Miracle-dz/UniFAR-FTUs huggingface dataset:
Dimensionality of Motion and Binding Valency Govern Receptor–Ligand Kinetics As Revealed by Agent-Based Modeling

Mathematical modeling and computer simulations have become an integral part of modern biological research. The strength of theoretical approaches is in the simplification of complex biological systems. We here consider the general problem of receptor–ligand binding in the context of antibody–antigen binding. On the one hand, we establish a quantitative mapping between macroscopic binding rates of a deterministic differential equation model and their microscopic equivalents as obtained from simulating the spatiotemporal binding kinetics by stochastic agent-based models. On the other hand, we investigate the impact of various properties of B cell-derived receptors—such as their dimensionality of motion, morphology, and binding valency—on the receptor–ligand binding kinetics. To this end, we implemented an algorithm that simulates antigen binding by B cell-derived receptors with a Y-shaped morphology that can move in different dimensionalities, i.e., either as membrane-anchored receptors or as soluble receptors. The mapping of the macroscopic and microscopic binding rates allowed us to quantitatively compare different agent-based model variants for the different types of B cell-derived receptors. Our results indicate that the dimensionality of motion governs the binding kinetics and that this predominant impact is quantitatively compensated by the bivalency of these receptors.
Intrinsic properties of a complete sample of HETE-2 Gamma-ray bursts A measure of the GRB rate in the Local Universe

Aims: Taking advantage of the forthcoming Catalog of the HETE-2 mission, the aim of this paper is to evaluate the main properties of HETE-2 GRBs - the E_peak, the T_90 and the E_iso - in their source frames and to derive their unbiased distribution. Methods: We first construct a complete sample containing all the bursts localized by the WXM on-board HETE-2, which are selected with a uniform criterion and whose observed parameters can be constrained. We then derive the intrinsic E_peak, T_90 and E_iso distributions using their redshift when it is available, or their pseudo-redshift otherwise. We finally compute the number of GRB (N_Vmax) within the visibility volume (V_max) of each GRB, in order to derive a weight for each detected burst accounting both for the detection significance and the star formation history of the universe. Results: The unbiased distributions obtained clearly show the predominence of X-ray flashes (XRFs) in the global GRB population. We also derive the rate of local GRBs: R0^H2 > 11 Gpc-3 yr-1, which is intermediate between the local rate obtained by considering only the high-luminosity bursts (~1 Gpc-3 yr-1) and that obtained by including the low-luminosity bursts (>200 Gpc-3 yr-1).
FECUNDITY AND LONGEVITY OF DIAPETIMORPHA INTROITA ( CRESSON ) ( HYMENOPTERA : ICHNEUMONIDAE ) REARED ON ARTIFICIAL DIETS : EFFECTS OF A LIPID EXTRACT FROM HOST PUPAE AND CULTURE MEDIA CONDITIONED WITH AN INSECT CELL LINE

Diapetimorpha introita (Cresson) (Hymenoptera: Ichneumonidae) is a native ectoparasitoid of Spodoptera spp. pupae. This parasitoid has been reared in the laboratory on an artificial diet devoid of any insect host components. However, wasps reared on this artificial diet had reduced fecundity. Efforts to increase fecundity included supplementing the diet with cell culture media conditioned with a cell line from ovaries of the fall armyworm, S. frugiperda, in one experiment and fortifying the diet with lipids extracted from pupae of S. frugiperda in a second experiment. In the first experiment, differences in mean oviposition and mean longevity among females reared on the artificial control diet ( artificial diet ), cell line-supplemented diet ( Sf9Cell ), and natural host ( Host ) were not significant. However, during the first 10 days of oviposition, Sf9Cell -reared females oviposited at a rate similar to the Host -reared parasitoids and at a rate faster than artificial -diet reared females. In the second experiment, females reared on the diet with added host lipid ( host lipid ) laid significantly more eggs than females on the artificial diet , however , longevity was not significantly affected by diet treatment. We conclude that total egg production by D. introita was improved on artificial diet supplemented with lipids from the natural host but was not increased by the addition of materials produced by an ovarial cell line derived from S. frugiperda. Future research efforts should focus on increasing fecundity of wasps reared on the artificial diet by identifying the lipid(s) or lipid-soluble material in the host pupal extract that is responsible for enhancing egg production in D. introita females.
Neural progenitor cells transplanted into the uninjured brain undergo targeted migration after stroke onset

