Miracle-dz/UniFAR-FTUs huggingface dataset:
High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer: consequences of different high-risk CTV sizes

Purpose To evaluate conventional brachytherapy (BT) plans using dose-volume parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are generated. Material and methods Fifty-five clinical high-dose-rate BT plans from 14 cervical cancer patients were retrospectively studied. All conventional plans were created using MRI with titanium tandem-and-ovoid applicator (T&O) for delivery. For each conventional plan, a MRIG-CBT plan was retrospectively generated using hybrid inverse optimization. Three categories of high risk (HR)-CTV were considered based on volume: non-bulky (< 20 cc), low-bulky (> 20 cc and < 40 cc) and bulky (≥ 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and D0.1cc of rectum, bladder, and sigmoid colon were analyzed. Results Tumor coverage (HR-CTV D90) of the conventional plans was considerably affected by the HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large targets (> 40 cc) when using T&O applicator approach. Conclusions MRIG-CBT plans displayed considerable improvement for tumor coverage and OAR sparing over conventional treatment. When the HR-CTV volume exceeded 40 cc, its improvements were diminished when using a conventional intracavitary applicator.
Trafficking, Persistence, and Activation State of Adoptively Transferred Allogeneic and Autologous Simian Immunodeficiency Virus-Specific CD8+ T Cell Clones during Acute and Chronic Infection of Rhesus Macaques

Despite multiple lines of evidence suggesting their involvement, the precise role of CD8+ T cells in controlling HIV replication remains unclear. To determine whether CD8+ T cells can limit retroviral replication in the absence of other immune responses, we transferred 1–13 × 109 allogeneic in vitro expanded SIV-specific CD8+ T cell clones matched for the relevant restricting MHC-I allele into rhesus macaques near the time of i.v. SIV challenge. Additionally, in vitro expanded autologous SIV-specific CD8+ T cell clones were infused 4–9 mo postinfection. Infused cells did not appreciably impact acute or chronic viral replication. The partially MHC-matched allogeneic cells were not detected in the blood or most tissues after 3 d but persisted longer in the lungs as assessed by bronchoalveolar lavage (BAL). Autologous cells transferred i.v. or i.p. were found in BAL and blood samples for up to 8 wk postinfusion. Interestingly, despite having a nominally activated phenotype (CD69+HLA-DR+), many of these cells persisted in the BAL without dividing. This suggests that expression of such markers by T cells at mucosal sites may not reflect recent activation, but may instead identify stable resident memory T cells. The lack of impact following transfer of such a large number of functional Ag-specific CD8+ T cells on SIV replication may reflect the magnitude of the immune response required to contain the virus.
PROBABILITY OF SPONTANEOUS ABORTION IN MULTIPARAE.

Summary. Data on abortion incidence in reproductive histories of multiparae are re-analysed to obtain the probability of abortion at a given pregnancy. Division of the data statistically into abortion-prone and abortion-resistant components indicates (a) that there is a greater proportion of the former in the higher pregnancy groups; it is suggested that this may be partly responsible for the apparent increase in abortion incidence with parity and age; (b) that in the abortion-resistant component the probability of abortion at each pregnancy remains constant at about 0\m=. \12;(c) that in the abortion-prone component the probability of abortion diminishes from 0\m=. \76 in the fourth pregnancy to 0\m=. \40in the ninth. These findings are discussed.
Tyrosine 763 of the murine granulocyte colony-stimulating factor receptor mediates Ras-dependent activation of the JNK/SAPK mitogen-activated protein kinase pathway

