Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor necrosis factor‐α induces prostate cancer cell migration in lymphatic metastasis through CCR7 upregulation

Understanding the mechanism of lymph node metastasis, a poor prognostic sign for prostate cancer, and the further dissemination of the disease is important to develop novel treatment strategies. Recent studies have reported that C‐C chemokine receptor 7 (CCR7), whose ligand is CCL21, is abundantly expressed in lymph node metastasis and promotes cancer progression. Tumor necrosis factor‐α (TNF‐α) is chronically produced at low levels within the tumor microenvironment. The aim of this study was to determine whether TNF‐α promotes prostate cancer dissemination from metastatic lymph nodes through activation of the CCL21/CCR7 axis. First, human prostate cancer cells were determined to express both TNF‐α and CCR7. Second, low concentrations of TNF‐α were confirmed to induce CCR7 in prostate cancer cells through phosphorylation of ERK. Finally, CCL21 was found to promote the migration of prostate cancer cells through phosphorylation of the protein kinase p38. Our results suggest that TNF‐α leads to the induction of CCR7 expression and that the CCL21/CCR7 axis might increase the metastatic potential of prostate cancer cells in lymph node metastasis.
The Material Properties of Gelatin Gels

Abstract : A collection of physical and mechanical properties have been examined for 20% gelatin gels made from Pharmagel A. Among those parameters measured are density, thermal conductivity, specific heat, specific capacitance, ultrasonic wave velocity, and coefficient of rolling friction. The critical field strength above which electrical properties change radically is documented. An equivalent passive circuit model is proposed. Fracture stress and elastic modulii are measured. Shear stress at fracture and shear modulii are measured. Fracture strains are also documented for many strain rates. The gelatin is examined for piezo-electric effects and electro-optic effects which would modify its stress birefringence by application of an electric field. Surface polarization effects are also examined. The nature of the fracture surface as a function of crack propagation rate is characterized. A visco-elastic transition strain rate is also documented. Finally, changes of density with storage time at fixed temperature and humidity and changes of density with variations in composition are examined.
Model-checking verification of publish-subscribe architectures in web service contexts

In this paper we consider a Timed Automata model for the Publish/Subscribe paradigm, where special attention is given to its temporal aspects. Despite this special interest, we present a generic model for publishing and managing WS-resourses in the context of Web services with distributed resources. The model includes operations for clients to discover and subscribe to resources, with the intention of being notified when the resource property values fulfill certain conditions. Furthermore, error handling is provided in case discovery fails or a resource life has expired. Model-checking is used to verify the model soundness, by means of the UPPAAL tool, and a specific case study is presented to illustrate how the model deals with the scalability problem.
Energy-Performance Considerations for Data Offloading to FPGA-Based Accelerators Over PCIe

Modern data centers increasingly employ FPGA-based heterogeneous acceleration platforms as a result of their great potential for continued performance and energy efficiency. Today, FPGAs provide more hardware parallelism than is possible with GPUs or CPUs, whereas C-like programming environments facilitate shorter development time, even close to software cycles. In this work, we address limitations and overheads in access and transfer of data to accelerators over common CPU-accelerator interconnects such as PCIe. We present three different FPGA accelerator dispatching methods for streaming applications (e.g., multimedia, vision computing). The first uses zero-copy data transfers and on-chip scratchpad memory (SPM) for energy efficiency, and the second uses also zero-copy but shared copy engines among different accelerator instances and local external memory. The third uses the processor’s memory management unit to acquire the physical address of user pages and uses scatter-gather data transfers with SPM. Even though all techniques exhibit advantages in terms of scalability and relieve the processor from control overheads through using integrated schedulers, the first method presents the best energy-efficient acceleration in streaming applications.
Serum concentration of anti‐Müllerian hormone is not associated with semen quality

