Miracle-dz/UniFAR-FTUs huggingface dataset:
Segment‐related, mosaic neurogenetic pattern in the forebrain and mesencephalon of early chick embryos: I. Topography of ache‐positive neuroblasts up to stage HH18

Histochemical mapping of AChE‐positive neuroblasts in sectioned and whole‐mounted preparations of the chick embryo mesencephalon and prosencephalon allows a correlation of early neural tube morphogenesis (segmentation, longitudinal compartmentation) with the heterochronic pattern of neurogenesis. One significant finding is that the initial appearance of neuroblasts in the forebrain does not follow neuromeric segmentation, but evolves in parallel with it. Early neuroblasts appear as separate, distinct groups within specific matrix territories at the center of the transverse neuromeric segments. Neighbouring segments display different spatiotemporal patterns of neurogenesis. Overall gradients of differentiation in the rostrocaudal and ventrodorsal directions are absent, whereas a clear‐cut segment‐related, mosaic pattern becomes evident. Notwithstanding this, gross regularities of heterochrony in the neurogenetic behavior of the different segments lead to a definition of elemental longitudinal compartments of the forebrain and mesencephalon (floor, paramedian, basal, and alar regions) on the basis of precocious differentiation of the basal region and retarded differentiation of the paramedian and alar regions.
Exponential Stability of Switched Linear Hyperbolic Initial-Boundary Value Problems

We consider the initial-boundary value problem governed by systems of linear hyperbolic partial differential equations in the canonical diagonal form and study conditions for exponential stability when the system discontinuously switches between a finite set of modes. The switching system is fairly general in that the system matrix functions as well as the boundary conditions may switch in time. We show how the stability mechanism developed for classical solutions of hyperbolic initial boundary value problems can be generalized to the case in which weaker solutions become necessary due to arbitrary switching. We also provide an explicit dwell-time bound for guaranteeing exponential stability of the switching system when, for each mode, the system is exponentially stable. Our stability conditions only depend on the system parameters and boundary data. These conditions easily generalize to switching systems in the nondiagonal form under a simple commutativity assumption. We present tutorial examples to illustrate the instabilities that can result from switching.
Herceptin Conjugates Linked by EDC Boost Direct Tumor Cell Death via Programmed Tumor Cell Necrosis

Tumor-targeted antibody therapy is one of the safest biological therapeutics for cancer patients, but it is often ineffective at inducing direct tumor cell death and is ineffective against resistant tumor cells. Currently, the antitumor efficacy of antibody therapy is primarily achieved by inducing indirect tumor cell death, such as antibody-dependent cell cytotoxicity. Our study reveals that Herceptin conjugates, if generated via the crosslinker EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride), are capable of engendering human epidermal growth factor receptor 2 (Her2) positive tumor cells death. Using a high-performance liquid chromatography (HPLC) system, three peaks with estimated molecular weights of antibody monomer, dimer, and trimer were isolated. Both Herceptin trimer and dimer separated by HPLC induced significant levels of necrotic tumor cell death, although the trimer was more effective than the dimer. Notably, the Herceptin trimer also induced Herceptin-resistant tumor cell death. Surprisingly different from the known cell death mechanism that often results from antibody treatment, the Herceptin trimer elicited effective and direct tumor cell death via a novel mechanism: programmed cell necrosis. In Her2-positive cells, inhibition of necrosis pathways significantly reversed Herceptin trimer-induced cell death. In summary, the Herceptin trimer reported herein harbors great potential for overcoming tumor cell resistance to Herceptin treatment.
Modulation of GSK-3β Activity in Venezuelan Equine Encephalitis Virus Infection

