Miracle-dz/UniFAR-FTUs huggingface dataset:
Trimethyl Chitosan Nanoparticles Encapsulated Protective Antigen Protects the Mice Against Anthrax

Anthrax is an era old deadly disease against which there are only two currently available licensed vaccines named anthrax vaccine adsorbed and precipitated (AVP). Though they can provide a protective immunity, their multiple side-effects owing to their ill-defined composition and presence of toxic proteins (LF and EF) of Bacillus anthracis, the causative organism of anthrax, in the vaccine formulation makes their widespread use objectionable. Hence, an anthrax vaccine that contains well-defined and controlled components would be highly desirable. In this context, we have evaluated the potential of various vaccine formulations comprising of protective antigen (PA) encapsulated trimethyl-chitosan nanoparticles (TMC-PA) in conjunction with either CpG-C ODN 2395 (CpG) or Poly I:C. Each formulation was administered via three different routes, viz., subcutaneous (SC), intramuscular (IM), and intraperitoneal in female BALB/c mice. Irrespective of the route of immunization, CpG or Poly I:C adjuvanted TMC-PA nanoparticles induced a significantly higher humoral response (total serum IgG and its isotypes viz., IgG1, IgG2a, and IgG2b), compared to their CpG or Poly I:C PA counterparts. This clearly demonstrates the synergistic behavior of CpG and Poly I:C with TMC nanoparticles. The adjuvant potential of TMC nanoparticles could be observed in all the three routes as the TMC-PA nanoparticles by themselves induced IgG titers (1–1.5 × 105) significantly higher than both CpG PA and Poly I:C PA groups (2–8 × 104). The effect of formulations on T-helper (Th) cell development was assessed by quantifying the Th1-dependant (TNF-α, IFN-γ, and IL-2), Th2-dependant (IL-4, IL-6, and IL-10), and Th17-type (IL-17A) cytokines. Adjuvanation with CpG and Poly I:C, the TMC-PA nanoparticles triggered a Th1 skewed immune response, as suggested by an increase in the levels of total IgG2a along with IFN-γ cytokine production. Interestingly, the TMC-PA group showed a Th2-biased immune response. Upon challenge with the B. anthracis Ames strain, CpG and Poly I:C adjuvanted TMC-PA nanoparticles immunized via the SC and IM routes showed the highest protective efficacy of ~83%. Altogether, the results suggest that CpG or Poly I:C adjuvanted, PA-loaded TMC nanoparticles could be used as an effective, non-toxic, second generation subunit-vaccine candidate against anthrax.
Detection of Parameter Change in Random Coefficient Integer-Valued Autoregressive Models

This paper considers the problem of testing for parameter change in random coefficient integer-valued autoregressive models. To overcome some size distortions of the existing estimate-based cumulative sum (CUSUM) test, we suggest estimating function-based test and residual-based CUSUM test. More specifically, we employ the estimating function of the conditional least squares estimator. Under the regularity conditions and the null hypothesis, we derive their limiting distributions, respectively. Simulation results demonstrate the validity of the proposed tests. A real data analysis is performed on the polio incidence data.
“Nash-in-Nash” Bargaining: A Microfoundation for Applied Work

A “Nash equilibrium in Nash bargains” has become a workhorse bargaining model in applied analyses of bilateral oligopoly. This paper proposes a noncooperative foundation for “Nash-in-Nash” bargaining that extends Rubinstein’s alternating offers model to multiple upstream and downstream firms. We provide conditions on firms’ marginal contributions under which there exists, for sufficiently short time between offers, an equilibrium with agreement among all firms at prices arbitrarily close to Nash-in-Nash prices, that is, each pair’s Nash bargaining solution given agreement by all other pairs. Conditioning on equilibria without delayed agreement, limiting prices are unique. Unconditionally, they are unique under stronger assumptions.
Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.
Finite-Time Observer Based Guidance and Control of Underactuated Surface Vehicles With Unknown Sideslip Angles and Disturbances

