Miracle-dz/UniFAR-FTUs huggingface dataset:
Two Regions of Bacillus subtilis Transcription Factor SpoIIID Allow a Monomer To Bind DNA

ABSTRACT Nutrient limitation causes Bacillus subtilis to develop into two different cell types, a mother cell and a spore. SpoIIID is a key regulator of transcription in the mother cell and positively or negatively regulates more than 100 genes, in many cases by binding to the promoter region. SpoIIID was predicted to have a helix-turn-helix motif for sequence-specific DNA binding, and a 10-bp consensus sequence was recognized in binding sites, but some strong binding sites were observed to contain more than one match to the consensus sequence, suggesting that SpoIIID might bind as a dimer or cooperatively as monomers. Here we show that SpoIIID binds with high affinity as a monomer to a single copy of its recognition sequence. Using charge reversal substitutions of residues likely to be exposed on the surface of SpoIIID and assays for transcriptional activation in vivo and for DNA binding in vitro, we identify two regions essential for DNA binding, the putative recognition helix of the predicted helix-turn-helix motif and a basic region near the C terminus. SpoIIID is unusual among prokaryotic DNA-binding proteins with a single helix-turn-helix motif in its ability to bind DNA monomerically with high affinity. We propose that the C-terminal basic region of SpoIIID makes additional contacts with DNA, analogous to the N-terminal arm of eukaryotic homeodomain proteins and the “wings” of winged-helix proteins, but structurally distinct. SpoIIID is highly conserved only among bacteria that form endospores, including several important human pathogens. The need to conserve biosynthetic capacity during endospore formation might have favored the evolution of a small transcription factor capable of high-affinity binding to DNA as a monomer, and this unusual mode of DNA binding could provide a target for drug design.
Competition and segmentation in spoken word recognition

Spoken utterances contain few reliable cues to word boundaries, but listeners nonetheless experience little difficulty identifying words in continuous speech. The authors present data and simulations that suggest that this ability is best accounted for by a model of spoken-word recognition combining competition between alternative lexical candidates, and sensitivity to prosodic structure. In a word-spotting experiment, stress pattern effects emerged most clearly when there were many competing lexical candidates for part of the input. Thus, competition between simultaneously active word candidates can modulate the size of prosodic effects, which suggests that spoken-word recognition must be sensitive both to prosodic structure and to the effects of competition. A version of the Shortlist model (D. G. Norris, 1994b) incorporating the Metrical Segmentation Strategy (A. Cutler & D. Norris, 1988) accurately simulates the results using a lexicon of more than 25,000 words.
Hashimoto’s encephalopathy

The authors report a patient who had five relapses of encephalopathy with seizures and aseptic meningitis that coincided with the end of the menstrual cycle. High titers of antithyroid antibodies and the patient’s response to corticosteroids suggested Hashimoto’s encephalopathy. Pharmacologic suppression of the menstrual cycle made it possible to withdraw corticosteroids.
Synthetic chemerin-derived peptides suppress inflammation through ChemR23

Chemerin is a chemotactic protein that binds to the G protein–coupled receptor, ChemR23. We demonstrate that murine chemerin possesses potent antiinflammatory properties that are absolutely dependent on proteolytic processing. A series of peptides was designed, and only those identical to specific C-terminal chemerin sequences exerted antiinflammatory effects at picomolar concentrations in vitro. One of these, chemerin15 (C15; A140-A154), inhibited macrophage (MΦ) activation to a similar extent as proteolyzed chemerin, but exhibited reduced activity as a MΦ chemoattractant. Intraperitoneal administration of C15 (0.32 ng/kg) to mice before zymosan challenge conferred significant protection against zymosan-induced peritonitis, suppressing neutrophil (63%) and monocyte (62%) recruitment with a concomitant reduction in proinflammatory mediator expression. Importantly, C15 was unable to ameliorate zymosan-induced peritonitis in ChemR23−/− mice, demonstrating that C15's antiinflammatory effects are entirely ChemR23 dependent. In addition, administration of neutralizing anti-chemerin antibody before zymosan challenge resulted in a significant exacerbation of peritoneal inflammation (up to 170%), suggesting an important endogenous antiinflammatory role for chemerin-derived species. Collectively, these results show that chemerin-derived peptides may represent a novel therapeutic strategy for the treatment of inflammatory diseases through ChemR23.
Using Biased Coins as Oracles

