gebhart/patrepeval huggingface dataset:
Nonparametric causal mediation analysis for stochastic interventional (in)direct effects (2020)

Causal mediation analysis has historically been limited in two important ways: (i) a focus has traditionally been placed on binary treatments and static interventions, and (ii) direct and indirect effect decompositions have been pursued that are only identifiable in the absence of intermediate confounders affected by treatment. We present a theoretical study of an (in)direct effect decomposition of the population intervention effect, defined by stochastic interventions jointly applied to the treatment and mediators. In contrast to existing proposals, our causal effects can be evaluated regardless of whether a treatment is categorical or continuous and remain well-defined even in the presence of intermediate confounders affected by treatment. Our (in)direct effects are identifiable without a restrictive assumption on cross-world counterfactual independencies, allowing for substantive conclusions drawn from them to be validated in randomized controlled trials. Beyond the novel effects introduced, we provide a careful study of nonparametric efficiency theory relevant for the construction of flexible, multiply robust estimators of our (in)direct effects, while avoiding undue restrictions induced by assuming parametric models of nuisance parameter functionals. To complement our nonparametric estimation strategy, we introduce inferential techniques for constructing confidence intervals and hypothesis tests, and discuss open source software implementing the proposed methodology.
Mechanism of Action and Pharmacology of Patiromer, a Nonabsorbed Cross-Linked Polymer That Lowers Serum Potassium Concentration in Patients With Hyperkalemia (2016)

Hyperkalemia is a potentially life-threatening condition, and patients who have chronic kidney disease, who are diabetic, or who are taking renin-angiotensin-aldosterone system inhibitors are at increased risk. Therapeutic options for hyperkalemia tend to have limited effectiveness and can be associated with serious side effects. Colonic potassium secretion can increase to compensate when urinary potassium excretion decreases in patients with renal impairment, but this adaptation is insufficient and hyperkalemia still results. Patiromer is a novel, spherical, nonabsorbed polymer designed to bind and remove potassium, primarily in the colon, thereby decreasing serum potassium in patients with hyperkalemia. Patiromer has been found to decrease serum potassium in patients with hyperkalemia having chronic kidney disease who were on renin-angiotensin-aldosterone system inhibitors. Results of nonclinical studies and an early phase clinical study are reported here. Two studies with radiolabeled drug, one in rats and the other in dogs, confirmed that patiromer was not absorbed into the systemic circulation. Results of an in vitro study showed that patiromer was able to bind 8.5 to 8.8 mEq of potassium per gram of polymer at a pH similar to that found in the colon and had a much higher potassium-binding capacity compared with other resins, including polystyrene sulfonate. In a study in hyperkalemic rats, a decrease in serum potassium was observed via an increase in fecal potassium excretion. In a clinical study in healthy adult volunteers, a significant increase in fecal potassium excretion and a significant decrease in urinary potassium excretion were observed. Overall, patiromer is a high-capacity potassium binder, and the chemical and physical characteristics of patiromer may lead to good clinical efficacy, tolerability, and patient acceptance.
Propagation of AC Background Harmonics in MMC HVdc Multiterminal Systems Due to Resonances and Mitigation Measures (2017)

Modular multilevel converter (MMC)-based multiterminal HVdc (MTdc) transmission is a favorable option for asynchronously interconnecting several weak ac systems. This paper investigates the potential resonance of such an MMC-MTdc system excited by background harmonics in any of the MMC's ac systems and the undesirable transfer of these harmonics to the remote ac systems. First, the harmonic transfer rule across one MMC is established using phase leg voltage analysis and it is then used to develop an equivalent circuit model of the MMC-MTdc system. This model is used to investigate the mechanism of resonance excited by ac-side background harmonics. Finally, a control strategy is proposed to mitigate this resonance. Analytically calculated results from the derived model and the proposed control strategy are validated via electromagnetic transients simulation of a five-terminal MMC-MTdc network.
Supplementary Figures S1-S10 from Assessing Immune-Related Adverse Events of Efficacious Combination Immunotherapies in Preclinical Models of Cancer (2023)

