gebhart/patrepeval huggingface dataset:
Sensitive Method for Measuring Telomere Lengths by Quantifying Telomeric DNA Content of Whole Cells (1998)

Recently, a new method for measuring telomere lengths based on telomere DNA content was developed. The method, which is based on the ratio of telomere to centromere DNA content (TC ratio), is highly sensitive, allowing the analysis of small quantities of DNA. However, the method required the isolation of DNA, which can be difficult or impossible for small numbers of cells. Here, we suggest an improvement of this method that can directly estimate telomere lengths from whole cells. We optimized the method for whole cells and purified DNA and found that accurate TC ratios can be obtained from as little as 9 ng of DNA or 800 whole cells. There was no statistically significant difference between the ratios obtained with purified DNA or with whole cells, indicating that the isolation of DNA is not necessary for small samples.
An area-efficient, integrated, linear regulator with ultra-fast load regulation (2004)

We demonstrate a fully-integrated linear regulator for multi-supply-voltage microprocessors implemented in a 90 nm CMOS technology. Ultra-fast, single-stage load regulation achieves 0.54 ns response time at 94% current efficiency. This enables 10% peak-to-peak output noise for a 100 mA load step with only a small on-chip decoupling capacitor of 0.6 nF. A PMOS pull-up transistor in the output stage results in a small regulator area of 0.008 mm/sup 2/ and the 0.6 nF MOS capacitor area of 0.090 mm/sup 2/.
Use of colony assays and anti-T cell immunotoxins to elucidate the immunobiologic features of leukemic progenitor cells in T-lineage acute lymphoblastic leukemia. (1988)

The specific binding of radioiodinated rIL-2 to fresh marrow blasts from T-lineage acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated rIL-2 molecules bound per blast ranged from undetectable to 1948. In colony assays, 72% of 32 cases analyzed showed a significant proliferative response to rIL-2, which depended on PHA-stimulated lymphocyte conditioned medium activation. Colony stimulation indices correlated with the number of radioiodinated rIL-2 molecules bound per blast but not with expression of CD25/Tac Ag on fresh marrow blasts or primary colony blasts. These findings provide evidence that in T-lineage ALL functional IL-2R proteins are expressed on leukemic progenitor blasts which may be distinct from Tac Ag. We used the mAb 35.1, T101, and G3.7 to test for expression of CD2, CD5, and CD7 on fresh marrow blasts from 126 T-lineage ALL patients. CD2, CD5, and CD7 were expressed in 84%, 93%, and 99% of cases, respectively. Furthermore, colony blasts that represent the early progeny of leukemic progenitor blasts were also CD2+CD5+CD7+. Ricin conjugates of 35.1, T101, and G3.7 mAb were used as Ag-specific cytotoxic probes to test for expression of CD2, CD5, and CD7 at the level of T-lineage leukemic progenitor blasts. Each immunotoxin was able to selectively eliminate greater than 99% of leukemic progenitor blasts, providing unique and direct evidence that these cells co-express CD2, CD5, and CD7. Neither mixtures of anti-CD5 and anti-CD7 nor anti-CD2, anti-CD5, and anti-CD7 immunotoxins were more effective against blast progenitor cells than the individual immunotoxins alone, confirming that CD2, CD5, and CD7 are not expressed on non-overlapping progenitor cell subpopulations.
Structural tailoring of hydrogen-bonded poly(acrylic acid)/poly(ethylene oxide) multilayer thin films for reduced gas permeability (2014)

Hydrogen bonded poly(acrylic acid) (PAA)/poly(ethylene oxide) (PEO) layer-by-layer assemblies are highly elastomeric, but more permeable than ionically bonded thin films. In order to expand the use of hydrogen-bonded assemblies to applications that require a better gas barrier, the effect of assembling pH on the oxygen permeability of PAA/PEO multilayer thin films was investigated. Altering the assembling pH leads to significant changes in phase morphology and bonding. The amount of intermolecular hydrogen bonding between PAA and PEO is found to increase with increasing pH due to reduction of COOH dimers between PAA chains. This improved bonding leads to smaller PEO domains and lower gas permeability. Further increasing the pH beyond 2.75 results in higher oxygen permeability due to partial deprotonation of PAA. By setting the assembling pH at 2.75, the negative impacts of COOH dimer formation and PAA ionization on intermolecular hydrogen bonding can be minimized, leading to a 50% reduction in the oxygen permeability of the PAA/PEO thin film. A 20 bilayer coating reduces the oxygen transmission rate of a 1.58 mm natural rubber substrate by 20 ×. These unique nanocoatings provide the opportunity to impart a gas barrier to elastomeric substrates without altering their mechanical behavior.
P2‐444: The Role of CNI‐1493 in the function of primary microglia with respect to β‐Amyloid (2011)

