gebhart/patrepeval huggingface dataset:
276 Engineering of synthetic chemokine receptors into iPSC-derived CAR-T cells to increase homing and enhance trafficking into solid tumors (2022)

<h3>Background</h3> Despite the success of chimeric antigen receptor (CAR)-T cells in treating hematological malignancies, the efficacious treatment of solid tumors has been hampered by lack of CAR-T cell persistence, tumor-associated antigen heterogeneity, and the immuno-suppressive tumor microenvironment (TME). In addition, trafficking of CAR-T cells to solid tumors, potentially due to a chemokine-chemokine receptor mismatch between the tumor and the CAR-T cells, has proven ineffective. Early and sustained detection of T cells within a solid tumor has been associated with better outcomes across several clinical trials, suggesting that strategies focused on enabling CAR-T cell homing and trafficking can generate significant therapeutic benefit. <h3>Methods</h3> IL8/CXCL8, a ligand for the chemokine receptor CXCR2, has been detected in many cancer types including ovarian, breast, prostate and renal and is often associated with poor prognosis and overall survival. We have previously shown high baseline expression and inducible upregulation of IL8 following chemo- or radiotherapy conditioning in multiple tumor lines. We therefore engineered CXCR2 into induced pluripotent stem cell (iPSC)-derived CAR-T (CAR iT) cells to express a synthetic CXCR2 transgene. <h3>Results</h3> CXCR2-engineered iPSCs were differentiated to manufacture alpha-beta CAR iT cells expressing uniform and high levels of the chemokine receptor (&gt;90% CXCR2 expression). Importantly, CXCR2 expression did not affect CAR-dependent effector function. CXCR2 engineered CAR iT cells demonstrated specific and functional <i>in vitro</i> chemotactic migration to recombinant IL8 and tumor preconditioned media (up to 3 fold increase compared to control CAR iT cells). In preclinical <i>in vivo</i> assessment with either (i) an aggressive ovarian xenograft model that produces high levels of CXCL8, or (ii) a triple negative breast cancer xenograft model that expresses CXCL8 following cyclophosphamide/fludarabine preconditioning, CXCR2-engineered CAR iT cells demonstrated enhanced infiltration (SKOV3 model; 6.01e6 cells/gr tumor vs 0.94e6 cells/gr tumor with CXCR2+ CAR iT cells vs control CAR iT cells, respectively) and increased retention specifically within the solid tumor microenvironment, resulting in improved tumor control (SKOV3 model; 81.3% TGI vs 60.9% TGI with CXCR2+ CAR iT cells vs control CAR iT cells, respectively). <h3>Conclusions</h3> Preclinical data demonstrate that the engineering of synthetic chemokine receptors to further direct off-the-shelf CAR iT cells to the tumor site is an exciting strategy to improve anti-tumor activity, including as part of a multiplexed-engineering strategy for overcoming challenges in treating solid tumors.
Classification of Postprandial Glycemic Status with Application to Insulin Dosing in Type 1 Diabetes—An In Silico Proof-of-Concept (2019)

In the daily management of type 1 diabetes (T1D), determining the correct insulin dose to be injected at meal-time is fundamental to achieve optimal glycemic control. Wearable sensors, such as continuous glucose monitoring (CGM) devices, are instrumental to achieve this purpose. In this paper, we show how CGM data, together with commonly recorded inputs (carbohydrate intake and bolus insulin), can be used to develop an algorithm that allows classifying, at meal-time, the post-prandial glycemic status (i.e., blood glucose concentration being too low, too high, or within target range). Such an outcome can then be used to improve the efficacy of insulin therapy by reducing or increasing the corresponding meal bolus dose. A state-of-the-art T1D simulation environment, including intraday variability and a behavioral model, was used to generate a rich in silico dataset corresponding to 100 subjects over a two-month scenario. Then, an extreme gradient-boosted tree (XGB) algorithm was employed to classify the post-prandial glycemic status. Finally, we demonstrate how the XGB algorithm outcome can be exploited to improve glycemic control in T1D through real-time adjustment of the meal insulin bolus. The proposed XGB algorithm obtained good accuracy at classifying post-prandial glycemic status (AUROC = 0.84 [0.78, 0.87]). Consequently, when used to adjust, in real-time, meal insulin boluses obtained with a bolus calculator, the proposed approach improves glycemic control when compared to the baseline bolus calculator. In particular, percentage time in target [70, 180] mg/dL was improved from 61.98 (± 13.89) to 67.00 (± 11.54; p < 0.01) without increasing hypoglycemia.
Eco-Friendly High-Strength Composites Based on Hot-Pressed Lignocellulose Microfibrils or Fibers (2021)

