Miracle-dz/UniFAR-FTUs huggingface dataset:
The next generation of orthotopic thyroid cancer models: immunocompetent orthotopic mouse models of BRAF V600E-positive papillary and anaplastic thyroid carcinoma.

BACKGROUND While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. METHODS We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous Braf(V600E/WT) and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. RESULTS Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. CONCLUSIONS We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system.
Value of the Diffusion-Weighted MRI in the Differential Diagnostics of Malignant and Benign Kidney Neoplasms – Our Clinical Experience

Summary Background Diffusion-weighted imaging (DWI) is an MRI modality using strong bipolar gradients to create a sensitivity of the signal to the thermally-induced Brownian motions of water molecules and in vivo measurement of molecular diffusion. The apparent diffusion coefficient (ADC) is a quantitative parameter calculated from DWI images which is used as a measure of diffusion. DWI allows to obtain comprehensive information on morphological and functional state of the kidney during a single examination without contrast medium administration. The purpose of the study was to evaluate the value of DWI in differentiating benign and malignant solid kidney tumors based on the initial stage of the study. Material/Methods The study included 19 adult patients with pathologically verified renal tumors: 9 patients with clear cell subtype of the renal cell carcinoma, 5 patients with oncocytoma and 5 patients with angiomyolipoma (AML). In addition, 5 healthy volunteers with completely normal findings according to kidney ultrasound were included into this study and set as reference. All patients underwent renal MR imaging which included DWI with subsequent ADC measurement. MR imaging was performed with a 1.5 T body scanner using an eight-channel phased-array body coil. Results The mean ADC value of ccRCC was significantly lower than that of normal renal parenchyma (2.11±0.25×10−3 mm2/s vs. 3.36±0.41×10−3 mm2/s, p<0.01). There was a significant difference in ADC between the malignant and benign renal lesions: in patients with angiomyolipoma the ADC value was 2.36±0.32×10−3 mm2/s vs. 2.11±0.25×10−3 mm2/s; p<0.05 and in patients with oncocytoma – 2.75±0.27×10−3 mm2/s vs. 2.11±0.25×10−3 mm2/s; p<0.05. The difference in ADC values in patients with high and low ccRCC grades was observed. Conclusions DWI can be used to characterize renal lesions; the ADC of a renal lesion can be potentially used as an additional parameter to help determine the appropriate clinical management.
Escort: A Path-Based OS Security Architecture

Escort is the security architecture for Scout, a conﬁgurable operating system designed for network appliances. Scout is unique in that it is designed around paths —a communication-centric abstraction that en-capsulates information ﬂows through the system—rather than the more traditional processes and servers. Scout uses paths to make end-to-end resource allocation decisions. Escort extends this idea to isolate these information ﬂows, as well as to provide end-to-end accountability. This paper introduces the Escort security architecture, shows how it can be used to enforce common security policies, and evaluates its design according to several well-established criteria.
Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography.

PURPOSE Two optical coherence tomography (OCT) modalities can visualize the choroid: high-penetration OCT (HP-OCT) using a long wavelength, and enhanced depth imaging technique using Heidelberg OCT (EDI-OCT). The purpose of this study was to compare and investigate the agreement among the retinal/choroidal thickness parameters. METHODS Twenty-four eyes of 12 healthy volunteers were examined simultaneously using the prototype swept-source HP-OCT and EDI-OCT. Six independent examiners measured the central retinal/choroidal thicknesses on horizontal B-scan images. The reliability was evaluated by intraclass correlation coefficient (ICC). Intervisit reproducibility was assessed by examining 10 of the volunteers 4 months later. RESULTS Using HP-OCT, the average of all measurements was 209.1 ± 12.9 μm in the retina and 292.7 ± 77.3 μm in the choroid, and using EDI-OCT, 212.5 ± 13.3 μm in the retina and 283.7 ± 84.1 μm in the choroid. An intersystem comparison showed that the ICCs were 0.661 (95% confidence interval [CI], 0.535-0.754) for the retina and 0.921 (95% CI, 0.875-0.948) for the choroid. Using HP-OCT, the interexaminer ICC reproducibility values were 0.630 (95% CI, 0.447-0.791) for the retinal thickness and 0.912 (95% CI, 0.835-0.958) for the choroidal thickness; using EDI-OCT, the values for the retinal and choroidal thicknesses were 0.788 (95% CI, 0.607-0.898) and 0.970 (95% CI, 0.948-0.985), respectively. The intervisit ICC values for the retinal and choroidal thicknesses were 0.504 (95% CI, 0.376-0.609) and 0.893 (95% CI, 0.864-0.916). CONCLUSIONS The retinal and choroidal thicknesses were well-correlated between the instruments. Higher reliability and reproducibility are expected for the choroidal thickness measurements despite with higher morphologic interindividual variations.
Coherent control in multiphoton fluorescence imaging