ß-Amyloid(Aß) oligomer toxicity is a crucial factor in the development of Alzheimer's disease. The aim of therapeutic research is to target the modification of secretase activity, increase A degradation, reduce Aß formation and modulate Aß-induced neuroinflammation. Recently, the p38 MAP kinase inhibitor CNI-1493 has been shown to reduce plaque load and has led to an improvement in memory performance in a transgenic mouse model. MTT assays were performed to quantify cell viability following treatment of primary microglia with Aß and CNI-1493. FACS analysis was used to measure phagocytosis of primary microglia cells in response to treatment with CNI-1493. We used ELISA to analyse variations in cytokine concentrations. Western-blot/dot-blot techniques were used to show the interaction of CNI-1493 with Aß-oligomers. RT-PCR was used to analyse secretase expression, and secretase function was determined using fluorimetric assays. CNI-1493 is able to prevent oligomer formation in microglia as shown by dot blot analysis. Coincubation of CNI-1493 and Aß led to a reduction in cell death as shown by MTT assays. Interestingly, a concomitant significant reduction was found in the A-induced release of IL-6 and TNF-α in the presence of CNI-1493. Another important function of microglia is the ability to perform phagocytosis. Uptake of labelled Aß in primary microglia cells was increased in response to treatment with CNI-1493. Finally, there is evidence that microglia do produce Aß. We examined the influence of CNI-1493 on these secretases and found an increase in α-secretase activity in primary microglia. We found a reduction in oligomer formation after treatment with CNI-1493. In addition, this lead to a reduction in cytokine secretion, thereby reducing inflammation in this in vitro model. In addition, we observed an increase in phagocytic activity in primary microglia in vitro following CNI-1493 treatment. This may point to increased clearance of Aß which is essential for the clearance of Aß in AD. We hypothesize that CNI-1493 not only reduces neuroinflammation and consequent neurodegeneration, but also leads to a shift in APP-signalling towards the non-amyloidogenic pathway. In summary, we consider CNI-1493 a promising candidate for the treatment of AD.
Abstract 5272: Sensitive bioluminescent assays for monitoring changes in tumor and immune cell metabolism (2019)

The tumor microenvironment is complex, containing diverse cell populations with individual nutrient requirements. Tumor and immune cells must respond to the dysregulated and changing conditions of the tumor microenvironment, as well as compete for fuels, to remain functional and viable. As metabolism is critical for proper cell function, e.g. for effective immune cell activity, understanding the metabolic needs of these cells is essential. We have developed a series of bioluminescent metabolite detection assays for monitoring cell metabolism. The assays share a common NAD(P)H bioluminescent detection technology that can be coupled with specific dehydrogenases to monitor key metabolic pathways such as: glycolysis with glucose and lactate detection; glutamine metabolism with glutamine and glutamate measurements; and lipolysis and lipogenesis with glycerol and triglyceride measurements. The assays were developed to have high sensitivity permitting detection of low levels of metabolites (femtomole detection limit), an important feature when samples contain only a few cells or small volumes. The assays can be used in a non-lytic format by analyzing metabolites in samples of collected cell culture medium. In this way changes over time can be monitored and the cells remain intact for additional measurements, such as multiplexing with viability or cytotoxicity assays. We have used these assays to study the metabolic activity of tumor cell lines and T cells. The induction of aerobic glycolysis is an early step in the activation of T cells. Here we present an example of detecting T cell activation in vitro by monitoring glycolysis and quantitating the increase in lactate secretion over time. Activation was observed only in the presence of both glucose and glutamine, confirming the requirements for both fuels and biochemical pathways for activation. In addition to understanding fuel requirements of cells, we also used the assays to follow changes of metabolic pathways in cancer cell lines treated with small molecule compounds. Treatment with such compounds could provide a means of manipulating tumor nutrient usage and metabolite secretion in the tumor microenvironment. In our experiments, metabolite levels were found to be altered by effectors of glycolysis, oxidative phosphorylation and glutamine metabolism. Multiplexing with viability and cytotoxicity assays provided information about cell health during the experiments.Citation Format: Donna Marie Leippe, Natasha Karassina, Michael P. Valley, Gediminas Vidugiris, James J. Cali, Jolanta Vidugiriene. Sensitive bioluminescent assays for monitoring changes in tumor and immune cell metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5272.
Empirical force field calculations. Part 28. Conformations and pseudorotations of 1,3‐dioxolane and some methyl‐substituted derivatives (1987)

