gebhart/patrepeval huggingface dataset:
Combination of T-Cell Bispecific Antibodies With PD-L1 Checkpoint Inhibition Elicits Superior Anti-Tumor Activity (2020)

T-cell Bispeciﬁc Antibodies (TCBs) elicit anti-tumor responses by cross-linking T-cells to tumor cells and mediate polyclonal T-cell expansion that is independent of T-cell receptor specificity. TCBs thus offer great promise for patients who lack antigen-speciﬁc T-cells or have non-inflamed tumors, which are parameters known to limit the response of checkpoint inhibitors. The current study deepens the understanding of TCB mode of action and elaborates on one of the adaptive resistance mechanisms following its treatment <i>in vivo</i> in humanized mice and syngeneic pre-clinical tumor models. Single-agent TCB treatment reduced tumor growth compared with controls and led to a 2-10-fold increase in tumor-infiltrating T-cells, regardless of the baseline tumor immune cell infiltration. TCB treatment strongly induced the secretion of CXCL10 and increased the frequency of intra-tumor CXCR3+ T-cells pointing to the potential role of the CXCL10-CXCR3 pathway as one of the mechanisms for T-cell recruitment to tumors upon TCB treatment. Tumor-infiltrating T-cells displayed a highly activated and proliferating phenotype, resulting in the generation of a highly inflamed tumor microenvironment. A molecular signature of TCB treatment was determined (CD8, PD-1, MIP-a, CXCL10, CXCL13) to identify parameters that most robustly characterize TCB activity. Parallel to T-cell activation, TCB treatment also led to a clear upregulation of PD-1 on T-cells and PD-L1 on tumor cells and T-cells. Combining TCB treatment with anti-PD-L1 blocking antibody improved anti-tumor efficacy compared to either agent given as monotherapy, increasing the frequency of intra-tumoral T-cells. Together, the data of the current study expand our knowledge of the molecular and cellular features associated with TCB activity and provide evidence that the PD-1/PD-L1 axis is one of the adaptive resistance mechanisms associated with TCB activity. This mechanism can be managed by the combination of TCB with anti-PD-L1 blocking antibody translating into more efficacious anti-tumor activity and prolonged control of the tumor outgrowth. The elucidation of additional resistance mechanisms beyond the PD-1/PD-L1 axis will constitute an important milestone for our understanding of factors determining tumor escape and deepening of TCB anti-tumor responses in both solid tumors and hematological disorders.
Mechanistic Analysis of the Phosphonate Transition-state Analogue-derived Catalytic and Non-catalytic Antibody (2007)

The esterolytic catalytic antibody (catAb) has the positive charged region interacting with the carbonyl group of the ester substrate. To examine how such a region interacts with the substrate, we compared the catAb with the non-catalytic antibody (non-catAb) for interaction with the non-cleavable amide substrate (a mimic of the ester substrate) and the two end products. Surface plasmon resonance (SPR) analysis revealed that the amide substrate gave the equivalent K(d) values for the two antibodies, whereas both the on-rate and off-rate of the catAb were five-times lower than those of the non-catAb. In agreement with SPR analysis, saturation transfer difference (STD) NMR spectroscopy detected the STD signals only between the catAb and one of the product, suggesting the slower exchange rates of the amide substrate in the catAb as compared with the mixing times, whereas it was not the case with the non-catAb. Transferred nuclear Overhauser effect NMR spectroscopy showed the negative signals for only between the non-catAb and the amide substrate or the product, again suggesting the lower off-rates of the catAb as compared with the mixing times. The decreased interaction rates should be the primary consequence of the positively charged region in the combining site in the catAb.
Cellular and circuit mechanisms underlying spinocerebellar ataxias (2016)