Unbleached lignocellulosic wood fiber materials of low porosity are of great interest as eco-friendly load-bearing materials because their yield is much higher than that for "pure" wood cellulosics. The difference between comparable materials based on lignocellulose fibers or nanocellulose is investigated. The structure, surface area, mechanical properties, moisture sorption, and optical properties of films based on fibers or microfibrillated lignocellulose (MFLC) were characterized as a function of lignin content, and the environmental impact was compared. The modulus and tensile strength of comparable fiber and MFLC films (≈25% porosity) increased up to an optimum lignin content (11–17%) and then decreased at a very high lignin content. Hot-pressed MFLC films with little porosity showed excellent properties, 230–260 MPa strength, 17–20 GPa modulus, and 81 MPa wet strength. The mechanical property values of hot-pressed wood fibers with 25% porosity were also as high as 154 MPa strength and 13.2 GPa modulus, which are higher than those of comparable materials reported in the literature. Because hot-pressed lignocellulose fibers can be readily recycled and show low cumulative energy demand, they are candidates for semistructural engineering materials. MFLC is of great interest for coatings, films, adhesives, and as additives or in high-technology applications.
40‐3: Distinguished Paper: Realization of Ultra‐High Efficient Fluorescent Blue OLED (2022)

The bilayer structure for an emitting layer (EML) was developed to improve performances of a fluorescence blue organic light emitting diode. By functionally separating the EML into the charge recombination and the Triplet‐Triplet Fusion (TTF) zone, we successfully suppressed the quenching of triplet excitons by excess carriers to make more TTF efficient and the local degradation within the EML to make the lifetime longer. In the bottom emission device with the bilayer EML, 12% of external quantum efficiency (EQE) and 450 hours of LT95 were achieved. Furthermore, we achieved over 14% of EQE by optimizing the material combinations.
40-GHz Mode-Locked Fiber-Ring Laser Using a Mach–Zehnder Interferometer With Integrated SOAs (2004)

A 40-GHz mode-locked fiber-ring laser based on an optically controlled modulator is presented and analyzed in detail. The modulator is a monolithic InGaAsP-InP Mach-Zehnder interferometer with integrated semiconductor optical amplifiers, which allows optical pulse generation synchronized to an external optical clock pulse stream. The laser generates nearly transform-limited Gaussian pulses of 2.5-ps width and up to 9-mW mean output power with less than 130 fs of timing jitter, and it is wavelength tunable over more than 30 nm. The relationship between key laser parameters and the output pulse characteristics is analyzed experimentally and numerically. An improved cavity design permits the generation of shorter pulses of 1.0-ps width.
Human Monoclonal Antibodies: Recent Achievements (1994)

The latest developments include an anti-HIV antibody that has 1,000 times the affinity of natural antibody and that neutralizes primary clinical isolates, and an anti-RSV antibody that reduces viral titers in mice by 12,000-fold within 24 hours.
Abstract 1873: The role of p21-activated kinase 4 (PAK4) in cancer stemness and epithelial-to-mesenchymal transition (2016)