Abstract The conformations and pseudorotations of 1,3‐dioxolane ( 1 ), cis ‐ and trans ‐4,5‐dimethyl‐1,3‐dioxolane ( 2 and 3 ) and the corresponding 2,2‐dimethyl derivatives ( 4, 5 and 6 ) have been studied with molecular mechanics using the MM2 force field. Free pseudorotation occurs in 1 and 4 (Δ E = 1.5 kJ/mol) and pseudolibration in 2, 3, 5 and 6 (Δ E = 6, 7, 11 and 14 kJ/mol, respectively). The steric energies of 3 and 6 are lower than those of 2 and 5 since the 4‐ and 5‐methyl groups can both occupy a pseudo‐equatorial position in the minimum energy conformation of the trans isomers. Estimates of Δ H ° f (25°C, gas, kJ/mol) are: 2 , ‐ 376.1; 3 , ‐ 380.5; 4 , ‐ 387.2; 5 , ‐ 464.4; 6 , ‐ 470.1. Vicinal proton coupling constants were calculated from the appropriate torsion angles and averaged over the pseudorotation circuit. They are in good agreement with experimental values. The 1,3‐dioxolanes can be used as model compounds for borate monoesters of vicinal diols. The 13 C chemical shifts of C(2) in 1,3‐dioxolanes correlate well with the 11 B chemical shifts in the corresponding borate monoesters.
Immunology and Technology of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccines (2022)

We have experienced an enormous cohesive effort of the scientific community to understand how the immune system reacts to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and how to elicit protective immunity via vaccination. This effort resulted in the development of vaccines in record time with high levels of safety, efficacy, and real-life effectiveness. However, the rapid diffusion of viral variants that escape protective antibodies prompted new studies to understand SARS-CoV-2 vulnerabilities and strategies to guide follow-up actions to increase, and maintain, the protection offered by vaccines. In this review, we report the main findings on human immunity to SARS-CoV-2 after natural infection and vaccination; we dissect the immunogenicity and efficacy of the different vaccination strategies that resulted in products widely used in the population; and we describe the impact of viral variants on vaccine-elicited immunity, summarizing the main discoveries and challenges to stay ahead of SARS-CoV-2 evolution. SIGNIFICANCE STATEMENT: This study reviewed findings on human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), analyzed the immunogenicity and efficacy of the various vaccines currently used in large vaccination campaigns or candidates in advanced clinical development, and discussed the challenging task to ensure high protective efficacy against the rapidly evolving SARS-CoV-2 virus. This manuscript was completed prior to the emergence of the Omicron variant and to global vaccine boosting efforts.
Sum-rate maximization for bi-directional full-duplex MIMO systems under multiple linear constraints (2014)

We consider a full-duplex bi-directional communication between two nodes that suffer from self-interference, where the nodes are equipped with multiple antennas. We focus on the effect of a residual self-interference due to independent and identically distributed (i.i.d.) channel estimation errors and limited dynamic ranges of the transmitters and receivers. We consider the design of source covariance matrices at the nodes for sum-rate maximization problem subject to multiple generalized linear constraints. The non-convex sum-rate optimization problem is solved using two sup-optimal techniques, which are proven to converge to a local optimum point. These algorithms exploit both spatial and temporal freedoms of the source covariance matrices of the multiple-input multiple-output (MIMO) links between the nodes to achieve higher sum-rate.
Immunoglobulin Transgene" Effect on Differentiation- Specific Molecules (1990)

