Miracle-dz/UniFAR-FTUs huggingface dataset:
Harnessing antitumor immunity: Employment of tumor recall antigens to optimize the inflammatory response to cancer

The advent of immunotherapy for cancer has contributed to the era of personalized medicine for cancer. The various immunotherapy-based treatments that have been explored thus far include monoclonal antibody therapy, tumor vaccines, immune checkpoint blockade and adoptive T cell transfer, among others. The groundwork for all these immunotherapeutic modalities rests within the tumor microenvironment, specifically the immune factors that influence the tumor-drug interface. Prior to therapeutic design, the tumor microenvironmental interactions and the current barriers to successful treatment must first be understood. In the present review, it is proposed that cancer cell eradication within the tumor niche may be achieved by reprogramming of the immune microenvironment in favor of a pro-inflammatory antitumor profile at an early stage. This pro-inflammatory profile may, in turn, be influenced by tumor recall antigens, which function to stimulate the cell-mediated or humoral responses involved in antitumor immunity. These measures serve to counteract the immunotolerant state of the tumor microenvironment. Such measures are critical to therapeutic successes.
AIG rewriting using 5-input cuts

Rewriting is a common approach to logic optimization based on local transformations. Most commercially available logic synthesis tools include a rewriting engine that may be used multiple times on the same netlist during optimization. This paper presents an And-Inverter graph (AIG) based rewriting algorithm using 5-input cuts. The best circuits are pre-computed for a subset of NPN classes of 5-variable functions. Cut enumeration and Boolean matching are used to identify replacement candidates. The presented approach is expected to complement existing rewriting approaches which are usually based on 4-input cuts. The experimental results show that, by adding the new rewriting algorithm to ABC synthesis tool, we can further reduce the area of heavily optimized large circuits by 5.57% on average.
Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Intratumoral injection of CTL-stimulatory agents could provide another avenue for immunotherapy. TriMix mRNA, comprising three DC-oriented stimulatory mRNAs, was examined in mouse models and provides a rationale for clinical testing in solid and accessible tumors. Modulating the activity of tumor-infiltrating dendritic cells (TiDC) provides opportunities for novel cancer interventions. In this article, we report on our study of the uptake of mRNA by CD8α+ cross-presenting TiDCs upon its intratumoral (i.t.) delivery. We exploited this property to deliver mRNA encoding the costimulatory molecule CD70, the activation stimuli CD40 ligand, and constitutively active Toll-like receptor 4, referred to as TriMix mRNA. We show that TiDCs are reprogrammed to mature antigen-presenting cells that migrate to tumor-draining lymph nodes (TDLN). TriMix stimulated antitumor T-cell responses to spontaneously engulfed cancer antigens, including a neoepitope. We show in various mouse cancer models that i.t. delivery of TriMix mRNA results in systemic therapeutic antitumor immunity. Finally, we show that the induction of antitumor responses critically depends on TiDCs, whereas it only partially depends on TDLNs. As such, we provide a platform and a mechanistic rationale for the clinical testing of i.t. administration of TriMix mRNA. Cancer Immunol Res; 4(2); 146–56. ©2015 AACR.
Landsat-8 on-orbit and Landsat-9 pre-launch sensor radiometric characterization

