Miracle-dz/UniFAR-FTUs huggingface dataset:
A Real-Time Opponent Modeling System for Rush Football

One drawback with using plan recognition in adversarial games is that often players must commit to a plan before it is possible to infer the opponent's intentions. In such cases, it is valuable to couple plan recognition with plan repair, particularly in multi-agent domains where complete replanning is not computationally feasible. This paper presents a method for learning plan repair policies in real-time using Upper Confidence Bounds applied to Trees (UCT). We demonstrate how these policies can be coupled with plan recognition in an American football game (Rush 2008) to create an autonomous offensive team capable of responding to unexpected changes in defensive strategy. Our real-time version of UCT learns play modifications that result in a significantly higher average yardage and fewer interceptions than either the baseline game or domain-specific heuristics. Although it is possible to use the actual game simulator to measure reward offline, to execute UCT in real-time demands a different approach; here we describe two modules for reusing data from offline UCT searches to learn accurate state and reward estimators.
Update on immune checkpoint inhibitors in gynecological cancers

In recent years, progress in our understanding of immune-modulatory signaling pathways in immune cells and the tumor microenvironment (TME) has led to rejuvenated interest in cancer immunotherapy. In particular, immunotherapy targeting the immune checkpoint receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell-death 1 (PD-1), and programmed cell-death ligand 1 (PD-L1) have demonstrated clinical activity in a wide variety of tumors, including gynecological cancers. This review will focus on the emerging clinical data on the therapeutic role of immune checkpoint inhibitors, and potential strategies to enhance the efficacy of this class of compounds, in the context of gynecological cancers. It is anticipated that future biomarker-directed clinical trials will provide further insights into the mechanisms underlying response and resistance to immunotherapy, and help guide our approach to designing therapeutic combinations that have the potential to enhance the benefit of immunotherapy in patients with gynecologic cancers.
Combined Effects of Prepregnancy Body Mass Index and Weight Gain During Pregnancy on the Risk of Preterm Delivery

Background: The association between excessive gestational weight gain and preterm delivery is unclear, as is the association between low gestational weight gain and preterm delivery among overweight and obese women. Methods: Using data from the Pregnancy Risk Assessment Monitoring System in 21 states, we estimated the risk of very (20–31 weeks) and moderately (32–36 weeks) preterm delivery associated with a combination of prepregnancy body mass index (BMI) and gestational weight gain among 113,019 women who delivered a singleton infant during 1996–2001. We categorized average weight gain (kilograms per week) as very low (<0.12), low (0.12–0.22), moderate (0.23–0.68), high (0.69–0.79), or very high (>0.79). We categorized prepregnancy BMI (kg/m2) as underweight (<19.8), normal (19.8–26.0), overweight (26.1–28.9), obese (29.0–34.9), or very obese (≥35.0). We examined associations for all women and for all women with no complications adjusting for covariates. Results: There was a strong association between very low weight gain and very preterm delivery that varied by prepregnancy BMI, with the strongest association among underweight women (adjusted odds ratio = 9.8; 95% confidence interval = 7.0–13.8) and the weakest among very obese women (2.3; 1.8–3.1). Very low weight gain was not associated with moderately preterm delivery for overweight or obese women. Women with very high weight gain had approximately twice the odds of very preterm delivery, regardless of prepregnancy BMI. Conclusions: This study supports concerns about very low weight gain during pregnancy, even among overweight and obese women, and also suggests that high weight gain, regardless of prepregnancy BMI, deserves further investigation.
The Koala Component Model for Consumer Electronics Software

Most consumer electronics today contain embedded software. In the early days, developing CE software presented relatively minor challenges, but in the past several years three significant problems have arisen: size and complexity of the software in individual products; the increasing diversity of products and their software; and the need for decreased development time. The question of handling diversity and complexity in embedded software at an increasing production speed becomes an urgent one. The authors present their belief that the answer lies not in hiring more software engineers. They are not readily available, and even if they were, experience shows that larger projects induce larger lead times and often result in greater complexity. Instead, they believe that the answer lies in the use and reuse of software components that work within an explicit software architecture. The Koala model, a component-oriented approach detailed in this article, is their way of handling the diversity of software in consumer electronics. Used for embedded software in TV sets, it allows late binding of reusable components with no additional overhead.
Blood blister-like aneurysms of the internal carotid artery trunk causing subarachnoid hemorrhage: treatment and outcome.