Mice transgenic for y2b Ig heavy chain were examined for alterations in B-cell differentiation and endogenous Ig gene rearrangement and expression. Fresh bone marrow from these mice was markedly reduced in BP-1 cells and there were small reductions in B220 and sIg cells. A-MuLV (Abelson murine leukemia virus) transformants from these bone marrow cells showed little alteration in Ig gene rearrangement and expression when compared to controls, however. Isolation of the B-lymphoid compartment from these mice in vitro using LBMC (lymphoid bone marrow cultures) enabled more detailed characterization of the effects of the transgene. LBMC derived from y2b transgenic mice had similar growth kinetics, but a 4-5-week delay in the expression of endogenous mu Ig in comparison to control cultures. Nucleic acids derived from these early cultures prior to endogenous mu Ig expression showed reduced Ig JH rearrangements, some sterile mu transcription, low levels of BP-1 expression, and virtually undetectable TdT (terminal deoxynucleotidyl transferase) expression. Thus, this y2b transgene appears able to affect early B-lymphocyte development.
Stereoselective Cyclopropanation in the Synthesis of 3′-Deoxy-3′-C-hydroxymethyl-2′,3′-methylene-uridine (2014)

The synthesis of the novel 2',3'-cyclopropane nucleoside 3'-deoxy-3'-C-hydroxymethyl-2',3'-methylene-uridine is described. Stereoselective construction of the cyclopropane ring was achieved via Simmons-Smith cyclopropanation of a benzyl protected silyl enol ether, which was itself derived from 1,2-O-isopropylidene-α-D-xylofuranose.
Integrated Next-Generation Sequencing and Avatar Mouse Models for Personalized Cancer Treatment (2014)

The use of full genomic analysis for cancer care is encouraging but presents important challenges that will need to be solved for broad clinical application. Avatar models are a promising investigational platform for therapeutic decision making. While limitations still exist, this strategy should be further tested.
Similarity-aware indexing for real-time entity resolution (2009)

Entity resolution, also known as data matching or record linkage, is the task of identifying and matching records from several databases that refer to the same entities. Traditionally, entity resolution has been applied in batch-mode and on static databases. However, many organisations are increasingly faced with the challenge of having large databases containing entities that need to be matched in real-time with a stream of query records also containing entities, such that the best matching records are retrieved. Example applications include online law enforcement and national security databases, public health surveillance and emergency response systems, financial verification systems, online retail stores, eGovernment services, and digital libraries.
Concurrent C++: Concurrent programming with class(es) (1988)

Abstract C++ and Concurrent C are both upward‐compatible supersets of C that provide data abstraction and parallel programming facilities, respectively. Although data abstraction facilities are important for writing concurrent programs, we did not provide data abstraction facilities in Concurrent C because we did not want to duplicate the C++ research effort. Instead, we decided that we would eventually integrate C++ and Concurrent C facilities to produce a language with both data abstraction and parallel programming facilities, namely, Concurrent C++. Data abstraction and parallel programming facilities are orthogonal. Despite this, the merger of Concurrent C and C++ raised several integration issues. In this paper, we will give introductions to C++ and Concurrent C, give two examples illustrating the advantages of using data abstraction facilities in concurrent programs, and discuss issues in integrating C++ and Concurrent C to produce Concurrent C++.
Analytic modeling of antibody versus nanocell delivery of photosensitizer (2010)

Delivery of therapeutic agents to solid tumors is challenging, and the issues that govern this can be distilled down into parameters which allow computational modeling. In this paper, the basic rate equations and diffusion kernel for the time and space modeling of delivery are developed, along with an analytical solution to this equation. The model is then used to compare delivery of Avastin antibody relative to delivery encapsulated in a nanocell delivery vehicle. The key factors are the plasma clearance or excretion rates, and the binding, or not, as it transports into the tumor tissue. A reduction in the plasma clearance rate inherently increases available delivery over time, and additionally the reduction in binding from antibody to nanocell allows higher penetration into the tumor at the longer circulation times.
Characterization of Cu(In, Ga)Se<inf>2</inf> thin films and devices sputtered from a single target without additional selenization (2011)

