gebhart/patrepeval huggingface dataset:
Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation-Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement (2018)

<b>Purpose:</b> Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed.<b>Patients and Methods:</b> We describe a heavily pretreated patient with ovarian cancer with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune checkpoint inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (i.e., automated quantitative analysis, AQUA) and whole-exome sequencing (WES) techniques.<b>Results:</b> The patient harbored a recurrent/metastatic radiation and chemotherapy-resistant high-grade ovarian carcinoma with clear cell features. While progressing on any standard treatment modality, she demonstrated a remarkable complete response to the anti-PD1 immune checkpoint inhibitor pembrolizumab. WES results were notable for the presence a relative low number of mutations (tumor mutation load/Mb = 4.31, total mutations = 164) and a peculiar structural variant disrupting the 3' region of the <i>PD-L1</i> gene causing aberrant PD-L1 surface expression as confirmed by IHC and AQUA technology. Heavy infiltration of the PD-L1-mutated and PD-L1-overexpressing tumor with T-cell lymphocytes (i.e., CD4<sup>+</sup>/CD8<sup>+</sup> TIL), CD68<sup>+</sup> macrophages, and CD20<sup>+</sup> B cells was detected in the surgical specimen strongly suggesting immune evasion as a key mechanism of tumor growth and survival. Patient's complete clinical responses remain unchanged at the time of the writing of this report with no significant side effects reported to date.<b>Conclusions:</b> Anti-PD1 inhibitors may represent a novel treatment option for recurrent/metastatic human tumors refractory to salvage treatment harboring <i>PD-L1</i> gene structural variations causing aberrant PD-L1 expression. <i>Clin Cancer Res; 24(14); 3282-91. ©2018 AACR</i><i>See related commentary by Lheureux, p. 3233</i>.
Artifacts in dynamic CEST MRI due to motion and field shifts (2018)

Dynamic CEST studies such as dynamic glucose enhanced imaging, have gained a lot of attention recently, as it monitors the uptake and wash‐out of glucose shown in tumor models in animals (1,2) and patients with glioblastoma (3,4). The expected CEST effects after injection are rather small in tissue especially at clinical field strengths (1-2 %). Small movements during the dynamic CEST measurement together with a subtraction-based evaluation can lead to pseudo CEST effects of the same order of magnitude. These artifacts are studied herein.
THE ULTRASTRUCTURE OFSCENEDESMUS(CHLOROPHYCEAE). II. CELL DIVISION AND COLONY FORMATION1 (1975)

SUMMARY Cell division in Scenedesmus is fairly typical of other chlorococcalean genera. The closed spindle has centrioles at polar fenestrae and apparently a series of nuclear divisions precedes cytokinesis. The phycoplast system of cytokinetic microtubules predicts the path of cleavage furrows whose mode of formation is obscure. Before and during cell division, the endoplasmic reticulum invariably accumulates granular material which later, during cytokinesis, appears to he secreted via the golgi bodies. Similar dense granular material then at accumulates outside the forming daughter cells but inside the parental wall, as the latter begins eroding away. By the end of colony formation, the cellulosic parental wall has disappeared, leaving its outer sheath and attached ornamentative features (spines, combs, reticulate or warty layer, etc.) intact as a “ghost.” The spines and combs of new colonies appear to condense out of the extracellular aggregate; their precise mode of formation is obscure. As they form, the daughter cells, having become rearranged within the parental wall, stick to one another apparently at specific sites on their outer surface. A trilaminar (sporopollenin‐containing) layer arises first in each cell at these adhesive sites and immediately afterwards, dense material aggregates between the adjacent layers to give rise to the coenobial adhesive. Plaques of the trilaminar layer later appear over the rest of the cell's surface; they grow and fuse so that eventually each cell is enclosed by one continuous Trilaminar Sheath (TLS). While the plaques are forming, another dense layer materializes around the whole coenobium. Depending on the species, this layer turns into either the warty layer, in which instance it is applied directly on to the surface of the TLS except near the coenobial adhesive, or else it becomes the reticulate layer, in which instance it remains entirely separate from the TLS, soon acquiring the complex system of propping spikelets which suspend it from the coenobial surface. When fully farmed, the daughter coenobium is tightly compressed within the parental TLS, with its spines folded lengthwise along the daughter cells. Release of the colony follows a quite explosive rupturing of the parental TLS, and immediately upon release, the daughter colony flattens out and erects its spines.
Optical Shock Wave Imaging for Aviation Security (2003)