OBJECT The object of this study was to evaluate cases of subarachnoid hemorrhage (SAH) from ruptured blood blister-like aneurysms (BBAs) of the internal carotid artery (ICA) trunk. METHODS The authors performed a single-center, retrospective study. Data analyzed were patient age, sex, Hunt and Hess grade, Fisher grade, time from SAH to hospitalization, aneurysm size and location, collateral capacity of the circle of Willis, time from hospitalization to aneurysm repair, type of aneurysm repair, complications, and Glasgow Outcome Scale (GOS) score at follow-up. RESULTS A total of 211 patients suffered SAH from ICA aneurysms. Of these, 14 patients (6.6%) had ICA trunk BBAs; 6 men and 8 women. The median age was 47.8 years (range 29.9-67.7 years). The Hunt and Hess grade was IV or V in 7 cases, and SAH was Fisher Grade 3 + 4 in 6. All aneurysms were small (< 1 cm), without relation to vessel bifurcations, and usually located anteromedially on the ICA trunk. Three patients were treated with coil placement and 11 with clip placement. Of the 7 patients in whom the ICA was preserved, only 1 had poor outcome (GOS Score 2). In contrast, cerebral infarcts developed in all patients treated with ICA sacrifice, directly postoperatively in 2 and after delay in 5. Six patients died, 1 survived in poor condition (GOS Score 3; p < 0.001). CONCLUSIONS Internal carotid BBAs are rare, small, and difficult to treat endovascularly, with only 2 of 14 patients successfully treated with coil placement. The BBAs rupture easily during surgery (ruptured in 6 of 11 surgical cases). Intraoperative aneurysm rupture invariably led to ICA trap ligation. Sacrifice of the ICA within 48 hours of an SAH led to very poor outcome, even in patients with adequate collateral capacity on preoperative angiograms, probably because of vasospasm-induced compromise of the cerebral collaterals.
Do multivitamin supplements attenuate the risk for diabetes-associated birth defects?

OBJECTIVE To evaluate whether the risk for birth defects associated with maternal diabetes is attenuated by use of multivitamin supplements during the periconceptional period. METHODS In the population-based Atlanta Birth Defects Case-Control Study, we identified case infants who had nonsyndromic birth defects that were reported to be associated with diabetes (n = 3278) and were born during 1968-1980 to residents of metropolitan Atlanta. Controls were infants without birth defects (n = 3029). Maternal diabetes was defined as reported diabetes with onset before the date of birth of the index infant, and periconceptional use of multivitamins was defined as reported regular use of multivitamin supplements from 3 months before pregnancy through the first 3 months of pregnancy. RESULTS Offspring of mothers with diabetes had an increased risk for selected birth defects. However, the increased risk was limited to offspring of mothers who had diabetes and had not taken multivitamins during the periconceptional period (odds ratio: 3.93; 95% confidence interval: 1.79-8.63). Offspring of mothers who had diabetes and had taken multivitamins during the periconceptional period had no increased risk for birth defects (odds ratio: 0.15; 95% confidence interval: 0.00-1.99). CONCLUSIONS Periconceptional use of multivitamin supplements may reduce the risk for birth defects among offspring of mothers with diabetes.
Histone octamer function in vivo: mutations in the dimer–tetramer interfaces disrupt both gene activation and repression