Landsat-8 has been operating on-orbit for 5+ years. Its two sensors, the Operational Land Imager (OLI) and Thermal Infrared Sensor (TIRS), are continuing to produce high quality data. The OLI has been radiometrically stable at the better than 0.3% level on a band average basis for all but the shortest wavelength (443 nm) band, which has degraded about 1.3% since launch. All on-board calibration devices continue to perform well and consistently. No gaps in across track coverage exist as 100% operability of the detectors is maintained. The variability over time of detector responsivity within a band relative to the average is better than 0.05% (1 sigma), though there are occasional detectors that jump up to 1.5% in response in the Short-Wave InfraRed (SWIR) bands. Signal-to-Noise performance continues at 2-3x better than requirements, with a small degradation in the 443 nm band commensurate with the loss in sensitivity. Pre-launch error analysis, combined with the stability of the OLI indicates that the absolute reflectance calibration uncertainty is better than 3%; comparisons to ground measurements and comparisons to other sensors are consistent with this. The Landsat-8 TIRS is similarly radiometrically stable, showing changes of at most 0.3% over the mission. The uncertainty in the absolute calibration as well as the detector to detector variability are largely driven by the stray light response of TIRS. The current processing corrects most of the stray light effects, resulting in absolute uncertainties of ~1% and reduced striping. Efforts continue to further reduce the striping. Noise equivalent delta temperature is about 50 mK at typical temperatures and 100% detector operability is maintained. Landsat-9 is currently under development with a launch no earlier than December 2020. The nearly identical OLI-2 and upgraded TIRS-2 sensors have completed integration and are in the process of instrument level performance characterization including spectral, spatial, radiometric and geometric testing. Component and assembly level measurements of the OLI-2, which include spectral response, radiometric response and stray light indicate comparable performance to OLI. The first functional tests occurred in July 2018 and spatial performance testing in vacuum is scheduled for August 2018. Similarly, for TIRS-2, partially integrated instrument level testing indicated spectral and spatial responses comparable to TIRS, with stray light reduced by approximately an order of magnitude from TIRS.
Abdominal Cocoon: An Animal Model for a Complication of Peritoneal Dialysis

Objective The purpose of this work was to develop an animal model of sclerosing encapsulating peritonitis, a complication of continuous ambulatory peritoneal dialysis in which the intestines are conglomerated into an ovoid cocoonlike structure. Design Toward this end, rats were injected with a chemical irritant (household bleach) intraperitoneally. One week later, before the resultant peritonitis could cause adhesions, 10 or 25 mL of fresh whole rat blood was injected into the peritoneal cavity. Two weeks later, the effect of the treatments was evaluated by macroscopic and microscopic study. Results The irritant caused a chemical peritonitis. The subsequently injected blood clotted on the surfaces of the inflamed intestines, and contraction of the clot (syneresis) was responsible for bringing the intestinal loops together. This conglomeration was made permanent by the fibrosis evoked by the chemical peritonitis. The end result was an ovoid encapsulated mass of intestines and other viscera. Conclusion An animal model for an abdominal cocoon has been produced. It can be used for studies of the pathogenesis and prevention of this complication of peritoneal dialysis.
Structural characterization of the metamorphic basement from North Dobrogean Promontory (Romania) using geophysical well logging

Metamorphic processes, leading to mineralogical and structural changes of the rocks in response to physical (pressure, temperature) and chemical conditions, can be associated with the development of sinmetamorphic or post-metamorphic fractures. The post-metamorphic ones are directly related to tectonic stress. In addition, tectonic stress may cause the reorientation of minerals on a direction perpendicular to the stress direction, generating foliations (schistosity). This paper presents a structural analysis of the pre-Alpine metamorphic basement and its relations with the sedimentary cover by using geophysical data recorded in an exploration well located in the North Dobrogean Promontory (Romania). The analysis was based on quad-combo wireline logs, spectral gamma ray, sonic cross-dipole and borehole electrical imaging data. The imaging analysis allowed the identification and characterization of metamorphic foliations, sedimentary bedding, natural fractures and the determination of tectonic stress orientation. A brittleness index was computed by means of elastic parameters derived from density and sonic compressional and shear logs. Also, a fracture intensity characterization by using fracture area per volume of rock was conducted. The integration of geophysical well loging with mud logging and drilling data allowed us to carry out a detailed analysis of the metamorphic basement in the studied area.
University of Birmingham Stability of the CpG island methylator phenotype during glioma progression and identification of methylated loci in secondary glioblastomas

