gebhart/patrepeval huggingface dataset:
Abrogated AID Function Prolongs Survival and Diminishes Renal Pathology in the BXSB Mouse Model of Systemic Lupus Erythematosus (2020)

Almost a decade has passed since the approval of belimumab, an mAb directed against B lymphocyte stimulation and the first targeted therapy approved for systemic lupus erythematous (SLE) in over 50 y. Although well tolerated, the efficacy of belimumab remains limited and is not labeled for patients suffering from nephritis, the leading cause of patient mortality. We sought to explore alternative targets of autoreactive B lymphocytes through manipulation of affinity maturation. The BXSB/MpJ mouse, a well-established model of human SLE, develops elevated antinuclear Abs and immune complex-mediated nephritis along with other manifestations of SLE-like disease. To limit interfering with critical background genetics, we used CRISPR-Cas9 to disrupt activation-induced cytidine deaminase (AID; <i>Aicda</i>) directly in BXSB zygotes. Homozygous null mice demonstrated significantly prolonged survival compared with wild-type. Although mice continued to develop plasma cells, splenic follicular structure was restored, and renal pathology was reduced. Mice developed expanded germinal center B lymphocyte populations as in other models of AID deficiency as well as increased populations of CD73<sup>+</sup> B lymphocytes. Treatment with the small molecule inhibitor of RAD51, 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid, resulted in minimal changes in disease markers in BXSB mice. The prolonged survival in AID-deficient BXSB mice appears attributed primarily to the reduced renal pathology, warranting further exploration, as current therapeutics targeting lupus nephritis are limited and, thus, in great demand.
Motif Extraction: Normalization of Scores (1996)

This paper examines a method to normalize a score of a stochastic motif, represented by a hidden Markov model (HMM). The accuracy of the Z score method, which is one of the score normalization method, is compared with that of the whole search method.
Development of candidate vaccines against infection caused by shiga-toxin producing Escherichia coli. Part 2 (2020)

Prevention and treatment of hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS) caused by Shiga-toxin producing Escherichia coli (STEC) continues to be a public health concern. The main reason for the problem is the lack of vaccines and lack of evidence for using of antibacterial etiotropic drugs to treat this infection. A promising scientific approach to create specific agents against STEC infection is the development of subunit recombinant vaccines. The analysis of experimental studies presented in this review shows that effective subunit vaccines against STEC infection can be created on the basis of known immunogenic determinants of HC and HUS causative agents – EspA, EspB, and Tir proteins, intimin, as well as H7 antigen of E. coli O157:H7 and nontoxic proteins of Shiga toxins Stx1 and Stx2 A and B subunits. Using these epitopes, three types of subunit vaccines are designed: antibacterial vaccine, vaccine protecting the macroorganism from systemic intoxication caused by Shiga toxins, and vaccines that simultaneously induce the antibacterial and antitoxic immunity. Since the epitopes listed above are weak immunogenic, to increase their immunogenicity, complex chimeric antigenic structures containing protein inducers are constructed that significantly increase the immune response to target specific epitopes. Mineral adjuvants are also widely used to increase the immunogenicity of STEC epitopes. All three types of created candidate subunit vaccines, at subcutaneous, intramuscular and intranasal application induce production of specific IgG and secretory IgA antibodies in animals and protect them from the infection caused by the STEC strains. Key words: STEC, hemorrhagic colitis, immunodominant antigens, Shiga toxins, EspA, EspB, Tir, intimine, IgG, sIgA
Confinement-Induced Morphological Changes in Diblock Copolymer Films (1996)

We have studied the ordering behavior of a (diblock copolymer, poly(styrene-d8)−poly(2-vinylpyridine) (dPS−PVP), in a confined geometry by neutron reflectivity, transmission electron microscopy, and atomic force microscopy. The diblock copolymer was confined between a silicon substrate (Si) on one side and a glassy polymer, poly(2-methylvinylcyclohexane) (P2MVCH), on the other side. In such a geometry, incompatibility between the natural domain period of the diblock copolymer (D*) and the film thickness (L) creates frustration that can be varied by controlling the copolymer film thickness. As the degree of frustration is increased (i.e., film thickness is decreased), the domain periods of the lamellae become progressively distorted from D*, and the lamellae orient with dPS/PVP interfaces parallel to the confining surfaces. The dPS block wets the P2MVCH confining wall and the PVP block wets the Si substrate. There is a limit, however, to the extent of distortion of the lamellar domain period; a further increase in frustration results in a sharp transition to a complex layered morphology that has a heterogeneous in-plane structure adjacent to the P2MVCH confining wall. In this morphology, both the dPS and PVP are located near the P2MVCH confining wall and only PVP is located at the Si confining wall. The sharp transition in the morphology is interpreted in the context of competing surface and bulk interactions. By removal of one of the confining walls, the frustration is relieved and a lamellar structure parallel to the surfaces is recovered with a domain period of D*.
A new mechanism for excitation of electrostatic ion cyclotron waves and associated perpendicular ion heating (1985)