Endogenous neural stem cells normally reside in their niche, the subventricular zone, in the uninjured rodent brain. Upon stroke, these cells become more proliferative and migrate away from the subventricular zone into the surrounding parenchyma. It is not known whether this stroke‐induced behavior is due to changes in the niche or introduction of attractive cues in the infarct zone, or both. A related question is how transplanted neural stem cells respond to subsequent insults, including whether exogenous stem cells have the plasticity to respond to subsequent injuries after engraftment. We addressed this issue by transplanting neural progenitor cells (NPCs) into the uninjured brain and then subjecting the animal to stroke. We were able to follow the transplanted NPCs in vivo by labeling them with superparamagnetic iron oxide particles and imaging them via high‐resolution magnetic resonance imaging (MRI) during engraftment and subsequent to stroke. We find that transplanted NPCs that are latent can be activated in response to stroke and exhibit directional migration into the parenchyma, similar to endogenous neural NPCs, without a niche environment. © 2007 Wiley‐Liss, Inc.
Technique to study three‐dimensional spatial arrangement of synaptic vesicles using data from single sections

Synaptic vesicles are membrane‐bound organelles storing neurotransmitters in presynaptic terminals and releasing them into the synaptic cleft. Coordinated movements of synaptic vesicles relate to synaptic function and their spatial arrangement can provide useful information about the activity of a synapse. This article presents a technique to extract quantitative information about three‐dimensional (3D) spatial arrangement of synaptic vesicles from measurements performed on single ultrathin random sections of a presynaptic terminal. The technique presumes quantification of a 2D density as well as 2D spatial pattern formed by vesicle profiles using a minimum spanning tree (MST) algorithm, in digitized micrographs of a presynaptic terminal. Further, original software was used to simulate a 3D spatial arrangement of synaptic vesicles and their random sectioning. A 3D density and pattern of synaptic vesicles were used as basic input parameters of the model, while a 2D density and MST quantities for vesicle profiles served as output, model‐derived parameters allowing one to compare and fit simulated distributions to experimental ones. Pilot simulations performed to check the validity of the technique have shown that a 2D density and MST quantities of vesicle profiles closely relate to a 3D density and spatial pattern of vesicles. The technique was demonstrated in the analysis of spatial distribution of synaptic vesicles in axonal terminals forming asymmetric synaptic densities in the stratum radiatum of the CA1 subfield of the murine hippocampus. Microsc. Res. Tech. 62:201–210, 2003. © 2003 Wiley‐Liss, Inc.
TP Receptor Antagonism: A New Concept in Atherothrombosis and Stroke Prevention

Conventional antiplatelet agents such as aspirin, ticlopidine, and clopidogrel are currently used in the prevention of cardiovascular and cerebrovascular events. However, side effects such as bleeding complications and gastrointestinal disorders and, in some patients, resistance have made the development of new agents desirable. Recently, thromboxane receptors (thromboxane and prostaglandin endoperoxide PGG2-PGH2 receptors) called TP receptors have received increasing attention. These receptors are membrane-bound G-coupled receptors found not only on platelets but also on macrophages, monocytes, vascular endothelial cells, and smooth muscle cells. Antagonists of TP receptors have advantages over aspirin as they not only block the effect of thromboxane A2 on platelets, but also inhibit other ligands such as prostaglandin endoperoxides and isoprostanes. Given the distribution of TP receptors in platelets, in circulating inflammatory cells, in the vascular wall and in atherosclerotic plaques, they also inhibit the effects of thromboxane A2 over TP receptors on vascular cells or in the plaque. Terutroban (Triplion® or S18886), a new oral specific TP receptor antagonist, has, aside from being an antithrombotic agent, important vascular properties. It improves endothelial function and has an antiatherosclerotic effect. The potential therapeutic applications of terutroban in the prevention of atherothrombosis, particularly in the cerebrovascular and cardiovascular fields including stroke and coronary artery disease, are based on a number of convincing experimental animal and clinical studies. A large trial is currently comparing the efficacy and safety of terutroban versus aspirin in secondary prevention of cardiovascular events in patients who have suffered a stroke or transient ischemic attack (PERFORM Study).
Stem cell transplantation as a therapeutic approach to organ failure.

BACKGROUND Stem cell transplantation is one of the next great frontiers for surgery. Stem cells, which are undifferentiated and self-renewing, have shown the ability to differentiate into cardiomyocytes, as well as many other cell types for potential therapeutic use by surgeons. MATERIALS AND METHODS As a result, stem cells have the potential to undo irreversible cellular damage, something traditional therapies could not cure. However, numerous issues must be resolved to permit safe and effective clinical application of stem cell therapy. These include the interpretation of cellular labeling, the origin of replicating myocytes, the homing mechanism of stem cells, and the differentiation process. RESULTS Successful translational research will depend on precise delivery of these cells in real time to the area of interest, e.g., the spinal cord, liver, or heart. Surgeons will be better able to excise and replace/regrow, rather than excise alone. As such, a basic understanding of stem cell biology will benefit the surgeon scientist and clinical surgeon. CONCLUSIONS The review: 1) discusses myocardial regeneration; 2) defines and categorizes stem cells; 3) presents evidence of stem cell transdifferentiation into cardiomyocytes; and, 4) delineates the therapeutic potential of stem cells in the treatment of ischemic heart disease.
The COLON study : Co lorectal cancer : L ongitudinal , O bservational study on N utritional and lifestyle factors that may influence colorectal tumour recurrence , survival and quality of life

