Miracle-dz/UniFAR-FTUs huggingface dataset:
Doubly Robust and Efficient Estimation of Marginal Structural Models for the Hazard Function

In social and health sciences, many research questions involve understanding the causal effect of a longitudinal treatment on mortality (or time-to-event outcomes in general). Often, treatment status may change in response to past covariates that are risk factors for mortality, and in turn, treatment status may also affect such subsequent covariates. In these situations, Marginal Structural Models (MSMs), introduced by Robins (1997. Marginal structural models Proceedings of the American Statistical Association. Section on Bayesian Statistical Science, 1–10), are well-established and widely used tools to account for time-varying confounding. In particular, a MSM can be used to specify the intervention-specific counterfactual hazard function, i. e. the hazard for the outcome of a subject in an ideal experiment where he/she was assigned to follow a given intervention on their treatment variables. The parameters of this hazard MSM are traditionally estimated using the Inverse Probability Weighted estimation Robins (1999. Marginal structural models versus structural nested models as tools for causal inference. In: Statistical models in epidemiology: the environment and clinical trials. Springer-Verlag, 1999:95–134), Robins et al. (2000), (IPTW, van der Laan and Petersen (2007. Causal effect models for realistic individualized treatment and intention to treat rules. Int J Biostat 2007;3:Article 3), Robins et al. (2008. Estimaton and extrapolation of optimal treatment and testing strategies. Statistics in Medicine 2008;27(23):4678–721)). This estimator is easy to implement and admits Wald-type confidence intervals. However, its consistency hinges on the correct specification of the treatment allocation probabilities, and the estimates are generally sensitive to large treatment weights (especially in the presence of strong confounding), which are difficult to stabilize for dynamic treatment regimes. In this paper, we present a pooled targeted maximum likelihood estimator (TMLE, van der Laan and Rubin (2006. Targeted maximum likelihood learning. The International Journal of Biostatistics 2006;2:1–40)) for MSM for the hazard function under longitudinal dynamic treatment regimes. The proposed estimator is semiparametric efficient and doubly robust, offering bias reduction over the incumbent IPTW estimator when treatment probabilities may be misspecified. Moreover, the substitution principle rooted in the TMLE potentially mitigates the sensitivity to large treatment weights in IPTW. We compare the performance of the proposed estimator with the IPTW and a on-targeted substitution estimator in a simulation study.
Multiple phase-screen calculation of the temporal behavior of stochastic waves

An analytical/numerical technique is presented that provides a solution to the parabolic wave equation and allows for direct calculation of the received time-domain signal after propagation of a wide-bandwidth waveform through a turbulent ionized medium. The results are applicable to the case of satellite communication or to radar observation through a frequency-selective transionospheric propagation channel. A number of examples of the application of multiple phase-screen (MPS) techniques are given that enhance intuitive understanding of wave propagation. Numerical predictions of scattering through a striated barium cloud are compared to experimental observations. Good agreement is also shown between MPS calculations and theoretical results for cases in both weak and strong scattering regimes.
The Crash Compatibility of Cars and Light Trucks

This paper investigates the compatibility of cars, light trucks, and vans (LTVs) involved in traffic crashes. An analysis of U.S. crash statistics shows that, although LTVs currently account for approximately one–third of registered U.S. passenger vehicles, collisions between cars and LTVs account for over one–half of all fatalities in light vehicle–to–vehicle crashes. In these crashes, 81 percent of the fatally injured are found to be occupants of the car. These statistics suggest that LTVs and passenger cars are incompatible in traffic crashes, and that LTVs are the more aggressive of the two vehicle classes. The fundamental incompatibility between cars and LTVs is observed even when the analysis is restricted to collisions between vehicles of model year 1990 or later - indicating that, despite the availability of newer safety countermeasures, e.g., airbags, the incompatibility between cars and LTVs will persist in future fleets. Through examination of crash test results, field crash statistics, and vehicle measurements, the paper explores the design imbalances between cars and LTVs, e.g., mass, stiffness, and geometry, which lead to these severe crash incompatibilities.
A New NBTI Model Based on Hole Trapping and Structural Relaxation in MOS Dielectrics

