gebhart/patrepeval huggingface dataset:
Data from Untouched GMP-Ready Purified Engineered Immune Cells to Treat Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Engineering T cells with receptors to redirect the immune system against cancer has most recently been described as a scientific breakthrough. However, a main challenge remains the GMP-grade purification of immune cells selectively expressing the introduced receptor in order to reduce potential side effects due to poorly or nonengineered cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; In order to test a novel purification strategy, we took advantage of a model γδT cell receptor (TCR), naturally interfering with endogenous TCR expression and designed the optimal retroviral expression cassette to achieve maximal interference with endogenous TCR chains. Following retroviral transduction, nonengineered and poorly engineered immune cells characterized by a high endogenous αβTCR expression were efficiently depleted with GMP-grade anti-αβTCR beads. Next, the engineered immune cells were validated for TCR expression, function against a panel of tumor cell lines and primary tumors and potential allo-reactivity. Engineered immune cells were further validated in two humanized mouse tumor models.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The untouched enrichment of engineered immune cells translated into highly purified receptor-engineered cells with strong antitumor reactivity both &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. Importantly, this approach eliminated residual allo-reactivity of engineered immune cells. Our data demonstrate that even with long-term suboptimal interference with endogenous TCR chains such as in resting cells, allo-reactivity remained absent and tumor control preserved.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; We present a novel enrichment method for the production of untouched engineered immune cells, ready to be translated into a GMP-grade method and potentially applicable to all receptor-modified cells even if interference with endogenous TCR chains is far from complete. &lt;i&gt;Clin Cancer Res; 21(17); 3957–68. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Abstract T P232: Combination Therapy With Taurine Plus Tissue Plasminogen Activator in a Rat Model of Embolic Stroke (2015)

Background: Tissue plasminogen activator (tPA) is the only FDA-approved therapy for acute ischemic stroke, but it has narrow therapeutic window (within 4.5h) and increased risks of intracerebral hemorrhage. Taurine, an endogenous 2-aminoethansulfolic amino acid, exhibits a plethora of physiological functions. It has been found to protect against ischemic brain injury in animal models of stroke by diverse mechanisms. Strikingly, published data show that the therapeutic window of taurine was at least 8h after the onset of ischemic stroke, thus potentially allowing for delayed or more effective thrombolysis. In this study we investigated whether combination therapy with taurine plus tPA can block hemorrhagic transformation and thus extend the time window of tPA after delayed tPA treatment for ischemic stroke. Methods and Results: Male adult rats (330-380g) were subjected to embolic middle cerebral artery occlusion and then randomized into different treatment groups: saline injected at 4h; taurine (50 mg/kg) at 4h, tPA (10 mg/kg) at 6h, and combination therapy with taurine at 4h plus tPA at 6h after the onset of ischemia. Delayed 6-hour tPA did not decrease infarction but instead worsened brain hemorrhage. Combining taurine with delayed 6-hour tPA reduced tissue infarction, attenuated blood-brain barrier disruption by reduced degradation of tight junction proteins (claudin-5 and collagen IV), and ameliorated brain hemorrhage. These protective effects are correlated with decreased brain matrix metallopeptidase-9 activity possibly through inactivation of NF-kB and CD147 (a potent inducer of MMPs) in the postischemic brain, particularly in the cerebral microvessels (using structurally intact microvessels isolated from the brain). Conclusion: The present study demonstrates for the first time that combination therapy with taurine may attenuate delayed tPA-associated hemorrhagic transformation and extend tPA treatment time windows in a clinically relevant thromboembolic stroke model. Inhibition of MMP-9 in brain microvessels via inactivation of NF-κB and CD147 signaling may underlie the protective mechanisms of taurine.
Electroactive Self-Assembled Monolayers that Permit Orthogonal Control over the Adhesion of Cells to Patterned Substrates (2006)