&lt;p&gt;Kinetics of Treg depletion in tumor-bearing Foxp3-DTR mice (S1); Development of blepharitis in tumor-bearing Foxp3-DTR mice after multiple DT treatment (S2); Prolonged Treg depletion induces severe irAEs in MC38 tumor-bearing mice (S3); Transient Treg depletion or multiple anti-CTLA-4 and anti-PD-1 treatment induce similar biochemical autoimmunity in tumor-bearing mice (S4); Transient Treg depletion of tumor-bearing mice increases the expression of PD-1, TIM-3 and CD137 on T cells from spleen but not tumor (S5); Transient Treg depletion in combination with anti-PD-1, anti-TIM-3 or anti-CD137 can all suppress established 4T1.2 or MC38 tumor growth (S6); Transient Treg depletion in combination with anti-PD-1, anti-TIM-3 or anti-CD137 differentially suppressed established CT26L5 tumor growth (S7); Transient Treg depletion in combination with anti-CD137 in tumor-bearing Foxp3-DTR mice induces severe irAEs (S8); Transient Treg depletion in combination with anti-CD137 increases the proportion of CD8+ T cells in multiple organs of tumor-bearing mice (S9); Transient Treg depletion in combination with anti-CD137 increases inflammatory cytokines in sera of tumor bearing mice (S10).&lt;/p&gt;
Scheduling of turbo decoding on a multiprocessor platform to manage its processing effort variability (2008)

This paper presents means of mapping and scheduling portions of a wide-band code division multiple access (WCDMA) application on a homogeneous multi processor system-on-chip (MPSoC). We focus on the turbo decoder, which is a computationally intensive part of the application and which presents a significant processing variability. Our model allows deriving and validating a flexible scheduling method for turbo decoding tasks, which is adapted to the variable processing effort required by the decoder. Using a proposed performance model, the efficiency of this scheduling method is demonstrated. A proposed flexible scheduling (FS) method, when compared to a worst case execution time (WCET) scheduling method, allows increasing the number of users from 14 to 29, while keeping an acceptable quality of service, as reflected in a very small degradation of less than 0.15 dB of the decoding gain.
DFT technique for RF PLLs using built-in monitors (2009)

International audience
Audiovestibular Dysfunction Associated with Adoptive Cell Immunotherapy for Melanoma (2012)

Adoptive cell immunotherapy targeting pigment-pathway cell proteins, a novel therapy for melanoma, can induce hearing loss and vestibular dysfunction. The presumed mechanism of autoimmune attack on normal melanocytes in the cochlear stria vascularis and in the vestibular organs demonstrates the importance of melanocytes in normal inner ear function.
Novel stabilin-1 interacting chitinase-like protein (SI-CLP) is up-regulated in alternatively activated macrophages and secreted via lysosomal pathway (2005)

Mammalian Glyco_18-domain-containing proteins include catalytically active chitinases and chitinase-like proteins with cytokine activity involved in host defense and Th2-type inflammatory reactions. Here, we describe a novel human Glyco_18-domain-containing protein, SI-CLP, as an interacting partner of the endocytic/sorting receptor stabilin-1. Similarly to the chitinase-like cytokines YKL-39, YKL-40, and YM1/2, SI-CLP lacks a chitin-binding domain and catalytic amino acids. Using a novel mAb 1C11, we demonstrated that SI-CLP is sorted into late endosomes and secretory lysosomes in human alternatively activated macrophages. The direct interaction of SI-CLP with stabilin-1, their colocalization in the trans-Golgi network, and the reduced sorting of SI-CLP into lysosomes in macrophages treated with stabilin-1 siRNA suggest that stabilin-1 is involved in intracellular sorting of SI-CLP. Expression of SI-CLP in macrophages was strongly up-regulated by the Th2 cytokine IL-4 and by dexamethasone. This effect was suppressed by IFNgamma but not affected by IL-10. In contrast, expression of YKL-40 was induced by IFNgamma and suppressed by dexamethasone. Macrophages treated with IL-4 secreted SI-CLP, while costimulation with dexamethasone blocked secretion and resulted in intracellular accumulation of SI-CLP. The 1C11 mAb detected SI-CLP in human bronchoalveolar lavage and peripheral-blood leukocytes (PBLs), and can be used to analyze the role of SI-CLP in human disorders.
The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts (2008)

