Miracle-dz/UniFAR-FTUs huggingface dataset:
Beyond Log-Supermodularity: Lower Bounds and the Bethe Partition Function

A recent result has demonstrated that the Bethe partition function always lower bounds the true partition function of binary, log-supermodular graphical models. We demonstrate that these results can be extended to other interesting classes of graphical models that are not necessarily binary or log-supermodular: the ferromagnetic Potts model with a uniform external field and its generalizations and special classes of weighted graph homomorphism problems.
Quinine Inhibits Vascular Contraction Independent of Effects on Calcium or Myosin Phosphorylation

This report contains results of studies designed to determine whether quinine has direct effects on myofilament Ca2+sensitization in addition to effects on Ca2+. Quinine decreased the EC50 value and maximal contraction of intact arterial strips to histamine. Incubation of arterial strips with indomethacin or 1H-[1,2,4]oxadiazole[4,3-α]quinoxalin-1-one did not alter quinine inhibition, suggesting that the effect is not mediated via cyclooxygenase or cGMP. Pretreatment of strips with quinine had no effect on the histamine-dependent increases in myosin light chain phosphorylation levels. Quinine inhibited Ca2+-induced contraction in α-toxin permeabilized strips, but not the Ca2+-induced contraction in Triton X-100 permeabilized strips. Pretreatment of the α-toxin permeabilized strips with quinine before stimulation with guanosine-5′-O-(3-thio)triphosphate (GTPγS) did not have any effect on the response. In conclusion, quinine inhibited Ca2+-dependent contractions of the α-toxin permeabilized strips, which retain modulatory pathways both upstream and downstream from the contractile proteins but did not inhibit GTPγS-dependent contraction of the α-toxin permeabilized preparation important in upstream modulation of the contraction. Moreover, quinine did not inhibit the Ca2+-dependent contractions of the Triton X-100 permeabilized strips, which are devoid of all modulatory pathways. This suggests that quinine does not act upstream from or directly on the contractile proteins. A more likely site of action may be downstream of the contractile proteins and specifically at the coupling of the contractile proteins with the physiological endpoint of force development.
Biomarkers for the diagnosis and management of drug-induced liver injury.

There is a pressing need for new clinical tests that will help physicians distinguish drug-induced liver injury (DILI) from other, more common causes of liver injury, and that can identify which specific drug is the culprit when DILI occurs in the setting of polypharmacy. In situations where there are few alternative treatments, new tests are needed that can differentiate patients with DILI who would develop progressive liver injury if treatment is not stopped from patients who can safely continue drug therapy via "adaptation. " Although there has been little progress in developing and validating such tests, new insights into the mechanisms underlying DILI suggest that the desired biomarkers probably exist and can be discovered through the application of new technologies for blood and possibly urine analyses. Such discovery efforts will require the establishment of well-annotated serum and urine banks from prospective clinical trials of drugs capable of causing progressive liver injury.
Use of websites for disseminating health information in developing countries: an experience from Sri Lanka

The Internet is a relatively new medium for disseminating health information. Most studies on Internet usage for disseminating health information were carried out in developed countries. Very few studies were carried out in developing countries. This study was designed to investigate the quantitative and qualitative information about health related websites in Sri Lanka. Google and Yahoo search engines were used to search for Sri Lankan health websites. The key words used were 'Sri Lanka health', 'Sri Lanka medicine', Sri Lanka drug', 'Sri Lanka treatment'. Ninety eight websites were selected and data collected from 86 of these websites which were online during the period of data collection. Results show that 87.2% of websites contained less than 100 web pages. 39.5% and 20.9% of websites were owned by local non-business organizations and business organizations, respectively while 61.6% of websites were non-profitable websites. 93% of the websites were published only in English. Only 8.1% of websites provide health educational content for general public as their main content. 64.4% of websites are controlled by a Sri Lankan or a Sri Lankan organization. Quality Score is higher in the websites owned by local non-business organizations over the business organizations as well as non-profitable websites over profitable websites. Quality Score of the websites does not depend on the period of existence or whether website originated from Sri Lanka. We conclude that the total number of websites has not increased compared to the increase in internet usage during last few years in Sri Lanka. Internet is an underutilized health education tool despite the rapid growth of internet usage in Sri Lanka. Even though Internet usage has grown rapidly in most developing countries, dissemination of health information through internet may not have been developed adequately in such countries.
Combined intra- and inter-domain traffic engineering using hot-potato aware link weights optimization