This article describes an electroactive substrate that displays two independent dynamic functions for controlling the adhesion of cells. The approach is based on self-assembled monolayers on gold that are patterned into regions presenting the Arg-Gly-Asp peptide cell adhesion ligand. The patterned regions differ in the electrochemical properties of the linkers that tether the peptides to the monolayer. In this work, three distinct chemistries are employed that provide for release of the ligand on application of a negative potential, release of the ligand on application of a positive potential, and no change in response to a potential. Cells were allowed to attach to a monolayer patterned into circular regions comprising the three chemistries. Treatment with electric potentials of 650 or -650 mV resulted in the selective release of adherent cells only from regions that display the relevant electroactive groups. This example establishes the preparation of dynamic substrates with multiple functions and will be important to preparing model cultures derived from multiple cell types, with control over the temporal interactions of each cell population.
Forrestiacids A and B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products (2021)

Abstract Forrestiacids A ( 1 ) and B ( 2 ) are a novel class of [4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii , an endangered member of the Asian Douglas Fir Family. The intermolecular hetero‐Diels–Alder adducts feature an unusual bicyclo[2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X‐ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC 50 s &lt;5 μM ) of ATP‐citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL‐related diseases with strong links to traditional medicines.
Abstract 3430: The protein phosphatase 4 complex is a tumor suppressor in prostate cancer (2020)

Abstract Regions of recurring chromosomal deletions have been annotated in clinical prostate cancer (PCa), but for many of them there is an incomplete understanding of their contributions to disease progression. From an in vivo shRNA enrichment screen of the PCa deletome, we identified the serine threonine protein phosphatase 4 (PP4) regulatory subunit 2 (PPP4R2) as a candidate tumor suppressor, which undergoes copy number loss in 16% of primary PCa. Knockdown or CRISPR-Cas9 mediated knockout of PPP4R2 increased the growth rate of PCa xenograft tumors. Along with the catalytic subunit PP4C and an additional regulatory subunit (either PP4R3A or PP4R3B), PP4R2 forms two distinct heterotrimeric phosphatase holoenzymes. PP4R2 was critical for holoenzyme stability, as its deletion resulted in rapid, moderate downregulation of the other PP4 subunit proteins. The increased tumor growth rate and downregulation of PP4C resulting from loss of PP4R2 could be replicated by combined deletion of PPP4R3A and PPP4R3B, or by directly targeting PPP4C itself. Collectively, these findings implicated PP4C as the likely direct mediator of tumor suppression through the PP4 complex. This was confirmed in both PPP4R2 and PPP4R3A/PPP4R3B knockout cells in vivo by restoring PP4C to its normal physiological level through a dox-inducible cDNA, which reversed the accelerated tumor growth rate conferred by the deletion of the regulatory subunits. Phosphatase activity of PP4C was critical, as add-back of a catalytically dead PP4C mutant (D82A) was unable to reverse the growth rate of PPP4C knockout tumors. Interestingly, we found that the androgen receptor (AR), which is the principal therapeutic target for PCa, was co-immunoprecipitated by PP4C and its regulatory subunits. This suggests that AR could be a substrate for PP4C and is potentially present in a hyperphosphorylated and hyperactivated state in PCa that have decreased PP4 phosphatase activity. Our findings highlight a previously unappreciated tumor suppressor role for the PP4 complex in PCa, with the regulatory subunit PP4R2 providing a key function in stabilizing PP4C and thereby preserving its phosphatase activity. Citation Format: Philip A. Watson, Kayla E. Lawrence, Tejasveeta V. Nadkarni, Taslima F. Ishmael, Eugine Lee, Aura C. Agudelo Rivera, Jillian R. Love, John Wongvipat, Ling Cai, Abbas Nazir, Phillip J. Iaquinta, Kenneth Chang, Yupu Liang, Greg J. Hannon, Charles L. Sawyers. The protein phosphatase 4 complex is a tumor suppressor in prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3430.
Assessment of Torque Components in Brushless Permanent-Magnet Machines Through Numerical Analysis of the Electromagnetic Field (2005)