Suffering from complex sideslip angles, path following control of an under actuated surface vehicle (USV) becomes significantly challenging and remains unresolved. In this paper, a finite-time observer based guidance and control (FOGC) scheme for path following of an USV with time-varying and large sideslip angles and unknown external disturbances is proposed. The salient features of the proposed FOGC scheme are as follows: 1) time-varying large sideslip angle is exactly estimated by a finite-time sideslip observer, and thereby contributing to the sideslip-tangent line-of-sight guidance law which significantly enhances the robustness of the guidance system to unknown sideslip angles which are significantly large and time-varying; 2) a finite-time disturbance observer (FDO) is devised to exactly observe unknown external disturbances, and thereby implementing FDO-based surge and heading robust tracking controllers, which possess remarkable tracking accuracy and precise disturbance rejection, simultaneously; and 3) by virtue of cascade analysis and Lyapunov approach, global asymptotic stability of the integrated guidance-control system is rigorously ensured. Simulation studies and comparisons are conducted to demonstrate the effectiveness and superiority of the proposed FOGC scheme.
Circadian Differences in the Contribution of the Brain Renin-Angiotensin System in Genetically Hypertensive Mice

Objective: Genetically hypertensive BPH/2J mice are recognized as a neurogenic model of hypertension, primarily based on sympathetic overactivity and greater neuronal activity in cardiovascular regulatory brain regions. Greater activity of the central renin angiotensin system (RAS) and reactive oxygen species (ROS) reportedly contribute to other models of hypertension. Importantly the peripheral RAS contributes to the hypertension in BPH/2J mice, predominantly during the dark period of the 24 h light cycle. The aim of the present study was to determine whether central AT1 receptor stimulation and the associated ROS signaling contribute to hypertension in BPH/2J mice in a circadian dependent manner. Methods: Blood pressure (BP) was measured in BPH/2J and normotensive BPN/3J mice (n = 7–8) via pre-implanted telemetry devices. Acute intracerebroventricular (ICV) microinjections of AT1 receptor antagonist, candesartan, and the superoxide dismutase (SOD) mimetic, tempol, were administered during the dark and light period of the 24 h light cycle via a pre-implanted ICV guide cannula. In separate mice, the BP effect of ICV infusion of the AT1 receptor antagonist losartan for 7 days was compared with subcutaneous infusion to determine the contribution of the central RAS to hypertension in BPH/2J mice. Results: Candesartan administered ICV during the dark period induced depressor responses which were 40% smaller in BPH/2J than BPN/3J mice (Pstrain < 0.05), suggesting AT1 receptor stimulation may contribute less to BP maintenance in BPH/2J mice. During the light period candesartan had minimal effect on BP in either strain. ICV tempol had comparable effects on BP between strains during the light and dark period (Pstrain > 0.08), suggesting ROS signaling is also not contributing to the hypertension in BPH/2J mice. Chronic ICV administration of losartan (22 nmol/h) had minimal effect on BPN/3J mice. By contrast in BPH/2J mice, both ICV and subcutaneously administered losartan induced similar hypotensive responses (−12.1 ± 1.8 vs. −14.7 ± 1.8 mmHg, Proute = 0.31). Conclusion: While central effects of peripheral losartan cannot be excluded, we suggest the hypotensive effect of chronic ICV losartan was likely peripherally mediated. Thus, based on both acute and chronic AT1 receptor inhibition and acute ROS inhibition, our findings suggest that greater activation of central AT1 receptors or ROS are unlikely to be mediating the hypertension in BPH/2J mice.
Envy-free divisions of a partially burnt cake

Consider $n$ players having preferences over the connected pieces of a cake, identified with the interval $[0,1]$. A classical theorem due to Stromquist ensures under mild conditions that it is possible to divide the cake into $n$ connected pieces and assign these pieces to the players in an envy-free manner, i.e, no player strictly prefers a piece that has not been assigned to her. One of these conditions, considered as crucial, is that no player is happy with an empty piece. We prove that, even if this condition is not satisfied, it is still possible to get such a division when $n$ is a prime number or is equal to $4$. When $n$ is at most $3$, this has been previously proved by Erel Segal-Halevi, who conjectured that the result holds for any $n$. The main step in our proof is a new combinatorial lemma in topology, close to a conjecture by Segal-Halevi and which is reminiscent of the celebrated Sperner lemma: Instead of restricting the labels that can appear on each face of the simplex, the lemma considers labelings that enjoy a certain symmetry on the boundary.
Bufalin induces DNA damage response under hypoxic condition in myeloma cells

