gebhart/patrepeval huggingface dataset:
Leukocyte Telomere Length in the Finnish Diabetes Prevention Study (2012)

Leukocyte telomere length (TL) is considered a biomarker for biological aging. Shortened TL has been observed in many complex diseases, including type 2 diabetes (T2DM). Lifestyle intervention studies, e.g. the Diabetes Prevention Study (DPS), have shown a decrease in the incidence of T2DM by promoting healthy lifestyles in individuals with impaired glucose tolerance (IGT). Our aim was to study in the DPS the influence of the lifestyle intervention on TL. TL was measured by quantitative PCR-based method at two time points (N = 334 and 343) on average 4.5 years apart during the active intervention and post-intervention follow-up. TL inversely correlated with age. Our main finding was that TL increased in about two thirds of the individuals both in the intervention and in the control groups during follow-up; TL increased most in individuals with the shortest TL at the first measurement. TL was not associated with development of T2DM, nor did lifestyle intervention have an effect on TL. No association between insulin secretion or insulin resistance indices and TL was observed. We did not detect an association between TL and development of T2DM in the DPS participants. It could be due to all participants being overweight and having IGT at baseline, both of which have been found to be independently associated with shorter leukocyte TL in some earlier studies. TL had no substantial role in worsening of glucose tolerance in people with IGT. Our study confirms that leukocyte TL can increase with time even in obese people with impaired glucose metabolism.
An open system approach to higher learning: the role of joint ventures with business (2000)

The gap between higher learning practices and business expectations in terms of preparing engineering, technology, and business students is significant. This paper offers an innovative approach toward narrowing that gap. The approach offered stresses an open system orientation and partnerships between business and education. This approach was utilized successfully, resulting in win‐win outcomes for both business and higher education. The results of a mini‐case study are presented and their implications are discussed.
Effect on Patient Safety of a Resident Physician Schedule Without 24-Hour Shifts (2020)

(Abstracted from N Engl J Med 2020;382:2514–2523) Over the last 4 decades, a body of literature has studied the effect of extended shifts (working ≥24 hours) for resident physicians on their alertness and performance, and by extension, patient safety. Since then, the results of further studies have been inconsistent.
A new approach method to obtain theL1generalized analytic Fourier–Feynman transform (2018)

In this paper, we first introduce the concept of the ⊗-product on function space. We then proceed to use this concept to obtain several integration formulas. In addition, we establish various relationships which exist. Also, we establish the relationships among the ⊗-product, the generalized convolution product and the first variation.
Sequential defects in cardiac lineage commitment and maturation cause hypoplastic left heart syndrome (2021)

ABSTRACT Background Complex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role. Methods To identify perturbations in gene programs controlling ventricular muscle lineage development in HLHS, we performed: i) whole-exome sequencing of 87 HLHS parent-offspring trios, ii) nuclear transcriptomics of cardiomyocytes from ventricles of 4 patients with HLHS and 15 controls at different stages of heart development, iii) single cell RNA sequencing and iv) 3D modeling in iPSCs from 3 patients with HLHS and 3 controls. Results Gene set enrichment and protein network analyses of damaging de-novo mutations and dysregulated genes from ventricles of patients with HLHS suggested alterations in specific gene programs and cellular processes critical during fetal ventricular cardiogenesis, including cell-cycle and cardiomyocyte maturation. Single-cell and 3D modeling with iPSCs demonstrated intrinsic defects in the cell-cycle/UPR/autophagy hub resulting in disrupted differentiation of early cardiac progenitor lineages leading to defective cardiomyocyte-subtype differentiation/maturation in HLHS. Additionally, premature cell-cycle exit of ventricular cardiomyocytes from HLHS patients prevented normal tissue responses to developmental signals for growth leading to multinucleation/polyploidy, accumulation of DNA damage, and exacerbated apoptosis, all potential drivers of left ventricular hypoplasia in absence of hemodynamic cues. Conclusions Our results highlight that despite genetic heterogeneity in HLHS, many mutations converge on sequential cellular processes primarily driving cardiac myogenesis, suggesting novel therapeutic approaches.
Viral proteomics: global evaluation of viruses and their interaction with the host (2007)