Degenerative ataxias are a common form of neurodegenerative disease that affect about 20 individuals per 100,000. The autosomal dominant spinocerebellar ataxias (SCAs) are caused by a variety of protein coding mutations (single nucleotide changes, deletions and expansions) in single genes. Affected genes encode plasma membrane and intracellular ion channels, membrane receptors, protein kinases, protein phosphatases and proteins of unknown function. Although SCA-linked genes are quite diverse they share two key features: first, they are highly, although not exclusively, expressed in cerebellar Purkinje neurons (PNs), and second, when mutated they lead ultimately to the degeneration of PNs. In this review we summarize ataxia-related changes in PN neurophysiology that have been observed in various mouse knockout lines and in transgenic models of human SCA. We also highlight emerging evidence that altered metabotropic glutamate receptor signalling and disrupted calcium homeostasis in PNs form a common, early pathophysiological mechanism in SCAs. Together these findings indicate that aberrant calcium signalling and profound changes in PN neurophysiology precede PN cell loss and are likely to lead to cerebellar circuit dysfunction that explains behavioural signs of ataxia characteristic of the disease.
Supplementary Figure S2 from First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20<sup>+</sup> Non-Hodgkin Lymphomas (2023)

&lt;p&gt;Immune cell fractions derived from flow cytometry were highly concordant with those derived from RNA-Seq deconvolution in baseline blood samples from patients with follicular lymphoma. Pearson correlations were computed for each immune subset. Solid lines were fitted using linear regression.&lt;/p&gt;
Synthesis and Characterization of Chiral Periodic Mesoporous Organosilicas (2007)

Händisches in Händen: Periodische mesoporöse Organosilicate mit chiralen Kanälen wurden mithilfe eines achiralen fluorierten Tensids (FC-4911) und Cetyltrimethylammoniumbromid als strukturdirigierende Agentien hergestellt. Spiralförmige, aus 1,4-Bis(triethoxysilyl)benzol erhaltene Proben weisen eine periodische Struktur mit kristallartigen mesoporösen Wänden auf (siehe TEM-Bild). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2007/z702666_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Polymorphs, pseudopolymorphs and the crystal engineer: friends and foes (2017)

The goal of the crystal engineer to design solids with predictable properties is generally predicated on the idea that molecular components that form a solid will assemble via supramolecular synthons. While supramolecular synthons will typically form with success vis-a-vis organic solution-phase chemistry, a last 'stance' in crafting the structure of an organic solid may likely depend on influences of polymorphism and related pseudopolymorphism. Indeed, the ability of components that make up a crystal lattice to form different crystal structures -exhibit polymorphism -can affect properties such as solubility, gas uptake, and reactivity, and have ramifications, for example, to legal issues surrounding pharmaceutics. The common practice of chemists to form crystals from solution also means that it is important to consider the crystal landscape to involve incorporation(s) of solvent -pseudopolymorphism. In this presentation, the terms polymorphism and pseudopolymorphism will be discussed with examples from our laboratory and the recent literature. An attempt will be made to discuss how polymorphism and pseudopolymorphism impact the practice of crystal engineering as related to the design and tailoring of organic solids.
Self‐Stiffening Behavior of Reinforced Carbon Nanotubes Spheres (2017)

Strong van der Waals forces between individual carbon nanotubes pose a major hurdle for effective use of nanotubes as reinforcement in nanocomposite due to agglomeration. In this paper, the authors show that van der Waals forces in combination with functionalization of carbon nanotubes, can be utilized to design nanocomposites mimicking stiffening behavior normally observed in biological materials such as fibrin gels, health bones, actin filaments in cytoskeletons etc. Carbon nanotube spheres are used as reinforcement in an elastomer matrix and when subjected to dynamic loads exhibit significant self‐stiffening. Increased stiffness is also observed in dynamic loading after every relaxation cycle. The authors further show high energy absorption of the nanocomposite in impact tests. Authors study shows that the rational design of macroscale materials from nano‐scale constituents can be achieved utilizing simple methodology to produce multifunctional materials with broad applications.
Synergistic growth-inhibitory effects of two tyrosine kinase inhibitors, dasatinib and PKC412, on neoplastic mast cells expressing the D816V-mutated oncogenic variant of KIT (2007)

Combinations of targeted drugs may represent an interesting pharmacologic approach for the treatment of aggressive SM or MCL.
Evaluation of outgassing from a fluorinated resist for 157-nm lithography (2004)