Negative bias temperature instability (NBTI) is one of the major reliability concerns for analog and digital MOS devices. NBTI understanding and modeling is receiving a growing interest for failure prediction, depending on the temperature and duty cycle of dynamic-stress conditions. In this framework, we present a new NBTI model based on hole trapping and thermally activated relaxation. The model unifies previous concepts of hole tunneling/trapping and structural relaxation initiated by hole trapping. Simulation results can account for the time and temperature dependence of NBTI stress, NBTI recovery, and the dependence on thickness and nitridation technology of the gate dielectric. The numerical model may be used for physics-based reliability predictions of NBTI effects as a function of time, temperature, and stress regime.
Relationship of the Anticomplement Coombs Test to the Classes of Immunoglobulins 1

The agglutination in saline and the enhancement by anti‐IgG and anti‐C′ Coombs sera of human blood‐group antibodies fractionated by density‐gradient ultracentrifugation and anion‐exchange chromatography, as well as the effect of 0.1M penicillamine on these fractions, have been studied. All of the IgM antibodies agglutinated cells after exposure to C′ and anti‐C′ but not after exposure to anti‐IgG Coombs serum. All IgG antibodies were strongly agglutinated by anti‐IgG, and some (including two unusual anti‐Rh sera) were also agglutinated by anti‐C′ after exposure to C′. A complement‐fixing IgG Donath‐Landsteiner antibody was found to be capable of attaching to erythrocytes in the cold in the absence of complement. If complement has been fixed, the antibody can be subsequently eluted by warming without affecting the attachment of β1c‐globulin. No enhancement of IgM antibody titers could be produced by anti‐IgM Coombs sera unless the Coombs sera also contained anti‐C′. An unidentified anti‐A antibody, approximately 7S, agglutinated more strongly with anti‐C′ than with anti‐IgG Coombs serum.
An observational case study of mesoscale atmospheric circulations induced by soil moisture

Numerical and theoretical studies have shown that mesoscale gradients in land surface properties can induce circulations in the atmosphere. This study provides the first well‐resolved observations of such flows induced by soil moisture from recent rainfall, and is based on aircraft data in the Sahel. Satellite imagery was used to identify fine scale soil moisture features within a wet zone spanning 160 km. Above the wet soil, the planetary boundary layer was up to 3 K cooler, 3 gkg−1 moister and extended to only half the depth of nearby drier areas. Mesoscale perturbations to the background flow were found, consistent with low level divergence over wet soil and convergence in drier areas. The soil moisture and atmospheric wind patterns were statistically coherent on wavelengths down to 20 km. These results suggest that mesoscale convergence lines forced by soil moisture may play a significant role in the meteorology of the Sahel.
Protein–DNA chimeras: synthesis of two-arm chimeras and non-mechanical effects of the DNA spring

DNA molecular springs have recently been used to control the activity of enzymes and ribozymes. In this approach, the mechanical stress exerted by the molecular spring alters the enzyme’s conformation and thus the enzymatic activity. Here we describe a method alternative to our previous one to attach DNA molecular springs to proteins, where two separate DNA ‘arms’ are coupled to the protein and subsequently ligated. We report certain non-mechanical effects associated with the DNA spring observed in some chimeras with specific DNA sequences and the nucleotide binding enzyme guanylate kinase. If a ssDNA ‘arm’ is attached to the protein by one end only, we find that in some cases (depending on the DNA sequence and attachment point on the protein’s surface) the unhybridized DNA arm inhibits the enzyme, while hybridization of the DNA arm leads to an apparent activation of the enzyme. One interpretation is that, in these cases, hybridization of the DNA arm removes it from the vicinity of the active site of the enzyme. We show how mechanical and non-mechanical effects of the DNA spring can be distinguished. This is important if one wants to use the protein–DNA chimeras to quantitatively study the response of the enzyme to mechanical perturbations.
An exterior for the Gödel spacetime

We match the vacuum, stationary, cylindrically symmetric solution of Einstein's field equations with , in a form recently given by Santos, as an exterior to an infinite cylinder of dust cut out of a Godel universe. There are three cases, depending on the radius of the cylinder. Closed timelike curves are present in the exteriors of some of the solutions. There is a considerable similarity between the spacetimes investigated here and those of van Stockum, referring to an infinite cylinder of rotating dust matched to vacuum, with .
Depth of Automatic Spreading Activation: Mediated Priming Effects in Pronunciation but Not in Lexical Decision