Within the core histone octamer each histone H4 interacts with each H2A–H2B dimer subunit through two binding surfaces. Tyrosines play a central role in these interactions with H4 tyrosines 72 and 88 contacting one H2A–H2B dimer subunit, and tyrosine 98 contacting the other. To investigate the roles of these interactions in vivo, we made site‐directed amino acid substitutions at each of these tyrosine residues. Elimination of either set of interactions is lethal, suggesting that binding of the tetramer to both dimers is essential. Temperature‐sensitive mutants were obtained through single amino acid substitutions at each of the tyrosines. The mutants show both strong positive and negative effects on transcription. Positive effects include Spt‐ and Sin‐phenotypes resulting from mutations at each of the three tyrosines. One allele has a strong negative effect on the expression of genes essential for the G1 cell cycle transition. At restrictive temperature, mutant cells fail to express the CLN1, CLN2, SWI4 and SWI6 genes, and have reduced levels of CLN3 mRNA. These results demonstrate the critical role of histone dimer–tetramer interactions in vivo, and define their essential role in the expression of genes regulating G1 cell cycle progression.
A Multi-Component Day-Camp Weight-Loss Program Is Effective in Reducing BMI in Children after One Year: A Randomized Controlled Trial

The objective of the present study was to evaluate the effectiveness of a one-year multi-component immersive day-camp weight-loss intervention for children with overweight and obesity. The study design was a parallel-group randomized controlled trial. One hundred fifteen 11-13-year-old children with overweight and obesity were randomized into either: A six-week day-camp intervention arm focusing on increased physical activity, and healthy diet followed by a subsequent one-year family-based intervention, or a standard intervention arm consisting of one weekly exercise session for six weeks. Body mass index (BMI) was the primary outcome. BMI z-score, clustered cardiovascular risk z-score, and body composition were secondary outcomes. All outcomes were measured at baseline, six week-, and 52 week follow-up. After six weeks, children from the day-camp intervention arm had improved their BMI (-2.2 kg/m2 (95% CI -2.6 to -1.7, P<0.001)) and all secondary outcomes when compared to the children from the standard intervention arm. After 52 weeks, the day-camp intervention arm had a lower BMI (-1.2 kg/m2 (95% CI -1.8 to -0.5, P = 0.001)), and BMI z-score (-0.20 (95% CI -0.35 to -0.05, P = 0.008)), and clustered cardiovascular risk z-score (-0.23 (95% CI -0.37 to -0.08, P = 0.002)) compared to the standard intervention arm. No group differences were detected in body composition after 52 weeks. This study shows that the day-camp intervention arm is effective in reducing BMI and improving the metabolic health of children with overweight and obesity. However, the effects seem to be diminishing over time.
Connectivity-Based Localization of Large Scale Sensor Networks with Complex Shape

We study the problem of localizing a large sensor network having a complex shape, possibly with holes. A major challenge with respect to such networks is to figure out the correct network layout, i.e., avoid global flips where a part of the network folds on top of another. Our algorithm first selects landmarks on network boundaries with sufficient density, then constructs the landmark Voronoi diagram and its dual combinatorial Delaunay complex on these landmarks. The key insight is that the combinatorial Delaunay complex is provably globally rigid and has a unique realization in the plane. Thus an embedding of the landmarks by simply gluing the Delaunay triangles properly recovers the faithful network layout. With the landmarks nicely localized, the rest of the nodes can easily localize themselves by trilateration to nearby landmark nodes. This leads to a practical and accurate localization algorithm for large networks using only network connectivity. Simulations on various network topologies show surprisingly good results. In comparison, previous connectivity-based localization algorithms such as multi-dimensional scaling and rubberband representation generate globally flipped or distorted localization results.
The voltage-activated hydrogen ion conductance in rat alveolar epithelial cells is determined by the pH gradient