Hypoxia serves a crucial role in the development of drug resistance in various cancer cells. Therefore, many attempts targeting hypoxia are underway to overcome the drug resistance mediated by hypoxia. This strategy is useful for multiple myeloma (MM) cells, as MM cells reside within the bone marrow, where oxygen concentrations are relatively low. A natural compound library was screened to identify compounds exerting cytotoxicity in MM cells under hypoxic conditions. Bufalin exhibited marked cytotoxicity to MM cells under normoxic and hypoxic conditions. No significant toxicity was observed in lymphocytes obtained from healthy donors. Under normoxic conditions, bufalin induced a DNA double strand break (DSB) response, ROS induction and apoptosis within 24 with a rapid response compared with melphalan. Interestingly, the bufalin-induced DSB response was not impaired by low oxygen concentrations while the DSB response by melphalan was reduced. Furthermore, treatment with bufalin abolished HIF-1α expression under hypoxia, suggesting that bufalin exerts cytotoxicity under hypoxia by regulating HIF-1α. These results indicate that bufalin induces apoptosis in MM cells through DSB under hypoxic conditions by inhibiting HIF-1α, suggesting that bufalin could be useful for eradication of drug-resistant MM cells in the hypoxic microenvironment.
Alterations in the Functional Connectivity of Frontal Lobe Networks Preceding Emergence Delirium in Children

Background:This study aimed to characterize the electroencephalogram in children who emerged with emergence delirium (ED) compared with children without ED using methods that involved the assessment of cortical functional connectivity. Methods:Children aged 5 to 15 yr had multichannel electroencephalographic recordings during induction and emergence from anesthesia during minor surgical procedures. Of these, five children displayed ED after sevoflurane anesthesia. Measures of cortical functional connectivity previously used to evaluate anesthetic action in adults were compared between ED and age-, sex-, and anesthetic-matched non-ED children during emergence from anesthesia. Results:At the termination of sevoflurane anesthesia, the electroencephalogram in both ED and control patients showed delta frequency slowing and frontally dominant alpha activity, followed by a prolonged state with low-voltage, fast frequency activity (referred to as an indeterminate state). In children with ED, arousal with delirious behavior and a variety of electroencephalogram patterns occurred during the indeterminate state, before the appearance of normal wake or sleep patterns. The electroencephalogram in children without ED progressed from the indeterminate state to classifiable sleep or drowsy states, before peaceful awakening. Statistically significant differences in frontal lobe functional connectivity were identified between children with ED and non-ED. Conclusions:ED is associated with arousal from an indeterminate state before the onset of sleep-like electroencephalogram patterns. Increased frontal lobe cortical functional connectivity observed in ED, immediately after the termination of sevoflurane anesthesia, will have important implications for the development of methods to predict ED, the design of preventative strategies, and efforts to better understand its pathophysiology.
Modeling Gesture-Typing Movements

Word–Gesture keyboards allow users to enter text using continuous input strokes (also known as gesture typing or shape writing). We developed a production model of gesture typing input based on a human motor control theory of optimal control (specifically, modeling human drawing movements as a minimization of jerk—the third derivative of position). In contrast to existing models, which consider gestural input as a series of concatenated aiming movements and predict a user’s time performance, this descriptive theory of human motor control predicts the shapes and trajectories that users will draw. The theory is supported by an analysis of user-produced gestures that found qualitative and quantitative agreement between the shapes users drew and the minimum jerk theory of motor control. Furthermore, by using a small number of statistical via-points whose distributions reflect the sensorimotor noise and speed–accuracy trade-off in gesture typing, we developed a model of gesture production that can predict realistic gesture trajectories for arbitrary text input tasks. The model accurately reflects features in the figural shapes and dynamics observed from users and can be used to improve the design and evaluation of gestural input systems.
The Post-Annealing Effect on the Pinning Properties of GdBa2Cu3O 7−δ Coated Conductors via RCE-DR