For the calculation of torque in brushless (BL) alternating current motors a local method is proposed, based on the Maxwell stress theory and the filtered contributions due to the harmonics of the magnetic vector potential in the motor air gap. By considering the space fundamental field only, the method can efficiently estimate the average synchronous torque for a variety or motor topologies, including concentrated winding designs. For BL direct current motor analysis a global method is introduced, based on the virtual work principle expressed in terms of energy components in various motor regions. The method leads to simplifications in the average torque calculation and enables the direct identification of the cogging and ripple components. The mathematical procedures have been validated against experiments and other numerical techniques.
Experimental glioma with high bHLH expression harbor increased replicative stress and are sensitive toward ATR inhibition (2020)

Gliomas overexpressing (b)HLH TFs are sensitive toward inhibition of the ATR kinase. The combination of ATR inhibition plus temozolomide or radiation therapy in this molecular subgroup are warranted.
Measurement of pressure produced at a solid surface by an acoustically driven cavitation bubble cloud (2006)

A cavitation bubble cloud typically acts as a strong acoustic scatterer; however, at certain frequencies and amplitudes waves transmitted by a cloud are amplified. A long-term goal is to break up kidney stones by using a two-frequency ultrasound forcing method with one frequency that generates the cloud followed by a lower second frequency that excites its violent collapse. The goal of this study is to determine the frequency and pressure amplitudes which produce the largest pressures as measured by a PVDF membrane on the stone surface. Reflection was also measured by a concave PVDF sensor placed 40 mm from the surface, and cloud sizes were determined by high-speed camera images. Transmission is quantified by the force. Reflection and transmission showed a reciprocal relation: peak in transmission corresponded to a minimum in reflection. The largest cloud observed created the largest reflection, whereas the smallest clouds created the largest transmitted signals. Forces generated by the small clouds were five times larger than the amplitude without a cloud. Thus, in using a two-frequency excitation combination, the pressures generated by the cloud cavitation might be optimized for lithotripsy applications. [Work supported in part by NIH DK43881 and NSBRI SMS00402.]
Space-time block codes achieving generalized optimal diversity (2006)

We propose a generalized code structure for constructing space-time codes (STCs) that can achieve generalized optimum diversity (GOD) with minimum delay. As a GOD code, it can achieve the full diversity and a maximum coding gain for any number of transmit antennas ( t N ) and any rate ( R ), if the rate is less than or equal to the rank of the channel matrix. As a minimum delay code, the structure requires only t N time slots in order to achieve the full diversity. The proposed structure combines mutu- ally exclusive R data symbols with complex weights at each transmit antenna and the same set of data symbols is repeated at every time slot in a code block, but is transmitted through different transmit antennas with different sets of complex weights. In addi- tion, the structure does not need any restrictions to the complex weights, thus the code can be designed with the maximum degrees of freedom. The design of an optimum code would be done by finding the set of the complex weights so that the minimum abso- lute determinant of code word difference matrices could be maxi- mized. The optimum code could be easily designed so that two types of constraints, that is, the power constraints and the orthogo- nality constraint could be satisfied. The two constraints make the channel resource fully utilized when the channel state information (CSI) is not available at the transmitter and also reduce to the uni- tary constraint for capacity lossless code design in the case of t N R = . We give two STC design examples: (1) an STC with rate 2 for two transmit antennas and (2) an STC with rate 3 for three transmit antennas. We also provide some guidelines for code de- sign. Computer simulations are performed to demonstrate the per- formance of the proposed designs. From simulation results, we see that the proposed code structure and code designs can achieve GOD with minimum delay.
Suppression of TGA Mutations in the Bacillus subtilis spoIIR Gene by prfB Mutations (1998)