Lexical decision and pronunciation experiments were conducted to investigate whether activation automatically spreads beyond directly associated concepts within the memory network. Prime-target pairs were constructed such that there was a relation between the prime (e.g., lion) and the target (e.g., stripes) only through a mediating concept (e.g., tiger). The lexical decision results yielded facilitation of directly related priming conditions (e.g., lion-tiger and tiger-stripes); however, the mediated condition (e.g., lion-stripes) did not facilitate performance compared to either a neutral prime or an unrelated prime condition. In contrast, the pronunciation results yielded facilitation of both directly related and mediated priming conditions. The results were viewed as supporting the notion that activation spreads beyond directly related concepts in semantic memory. It is suggested that characteristics of the lexical decision task masked the appearance of a mediated priming effect. Implications of an automatic spread of activation beyond directly related concepts are discussed.
Conservation of the Salt Overly Sensitive Pathway in Rice1[C][W][OA]

The salt tolerance of rice (Oryza sativa) correlates with the ability to exclude Na+ from the shoot and to maintain a low cellular Na+/K+ ratio. We have identified a rice plasma membrane Na+/H+ exchanger that, on the basis of genetic and biochemical criteria, is the functional homolog of the Arabidopsis (Arabidopsis thaliana) salt overly sensitive 1 (SOS1) protein. The rice transporter, denoted by OsSOS1, demonstrated a capacity for Na+/H+ exchange in plasma membrane vesicles of yeast (Saccharomyces cerevisiae) cells and reduced their net cellular Na+ content. The Arabidopsis protein kinase complex SOS2/SOS3, which positively controls the activity of AtSOS1, phosphorylated OsSOS1 and stimulated its activity in vivo and in vitro. Moreover, OsSOS1 suppressed the salt sensitivity of a sos1-1 mutant of Arabidopsis. These results represent the first molecular and biochemical characterization of a Na+ efflux protein from monocots. Putative rice homologs of the Arabidopsis protein kinase SOS2 and its Ca2+-dependent activator SOS3 were identified also. OsCIPK24 and OsCBL4 acted coordinately to activate OsSOS1 in yeast cells and they could be exchanged with their Arabidopsis counterpart to form heterologous protein kinase modules that activated both OsSOS1 and AtSOS1 and suppressed the salt sensitivity of sos2 and sos3 mutants of Arabidopsis. These results demonstrate that the SOS salt tolerance pathway operates in cereals and evidences a high degree of structural conservation among the SOS proteins from dicots and monocots.
Effects of 1 GeV/nucleon 56Fe Particles on Longevity, Carcinogenesis and Neuromotor Ability in Atm-Deficient Mice

Abstract As therapeutic uses of high-LET radiation become more prevalent and human space exploration continues to be a focus of NASA, it is important to understand the biological effects of high-LET radiation and the role of genetics in sensitivity to high-LET radiation. To study genetic susceptibility to radiation, we used mice deficient in Atm activity (AtmΔSRI). ATM is important in DNA repair, apoptosis and cell cycle regulation. Although homozygous mutations in ATM are rare, the prevalence of ATM heterozygosity is estimated to be 1% and results in an increased cancer risk. We found that the effects of 1 Gy 1 GeV/nucleon 56Fe particles on life span and tumorigenesis are genotype- and sex-specific. Significant effects of 1 Gy 1 GeV/nucleon 56Fe particles on incidence of non-cancer end points were seen; however, 2 Gy 1 GeV/nucleon 56Fe particles significantly affected neuromotor ability. Our results represent an extensive investigation into the late effects of high-LET radiation exposure in a sex- and genotype-dependent manner and provide a baseline for understanding the long-term risks of high-LET radiation.
ACCURACY OF A LOW-COST NOVEL COMPUTER-VISION DYNAMIC MOVEMENT ASSESSMENT: POTENTIAL LIMITATIONS AND FUTURE DIRECTIONS

