 66 years (range 30–85) have been enrolled: diffuse large B-cell lymphoma (DLBCL, n=18), follicular lymphoma (FL, n=11), transformed FL (n=4), and small lymphocytic lymphoma (n=2). Enrolled patients were heavily pre-treated: 26 pts had received ≥ 3 prior regimens, all pts had received prior rituximab, and 7 pts received prior high-dose therapy followed autologous or allogenic stem cell transplantation. Overall, pts received a median of 4 doses (range 1–25) of DCDT2980S in 7 dose-escalation cohorts, and 2 expansion cohorts at the RP2D. All 3 pts treated with DCDT2980S at 3.2 mg/kg developed Grade 4 neutropenia following the first dose, one of which constituted a DLT. No DLTs were reported in the 6 pts treated at 2.4 mg/kg, which is the RP2D. Across all dose levels, the most common treatment-emergent adverse events (AE) in ≥ 20% of pts were diarrhea (34%), fatigue (34%), nausea (31%), neutropenia (26%), decreased appetite (23%), vomiting (23%), and peripheral edema (20%). Treatment-emergent Grade ≥ 3 AEs were reported in 9 (27%) pts including 5 out of 9 pts who were treated at the RP2D of 2.4 mg/kg. Overall, neutropenia (24%) was the only Grade ≥ 3 AE in ≥ 10% of pts (24%) and was the only Grade ≥ 3 AE reported in > 1 pt (n=2) treated at the RP2D. Eight (26%) pts across all dose levels experienced a serious AE (SAE) of which one Grade 3 dehydration in a pt treated at 3.2 mg/kg was attributed to DCDT2980S. Treatment discontinuation due to AEs occurred in 3 pts: Grade 3 neutropenia (n=1) and Grade 3 peripheral sensory neuropathy (n=2). No deaths were reported within 30 days of the last dose of DCDT2980S. Assessment of Cycle 1 PK after the first dose of DCDT2980S indicated that the exposure of antibody-conjugated MMAE (acMMAE), total antibody, and free MMAE increased with dose. The clearance estimates of both acMMAE and total antibody were similar across doses from 1.0–3.2 mg/kg. The volume of distribution estimates for acMMAE and total antibody approximated plasma volume and did not change with dose and suggest dose-proportional increase of acMMAE and total antibody exposures for doses of 1.0–3.2 mg/kg. Early evidence of anti-tumor activity was observed. At the RP2D of 2.4 mg/kg, 2 of 3 pts with DLBCL had > 75% reduction in tumor sum of perpendicular dimensions (SPD) and negative PET scans; 1 partial response was noted in a pt with FL treated at 1.8 mg/kg. These 3 pts continue on study, each having received at least 8 cycles of study treatment. Two additional pts with DLBCL receiving 0.5 mg/kg and 3.2–2.4 mg/kg had > 50% reduction in tumor SPD and discontinued study treatment after 8 and 6 cycles, respectively, to undergo stem cell transplant. Conclusions: In this early experience, DCDT2980S is well tolerated, has a favorable safety profile and has evidence of anti-tumor activity in in a heavily pretreated pts with relapsed/refractory B-cell NHL. Updated clinical data will be presented. These results support additional clinical evaluation of DCDT2980S in B-cell malignancies. Disclosures: Advani: Genentech: Research Funding. Off Label Use: anti-CD79b Antibody-Drug Conjugate (ADC) DCDS4501A. Lebovic:Genentech: Speakers Bureau. Brunvand:Genentech: Speakers Bureau. Chen:Genentech: Research Funding. Chang:Genentech: Research Funding. Ho:Genentech: Employment. Kahn:Genentech: Employment. Lu:Genentech: Employment. Su:Genentech: Employment. Chu:Genentech: Employment.