Background: Grade IV glioblastomas exist in two forms, primary ( de novo ) glioblastomas (pGBM) that arise without precursor lesions, and the less common secondary glioblastomas (sGBM) which develop from earlier lower grade lesions. Genetic heterogeneity between pGBM and sGBM has been documented as have differences in the methylation of individual genes. A hypermethylator phenotype in grade IV GBMs is now well documented however there has been little comparison between global methylation profiles of pGBM and sGBM samples or of methylation profiles between paired early and late sGBM samples. Methods: We performed genome-wide methylation profiling of 20 matched pairs of early and late gliomas using the Infinium HumanMethylation450 BeadChips to assess methylation at >485,000 cytosine positions within the human genome. Results: Clustering of our data demonstrated a frequent hypermethylator phenotype that associated with IDH1 mutation in sGBM tumors. In 80% of cases, the hypermethylator status was retained in both the early and late tumor of the same patient, indicating limited alterations to genome-wide methylation during progression and that the CIMP phenotype is an early event. Analysis of hypermethylated loci identified 218 genes frequently methylated across grade II, III and IV tumors indicating a possible role in sGBM tumorigenesis. Comparison of our sGBM data with TCGA pGBM data indicate that IDH1 mutated GBM samples have very similar hypermethylator phenotypes, however the methylation profiles of the majority of samples with WT IDH1 that do not demonstrate a hypermethylator phenotype cluster separately from sGBM samples, indicating underlying differences in methylation profiles. We also identified 180 genes that were methylated only in sGBM. Further analysis of these genes may lead to a better understanding of the pathology of sGBM vs pGBM. Conclusion: This is the first study to have documented genome-wide methylation changes within paired early/late astrocytic gliomas on such a large CpG probe set, revealing a number of genes that maybe relevant to secondary gliomagenesis.
Load-dependent destabilization of the γ-rotor shaft in FOF1 ATP synthase revealed by hydrogen/deuterium-exchange mass spectrometry

Significance FOF1, or ATP synthase, is often referred to as the “world’s smallest motor. ” Similar to automotive engines, it employs a rotating shaft that interacts with mechanical actuators. When operating a combustion engine under load, the bearings exert significant forces on the crankshaft, leading to enhanced mechanical stress. Here, we demonstrate that analogous load-dependent effects occur in molecular motors. When FOF1 pumps protons against a transmembrane gradient, the rotor shaft undergoes structural destabilization attributed to resistive forces in its apical bearing. The effect disappears when the transmembrane gradient opposing proton pumping is short-circuited by an uncoupler, as predicted by fundamental principles of mechanics. Our observations highlight fascinating parallels between engine operation on the macroscale and the nanoscale. FoF1 is a membrane-bound molecular motor that uses proton-motive force (PMF) to drive the synthesis of ATP from ADP and Pi. Reverse operation generates PMF via ATP hydrolysis. Catalysis in either direction involves rotation of the γε shaft that connects the α3β3 head and the membrane-anchored cn ring. X-ray crystallography and other techniques have provided insights into the structure and function of FoF1 subcomplexes. However, interrogating the conformational dynamics of intact membrane-bound FoF1 during rotational catalysis has proven to be difficult. Here, we use hydrogen/deuterium exchange mass spectrometry to probe the inner workings of FoF1 in its natural membrane-bound state. A pronounced destabilization of the γ C-terminal helix during hydrolysis-driven rotation was observed. This behavior is attributed to torsional stress in γ, arising from γ⋅⋅⋅α3β3 interactions that cause resistance during γ rotation within the apical bearing. Intriguingly, we find that destabilization of γ occurs only when FoF1 operates against a PMF-induced torque; the effect disappears when PMF is eliminated by an uncoupler. This behavior resembles the properties of automotive engines, where bearings inflict greater forces on the crankshaft when operated under load than during idling.
A study of three dynamic approaches to handle widely shared data in shared-memory multiprocessors