Recently, genome wide association studies (GWAS) have identified a number of single nucleotide polymorphisms (SNPs) as being associated with coronary heart disease (CHD). We estimated the effect of these SNPs on incident CHD, stroke and total mortality in the prospective cohorts of the MORGAM Project. We studied cohorts from Finland, Sweden, France and Northern Ireland (total N=33,282, including 1,436 incident CHD events and 571 incident stroke events). The lead SNPs at seven loci identified thus far and additional SNPs (in total 42) were genotyped using a case-cohort design. We estimated the effect of the SNPs on disease history at baseline, disease events during follow-up and classic risk factors. Multiple testing was taken into account using false discovery rate (FDR) analysis. SNP rs1333049 on chromosome 9p21.3 was associated with both CHD and stroke (HR=1.20, 95% CI 1.08-1.34 for incident CHD events and 1.15, 0.99-1.34 for incident stroke). SNP rs11670734 (19q12) was associated with total mortality and stroke. SNP rs2146807 (10q11.21) showed some association with the fatality of acute coronary event. SNP rs2943634 (2q36.3) was associated with high density lipoprotein (HDL) cholesterol and SNPs rs599839, rs4970834 (1p13.3) and rs17228212 (15q22.23) were associated with non-HDL cholesterol. SNPs rs2943634 (2q36.3) and rs12525353 (6q25.1) were associated with blood pressure. These findings underline the need for replication studies in prospective settings and confirm the candidacy of several SNPs that may play a role in the etiology of cardiovascular disease.
Treatment patterns and burden of complications associated with sickle cell disease: A US retrospective claims analysis (2022)

Complications associated with sickle cell disease (SCD) that are highly impactful for patients but until recently have been less understood include priapism, nephropathy, and neurologic injury. We conducted a retrospective study using US administrative claims data from July 01, 2013 through March 31, 2020 to analyze incidence of these complications, SCD treatment patterns, and healthcare resource utilization (HCRU) and costs among 2524 pediatric and adult patients with SCD (mean [SD] age 43.4 [22.4] years). The most common treatments during follow-up were short-acting opioids (54.0% of patients), red blood cell transfusion (15.9%), and hydroxyurea (11.0%). SCD complications occurred frequently; in the overall population, the highest follow-up incidences per 1000 person-years were for acute kidney injury (53.1), chronic kidney disease (40.6), and stroke (39.0). Complications occurred across all age groups but increased in frequency with age; notably, acute kidney injury was 69.7 times more frequent among ages 65+ than ages 0-15 (<i>p</i> < 0.001). Follow-up per-patient-per-month HCRU also increased with age; however, all-cause healthcare costs were similarly high for all age groups and were driven primarily by inpatient stays. Patients with SCD across the age spectrum have a high burden of complications with the use of current treatments, suggesting unmet needs for treatment management.
259 EFFECTS OF BIPHASIC PACING IN LARGE ANIMAL SPECIES. (2006)

<h3></h3> Hemodynamics of paced beats containing some anodal component differ from those induced by the conventional cathodal waveform in rabbits, canines, and ferrets. We investigated this phenomenon in the pig (Sus domesticus). Upstroke (dP/dt+) and relaxation (dP/dt2) of left ventricular pressure curve were measured in two 50 kg subjects paced slightly above intrinsic rate with cathodal (C) and anodal followed by cathodal biphasic (B) pacing pulses. The first animal had preexistent atrial fibrillation and developed ventricular fibrillation due to a reversion attempt with unsynchronized cardioversion. After eventual resuscitation and defibrillation, sinus rhythm resumed, although with pressure measurements significantly depressed compared to the second subject. Measurements in each animal were made over 15 min period following mode changes. Only small differences in raw data between pacing modes were observed. However, after normalization of data to express percent change from start (initial) values in each mode, we obtained graphs showing dP/dt+ and dP/dt2 readings constant or slightly increasing for B pacing. C pacing showed 7 and 8% depressions of dP/dt2 eventually returning toward initial readings over the 15 min follow-up periods. Data are most consistent with altered relaxation properties, but the issue of increased contractility is unclear since concomitant volume measurements were not done. Time dependence of hemodynamic changes in upstroke and relaxation suggests that feedback loops in the heart may be responding to initial perturbations induced by the pacing modes. Pressure-volume loops need to be performed in order to clarify the mechanism.
Left ventricular assist devices psychosocial burden and implications for heart transplant programs (1996)