Impaired semen quality is frequent in Western countries and is the main reason or contributing reason in up to 50% of cases of couple infertility. Male factor infertility is mainly determined by examination of semen samples according to the World Health Organization's 2010 guidelines. AMH has both autocrine and paracrine properties through a direct effect via the AMH type II receptor and is therefore thought to be involved in spermatogenesis. We aimed to study the association between the serum concentration of AMH and semen quality in a cross‐sectional study including 970 young Danish men from the general population. All participants provided a semen sample, had a blood sample drawn, underwent a physical examination, and answered a questionnaire including information on lifestyle and medical history. Serum concentrations of reproductive hormones [AMH, luteinizing hormone (LH), follicle‐stimulating hormone (FSH), total testosterone (T), calculated free T, oestradiol (E2) and inhibin B] and semen parameters (semen volume, sperm concentration, and percentages of motile and morphologically normal spermatozoa) were determined. We found no association between serum AMH and semen quality, except for a significant (p = 0.011) trend for lower percentage of normal morphology with higher AMH. AMH quartile was positively associated with serum inhibin B (p < 0.001), inhibin B/FSH ratio (p < 0.001) and T/E2 ratio (0.016), and negatively associated with FSH (p = 0.004), LH (p = 0.005) and E2 (p = 0.028). There was no association between AMH quartile and T, calculated free T or total T/LH ratio. In conclusion, serum AMH is not useful as a marker of semen quality, and semen analysis using WHO criteria is still the golden standard in the evaluation of the infertile man.
Regulation of TH17 Cells and Associated Cytokines in Wound Healing, Tissue Regeneration, and Carcinogenesis

Wound healing is a crucial process which protects our body against permanent damage and invasive infectious agents. Upon tissue damage, inflammation is an early event which is orchestrated by a multitude of innate and adaptive immune cell subsets including TH17 cells. TH17 cells and TH17 cell associated cytokines can impact wound healing positively by clearing pathogens and modulating mucosal surfaces and epithelial cells. Injury of the gut mucosa can cause fast expansion of TH17 cells and their induction from naïve T cells through Interleukin (IL)-6, TGF-β, and IL-1β signaling. TH17 cells produce various cytokines, such as tumor necrosis factor (TNF)-α, IL-17, and IL-22, which can promote cell survival and proliferation and thus tissue regeneration in several organs including the skin, the intestine, and the liver. However, TH17 cells are also potentially pathogenic if not tightly controlled. Failure of these control mechanisms can result in chronic inflammatory conditions, such as Inflammatory Bowel Disease (IBD), and can ultimately promote carcinogenesis. Therefore, there are several mechanisms which control TH17 cells. One control mechanism is the regulation of TH17 cells via regulatory T cells and IL-10. This mechanism is especially important in the intestine to terminate immune responses and maintain homeostasis. Furthermore, TH17 cells have the potential to convert from a pro-inflammatory phenotype to an anti-inflammatory phenotype by changing their cytokine profile and acquiring IL-10 production, thereby limiting their own pathological potential. Finally, IL-22, a signature cytokine of TH17 cells, can be controlled by an endogenous soluble inhibitory receptor, Interleukin 22 binding protein (IL-22BP). During tissue injury, the production of IL-22 by TH17 cells is upregulated in order to promote tissue regeneration. To limit the regenerative program, which could promote carcinogenesis, IL-22BP is upregulated during the later phase of regeneration in order to terminate the effects of IL-22. This delicate balance secures the beneficial effects of IL-22 and prevents its potential pathogenicity. An important future goal is to understand the precise mechanisms underlying the regulation of TH17 cells during inflammation, wound healing, and carcinogenesis in order to design targeted therapies for a variety of diseases including infections, cancer, and immune mediated inflammatory disease.
Effects of Caregiving Status and Changes in Depressive Symptoms on Development of Physical Morbidity Among Long-Term Cancer Caregivers