In this paper we argue that widely shared data are a more serious problem than previously recognized, and that furthermore, it is possible to provide transparent support that actually gives an advantage to accesses to widely shared data by exploiting their redundancy to improve accessibility. The GLOW extensions to cache coherence pmtocofs -previously proposedprovide such support for widely shared data by defining functionality in the network domain. However in their static form the GLOW extensions relied on the user to identify and expose widely shared data to the hardware. This approach suffers because: i) it requires modification of the programs, ii) it is not always possible to statically idenhfi the widely shared data, and iii) it is incompatible with cornmod@ hardware. To address these issues, we study three dynamic schemes to discover widely shared data at runtime. The first scheme is inspired by read-combining and is based on observing requests in the network switches the GLOW agents. The agents intercept requests whose addresses have been observed recently. This scheme tracks closely the pegormance of the static GLOW while it always outpelfomrs ordinary congestion-based readcombining. In the second scheme, the memory directory discovers widely shared data by counting the number of reaa! s between writes. Information about the widely shared nature of data is distributed to the nodes which subsequently use special wide sharing requests to access them. Simulations confrm that this scheme works well when the widely shared nature of the data is persistent over time. The third and most significant scheme is based on predicting which load instructions are going to access widely shared data. Although the implementation of this scheme is not as straighrforwani in a commodity-parts environment, it outperforms all others.
An assessment of published evaluations of requirements management tools

Context: The traditional literature review is a low cost, relatively quick but potentially ineffective method for evaluating tools. Practitioners appear to place a greater emphasis on the practical constraints of an evaluation (e.g. that it is low cost and quick) and the efficacy of the technology to the company, rather than on generic scientific results. By contrast, academia appears to place greater emphasis on theory confirmation, rigour and validity, and their literature reviews focus on literature published in peer-reviewed journals and conferences, and tend not to consider the trade and ‘grey’ literature.
The effect of organic paddy field system to soil properties

This study aims to compare the soil properties among organic paddy field and other cultivation systems. Soil profile description was done to determine the soil horizons. The characteristics of organic paddy soil were better than others as it has C-organic in horizons I and II which were 2.09% and 2.00%, respectively; black soil color in horizon I (10 YR 2/1); microbial biomass C in horizon I and II which were 98.39 μg C/g soil and 418.01 μg C/g soil respectively; and microbial biomass N in horizon I and II which were 72.59 μg N/g soil and 59.11 μg N/g soil respectively. However, the unfavorable qualities of organic paddy soil including the clay leaching from horizon I (clay 24.56%) to horizon II (clay 40.16%) and high production potential of methane (CH4) (1.81 μg CH4/kg soil/day and 1.67 μg CH4/kg soil/day, respectively in horizon I and II) need to be anticipated. The high amount of C-organic in organic paddy field affects the soil color was darker, and the increasing of clay leaching, microbial biomass C and N, and potential of CH4 production.
Contamination of environmental surfaces by genital human papillomaviruses

Objective: To investigate contamination of environmental surfaces with human papillomaviruses (HPV) DNA in two genitourinary medicine (GUM) clinics and in an on-site staff leisure and fitness centre. Methods: Samples were collected from the treatment rooms and patients' toilets of two GUM clinics situated at two hospital sites and from the toilets of the staff leisure and fitness centre on one of the sites. Samples were tested for the presence of HPV DNA by nested polymerase chain reaction (PCR), and HPV amplicons were typed by reverse line hybridisation using HPV type specific oligonucleotide probes complementary to 35 HPV types. All samples were also tested for β globin DNA by PCR in order to assess their quality. Results: HPV DNA was found to be present at more than 50% of the sites sampled in one of the GUM clinics, but was absent in the second, and also from the staff leisure and fitness centre. All HPV DNA detected was found to be cell associated. The most commonly found HPV types were 6, 11, and 16, respectively. HPV infected cells were found to be localised mainly to surfaces used predominantly by medical staff. Conclusions: This study has identified contamination of the environment of a GUM clinic. Possible sources for the contamination of the clinic toilets were from genital sites via hands to the environment. Within the treatment rooms the most likely route of HPV DNA contamination of the environment was via the doctor's gloved hands.
Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis

We used an in vitro model of human nasopharyngeal tissue in organ culture to evaluate the effects of Neisseria meningitidis on human cilia and ciliary function. Encapsulated, viable meningococci damaged ciliated epithelium of nasopharyngeal organ cultures, whereas Neisseria subflava, a commensal species, did not. Meningococcus-induced ciliary damage was due to loss of ciliated cells to which meningococci were not attached. Damage was seen with piliated and nonpiliated meningococci and did not appear to require the presence of other specific meningococcal surface proteins. Meningococcal viability was a requirement for both ciliary damage and interactions of meningococci with microvilli of nonciliated epithelial cells. That is, filter-sterilized supernatants from meningococcus-infected organ cultures, heat-killed meningococci at high inoculum, and purified meningococcal or gonococcal lipopolysaccharide at concentrations of 100 micrograms/ml did not damage ciliary activity of nasopharyngeal organ cultures. In contrast, meningococcal lipopolysaccharide at 10 micrograms/ml markedly damaged ciliary activity of human fallopian tube organ cultures, suggesting a selective toxicity of lipopolysaccharide for specific human ciliated cells. Damage to nasopharyngeal ciliated epithelium by N. meningitidis may be an important first step in meningococcal colonization of the human nasopharynx, but meningococcal lipopolysaccharide does not appear to be directly responsible for this toxicity.
Risk Factors for Extended Duration and Timing of Peak Severity of Hot Flashes

Objective To identify risk factors associated with the duration of hot flashes and the time of peak hot flash severity in mid-life women. Methods A cohort of 647 women reporting hot flashes were followed for 1–7 years, with survey data and hormone measurements. Survival analysis determined the association of risk factors with the duration of hot flashes. Linear regression determined the association of risk factors with the time of peak severity. Final models were determined through stepwise model selection. Results Average hot flash duration was 2.5 years (range: 1–33), with peak severity on average at 2.96 years (range: 1–20). Duration of hot flashes was associated with race, education, menopause status, smoking history, BMI, alcohol consumption, leisure activity levels, and levels of estradiol and progesterone. In the final model, only race, alcohol consumption, leisure activity, and menopause were retained. White women had significantly shorter hot flash durations than non-white women. Women consuming at least 12 alcoholic drinks in the previous year had a significantly shorter duration of hot flashes with a smaller effect of hot flash duration on increasing in time to peak severity compared to those who consumed less than 12 alcoholic drinks in that year. Higher serum progesterone levels were associated with later peak severity if the duration of the hot flashes was less than 2 years and an earlier peak severity otherwise. Conclusions These results suggest that some behaviors (such as moderate alcohol consumption) are associated with shorter durations of hot flashes, and that progesterone was associated with the dynamics of hot flash severity.
Low phase noise high switching ring VCO with quadrature output

In this paper, novel two loop architecture of ring type voltage controlled oscillator (VCO) with low phase noise and low power dissipation in 0.18 µm CMOS technology is presented. To reduce phase noise and power dissipation, transistors in sub-feedback loop are operated in linear and cut off region and transistors in main loop of inverter are designed for fast switching with large voltage swing to minimize the switching current. The VCO has a frequency tuning range from 2.40 to 3.45GHz. The simulated result shows a phase noise of −107.56 dBc/Hz @ 1MHz offset from 2.6 GHz center frequency with a power consumption of 32 mW.
Integration and homogeneous functions

We show that integrating a (positively) homogeneous function f on a compact domain Ω ⊂ Rn reduces to integrating a related function on the boundary ∂Ω. The formula simplifies when the boundary ∂Ω is determined by homogeneous functions. Similar results are also presented for integration of exponentials and logarithms of homogeneous functions.
Magnetic Anomaly Interpretation of the Northern Congo Craton Boundary: Results from Depth Estimation and 2.5D Modeling

A magnetic-based geophysical study was performed across the southern part of Cameroon to investigate the boundary between the Archean Congo craton and the Pan-African metamorphic belt. Magnetic gradient techniques including Euler deconvolution and Tilt derivative have been applied to an aeromagnetic data profile to determine the depth of sources and their lateral extension. 2.5D magnetic modeling shows that the prominent magnetic positive anomalies observed on total magnetic map of south Cameroon are produced by deep and strongly magnetic bodies under the Pan-African formations mainly an important dyke formation structure with a high susceptibility of 0.041 (SI units), at an average depth of 4148 m and with a lateral extension of about 10 km. These bodies are interpreted to have emplaced at high crustal levels in a continental collision zone and were subsequently metamorphosed at granulite grade conditions, during the Pan-African orogeny about 620 Ma ago.