In multiphoton fluorescence laser-scanning microscopy ultrafast laser pulses, i.e. light pulses having pulse-width ≤ 1picosecond (1 ps = 10-12 s), are commonly used to circumvent the low multiphoton absorption cross-sections of common fluorophores. Starting with a discussion on how amplitude modulation of ultrashort pulse-train enhances the two-photon fluorescence providing deep insight into laser-induced photo-thermal damage, the effect of controlling time lag between phase-locked laser pulses on imaging is described. In addition, the prospects of laser pulse-shaping in signal enhancement (by temporal pulse-compression at the sample) and selective excitation of fluorophores (by manipulating the phase and/or amplitude of different frequency components within the pulse) are discussed with promising future applications lying ahead.
Characterizing Intelligence Gathering and Control on an Edge Network

There is a continuous struggle for control of resources at every organization that is connected to the Internet. The local organization wishes to use its resources to achieve strategic goals. Some external entities seek direct control of these resources, for purposes such as spamming or launching denial-of-service attacks. Other external entities seek indirect control of assets (e.g., users, finances), but provide services in exchange for them. Using a year-long trace from an edge network, we examine what various external organizations know about one organization. We compare the types of information exposed by or to external organizations using either active (reconnaissance) or passive (surveillance) techniques. We also explore the direct and indirect control external entities have on local IT resources.
Developing a Research Ideas Creation System through Reusing Knowledge Bases for Ontology Construction

Ideas creation is an important activity in various scenarios while research is one of them. A considerable number of research studies have been made in the past years in improving tools and methods to support idea generation. However, creativity of ideas has only been studied in sporadic attempts, and most of them only share little similarity in conditions. Moreover, since knowledge is the basis of all kinds of idea generation, knowledge reuse is very valuable in order to enhance the generation process and the results' quality including creativity. Besides the idea generation methods and techniques have recently been developed in our earlier work, this study focuses on the reuse of the knowledge bases for ontology construction. It aims to enhance the effectiveness and innovation of generated research ideas. Specifically, this paper presents an ideas creation framework with knowledge reuse process as a creative computing. In particular, ontologies merging techniques with supporting algorithms are proposed and designed. Furthermore, a case study is presented with reused and new-formed ontologies, in which formal algorithms are used to calculate and incorporate the knowledge reuse. The main contribution of this paper is a set of rules to support knowledge reuse for the ontology construction in the ideas creation framework.
Hepatic Progenitor Cells Contribute to the Progression of 2-Acetylaminofluorene/Carbon Tetrachloride-Induced Cirrhosis via the Non-Canonical Wnt Pathway

Hepatic progenitor cells (HPCs) appear to play an important role in chronic liver injury. In this study, cirrhosis was induced in F-344 rats (n = 32) via subcutaneous injection of 50% carbon tetrachloride (CCl4) twice a week for 8 weeks. Then, 30% CCl4 was administered in conjunction with intragastric 2-acetylaminofluorine (2-AAF) for 4 weeks to induce activation of HPCs. WB-F344 cells were used to provide direct evidence for differentiation of HPCs to myofibroblasts. The results showed that after administration of 2-AAF, the hydroxyproline content and the expressions of α-SMA, Col I, Col IV, TGF-β1, CD68, TNF-α, CK19 and OV6 were significantly increased. OV6 and α-SMA were largely co-expressed in fibrous septum and the expressions of Wnt5b, frizzled2, frizzled3 and frizzled6 were markedly increased, while β-catenin expression was not statistically different among the different groups. Consistent with the above results, WB-F344 cells, treated with TGF-β1 in vitro, differentiated into myofibroblasts and α-SMA, Col I, Col IV, Wnt5b and frizzled2 expressions were significantly increased, while β-catenin expression was decreased. After blocking the non-canonical Wnt pathway via WIF-1, the Wnt5b level was down regulated, and α-SMA and F-actin expressions were significantly decreased in the WIF-1-treated cells. In conclusion, these results indicate that HPCs appear to differentiate into myofibroblasts and exhibit a profibrotic effect in progressive cirrhosis via activation of the non-canonical Wnt pathway. Blocking the non-canonical Wnt pathway can inhibit the differentiation of HPCs into myofibroblasts, suggesting that blocking this pathway and changing the fate of differentiated HPCs may be a potential treatment for cirrhosis.
On sums of independent random variables with unbounded variance, and estimating the average degree in a graph