Typically, Cu(In, Ga)Se <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> (CIGS) thin films for photovoltaic devices are deposited by co-evaporation or, alternately, by deposition of the metals with, or followed by, treatment in a selenium environment. In this proceeding, we describe CIGS films that are instead deposited by RF magnetron sputtering from a single quaternary target without any additional selenization. Devices built with these films exhibit efficiencies as high as 9.9%. These results represent the first report of working CIGS devices fabricated by sputtering without additional selenization. We demonstrate that deposition power can be varied in order to change the film morphology and improve device performance.
Persistence of immunogenic pulmonary metastases in the presence of protective anti-melanoma immunity. (2001)

We have developed a murine melanoma model that allows us to investigate the mechanisms by which spontaneous, immunogenic melanoma metastases escape immunological destruction in syngeneic mice. In the current study, we tested the hypothesis that loss of immunogenicity is an obligatory step in the persistence of pulmonary metastases. Fragments of syngeneic K1735-M2 tumor were implanted in the outer edge of one pinna per C3H/HeN mouse, and the growing tumors were removed 2-3 weeks later. Two weeks after removal of the tumors, the mice demonstrated effective T-cell-mediated immunity to s.c. challenge with K1735-M2 cells. However, lung metastases appeared in 23% of the immunized mice within 9-12 weeks after the initial tumor implantation. The expression of protective immunity to s.c. tumors required the presence of both CD4+ and CD8+ T cells. The immunized mice had specific CTLs capable of killing both K1735-M2 melanoma cells and the cells of nine independently derived melanoma metastases. Furthermore, K1735-M2 immunization protected these mice from s.c. tumor challenge with all nine metastatic cell lines. Our results demonstrate that the persistence of these metastases within the lung was not attributable to emergence of antigen-loss variants in immunized hosts. Our model provides an approach to investigate other mechanisms by which spontaneous metastases escape from immunological control and an opportunity to improve immunotherapy of melanoma metastases.
Constitutive Activation of Integrin α9 Augments Self-Directed Hyperplastic and Proinflammatory Properties of Fibroblast-like Synoviocytes of Rheumatoid Arthritis (2017)

Despite advances in the treatment of rheumatoid arthritis (RA), currently approved medications can have significant side effects due to their direct immunosuppressive activities. Additionally, current therapies do not address residual synovial inflammation. In this study, we evaluated the role of integrin α9 and its ligand, tenascin-C (Tn-C), on the proliferative and inflammatory response of fibroblast-like synoviocytes (FLSs) from RA patients grown in three-dimensional (3D)-micromass culture. FLSs from osteoarthritis patients, when grown in the 3D-culture system, formed self-directed lining-like structures, whereas FLSs from RA tissues (RA-FLSs) developed an abnormal structure of condensed cellular accumulation reflective of the pathogenic features of RA synovial tissues. Additionally, RA-FLSs grown in 3D culture showed autonomous production of proinflammatory mediators. Predominant expression of α9 and Tn-C was observed in the condensed lining, and knockdown of these molecules abrogated the abnormal lining-like structure formation and suppressed the spontaneous expression of matrix metalloproteinases, IL-6, TNFSF11/RANKL, and cadherin-11. Disruption of α9 also inhibited expression of Tn-C, suggesting existence of a positive feedback loop in which the engagement of α9 with Tn-C self-amplifies its own signaling and promotes progression of synovial hyperplasia. Depletion of α9 also suppressed the platelet-derived growth factor-induced hyperplastic response of RA-FLSs and blunted the TNF-α-induced expression of matrix metalloproteinases and IL-6. Finally, α9-blocking Ab also suppressed the formation of the condensed cellular lining by RA-FLSs in 3D cultures in a concentration-related manner. This study demonstrates the central role of α9 in pathogenic behaviors of RA-FLSs and highlights the potential of α9-blocking agents as a nonimmunosuppressive treatment for RA-associated synovitis.