The relevance of the uterine secretions during early embryonic development is due to its role as the only source of nutrients for embryo prior to implantation. Probing of the uterine secretions during early pregnancy without compromising gestation would be an important tool for the identification of fertility markers. Manipulations of the uterus could lead to a local increase in blood flow, which could result from the physical stimulation or tissue damage and inflammation. This study aimed to evaluate the effects of low-volume flushing of the uterine horn contralateral to the ovulation on uterine vascular perfusion and endometrial thickness 6 days after artificial insemination (AI). Transrectal B-mode and color Doppler ultrasonography (MyLab30 Vet Gold; Esaote Healthcare) were used to compare changes on endometrial thickness and uterine vascular perfusion, respectively. Examinations were carried out on 15 Nelore cows just prior to the flushing procedure (0 h), 6 and 24 h later. Cows were inseminated after oestrus detection and uterine flushings were performed 6 d after AI. The uterine horn, contralateral to the corpus luteum, was flushed with 20 mL of PBS using a Foley catheter. After massage of the uterine horn, flushing was collected in a syringe by suction. Vascular perfusion was estimated by scoring the extent of colored areas within the endometrium and mesometrium. Vascular perfusion scores indicated nil (1), minimal (2), intermediate (3), and maximal (4) vascular perfusion. Endometrial thickness was measured by taking the maximum diameter and its perpendicular diameter; these values were summed and then divided by four. Data that were not normally distributed were transformed to natural logarithms or ranks. For each variable, the main effect of side (flushed and nonflushed horns), hour, and their interaction were analyzed using the PROC MIXED procedure from the SAS software. The least significant difference method was used for the comparison of means among hours. An hour effect was detected for endometrial and mesometrial scores of vascular perfusion (Table 1), representing an increased vascular perfusion about 6 h after the flushing procedure and a return to basal perfusion at 24 h. Results indicate that the unilateral flushing procedure increases vascular perfusion on both uterine horns. For endometrial thickness, no effect of side, hour, or their interaction was detected. In conclusion, unilateral low-volume uterine flushing results in a transitory increase in uterine blood flow about 6 h post-flushing. Further studies are needed to evaluate other inflammatory characteristics and the potential effect on pregnancy rate in response to the uterine flushing procedure performed during early pregnancy. Table 1.Scores of endometrial and mesometrial vascular perfusion and endometrial thickness of both uterine horns at the time of uterine flushing (0 h), 6 and 24 h post-flushing (mean ± standard error of the mean)

Background: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL). Most patients with MCL relapse after first-line immunochemotherapy, with poor responses to salvage therapy. Chimeric antigen receptor (CAR) T cell therapy has shown clinical efficacy in patients with relapsed/refractory (R/R) NHL. We report the results of the dose-finding and dose-expansion parts of the ongoing phase 1 TRANSCEND NHL 001 study (NCT02631044) in patients with R/R MCL (MCL cohort) who received lisocabtagene maraleucel (liso-cel), an investigational, CD19-directed, defined composition, 4-1BB CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells. Methods: Eligible patients had confirmed MCL (cyclin D1 expression, t[11;14]) with R/R disease after ≥1 prior line of therapy. After lymphodepleting chemotherapy, patients received liso-cel infusion at 1 of 2 dose levels (DLs): DL1 (50 × 106 CAR+ T cells) or DL2 (100 × 106 CAR+ T cells). Bridging therapy was allowed between leukapheresis and initiation of lymphodepleting chemotherapy. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response, progression-free survival, overall survival, and pharmacokinetics (PK). Results: At data cutoff, 41 patients had undergone leukapheresis and 32 had received liso-cel (DL1, n = 6; DL2, n = 26). Among the 32 patients who received liso-cel, the median (range) age was 67 (36‒80) years and 27 patients (84%) were male. Twelve patients (37.5%) had blastoid morphology, 23 (72%) had documented Ki67 ≥30%, 7 (22%) had a TP53 mutation, and 11 (34%) had a complex karyotype. Patients had a median (range) sum of the product of perpendicular diameters before lymphodepleting chemotherapy of 28.7 (0-209.6) cm2 and median lactate dehydrogenase of 251.5 (117-811) U/L. Patients had received a median (range) of 3 (1-7) prior systemic therapies, and most (72%) were refractory to their last prior therapy. Of 28 patients (87.5%) who had received a prior Bruton tyrosine kinase inhibitor, 11 (34%) were refractory to the therapy. Seventeen patients (53%) received bridging therapy. Eighteen patients (56%) had serious treatment-emergent adverse events (TEAEs), and 27 (84%) had grade ≥3 TEAEs, primarily neutropenia (41%), anemia (34%), and thrombocytopenia (31%). Grade ≥3 thrombocytopenia was more frequent at DL2 (n = 9/26 [35%]) than at DL1 (n = 1/6 [17%]). Prolonged grade ≥3 cytopenias (present at study Day 29) occurred in 11 patients (34%). Sixteen patients (50%; DL1, n = 2/6 [33%]; DL2, n = 14/26 [54%]) had cytokine release syndrome (CRS), including 1 grade 4 event at DL2. There were no grade 3 or 5 CRS events. Median (range) time to CRS onset and resolution was 6 (2‒10) days and 4 (2‒9) days, respectively. Nine patients (28%) had neurological events (NEs), all at DL2, including 3 grade 3 NEs. No grade 4 or 5 NEs were reported. Median (range) time to NE onset and resolution was 8 (2‒25) days and 3 (1‒51) days, respectively. Ten patients (31%) received tocilizumab and/or corticosteroids for treatment of CRS and/or NEs. Grade 5 TEAEs occurred