Miracle-dz/UniFAR-FTUs huggingface dataset:
Causal inference with multiple time series: principles and problems

I review the use of the concept of Granger causality for causal inference from time-series data. First, I give a theoretical justification by relating the concept to other theoretical causality measures. Second, I outline possible problems with spurious causality and approaches to tackle these problems. Finally, I sketch an identification algorithm that learns causal time-series structures in the presence of latent variables. The description of the algorithm is non-technical and thus accessible to applied scientists who are interested in adopting the method.
Reversal of an epigenetic switch governing cell chaining in Bacillus subtilis by protein instability

Bacillus subtilis forms long chains of cells during growth and biofilm formation. Cell separation is mediated by autolysins, whose genes are under the negative control of a heteromeric complex composed of the proteins SinR and SlrR. Formation of the SinR–SlrR complex is governed by a self‐reinforcing, double‐negative feedback loop in which SinR represses the gene for SlrR and SlrR, by forming the SinR–SlrR complex, titrates SinR and prevents it from repressing slrR. The loop is a bistable switch and exists in a SlrRLOW state in which autolysin genes are on, and a SlrRHIGH state in which autolysin genes are repressed by SinR–SlrR. Cells in the SlrRLOW state are driven into the SlrRHIGH state by SinI, an antirepressor that binds to and inhibits SinR. However, the mechanism by which cells in the SlrRHIGH state revert back to the SlrRLOW state is unknown. We report that SlrR is proteolytically unstable and present evidence that self‐cleavage via a LexA‐like autopeptidase and ClpC contribute to its degradation. Cells producing a self‐cleavage‐resistant mutant of SlrR exhibited more persistent chaining during growth and yielded biofilms with enhanced structural complexity. We propose that degradation of SlrR allows cells to switch from the SlrRHIGH to the SlrRLOW state.
The extent of lymphadenectomy for pTXNO prostate cancer does not affect prostate cancer outcome in the prostate specific antigen era.

PURPOSE Recent data suggest that extended lymph node dissection in prostate cancer may be necessary for accurate staging. With limited lymph node dissection apparently node negative cases might be under staged. We determined the impact that the number of lymph nodes removed at radical retropubic prostatectomy (RRP) has on cancer progression and cause specific survival in pTXNO cases. MATERIALS AND METHODS We reviewed the RRP prostate cancer database on 7,036 patients with clinical T1 to T3 disease, no adjuvant therapy and node negative disease in the prostate specific antigen (PSA) era from 1987 to 2000. Factors evaluated were the number of lymph nodes obtained at RRP, preoperative PSA, clinical and pathological stage and grade, margin status, year of surgery and specific surgeon for 5 surgeons who operated throughout the period and performed more than 500 RRPs. Cox analysis was done to determine the RR of progression (PSA or systemic) and prostate cancer death for the number of lymph nodes excised. RESULTS Median patient age was 65 years and median preoperative PSA was 6.6 ng/ml. At pathological evaluation 5,379 tumors (77%) were organ confined, 4,491 (65%) were Gleason score 5 to 6 and 2,027 (29%) were Gleason score 7 to 10. The median number of nodes obtained significantly decreased from 14 in 1987 to 1989 to 5 in 1999 to 2000 (p <0.001). Ten years after RRP Kaplan-Meier estimates were 63% of cases free of PSA progression, 95% free of systemic progression and 98% free of prostate cancer related death. Median followup was 5.9 years. After adjusting for pathological factors (PSA, grade, stage, margin status and surgical date) the number of lymph nodes obtained at lymphadenectomy was not significantly associated with PSA progression (for each additional node (RR 0.99, 95% CI 0.98 to 1.02, p = 0.90), systemic progression (RR 0.99, 95% CI 0.96 to 1.03, p = 0.68) or cause specific survival (RR 1.01, 95% CI 0.96 to 1.06, p = 0.75). CONCLUSIONS The extent of lymphadenectomy does not appear to affect prostate cancer outcome in lymph node negative cases. This includes patients with high preoperative PSA, high pathological grade and extracapsular disease. These results suggest that under staging is not present in apparently node negative cases with limited lymphadenectomy and, even if present, its impact on outcome is likely to be negligible.
Regulation of neurofilament dynamics by phosphorylation