Viruses constantly adapt to and modulate the host environment during replication and propagation. Both DNA and RNA viruses encode multifunctional proteins that interact with and modify host cell proteins. While viral genomes were the first complete sequences known, the corresponding proteomes are only now elucidated, with some surprising results. Even more daunting is the task to globally monitor the impact of viral infection on the proteome of the host cell and many technical hurdles must still be overcome in order to facilitate robust and reproducible measurements. Further complicating the picture is the dynamic nature of proteins, including post-translational modifications, enzymatic cleavage and activation or destruction by proteolytic events. Nevertheless, several promising studies have been published using high-throughput methods directly measuring protein abundance. Particularly, quantitative or semiquantitative mass spectrometry-based analysis of viral and cellular proteomes are now being used to characterize viruses and their host interaction. In addition, the full set of interactions between viral and host proteins, the interactome, is beginning to emerge, with often unexpected interactions that need to be carefully validated. In this review, we will discuss two major areas of viral proteomics: first, virion proteomics (such as the protein characterization of viral particles) and second, proteoviromics, including the viral protein interactomics and the quantitative analysis of host cell proteome during viral infection.
Evolution: Much More than Genetics. The Need for a Holistic View~!2009-09-30~!2009-10-30~!2009-12-24~! (2010)

Since Darwin's time we have known that natural selection, acting upon variations, is the key to understanding biological evolution. After passing through the filter of natural selection, these changes generate new life-forms. Such lines of thought are still widely advocated today in science, but many non-scientists continue to accept creationism, Lamarckism and other ideas not supported by evidence. Even though many books and papers are published yearly to explain Darwinian evolution, and many documentary films are shown on TV, resistance to Darwinian evolution does not decrease. In fact, it is on the increase, not only in the USA but recently also in Europe. Perhaps those of us who write and lecture on Darwinian evolution are doing something wrong. For example, many books on the subject emphasize genetic mechanisms, although it is obvious that the evolution of the genome alone cannot suffice to explain the evolution of life on Earth in all its manifestations. In this paper we present an all-embracing vision of the evolution of life --a coevolutionary process that is not strictly biological but also environmental, social and cultural, and which takes into account the important role played by incorporations and interactions in networks. We believe that it is only by emphasizing the continuity between matter on the one hand and biological, social and cultural evolution on the other that the gap between micro-and macro-evolution can be filled in an understandable way for non-scientists in need of a comprehensive view.
Darstellung von Windsichtertrennkurven durch ein stochastisches Modell (1969)

Abstract Bei der Sichtung im Schwerefeld oder im Fliehkraftfeld wird die Teilchenbewegung durch determinierte Kräfte, wie Schwere, Fliehkraft und mittleren Strömungswiderstand, und durch in ihrer Gesamtheit als zufällig anzusehende Einwirkungen aufgrund gegenseitiger Wechselwirkung zwischen den Teilchen, Wandstößen und Turbulenz der Strömung beeinflußt. Die den Teilchen aufgeprägte Bewegung wird daher zufälliger Natur sein. Ein mathematisches Modell dieses Zufallsprozesses liefert eine physikalisch begründete Trennkurvenformel, deren Brauchbarkeit eine vergleichende Darstellung gemessener Trennkurven verschiedener Analysensichter zeigt. Darüber hinaus liefert das mathematische Modell Einblicke in den Mechanismus des Sichtvorganges.
Structure—activity relationships of ß-endorphin by synthesis —1977 (1979)