in 2 patients (at DL2): one patient with high tumor burden had tumor lysis syndrome and 1 patient had cryptococcal meningoencephalitis. DL2 was selected for dose expansion. Of 32 patients, 27 responded to liso-cel (ORR, 84%: DL1, n = 4/6 [67%]; DL2, n = 23/26 [88%]), and 19 (59%) achieved a CR (DL1, n = 2/6 [33%]; DL2, n = 17/26 [65%]). Among the 12 patients with blastoid morphology, 9 patients had a response (ORR, 75%), including 7 (58%) who achieved a CR. Overall, the median (range) time to first CR was 1 (1-6) month. At data cutoff, 20 (74%) of 27 responders were censored with an ongoing response or had completed the study. Median (range) follow-up duration was 10.9 (1.2-24.8) months for DL1 and 3.1 (0.4-23.0) months for DL2. Preliminary PK analysis indicated that median maximum expansion was higher among patients at DL2 than at DL1. Conclusions: In this phase 1 study of patients with R/R MCL, treatment with liso-cel was associated with a low incidence of grade ≥3 CRS and NEs, late onset of CRS/NEs, and promising clinical activity. Dose confirmation is ongoing at DL2 in the MCL cohort. Disclosures Palomba: Pharmacyclics: Honoraria; Juno: Honoraria; Celgene: Honoraria; Merck: Honoraria; Novartis: Honoraria; Regeneron: Research Funding; Juno: Research Funding; Genentech: Research Funding. Gordon:Zylem Biosciences: Patents & Royalties: Patents, No Royalties. Siddiqi:Juno: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BeiGene: Other: DMC member; Juno Therapeutics, Pharmacyclics LLC, an AbbVie Company, AstraZeneca, Celgene, Kite Pharma, and BeiGene: Consultancy; Pharmacyclics LLC, an AbbVie Company, Seattle Genetics, Janssen, and AstraZeneca: Speakers Bureau; Pharmacyclics LLC, an AbbVie Company, Juno Therapeutics, KITE Pharma, AstraZeneca, TG Therapeutics, Celgene, Oncternal, and BeiGene: Research Funding; AstraZeneca: Other: Travel/accommodations/expenses; Astrazenca: Membership on an entity's Board of Directors or advisory committees; PCYC: Membership on an entity's Board of Directors or advisory committees. Abramson:Celgene: Honoraria, Other: Scientific Advisory Board; Juno Therapeutics: Other: Scientific Advisory Board; AbbVie: Other: Scientific Advisory Board; EMD Serono: Other: Scientific Advisory Board; Genentech/Roche: Other: Scientific Advisory Board; Janssen: Other: Scientific Advisory Board; Karyopharm: Other: Scientific Advisory Board; Gilead: Other: Scientific Advisory Board; Verastem: Other: Scientific Advisory Board; Bayer: Other: Scientific Advisory Board; Merck: Other; KIte Pharma: Other; Novartis: Other; Amgen: Other; Seattle Genetics: Other; Allogene: Other; Morphosys: Other; C4 Therapeutics: Other; BeiGene: Other; AstraZeneca: Honoraria; Incyte: Honoraria. Kamdar:Seattle Genetics: Speakers Bureau; Karyopharm: Consultancy; BMS: Consultancy; Abbvie: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy. Lunning:Acrotech: Consultancy; ADC Therapeutics: Consultancy; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; Curis: Research Funding; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; TG Therapeutics: Research Funding; Verastem: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria. Maloney:Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; A2 Biotherapeutics: Consultancy, Current equity holder in publicly-traded company, Honoraria; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties: Patents are pending, but not issued, licensed, no royalties, no licensees., Research Funding; Bioline Rx: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Andreadis:Genentech: Other: Spouse Employee (salary and stock); Novartis: Research Funding; Celgene/Juno: Research Funding; Amgen: Research Funding; Merck: Research Funding; Gilead/Kite: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Astellas: Other: Advisor; Seattle Genetics: Other: Advisor; Karyopharm: Other: Advisor; Incyte: Other. Arnason:Regeneron: Consultancy; Juno: Consultancy. Ghosh:Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Genmab: Consultancy, Speakers Bureau; AbbVie: Speakers Bureau; Karyopharm: Consultancy; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Kite/Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Roche/Genentech: Research Funding; SGN: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Celgene/Bristol-Myers Squibb: Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau. Mehta:Innate Pharmaceuticals: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding; Gelgene/BMS: Research Funding; Oncotartis: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Juno Parmaceuticals/BMS: Research Funding; fortyseven Inc/Gilead: Research Funding; Takeda: Research Funding; Roche-Genentech: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Affimed: Research Funding. Farazi:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Garcia:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb Company: Current equity holder in publicly-traded company. Dehner:Juno Therapeutics, a Bristol-Myers Squibb Company: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Ogasawara:Bristol-Myers Squibb: Current Employment; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Gao:Bristol-Myers Squibb: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Current Employment. Wang:Juno: Consultancy, Research Funding; Acerta Pharma: Research Funding; Loxo Oncology: Consultancy, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; InnoCare: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; Lu Daopei Medical Group: Honoraria; Beijing Medical Award Foundation: Honoraria; OncLive: Honoraria; Molecular Templates: Research Funding; Verastem: Research Funding; Dava Oncology: Honoraria; Guidepoint Global: Consultancy; Pulse Biosciences: Consultancy; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Oncternal: Consultancy, Research Funding; Nobel Insights: Consultancy; OMI: Honoraria, Other: Travel, accommodation, expenses; Targeted Oncology: Honoraria; BioInvent: Research Funding; VelosBio: Research Funding.