Neurofilament (NF) phosphorylation has long been considered to regulate axonal transport rate and in doing so to provide stability to mature axons. Studies utilizing mice in which the C‐terminal region of NF subunits (which contains the vast majority of phosphorylation sites) has been deleted has prompted an ongoing challenge to this hypothesis. We evaluate the collective evidence to date for and against a role for NF C‐terminal phosphorylation in regulation of axonal transport and in providing structural support for axons, including some novel studies from our laboratory. We present a few suggestions for further experimentation in this area, and expand upon previous models for axonal NF dynamics. Finally, we address how C‐terminal phosphorylation is regionally and temporally regulated by a balance of kinase and phosphatase activities, and how misregulation of this balance can contribute to motor neuron disease.
Decreased expression of B7 costimulatory molecules and major histocompatibility complex class‐I in human hepatocellular carcinoma

Background and Aim: We analyzed the expression of antigen‐processing and antigen‐presenting molecules in surgically resected fresh samples of human hepatocellular carcinoma (HCC) tissue to elucidate a mechanism of immune escape. We also examined the expression of interleukin (IL)‐10 protein, which might act to downregulate expression of antigen‐processing and antigen‐presenting molecules.
Identification of a Novel Human Kinase Supporter of Ras (hKSR-2) That Functions as a Negative Regulator of Cot (Tpl2) Signaling*

Kinase suppressor of Ras (KSR) is an integral and conserved component of the Ras signaling pathway. Although KSR is a positive regulator of the Ras/mitogen-activated protein (MAP) kinase pathway, the role of KSR in Cot-mediated MAPK activation has not been identified. The serine/threonine kinase Cot (also known as Tpl2) is a member of the MAP kinase kinase kinase (MAP3K) family that is known to regulate oncogenic and inflammatory pathways; however, the mechanism(s) of its regulation are not precisely known. In this report, we identify an 830-amino acid novel human KSR, designated hKSR-2, using predictions from genomic data base mining based on the structural profile of the KSR kinase domain. We show that, similar to the known human KSR, hKSR-2 co-immunoprecipitates with many signaling components of the Ras/MAPK pathway, including Ras, Raf, MEK-1, and ERK-1/2. In addition, we demonstrate that hKSR-2 co-immunoprecipitates with Cot and that co-expression of hKSR-2 with Cot significantly reduces Cot-mediated MAPK and NF-κB activation. This inhibition is specific to Cot, because Ras-induced ERK and IκB kinase-induced NF-κB activation are not significantly affected by hKSR-2 co-expression. Moreover, Cot-induced interleukin-8 production in HeLa cells is almost completely inhibited by the concurrent expression of hKSR-2, whereas transforming growth factor β-activated kinase 1 (TAK1)/TAK1-binding protein 1 (TAB1)-induced interleukin-8 production is not affected by hKSR-2 co-expression. Taken together, these results indicate that hKSR-2, a new member of the KSR family, negatively regulates Cot-mediated MAP kinase and NF-κB pathway signaling.
Resolving protein structure‐function‐binding site relationships from a binding site similarity network perspective