We prove the following inequality: for every positive integer n and every collection X1,. , Xn of nonnegative independent random variables that each has expectation 1, the probability that their sum remains below n+1 is at least α > 0. Our proof produces a value of α = 1/13 ≅ 0.077, but we conjecture that the inequality also holds with α = 1/e ≅ 0.368. As an example for the use of the new inequality, we consider the problem of estimating the average degree of a graph by querying the degrees of some of its vertices. We show the following threshold behavior: approximation factors above 2 require far less queries than approximation factors below 2. The new inequality is used in order to get tight (up to multiplicative constant factors) relations between the number of queries and the quality of the approximation. We show how the degree approximation algorithm can be used in order to quickly find those edges in a network that belong to many shortest paths.
Accuracy of Highly Sexually Active Gay and Bisexual Men's Predictions of Their Daily Likelihood of Anal Sex and Its Relevance for Intermittent Event-Driven HIV Pre-Exposure Prophylaxis

Objective:We sought to examine highly sexually active gay and bisexual men's accuracy in predicting their sexual behavior for the purposes of informing future research on intermittent event-driven HIV Pre-Exposure Prophylaxis. Design:For 30 days, 92 HIV-negative men completed a daily survey about their sexual behavior (n = 1688 days of data) and indicated their likelihood of having anal sex with a casual male partner next day. Method:We used multilevel modeling to analyze the association between self-reported likelihood of and subsequent engagement in anal sex. Results:We found a linear association between men's reported likelihood of anal sex with casual partners and the actual probability of engaging in sex, although men overestimated the likelihood of sex. Overall, we found that men were better at predicting when they would not have sex than when they would, particularly if any likelihood value greater than 0% was treated as indicative that sex might occur. We found no evidence that men's accuracy of prediction was affected by whether it was a weekend or whether they were using substances, although both did increase the probability of sex. Discussion:These results suggested that, men taking event-driven intermittent Pre-Exposure Prophylaxis, 14% of doses could have been safely skipped with a minimal rate of false negatives using guidelines of taking a dose unless there was no chance (ie, 0% likelihood) of sex on next day. This would result in savings of over US $1300 per year in medication costs per participant.
Combined intratumoral injection of bone marrow-derived dendritic cells and systemic chemotherapy to treat pre-existing murine tumors.

Dendritic cells (DCs) are attractive candidates for innovative cancer immunotherapy by virtue of their potential to function as professional antigen-presenting cells for initiating cellular immune responses. In this study, we evaluated a possible synergy of conventional chemotherapy together with intratumoral injection of syngeneic bone marrow-derived DCs for the treatment of preexisting tumors. Using murine CT26 colon adenocarcinoma cells (parental or modified to express beta-galactosidase as a model tumor antigen) to produce s.c. tumors in syngeneic BALB/c mice, the data demonstrate that direct injections of DCs at the tumor site result in partial eradication of established tumors. Strikingly, the addition of systemic chemotherapy (cyclophosphamide) combined with local intratumoral injection of DCs led to complete tumor regression in the treated animals. The tumor-free mice were able to resist a repeat challenge with the same tumor, suggesting that the animals had acquired long term antitumor immunity. Supporting evidence for the paradigm of systemic chemotherapy and intratumoral administration of DCs was obtained using melanoma B16 syngeneic tumor treated with Adriamycin plus DCs. These novel findings raise the possibility of using this potent strategy of combined intratumoral injections of DCs and systemic chemotherapy for cancer treatment.
A change analysis process to characterize software maintenance projects

In order to improve software maintenance processes, we need to be able to first characterize and assess them. This task needs to be performed in depth and with objectivity since the problems are complex. One approach is to set up a measurement program specifically aimed at maintenance. However, establishing a measurement program requires that one understands the issues and is able to characterize the maintenance environment and processes in order to collect suitable and cost-effective data. Also, enacting such a program and getting usable data sets takes time. A short term substitute is needed. We propose a characterization process aimed specifically at maintenance and based on a general qualitative analysis methodology. This process is rigorously defined in order to be repeatable and usable by people who are not acquainted with such analysis procedures. A basic feature of our approach is that maintenance changes are analyzed in order to understand the flaws in the change process. Guidelines are provided and a case study is shown that demonstrates the usefulness of the approach. <<ETX>>
Comparison of Two Weight-Based Desmopressin Dosing Strategies for Spontaneous Bleeding