During isolation of melanotropins from camel pituitary glands (Li et al., 1975), we were unable to find β-LPH, but obtained an untriakontapeptide (Li and Chung, 1976a) with an amino acid sequence identical to the COOH-terminal 31-residues of ovine lipotropin (βs-LPH61-91) (Li and Chung, 1976b and figure 21.1). The peptide possesses very low lipotropic activity but significant opiate activity (Li and Chung, 1976a), as displayed in a preparation of guinea pig ileum (GPI) and in the opiate receptor binding assay (Cox et al., 1976). This untriakontapeptide was designated β-endorphin (Li and Chung, 1976a). A similar untriakontapeptide with opiate activity was obtained from porcine (Bradbury et al., 1976; Graf et al., 1976), ovine (Chrétien et al., 1976) and bovine (Li et al., 1977) pituitary glands.
Comparison of protection requirements in IE2-, IE3-, and IE4-class motors (2015)

In this paper, an overview of the main motor features influencing the protection devices settings is presented, pointing out key differences between three-phase direct-on-line motors of different efficiency classes. The results of experimental tests and simulations are presented and discussed in the scope of the motor protection against overload, short-circuit, current unbalance and locked-rotor conditions, for 7.5-kW, 4-pole, IE2- and IE3-class squirrel-cage induction motors and for IE4-class line-start permanent-magnet motors, offering important data related to their electrical and thermal behavior. Two commercial digital thermal-magnetic motor protection devices, whose thermal models were in most cases designed for IE1- and IE2-class motors, are evaluated in terms of operation effectiveness in the tested motors. This work is important for industry due to the significant penetration of IE3-class induction motors, as well as to the recent introduction in the market of IE4-class induction motors and line-start permanent magnet motors.
Determination of hexahydrophthalic anhydride adducts to human serum albumin (2003)

Hexahydrophthalic anhydride (HHPA) is a highly sensitizing industrial chemical that is known to covalently bind to endogenous proteins. The aim of this study was to determine the binding sites of HHPA to human serum albumin (HSA). Conjugates between HSA and HHPA, at two different molar ratios, were synthesized under physiological conditions. The conjugates were digested with trypsin and Pronase E to obtain specific peptides and amino acids, which were separated by liquid chromatography (LC). Fractions containing modified peptides were detected through quantification of hydrolysable HHPA using LC coupled to a triple quadrupole mass spectrometer with electrospray ionization. Modified residues in albumin were identified by sequence analyses using nanoelectrospray quadrupole time-of-flight mass spectrometry. A total of 36 HHPA adducts were found in the HSA-HHPA conjugate with 10 times molar excess of added HHPA. In the conjugate with a molar ratio of 1:0.1 of added HHPA, seven HHPA adducts were found bound to Lys(137) (domain IB), Lys(190), Lys(199) and Lys(212) (domain IIA), Lys(351) (domain IIB), and Lys(432) and Lys(436) (domain IIIA). Moreover, several of these adducted albumin peptides were detected in nasal lavage fluid from one volunteer exposed to HHPA. The binding sites of HHPA to HSA have been determined, thus identifying potential allergenic chemical structures. This knowledge generates the possibility of developing methods for the biological monitoring of HHPA exposure by analysing tryptic peptides including these binding sites.
Collisional losses from a light-force atom trap (1989)

We have studied the collisional loss rates for very cold cesium atoms held in a spontaneous-force optical trap. In contrast with previous work, we find that collisions involving excitation by the trapping light fields are the dominant loss mechanism. We also find that hyperfine changing collisions between atoms in the ground state can be significant under some circumstances.
A novel method that leverages existing data to conduct comparative analyses of competing assets: Sugemalimab and agents targeting the PD-L1/PD-1 axis as an example. (2023)