Voltage-activated H+ currents were studied in rat alveolar epithelial cells using tight-seal whole-cell voltage clamp recording and highly buffered, EGTA-containing solutions. Under these conditions, the tail current reversal potential, Vrev, was close to the Nernst potential, EH, varying 52 mV/U pH over four delta pH units (delta pH = pHo - pHi). This result indicates that H+ channels are extremely selective, PH/PTMA > 10(7), and that both internal and external pH, pHi, and pHo, were well controlled. The H+ current amplitude was practically constant at any fixed delta pH, in spite of up to 100-fold symmetrical changes in H+ concentration. Thus, the rate-limiting step in H+ permeation is pH independent, must be localized to the channel (entry, permeation, or exit), and is not bulk diffusion limitation. The instantaneous current- voltage relationship exhibited distinct outward rectification at symmetrical pH, suggesting asymmetry in the permeation pathway. Sigmoid activation kinetics and biexponential decay of tail currents near threshold potentials indicate that H+ channels pass through at least two closed states before opening. The steady state H+ conductance, gH, as well as activation and deactivation kinetic parameters were all shifted along the voltage axis by approximately 40 mV/U pH by changes in pHi or pHo, with the exception of the fast component of tail currents which was shifted less if at all. The threshold potential at which H+ currents were detectably activated can be described empirically as approximately 20-40(pHo-pHi) mV. If internal and external protons regulate the voltage dependence of gH gating at separate sites, then they must be equally effective. A simpler interpretation is that gating is controlled by the pH gradient, delta pH. We propose a simple general model to account for the observed delta pH dependence. Protonation at an externally accessible site stabilizes the closed channel conformation. Deprotonation of this site permits a conformational change resulting in the appearance of a protonation site, possibly the same one, which is accessible via the internal solution. Protonation of the internal site stabilizes the open conformation of the channel. In summary, within the physiological range of pH, the voltage dependence of H+ channel gating depends on delta pH and not on the absolute pH.
A molecular understanding of d-homoestrone-induced G2/M cell cycle arrest in HeLa human cervical carcinoma cells

2‐Methoxyestradiol (ME), one of the most widely investigated A‐ring‐modified metabolites of estrone, exerts significant anticancer activity on numerous cancer cell lines. Its pharmacological actions, including cell cycle arrest, microtubule disruption and pro‐apoptotic activity, have already been described in detail. The currently tested d‐ring‐modified analogue of estrone, d‐homoestrone, selectively inhibits cervical cancer cell proliferation and induces a G2/M phase cell cycle blockade, resulting in the development of apoptosis. The question arose of whether the difference in the chemical structures of these analogues can influence the mechanism of anticancer action. The aim of the present study was therefore to elucidate the molecular contributors of intracellular processes induced by d‐homoestrone in HeLa cells. Apoptosis triggered by d‐homoestrone develops through activation of the intrinsic pathway, as demonstrated by determination of the activities of caspase‐8 and ‐9. It was revealed that d‐homoestrone‐treated HeLa cells are not able to enter mitosis because the cyclin‐dependent kinase 1‐cyclin B complex loses its activity, resulting in the decreased inactivation of stathmin and a concomitant disturbance of microtubule formation. However, unlike 2‐ME, d‐homoestrone does not exert a direct effect on tubulin polymerization. These results led to the conclusion that the d‐homoestrone‐triggered intracellular processes resulting in a cell cycle arrest and apoptosis in HeLa cells differ from those in the case of 2‐ME. This may be regarded as an alternative mechanism of action among steroidal anticancer compounds.
Mutation of Asp(171) and Asp(262) of the chemokine receptor CXCR4 impairs its coreceptor function for human immunodeficiency virus-1 entry and abrogates the antagonistic activity of AMD3100.

The bicyclam AMD3100 is a highly potent and selective CXCR4 antagonist with strong antiviral activity against human immunodeficiency virus (HIV)-1 and HIV-2, which use CXCR4 as coreceptor for host cell entry. Here, we investigated the interaction of AMD3100 with CXCR4 at the molecular level by mutational analysis. We established a set of stably transfected U87.CD4 cell lines expressing different mutant forms of CXCR4 (i.e., CXCR4[WT], CXCR4[D171N], CXCR4[D262N], CXCR4[D171N,D262N], and CXCR4[H281A]), to compare the activity of the compound against mutated versus wild-type CXCR4. We found that the antagonistic action of AMD3100 against CXCR4--as assessed by the inhibitory effects of the compound on stromal cell-derived factor (SDF-1) binding to its receptor and on SDF-1-induced intracellular calcium signaling, and by displacement of the CXCR4-specific antibody, clone 12G5--was greatly reduced by substitution of Asp(171) and/or Asp(262) by neutral asparagine residue(s). Both aspartates, but most particularly Asp(262), also proved essential for the anti-HIV-1 activity of AMD3100 against the viruses NL4.3, IIIB, and HE. In contrast, substitution of His(281) by a neutral alanine potentiated the antagonistic and antiviral effects of the compound in the different assay systems. Importantly, compared with the wild-type receptor, CXCR4[D262N] was much less effective, whereas CXCR4[D171N,D262N] completely failed as a coreceptor for infection by HIV-1 NL4.3. Thus, the negatively charged aspartate residues at positions 171 and 262, located in transmembrane domains 4 and 6 of the 7-transmembrane receptor, respectively, may represent crucial sites for electrostatic interaction of the positive charges of the bicyclams, as well as for the highly basic V3 loop of the gp120 envelope protein of certain HIV-1 strains.
Assembly of Multiple CotC Forms into the Bacillus subtilis Spore Coat