Background: There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and quality of life. This paper describes the background and design of the “COlorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life” – COLON – study. The main aim of this study is to assess associations of diet and other lifestyle factors, with colorectal cancer recurrence, survival and quality of life. We extensively investigate diet and lifestyle of colorectal cancer patients at diagnosis and during the following years; this design paper focusses on the initial exposures of interest: diet and dietary supplement use, body composition, nutrient status (e.g. vitamin D), and composition of the gut microbiota. Methods/Design: The COLON study is a multi-centre prospective cohort study among at least 1,000 incident colorectal cancer patients recruited from 11 hospitals in the Netherlands. Patients with colorectal cancer are invited upon diagnosis. Upon recruitment, after 6 months, 2 years and 5 years, patients fill out food-frequency questionnaires; questionnaires about dietary supplement use, physical activity, weight, height, and quality of life; and donate blood samples. Diagnostic CT-scans are collected to assess cross-sectional areas of skeletal muscle, subcutaneous fat, visceral fat and intermuscular fat, and to assess muscle attenuation. Blood samples are biobanked to facilitate future analyse of biomarkers, nutrients, DNA etc. Analysis of serum 25-hydroxy vitamin D levels, and analysis of metabolomic profiles are scheduled. A subgroup of patients with colon cancer is asked to provide faecal samples before and at several time points after colon resection to study changes in gut microbiota during treatment. For all patients, information on vital status is retrieved by linkage with national registries. Information on clinical characteristics is gathered from linkage with the Netherlands Cancer Registry and with hospital databases. Hazards ratios will be calculated for dietary and lifestyle factors at diagnosis in relation to recurrence and survival. Repeated measures analyses will be performed to assess changes over time in dietary and other factors in relation to recurrence and survival.
Enhanced Recognition of Acute Lymphoblastic Leukemia Cells in Microscopic Images based on Feature Reduction using Principle Component Analysis

Purpose- Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer of white blood cells which is categorized into three types of L1, L2, and L3. It is usually detected through screening of blood and bone marrow smears by pathologists. Since manual detection is time-consuming and boring, computer-based systems are preferred for convenient detection. The rigorous similarity between morphology of ALL types and that of normal, reactive and atypical lymphocytes, makes the automatic recognition a challenging problem. In this paper, we tried to improve the sensitivity of detection based on principle component analysis (PCA). Methods- After segmenting cell nucleus using fuzzy c-means clustering algorithm, several geometric and statistical features are extracted. Then the feature space dimensionality is reduced based on (PCA). The first 8 components of the feature space are applied to support vector machine (SVM) classifier. Then the cancerous and lymphocyte cells are classified into their subtypes. Results- For evaluating the proposed method, we used an expert pathologist’s classification as a reference. Classification was evaluated by three parameters: sensitivity, specificity and accuracy. A comparison with our previous work showed that using dimensionality reduced feature space based on PCA, instead of using individually selected features, improved the average sensitivity and precision of classification more than 10%. Conclusion- The results show that proposed algorithm performs better than our previous work. Its acceptable performance for the diagnosis of ALL and its subtypes as well as other lymphocyte types makes it an assistant diagnostic tool for pathologists.
Cancer Incidence among Swedish Patients Exposed to Radioactive Thorotrast: A Forty-Year Follow-up Survey

Abstract Nyberg, U. , Nilsson, B. , Travis, L. B. , Holm, L-E. and Hall, P. Cancer Incidence among Swedish Patients Exposed to Radioactive Thorotrast: A Forty-Year Follow-up Survey. Radiat. Res. 157, 419–425 (2002). Thorotrast is an α-particle-emitting radiological contrast medium that caused chronic exposure to internal α-particle radiation when it was administered systemically. Cancer incidence in 432 Swedish patients exposed to Thorotrast was evaluated by computerized linkage of the cohort with the Swedish Cancer Register. Standardized incidence ratios (SIRs) were calculated as the ratio of observed cases in the cohort to expected cases in the general population. A total of 170 cancers occurring in 152 individuals were reported, whereas only 57 cases were expected. The SIR was significantly increased for cancer at all sites (3.0), with the largest excesses noted for primary liver and gallbladder cancer (SIR = 39.2). Other significantly elevated risks were observed for liver cancer not specified as primary, small intestine cancer, stomach cancer, leukemia, kidney cancer, CNS tumors, and pancreatic cancer. Among women, there was a significantly increased risk for lung cancer, based on a small number. Our results show that cumulative radiation exposure is directly related to carcinogenesis in the liver and gallbladder, which is consistent with earlier findings. In addition, there may be a relationship between radiation exposure and the development of other solid tumors.
p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer.