A new mechanism for exciting the kinetic ion cyclotron waves in the presence of a nonuniform electric field perpendicular to the external magnetic field is given. Application of this instability to various space plasmas is discussed. The new instability mechanism may provide a more efficient agent for perpendicular ion heating than other EIC generation processes, since the linear growth rate is insensitive to the temperature ratio.
Prevalence of hyperinsulinemia in young, nonobese Japanese men (1997)

These results demonstrated that the prevalence of hyperinsulinemia among the present sample of young, nonobese, Japanese men was 12% and that the prevalence increased with blood pressure elevation. Furthermore, hypertriglyceridemia and sympathetic nerve hyperactivity appear to be related to hyperinsulinemia and the emergence of hypertension.
Proteasome inhibitors in Waldenström macroglobulinemia (2013)

In this issue of Blood , Dimopoulos and colleagues report on a prospective multicenter clinical trial conducted by the European Myeloma Network (EMN) that evaluated the activity of bortezomib, dexamethasone, and rituximab (BDR) in patients with untreated, symptomatic Waldenstrom macroglobulinemia (WM). 1
A minimum variance method for genome-wide data-driven normalization of quantitative real-time polymerase chain reaction expression data (2014)

Advances in multiplex qRT-PCR have enabled increasingly accurate and robust quantification of RNA, even at lower concentrations, facilitating RNA expression profiling in clinical and environmental samples. Here we describe a data-driven qRT-PCR normalization method, the minimum variance method, and evaluate it on clinically derived Mycobacterium tuberculosis samples with variable transcript detection percentages. For moderate to significant amounts of nondetection (∼50%), our minimum variance method consistently produces the lowest false discovery rates compared to commonly used data-driven normalization methods.
Development of Protective Coatings for Silicon Devices (2003)

Ceramic coatings can be effectively used as a surface protective layer for silicon-based devices due to their inertness and good mechanical properties. One challenge is to avoid the weaknesses that ceramic coatings inherently possess, i.e., low strain tolerance, brittleness, high temperature required to process the film, and difficulty to produce a uniform, dense layer. Therefore, in an attempt to process strain-tolerant ceramic coatings at low temperatures, we develop an aqueous solution precursor processing route. Nanometer scale organic coatings, fabricated by self-assembly processes on the silicon, are used as a ‘template’ to aid the subsequent deposition of hard ceramic coatings (ZrO2). The ceramic coatings are deposited by spin coating. The organic self-assembled monolayer (SAM) coating provides temporary strain tolerance for the overlying hard coating upon mechanical and thermomechanical stresses before being decomposed at high temperatures. Molecular level understanding of the coating microstructure and micromechanics involved in the coating processes is systematically approached via experimental tools such as AFM and nanoindenter, as well as numerical simulation.
Correction: Fleischer et al. Similarities and Differences between Site-Selective Acylation and Phosphorylation of Amphiphilic Diols, Promoted by Nucleophilic Organocatalysts Decorated with Outer-Sphere Appendages. Catalysts 2023, 13, 361 (2023)

The authors wish to make the following corrections to this paper [...]
Towards the Antimicrobial Finishing of Poly(isoprene) (2012)

Abstract Summary: Anionically polymerised (poly)isoprene was functionalized with cysteamine applying thiol‐ene click chemistry. Subsequent quaternisation of the primary amino groups gave polymers with antimicrobial activity against Listeria monocytogenes , Eschericchia coli , Pseudomonas fluorescens and Staphylococcus aureus as revealed from tests performed according to the Japanese Industrial Standard Z2801:2000. The novel polymers feature sufficient thermal stability for the compounding with commodity polymers such as poly(propylene) and might be used as a non leaching additive to finish commodity polymers with antimicrobial acitivity.
Improved small gain conditions for input-to-state stability with respect to measurement functions: Discrete time networked system (2021)