We have evaluated the outgassing products and the in-situ transmittance of a contaminated CaF<sub>2</sub> substrate for monocyclic fluoropolymers with four protecting groups: methoxymethyl (MOM), tert-butoxycarbonyl (t-BOC), menthoxymethyl (MM), and 2-cyclohexylcyclohexyloxymethyl (CCOM). We have also evaluated the same type of fluoropolymer with seven kinds of photo-acid generators (PAGs) added to a base fluoropolymer solution. We found little correlation between the total amount of outgassing from the polymer and the decreasing rate of the CaF<sub>2</sub> substrate transmittance caused by outgassing adhesion. Although the MOM protecting group generated the largest amount of outgassing products, the most substantial decrease in the transmittance was observed for the t-BOC protecting group. Also, the outgassing products due to use of a PAG did not greatly reduce the absorption coefficient of a CaF<sub>2</sub> substrate regardless of the kind of PAG. Therefore, the absorption coefficient of the outgassing-contaminated CaF<sub>2</sub> substrate appears to be more sensitive to the type of protecting group, especially the t-BOC protecting group including a t-butyl unit, rather than the type of fluoropolymer or PAG. We analyzed the substrate surface contaminant due to the t-butyl unit by x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and time-of-flight secondary ion mass spectrometry (TOF-SIMS), and found that increasing amounts of organic compounds, containing mainly C- and H-atoms, were adhered to and deposited on the substrate surface with an increasing irradiation dose. We speculate that the contaminants on a CaF<sub>2</sub> surface with or without an anti-reflective coating were formed not only through mere physical adsorption, but also through certain chemical combinations. We conclude that in terms of material design of the fluoropolymer resist for 157-nm lithography, we need to pay attention to the protecting group of polymers, especially the t-BOC or t-butyl protecting group, which generates isobutene product during 157-nm irradiation.
Relationship Between Serum Concentrations of the Growth Factor Pleiotrophin and Pleiotrophin-Positive Tumors (1998)

Elevated serum pleiotrophin levels can indicate the presence of tumors expressing this factor. Monitoring serum levels of pleiotrophin may prove useful in determining the pharmacologic efficacy of cytotoxic or anti-pleiotrophin therapy.
Near-Field Wireless Power Transfer with Dynamic Metasurface Antennas (2022)

Radio frequency wireless power transfer (WPT) enables charging low-power mobile devices without relying on wired infrastructure. Current existing WPT systems are typically designed assuming far-field propagation, where the radiated energy is steered in given angles, resulting in limited efficiency and possible radiation in undesired locations. When large arrays at high frequencies, such as dynamic metasurface antenna (DMA), are employed, WPT might take place in the radiating nearfield (Fresnel) region where spherical wave propagation holds, rather than plane wave propagation as in the far-field. In this paper, we study WPT systems charging multiple devices in the Fresnel region, where the energy transmitter is equipped with an emerging DMA, exploring how the antenna configuration can exploit the spherical wavefront to generate focused energy beams. In particular, after presenting a mathematical model for DMA-based radiating near-field WPT systems, we characterize the weighted sum-harvested energy maximization problem of the considered system, and we propose an efficient solution to jointly design the DMA weights and digital precoding vector. Simulation results show that our design generates focused energy beams that are capable of improving energy transfer efficiency in the radiating near-field with minimal energy pollution.
Modulation of Aβ generation by small ubiquitin-like modifiers does not require conjugation to target proteins (2007)

The sequential processing of the APP (amyloid precursor protein) by the beta- and gamma-secretase and generation of the Abeta (amyloid-beta) peptide is a primary pathological factor in AD (Alzheimer's disease). Regulation of the processing or turnover of these proteins represents potential targets for the development of AD therapies. Sumoylation is a process by which SUMOs (small ubiquitin-like modifiers) are covalently conjugated to target proteins, resulting in a number of functional consequences. These include regulation of protein-protein interactions, intracellular trafficking and protein stability, which all have the potential to impact on several aspects of the amyloidogenic pathway. The present study examines the effects of overexpression and knockdown of the major SUMO isoforms (SUMO1, 2 and 3) on APP processing and the production of Abeta peptides. SUMO3 overexpression significantly increased Abeta40 and Abeta42 secretion, which was accompanied by an increase in full-length APP and its C-terminal fragments. These effects of SUMO3 were independent of its covalent attachment or chain formation, as mutants lacking the motifs responsible for SUMO chain formation or SUMO conjugation led to similar changes in Abeta. SUMO3 overexpression also up-regulated the expression of the transmembrane protease BACE (beta-amyloid-cleaving enzyme), but failed to affect levels of several other unrelated proteins. Suppression of SUMO1 or combined SUMO2+3 by RNA interference did not affect APP levels or Abeta production. These findings confirm a specific effect of SUMO3 overexpression on APP processing and the production of Abeta peptides but also suggest that endogenous sumoylation is not essential and likely plays an indirect role in modulating the amyloid processing pathway.
Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract (2014)