ABSTRACT We report evidence that the CotC polypeptide, a previously identified component of the Bacillus subtilis spore coat, is assembled into at least four distinct forms. Two of these, having molecular masses of 12 and 21 kDa, appeared 8 h after the onset of sporulation and were probably assembled on the forming spore immediately after their synthesis, since no accumulation of either of them was detected in the mother cell compartment, where their synthesis occurs. The other two components, 12.5 and 30 kDa, were generated 2 h later and were probably the products of posttranslational modifications of the two early forms occurring directly on the coat surface during spore maturation. None of the CotC forms was found either on the spore coat or in the mother cell compartment of a cotH mutant. This indicates that CotH serves a dual role of stabilizing the early forms of CotC and promoting the assembly of both early and late forms on the spore surface.
Pregnancy Loss Ascribable to Parvovirus B19/Erythrovirus Is Associated with a High Prevalence of Trisomy

Introduction: In most cases of stillbirth, the cause is still unknown. Aim: The impact of parvovirus B19/erythrovirus infection and chromosomal abnormalities in stillborns and neonatal deaths. Material and Methods: 57 consecutive cases, 23 second-trimester abortions (from gestational weeks 16 to 22), 27 intrauterine fetal deaths (from gestational week 22 onwards) and 7 early neonatal deaths were examined for intrauterine parvovirus B19 infection with PCR, dot blot, Southern blot, in situ hybridization, specific IgM and IgG antibodies in maternal serum, fetal serum, placenta and fetal liver tissue. Chromosomal analysis and extensive histopathology were performed on all fetuses. Results: A sensitive PCR was developed and enabled detection of 9 (15.8%) parvovirus B19-infected fetuses. Parvovirus B19 IgM and IgG antibody tests were in good concordance with PCR findings. 5 of 9 infected fetuses had a concurrent abnormality that could have contributed to fetal death, 4 of which (44%) were trisomy karyotypes, compared to 0/48 in the non-B19-infected group (p = 0.0004). Conclusion: Combination of PCR and specific parvovirus B19 IgG/IgM tests enabled high detection rates of parvovirus B19 infection in this series of 57 consecutive pregnancies with adverse outcomes. The high mortality rate in the B19-infected fetuses was partly explained by a high occurrence of fetal trisomy, compared to non-B19-infected fetuses, suggesting a higher vulnerability of the former. After correction for this concomitant karyotype abnormality, the percentage of presumably lethal infection due to parvovirus B19 was 8.8%.
Attention Biases Visual Activity in Visual Short-term Memory

In the current study, we tested whether representations in visual STM (VSTM) can be biased via top–down attentional modulation of visual activity in retinotopically specific locations. We manipulated attention using retrospective cues presented during the retention interval of a VSTM task. Retrospective cues triggered activity in a large-scale network implicated in attentional control and led to retinotopically specific modulation of activity in early visual areas V1–V4. Importantly, shifts of attention during VSTM maintenance were associated with changes in functional connectivity between pFC and retinotopic regions within V4. Our findings provide new insights into top–down control mechanisms that modulate VSTM representations for flexible and goal-directed maintenance of the most relevant memoranda.