This paper is about shock wave propagation inside an aircraft fuselage, caused either by a terrorist device or by an accidental explosion. The concern over blasts inside airframes, stemming from past terrorist attacks on commercial aviation using concealed explosives, continues unabated and extends to luggage, passengers, and air cargo. In earlier publications by the present authors, it was noted that all previous aviation security studies lacked optical shock imaging, the principal tool of explosion and shock wave research. In an effort to correct this, high-speed schlieren shock wave cinematography methods on a large scale are demonstrated here for aircraft hardening studies. This capability is used to examine shock propagation in realistic aircraft interior scenarios, as well as to carry out some basic experiments toward an improved understanding of internal blast wave behavior.
Pretest probability assessment derived from attribute matching (2005)

Attribute matching estimated a very low PTP for ACS in a significantly larger proportion of ED patients compared with a validated LRE.
SHOULDER PROSTHESIS AFTER RADIOTHERAPY (2004)

Purpose: The purpose of this study was to analyse outcome of shoulder prostheses after radiotherapy, to define a specific clinicoradiological entity, and evaluate incidence of complications. Material and methods: Fourteen shoulder prostheses were implanted in 13 women who had been treated for breast cancer with complementary radiotherapy and one man treated for Hodgkin’s lymphoma. The time from radiothearpy to implantation was 16 years, seven months. Two forms were identified on the preoperative x-rays: seven cases with typical avascular osteonecrosis according to the Arlet and Ficat classification, and seven cases with a radiographic presentation of arthritis or degenerative disease. Humeral prostheses were used in five cases and a total shoulder arthroplasty in nine. Results: Four implants had to be removed, three for sepsis, and five patients required revision surgery. The mean postoperative Constant score for the ten prostheses still in place was 53.1 points with a mean elevation of 111° at three years seven months follow-up. The gain in pain score was 8.5 points with a mean result of 10.9 points. The results were different depending on the initial radiological form, with less favourable outcome observed in typical osteonecrosis. Discussion: This study demonstrated a particular radio-clinical entity independent of classical osteonecrosis of the humeral head. The surgical procedure was more difficult and the outcome was less satisfactory than in the classical forms with a high rate of complications.
Cellular variable stiffness materials for ultra-large reversible deformations in reconfigurable structures (2006)

Structures that can physically adapt to fulfill many roles can enable a new generation of high-performance military systems. The key to achieving substantial benefit from shape-changing operations is large changes in structural geometry and stiffness. In this study, we demonstrate variable stiffness cellular materials capable of large global changes in area through local buckling modes. Furthermore, stiffness properties and Poisson ratios may be tailored to provide desirable structural reconfiguration properties such as negative Poisson ratio and highly anisotropic stiffness. However, stiffness properties of cellular materials are two to three orders of magnitude below their constitutive materials properties. Their elastic properties can vary considerably as a function of the applied strain level due to the redistribution of structural material within the cells. Another complication is the difficulty in controlling the local buckling mode due to sensitivity to boundary conditions and loading conditions.
Reconstitution in vitro de la biosynthèse de la microcine J25, peptide antimicrobien structuré en lasso (2007)