An unexpectedly high proportion of TGA nonsense mutations was obtained in a collection of chemically induced mutations in the spoIIR locus of Bacillus subtilis. Of 11 different mutations obtained, TGA mutations were found in four codons, whereas only three codons yielded missense mutations. Six suppressors of the TGA mutations were isolated, and five of the suppressing mutations were mapped to the prfB gene encoding protein release factor 2. These are the first mutations shown to map to the B. subtilis prfB locus. The sequence of the prfB gene was completed, and two revisions of the published sequence were made. The five prfB mutations also resulted in suppression of the catA86-TGA mutation to between 19 and 54% of the expression of catA86(+), compared to the readthrough level of 6% in the prfB+ strain. N-terminal sequencing of suppressed catA86-TGA-specified protein demonstrated that the amino acid inserted at UGA because of the prfB1 mutations was tryptophan.
Supramolecular Interactions (2012)

Abstract This chapter provides an overview of noncovalent interactions in the field of supramolecular chemistry. The use of noncovalent forces to form supramolecular structures is documented. Supramolecular interactions can be both directional and nondirectional and can enable chemists to develop discrete assemblies and networks of molecules and/or ions with prescribed properties and functions. Concepts of host‐guest chemistry, molecular recognition, and self‐assembly emerge from an understanding of how supramolecular interactions control assembly processes. Examples that highlight the utility of employing supramolecular interactions to form functional structures and materials are given.
Endotheliale PSGL-1 Expression in Sepsis und Colitis der Maus Endothelial PSGL-1 expression in sepsis and colitis of the mouse (2006)

Introduction: P-selectin is a major adhesion molecule which is important for recruiting circulating leukocytes and platelets to sites of inflammation like in experimental colitis. So far, its ligand, P-selectin glycoprotein ligand-1 (PSGL-1), has been found on circulating leukocytes and platelets. The present study aimed to quantify endothelial PSGL-1 expression in different regional vascular beds under physiological and inflammatory conditions. Methods: The dual radiolabeled monoclonal antibody (mAb) technique was used to quantify the expression of endothelial PSGL-1 in different vascular beds, including the intestine (small and large), lung, liver, kidneys and brain, in two different animal models, 1. Lipopolysaccharide (LPS) -induced sepsis and 2. Dextran sulphate sodium (DSS) -induced colitis. Healthy wildtype (WT) mice (C57Bl/6J), PSGL-1 knockout (KO) mice and WT mice transplanted with bone marrow (BM) from PSGL-1 KO mice (chimeras deficient in PSGL-1 on circulating blood cells) all served as controls. Sepsis was induced by intraperitoneal injection of LPS, colitis was induced by administration of 3 % DSS in drinking water for 7 days (d0-6). Statistical significance was set at P < 0.05 using ANOVA/Fisher’s post-hoc test. Results: In contrast to PSGL-1 KO animals, healthy WT controls showed a significant constitutive expression of PSGL-1 in almost every organ. Systemic administration of LPS increased PSGL-1 expression in the vasculature of the intestines (small and large), kidneys, and brain as early as four hours. The LPS-induced increase in PSGL-1 was not associated with neutrophil accumulation since pretreatment with anti-neutrophil serum did not reduce its expression. PSGL-1 expression was also detectable in numerous organs of BM transplanted animals lacking PSGL-1 on circulating blood cells. Compared to untreated controls, mice with DSS-induced colitis also showed significantly increased PSGL-1 expression in the large bowel, liver, lung and brain. Conclusions: Our results demonstrate constitutive PSGL-1 expression in different regional vascular beds. Its expression is significantly increased in response to inflammatory stimuli such as sepsis and colitis. (DFG VO 998/1-1 and NIH DK65649)
Fuzzy prophet (2011)