Objective: Cancer caregiving burden is known to vary across the survivorship trajectory and has been linked with caregivers’ subsequent health impairment. Little is known, however, regarding how risk factors during long-term survivorship relate to vulnerability to caregivers’ health during that period. This study examined effects of caregiving status and depressive symptoms on development of physical morbidity by 5 years postdiagnosis. Method: Family caregivers (N = 491; Mage = 55.78) completed surveys at 2 (Time 1 [T1]) and 5 years (T2) after their care recipients’ cancer diagnosis. Demographic and caregiving context variables known to affect caregivers’ health were assessed at T1. Self-reported depressive symptoms and a list of physical morbid conditions were assessed at T1 and T2. Caregiving status (former, current, or bereaved) was assessed at T2. Results: Hierarchical negative binomial regression revealed that current caregivers at T2 (p = .02), but not those bereaved by T2 (p = .32), developed more physical morbid conditions between T1 and T2 compared with former caregivers, controlling for other variables. Independently, caregivers reporting either newly emerging or chronically elevated depressive symptoms at T2 (ps < .03), but not those whose symptoms remitted at T2 (p = .61), showed greater development of physical morbidity than did those reporting minimal depressive symptoms at both T1 and T2. Conclusions: Results highlight the roles of long-term caregiving demands and depressive symptoms in cancer caregivers’ premature physical health decline. Clinical attention through the long-term survivorship trajectory should be emphasized for caregivers of patients with recurrent or prolonged illness and to address caregivers’ elevated depressive symptoms.
Determination of a radotinib dosage regimen based on dose–response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia

Radotinib is a second‐generation BCR‐ABL1 tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia in chronic phase (CP‐CML). Here, using the data from a Phase 3 study conducted in patients with newly diagnosed CP‐CML, the dose–efficacy as well as dose–safety relationship analyses were performed to determine a safe and effective initial dosage regimen of radotinib. A significant positive association was detected between the starting dose of radotinib adjusted for body weight (Dose/BW) and the probability of dose‐limiting toxicity (≥grade 3 hematologic and nonhematologic toxicity) (P = 0.003). In contrast, a significant inverse association was discovered between Dose/BW and the probability of major molecular response (BCR‐ABL1/ABL1 ≤ 0.1%) when controlled for sex (P = 0.033). Moreover, frequent dose interruptions and reductions secondary to radotinib toxicities occurred in the Phase 3 study, resulting in nearly half (44%) of patients receiving a reduced dose at a 12‐month follow‐up. In conclusion, the results of this study demonstrate the need for initial radotinib dose attenuation to improve the long‐term efficacy and safety of radotinib. Hence, the authors suggest a new upfront radotinib dose of 400 mg once daily be tested in patients with newly diagnosed CP‐CML.
Late Gadolinium Enhancement for Prediction of Mutation-Positive Hypertrophic Cardiomyopathy on the Basis of Panel-Wide Sequencing.

BACKGROUND Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) revealed a substantial variation in the extent of myocardial scarring, a pathological hallmark of hypertrophic cardiomyopathy (HCM). However, few data exist regarding the relationship between the presence of gene mutations and the extent of LGE. Therefore, we aimed to investigate whether variations in the extent of LGE in HCM patients can be explained by the presence or absence of disease-causing mutations.Methods and Results:We analyzed data from 82 unrelated HCM patients who underwent both LGE-CMR and next-generation sequencing. We identified disease-causing sarcomere gene mutations in 44 cases (54%). The extent of LGE on CMR was an independent factor for predicting mutation-positive HCM (odds ratio 2.12 [95% confidence interval 1.51-3.83], P<0.01). The area under the curve of %LGE was greater than that of the conventional Toronto score for predicting the presence of a mutation (0.96 vs. 0.69, P<0.01). Sensitivity, specificity, positive predictive value, and negative predictive value of %LGE (cutoff >8.1%) were 93.2%, 89.5%, 91.1%, and 91.9%, respectively. CONCLUSIONS The results demonstrated that %LGE clearly discriminated mutation-positive from mutation-negative HCM in a clinically affected HCM population. HCM with few or no myocardial scars may be genetically different from HCM with a higher incidence of myocardial scars.
Environmental Role of Pathogenic Traits in Vibrio cholerae