Abstract Background Most patients (pts) with r/r FL remain incurable and eventually relapse or progress. Previously, a Ph1 study of relma-cel (NCT03344367) had demonstrated preliminary safety and efficacy in r/r B-NHL pts, including those with r/r FL. A Ph2 pivotal study in r/r FL pts had been enrolled and preliminary efficacy, safety and PK was presented. Methods Adult pts were eligible with histologically confirmed grade (Gr)1-3a r/r FL on the basis of the 2016 WHO Classification, having failed ≥ 2-line prior therapies or relapsed after auto-HSCT, without allogeneic transplant within 90 days or primary central nervous system (CNS) lymphoma, and with ECOG performance score of 0-1. Pts were randomized to receive either 100×10 6 (low dose) or 150×10 6 (high dose) relma-cel (1:1) following fludarabine 25 mg/m 2 & cyclophosphamide 250 mg/m 2 daily×3. Pts were evaluated for efficacy (Cheson, 2014), toxicity (cytokine release syndrome [CRS] by Lee 2014, and others by CTCAE v4.03), and PK (by qPCR and flow cytometry). Primary endpoint was complete response rate (CRR). Secondary endpoints included objective response rate (ORR), frequency/severity of AEs, duration of response (DOR), duration of complete response (DoCR), duration of partial response (DoPR), time to primary remission (TTR), time to primary complete remission (TTCR), progression free survival (PFS), overall survival (OS), and CAR-T cell expansion. Disease response was by investigator assessment, a sensitivity analysis was also conducted using an independent review committee. Results Between June 2018 and June 2021, 28 r/r FL pts were enrolled and treated. As of the data cut-off of June 11, 2021, 20 pts were treated with relma-cel with ≥ 1 month of follow-up. Among these 20 pts, the median age was 54.5 years (range, 36-71), 50% of pts were male, 85% had ECOG 0, 10% had a sum of perpendicular diameters (SPD) ≥ 5000 mm 2, and 36% (5/14) had a FLIPI2 score≥ 3. Pts had received a median of 3.5 prior lines of therapy, 6 (30%) pts had received at least five lines of treatment and 65% were refractory to last prior treatment, 85% were relapsed, 50% were both relapsed and refractory. Relma-cel was successfully manufactured in all pts. Best ORR was 100% (19/19), and best CRR was 95% (18/19). For the mITT (n=19, one pt who developed gastric adenocarcinoma, was excluded, but also achieved CR), ORR at 1 month was 100%(19/19) and CRR was 63% (12/19). CRR at 3 months for 17 pts &gt; 3 months post treatment, was 82%(14/17). At a median follow-up of 8.9 months, the median duration of response [DOR], progression-free survival (PFS) and overall survival (OS) were not reached. Twenty pts who received relma-cel were evaluable for safety. Gr ≥3 AEs related to relma-cel occurred in 80% of pts, most commonly neutrophil count decreased (35%), lymphocyte count decreased (30%) and white blood cell count decreased (25%). CRS occurred in 35% (all Gr 1), and only 2 pts received tocilizumab. Median CRS onset was 7 days (range, 5-9), with median duration of 5 days. Two (10%) pts experience neurotoxicity (NT), both Gr 1, with onsets of 4 and 9 days, and duration of 25 and 7 days, respectively. No deaths occurred. Safety data, tocilizumab/steroids usage and PK parameters are shown in the Table. Conclusion With median follow-up of 8.9 months, relma-cel treatment in r/r FL pts had resulted in high tumor remission rates and a manageable toxicity profile in the first 20 pts treated. Data for additional patients will be presented. Table： The summary of AEs (AE, TEAE, CRS, NT), the usage of tocilizumab/steroids and PK Parameters Figure 1 Figure 1. Disclosures Yang: JW Therapeutics: Current Employment. Zhang: JW Therapeutics: Current Employment. Ma: JW Therapeutics: Current Employment. Zhou: JW Therapeutics: Current Employment. Zheng: JW Therapeutics: Current Employment.