Left ventricular assist devices (LVADs) driven by external sources and capable of sustaining life over weeks to months as a bridge to heart transplantation have been implanted in over 300 patients in the United States. Because of the limited availability of organs for transplantation, the remarkable degree to which LVADs reverse end-organ dysfunction, and patient acceptance, proposals for home LVAD treatment and for use of the LVAD as a permanent treatment for heart failure are being considered. LVAD therapy is associated with characteristic psychiatric and psychosocial problems, however, which must be addressed to optimize results. Among the first 30 LVAD patients treated at our center, psychiatric interventions were frequently required for family stress, major depression, organic mental syndromes, and serious adjustment disorders. Psychiatric problems most often occurred in patients with ongoing medical complications following LVAD implantation, and often significantly impaired rehabilitation. Both depression and organic mental syndromes were frequently associated with preexisting cerebrovascular disease, which was sometimes occult, and with strokes complicating LVAD therapy. Aggressive treatment of depression played a major role in improving functional status. LVADs may decompress heart transplant waiting lists and make it possible to optimize patients' physiological and functional status before transplantation. With increased LVAD use, however, neuropsychiatric factors can be expected to play a large role in determining quality of life and outcome both before and after heart transplantation.
Free‐Standing Gold‐Nanoparticle Monolayer Film Fabricated by Protein Self‐Assembly of α‐Synuclein (2015)

Abstract Free‐standing nanoparticle films are of great importance for developing future nano‐electronic devices. We introduce a protein‐based fabrication strategy of free‐standing nanoparticle monolayer films. α‐Synuclein, an amyloidogenic protein, was utilized to yield a tightly packed gold‐nanoparticle monolayer film interconnected by protein β‐sheet interactions. Owing to the stable protein–protein interaction, the film was successfully expanded to a 4‐inch diameter sheet, which has not been achieved with any other free‐standing nanoparticle monolayers. The film was flexible in solution, so it formed a conformal contact, surrounding even microspheres. Additionally, the monolayer film was readily patterned at micrometer‐scale and thus unprecedented double‐component nanoparticle films were fabricated. Therefore, the free‐floating gold‐nanoparticle monolayer sheets with these properties could make the film useful for the development of bio‐integrated nano‐devices and high‐performance sensors.
Mesoporous Organosilicas Prepared with PEO-Containing Triblock Copolymers with Different Hydrophobic Moieties (2001)

Financial supports from the National Research Laboratory Fund from the Ministry of Science and Technology (MOST) and the Brain Korea 21 Program at Seoul National University from the Ministry of Education are greatly appreciated.
Phase development in partial-melt processing of silver-clad Bi{sub 2.15}Sr{sub 1.83}Ca{sub 1.02}Cu{sub 2}O{sub x} tapes (1996)

Ag-clad Bi{sub 2.15}Sr{sub 1.83}Ca{sub 1.02}Cu{sub 2}O{sub x} tapes were fabricated by the powder-in-tube method and heated in air to maximum temperatures of 880--895{degrees}C. The tapes were characterized by differential thermal analysis, scanning electron microscopy, energy-dispersive X-ray analysis, and X-ray diffraction. Microstructures of tapes that were heated at 885--895{degrees}C were similar, and, at a given temperature, remained stable for up to 1.0 h, which was the longest time used. The most significant microstructural features in specimens quenched from the melt were voids of up to {approx}400 {mu}m in diameter. CuO was a minor phase in the melt, but grew significantly upon cooling to become the major nonsuperconducting phase when solidification was complete.
Highly Efficient Light Extraction GaN-based Light Emitting Diode with Nano-rods in Micro-holes Compound Structure (2014)

We demonstrated a high-power GaN-based light emitting diodes (LEDs) which have micro-hole array and nano-rods compound structure by nanoimprint lithography (NIL). The nanorods structure inside the micro-hole could efficiently guide the trapped light from the GaN epilayer. Therefore, the light output power of LED with micro-hole array and nanorods was as high as 1.27 times, as compared with standard LED.
Effect of Aspirin vs Enoxaparin on Symptomatic Venous Thromboembolism in Patients Undergoing Hip or Knee Arthroplasty (2022)

ANZCTR Identifier: ACTRN12618001879257.
Using Body-worn Accelerometers to Detect Physiological Changes During Periods of Blast Overpressure Exposure (2022)