Alphaviruses, including Venezuelan Equine Encephalitis Virus (VEEV), cause disease in both equine and humans that exhibit overt encephalitis in a significant percentage of cases. Features of the host immune response and tissue-specific responses may contribute to fatal outcomes as well as the development of encephalitis. It has previously been shown that VEEV infection of mice induces transcription of pro-inflammatory cytokines genes (e.g., IFN-γ, IL-6, IL-12, iNOS and TNF-α) within 6 h. GSK-3β is a host protein that is known to modulate pro-inflammatory gene expression and has been a therapeutic target in neurodegenerative disorders such as Alzheimer's. Hence inhibition of GSK-3β in the context of encephalitic viral infections has been useful in a neuroprotective capacity. Small molecule GSK-3β inhibitors and GSK-3β siRNA experiments indicated that GSK-3β was important for VEEV replication. Thirty-eight second generation BIO derivatives were tested and BIOder was found to be the most potent inhibitor, with an IC50 of ∼0.5 µM and a CC50 of >100 µM. BIOder was a more potent inhibitor of GSK-3β than BIO, as demonstrated through in vitro kinase assays from uninfected and infected cells. Size exclusion chromatography experiments demonstrated that GSK-3β is found in three distinct complexes in VEEV infected cells, whereas GSK-3β is only present in one complex in uninfected cells. Cells treated with BIOder demonstrated an increase in the anti-apoptotic gene, survivin, and a decrease in the pro-apoptotic gene, BID, suggesting that modulation of pro- and anti-apoptotic genes contributes to the protective effect of BIOder treatment. Finally, BIOder partially protected mice from VEEV induced mortality. Our studies demonstrate the utility of GSK-3β inhibitors for modulating VEEV infection.
Resistin in Rodents and Humans

Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.
Emerging therapeutics for advanced thyroid malignancies: rationale and targeted approaches

Introduction: Thyroid cancer is an emerging public health concern. In the USA, its incidence has doubled in the past decade, making it the eighth most commonly diagnosed neoplasm in 2010. Despite this alarming increase, most thyroid cancer patients benefit from conventional approaches (surgery, radioiodine, radiotherapy, TSH suppression with levothyroxine) and are often cured. Nevertheless, a minority have aggressive tumors resistant to cytotoxic and other historical therapies; these patients sorely need new treatment options. Areas covered: Herein the biology and molecular characteristics of the common histological types of thyroid cancer are reviewed to provide context for subsequent discussion of recent developments and emerging therapeutics for advanced thyroid cancers. Expert opinion: Several kinase inhibitors, especially those targeting VEGFR and/or RET, have already demonstrated promising activity in differentiated and medullary thyroid cancers (DTC, MTC). Although of minimal benefit in DTC and MTC, cytotoxic chemotherapy with anti-microtubule agents and/or anthracyclines in combination with intensity-modulated radiation therapy appears to extend survival for patients with locoregionally confined anaplastic thyroid cancer (ATC), but to have only modest benefit in metastatic ATC. Further discovery and development of novel agents and combinations of agents will be critical to further progress in treating advanced thyroid cancers of all histotypes.
Effectiveness of aromatherapy with light thai massage for cellular immunity improvement in colorectal cancer patients receiving chemotherapy.

BACKGROUND Patients with colorectal cancer are usually treated with chemotherapy, which reduces the number of blood cells, especially white blood cells, and consequently increases the risk of infections. Some research studies have reported that aromatherapy massage affects the immune system and improves immune function by, for example, increasing the numbers of natural killer cells and peripheral blood lymphocytes. However, there has been no report of any study which provided good evidence as to whether aromatherapy with Thai massage could improve the immune system in patients with colorectal cancer. The objectives of this study were to determine whether the use of aromatherapy with light Thai massage in patients with colorectal cancer, who have received chemotherapy, can result in improvement of the cellular immunity and reduce the severity of the common symptoms of side effects. MATERIALS AND METHODS Sixty-six patients with colorectal cancer in Phichit Hospital, Thailand, were enrolled in a single-blind, randomised-controlled trial. The intervention consisted of three massage sessions with ginger and coconut oil over a 1-week period. The control group received standard supportive care only. Assessments were conducted at pre-assessment and at the end of one week of massage or standard care. Changes from pre-assessment to the end of treatment were measured in terms of white blood cells, neutrophils, lymphocytes, CD4 and CD8 cells and the CD4/CD8 ratio and also the severity of self-rated symptom scores. RESULTS The main finding was that after adjusting for pre-assessment values the mean lymphocyte count at the post-assessment was significantly higher (P=0.04) in the treatment group than in the controls. The size of this difference suggested that aromatherapy with Thai massage could boost lymphocyte numbers by 11%. The secondary outcomes were that at the post assessment the symptom severity scores for fatigue, presenting symptom, pain and stress were significantly lower in the massage group than in the standard care controls. CONCLUSIONS Aromatherapy with light Thai massage can be beneficial for the immune systems of cancer patients who are undergoing chemotherapy by increasing the number of lymphocytes and can help to reduce the severity of common symptoms.
Periodontal status of HIV-positive patients.