Introduction: Marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma (LPL)/Waldenstrom's macroglobulinemia (WM) comprise approximately 7% and 2%, respectively, of non-Hodgkin's lymphomas (NHL) (Teras 2016). MZL is further subclassified as splenic MZL (sMZL), nodal MZL (nMZL), or extranodal MZL (eMZL). Standard first-line therapies for LPL/WM include rituximab plus an alkylating agent and/or proteasome inhibitor or ibrutinib (Castillo 2017), while standard first-line treatment for MZL varies by subtype (Rosand 2017). There are limited treatment options for patients who have relapsed after first-line therapy. Idelalisib, a selective oral inhibitor of PI3Kδ, demonstrated efficacy in indolent NHL (iNHL), including MZL and LPL/WM, at a median follow-up of 9.7 months (mos) in a phase 2 study (NCT01282424; 101-09; Gopal 2014). Here, we present the final, long-term results for patients with double-refractory MZL and LPL/WM from the 101-09 study. Methods: Eligible iNHL patients had measurable disease and were refractory to both rituximab and an alkylating agent. Refractory status was defined as lack of response to or progression of lymphoma within 6 mos of completion of preceding therapy, documented by imaging. Oral idelalisib 150 mg twice daily was administered continuously until disease progression or intolerance. Responses were evaluated by an independent review committee using standard criteria (Cheson 2007; Owen 2013). Endpoints included overall response rate (ORR), time to response, duration of response (DOR), lymph node response, progression-free survival (PFS), overall survival, and safety. The final data cutoff date was 22 Oct 2018. Results: Of 125 patients enrolled, 15 (12%) had MZL (sMZL, n = 1; nMZL, n = 5; eMZL, n = 9) and 10 (8.0%) had LPL/WM. Median age was 65 years and most were non-Hispanic (n = 24; 96%) and White (n = 23; 92%). At diagnosis, 80% of MZL and 100% of LPL/WM patients had stage IV disease. The largest lesion at baseline was ≥5 cm for 5 (33%) MZL and 3 (30%) LPL/WM patients. Baseline median IgM level was elevated for 80% of LPL/WM patients (median 1.9, IQR 1.0-2.7 g/dL). Baseline beta2-microglobulin level was >3 µg/mL for 1 of 9 LPL/WM patients with values recorded (median 2.5 [range 1.7-3.1] µg/mL). For MZL and LPL/WM patients, 7 (47%) and 7 (70%) had ≥3 prior therapies, respectively. Common regimens for all 25 patients included rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (44%), rituximab-cyclophosphamide-vincristine-prednisone (40%), rituximab only (28%), bendamustine only (24%), and bendamustine-rituximab (20%). For MZL, the ORR (95% confidence interval [CI]) was 47% (21%, 73%), with median duration of therapy of 6.4 (range 1.8-37) mos. Of 7 responders, 1 had a complete response and 6 had partial responses (PR). Seven had stable disease (SD) and 1 had progressive disease (PD). Fourteen (93%) patients had reduction in lymph nodes, with 8 (53%) having ≥50% reduction in the sum of the products of the greatest perpendicular diameters (SPD). Median PFS was 6.6 (95% CI 3.5, 22) mos and median DOR was 18 (range 0-18) mos (Table). For LPL/WM, the ORR (95% CI) was 80% (44%, 98%), with a median duration of therapy of 29 (range 6.4-51) mos. Of 8 responders, 7 had PR and 1 had a minor response. There was 1 SD and 1 PD. Nine (90%) patients had lymph node reduction, with 5 (50%) having ≥50% reduction in SPD. Median PFS was 22 (95% CI 1.4, 56) mos and median DOR was 20 (range 1.7-50) mos (Table). All 25 patients had ≥1 treatment-emergent adverse event (TEAE), 16 (64%) had a serious AE, and 11 (44%) had dose reduced due to a TEAE. Grade ≥3 TEAEs occurred for 22 (88%) patients; neutropenia (n = 7, 28%), diarrhea (7, 28%), alanine aminotransferase increased (4, 16%), asthenia (3, 12%), and pneumonia (3, 12%) were the most frequent. All patients eventually discontinued treatment due to disease progression (14, 56%), AE (6, 24%), death (3, 12%), investigator request (1, 4%), or other (1, 4%). Ten patients have died, 3 during the study and 7 during the long-term follow-up. Conclusions: Monotherapy with idelalisib showed high rates of antitumor activity in this small subset of patients with MZL and LPL/WM refractory to prior therapy with rituximab and an alkylating agent; prolonged disease control was achieved for LPL/WM patients. No new safety signals were identified despite longer follow-up. Disclosures Wagner-Johnston: Bayer: Membership on an entity's Board of Directors or advisory committees; Jannsen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Schuster:Genentech: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Patents & Royalties: Combination Therapies of CAR and PD-1 Inhibitors with royalties paid to Novartis, Research Funding; AstraZeneca: Honoraria; Pharmacyclics: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Acerta: Honoraria, Research Funding; Loxo Oncology: Honoraria; Nordic Nanovector: Honoraria; Pfizer: Honoraria; AbbVie: Honoraria, Research Funding; Gilead: Honoraria, Research Funding. de Vos:Verastem: Consultancy; Portola Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy. Salles:Epizyme: Consultancy, Honoraria; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Amgen: Honoraria, Other: Educational events; BMS: Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees. Jurczak:Bayer: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Celtrion: Research Funding; MorphoSys: Research Funding; Gilead: Research Funding; Roche: Research Funding; Servier: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Rajakumaraswamy:Gilead Sciences, Inc.: Employment. Xing:Gilead Sciences, Inc.: Employment. Gopal:Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte.: Consultancy; Teva, Bristol-Myers Squibb, Merck, Takeda, Seattle Genetics, Pfizer, Janssen, Takeda, and Effector: Research Funding; Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte: Honoraria. OffLabel Disclosure: Idelalisib is a selective oral inhibitor of PI3K-delta that has shown antitumor activity in previously treated indolent non-Hodgkins lymphomas in phase 1 and 2 studies. It is approved for treatment of relapsed follicular lymphoma that has progressed on 2 prior systemic therapies, relapsed chronic lymphocytic leukemia in combination with rituximab when rituximab alone would be considered appropriate due to other comorbidities, and relapsed small lymphocytic lymphoma that has progressed on 2 prior systemic therapies. In this presentation, we provide results of 2 less common subgroups of indolent non-Hodgkins lymphoma, Âmarginal zone lymphoma and lymphoplasmacytic lymphoma/Waldenstrom's Macroglobulinemia, Âfrom the completed phase 2 trial with long-term follow-up.