Abstract The p21-activated kinase 4 (PAK4) is a key downstream effector of the Rho family GTPases. PAK4 is found to be over-expressed in many oncogenic Ras-driven cancers and cell lines but not in their normal counterparts. Mesenchymal pancreatic ductal adenocarcinoma (PDAC) stem cells (CSCs) that are triple positive for stemness markers (CD133+, CD44+, and EpCam+) as well as Ras and snail transduced human mammary epithelial cells (HMLER-snail) showed enhanced expression of PAK4 along with activation of Rho, Rac1 and CDC42. PAK4 RNA interference resulted in disruption of PDAC CSC spheroids, reduction of mesenchymal markers (i.e. vimentin and snail) and suppression of CSCs potential to form subcutaneous tumors in mice. These findings point to a novel role of PAK4 in promoting oncogenic Ras-driven EMT and stemness. Using PDAC CSCs (MiaPaCa-2 and L3.6pl) and human mammary epithelial cells (HMECs) that are transduced with Ras and the EMT promoter snail (HMLE-Snail and HMLER-Snail), we investigated the impact of PAK4 allosteric modulators [PAMs (KPT-7189, KPT-7523, KPT-9274 and KPT-9307)] on the reversal of EMT and stemness. The toxicity and efficacy of PAMs were evaluated in vitro and in multiple sub-cutaneous xenograft models. PAMs show anti-proliferative activity in vitro against different PDAC CSCs and HMECs while sparing normal cells. Cell growth inhibition was concurrent with apoptosis induction, suppression of colony formation and reversal of mesenchymal morphology to epithelial (MET). PAMs not only reduced PAK4 RNA and protein steady state levels but also inhibited proliferative and anti-apoptotic signals downstream of PAK4. PAMs caused suppression of EMT markers (EpCAM, vimentin and snail) and re-expression of an epithelial promoter E-cadherin. PAM treatment inhibited RhoA, Rac1 and CDC42 activation in GLISA assays. KPT-9274 showed remarkable anti-tumor activity in sub-cutaneous xenograft models of CSCs and residual tumors showed suppression of EMT markers that was concurrent with inhibition of PAK4 signaling. These studies open a novel therapeutic opportunity against EMT and cancer stem cells through PAK4 inhibition. Citation Format: Asfar S. Azmi, Irfana Muqbil, Amro Aboukameel, William Senapedis, Erkan Baloglu, Yosef Landesman, Sharon Shacham, Michael Kauffman, Philip A. Philip, Ramzi M. Mohammad. The role of p21-activated kinase 4 (PAK4) in cancer stemness and epithelial-to-mesenchymal transition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1873.
ChemInform Abstract: VISIBLE LIGHT INDUCED WATER CLEAVAGE IN COLLOIDAL SOLUTIONS OF CHROMIUM‐DOPED TITANIUM DIOXIDE PARTICLES (1982)

Abstract Die Oberflächendotierung von kolloidalen TiO, ‐Teilchen mit Cr‐Ionen aus wäßriger H 2 SO 4 ‐Lösung erzeugt sehr kleine ( 0.1 u) Mischoxidteilchen, die Licht im Bereich 400‐550 nm (zusätzlich zur Bandlücken‐Absorption) absorbieren.
Stimuli-Responsive Amphiphilic Pillar[n]arene Nanovesicles for Targeted Delivery of Cancer Drugs (2021)

Cancer chemotherapeutics face several challenges, including uncontrollable drug release, off-target toxic effects, and poor bioavailability. Recently, supramolecular nanovesicles, such as calix[n]arenes (CXs), cyclodextrins (CDs), cucurbiturils (CBs), and pillar[n]arenes (PRs), have attracted attention as potential smart nanocarriers for chemotherapeutics because of their exceptional cavities that can achieve high encapsulation capacity and accommodate both hydrophilic and hydrophobic drugs. In addition, they can be functionalized with different stimuli-responsive groups, which facilitate controlled drug release. Supramolecular nanovesicles, loaded with drugs and decorated with stimuli-responsive targeting moieties, are designed by either host–guest complexation or self-assembly of amphiphilic cavitands. Pillar[n]arenes, in particular, are novel supramolecular host molecules that have recently been employed in cancer targeted drug delivery because of their symmetric pillar-shaped structure, simplicity of functionalization, and biocompatibility. This review summarizes state-of-the-art strategies for developing single or multiple stimuli-responsive pillar[n]arene nanovesicles for effective cancer treatment.
Enzyme-catalyzed DNA unwinding: Studies on Escherichia coli rep protein (1979)

Replication in vitro of the replicative form (RF) I DNA of bacteriophage varphiX174 requires the phage-induced cistron A (cisA) protein, the host rep protein, DNA-binding protein, ATP, and DNA polymerase III plus replication factors. The rep protein is a single-stranded DNA-dependent ATPase. In this paper we show that varphiX174 RF I DNA cut by the cisA protein acts as a duplex DNA cofactor for the rep protein ATPase activity, provided that DNA-binding protein is present. In this latter reaction the duplex DNA is unwound by the rep protein with concomitant hydrolysis of ATP. The extents of ATP hydrolysis, DNA unwinding, and, where appropriate, DNA synthesis are proportional to the amounts of DNA-binding protein present. Two ATP molecules are hydrolyzed per base pair unwound. We propose that the obligatory requirement for the cisA protein in the unwinding of varphiX174 RF I DNA is not simply due to its endonuclease activity but rather is due to its provision of a site for the binding of the rep protein. The rep protein in the presence of DNA-binding protein, but in the absence of cisA protein, unwinds duplex DNA when one strand extends to generate a single-stranded leader region preceding the duplex. We show that rep protein translocates along the leader single strand in a 5'-to-3' direction only and then invades the duplex DNA. The rep protein shows a directional specificity for translocation and unwinding. A model is presented to explain the mechanism of DNA unwinding catalyzed by the rep protein.
Enabling 5G — A substrate material perspective: AEM, ET/ID (2018)