A well-known approach to intradomain traffic engineering consists in finding the set of link weights that minimizes a network-wide objective function for a given intradomain traffic matrix. This approach is inadequate because it ignores a potential impact on interdomain routing due to hot-potato routing policies. This may result in changes in the intradomain traffic matrix that have not been anticipated by the link weights optimizer, possibly leading to degraded network performance. We propose a BGP-aware link weights optimization method that takes these hot-potato effects into account. This method uses the interdomain traffic matrix and other available BGP data, to extend the intradomain topology with external virtual nodes and links, on which all the well-tuned heuristics of a classical link weights optimizer can be applied. Our method can also optimize the traffic on the interdomain peering links.
Impact of Simian Immunodeficiency Virus Infection on Chimpanzee Population Dynamics

Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002–2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of −6.5% to −7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002–2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen.
Target Director Turnover in Acquisitions: A Conceptual Framework

Manuscript Type: Conceptual Research Question/Issue: Director turnover post-acquisition is a complex and multi-faceted phenomenon that needs to be examined beyond the agency lens. In this article, we examine the likelihood of non-executive director turnover in target firms following an acquisition. Research Findings/Insight: Acquisitions present an interesting case where conflict of interests may arise between shareholders and directors. This study proposes that the likelihood of target non-executive director turnover depends on the factors that determine the performance of directors in their monitoring, advisory and social roles pre-acquisition and during the acquisition process. Theoretical/Academic Implications: While there are multiple studies examining the likelihood of turnover of executive directors (TMTs) following an acquisition, there is no systematic conceptual research explaining the likelihood of turnover of non-executive directors. We draw on three theoretical perspectives--agency theory, resource based view and the social capital perspective to comprehensively investigate target non-executive director turnover postacquisition. We further clarify the boundaries of these theoretical arguments concerning their implications for target non-executive director turnover. Practitioner/Policy Implications: One of the most important tasks for the newly formed firm post-acquisition is to build the new leadership team, including a new board. In view of the important roles directors take on in modern corporations, it is critical to understand how the new board should be constituted and what members of the target firm are more likely to join that new board.
Osteoarthritis and meniscus disorders of the knee as occupational diseases of miners

Aim: To determine whether kneeling or squatting for prolonged periods is sufficiently causally associated with an increased risk of injury or degenerative disease of the knee joint as to meet the classic criteria to be considered an occupational disease of coal miners for whom these are or have been routine working postures. Method: Systematic literature searches were made for studies relating to kneeling and squatting as part of the working environment of coal mines and the role of these postures in causation of knee disorders in coal miners, analogous occupations, populations, and communities. The working environment and potentially damaging forces on the knee when kneeling or squatting were described. Papers on the incidence or prevalence of knee disorders in occupational and other groups were scored against five criteria independently by each author, and from this a single consensus score representing the overall strength of evidence given by the research was awarded. The evidence was then weighed against the criteria for an occupational disease. Results: Nineteen published papers were scored, the majority of which focussed on osteoarthritis as the outcome of interest. Few of the studies found focussed specifically on miners, and those that did tended to involve small numbers of subjects and were carried out before 1960, when the mining population was at its largest but epidemiological evidence of the risk factors for knee disorders was not well established. The non-mining studies in the review represent groups of workers with a similar or lesser kneeling content in their work. Conclusion: The papers reviewed provide sufficient evidence to conclude that work involving kneeling and/or squatting is causally associated with an increased risk of osteoarthritis of the knee. In some of the more recent epidemiologically sound studies, frequent or prolonged kneeling or squatting doubles the general risk of osteoarthritis of the knees found in the general population. This may be of particular importance in welfare and medico-legal situations. There was also evidence to suggest that lifting, in combination with kneeling/squatting, an activity also performed by miners in the course of their work, is associated with an excess risk of osteoarthritis above that attributed to kneeling/squatting alone.
Role of human TLR4 in respiratory syncytial virus-induced NF-κB activation, viral entry and replication