As the semiconductor industry strives for downsizing and high speed, it is confronted with increasing scaling uncertainty as devices decrease to the nanoscale. Nano-magnetic logic (NML) is an alternative approach to synthesize the digital logic circuits with high-density and low-power consumption. We introduced an optimal design of content addressable memory (CAM) memory based on perpendicular nano-magnetic logic (pNML). The main aim of this implementation is to synthesize CAM memory in terms of latency and other design parameters. The implementation of the design is a multilayer approach, which is optimal. The synthesis approach and optimization are perfectly scalable across layout construction of designs. Here a new logic gate in pNML technology is designed which is mainly used for matching of two input numbers. According to insight, both memory unit and a matching unit in the pNML are introduced in the state-of-the-artwork for the first time to synthesize design in high-speed pNML application. MAGCAD tool is used for the design of all the proposed pNML layouts.

Drone use in geoscience research and teaching is becoming widespread, with diverse applications documented. Many studies favour consumer-level drones, however, recent developments in so-called ‘microdrones’ (takeoff weight <250 g) necessitates further investigation to determine possible benefits, limitations, and future developments. Microdrone deployment is often advantageous in numerous jurisdictions due to fewer regulations, lower cost, and simple transportation. In this study, we deployed a DJI Mini 2 microdrone to study the ca. 201 Ma North Mountain Basalt (NMB) exposed in coastal outcrops along the Bay of Fundy, Nova Scotia, Canada. We report benefits of the microdrone as a field aid with three related approaches: 1) general site location and characterisation, 2) drone-based photogrammetry using ArcGIS Drone2Map, and 3) quantitative fracture mapping using FracPaQ. Application of these methods, showed that microdrone-acquired imagery from the NMB exposures provides a valuable resource for interpretation post-fieldwork. The microdrone-derived data shows, two near-perpendicular fracture sets in the NMB: ~NNE-SSW and ~ESE-WNW, with some variation along the coastline. Overall, we determined that microdrones offer field-based geoscientists a valuable tool due to quick deployment, a simple image capture process and relatively straight forward data processing, and thus predict that this approach to enhancing fieldwork will continue to advance.

ABSTRACTThis paper presents the experimental and numerical study of hydrophobic interaction forces at nanometer scale in the scope of engineering micron-sized building blocks for self-assembly in liquid. The hydrophobic force distance relation of carbon, Teflon and dodeca-thiols immersed in degassed and deionized water has been measured by atomic force microscopy. Carbon and dodeca-thiols showed comparable attractive and binding forces in the rage of pN/nm2. Teflon showed the weakest binding and no attractive force. Molecular dynamic simulations were performed to correlate the molecular arrangement of water molecules and the hydrophobic interactions measured by atomic force microscopy. The simulations showed a depletion zone of 2Å followed by a layered region of 8Å in the axis perpendicular to the hydrophobic surface.