While it is well known that a Turing machine equipped with the ability to flip a fair coin cannot compute more that a standard Turing machine, we show that this is not true for a biased coin. Indeed, any oracle set X may be coded as a probability pX such that if a Turing machine is given a coin which lands heads with probability pX it can compute any function recursive in X with arbitrarily high probability. We also show how the assumption of a non- recursive bias can be weakened by using a sequence of increasingly accurate recursive biases or by choosing the bias at random from a distribution with a non-recursive mean. We conclude by briefly mentioning some implications regarding the physical realisability of such methods.
Relapse versus reinfection with Clostridium difficile

SUMMARY Relapse of Clostridium, difficile-associated diarrhoea occurs in 15–20% of patients; however, whether relapse is due to an endogenous source of the organism or reinfection from the environment remains unclear. Restriction enzyme analysis (REA) of chromosomal DNA was used to type multiple isolates from ten patients who had experienced apparent relapses. More than half the relapses were due to infection with a new strain of C. difficile. The remaining patients were infected with the same strain, but whether this strain was acquired from the environment or from endogenous sources could not be determined. Relapses with a different strain of C. difficile could occur if an individual harboured more than one strain in their gastrointestinal tract. To investigate this possibility ten other patients were assessed for carriage of multiple strains. Ten colonies from a primary culture plate from each patient were typed by REA and tested for their ability to produce cytotoxin. All isolates from the same patient were identical by both methods, indicating that multiple carriage of strains may be a rare event.
Effect of 25-hydroxyvitamin D3 on rotavirus replication and gene expressions of RIG-I signalling molecule in porcine rotavirus–infected IPEC-J2 cells

The study evaluated whether a 25-hydroxyvitamin D3 (25D3) supplementation decreases the replication of rotavirus by the retinoic acid-inducible gene I (RIG-I) signalling pathway in a porcine small intestinal epithelial cell line (IPEC-J2). The results show that IPEC-J2 cells express high baseline levels of 1α-hydroxylase (CYP27B1), which converts inactive 25D3 to the active 1,25-dihydroxyvitamin D3 (1,25D3). Porcine rotavirus (PRV) infection alone resulted in a significant increase in CYP27B1 mRNA, which augmented the production of active vitamin D. Physiological concentrations of 25D3 were found to decrease PRV replication in IPEC-J2 cells. RIG-I plays an important role in the recognition of double-stranded RNA virus by host cells. Upon recognition, RIG-I triggers a series of signalling molecules such as interferon-β (IFN-β) promoter stimulator 1 (IPS-1) leading to the expression of type I interferons (IFN-β). Active 25D3 that was generated by PRV-infected IPEC-J2 cells led to an increased expression of toll-like receptors 3 (TLR3), RIG-I, IPS-1, IFN-β and IFN-stimulated genes 15 (ISG15) with important innate immune functions. Inhibiting CYP27B1 also failed to increase RIG-I, IPS-1, IFN-β and ISG15 mRNA expression. These observations suggest that 25D3 can directly inhibit PRV in IPEC-J2 cells, which requires this active form of vitamin D. The anti-rotavirus effect of 25D3 is mediated at least in part by RIG-I signalling pathways in IPEC-J2 cells.
A reconfigurable on-line learning spiking neuromorphic processor comprising 256 neurons and 128K synapses