TLRs play a key role in innate immune defenses. It was previously reported that purified respiratory syncytial virus (RSV) fusion protein elicits an inflammatory response in hematopoietic cells, which required expression of TLR4 and its co-receptor CD14. However, a biological role of TLR4 in immunity to RSV, as initially proposed, has remained inconclusive and controversial. Here, we directly assess the role of human TLR4 and its co-receptors in NF-κB activation, viral entry and replication using intact virions rather than purified RSV components. We used HEK 293 reporter cells that are highly permissive for RSV and that either express or a lack a functional human TLR4/MD-2/CD14 complex. We demonstrate that RSV-mediated NF-κB activation, viral entry and replication are independent of the expression of a functional human TLR4/MD-2/CD14 complex and that, in turn, human TLR4 activation by LPS remains unaffected in RSV-infected cells. Thus, although isolated viral compounds such as purified RSV F protein may bind TLR4 and/or CD14, a direct interaction between intact RSV particles and the human TLR4 receptor complex does not seem to play a biological role in RSV pathogenesis.
Effects of Single-Dose Interleukin-12 Exposure on Interleukin-12 – Associated Toxicity and Interferon-g Production

Interleukin-12 (IL-12) is a key regulator of cell-mediated imhave accounted for the profound difference in toxicity. The focus of the investigation therefore shifted to the schedule munity that has therapeutic potential in cancer and infectious disease. In a previous Phase 1 dose escalation study of rhIL-12 administration. We determined that a single injection of rhIL-12 2 weeks before consecutive dosing included of a single test dose of recombinant human IL-12 (rhIL-12) followed 14 days later by cycles of five consecutive daily in the Phase 1 study, but not in the schedule of administration in the Phase 2 study, has a profound abrogating effect intravenous injections every 3 weeks, we showed that a dose level up to 500 ng/kg could be administered with acon IL-12–induced interferon-g (IFN-g) production and toxicity. This observation of schedule-dependent toxicity of IL-12 ceptable levels of safety. Based on these results, a Phase 2 study was conducted. In the Phase 2 study, however, adminhas been verified in mice, as well as nonhuman primates. In this regard, a single injection of IL-12 before consecutive istration of rhIL-12 at this same dose level resulted in severe toxicities with some patients unable to tolerate more than daily dosing protected mice and cynomolgus monkeys from acute toxicity including mortality and was associated with two successive doses. Of the 17 patients receiving rhIL-12 in the Phase 2 study, 12 patients were hospitalized and two an attenuated IFN-g response. Because of this unique biologic response, careful attention to the schedule of adminispatients died. A thorough scientific investigation to determine the cause of this unexpected toxicity failed to identify tration is required to assure safe and effective clinical development of this highly promising cytokine. any difference in the drug products used or the patient populations enrolled in the Phase 1 and Phase 2 studies that could q 1997 by The American Society of Hematology.
The newly diagnosed vestibular schwannoma: radiosurgery, resection, or observation?

OBJECT Management recommendations for patients with smaller-volume or newly diagnosed vestibular schwannomas (< 4 cm(3)) need to be based on an understanding of the anticipated natural history of the tumor and the side effects it produces. The natural history can then be compared with the risks and benefits of therapeutic intervention using a minimally invasive strategy such as stereotactic radiosurgery (SRS). METHODS The authors reviewed the emerging literature stemming from recent recommendations to "wait and scan" (observation) and compared this strategy with published outcomes after early intervention using SRS or results from matched cohort studies of resection and SRS. RESULTS Various retrospective studies indicate that vestibular schwannomas grow at a rate of 0-3.9 mm per year and double in volume between 1.65 and 4.4 years. Stereotactic radiosurgery arrests growth in up to 98% of patients when studied at intervals of 10-15 years. Most patients who select "wait and scan" note gradually decreasing hearing function leading to the loss of useful hearing by 5 years. In contrast, current studies indicate that 3-5 years after Gamma Knife surgery, 61%-80% of patients maintain useful hearing (speech discrimination score > 50%, pure tone average < 50). CONCLUSIONS Based on published data on both volume and hearing preservation for both strategies, the authors devised a management recommendation for patients with small vestibular schwannomas. When resection is not chosen by the patient, the authors believe that early SRS intervention, in contrast to observation, results in long-term tumor control and improved rates of hearing preservation.
Complete mole coexistent with a twin fetus