This paper reports on recent advances in material innovation and substrate technologies enabling 5G. In particular, key requirements of 5G standards such as substrate linearity, power efficiency and RF/Analog performance are discussed. The characteristics of the initial substrate define the performance and architecture of the 5G devices and circuits. The results presented in this work summarize close cooperation between RF design, device technologies and advanced substrate manufacturing.
Cover Picture: Metallomacrocycles That Incorporate Cofacially Aligned Diimide Units (Chem. Asian J. 5/2006) (2006)

The weak‐link approach is illustrated by the reaction of hemilabile phosphinoalkyl thioether ligands that contain incorporated pyromellitic and naphthalene diimide moieties with [Cu(CH 3 CN) 4 ]PF 6 or [{Rh(norbornadiene)Cl} 2 ]. As a consequence, the two diimide units become cofacially aligned, as shown in the cover picture, within a supramolecular macrocyclic architecture. The introduction of ancillary ligands to the intermediates causes the weak thioether–metal bonds to break, thus generating a large macrocycle in which the distance between diimide units is significantly larger than for the intermediates. For more information, see the Full Paper by C. A. Mirkin and co‐workers on page 686 ff.
α-Amylase activity during pullulan production and α-amylase gene analyses of Aureobasidium pullulans (2010)

Aureobasidium pullulans is the source of commercially produced pullulan, a high molecular weight polysaccharide that is used in the manufacture of edible films. It has been proposed that α-amylase decreases the molecular weight of pullulan in late cultures. Based on a recent phylogenetic analysis, five representative strains were chosen to study the relationship between α-amylase and pullulan production. In sucrose-grown cultures, pullulan yields increased over time while the molecular weight of pullulan generally decreased. However, no α-amylase activity was detected in these cultures. Low levels of α-amylase were present in starch-grown culture, but pullulan analysis was complicated by residual starch. To facilitate further studies on the role of α-amylase in the reduction of pullulan molecular weight, the α-amylase gene from A. pullulans NRRL Y-12974 was cloned and characterized. The coding region of the complete α-amylase gene contains 2,247 bp, including 7 introns and 8 exons. The putative mRNA was 1,878 bp long, encoding an α-amylase of 625 amino acid residues. Southern blot analysis indicated that there was only one copy of this gene in the genome. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that the gene was transcribed in both sucrose- and starch-grown cultures. It is possible that very low levels of α-amylase attack the minor maltotetraose subunits of pullulan and cause the reduction of molecular weight.
Identification of Amino Acid Residues That Direct Differential Ligand Selectivity of Mammalian and Nonmammalian V1a Type Receptors for Arginine Vasopressin and Vasotocin (2004)

Arginine vasotocin (VT) is the ortholog in all nonmammalian vertebrates of arginine vasopressin (AVP) in mammals. We have previously cloned an amphibian V1atype vasotocin receptor (VT1R) that exhibited higher sensitivity for VT than AVP, while the mammalian V1a type receptor (V1aR) responded better to AVP than VT. In the present study, we identified the amino acid residues that confer differential ligand selectivity for AVP and VT between rat V1aR and bullfrog VT1R (bfVT1R). A chimeric rat V1aR having transmembrane domain (TMD) VI to the carboxyl-terminal tail (C-tail) of bfVT1R showed a reverse ligand preference for AVP and VT, whereas a chimeric VT1R with TMD VI to the C-tail of rat V1aR showed a great increase in sensitivity for AVP. A single mutation (Ile(315(6.53)) to Thr) in TMD VI of V1aR increased the sensitivity for VT, while a single mutation (Phe(313(6.51)) to Tyr or Pro(334(7.33)) to Thr) reduced sensitivity toward AVP. Interestingly the triple mutation (Phe(313(6.51)) to Tyr, Ile(6.53) to Thr, and Pro(7.33) to Thr) of V1aR increased sensitivity to VT but greatly reduced sensitivity to AVP, behaving like bfVT1R. Further, like V1aR, a double mutant (Tyr(306(6.51)) to Phe and Thr(327(7.33)) to Pro) of bfVT1R showed an increased sensitivity to AVP. These results suggest that Phe/Tyr(6.51), Ile/Thr(6.53), and Pro/Thr(7.33) are responsible for the differential ligand selectivity between rat V1aR and bfVT1R. This information regarding the molecular interaction of VT/AVP with their receptors may have important implications for the development of novel AVP analogs.
Mathematical Modeling of Liquid‐Junction Photovoltaic Cells: II . Effect of System Parameters on Current‐Potential Curves (1984)