The receptor for granulocyte colony-stimulating factor (G-CSF) can mediate differentiation and proliferation of hemopoietic cells. A proliferative signal is associated with activation of the ERK mitogen-activated protein kinase (MAPK) pathway. To determine whether other MAPK pathways are activated by G-CSF signalling, we have investigated activation of JNK/SAPK in cells proliferating in response to G-CSF. Here we show that G-CSF and interleukin-3 activate JNK/SAPK in two hemopoietic cell lines. The region of the G-CSF receptor required for G-CSF-induced JNK/SAPK activation is located within the C-terminal 68 amino acids of the cytoplasmic domain, which contains Tyr 763. Mutation of Tyr 763 to Phe completely blocks JNK/SAPK activation. However, the C-terminal 68 amino acids are not required for ERK2 activation. We show that activation of JNK/SAPK, like that of ERK2, is dependent on Ras but that higher levels of Ras-GTP are associated with activation of JNK/SAPK than with activation of ERK2. Two separate functional regions of the G-CSF receptor contribute to activation of Ras. The Y763F mutation reduces G-CSF-induced Ras activation from 30 to 35% Ras-GTP to 10 to 13% Ras-GTP. Low levels of Ras activation (10 to 13% Ras-GTP), which are sufficient for ERK2 activation, require only the 100 membrane-proximal amino acids. High levels of Ras-GTP provided by expression of oncogenic Ras are not sufficient to activate JNK/SAPK. An additional signal, also mediated by Tyr 763, is required for activation of JNK/SAPK.
Narcolepsy: A review of evidence for autoimmune diathesis

Sporadic narcolepsy with cataplexy is a disabling disease that is strongly associated with the major histocompatibility class II allele HLA DQB1*0602 and is characterized by profound reduction in the cerebrospinal fluid (CSF) concentration of hypocretin 1 levels. This article provides a comprehensive review of the evidence that neurologic autoimmunity is the pathogenic basis of narcolepsy with cataplexy. Despite this evidence, specific antibody markers for narcolepsy have been elusive. Clinical trials using intravenous immunoglobulin infusions in recent onset narcolepsy with cataplexy have led to improvement in cataplexy in some patients. Future research must focus on elucidation of immune markers and early ameliorative treatments for narcolepsy.
Latitude of the study place and age of the patient are associated with incidence of mediastinitis and microbiology in open-heart surgery: a systematic review and meta-analysis

Objective We aimed to summarize the pooled frequency of mediastinitis following open-heart surgery caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria. Design This study was a systematic review and a meta-analysis of prospective and retrospective cohort studies. Materials and methods We searched the literature, and a total of 97 cohort studies were identified. Random-effect model was used to synthesize the results. Heterogeneity between studies was examined by subgroup and meta-regression analyses, considering study and patient-level variables. Small-study effect was evaluated. Results Substantial heterogeneity was present. The estimated incidence of mediastinitis evaluated from 97 studies was 1.58% (95% confidence intervals [CI] 1.42, 1.75) and that of Gram-positive bacteria, Gram-negative bacteria, and MRSA bacteria evaluated from 63 studies was 0.90% (95% CI 0.81, 1.21), 0.24% (95% CI 0.18, 0.32), and 0.08% (95% CI 0.05, 0.12), respectively. A meta-regression pinpointed negative association between the frequency of mediastinitis and latitude of study place and positive association between the frequency of mediastinitis and the age of the patient at operation. Multivariate meta-regression showed that prospective cohort design and age of the patients and latitude of study place together or in combination accounted for 17% of heterogeneity for end point frequency of mediastinitis, 16.3% for Gram-positive bacteria, 14.7% for Gram-negative bacteria, and 23.3% for MRSA bacteria. Conclusion Evidence from this study suggests the importance of latitude of study place and advanced age as risk factors of mediastinitis. Latitude is a marker of thermally regulated bacterial virulence and other local surgical practice. There is concern of increasing risk of mediastinitis and of MRSA in elderly patients undergoing sternotomy.
Mesoscale simulation of a very heavy rainfall event over mumbai, using the weather research and forecasting (wrf) model