Age-related cataract is a leading cause of blindness worldwide, especially in developing countries where access to cataract surgery remains limited. Previous linkage and candidate gene studies suggested genetic influences on age-related nuclear cataract but few genetic markers have been identified thus far. We conducted genome-wide association studies on 4569 Asians (including 2369 Malays and 2200 Indians), and replicated our analysis in 2481 Chinese from two independent cohorts (1768 Chinese in Singapore and 803 Chinese in Beijing). We confirmed two genome-wide significant loci for nuclear cataract in the combined meta-analysis of four cohorts (n = 7140). The first locus was at chromosome 3q25.31 in KCNAB1 (rs7615568, fixed-effect Pmeta = 2.30 × 10(-8); random-effect Pmeta = 1.08 × 10(-8)). The second locus was at chromosome 21 in the proximity of CRYAA (rs11911275, fixed-effect Pmeta = 2.77 × 10(-8); random-effect Pmeta = 1.98 × 10(-9)), a major protein component of eye lens. The findings were further supported by up-regulation and down-regulation of KCNAB1 and CRYAA in human lens capsule, respectively, as the severity of nuclear cataract increases. The results offer additional insights into the pathogenesis of nuclear cataract in Asians.
Saturation and Subcooled Boiling on Copper Nano-Dendrites Surfaces (2010)

Nucleate boiling of PF-5060 liquid on nano-dendrites surfaces is investigated at saturation and ΔTsub = 10, 20 and 30 K. The electrochemically deposited surfaces layers on 10 × 10 mm Cu substrates are ∼ 139, 171 and 220 μm thick. CHF and hMNB are significantly higher and occur at lower ΔTsat than has been reported on plane, macro-, micro- and nano-structured surfaces. CHF increases linearly 4.5%/K, while hMNB, occurring at end of the fully developed nucleate boiling region, decreases and corresponding ΔTsat increases with increased subcooling. For the 171 μm-thick surface: CHFsat of 27.8 W/cm2 increases to 63.25 W/cm2 at ΔTsub = 30 K, while saturation hMNB of 13.5 W/cm2.K decreases to 12.7 W/cm2.K at 30 K subcooling. ΔTsat at hMNB and CHF increases from 2.0 K and 2.16 K at saturation to 4.2 and 6.42 K at 30 K subcooling.
Resolving Endurance and Program Time Trade-Off of 40nm TaOx-Based ReRAM by Co-Optimizing Verify Cycles, Reset Voltage and ECC Strength (2017)

Trade-off between reliability and program time in 40nm TaO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> -based Resistive random access memory (ReRAM) is experimentally investigated. By evaluating bit error rate (BER) and the current distributions, the complicated trade-off among Set/Reset cycles, reset voltage (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">RESET</sub> ) and with or without verify are investigated. At lower Set/Reset cycles, the current window is enhanced by introducing Set/Reset cycles and increasing V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">RESET</sub> . However, at higher Set/Reset cycles, the excessive stress caused by the verify and high V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">RESET</sub> increases BER. Because of this "twisted" characteristics, verify should not be performed at higher Set/Reset cycles. To explain these complicated errors, the physical model based on oxygen vacancy (Vo), diffusion is described. Finally, the system-level solution to minimize errors by dynamically co-optimizing ECC strength, verify cycles and the Reset voltage based on Set/Reset cycles is proposed.
Cyber-Physical Attacks With Control Objectives (2017)