OBJECTIVE To assess the periodontal status of HIV positive individuals and to compare it with age-and gender-matched controls. MATERIALS AND METHODS The cross-sectional study comprised fifty-two HIV positive individuals and fifty-two controls. OHI-S and PI were recorded by a single pre-trained and pre-calibrated examiner. RESULTS Based on antiretroviral therapy use, mean OHI-S was higher among HIV positive females undergoing therapy. A significant gender difference was observed in the PI score among those on antiretroviral therapy, with females having a lower score (p = 0.04). Also, significant gender difference was observed in the mean PI score among HIV positive individuals, with males having a higher score. CONCLUSION There was a significant difference in the overall mean OHI-S score among HIV positive individuals and controls (p = 0.03). However, no significant difference was observed when the overall PI score was calculated for both groups (p = 0.95).
A New Computational Method for Prediction of Transient Hygroscopic Stresses during Moisture Desorption in Laminated Composite Plates with Different Degrees of Anisotropy

A theoretical study is presented for predicting the hygrothermal behavior of laminated composite plates during moisture desorption. This investigation is aimed at overcoming the computational difficulties in the determination of transient hygroscopic stress distribution through laminated plates and in the evaluation of the effect of anisotropy on the evolution of such stresses. To calculate such stresses during desorption phase, we present a new method by which we are able to predict directly the evolution of transient hygroscopic stresses within laminated composite plates without the calculation of moisture concentrations as in the case of Benkeddad’s method in which we are obliged to determine the moisture distribution across the plate before the calculation of such stresses. This is very important and must be taken into account in the design of composite material, particularly aerospace structures for example, aircraft. The second part of this investigation is devoted to the analysis of the effect of anisotropy on the hygrothermal behavior of laminated plates during moisture desorption. The polar representation method of anisotropic properties is selected as a convenient tool for this study. By this method, the author is able to assess the anisotropy of composite laminated plates using the degree of anisotropy. Some stacking sequences with different in-plane degree of anisotropy were investigated in order to show the effect of anisotropy on the transverse hygroscopic stresses. Finally, the results of this paper can be used to guide the derivation of future by opening a way for the optimal design of composite structures submitted to a moist environment.
Diabetes in Sports

Context: Exercise is recommended for individuals with diabetes mellitus, and several facets of the disease must be considered when managing the diabetic athlete. The purpose of this article is to review diabetes care in the context of sports participation. Evidence Acquisition: Relevant studies were identified through a literature search of MEDLINE and the Cochrane database, as well as manual review of reference lists of identified sources. Results: Diabetics should be evaluated for complications of long-standing disease before beginning an exercise program, and exercise should be modified appropriately if complications are present. Athletes who use insulin or oral insulin secretogogues are at risk for exercise-induced immediate or delayed hypoglycemia. Diabetics are advised to engage in a combination of regular aerobic and resistance exercise. Insulin-dependent diabetics should supplement carbohydrate before and after exercise, as well as during exercise for events lasting longer than 1 hour. Adjustment of insulin dosing based on planned exercise intensity is another strategy to prevent hypoglycemia. Insulin-dependent athletes should monitor blood sugar closely before, during, and after exercise. Significant hyperglycemia before exercise should preclude exercise because the stress of exercise can paradoxically exacerbate hyperglycemia and lead to ketoacidosis. Athletes should be aware of hypoglycemia symptoms and have rapidly absorbable glucose available in case of hypoglycemia. Conclusion: Exercise is an important component of diabetes treatment, and most people with diabetes can safely participate in sports at recreational and elite levels with attention to appropriate precautions.
Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammation via Bee Venom Phospholipase A2 in Mice

Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A2 (bvPLA2) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA2 in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA2 six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA2 treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA2 treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes’ mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA2 on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA2 in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA2 are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA2 in radiation pneumonitis and fibrosis treatments.
Optogenetic silencing of locus coeruleus activity in mice impairs cognitive flexibility in an attentional set-shifting task