The simulation of a severe weather phenomenon, in this case the unprecedented heavy rainfall over Mumbai in India on July 26, 2005, was selected for this study. The mesoscale numerical weather prediction model used here utilized the Advanced Research Weather Research Forecast model (version 3.0.1), as developed at the National Center for Atmospheric Research (NCAR) in the USA. The study used the Kian-Fritsch (KF), Betts–Miller–Janjic (BMJ) and Grell–Devenyi ensemble (GD) cumulus parameterization schemes across three nested domain configurations. The precipitation simulation results were compared with rainfall observation data from the Tropical Rainfall Measuring Mission. The NCEP analyses, with a 1 1 degree resolution and 26 levels, were utilized to verify the simulation’s resulting large-scale circulation pattern, moisture content and relative humidity fields. The 24-hour simulated cumulative rainfall data was created from the different measurements taken at 0300 UTC on July 27, 2005 over Mumbai. It can be observed that the maximum rainfall simulated from the KF, BMJ and GD schemes at 0000 UTC on July 25, 2005, under the initial conditions, was 48, 64 and 32 cm respectively, while the TRMM shows a maximum rainfall of 32 cm at that time. The centre of maximum rainfall was reduced drastically for all 0000 UTC measurements taken on July 26 (the following day), where the initial condition experiments simulated a rainfall amount of only 16 cm. The specific location of the intense rainfall around Mumbai was very-well simulated in the BMJ for 0000 UTC July 25 initial conditions.
Systematic Review and Meta-Analysis of Linezolid versus Daptomycin for Treatment of Vancomycin-Resistant Enterococcal Bacteremia

ABSTRACT Limited therapeutic options exist for the treatment of vancomycin-resistant Enterococcus (VRE) bacteremia; the most commonly used are daptomycin and linezolid. We attempted a systematic review and meta-analysis of the comparative efficacy of those two agents. Studies comparing daptomycin to linezolid treatment for VRE bacteremia, published until August 2012, were identified from the MEDLINE, EMBASE, CENTRAL, ISI Web of Science, and SCOPUS databases. All comparative studies on patients older than 18 years of age that provided mortality data were considered eligible for this systematic review and meta-analysis. Τhe primary outcome of the meta-analysis was 30-day all-cause mortality. Ten retrospective studies including 967 patients were identified. Patients treated with daptomycin had significantly higher 30-day all-cause mortality (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08 to 2.40) and infection-related mortality (OR, 3.61; 95% CI, 1.42 to 9.20) rates than patients treated with linezolid. When data from all 10 studies were combined, overall mortality was also significantly increased among patients treated with daptomycin (OR, 1.41; 95% CI, 1.06 to 1.89). These findings were confirmed when odds ratios adjusted for potential confounders were pooled. Relapse rates among patients treated with daptomycin were also higher (OR, 2.51; 95% CI, 0.94 to 6.72), although this difference did not reach statistical significance. Adverse event rates were not significantly different between the two groups. Notwithstanding the absence of randomized prospective data, available evidence suggests that mortality rates may be higher with daptomycin than with linezolid among patients treated for VRE bacteremia.
Health-protective behaviours and risk of fall-related hip fractures: a population-based case-control study.

BACKGROUND Fall-related hip fractures are one of the most common causes of disability and mortality in older age. The study aimed to quantify the relationship between lifestyle behaviours and the risk of fall-related hip fracture in community-dwelling older people. The purpose was to contribute evidence for the promotion of healthy ageing as a population-based intervention for falls injury prevention. METHODS A case-control study was conducted with 387 participants, with a case-control ratio of 1:2. Incident cases of fall-related hip fracture in people aged 65 and over were recruited from six hospital sites in Brisbane, Australia, in 2003-04. Community-based controls, matched by age, sex and postcode, were recruited via electoral roll sampling. A questionnaire designed to assess lifestyle risk factors, identified as determinants of healthy ageing, was administered at face-to-face interviews. RESULTS Behavioural factors which had a significant independent protective effect on the risk of hip fracture included never smoking [adjusted odds ratio (AOR): 0.33 (0.12-0.88)], moderate alcohol consumption in mid- and older age [AOR: 0.49 (0.25-0.95)], not losing weight between mid- and older age [AOR: 0.36 (0.20-0.65)], playing sport in older age [AOR: 0.49 (0.29-0.83)] and practising a greater number of preventive medical care [AOR: 0.54 (0.32-0.94)] and self-health behaviours [AOR: 0.56 (0.33-0.94)]. CONCLUSION With universal exposures, clear associations and modifiable behavioural factors, this study has contributed evidence to reduce the major public health burden of fall-related hip fractures using readily implemented population-based healthy ageing strategies.
Religion's evolutionary landscape: Counterintuition, commitment, compassion, communion