Implementing compact, low-power artificial neural processing systems with real-time on-line learning abilities is still an open challenge. In this paper we present a full-custom mixed-signal VLSI device with neuromorphic learning circuits that emulate the biophysics of real spiking neurons and dynamic synapses for exploring the properties of computational neuroscience models and for building brain-inspired computing systems. The proposed architecture allows the on-chip configuration of a wide range of network connectivities, including recurrent and deep networks, with short-term and long-term plasticity. The device comprises 128 K analog synapse and 256 neuron circuits with biologically plausible dynamics and bi-stable spike-based plasticity mechanisms that endow it with on-line learning abilities. In addition to the analog circuits, the device comprises also asynchronous digital logic circuits for setting different synapse and neuron properties as well as different network configurations. This prototype device, fabricated using a 180 nm 1P6M CMOS process, occupies an area of 51.4 mm2, and consumes approximately 4 mW for typical experiments, for example involving attractor networks. Here we describe the details of the overall architecture and of the individual circuits and present experimental results that showcase its potential. By supporting a wide range of cortical-like computational modules comprising plasticity mechanisms, this device will enable the realization of intelligent autonomous systems with on-line learning capabilities.
Admissible Pruning Strategies based on plan minimality for Plan-Space Planning

Although plan space planners have been shown to be flexible and efficient in plan generation, they do suffer from the problem of "looping" - that is they may spend an inordinate amount of time. doing locally seemingly useful but globally useless refinements In this paper I review the anatomy of looping and argue that looping is intimately tied to the production of non minimal solutions I then propose two classes of admissible pruning techniques based on the notion of plan minimality I show that the first one is admissible for planners which do not protect their establishments but allow a precondition to be reestablished any number of times. The second one is admissible for planners which protect their establishments through causal links I also discuss the complexity of the proposed pruning strategies and then potential applications.
STEAMER: An Interactive Inspectable Simulation-Based Training System

The Steamer project is a research effort concerned with exploring the use of AI software and hardware technologies in the implementation of intelligent computer-based training systems. While the project addressed a host of research issues ranging from how people understand complex dynamic systems to the use of intelligent graphical interfaces, it is focused around the construction of a system to assist in propulsion engineering instruction. The purpose of this article is to discuss the underlying ideas which motivated us to initiate the Steamer effort, describe the current status of the project, provide a glimpse of our planned directions for the future, and discuss the implications of Steamer for AI applications in other instructional domains.
Bowel movement frequency, medical history and the risk of gallbladder cancer death: A cohort study in Japan

Few risk factors for gallbladder cancer have been identified with sufficient statistical power, because this cancer is rare. The present study was conducted to evaluate the association of bowel movement frequency and medical history with the risk of death from gallbladder cancer using the data set from a large‐scale cohort study. A total of 113,394 participants (42.0% males), aged 40 to 89 years, were followed up for 11 years. Information on the medical history of selected diseases, history of blood transfusions, frequency of stools, and tendency toward diarrhea at baseline was collected through a self‐administered questionnaire. The Cox proportional hazard model was used to estimate the hazard ratio (HR). During the follow‐up period, a total of 116 deaths (46 males, 70 females) from gallbladder cancer were identified. After adjustments for age and gender, history of hepatic disease (HR: 2.28; 95% confidence intervals (95% CI): 1.24–4.21), frequency of stool, and tendency toward diarrhea (HR: 0.26; 95% CI: 0.08‐0.83) were found to be significantly associated with the risk of death from gallbladder cancer. Compared with those who had a stool at least once a day, the HR was 2.06 (95% Cl: 0.82–5.18) for those who had a stool less than once in 6 days (P for trend=0.050). In this prospective study, constipation and a history of hepatic disease were found to elevate the risk of gallbladder cancer death, whereas a tendency toward diarrhea diminished it.
Observations of Internal Charging Currents in Medium Earth Orbit