Vibrio cholerae is a natural inhabitant of aquatic ecosystems. Some strains of V. cholerae can colonize human hosts and cause cholera, a profuse watery diarrhea. ABSTRACT Vibrio cholerae is a natural inhabitant of aquatic ecosystems. Some strains of V. cholerae can colonize human hosts and cause cholera, a profuse watery diarrhea. The major pathogenicity factors and virulence regulators of V. cholerae are encoded either in mobile genetic elements acquired in the environment (e.g., pathogenicity islands or lysogenic phages) or in the core genome. Several lines of evidence indicate that the emergence of numerous virulence traits of V. cholerae occurred in its natural environment, due to biotic and abiotic pressures. Here, we discuss the connections between the human host and the potential ecological roles of these virulence traits. Elucidating these connections will help us understand the emergence of this organism and other facultative bacterial pathogens.
Targeted DNA damage at individual telomeres disrupts their integrity and triggers cell death

Cellular DNA is organized into chromosomes and capped by a unique nucleoprotein structure, the telomere. Both oxidative stress and telomere shortening/dysfunction cause aging-related degenerative pathologies and increase cancer risk. However, a direct connection between oxidative damage to telomeric DNA, comprising <1% of the genome, and telomere dysfunction has not been established. By fusing the KillerRed chromophore with the telomere repeat binding factor 1, TRF1, we developed a novel approach to generate localized damage to telomere DNA and to monitor the real time damage response at the single telomere level. We found that DNA damage at long telomeres in U2OS cells is not repaired efficiently compared to DNA damage in non-telomeric regions of the same length in heterochromatin. Telomeric DNA damage shortens the average length of telomeres and leads to cell senescence in HeLa cells and cell death in HeLa, U2OS and IMR90 cells, when DNA damage at non-telomeric regions is undetectable. Telomere-specific damage induces chromosomal aberrations, including chromatid telomere loss and telomere associations, distinct from the damage induced by ionizing irradiation. Taken together, our results demonstrate that oxidative damage induces telomere dysfunction and underline the importance of maintaining telomere integrity upon oxidative damage.
Identifying Off‐Label Prescriptions Through Data Mining in Danish Community Pharmacy Servers: An Exploratory Study on Desmopressin, Diclofenac, Fucidin, Mirtazapine and Quetiapine

The term off‐label use describes the prescription and administration of medicines outside of the terms for which it officially has been approved, including age, dose and indication. Off‐label data can be generated from the Danish National Prescription Registry through combinations with diagnoses; however, the community pharmacy servers provide equal, local, albeit less data through a faster and less constrained collection process. The data collection for this exploratory study took place at five community pharmacies in Denmark. Five drugs were chosen for the investigation and collection of prescription data across a 2‐year period. Off‐label use by age was observed to be 1.9% for diclofenac, 1.7% for desmopressin and 2.3% for quetiapine. The percentages were based on total number of 3881, 925, 2712 prescriptions, respectively. Off‐label monitored by dosage appeared to be 75% for quetiapine; by box label text analysis, off‐label indication was found to be 10–15% and 15–23% for quetiapine and mirtazapine (from a total number of 3178 prescriptions), respectively. By route of administration where fucidin ointment was applied to the nose in 60 patients, 83% were prescribed off‐label (non‐dermatological). This exploratory study revealed that pharmacy servers represent a reliable and up‐to‐date source to collect a substantial amount of raw prescription data. The method gives straightforward and simple access to analysis of off‐label use by age and dose, whereas it is possible but difficult to interpret off‐label indications and route of administration from the box label text.
Classification of Exploit-Kit behaviors via machine learning approach

An Exploit-Kit (EK) is the cyber attacking tool which targets in finding vulnerabilities appeared on a web browser instance such as web-plugins, add-on instances usually installed in a web browser. Such instances may send some suitable malware payload through the vulnerabilities they found. This kind of such cyber-attack is known as the drive-by-download attack where malware downloading do not require any interaction from users. In addition, EK can do self-protection by imitating a benign website or responding to end-users with HTTP 404 error code whenever it encountered an unsupported target web browser. As a result, detecting EK requires a lot of effort. However, when an EK launches an attack, there are some patterns of interactions between a host and a victim. In this work, we obtain a set of data from www.malware-traffic-analysis.net and analyze those interactions in order to identify a set of features. We use such features to build a model for classifying interaction patterns of each EK type. Our experiments show that, with 5,743 network flows and 45 features, our model using Decision tree approach can classify EK traffic and EK type with accuracy of 97.74% and 97.11% respectively. In conclusion, our proposed work can help detect the behavior of EK with high accuracy.
Balancing different performance indices in complex robotic assembly processes