2609 Background: Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Numerous immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein-1/programmed death ligand-1 (PD-1/PD-L1) axis have garnered regulatory approvals. A novel method of comparative analysis that discerns differences/similarities amongst such agents could reduce redundancy and hopefully enhance true competition. Methods: We’ve described an approach for assessing efficacy that assumes changes in tumor quantity result from two simultaneous processes – exponential decay of the treatment-sensitive fraction of tumor at rate d, and exponential growth of the resistant fraction at rate g. Using this method, the USFDA analyzed data from 9934 patients with NSCLC enrolled in registration trials treated with chemotherapy, targeted therapies, and immunotherapies concluding g is inversely associated with survival across treatment types and encouraging prospective studies to evaluate whether g derived from early tumor measurements might serve as an earlier clinical trial endpoint (Gong ASCO 2020). Using data provided by EQRx and CStone we analyzed the GEMSTONE-302 trial comparing chemotherapy +/- the PD-L1 inhibitor sugemalimab in first line NSCLC. Results: 88% of the data could be analyzed. Regression without growth was seen in 10-12% of both arms with indistinguishable d values. Evidence of tumor growth was estimable as a g value in 68-71% with statistically slower g values and longer tumor doubling times (TDT) seen with sugemalimab + chemotherapy [0.0012/day (0.0005-0.0022); TDT 578d] than placebo + chemotherapy [0.0025/day (0.0013-0.0035); TDT 277d] p&lt;0.0001. A comparative analysis with FDA data from 1521 patients who received Combo ICI in front line, finds comparable/slightly slower g values for sugemalimab + chemotherapy using all or a fraction of the data. Conclusions: We used a method of analysis that estimates rates of tumor growth ( g) to analyze the efficacy of the PD-L1 antagonist, sugemalimab, in NSCLC. Because time is included in our equations the intervals of assessment are rendered inconsequential, making this method of analysis ideal for virtual comparisons. We confirmed the value of sugemalimab in the first-line setting by demonstrating its data track very closely with data aggregated from randomized trials reported by the USFDA in patients treated with Combo ICI in front line. Because g values can be estimated with fewer data it can be leveraged for early decisions. [Table: see text]
Immunomodulation of NK Cells through 4-1BB (CD137) to Improve the Anti-Lymphoma Activity of Rituximab: Antibody-Based Anti-Lymphoma Synergy (2010)

Abstract Abstract 422 Background: Antibody-dependent cell-mediated cytotoxicity (ADCC), largely mediated by natural killer (NK) cells, is thought to play an important role in the efficacy of rituximab, an anti-CD20 monoclonal antibody (mAb) used to treat patients with B cell lymphomas. CD137 is a costimulatory molecule expressed on a variety of immune cells following activation, including NK cells. We hypothesized that the anti-lymphoma activity of rituximab could be enhanced by stimulation of NK cells with an anti-CD137 agonistic mAb. Methods: Rituximab induced upregulation of CD137 on NK cells was assessed using lymphoma cell lines and primary lymphoma patient samples. In-vitro NK cell degranulation and cytotoxicity were assessed by CD107a mobilization and chromium release. A murine lymphoma tumor model targeted by mouse anti-mouse CD20 mAb was used to assess in-vivo synergy of anti-CD20 and anti-CD137 mAbs. Mechanism of synergy was explored by T cell, NK cell, and macrophage depletion in the immune competent mouse model. A xenotransplant model in SCID mice with disseminated, luciferase-labeled lymphoma was used to demonstrate efficacy of anti-CD137 mAb and rituximab, and sufficiency of an innate immune response. Results: NK cells in human primary lymphoma samples do not express CD137 at baseline, however these cells highly upregulate CD137 when encountering rituximab-coated tumor B cells. Rituximab-induced NK cell degranulation and cytotoxicity as measured by CD107a mobilization (p=.006) and chromium release (p=.01) are enhanced by anti-CD137 agonistic mAb. In a murine lymphoma model, anti-CD137 mAb significantly enhances anti-tumor activity of anti-CD20 mAb leading to complete tumor resolution (p&lt;.001) and prolonged survival (p=.048). Sequential administration of anti-CD20 mAb followed by anti-CD137 mAb (p=.027) is required for the synergistic effect. In-vivo administration of anti-CD20 mAb induces upregulation of CD137 on mouse NK cells (p=0.001), allowing subsequent targeting with anti-CD137 mAb. NK cell depletion completely abrogates the therapeutic effect of anti-CD20 plus anti-CD137 mAb combination (p&lt;.001). In a xenotransplant disseminated lymphoma model (Figure 1A), rituximab plus anti-CD137 mAb provided superior reduction in tumor burden, as quantified by bioluminescence (p=.001; Figure 1B), and prolonged overall survival (p=.013; Figure 1C). Conclusions: Our results demonstrate the synergy of anti-CD137 mAb and rituximab by stimulation of rituximab-activated NK cells with anti-CD137 mAb to enhance ADCC. These results support a novel, sequential antibody approach against B cell malignancies by targeting first the tumor and then the host immune system. Disclosures: No relevant conflicts of interest to declare.
An outlook on the evolution of mobile terminals: from monolithic to modular multiradio, multiapplication platforms (2006)