Background: The pharmacokinetics and pharmacodynamics of desmopressin are appropriate for adjusted body weight–based dosing, particularly in obese patients. Objective: The objective of this study was to describe desmopressin dosing strategies, with emphasis on hemostatic outcomes among patients without preexisting bleeding disorders. Methods: This was a single-center, retrospective cohort study of patients who received intravenous weight-based desmopressin for a hemostatic indication. Demographics, comorbidities, treatment setting, indication, site of bleeding, and outcomes were collected from the medical record. Primary outcomes included need for procedural intervention to achieve hemostasis, transfusion requirement, and death. Association between desmopressin dose and outcome was evaluated using χ2 or Fischer’s exact tests and logistic and linear regression models. Multiple regression analysis was conducted to identify other predictors of outcome in the data set. Results: A total of 109 patients were included (n = 26, dose adjustment; n = 83, no dose adjustment). Baseline characteristics were well-matched between groups: mean (SD) age of 57.0 (13.5) years; mean (SD) Charlson Comorbidity Score of 6.5 (2.8); 37% were obese; 76% were critically ill; 81% were actively bleeding without differences in site of bleeding; and crude mortality was 39%. No differences in death, mean units of packed red blood cells transfused, or need for procedural hemostasis were observed between adjusted weight– and actual weight–based desmopressin dosing. Conclusions: When used adjunctively to blood product transfusion in actively bleeding patients, use of adjusted body weight–based desmopressin did not negatively affect clinical outcomes. More data are needed to confirm this dosing strategy.
Architecture Reconstruction and Analysis of Medical Device Software

New research is underway at the FDA to investigate the benefits of integrating architecture analysis into safety evaluations of medical-device software. Due to the complexity in setting up testing environments for such software, the FDA is unable to conduct large-scale safety testing, instead, it must rely on other techniques to build an argument for whether the software is safe or not. The architecture analysis approach, formalized using relational algebra, is based on reconstructing abstract, yet precise, architectural views from source code to help build such arguments about safety. This paper discusses the use of the formal approach to analyze the Computer-Assisted Resuscitation Algorithm (CARA) software, which controls an infusion pump designed to provide automated assistance for transfusing blood. The results suggest that a) architecture analysis offers many insights related to software quality in general and testability (i.e., the ease of testing) and its impact on safety in particular, and b) architectural analysis results can be used to help configure static analysis tools to improve their performance for verifying safety properties.
CCK Stimulation of GLP-1 Neurons Involves α1-Adrenoceptor–Mediated Increase in Glutamatergic Synaptic Inputs

OBJECTIVE Glucagon-like peptide 1 (GLP-1) is involved in the central regulation of food intake. It is produced within the brain by preproglucagon (PPG) neurons, which are located primarily within the brain stem. These neurons project widely throughout the brain, including to the appetite centers in the hypothalamus, and are believed to convey signals related to satiety. Previous work demonstrated that they are directly activated by leptin and electrical activity of the afferent vagus. Another satiety hormone, cholecystokinin (CCK), has also been linked to activation of brain stem neurons, suggesting that it might act partially via centrally projecting neurons from the nucleus tractus solitarius (NTS). The aim of this study was to investigate the neuronal circuitry linking CCK to the population of NTS-PPG neurons. RESEARCH DESIGN AND METHODS Transgenic mice expressing yellow fluorescent protein (Venus) under the control of the PPG promoter were used to identify PPG neurons in vitro and to record their electrical and pharmacological profile. RESULTS PPG neurons in the NTS were excited by CCK and epinephrine, but not by the melanocortin receptor agonist melanotan II. Both CCK and epinephrine acted to increase glutamatergic transmission to the PPG neurons, and this involved activation of α1-adrenergic receptors. Inhibition of adrenergic signaling abolished the excitatory action of CCK. CONCLUSIONS CCK activates NTS-PPG cells by a circuit involving adrenergic and glutamatergic neurons. NTS-PPG neurons integrate a variety of peripheral signals that indicate both long-term energy balance and short-term nutritional and digestional status to produce an output signal to feeding and autonomic circuits.
Towards a Theory of Formal Classification

Classifications have been used for centuries with the goal of cataloguing and searching large sets of objects. In the early days it was mainly books; lately it has become Web pages, pictures and any kind of electronic information items. Classifications describe their contents using natural language labels, an approach which has proved very effective in manual classification. However natural language labels show their limitations when one tries to automate the process, as they make it almost impossible to reason about classifications and their contents. In this paper we introduce the novel notion of Formal Classification, as a graph structure where labels are written in a logical concept language. The main property of Formal Classifications is that each node can be associated to a normal form formula which univocally describes its contents. This in turn allows us to reduce document classification and query answering to fully automatic propositional reasoning.
Some dangers from 2G networks legacy support and a possible mitigation

We present in this short study, some of the well-known problems with the current legacy support for 2G cellular networks, and the security and authentication problems this poses, as demonstrated in recent document leaks about spying from US embassies [1]. We have conducted focused radio measurements in the Helsinki Metropolitan area on these security problems and present some of the findings here. Also, we propose some mitigation methods for the most likely scenarios that arise in supporting legacy 2G systems in modern operator networks.