Abstract. The aim of the study was to perform a preliminary validation of a low cost markerless motion capture system (CAPTURE) against an industry gold standard (Vicon). Measurements of knee valgus and flexion during the performance of a countermovement jump (CMJ) between CAPTURE and Vicon were compared. After correction algorithms were applied to the raw CAPTURE data acceptable levels of accuracy and precision were achieved. The knee flexion angle measured for three trials using Capture deviated by −3.8° ± 3° (left) and 1.7° ± 2.8° (right) compared to Vicon. The findings suggest that low-cost markerless motion capture has potential to provide an objective method for assessing lower limb jump and landing mechanics in an applied sports setting. Furthermore, the outcome of the study warrants the need for future research to examine more fully the potential implications of the use of low-cost markerless motion capture in the evaluation of dynamic movement for injury prevention.
Variation in Resource Use Within Diagnosis-related Groups: The Effect of Severity of Illness and Physician Practice

The diagnosis-related group (DRG)-based Medicare prospective payment system pays hospitals a fixed amount for the care of similar patients. The DRG definitions serve as the modifier of payment for Medicare patients. The dependence on these patient definitions raises many questions, among them the reason(s) for observed resource variability within a DRG. Various severity-of-illness measures have been shown to account for some of the resource variability noted within the DRGs. Most severity-of-illness studies to date, however, have not attempted to assess the effect of other known sources of resource variation, such as differing physician practice patterns. The authors examined the ability of severity of illness, as defined by disease staging, and physician practice variation to explain residual intra-DRG variability in length of stay. They demonstrate that physician practice variation accounts for more variance reduction than does severity of illness.
Expansion of genes encoding a novel type of dynamin in the genome of the pea aphid, Acyrthosiphon pisum

Screening of the entire genome of the pea aphid, Acyrthosiphon pisum, detected 15 genes for putative dynamin superfamily proteins – self‐assembling large GTPases that are involved in the fission and fusion of membranes. In addition to a single gene each for Dyn, Drp1, and Opa1, orthologues that are common in Metazoa, 12 genes encoding a novel type of dynamin were found. Phylogenetic analyses showed that these novel‐class genes are monophyletic. Quantitative reverse transcription‐PCR demonstrated that expressions of four novel‐class dynamin genes are highly up‐regulated in the midgut, through which aphids take in phloem‐sap diets and plant viruses. As this type of dynamin is absent from all other fully sequenced organisms, they may function in processes unique to aphids.
SCMA detection with channel estimation error and resource block diversity

Future Fifth generation wireless networks should support, among other things, very large number of simultaneous connections. To address this requirement, various schemes of non-orthogonal multiple access (NOMA) were proposed that allow to increase the number of simultaneously active users. One of NOMA schemes is sparse code multiple access (SCMA), where sparse multidimensional codewords allow to use iterative detecting algorithms with reasonable complexity. In the paper, SCMA detection at different allocation of codeword symbols in resource blocks is investigated in the presence of channel estimation error. Uncoded and turbo coded SCMA is analyzed. Uplink channel with Rayleigh flat block fading is assumed. The effect of diversity at spreading codewords over the resource blocks is considered. The allocation of uncoded SCMA codeword symbols in four resource blocks decreases bit error rate, consequently permissible variance of channel estimation error can be increased. Simulation results show that required accuracy of the channel estimation depends on the turbo code block length. For maximum utilization of turbo code error-correction capability with short blocks (40 bits) normalized variance of channel estimation error should be less than 10−3. For turbo code with long blocks (1024 bits), estimation can be less accurate, with normalized variance up to 10−2. With such channel estimation accuracy, power loss is about 0.6–0.7 dB compared with the case of perfect estimation. The spreading of SCMA codewords over four resource blocks decreases the number of channel coefficients for estimation and increases bit error rate for coded system. SCMA with long blocks of turbo code and channel interleaving is also analyzed. The channel interleaving improves BER performance, but the scheme with spread codewords still does not outperform the scheme with allocation of codeword symbols into one resource block.
MicroRNA-125b Confers the Resistance of Breast Cancer Cells to Paclitaxel through Suppression of Pro-apoptotic Bcl-2 Antagonist Killer 1 (Bak1) Expression*