Terminals, including traditional cellular phones, have historically been optimized for a small number of services over a specific network. With the convergence of consumer electronics and Internet-based services, voice and video are now being offered on a variety of access networks, and many functions are being combined into single devices. In addition to new sophisticated audio/video coding and graphics capabilities, there is a growing demand for cheap and ubiquitous broadband wireless Internet access. This demand is driving the need for multiradio platforms that include new licensed and unlicensed air interface technologies, such as WLAN, UWB and Wimax. The proliferation of new applications and wireless standards has created the need for a dramatic change in the portable/mobile terminal architecture. This paper presents an overview of the evolution of mobile terminal architectures, from monolithic to flexible, modular, and capable of meeting the increasing demand for an ever larger number of features at the right cost and time to market.
The pharmacokinetics of aztreonam and penetration into the bronchial secretions of critically ill patients (1989)

The pharmacokinetics of aztreonam were studied in ten critically ill intubated patients with lower respiratory tract infections. Serum and urinary concentrations of the drug and its penetration into bronchial secretions after a 2-g intravenous bolus were measured. Using a two-compartment linear model a terminal half-life of 1.87 + 0.46 h was determined. No interpatient differences were found for half-life values, AUC or volume of distribution, except in the case of one obese patient. The greatest variability was observed in the clearance values, and in particular the extrarenal clearance which ranged from 0.3 to 9.6 1/h. Maximum concentrations in bronchial secretions were reached very quickly in the 2 h after drug administration, with a range of 4.8-18.7 mg/l. No accumulation of aztreonam after repeated doses was detected.
Studying That Smile (2008)

A description of multispectral image capture is presented from a signal processing point of view. Indeed, this article is based on an equation that models the multispectral acquisition of images. The main components of this equation are described. They correspond to the lighting conditions, the filters, the sensor sensitivity, and associated noise sources. Moreover, the optimization problems involved in the design of multispectral cameras, their calibration, and the processing of the obtained data are introduced within the same mathematical framework.
High-resolution SPECT using multipinhole collimation (2003)

The authors present a novel SPECT imaging technique for small animal research based on multipinhole collimation. This new method is an extension of single-pinhole tomography and combines high resolution with increased system sensitivity. This paper describes the multipinhole imaging system and its preliminary characterization on simulated and measured phantom data.
A mussel-inspired poly(γ-glutamic acid) tissue adhesive with high wet strength for wound closure (2017)

A novel mussel-inspired γ-PGA–DA tissue-adhesive hydrogel <italic>via</italic> a horseradish peroxidase-mediated reaction with robust tissue adhesive strength and hemostasis performance when wet.
CO 2 Conversion to Formic Acid in a Three Compartment Cell with Sustainion™ Membranes (2017)

Formic acid generated from CO2 has been proposed both as a key intermediate renewable chemical feedstock as well as a potential energy storage chemical media for hydrogen. In this paper, we describe a novel three compartment electrochemical cell configuration with the capability of directly producing a pure formic acid product in the concentration range of 5 – 20 wt% at high current densities and Faradaic yields. The electrochemical cell employs a Dioxide Materials Sustainion™ anion membrane, allowing for the improved CO2 electrochemical reduction performance. Stable electrochemical cell performance for more than 500 hours has been experimentally demonstrated.