La microcine J25 (MccJ25) est un peptide antimicrobien de 21 acides aminés produit selon la voie ribosomiale et sécrété par une souche d'Escherichia coli. MccJ25 présente une structure très originale dite en lasso, impliquant un cycle lactame formé entre l'extrémité N-terminale et la chaîne latérale de l'acide glutamique en position 8, la région C-terminale étant piégée et fermement maintenue stériquement dans le cycle. De telles structures en lasso ont été décrites également pour quelques peptides naturels inhibiteurs d'enzymes, mais la voie de biosynthèse de tous ces peptides est inconnue. Le système génétique de MccJ25 est bien caractérisé. Il comporte un gène codant McjA, le précurseur de la microcine constitué de 58 acides aminés, un gène codant McjD, une protéine impliquée dans l'export de MccJ25 conférant à la souche productrice la résistance à MccJ25, et deux gènes codant McjB et McjC, deux protéines supposées être impliquées dans la maturation de McjA pour former la microcine active. Les recherches d'homologies ne permettent pas de prévoir la fonction de McjB et McjC, et par conséquent de proposer un mécanisme de maturation du précurseur McjA. Dans le but de caractériser la voie de biosynthèse de MccJ25, nous avons entrepris des expériences d'inactivation/complémentation des gènes mcjB et mcjC, qui ont montré que les deux protéines McjB et McjC sont requises pour la production de MccJ25 par la souche productrice. Parallèlement, les protéines recombinantes McjA, McjB et McjC munies d'une étiquette histidine ont été surexprimées puis purifiées afin de réaliser des expériences de reconstitution in vitro de la biosynthèse de MccJ25. La formation de MccJ25 a été détectée (i) par des tests d'activité antimicrobienne spécifique de MccJ25 et (ii) par couplage chromatographie liquide haute performance - spectrométrie de masse. Nous avons montré qu'in vitro, la protéine His6-McjA peut être convertie en MccJ25 sous l'action combinée de His6-McjB et His6-McjC, en présence d'ATP et de Mg2+. Ce résultat est la première reconstitution in vitro de la maturation d'un peptide en lasso et présente un intérêt biotechnologique important en terme de biosynthèse de peptides de structure complexe.
Effect of primary particle size and aggregate size of modified graphene oxide on toughening of unsaturated polyester resin (2019)

Graphene‐based nanomaterial tougheners can effectively toughen thermosetting resins at an extremely low loading level with minimal change in T g or modulus. However, previous research has indicated that this toughening effect shows only small responses to changing graphene oxide (GO) surface modifications, resin dispersion processing methods, and GO loading levels. It is hypothesized that the physical dimensions of GO particles affect the toughening behavior of graphene‐based additives. In this study, the sizes of primary and aggregated surface‐modified GO (mGO) particles were measured directly using scanning electron microscopy. The effects of the differences in size on fracture toughness ( K IC ), bending modulus, and flexural strength of an unsaturated polyester resin were evaluated. The sizes of primary mGO particles were estimated from the sizes of GO particles prior to their surface modification and the sizes of mGO aggregates after dispersion in the resin. This study shows that as little as 0.005 wt% mGO can increase K IC by nearly 20%. This toughening effect is independent of primary particle size. Reducing mGO aggregate sizes by chemical modification or sonication shifts the optimal loading level of mGO‐based tougheners to lower concentrations, but the maximal achievable toughness cannot be changed by improving dispersion or particle–matrix interactions. POLYM. COMPOS., 40:3886–3894, 2019. © 2019 Society of Plastics Engineers
Costimulatory pathways in transplantation: challenges and new developments (2009)

T cells are central to graft rejection, and therefore preventing T cells from recognizing and destroying allografts remains an important area of transplant research. However, T cells are also required for transplant tolerance; a subset can enforce a state of tolerance by functioning as regulatory cells. As both rejection and regulation directed against alloantigens require T-cell activation, costimulatory molecules undoubtedly play an important role in regulating both processes and ultimately the fate of the allograft. However, costimulation involves an incredibly complex array of interactions that may act contemporaneously or at different times; these interactions can have additive or opposing effects on T-cell activation or differentiation. While some costimulatory molecules mediate activation of naive T cells or generation of memory T cells, others inhibit T-cell activation and promote anergy or apoptosis. Moreover, a given pathway can have diametrically different effects on T-effector cells and regulatory T cells (Tregs). Such a complexity presents both challenges and opportunities in targeting T-cell costimulatory pathways to promote transplant tolerance. In this review article, we provide a summary of recent advances in our understanding of T-cell costimulatory pathways in regulating different phases of the T-cell response in transplant models. We focus specifically on costimulatory molecules in the immunoglobulin (Ig) superfamily, tumor necrosis factor (TNF)/TNF receptor superfamily, and in the emerging T-cell Ig domain and mucin domain family (TIM), highlighting their unique and redundant roles in regulating the T-effector and Treg responses after transplantation. Finally, we summarize emerging approaches toward inducing tolerance by tipping the balance between cytopathic T-effector cells and protective Tregs by selectively targeting specific T-cell costimulatory pathways that are critically involved.
Molecular architectures of benzoic acid-specific type III polyketide synthases (2017)