Repetitive exposure to non-concussive blast expo-sure may result in sub-clinical neurological symptoms. These changes may be reflected in the neural control gait and balance. In this study, we collected body-worn accelerometry data on individuals who were exposed to repetitive blast overpressures as part of their occupation. Accelerometry features were gener-ated within periods of low-movement and gait. These features were the eigenvalues of high-dimensional correlation matrices, which were constructed with time-delay embedding at multiple delay scales. When focusing on the gait windows, there were significant correlations of the changes in features with the cumulative dose of blast exposure. When focusing on the low-movement frames, the correlation with exposure were lower than that of the gait frames and statistically insignificant. In a cross-validated model, the overpressure exposure was predicted from gait features alone. The model was statistically significant and yielded an RMSE of 1.27 dB. With continued development, the model may be used to assess the physiological effects of repetitive blast exposure and guide training procedures to minimize impact on the individual.
Organoosmiumoxide — gezielte Synthesen und Strukturen (1990)

Nicht nur das bisher einfachste Alkylosmiumoxid , Me 4 OsO, das in der Gasphase stabil ist, und dessen Struktur (Bild rechts) durch Elektronenbeugungsanalyse aufgeklärt werden konnte, sondern auch das thermolabile Et 4 OsO und ein gemischt alkyliertes Derivat ließen sich in guten Ausbeuten herstellen. Ferner wird über das strukturell neuartige Trimer [{(py)OsO 2 Me 2 } 3 ] mit planarem Os 3 O 3 ‐Sechsring berichtet. magnified image
Mechanisms of Igf2 inhibition in thymic epithelial cells infected by coxsackievirus CV-B4 (2020)

ABSTRACT Epidemiological studies have evidenced a link between type 1 diabetes (T1D) and infections by enteroviruses, especially with coxsackievirus B4 (CV-B4). CV-B4 is able to infect human and murine thymic epithelial cells (TECs) and, in a murine TEC line, we have shown that the diabetogenic strain CV-B4 E2 decreases transcription of insulin-like growth factor 2 gene ( Igf2 ), coding for the self-peptide of the insulin family. Here we show that in CV-B4 infection of mice alters Igf2 transcripts isoforms in TECs, followed by a decrease of pro-IGF2 precursor in the thymus. CV-B4 infection of a murine TEC line decreases Igf2 P3 promoter activity by targeting the region −68 to −22 upstream of the transcription start site (TSS) whereas Igf2 transcripts stability is not affected, pointing towards a regulation of Igf2 transcription. Our data also show that CV-B4 decreases IL-6/STAT3 signaling in vitro . This study provides new knowledge about the regulation of intrathymic Igf2 transcription by CV-B4 and reinforces the hypothesis that CV-B4 infection of the thymus could break central self-tolerance of the insulin family by decreasing Igf2 transcription and IGF2 presentation in thymus epithelium. IMPORTANCE Coxsackievirus B4 represents one of the most important environmental factors associated to type 1 diabetes, autoimmune disease for which no curative treatment exist. The diabetogenic strain Coxsackievirus B4 E2 was previously shown to decrease Igf2 expression, important player for central tolerance towards insulin, in a thymic epithelial cell line. The understanding of Igf2 regulation mechanisms during coxsackievirus B4 infection represents an interest for the understanding of central tolerance development but also for Igf2 transcriptional regulation itself, still poorly understood. Here we demonstrate that, some transcripts isoforms of Igf2 are also decreased in thymic epithelial cells in vivo . Moreover, we show that this decrease is induced by an alteration of specific regions of Igf2 P3 promoter and may be linked by a decrease of STAT3 signaling. In fine we hope that this work could lead to future therapies leading to reprogramming central tolerance towards β cells antigens via Igf2 expression.
Continuous Delivery of Composite Solutions (2015)

To help drive top line growth of their businesses, the development and IT organizations are under increasing pressure to create and deliver applications at ever faster paces. The advent of Cloud Computing has not only lowered the cost of IT operations but also enabled the notion of continuous delivery, which promises to radically reduce frictions in DevOps processes and speed up the product delivery cycle. With increased demand on functionality and feature, we have also seen these applications becoming more sophisticated, often integrating multiple modern programming models and techniques with the traditional n-tier web application into a composite application. This paper proposes an architectural blueprint for improved continuous delivery of these complex composite applications. It treats a solution as a holistic entity comprised of application logic and software-defined environment that the logic relies on. It also proposes a collaborative approach to software-defined Platform-as-a-Service environment building. This being an ongoing research project, this paper also briefly describes prototype, work-in-progress and thoughts on future directions.