In this paper we study input-to-state stability with respect to measurement functions for discrete time networked systems. In such a networked system, the trajectory of each subsystem is affected by another in each time step, and this constraining system may change from step to step. We derive small gain conditions of input-to-state stability with respect to measurement functions for this type of discrete time networked system relying on the construction of dissipative-form finite time Lyapunov function. These conditions loosen those presented in [1] and [2]. Finally, we demonstrate the applicability of our results by applying them to the stability analysis of a distributed graph algorithm which does not satisfy the conditions of [1] and [2].
Squamous Cell Carcinoma of the Head and Neck in the Elderly (1995)

These findings suggest that HNSCC arising after the seventh decade of life less frequently involves a genetic change commonly found in younger patients. Heavy carcinogen exposure and p53 gene mutations are present less often in elderly individuals, whereas this group appears to be more susceptible to multiple cancers. The precise biologic factors involved in neoplastic transformation in this older population await discovery. Since aggressive therapy can be successfully tolerated by many elderly patients, an individualized approach to treatment is advocated.
Optimum on-chip power distribution networks for gigascale integration (GSI) (2001)

IR-drop and simultaneous switching noise (SSN) are the main concerns for the design of an on-chip power distribution network. Analytical models for IR-drop and SSN in an on-chip power distribution network are presented. These models are used to design an optimum power distribution network to meet the requirements for the system. Utilizing the methodology presented, the requirements for power distribution of future technology generations are demonstrated.
Automated DNA extraction, quantification, dilution, and PCR preparation for genotyping by high-resolution melting. (2010)

Genotyping by high-resolution amplicon melting uses only two PCR primers per locus and a generic, saturating DNA dye that detects heteroduplexes as well as homoduplexes. Heterozygous genotypes have a characteristic melting curve shape and a broader width than homozygous genotypes, which are usually differentiated by their melting temperature (T(m)). The H63D mutation, associated with hemochromatosis, is a single nucleotide polymorphism, which is impossible to genotype based on T(m), as the homozygous WT and mutant amplicons melt at the same temperature. To distinguish such homozygous variants, WT DNA can be added to controls and unknown samples to create artificial heterozygotes with all genotypes distinguished by quantitative heteroduplex analysis. By automating DNA extraction, quantification, and PCR preparation, a hands-off integrated solution for genotyping is possible. A custom Biomek® NX robot with an onboard spectrophotometer and custom programming was used to extract DNA from whole blood, dilute the DNA to appropriate concentrations, and add the sample DNA to preprepared PCR plates. Agencourt® Genfind™ v.2 chemistry was used for DNA extraction. PCR was performed on a plate thermocycler, high-resolution melting data collected on a LightScanner-96, followed by analysis and automatic genotyping using custom software. In a blinded study of 42 H63D samples, 41 of the 42 sample genotypes were concordant with dual hybridization probe genotyping. The incorrectly assigned genotype was a heterozygote that appeared to be a homozygous mutant as a result of a low sample DNA concentration. Automated DNA extraction from whole blood with quantification, dilution, and PCR preparation was demonstrated using quantitative heteroduplex analysis. Accuracy is critically dependent on DNA quantification.
Establishment and Characterization of a New Human Prostatic Carcinoma Cell Line (DuPro-1) (1991)

A new human prostate adenocarcinoma cell line (DuPro-1) has been established from the athymic nude mouse supported xenograft DU5683. This was accomplished by embedding dispersed xenograft cells in 0.1 by 5.0 cm. spaghetti-like strands of Basement Membrane MATRIGEL [BMM (Collaborative Research, Inc.)], a unique technique facilitating the transition to tissue culture. Now passed over 30 times, the cells display anchorage and serum concentration independent growth with a doubling time of 22 to 24 hours. Cells exhibit pronounced morphological differences when grown on BMM coated culture dishes, assuming a pseudoglandular configuration, in contrast to typical homogeneous monolayer growth on plastic culture dishes. Light and electron microscopy show cohesive sheets of anaplastic epithelial cells, consistent with prostate carcinoma. Karyotypic analysis revealed all human chromosomes, near tetraploidy, 10 to 12 markers, and 3 to 4 X chromosomes, without a Y chromosome. Cells injected s.c. or embedded in BMM and implanted in the subrenal capsule space are equally tumorigenic in male and female athymic mice, suggesting that DuPro-1 cells are hormonally insensitive. Embedding cells in BMM may be useful in developing other tissue culture cell lines from neoplasms difficult to initiate in vitro. DuPro-1 should provide a valuable means to study the biology, immunology, and chemosensitivity of human prostate cancer.
Properties of Garnet Ceramic Scintillators (2014)