The Galileo global navigation system will employ an array of satellites in medium Earth orbit (MEO). Internal charging is one of the primary hazards for any spacecraft in MEO, and accordingly, the Galileo test satellite, Giove-A, carries a detector, SURF, to undertake the measurement of internal charging currents at three different shielding depths. The currents are due to electrons stopped in three aluminum plates: the first plate is 0.5 mm thick and located under 0.5-mm Al-equivalent shielding, the second is 0.5 mm thick and located underneath the first plate, and the third is 1.0 mm thick and located underneath the second plate. Giove-A was successfully launched on December 28, 2005 into a 23 300-km circular 56deg inclination orbit. In this paper, we provide data on the internal charging currents observed in 2006, with particular emphasis on two large charging events, one in mid-April and one in mid-December. Comparisons are made to predictions using the DICTAT internal charging tool and the FLUMIC ldquoworst caserdquo trapped electron belt model. In general, the charging currents observed are safely within the standard DICTAT 3.5/FLUMIC 3.0 predictions but are exceeded in the most shielded plate on five calendar days during December 2006. The December event was unique in 2006 in that it was triggered by the arrival of a coronal mass ejection (CME) rather than being due to the effects of a fast solar wind stream flowing from a coronal hole. The currents measured in the December event were, however, an order of magnitude lower than those predicted using the ldquoanomalously large eventrdquo supplement to FLUMIC which models the most extreme electron enhancements associated with CMEs.
On designing better tools for learning APIs

Modern software development requires a large investment in learning application programming interfaces (APIs). Recent research found that the learning materials themselves are often inadequate: developers struggle to find answers beyond simple usage scenarios. Solving these problems requires a large investment in tool and search engine development. To understand where further investment would be most useful, we ran a study with 19 professional developers to understand what a solution might look like, free of technical constraints. In this paper, we report on design implications of tools for API learning, grounded in the reality of the professional developers themselves. The reoccurring themes in the participants' feedback were trustworthiness, confidentiality, information overload and the need for code examples as first-class documentation artifacts.
Primary prevention of cardiovascular disease in women

Abstract Ischemic heart disease is the primary cause of cardiovascular disease (CVD) mortality in both men and women. Strategies targeting traditional modifiable risk factors are essential – including hypertension, smoking, dyslipidemia and diabetes mellitus – particularly for atherosclerosis, but additionally for stroke, heart failure and some arrhythmias. However, challenges related to education, screening and equitable access to effective preventative therapies persist, and are particularly problematic for women around the globe and those from lower socioeconomic groups. The association of female-specific risk factors (e.g. premature menopause, gestational hypertension, small for gestational age births) with CVD provides a potential window for targeted prevention strategies. However, further evidence for specific effective screening and interventions is urgently required. In addition to population-level factors involved in increasing the risk of suffering a CVD event, efforts are leveraging the enormous potential of blood-based ‘omics’, improved imaging biomarkers and increasingly complex bioinformatic analytic approaches to strive toward more personalized early disease detection and personalized preventative therapies. These novel tactics may be particularly relevant for women in whom traditional risk factors perform poorly. Here we discuss established and emerging approaches for improving risk assessment, early disease detection and effective preventative strategies to reduce the mammoth burden of CVD in women.
Risk of arsenic contamination in groundwater affecting the Ganga Alluvial Plain, India.

Should chemical toxicity data from the peerreviewed, published scientific literature be considered reliable enough for government risk assessors to use? The Center for Regulatory Effectiveness (CRE) says no, arguing that studies subject to rigorous peer review and published in prominent scientific journals may not be sufficiently “reliable” to be used by the government. The CRE, selfdescribed as a regulatory watchdog group supported by business and trade associations, relies on the so-called Data Quality Act (2001), an obscure provision of a spending bill, which requires governmental agencies to develop guidelines for “ensuring and maximizing the quality, objectivity, utility, and integrity of information” they disseminate. The issue of whether the Data Quality Act will promote greater scientific rigor or whether it will stand in the way of regulatory decision making is coming to a head as the U.S. Environmental Protection Agency (EPA) assesses atrazine, one of most widely used herbicides in the United States. Atrazine has been banned or restricted in numerous countries, and significant published literature suggests that atrazine is an endocrine disruptor (Hayes et al. 2002a, 2002b, 2003; Laws et al. 2000; Stoker et al. 1999; 2000; Tavera-Mendoza et al. 2002; Sass 2003). Nevertheless, the CRE recently objected that since
FACTORS ASSOCIATED WITH THE INCIDENCE OF LOW BACK PAIN BASED ON THE NUMERIC PAIN RATING SCALE IN DAILY WORKERS AT THE BBPPT KOMINFO DEPOK PROJECT