The locus coeruleus (LC) is the sole source of noradrenergic projections to the cortex and essential for attention-dependent cognitive processes. In this study we used unilateral optogenetic silencing of the LC in an attentional set-shifting task (ASST) to evaluate the influence of the LC on prefrontal cortex-dependent functions in mice. We expressed the halorhodopsin eNpHR 3.0 to reversibly silence LC activity during task performance, and found that silencing selectively impaired learning of those parts of the ASST that most strongly rely on cognitive flexibility. In particular, extra-dimensional set-shifting (EDS) and reversal learning was impaired, suggesting an involvement of the medial prefrontal cortex (mPFC) and the orbitofrontal cortex. In contrast, those parts of the task that are less dependent on cognitive flexibility, i.e., compound discrimination (CD) and the intra-dimensional shifts (IDS) were not affected. Furthermore, attentional set formation was unaffected by LC silencing. Our results therefore suggest a modulatory influence of the LC on cognitive flexibility, mediated by different frontal networks.
Unreasonable effectiveness of learning neural networks: From accessible states and robust ensembles to basic algorithmic schemes

Significance Artificial neural networks are some of the most widely used tools in data science. Learning is, in principle, a hard problem in these systems, but in practice heuristic algorithms often find solutions with good generalization properties. We propose an explanation of this good performance in terms of a nonequilibrium statistical physics framework: We show that there are regions of the optimization landscape that are both robust and accessible and that their existence is crucial to achieve good performance on a class of particularly difficult learning problems. Building on these results, we introduce a basic algorithmic scheme that improves existing optimization algorithms and provides a framework for further research on learning in neural networks. In artificial neural networks, learning from data is a computationally demanding task in which a large number of connection weights are iteratively tuned through stochastic-gradient-based heuristic processes over a cost function. It is not well understood how learning occurs in these systems, in particular how they avoid getting trapped in configurations with poor computational performance. Here, we study the difficult case of networks with discrete weights, where the optimization landscape is very rough even for simple architectures, and provide theoretical and numerical evidence of the existence of rare—but extremely dense and accessible—regions of configurations in the network weight space. We define a measure, the robust ensemble (RE), which suppresses trapping by isolated configurations and amplifies the role of these dense regions. We analytically compute the RE in some exactly solvable models and also provide a general algorithmic scheme that is straightforward to implement: define a cost function given by a sum of a finite number of replicas of the original cost function, with a constraint centering the replicas around a driving assignment. To illustrate this, we derive several powerful algorithms, ranging from Markov Chains to message passing to gradient descent processes, where the algorithms target the robust dense states, resulting in substantial improvements in performance. The weak dependence on the number of precision bits of the weights leads us to conjecture that very similar reasoning applies to more conventional neural networks. Analogous algorithmic schemes can also be applied to other optimization problems.
The Dynamics of Decision Making in Penalty Kick Situations in Association Football

This paper reviews research on decision-making behavior of both goalkeeper and penalty taker during penalty kick situations in association football. Specifically, it adopts an ecological dynamics perspective on the behavior of both penalty taker and goalkeeper exemplifying how each might constrain the other's decisions. This conceptual framework is elucidated to suggest key ideas for designing experimental programs on the penalty kick. We conclude by discussing the implications of ecological dynamics to advance research and practice in the penalty kick.
Elucidation of Differential Accumulation of 1-Phenylethanol in Flowers and Leaves of Tea (Camellia sinensis) Plants

1-Phenylethanol (1PE) is a major aromatic volatile in tea (Camellia sinensis) flowers, whereas it occurs in a much smaller amounts in leaves. Enzymes involved in the formation of 1PE in plants and the reason why 1PE differentially accumulates in plants is unknown. In the present study, enzymes in the last step leading from acetophenone to 1PE were isolated from tea flowers by traditional biochemical chromatography. The two types of partially purified enzymes were proposed to be responsible for formations of (R)-1PE and (S)-1PE, respectively. Tea leaves also contained such enzymes having equivalent activities with flowers. Stable isotope labeling experiments indicated that weak transformation from l-phenylalanine to acetophenone in leaves mainly resulted in little occurrence of 1PE in leaves. This study provided an example that differential distribution of some metabolites in plant tissues was not only determined by enzyme(s) in the last step of metabolite formation, but also can be due to substrate availability.