BACKGROUND Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. PATIENTS AND METHODS Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. RESULTS p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. CONCLUSIONS We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.
A Short-Stroke Permanent Magnet Aerospace Actuator with High Force-to-Mass Ratio

High energy density rare earth permanent magnets have catalysed substantial improvements in the performance of linear actuators. The design of such a device using the 2D finite element method coupled to a particle swarm optimisation is described. A particular attribute of the design is that the pole shape has been optimised to ensure restoring magnetic forces act on the effector at zero current. A mathematical model is developed to study the dynamic performance of the device. A prototype was constructed from cobalt iron laminates and high energy product permanent magnets. Electrical winding tests and force measurements for the prototype are presented and compared with modelled values
Growth factors involved in aqueous humour-induced lens cell proliferation

Lens epithelial cell proliferation is regulated by growth factors in the aqueous humour of the eye. Although the lens fibre cell-differentiating factors are well defined, the factors in aqueous that promote lens cell proliferation are not. Mitogens present in aqueous primarily signal through the MAPK/ERK and PI3-K/Akt pathways. By characterising the signalling pathways involved in lens cell proliferation, we aim to identify the factors in aqueous that regulate this process in vivo. Using rat lens epithelial explants, 5′-2′-bromo-deoxyuridine and H3-thymidine incorporation were used to compare the effects of aqueous, insulin-like growth factor (IGF-1), platelet-derived growth factor (PDGF-A), epidermal growth factor (EGF) and fibroblast growth factor (FGF-2) on lens cell proliferation. Western blotting was employed to characterise ERK1/2 and Akt signalling induced by these mitogens. The above assays were also repeated in the presence of selective receptor inhibitors. Similar to aqueous, FGF induced a sustained ERK1/2 signalling profile (up to 6 h), unlike IGF, PDGF and EGF that induced a transient activation of ERK1/2. In the presence of a FGF receptor (FGFR) inhibitor, the sustained aqueous-induced ERK1/2 signalling profile was perturbed, resembling the transient IGF-, PDGF- or EGF-induced profile. In the presence of other growth factor receptor inhibitors, aqueous maintained its sustained, 6 h, ERK1/2 signalling profile, although ERK1/2 phosphorylation at earlier time periods was reduced. No one-specific receptor inhibitor could block aqueous-induced lens cell proliferation; however, combinations of inhibitors could, providing FGFR signalling was blocked. Multiple growth factors are likely to regulate lens cell proliferation in vivo, with a key role for FGF in aqueous-induced signalling and lens cell proliferation.
Spatial Crowdsourcing: Challenges, Techniques, and Applications

Crowdsourcing is a new computing paradigm where humans are actively enrolled to participate in the procedure of computing, especially for tasks that are intrinsically easier for humans than for computers. The popularity of mobile computing and sharing economy has extended conventional web-based crowdsourcing to spatial crowdsourcing (SC), where spatial data such as location, mobility and the associated contextual information, plays a central role. In fact, spatial crowdsourcing has stimulated a series of recent industrial successes including Citizen Sensing (Waze), P2P ride-sharing (Uber) and Real-time Online-To-Offline (O2O) services (Instacart and Postmates). In this tutorial, we review the paradigm shift from web-based crowdsourcing to spatial crowdsourcing. We dive deep into the challenges and techniques brought by the unique spatio-temporal characteristics of spatial crowdsourcing. Particularly, we survey new designs in task assignment, quality control, incentive mechanism design and privacy protection on spatial crowdsourcing platforms, as well as the new trend to incorporate crowdsourcing to enhance existing spatial data processing techniques. We also discuss case studies of representative spatial crowdsourcing systems and raise open questions and current challenges for the audience to easily comprehend the tutorial and to advance this important research area.
THE EFFECT OF A PARTIAL BARRIER ON THE MOVEMENT OF A HYBRID ZONE

Computer simulations of clines (Brues, 1972; Endler, 1977) as well as theoretical arguments (Nagylaki, 1975), have shown that steps in gene frequencies will be pulled to partial barriers (areas of reduced gene flow) if they form within approximately a cline width of the partial barrier.