The one‐dimensional mathematical model presented in a previous paper was used to calculate the effect of system variables on the performance of an n‐type semiconducting anode in contact with an , , electrolytic solution. The performance of the semiconductor electrode is influenced by kinetic limitations to interfacial reactions, dopant concentration, semiconductor thickness, the direction of illumination, and the amount of light absorbed in the semiconductor. An optimal dopant concentration and semiconductor thickness can be calculated for a given system.
Abstract 2549: Development of CAR T-cell therapy targeting glypican-3 in liver cancer (2018)

Abstract Background: Glypican-3 (GPC3) is a candidate therapeutic target in hepatocellular carcinoma (HCC). We have generated the HN3 and hYP7 antibodies that recognize the N-terminus and C-terminus of GPC3, respectively. Here, we engineered human T cells that express GPC3-specific chimeric antigen receptors (CARs) and evaluated their potential for the treatment of HCC. Methods: The GPC3-specific CARs (CAR.HN3 and CAR.hYP7) contain a CD3ζ chain and the 4-1BB co-stimulatory endodomain along with a truncated human EGFR polypeptide (huEGFRt) that retains the cetuximab epitope. A set of GPC3 positive-liver cancer cell lines including Hep3B, HepG2 and Huh7 were engineered to express the firefly luciferase gene. These cells were co-cultured with GPC3 CAR T cells at various ratios for 24 hours. A bioluminescent luciferase reporter assay was then used to evaluate the cytolytic activity of effector CAR T cells. We also evaluated the anti-tumor activity of CAR T cells in xenograft models with intraperitoneal injection of luciferase-expressing HCC cells into NOD/SCID/IL2gnull (NSG) mice. The tumor growth was measured via bioluminescence tumor imaging. Results: We found that the CAR.hYP7 cells targeting the C-terminus of GPC3 showed the highest cytolytic activity against GPC3-positive HCC cells. In two HCC intraperitoneal xenograft models (Hep3B and HepG2), luciferase-expressing HCC cells preferentially grew on the mouse liver. More importantly, we found that a single intraperitoneal treatment with a high dose of CAR.hYP7 cells (40 million per mouse) exhibited sustainable antitumor efficacy in the Hep3B model and all of the mice survived after 9 weeks post CAR T-cell treatment without recurrence. The serum levels of alpha fetoprotein (AFP) in mice treated with a high dose of CAR.hYP7 cells were less than 50 ng/ml, the threshold value for HCC diagnosis. Additionally, a single intraperitoneal treatment with a low dose of CAR.hYP7 cells (10 million per mouse) caused regression of liver tumor xenografts. In the low dose CAR.hYP7 group, Hep3B tumors in the mice grew locally and restricted to the fat tissues far from the mouse liver, indicating that CAR T cells prevented tumors from seeding and growing in the liver. Although CAR.HN3 cells targeting the N- terminus of GPC3 also exhibited high cytotoxicity to HCC cells in vitro, no significant Hep3B tumor growth inhibition was seen in the mice treated with CAR.HN3 cells. Conclusion: Our work suggests that GPC3-targeting CAR T cells, in particular CAR.hYP7, is a promising therapeutic intervention for liver cancer that can be translated to human use. Citation Format: Dan Li, Nan Li, Yifan Zhang, Haiying Fu, Madeline B. Torres, Qun Wang, Tim F. Greten, Mitchell Ho. Development of CAR T-cell therapy targeting glypican-3 in liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2549.
A Probabilistic Emergent Routing Algorithm for Mobile Ad Hoc Networks (2003)

Mobile ad hoc networks are infrastructure-less networks consisting of wireless, possibly mobile nodes which are organized in peer-to-peer and autonomous fashion. The highly dynamic topology, limited bandwidth availability and energy constraints make the routing problem a challenging one. In this paper we take a novel approach to the routing problem in MANETs by using swarm inteligenceinspired algorithms. The proposed algorithm uses Ant-like agents to discover and maintain paths in a MANET with dynamic topology. We present simulation results that measure the performance of our algorithm with respect to the characteristics of a MANET, the varying parameters of the algorithm itself as well as performance comparison with other well-known routing protocols. 1