Abstract We study inserting Co layer thickness-dependent spin transport and spin-orbit torques (SOTs) in the Pt/Co/Py trilayers by spin-torque ferromagnetic resonance. The interfacial perpendicular magnetic anisotropy (IPMA) energy density (K s = 2.7 erg/cm2), which is dominated by interfacial spin-orbit coupling (ISOC) in the Pt/Co interface, total effective spin-mixing conductance (G eff,tot ↑↓=0.42×15 Ω-1 m-2) and two-magnon scattering (β TMS= 0.46 nm2) are first characterized, and the damping-like torque (ξDL= 0.103) and field-like torque (ξFL=-0.017) efficiencies are also calculated quantitatively by varying the thickness of the inserting Co layer. The significant enhancement of ξDL and ξFL in Pt/Co/Py than Pt/Py bilayer system originates from the interfacial Rashba-Edelstein effect due to the strong ISOC between Co-3d and Pt-5d orbitals at the Pt/Co interface. Additionally, we find a considerable out-of-plane spin polarization SOT, which is ascribed to the spin anomalous Hall effect and possible spin precession effect due to IPMA-induced perpendicular magnetization at the Pt/Co interface. Our results demonstrate that the ISOC of the Pt/Co interface plays a vital role in spin transport and SOTs-generation. Our finds offer an alternative approach to improve the conventional SOTs efficiencies and generate unconventional SOTs with out-of-plane spin polarization to develop low power Pt-based spintronic via tailoring the Pt/FM interface.

ABSTRACTWe fabricated and patterned magnetic dots from Co/Pt multilayers and optimized the structure for strong inter-dot magnetic coupling. SQUID measurements show strong perpendicular anisotropy with characteristic sheared hysteresis loops. The films are fabricated by RF-magnetron sputtering and then patterned with a 50 keV Ga+ focused ion beam (FIB) tool. This keeps surface roughness low and feature sizes in the hundred-nanometer-regime are achievable by a single processing step. Simulations with the well established SRIM (Stopping and Range of Ions in Matter) code give an estimation of the beam diameter and help to estimate the FIB patterning potential. In order to show antiferromagnetic ordering large 48×48 dot arrays of (200×200) nm2 single domain dots were fabricated. The samples were demagnetized and scanned by magnetic force microscopy (MFM) in the remanent state. The demagnetized checkerboard patterns show no frustration over hundreds of dots. The fabricated single domain magnets are prospective building blocks for field-coupled magnetic logic devices.

Laticifers are secretory structures that produce latex, forming a specialized defense system against herbivory. Studies using anatomical approaches to investigate laticifer growth patterns have described their origin; however, their mode of growth, i.e., whether growth is intrusive or diffuse, remains unclear. Studies investigating how cytoskeleton filaments may influence laticifer shape establishment and growth patterns are lacking. In this study, we combined microtubule immunostaining and developmental anatomy to investigate the growth patterns in different types of laticifers. Standard anatomical methods were used to study laticifer development. Microtubules were labelled through immunolocalization of α-tubulin in three types of laticifers from three different plant species: nonanastomosing (Urvillea ulmacea), anastomosing unbranched with partial degradation of terminal cell walls (Ipomoea nil), and anastomosing branched laticifers with early and complete degradation of terminal cell walls (Asclepias curassavica). In both nonanastomosing and anastomosing laticifers, as well as in differentiating meristematic cells, parenchyma cells and idioblasts, microtubules were perpendicularly aligned to the cell growth axis. The analyses of laticifer microtubule orientation revealed an arrangement that corresponds to those cells that grow diffusely within the plant body. Nonanastomosing and anastomosing laticifers, branched or not, have a pattern which indicates diffuse growth. This innovative study on secretory structures represents a major advance in the knowledge of laticifers and their growth mode.

Abstract Purpose 177Lu-lilotomab satetraxetan targets the CD37 antigen and has been investigated in a first-in-human phase 1/2a study for relapsed non-Hodgkin lymphoma (NHL). Tumor dosimetry and response evaluation can be challenging after radioimmunotherapy (RIT). Changes in FDG PET/CT parameters after RIT and correlations with tumor-absorbed doses has not been examined previously in patients with lymphoma. Treatment-induced changes were measured at FDG PET/CT and ceCT to evaluate response at the lesion level after treatment, and correlations with tumor-absorbed doses were investigated. Methods Forty-five tumors in 16 patients, with different pre-treatment and pre-dosing regimens, were included. Dosimetry was performed based on multiple SPECT/CT images. FDG PET/CT was performed at baseline and at 3 and 6 months. SUVmax, MTV, TLG, and changes in these parameters were calculated for each tumor. Lesion response was evaluated at 3 and 6 months (PET3months and PET6months) based on Deauville criteria. Anatomical changes based on ceCT at baseline and at 6 and 12 months were investigated by the sum of perpendiculars (SPD). Results Tumor-absorbed doses ranged from 35 to 859 cGy. Intra- and interpatient variations were observed. Mean decreases in PET parameters from