Functional annotation is seldom straightforward with complexities arising due to functional divergence in protein families or functional convergence between non‐homologous protein families, leading to mis‐annotations. An enzyme may contain multiple domains and not all domains may be involved in a given function, adding to the complexity in function annotation. To address this, we use binding site information from bound cognate ligands and catalytic residues, since it can help in resolving fold‐function relationships at a finer level and with higher confidence. A comprehensive database of 2,020 fold‐function‐binding site relationships has been systematically generated. A network‐based approach is employed to capture the complexity in these relationships, from which different types of associations are deciphered, that identify versatile protein folds performing diverse functions, same function associated with multiple folds and one‐to‐one relationships. Binding site similarity networks integrated with fold, function, and ligand similarity information are generated to understand the depth of these relationships. Apart from the observed continuity in the functional site space, network properties of these revealed versatile families with topologically different or dissimilar binding sites and structural families that perform very similar functions. As a case study, subtle changes in the active site of a set of evolutionarily related superfamilies are studied using these networks. Tracing of such similarities in evolutionarily related proteins provide clues into the transition and evolution of protein functions. Insights from this study will be helpful in accurate and reliable functional annotations of uncharacterized proteins, poly‐pharmacology, and designing enzymes with new functional capabilities. Proteins 2017; 85:1319–1335. © 2017 Wiley Periodicals, Inc.
Spatial Variability Analysis of Soil Salinity and Alkalinity in an Endorreic Volcanic Watershed

Three areas with different soils were recognized from an automated electromagnetic survey, at detailed scale, within a desiccated alkaline-salt-lake, using an EM38 instrument connected to a GPS and a datalogger, mounted in vertical mode on a mobile platform at 25 cm aboveground. Secondary magnetic field, surface temperature and position of measurements were recorded. GPS accuracy was evaluated before and during the survey and positioning was optimized using Wide Area Augmentation System, as well as performing the survey during the period with the lower expected Degradation Of ositioning. The raw data corresponding to the apparent soil electrical conductivity, measured from the secondary magnetic field induced by the EM instrument, were grouped statistically into three clusters using a partitioning-around-medoids algorithm. Subsequent soil sampling within each cluster was performed for characterization purposes, and main soil properties were analyzed. Each cluster representative was found to be different from others in terms of soil depth, texture, pH and Electrical Conductivity. The semivariogram adjusted to the signal data, a Gaussian-type with low nugget effect, suggest that the lag between measurements was adequate for capturing the spatial structure of the apparent electrical conductivity variable. Also can be derived that the salinity values change smoothly along the transect of the alkaline-salt-lake according to 2nd order stationarity. The instrumental arrangement provided a combined salinity+texture gradients mapping at very detailed scale.
Cross-Country Evidence on Motherhood Employment and Wage Gaps: The Role of Work–Family Policies and Their Interaction

Abstract: This article investigates the effects of work–family policies on motherhood employment and wage gaps. We study twenty-eight European countries, including Central and Eastern European countries. We show that unless the leave period is exceptionally long, enhanced childcare and leave policies help women combine family responsibilities with paid work. The positive effect of leaves is, however, much weaker in countries where childcare is limited. In these countries, improving access to childcare is therefore a more efficient policy than offering extended leaves. Because extended leaves encourage women to stay outside of the labor market, they are found to lead to wage penalties.
A molecular model for the development of germ cell cancer

Human germ cell tumors comprise a heterogeneous group of neoplasms. Those of the adult testis, known as TGCTs, originate from carcinoma in situ (CIS), which are initiated during intra‐uterine development. We present here a molecular model for the development of TGCTs, including various parameters, such as apoptosis, chromosomal constitution, as well as genomic imprinting. We assume that TGCTs originate from a pluripotent, erased embryonic germ cell, of which aneuploidization is one of the early events. Subsequently, net loss and gain of specific chromosomal regions result in the consistent pattern of chromosomal aberrations that are observed in these tumors, including gain of 12p‐sequences. By means of analysis of a relatively small region of the short arm of chromosome 12, we are in the process of identifying the relevant genes. Possibly, this gene(s) suppresses apoptosis outside the specific micro‐environment of the seminiferous tubule. Int. J. Cancer: 83:809–814, 1999. © 1999 Wiley‐Liss, Inc.
A Prospective, Randomized Controlled Trial Comparing n-Butyl Cyanoacrylate Tissue Adhesive (LiquiBand) With Sutures for Skin Closure After Laparoscopic General Surgical Procedures