Religion is not an evolutionary adaptation per se, but a recurring cultural by-product of the complex evolutionary landscape that sets cognitive, emotional, and material conditions for ordinary human interactions. Religion exploits only ordinary cognitive processes to passionately display costly devotion to counterintuitive worlds governed by supernatural agents. The conceptual foundations of religion are intuitively given by task-specific panhuman cognitive domains, including folkmechanics, folkbiology, and folkpsychology. Core religious beliefs minimally violate ordinary notions about how the world is, with all of its inescapable problems, thus enabling people to imagine minimally impossible supernatural worlds that solve existential problems, including death and deception. Here the focus is on folkpsychology and agency. A key feature of the supernatural agent concepts common to all religions is the triggering of an “Innate Releasing Mechanism,” or “agency detector,” whose proper (naturally selected) domain encompasses animate objects relevant to hominid survival – such as predators, protectors, and prey – but which actually extends to moving dots on computer screens, voices in wind, and faces on clouds. Folkpsychology also crucially involves metarepresentation, which makes deception possible and threatens any social order. However, these same metacognitive capacities provide the hope and promise of open-ended solutions through representations of counterfactual supernatural worlds that cannot be logically or empirically verified or falsified. Because religious beliefs cannot be deductively or inductively validated, validation occurs only by ritually addressing the very emotions motivating religion. Cross-cultural experimental evidence encourages these claims.
A corpus based investigation of morphological disagreement in anaphoric relations

This paper investigates the causes of the comparatively low success rates in ﬁnding the antecedents of plural pronouns as compared to ﬁnding antecedents of singular pronouns. We are trying to show experimentally that considering morphological agreement as a strong constraint in pronoun resolution results in the erroneous interpretation of almost a quarter of the plural pronouns. The work is based on analysing sample texts from the British National Corpus and online technical manuals
Extra-Classical Tuning Predicts Stimulus-Dependent Receptive Fields in Auditory Neurons

The receptive fields of many sensory neurons are sensitive to statistical differences among classes of complex stimuli. For example, excitatory spectral bandwidths of midbrain auditory neurons and the spatial extent of cortical visual neurons differ during the processing of natural stimuli compared to the processing of artificial stimuli. Experimentally characterizing neuronal nonlinearities that contribute to stimulus-dependent receptive fields is important for understanding how neurons respond to different stimulus classes in multiple sensory modalities. Here we show that in the zebra finch, many auditory midbrain neurons have extra-classical receptive fields, consisting of sideband excitation and sideband inhibition. We also show that the presence, degree, and asymmetry of stimulus-dependent receptive fields during the processing of complex sounds are predicted by the presence, valence, and asymmetry of extra-classical tuning. Neurons for which excitatory bandwidth expands during the processing of song have extra-classical excitation. Neurons for which frequency tuning is static and for which excitatory bandwidth contracts during the processing of song have extra-classical inhibition. Simulation experiments further demonstrate that stimulus-dependent receptive fields can arise from extra-classical tuning with a static spike threshold nonlinearity. These findings demonstrate that a common neuronal nonlinearity can account for the stimulus dependence of receptive fields estimated from the responses of auditory neurons to stimuli with natural and non-natural statistics.
Sequence-specific DNA binding by MYC/MAX to low-affinity non-E-box motifs