Garnet-based ceramics have applications as downconverters in LED lighting, laser media, and as scintillators for the detection of high energy photons. In this presentation, we will discuss the properties of Ce 3+ -doped garnet ceramics within the context of their applicability in computerized tomography (CT) scanners. CT scintillator requirements are different versus those for PET and applications that require energy resolution due to the need to reducing both afterglow at various timeframes and radiation damage while having reduced transparency requirements. Therefore, we will discuss how we can modify garnet composition and processing in order to meet some of these requirements. These modifications in process and composition can also give some insight towards some of the potential defects that are responsible for worse (or better) garnet scintillators. Finally, we will address some of the potential paths for future research and development.
A New 18F-Labeled Folic Acid Derivative with Improved Properties for the PET Imaging of Folate Receptor–Positive Tumors (2010)

2'-(18)F-fluorofolic acid, obtained via an integrated approach, is a promising PET agent for folate receptor-positive tumors and outperforms previously reported (18)F-labeled folates.
QR Decomposition-Based Cyclic Prefixed Single-Carrier Transmissions for Cooperative Communications: Concepts and Research Landscape (2022)

As an alternative transmission scheme to orthogonal frequency division multiplexing (OFDM), cyclic prefixed single-carrier (CP-SC) transmissions have been widely adopted to overcome the shortcomings of OFDM. How to exploit the achievable full diversity in frequency selective fading channels is the key question in applying CP-SC-based transmissions. Thus, in this tutorial, we focus on recent research in the areas related to CP-SC transmissions for cooperative wireless systems. After explaining the basic concept and operation of CP-SC transmissions, we introduce various types of diversity that are achievable by CP-SC transmissions. To achieve these types of diversity, it is necessary to employ QR decomposition (QRD)-M-based data detection in the receiver. To verify the benefits of CP-SC transmissions in terms of diversity gain, we exemplify various wireless systems for relaying, spectrum sharing, physical layer security, and distributed cyclic delay diversity, and provide link-level simulations. Especially, as alternative metrics of reliability, which is one of the key features of 5G and beyond 5G (B5G) systems, we evaluate the average symbol error rate and outage probability. Finally, we discuss potential research directions involving CP-SC transmissions in emerging wireless communication systems.
ChemInform Abstract: KOBALT(II)‐KOMPLEXE DER VIERZAEHNIGEN MAKROCYCLUS 2,12‐DIMETHYL‐3,7,11,17‐TETRAAZA‐BICYCLO(11,3,1)HEPTADECAPENTAEN‐(1(17),2,11,13,15) (1970)

Abstract Die trigonal‐bipyramidalen low‐spin‐Komplexe (IIIa) bilden sich bei der Synthese des makrocyclischen Liganden aus dem Triamin (I) und dem Pyridin (II) in Gegenwart des entsprechenden Co(II)‐Sa1zes.
Carbonic Anhydrase-II Inhibition. What Are the True Enzyme–Inhibitory Properties of the Sulfamide Cognate of Topiramate? (2008)