Biphenyl synthase and benzophenone synthase constitute an evolutionarily distinct clade of type III polyketide synthases (PKSs) that use benzoic acid-derived substrates to produce defense metabolites in plants. The use of benzoyl-CoA as an endogenous substrate is unusual for type III PKSs. Moreover, sequence analyses indicate that the residues responsible for the functional diversification of type III PKSs are mutated in benzoic acid-specific type III PKSs. In order to gain a better understanding of structure-function relationships within the type III PKS family, the crystal structures of biphenyl synthase from Malus × domestica and benzophenone synthase from Hypericum androsaemum were compared with the structure of an archetypal type III PKS: chalcone synthase from Malus × domestica. Both biphenyl synthase and benzophenone synthase contain mutations that reshape their active-site cavities to prevent the binding of 4-coumaroyl-CoA and to favor the binding of small hydrophobic substrates. The active-site cavities of biphenyl synthase and benzophenone synthase also contain a novel pocket associated with their chain-elongation and cyclization reactions. Collectively, these results illuminate structural determinants of benzoic acid-specific type III PKSs and expand the understanding of the evolution of specialized metabolic pathways in plants.
Control inbound traffic: Evolving the control plane routing system with Software Defined Networking (2017)

The Border Gateway Protocol (BGP) is the current standard protocol for the inter-domain routing system. Although BGP makes easy to manipulate the output traffic by an Autonomous System (AS), it lacks other desired features such as convenient management of incoming traffic to an AS. Thus, we propose a framework to evolve the control plane routing system that is compatible with BGP (smooth transition), uses SDN technologies and can be used to management the incoming traffic of multihomed ASes. Based on our framework, a load balancing application was developed and applied to a scenario to depict the proof of concept of our framework. The results were compared and discussed with BGP AS-Path Prepending technique, shown an improvement of inbound traffic bandwidth utilization.
Cytarabine Either with Induction or Conditioning May Improve Outcomes Among Those Undergoing Autologous Transplantation in First or Second Remission for Mantle Cell Lymphoma (2012)

Abstract Abstract 4546 Introduction: Consolidation with autologous transplantation (AutoSCT) may extend progression free survival when administered following initial induction. Published data suggest intensive cytarabine containing induction may improve outcome when administered prior to autologous transplantation. Methods: We retrospectively evaluated all patients with MCL transplanted at our institution before 2010. We identified 57 patients, among whom 52 were transplanted in first or second remission. Results: 21 patients had received a cytarabine containing induction (most commonly R-HyperCVAD), among whom 14 also received cytarabine as a component of conditioning (BEAM+/−R). The most common induction in the remaining patients was R-CHOP. Among the 31 who did not receive a cytarabine based induction, 23 received cytarabine as a component of the pre-transplant conditioning regimen (BEAM+/−R). The median PFS for those getting cytarbine with induction and conditioning was approximately 28 months (at which time 51% of patients continued without progression). The median PFS for those getting cytarabine with conditioning only was approximately 38 months (at which time 47% continued without progression). Logrank analysis shows no statistically significant difference between these groups (p one-sided = 0.29). Alternatively, those who did not receive any cytarabine had a median PFS of 20 months, with no survival beyond 33 months. Logrank analysis shows this to be inferior to those receiving cytarabine with induction/conditioning (p one-sided = 0.049), as well as among those who received cytarabine with conditioning only (p one-sided = 0.001). Conclusions: In the absence of randomized comparisons it is difficult to draw firm conclusions on the role of induction. These analyses would suggest that among those with chemosensitive disease able to proceed to transplant, more modern conditioning with cytarabine containing regimens may make up for lack of exposure to this agent during induction. Disclosures: Sokol: Celgene: Honoraria, Speakers Bureau.
&gt;500-fs soliton pulse in a passively mode-locked surface-emitting laser with 100-mW average power (2003)