The MYC oncoprotein regulates transcription of a large fraction of the genome as an obligatory heterodimer with the transcription factor MAX. The MYC:MAX heterodimer and MAX:MAX homodimer (hereafter MYC/MAX) bind Enhancer box (E-box) DNA elements (CANNTG) and have the greatest affinity for the canonical MYC E-box (CME) CACGTG. However, MYC:MAX also recognizes E-box variants and was reported to bind DNA in a “non-specific” fashion in vitro and in vivo. Here, in order to identify potential additional non-canonical binding sites for MYC/MAX, we employed high throughput in vitro protein-binding microarrays, along with electrophoretic mobility-shift assays and bioinformatic analyses of MYC-bound genomic loci in vivo. We identified all hexameric motifs preferentially bound by MYC/MAX in vitro, which include the low-affinity non-E-box sequence AACGTT, and found that the vast majority (87%) of MYC-bound genomic sites in a human B cell line contain at least one of the top 21 motifs bound by MYC:MAX in vitro. We further show that high MYC/MAX concentrations are needed for specific binding to the low-affinity sequence AACGTT in vitro and that elevated MYC levels in vivo more markedly increase the occupancy of AACGTT sites relative to CME sites, especially at distal intergenic and intragenic loci. Hence, MYC binds diverse DNA motifs with a broad range of affinities in a sequence-specific and dose-dependent manner, suggesting that MYC overexpression has more selective effects on the tumor transcriptome than previously thought.
Dynamic Scheduling and Pricing in Wireless Cloud Computing

In this paper, we consider a wireless cloud computing system in which the service provider operates a data center and provides cloud services to its subscribers at dynamic prices. We propose a joint optimization of scheduling and pricing decisions for delay-tolerant batch services to maximize the service provider's long-term profit. Unlike the existing research on jointly scheduling and pricing that focuses on static or asymptotic analysis, we focus on a dynamic setting and develop a provably-efficient Dynamic Scheduling and Pricing (Dyn-SP) algorithm which, without the necessity of predicting the future information, can be applied to an arbitrarily random environment that may follow an arbitrary trajectory overtime. We prove that, compared to the optimal offline algorithm with future information, Dyn-SP produces a close-to-optimal average profit while bounding the job queue length in the data center. We perform a trace-based simulation study to validate Dyn-SP. In particular, we show both analytically and numerically that a desired tradeoff between the profit and queueing delay can be obtained by appropriately tuning the control parameter. Our results also indicate that, compared to the existing algorithms which neglect demand-side management, cooling system energy consumption, and/or the queue length information, Dyn-SP achieves a higher average profit while incurring (almost) the same average queueing delay.
Assessing Toxicity and Nuclear and Mitochondrial DNA Damage Caused by Exposure of Mammalian Cells to Lunar Regolith Simulants

Previous missions to the lunar surface implicated potential dangers of lunar soil. In future explorations, astronauts may spend weeks or months on the Moon, increasing the risk of inhaling lunar dust. In an effort to understand the biological impact of lunar regolith, cell cultures derived from lung or neuronal cells were challenged with lunar soil simulants to assess cell survival and genotoxicity. Lunar soil simulants were capable of causing cell death and DNA damage in neuronal and lung cell lines, and freshly crushed lunar soil simulants were more effective at causing cell death and DNA damage than were simulants as received from the supplier. The ability of the simulants to generate reactive oxygen species in aqueous suspensions was not correlated with their cytotoxic or genotoxic affects. Furthermore, the cytotoxicity was not correlated with the accumulation of detectable DNA lesions. These results determine that lunar soil simulants are, with variable activity, cytotoxic and genotoxic to both neuronal and lung‐derived cells in culture.
An Efficient Softcore Multiplier Architecture for Xilinx FPGAs

This work presents an efficient implementation of a softcore multiplier, i.e., a multiplier architecture which can be efficiently mapped to the slice resources of modern Xilinx FPGAs. Instead of dividing the multiplication into the generation of partial products and the summation using a compressor tree, as done in modern multipliers, an array-like architecture is proposed. Each row of the array generates a partial product which is directly added to results of previous rows using the fast carry chain. A radix-4 Booth encoding/decoding is used to reduce the I/O count of the partial product generation which makes it possible to map both, the Booth encoder and decoder, into a single 6-input look up table (LUT). Like a conventional Booth multiplier, this nearly halves the number of rows compared to a ripple carry array multiplier. In addition, the compressor tree is completely avoided and an efficient and regular structure retains that uses up to 50% less slice resources compared to previous approaches and offers a multiply accumulate (MAC) operation without extra resources.