Because of the recent advancement of sensing and information technology, robotic manufacturing process can be optimized based on the collected data. Even though the process parameters can be optimized, there is no investigation to balance the performance indices for a manufacturing process because its complexity. For robotic assembly processes, there are some methods to optimize the process parameters; however balancing the First Time Throughput (FTT) rate and cycle time is not investigated. In this paper, an innovative method is proposed to optimize the cycle time while achieving optimal FTT rate. A complex system modeling method is developed based on Gaussian Process Regression (GPR). A constraint multi-objective optimization problem is formulated to balance the cycle time and FTT rate. Experiments were performed to evaluate the relationship between the cycle time and FTT rate. A complex torque converter assembly process is used as an example. The experimental results demonstrate the effectiveness of the proposed method.
Multi-document Text Summarization for Competitor Intelligence: A Methodology

With increasing adoption of Internet and various social media technologies by companies, the web has become a rich source of information about many aspects of organizational activities. Hence one input towards gathering competitive intelligence is to mine the text sources available on the web for any particular company and use the summarized version of that information for strategic decision making. This paper discusses a methodological approach and an architecture for such summarization system which can be used for gathering competitor intelligence by the companies.
The Challenge: Assessment of risks posed by systemic insecticides to hymenopteran pollinators: New perception when we move from laboratory via (semi‐)field to landscape scale testing?

Insect pollination is an ecosystem service with a high economic value [1]. Many hymenopteran pollinators are threatened worldwide, and a pollinator decline (e.g., Potts et al. [2] and Winfree [3], but compare Ghazoul [4]) would, therefore, lead to higher production costs of crops. In addition, plant biodiversity and ecosystem stability may be at risk. Honeybees of the genus Apis are among the most important pollinating hymenopterans. Firstly, they form large colonies with several thousand individuals, which enable very efficient pollination of crops. Secondly, they are managed by beekeepers, who provide their services for agriculture wherever needed. The steady decline in colony numbers of Apis mellifera during the last decades has many causes. High annual winter losses of hives (15–30% of all managed hives in Europe), for example, are caused by parasites, microbial infections, malnutrition, pesticides, and climatic parameters. These factors interact, and beekeepers treat their colonies according to the representative threats. Although scientists regard the parasitic mite Varroa destructor as the main factor in colony losses, other anthropogenic stressors contribute. The role of the widely used neonicotinoids in colony losses is particularly controversially discussed in the public and scientific spheres. Neonicotinoids act as agonists of the insect nicotinic acetylcholine receptor (nAChR). On binding to the synaptic nAChR, the channel opens and cations can permeate through the channel pore [5]. This cation flux depolarizes the postsynaptic membrane. Cholinergic synaptic transmission is disturbed by In This Issue:
Gamma and infra‐slow oscillations shape neuronal firing in the rat subcortical visual system

Neuronal oscillations observed in sensory systems are physiological carriers of information about stimulus features. Rhythm in the infra‐slow range, originating from the retina, was previously found in the firing of subcortical visual system nuclei involved in both image and non‐image forming functions. The present study shows that the firing of neurons in the lateral geniculate nucleus is also governed by gamma oscillation (∼35 Hz) time‐locked to high phase of infra‐slow rhythm that codes the intensity of transient light stimulation. We show that both physiological rhythms are synchronized within and between ipsilateral nuclei of the subcortical visual system and are dependent on retinal activity. The present study shows that neurophysiological oscillations characterized by various frequencies not only coexist in the subcortical visual system, but also are subjected to complex interference and synchronization processes.