Paclitaxel (Taxol) is an effective chemotherapeutic agent for treatment of cancer patients. Despite impressive initial clinical responses, the majority of patients eventually develop some degree of resistance to Taxol-based therapy. The mechanisms underlying cancer cells resistance to Taxol are not fully understood. MicroRNA (miRNA) has emerged to play important roles in tumorigenesis and drug resistance. However, the interaction between the development of Taxol resistance and miRNA has not been previously explored. In this study we utilized a miRNA array to compare the differentially expressed miRNAs in Taxol-resistant and their Taxol-sensitive parental cells. We verified that miR-125b, miR-221, miR-222, and miR-923 were up-regulated in Taxol-resistant cancer cells by real-time PCR. We further investigated the role and mechanisms of miR-125b in Taxol resistance. We found that miR-125b was up-regulated in Taxol-resistant cells, causing a marked inhibition of Taxol-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to Taxol in cancer cells. Moreover, we demonstrated that the pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) is a direct target of miR-125b. Down-regulation of Bak1 suppressed Taxol-induced apoptosis and led to an increased resistance to Taxol. Restoring Bak1 expression by either miR-125b inhibitor or re-expression of Bak1 in miR-125b-overexpressing cells recovered Taxol sensitivity, overcoming miR-125-mediated Taxol resistance. Taken together, our data strongly support a central role for miR-125b in conferring Taxol resistance through the suppression of Bak1 expression. This finding has important implications in the development of targeted therapeutics for overcoming Taxol resistance in a number of different tumor histologies.
Nitric oxide affects mammalian distal colonic smooth muscle by tonic neural inhibition

1 The role of the l‐arginine‐nitric oxide (NO) pathway in tonic neural inhibition of spontaneous mechanical activity of distal colonic circular smooth muscle (DCCSM) was investigated in male Wistar rats. 2 Muscle strips were mounted in organ baths and spontaneous contractions recorded with isometric force transducers. They were characterized as low frequency (LFCs) 0.41 ± 0.03 N cm−2 or high frequency contractions (HFCs) 0.22 ± 0.04 N cm−2. The latter occurred intermittently to produce summation contractions (SCs) range 0.5–12 N cm−2. 3 Tetrodotoxin (100 nm) increased the forces of LFCs and SCs. Increase in force to tetrodotoxin did not occur after incubation of the muscle with NG‐monomethyl‐l‐arginine (l‐NMMA) 500 μm, an inhibitor of NO biosynthesis. 4 l‐NMMA but not its enantiomer d‐NMMA increased the force of LFCs (EC50:200 μm) and SCs (EC50:175 μm) in a concentration‐dependent manner which was reversed by l‐arginine but not by d‐arginine. 5 Muscle, precontracted by acetylcholine, relaxed to sodium nitroprusside (EC50:1.8 μm) NO gas (EV50:70 μl) and NO solutions (EC50:4 μm) in a concentration‐dependent manner. Guanosine 3′:5′‐cyclic monophosphate tissue concentrations (pmol mg−1 protein) were elevated in muscle after relaxation by sodium nitroprusside (500 μm) from 0.32 ± 0.06 to 1.2 ± 0.37 and by 1 ml of NO gas from 0.49 ± 0.05 to 1.54 ± 0.14. 6 These data suggest that DCCSM is under tonic neural inhibition mediated by NO biosynthesis.
The Sec62–Sec63 translocon facilitates translocation of the C-terminus of membrane proteins

ABSTRACT The Sec62–Sec63 complex mediates post-translational translocation of a subset of primarily secretory proteins into the endoplasmic reticulum (ER) in yeast. Therefore, it has been thought that membrane proteins, which are mainly co-translationally targeted into the ER, are not handled by the Sec62–Sec63 translocon. By systematic analysis of single and multi-spanning membrane proteins with broad sequence context [with differing hydrophobicity, flanking charged residues and orientation of transmembrane (TM) segments], we show that mutations in the N-terminal cytosolic domain of yeast Sec62 impair its interaction with Sec63 and lead to defects in membrane insertion and translocation of the C-terminus of membrane proteins. These results suggest that there is an unappreciated function of the Sec62–Sec63 translocon in regulating topogenesis of membrane proteins in the eukaryotic cell.