We report two cases of a complete hydatidiform mole coexistent with a live fetus diagnosed by DNA polymorphism analysis. A 27‐year‐old woman revealed symptoms of pre‐eclampsia and ultrasound showed multicystic tumor and placenta coexistent with a live fetus at 16 weeks’ gestation. The placenta with partly hydropic change and the fetus without anomaly were consequently evacuated. Another 30‐year‐old woman had a multicystic mass attached to a normal placenta with a 20‐week live fetus on ultrasound examination. A hysterotomy was carried out because of persistent bleeding due to placenta previa. In both cases, DNA was extracted from the placental tissue and the tumor, as well as from maternal and paternal blood. Genetic analysis demonstrated that the placental tumor consisted of only paternal origin, which is consistent with the diagnosis of complete hydatidiform mole.
Crosstalk between AMPK activation and angiotensin II-induced hypertrophy in cardiomyocytes: the role of mitochondria

AMP‐kinase (AMPK) activation reduces cardiac hypertrophy, although underlying molecular mechanisms remain unclear. In this study, we elucidated the anti‐hypertrophic action of metformin, specifically, the role of the AMPK/eNOS/p53 pathway. H9c2 rat cardiomyocytes were treated with angiotensin II (AngII) for 24 hrs in the presence or absence of metformin (AMPK agonist), losartan [AngII type 1 receptor (AT1R) blocker], Nω‐nitro‐L‐arginine methyl ester (L‐NAME, pan‐NOS inhibitor), splitomicin (SIRT1 inhibitor) or pifithrin‐α (p53 inhibitor). Results showed that treatment with metformin significantly attenuated AngII‐induced cell hypertrophy and death. Metformin attenuated AngII‐induced activation (cleavage) of caspase 3, Bcl‐2 down‐regulation and p53 up‐regulation. It also reduced AngII‐induced AT1R up‐regulation by 30% (P < 0.05) and enhanced AMPK phosphorylation by 99% (P < 0.01) and P‐eNOS levels by 3.3‐fold (P < 0.01). Likewise, losartan reduced AT1R up‐regulation and enhanced AMPK phosphorylation by 54% (P < 0.05). The AMPK inhibitor, compound C, prevented AT1R down‐regulation, indicating that metformin mediated its effects via AMPK activation. Beneficial effects of metformin and losartan converged on mitochondria that demonstrated high membrane potential (Δψm) and low permeability transition pore opening. Thus, this study demonstrates that the anti‐hypertrophic effects of metformin are associated with AMPK‐induced AT1R down‐regulation and prevention of mitochondrial dysfunction through the SIRT1/eNOS/p53 pathway.
Discovering common bug‐fix patterns: A large‐scale observational study

Background: Automatic program repair aims to reduce costs associated with defect repair. The detection and characterization of common bug‐fix patterns in software repositories play an important role in advancing this field. Aim: In this paper, we characterize the occurrence of known bug‐fix patterns in Java repositories at an unprecedented large scale. Furthermore, we propose a novel automatic technique for unveiling frequent and isolated repair actions corresponding to realistic bug fixes in Java. Method: The study was conducted for Java GitHub projects organized in two distinct data sets. The first data set (Boa) contains more than 4 million bug‐fix commits from 101 471 projects. The second data set (Defects4J) contains 369 real bug fixes from five open‐source projects. Results: We characterized the prevalence of the five most common bug‐fix patterns (identified in the work of Pan et al) in those bug fixes. The combined results showed direct evidence that developers often forget to add IF preconditions in the code.Conclusion: We discover a total of 155 repair actions from Defects4J patches and discuss 10 pervasive repair actions that occur across all analyzed Java projects. Moreover, the overall Precision and Recall values for the clustering approach were 0.62 and 0.64, respectively.
Neuroprotective Effects of Marine Algae

The marine environment is known as a rich source of chemical structures with numerous beneficial health effects. Among marine organisms, marine algae have been identified as an under-exploited plant resource, although they have long been recognized as valuable sources of structurally diverse bioactive compounds. Presently, several lines of studies have provided insight into biological activities and neuroprotective effects of marine algae including antioxidant, anti-neuroinflammatory, cholinesterase inhibitory activity and the inhibition of neuronal death. Hence, marine algae have great potential to be used for neuroprotection as part of pharmaceuticals, nutraceuticals and functional foods. This contribution presents an overview of marine algal neuroprotective effects and their potential application in neuroprotection.