Low back pain (LBP) is pain that is felt in the lower back area and originates in the spine, muscles, nerves, or other structures around the area. The prevalence rate of LBP in Indonesia in 2016 was 59.25%. This study aims to determine the factors associated with the incidence of low back pain in daily workers at the BBPPT Kominfo Depok project.Quantitative research with a cross-sectional study design. The population is daily field workers with a total of 70 people and the sampling technique is total sampling. Data collection was carried out in January 2023. Data analysis used the chi-square test α = 0.05. From the study results, the p-value of each variable was obtained, namely: Age (p-value 0.071 meaning that there is no significant relationship between age and the incidence of LBP), Body Mass Index (BMI) (p-value 1.000 meaning there is no significant relationship between BMI with the incidence of LBP), Smoking Habit (p-value 0.044 means that there is a significant relationship between smoking habits and the incidence of LBP), Working Mass (p-value 0.042 means that there is a significant relationship between working mass and the incidence of LBP), Working Time (p-value 0.017 means that there is a significant relationship between working time and the incidence of LBP) and Lifting Weight (p-value 0.013 means that there is a significant relationship between the lifting weight and the incidence of LBP). Smoking habits, years of service, length of work, and weight of lifting have a relationship with the incidence of LBP. Reducing the length of work for daily workers so that daily workers get sufficient rest time, and providing an adequate number of assistive devices so that workers do not lift objects or materials manually.
Opening the Black Box

564 As I have been transitioning into the editor role, it has become clear that there is confusion about the editorial and review process for C&RL. There have been numerous discussions on aspects of the process—selection, review, timeline—and other questions and misapprehensions. In the spirit of open access and transparency, this editorial will attempt to demystify the process, verify the integrity of the journal, and explain the journal’s standards and expectations while demonstrating how it is positioned and supported.
Induction of the sufA operon encoding Fe‐S assembly proteins by superoxide generators and hydrogen peroxide: involvement of OxyR, IHF and an unidentified oxidant‐responsive factor

A promoter (sufAp), inducible by various oxidants, directs transcription of the sufABCDSE operon encoding an alternative Fe‐S cluster assembly system in Escherichia coli. Superoxide generators and H2O2 induced expression of sufA–lacZ even in ΔsoxRS and ΔoxyR mutants, suggesting participation of an additional regulator(s) in oxidant induction of the sufA operon. Through deletion and linker scanning mutagenesis, we found three cis‐acting oxidant‐responsive elements (OREs). ORE‐I lies between −236 and −197 nucleotides from the transcription start site, overlapping extensively with the OxyR binding site reported previously. ORE‐II (−156 to −127) was found to be the site of IHF action. ORE‐III (−56 to −35) had no predictable binding sites for known regulators. Gel mobility shift assays with a 50 bp DNA probe containing ORE‐III revealed the presence of an ORE‐III‐specific factor that binds only when cells are treated with oxidants. S1 mapping analysis revealed that phenazine methosulphate (PMS) and H2O2 induced sufA expression by more than 40‐fold. In a ΔoxyR mutant, sufA was still induced more than 10‐fold. Fur, a ferric uptake regulator that negatively regulates this operon in response to iron availability, did not mediate the oxidant induction. Deletion of the suf operon caused cells to be more sensitive to superoxide‐generating agents without affecting sensitivity to H2O2. From these results, we propose that the oxidant induction of the sufA operon is mediated through OxyR, IHF, plus an unidentified oxidant‐responsive factor, and that the suf gene products are needed to defend cells against oxidative stress caused by superoxide generators.