The marketed drug topiramate (&lt;b&gt;1&lt;/b&gt;) is a moderate inhibitor of carbonic anhydrase-II (CA-II) (&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; or &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;d&lt;/sub&gt; = 0.3–0.6 µM), whereas sulfamide cognate &lt;b&gt;2&lt;/b&gt; is a comparatively weak inhibitor (&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; or &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;d&lt;/sub&gt; = 25–650 µM). From an X-ray cocrystal structure of &lt;b&gt;2&lt;/b&gt;·CA-II, Winum et al. (&lt;i&gt;J&lt;/i&gt;. &lt;i&gt;Med&lt;/i&gt;. &lt;i&gt;Chem&lt;/i&gt;. &lt;b&gt;2006&lt;/b&gt;, &lt;i&gt;49&lt;/i&gt;, 7024) proposed that an adverse steric interaction between the C8 methyl group in &lt;b&gt;2&lt;/b&gt; and Ala-65 of CA-II is responsible for the diminished CA-II inhibitory potency of &lt;b&gt;2&lt;/b&gt;. We performed a straightforward test of this Ala-65 effect by synthesizing and examining ligand &lt;b&gt;3&lt;/b&gt;, which lacks the offending (pro-&lt;i&gt;S&lt;/i&gt; or C8) methyl substituent in &lt;b&gt;2&lt;/b&gt;. We also prepared and evaluated related sulfamides &lt;b&gt;5&lt;/b&gt;, &lt;b&gt;7&lt;/b&gt;, and &lt;b&gt;9&lt;/b&gt;. In a CA-II inhibition assay (4-nitrophenyl acetate), the &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; for &lt;b&gt;3&lt;/b&gt; was ∼300 µM, indicating very weak inhibition, close to that for &lt;b&gt;2&lt;/b&gt; (4NPA, &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt; = 340 µM). In a CA-II binding assay (ThermoFluor), the &lt;i&gt;K&lt;/i&gt;&lt;sub&gt;d&lt;/sub&gt; for &lt;b&gt;3&lt;/b&gt; was &gt;57 µM, indicating very weak binding, lower than the affinity of &lt;b&gt;2&lt;/b&gt; (&lt;i&gt;K&lt;/i&gt;&lt;sub&gt;d&lt;/sub&gt; = 25 µM). Our results draw into question the proposed steric interaction between the C8 methyl of &lt;b&gt;2&lt;/b&gt; and Ala-65 of CA-II.
In-vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma (2022)

Abstract Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed metabolism in patient-derived xenografts (tumorgrafts) from diverse forms of RCC. Tumorgrafts from VHL -mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engage in oxidative and reductive glutamine metabolism. We used several approaches to suppress glutamine metabolism and test the effect on tumor growth. Genetic silencing of isocitrate dehydrogenase-1 or -2 impaired reductive labeling of TCA cycle intermediates and suppressed tumor growth. Glutaminase inhibition resulted in modest growth suppression and variable effects on glutamine metabolism in vivo. Infusions with [amide- 15 N]glutamine revealed persistent amidotransferase activity during glutaminase inhibition, and blocking these activities with the amidotransferase inhibitor JHU-083 also reduced tumor growth. We conclude that ccRCC tumorgrafts catabolize glutamine via multiple pathways, perhaps explaining why it has been challenging to achieve therapeutic responses in patients by inhibiting glutaminase. Teaser Glutamine fuels the TCA cycle and amidotransferase pathways in clear cell renal cell carcinoma.
22 kV SiC Emitter turn-off (ETO) thyristor and its dynamic performance including SOA (2015)

Ultra-high voltage (>10 kV) power devices based on SiC are gaining significant attentions since Si power devices are typically at lower voltage levels. In this paper, a world record 22kV Silicon Carbide (SiC) p-type ETO thyristor is developed and reported as a promising candidate for ultra-high voltage applications. The device is based on a 2cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> 22kV p type gate turn off thyristor (p-GTO) structure. Its static as well as dynamic performances are analyzed, including the anode to cathode blocking characteristics, forward conduction characteristics at different temperatures, turn-on and turn-off dynamic performances. The turn-off energy at 6kV, 7kV and 8kV respectively is also presented. In addition, theoretical boundary of the reverse biased safe operation area (RBSOA) of the 22kV SiC ETO is obtained by simulations and the experimental test also demonstrated a wide RBSOA.
Wall Deposition of Ultrafine Aerosol Particles by Thermophoresis in Nonisothermal Laminar Pipe Flow of Different Carrier Gas (1994)

Deposition of ultrafine aerosol particles by Brownian diffusion and thermophoresis in a nonisothermal laminar pipe flow is investigated theoretically and experimentally. The deposition rates of Ag and TiO 2 particles of 8–30 nm in diameter suspended either in N 2 , Ar or He gas are measured using a circular pipe with a nonuniform wall temperature distribution. The numerical calculation results considering the gas flow, temperature and particle distributions in the pipe show good agreement with the measured values. The particle deposition is enhanced with the increase of the wall temperature variation, but does not depend on the particle material. The difference in the deposition rates among the carrier gases is mostly attributable to the values of the Brownian diffusion coefficient. The enhancement of deposition by thermophoresis is of a similar magnitude among the carrier gases, which is explained in terms of the temperature distribution of the gases in the pipe.