baseline to 3 months were ΔSUVmax-3months 61%, ΔMTV3months 80%, and ΔTLG3months 77%. There was no overall correlation between tumor-absorbed dose and change in FDG PET or ceCT parameters at the lesion level or significant difference in tumor-absorbed doses between metabolic responders and non-responders after treatment. Conclusion Our analysis does not show any correlation between tumor-absorbed doses and changes in FDG PET or ceCT parameters for the included lesions. The combination regimen, including cold antibodies, may be one of the factors precluding such a correlation. Increased intra-patient response with increased tumor-absorbed doses was observed for most patients, implying individual variations in radiation sensitivity or biology. Trial registration ClinicalTrials.gov Identifier (NCT01796171). Registered December 2012

The theory of new axioms and laws describes nonparametric and nonlinear processes and contains 2 new axioms and 8 new laws. Unlike Classical Field Theory, it describes longitudinal or transverse non-uniform motions or complex longitudi- nal-transverse and transverse-longitudinal non-uniform motions with various parameters and with changing causes of the motion. According to the Axiom1 every unevenly rotation of one vector form open vortex which can be accelerating or decelerating and as well as transverse in 2D or longitudinal in 3D. From previous reports is understood that both the electron and the planet Earth are gravitational bodies as result. According Law1the reason for generating the electron is a transverse decelerating vortex in 2D coming from the proton which is rolled up from periphery to center and generates there longitudinal accelerating vortex in 3D. According Axiom2 the electron and the proton form resonance system. According Law2 the reason for the creation of the proton is a longitudinal vortex from out- side in 3D to the center, which generates there transverse accelerating vortex in 2D from center to periphery, perpendicular to the longitudinal vortex. It is well known the Rutherford's model of the analogy between the atomic structure and the structure of the solar system. But according new axiom and laws the reason for the creation of the planet Earth is in the generation a complex vortex in 2D (inside the third cylindrical resonator in volume of the Sun) from a longitudinal vortex in 3D ( coming from outside) . This complex vortex acts the energy control and management of Earth. It carries low-frequency power energy as a base and high-frequency pulses modulated onto the base. As described in previous report, low-frequency energy generates the inner planets in the Solar System (including Earth) and its low-frequency pulsation transforms their circular orbits into elliptical orbits. This article will describe how high frequency pulses create the personal, self-gravity of planet Earth in particular, and why they cause both a gravitational push from the outside to the body and a gravitational pull from the body out. In this report is used 2 new Axiom and 3 new Laws only.

Abstract The transverse momentum distribution of the $$ t\overline{t} $$ t t ¯ system is of both experimental and theoretical interest. In the presence of azimuthally asymmetric divergences, pursuing resummation at high logarithmic precision is rather demanding in general. In this paper, we propose the projected transverse momentum spectrum $$ \textrm{d}{\sigma}_{t\overline{t}}/\textrm{d}{q}_{\tau } $$ d σ t t ¯ / d q τ , which is derived from the classical $$ {\overrightarrow{q}}_{\textrm{T}} $$ q → T spectrum by integrating out the rejection component $$ {q}_{\tau_{\perp }} $$ q τ ⊥ with respect to a reference unit vector $$ \overrightarrow{\tau} $$ τ → , to serve as an alternative solution to remove these asymmetric divergences, in addition to the azimuthally averaged case $$ \textrm{d}{\sigma}_{t\overline{t}}/\textrm{d}\mid {\overrightarrow{q}}_{\textrm{T}}\mid $$ d σ t t ¯ / d ∣ q → T ∣ . In the context of the effective field theories, SCETII and HQET, we will demonstrate that in spite of the $$ {q}_{\tau_{\perp }} $$ q τ ⊥ integrations, the leading asymptotic terms of $$ \textrm{d}{\sigma}_{t\overline{t}}/\textrm{d}{q}_{\tau } $$ d σ t t ¯ / d q τ still observe the factorisation pattern in terms of the hard, beam, and soft functions in the vicinity of qτ = 0 GeV. Then, with the help of the renormalisation group equation techniques, we carry out the resummation at NLL+NLO, N2LL+N2LO, and approximate N2LL′+N2LO accuracy on three observables of interest, $$ \textrm{d}{\sigma}_{t\overline{t}}/d{q}_{\textrm{T},\textrm{in}},\textrm{d}{\sigma}_{t\overline{t}}/\textrm{d}{q}_{\textrm{T},\textrm{out}} $$ d σ t t ¯ / d q T , in , d σ t t ¯ / d q T , out , and $$ \textrm{d}{\sigma}_{t\overline{t}}/d\Delta {\phi}_{t\overline{t}} $$ d σ t t ¯ / d Δ ϕ t t ¯ , within the domain $$ {M}_{t\overline{t}} $$ M t t ¯ ≥ 400 GeV. The first two cases are obtained by choosing $$ \overrightarrow{\tau} $$ τ → parallel and perpendicular to the top quark transverse momentum, respectively. The azimuthal de-correlation $$ \Delta {\phi}_{t\overline{t}} $$ Δ ϕ t t ¯ of the $$ t\overline{t} $$ t t ¯ pair is evaluated through its kinematical connection to qT,out. This is the first time the azimuthal spectrum $$ \Delta {\phi}_{t\overline{t}} $$ Δ ϕ t t ¯ is appraised at or beyond the N2LL level including a consistent treatment of both beam collinear and soft radiation.