The aim of this study was to compare the efficacy of n-butyl-cyanoacrylate tissue adhesive (Liquiband) with nonabsorbable monofilament sutures for laparoscopic port site closure. Adult patients having elective laparoscopic procedures were randomly allocated to wound closure with sutures or tissue adhesive. End points included skin closure time, wound dressing requirements, wound complications, and cosmesis, assessed at discharge, 4 to 6 weeks and 3 months. Seventy-eight patients randomized to receive sutures and 76 to receive tissue adhesive were eligible for final analysis. Mean closure time was significantly longer for sutures (220 vs. 125 s, P<0.001). Fewer dressings were required in the tissue adhesive group immediately postoperatively (21% vs. 97%, P<0.001) and at discharge (24% vs. 82%, P<0.001). There were no significant differences in wound complications or in cosmesis at either 4 to 6 weeks or at 3 months. Tissue adhesive for laparoscopic port site closure offers potential savings with respect to time and has comparable wound complication rates and cosmetic outcomes when compared with nonabsorbable monofilament sutures.
The high prevalence of pain in emergency medical care.

Although there is a widely held belief that pain is the number 1 complaint in emergency medical care, few studies have actually assessed the prevalence of pain in the emergency department (ED). We conducted an analysis of secondary data by using explicit data abstraction rules to determine the prevalence of pain in the ED and to classify the location, origin, and duration of the pain. This retrospective cross-sectional study was conducted at an urban teaching hospital in Indianapolis, IN. Charts from 1,665 consecutive ED visits during a 7-day period were reviewed. Pain was defined as the word pain or a pain equivalent word (including aching, burning, and discomfort) recorded on the chart. Of the 1,665 visits, 61.2% had pain documented anywhere on the chart, 34.1% did not have pain, and 4.7% were procedures. Pain was a chief complaint for 52.2% of the visits. This high prevalence of pain has important implications for the allocation of resources as well as educational and research efforts in emergency medical care.
The NMR blood flowmeter--applications.

Nuclear Magnetic Resonance (NMR) permits the noninvasive measurement of blood flow signals unimpaired by clothes, bandages, casts, etc. The cylindrical crossed-coil NMR blood flowmeter was used to measure blood flow through a cross-section of the human forearm. Two calibration procedures are described: one for pulsatile flows and the other for flows with a high non-pulsatile component. Flow measurements from normal arms, from limbs with arterial obstruction, arteriovenous hemodialysis fistulas or other conditions are reported. An application of the flow scanning technique for separation of flow signals from individual arteries (e.g., ulnar and radial) is described. The flat crossed-coil NMR flowmeter was applied to detect blood flow from individual arteries (e.g., brachial, popliteal, etc.). Applications of a ranging technique developed to detect signals at predetermined depths are described.
Real-time cyclostationary analysis for cognitive radio via software defined radio

Cyclostationary analysis such as spectral correlation function (SCF) and spectral coherence function (SOF) has been accepted as an important tool in signal detection and radio frequency (RF) parameter estimation in cognitive radios. However, cyclostationary analysis requires extremely high resolution to fully observe the cyclic frequency features, leading to very high computational complexity and difficulty in real time implementation, especially on software defined radios where computational capability is limited. In this paper, we implement and demonstrate a real time SCF/SOF RF signal analyzer by adopting previously proposed two-stage dynamic resolution SCF/SOF estimation method using software defined radios. Specifically, high resolution SCF/SOF calculation is only performed near the expected cyclic feature locations obtained through a low complexity coarse estimation employing spectral analysis. This cyclostationary analysis based RF signal analyzer is capable of sensing the existence of primary users and estimating the carrier frequency and symbol rate accurately. Using Universal Software Radio Peripheral (USRP) software defined radio platform and GNU radio software, we implement and demonstrate such a cyclostationary analysis based RF signal analyzer in real time and validate the performance in realistic wireless communication channels.
Overcoming inertia in retirement saving : Why now and how?