We present Fuzzy Prophet, a probabilistic database tool for constructing, simulating and analyzing business scenarios with uncertain data. Fuzzy Prophet takes externally defined probability distribution (so called VG-Functions) and a declarative description of a target scenario, and performs Monte Carlo simulation to compute probability distribution of the scenario's outcomes. In addition, Fuzzy Prophet supports parameter optimization,where probabilistic models are parameterized and a large parameter space must be explored to find parameters that optimize or achieve a desired goal. Fuzzy Prophet's key innovation is to use 'fingerprints' that can identify parameter values producing correlated outputs of a user-provided stochastic function and to reuse computations across such values. Fingerprints significantly expedite the process of parameter exploration in offline optimization and interactive what-if exploration tasks.
Two széchenyis: From state patriotism to romantic nationalism (1993)

(1993). Two szechenyis: From state patriotism to romantic nationalism. History of European Ideas: Vol. 16, No. 1-3, pp. 273-280.
Modeling Contact Dynamics of Vanes With Adjustable Upstream Flow Angles (2012)

In this paper, a simulation method is proposed for a sub-category of compressor vanes showing nonlinear behavior due to an adjustable upstream flow angle. The proposed algorithm computes the forced response of a single vane based on the New-mark time stepping scheme after reducing the structural matrices using the Craig-Bampton method. The contacts are modeled by Coulomb friction and Newton impact constraints. Contact forces are determined using linear complementarity conditions with decoupled orthogonal friction force directions. Different discretization methods for the cylindrical contact partners are proposed. Finally, numerical results are shown in order to validate the proposed algorithms.
The Impact of Web Browser Reader Views on Reading Speed and User Experience (2019)

As reading increasingly shifts from paper to online media, many web browsers now provide a "Reader View,'' which modifies web page layout and design for better readability. However, research has yet to establish whether Reader Views are effective in improving readability and how they might change the user experience. We characterize how Mozilla Firefox's Reader View significantly reduces the visual complexity of websites by excluding menus, images, and content. We then conducted an online study with 391 participants (including 42 who self-reported having been diagnosed with dyslexia), showing that compared to standard websites the Reader View increased reading speed by 5% for readers on average, and significantly improved perceived readability and visual appeal. We suggest guidelines for the design of websites and browsers that better support people with varying reading skills.
Utilization of HFC-245fa in the Construction Industry (1999)

The effective use of insulation in both commercial and residential buildings is the key to energy conservation. The effectiveness of an insulation is dependent upon many factors. If the insulation is a foam plastic, the blowing agent used in the insulation is critical to its performance. There has been a transition in blowing agents over the last decade from CFC's to HCFC's and the industry will soon see another transition from HCFC's to a third generation blowing agent. The exact timing of these transitions is dependent upon the Montreal Protocol national and local regulations. Each transition in blowing agents requires modifications to the manufacturing process for the foam products. AlliedSignal is dedicated to providing an HFC blowing agent to the construction industry and has identified HFC-245fa (1,1,1,3,3-pentafluoropropane) as our third generation blowing agent. Since 1994, we have published a series of papers on the development of this blowing agent. This paper discusses some of the key considerations required in making the transition from HCFC-141b to HFC-245fa in areas of polyisocyanurate boardstock and spray foam. It also discusses progress made in the application of HFC-245fa in bunstock and pour in place panel applications. It will discuss the progress in areas such as raw materials and formulation optimization, possible equipment and processing parameters changes required to optimize performance, and a general discussion of foam properties, including flammability, in comparison to HCFC-141b blown foams. It will focus on providing the information which board and system manufacturers and spray foam applicators will need to make a successful transition. This includes information on gasket compatibility, gloves, system vapor pressures, system packaging and shipping requirements and product performance.
Phenotypic Features and Genetic Findings in Sacsin-Related Autosomal Recessive Ataxia in Tunisia (2003)

In Tunisia, autosomal recessive cerebellar ataxia related to the SACS gene demonstrated a homogenous phenotype and heterogeneous allelic mutations.
Supplementary Figure S13 from Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition (2023)

&lt;p&gt;Supplementary Figure S13 shows temporal changes in copy number profiles detected via 72-gene targeted sequencing&lt;/p&gt;