This paper studies attackers with control objectives against cyber-physical systems (CPSs). The goal of the attacker is to counteract the CPS's controller and move the system to a target state while evading detection. We formulate a cost function that reflects the attacker's goals, and, using dynamic programming, we show that the optimal attack strategy reduces to a linear feedback of the attacker's state estimate. By changing the parameters of the cost function, we show how an attacker can design optimal attacks to balance the control objective and the detection avoidance objective. Finally, we provide a numerical illustration based on a remotely controlled helicopter under attack.
Polycarbonates (2000)

Abstract Polycarbonates are an unusual and extremely useful class of polymers. The vast majority of polycarbonates are based on bisphenol A (BPA) and sold under the trade names Lexan, Makrolon, Calibre, and Panlite. BPA polycarbonates having high glass‐transition temperatures are widely regarded for optical clarity and exceptional impact resistance and ductility at room temperature and below. Other properties such as modulus, dielectric strength, or tensile strength are comparable to other amorphous thermoplastics at similar temperatures below their respective glass‐transition temperatures. Polycarbonates are prepared commercially by two processes: Schotten‐Baumann reaction of phosgene and an aromatic diol in an amine‐catalyzed interfacial condensation reaction, or via base‐catalyzed transesterification of a bisphenol with a monomeric carbonate such as diphenyl carbonate. Important products are also based on polycarbonates in blends with other polymers, copolymers, branched resins, flame‐retardant compositions, foams, and other materials. Polycarbonate, produced globally, has been the object of research studies, owing to its widespread utility and unusual properties. This article summarizes the preparation, properties, and utility of polycarbonates.
Rigorous electromagnetic analysis of diffraction by finite-number-of-periods gratings (1997)

The diffraction characteristics of finite-number-of-periods (FNP) gratings are determined by using rigorous electromagnetic analysis based on the two-region formulation of the exact boundary element method. Gratings with 5, 9, 13, and 17 periods are analyzed and compared with infinite-number-of-periods (INP) gratings in terms of diffraction efficiencies and field patterns. Both dielectric transmission diffractive devices and metallic reflection diffractive devices are treated for TE and TM normally incident light. Furthermore, both 2-level and 8-level grating structures are treated. The diffraction properties of FNP gratings are shown to approach smoothly those of INP gratings as the number of periods increases.
Identification of High-Potency Neuropeptide Y Analogues through Systematic Lactamization (1997)

In the pursuit of potent analogues of neuropeptide Y (NPY) that are selective for the Y1 receptor subtype, two lactam bridge scans of a centrally truncated parent compound were synthesized. A single lactam bridge (gamma-carboxyl of Glu to epsilon-amino of Lys) extending from residues i to i + 3 or i to i + 4 of the proposed alpha-helical region (residues 25-31 of NPY) was introduced in des-AA7-24[Gly6]NPY. Cyclogues (contraction of cyclic analogues), which were approximately one-half the size of native NPY, were initially screened for binding affinity at two discrete NPY receptor types using human neuroblastoma cell membranes, SK-N-MC and SK-N-BE2. Exploitation of the subtle differences present on each receptor type allowed for the identification of cyclogues which bound specifically to Y1 receptors with increased affinity when compared to the corresponding linear parent analogue, while one short Y1 specific cyclogue, des-AA2,3,5,7-24cyclo-(26/29)[Gly6,Glu26,Lys2 9,Pro34]NPY, bound with Ki = 16 nM. Other cyclogues showed distinct preference for Y2 receptors and bound in the low-nanomolar range. Functionally, the compounds inhibited the norepinephrine-stimulated accumulation of cAMP indicating that all acted as agonists with varying potencies.
New current–mode special function continuous-time active filters employing only OTAs and OPAMPs (2004)

This paper reports three current mode second order filters, each of which realizes a specific function without any external passive elements. These filters realize low-pass notch (LPN), high-pass notch (HPN) and all-pass (AP) functions. Two OPAMPs, a double output OTA and a single output OTA are employed for each circuit. The filter structures can be easily cascaded since they have high output impedances. This property is especially useful for achieving high-order filters using these LPN and HPN filters as building blocks. The presented theory is verified with macro models in SPICE simulations and, using the SPICE parameters of the layout technology, post layout simulations are carried out, with parasitics extracted from the layouts of the filter chips.