Saving for retirement is one of the most important financial matters people face during their lives. Whereas the Dutch, on average, accumulate sufficient retirement wealth, quite a few people will end up with lower savings than they expect or need. It is surprising that many people remain inactive even when action is needed. This paper by Job Krijnen, Marcel Zeelenberg and Seger Breugelmans (all TiU) addresses two questions about inertia. First, what reasons can explain people’s inertia in retirement saving? Second, how can our understanding of these reasons contribute to current and future developments in the Dutch retirement system? Overcoming inertia in retirement saving Why now and how?
Peripheral effects of the kappa-opioid agonist EMD 61753 on pain and inflammation in rats and humans.

The objective of the present study was to evaluate the effects of EMD 61753 (asimadoline), a kappa-opioid receptor agonist with restricted access to the central nervous system, on postoperative pain in patients who underwent knee surgery and on nociceptive thresholds and inflammation in rats treated with Freund's complete adjuvant. Patients treated with EMD 61753 (10 mg p.o.) tended to report an increase in pain, as evaluated by a visual analog scale and by the time to the first request for and the total amount of supplemental analgesic medication. The global tolerability of EMD 61753 was assessed as significantly inferior to that of a placebo by the investigator. In rats, the bilateral intraplantar (i.pl.) injection of EMD 61753 (0.1-3.2 mg) resulted in dose-dependent antinociception in both inflamed and noninflamed paws, with a peak at 5 min after injection, as evaluated by the paw pressure method. However, at later time points (1 h-4 days), a significant decrease in the paw pressure threshold was observed, confirming its tendency toward a hyperalgesic action in humans. This was accompanied by an increase in paw volume and paw temperature, with a peak at 6 h after injection. EMD 61753 (1.6 mg)-induced analgesia was blocked by the peripheral opioid receptor antagonist naloxone methiodide (2.5-10 mg/kg s.c.) and by the kappa receptor antagonist nor-binaltorphimine (0.1 mg; i.pl.). In contrast, EMD 61753 (1.6 mg)-induced hyperalgesia and increases in paw volume and paw temperature were blocked neither by naloxone methiodide (10-40 mg/kg s.c.) nor by dizocilpine maleate (0.003-0.009 mg i.pl.), a N-methyl-D-aspartic acid receptor antagonist. These data show differentially mediated peripheral actions of EMD 61753: kappa-opioid receptor-induced analgesia and nonopioid, non-N-methyl-D-aspartic acid hyperalgesic and proinflammatory effects.
Characterizing the Serious Game and Assessing Learning Goals

Serious games (SGs) are video or computer games designed for training or educational purposes. Thanks to the wide variety of opportunities they provide, e.g. interactivity, immersion, simulation, etc they have become universally embraced in both academic and non-academic fields alike. However, the selection of the most suitable SG with regard to a given learning goal seems to be less well addressed in the literature. This paper tries to bridge this research gap by building a new Characterizing and Assessing Serious Games Grid (CASGG). The research was based on a design science method. The CASGG was built during a series of meetings (i.e. working group with professionals (education experts), brainstorming with students and teachers) and pilot tests with students. Subsequently, it was tested in the higher education field with 41 graduate students to assess their learning performance according to leaning goals using a specific SG. The tested SG was StarBank the Game and the learning goal was to understand the principal mechanisms of banking. The findings revealed that there is no difference in terms of learning performance between students who have used the SG and those who have followed the theoretical course. With reference to learning satisfaction, the first category of students expressed much more enthusiasm and motivation for learning. Using the SG was for them more enjoyable and engaging. The game play succeeded in capturing their attention, challenging their curiosity and enhancing their interest in the theoretical knowledge. Moreover, owing to this research the design science approach proved most suitable for the building and application of the CASGG by demonstrating its practical feasibility and use. Regarding the context of SGs, the CASGG is actually not only an empirical elaboration of an SG assessment instrument, but also a starting point for further research in this area.