Summary form only given. Pulsed semiconductor lasers do not generally use the broad gain bandwidth to full advantage in the generation of sub-picosecond pulses. Here we show a breakthrough to the femtosecond level for Quantum-Well (QWs) VCSEL systems with high output power. We show a simple technology method to obtain fast recovery QW absorbers in the picosecond scale with low non-saturable losses. Our all-epitaxial VECSEL gain structure design gives a broadband smooth gain and efficient diode pumping. It was grown by MOCVD on a GaAs substrate. The bottom stack is an AlAs/GaAs Bragg structure, designed at 1030 nm. The active region consists of six strained balanced InGaAs/GaAsP QWs.
Acute graft-versus-host disease after allogeneic bone marrow transplantation. (1983)

In 25 patients receiving allogeneic bone marrow transplants methotrexate was used to prevent acute graft-versus-host disease (GVHD). Acute GVHD, grades 2 to 4, developed in only 5 (20%) of the patients. The incidence of acute GVHD in other series of recipients of bone marrow transplants has ranged from 5% to 76%. A review of the literature suggests that this variation cannot be completely accounted for by age, type of disease treated by transplantation or type of GVHD prophylaxis. However, transfusion of allogeneic lymphocytes that have not been completely inactivated by irradiation (e.g., in platelet and granulocyte preparations) and inadequate isolation-decontamination procedures may increase the probability of GVHD following bone marrow transplantation.
Intervertebral disc cell response to dynamic compression is age and frequency dependent (2008)

The maintenance of the intervertebral disc extracellular matrix is regulated by mechanical loading, nutrition, and the accumulation of matrix proteins and cytokines that are affected by both aging and degeneration. Evidence suggests that cellular aging may lead to alterations in the quantity and quality of extracellular matrix produced. The aims of this study were to examine the role of loading and maturation (a subset of aging), and the interaction between these two factors in intervertebral disc cell gene expression and biosynthesis in a controlled 3D culture environment. Cells were isolated from young (4-6 months) and mature (18-24 months) bovine caudal annulus fibrosus and nucleus pulposus tissue. Isolated cells were seeded into alginate and dynamically compressed for 7 days at either 0.1, 1, or 3 Hz or maintained as a free-swelling control. After 7 days, DNA and sulfated glycosaminoglycan contents were analyzed along with real time, quantitative reverse transcription-polymerase chain reaction analysis for collagen types I and II, aggrecan, and matrix metalloproteinase-3 gene expression. Results suggest that maturation plays an important role in intervertebral disc homeostasis and influences the cell response to mechanical loading. While isolated intervertebral disc cells responded to mechanical compression in 3D culture, the effect of loading frequency was minimal. Altered cellular phenotype and biosynthesis rates appear to be an attribute of the cell maturation process, potentially independent of changes in cellular microenvironment associated with lost nutrition and disc degeneration. Mature cells may have a decreased capacity to create or retain extracellular matrix components in response to mechanical loading compared to young cells.
A Study on Optical Diffraction Characteristics of Skewed MEMS Pitch Tunable Gratings (2007)

This paper presents a pitch tunable grating light valve integrated with high-voltage (40 V) driver circuits that target for image projection display devices. In our work, optical light angle is modulated by changing the period of the MEMS grating pixel by means of electrostatic actuation. In addition, we developed a MEMS grating light valve with a skewed angle for elimination of the inter-spot crosstalk. The skewed gratings were found to spread the +/- 1 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">st</sup> order diffraction off the axis. Optical diffraction angles of 6.6 degrees (OFF-state) and 3.3 degrees (ON-state) were obtained.