We report the post-annealing effect on the pinning properties of GdBa<sub>2</sub>Cu<sub>3</sub>O<sub>7−δ </sub> (GdBCO) coated conductors (CCs) fabricated by a reactive co-evaporation deposition and reaction process. The GdBCO CCs annealed at 750 °C in the PO<sub>2</sub> of 300 mtorr for 15 min show the most enhanced critical current densities (<italic>J<sub>c</sub></italic>) for <italic>B</italic>//<italic>c</italic> due to the stacking faults (SF) piled up along the <italic>c</italic>-axis. The minimum <italic>J<sub>c</sub></italic> values of post-annealed samples in relatively higher fields such as 5 T at 77 K and 7 T at 65 K were larger than those of pristine sample; although their minimum <italic>J<sub>c</sub></italic> values were lower in relatively lower fields such as 1 T at 77 K and 3 T at 65 K. In-field <italic>J<sub>c</sub> </italic> values for <italic>B</italic>//<italic>ab</italic> were closely related to the density of SFs within samples. Analysis results by transmission electron microscopy revealed that the SF density was remarkably reduced after the post-annealing process, which is responsible for enhanced minimum <italic>J<sub>c</sub></italic> values and significantly degraded <italic>J<sub>c</sub></italic> values for <italic>B</italic>//<italic>ab</italic> in relatively higher fields.
Obesity accelerates murine gastric cancer growth by modulating the Sirt1/YAP pathway

A previous study from our group using an in vivo model demonstrated that diet induced-obesity increases the risk of gastric cancer and may prompt its growth. However, the molecular mechanisms underlying this association remain unclear and require further investigation. The aim of the present study was to investigate the potential molecular mechanisms through which obesity affects gastric cancer growth. In a subcutaneous mouse model, tumors were significantly larger in obese mice compared with non-obese and lean mice. In addition, markedly increased levels of Sirt1 and YAP protein were observed in the nucleus of cells from subcutaneous tumors from obese mice compared with those from lean mice. Murine forestomach carcinoma (MFC) cells treated with 5% sera from obese mice exhibited significantly increased expression of Sirt1 and YAP compared with MFC cells treated with sera from lean mice. In addition, a positive correlation was observed between Sirt1 expression and YAP expression, and between Sirt1 expression and serum visfatin levels in mice. These results suggested that diet-induced obesity could promote murine gastric cancer growth by modulating the Sirt1/YAP signaling pathway.
Application of AAPM TG 119 to volumetric arc therapy (VMAT)

The purpose of this study was to create AAPM TG 119 benchmark plans for volumetric arc therapy (VMAT) and to compare VMAT plans with IMRT plan data. AAPM TG 119 proposes a set of test clinical cases for testing the accuracy of IMRT planning and delivery system. For these test cases, we generated two treatment plans, the first plan using 7–9 static dMLC IMRT fields and a second plan utilizing one‐ or two‐arc VMAT technique. Dose optimization and calculations performed using 6 MV photons and Eclipse treatment planning system. Dose prescription and planning objectives were set according to the TG 119 goals. Plans were scored based on TG 119 planning objectives. Treatment plans were compared using conformity index (CI) for reference dose and homogeneity index (HI) (for D5‐D95). F or test cases prostate, head‐and‐neck, C‐shape and multitarget prescription dose are 75.6 Gy, 50.4 Gy, 50 Gy and 50 Gy, respectively. VMAT dose distributions were comparable to dMLC IMRT plans. Our planning results matched TG 119 planning results. For treatment plans studied, conformity indices ranged from 1.05–1.23 (IMRT) and 1.04–1.23 (VMAT). Homogeneity indices ranged from 4.6%–11.0% (IMRT) and 4.6%–10.5% (VMAT). The ratio of total monitor units necessary for dMLC IMRT to that of VMAT was in the range of 1.1–2.0. AAPM TG 119 test cases are useful to generate VMAT benchmark plans. At preclinical implementation stage, plan comparison of VMAT and IMRT plans of AAPM TG 119 test case allowed us to understand basic capabilities of VMAT technique. PACS number: 87.55. Qr
Optimal code generation for expression trees

We discuss the problem of generating code for a wide class of machines, restricting ourselves to the computation of expression trees. After defining a broad class of machines and discussing the properties of optimal programs on these machines, we derive a necessary and sufficient condition which can be used to prove the optimality of any code generation algorithm for expression trees on this class. We then present a dynamic programming algorithm which produces optimal code for any machine in the class; this algorithm runs in time which is linearly proportional to the number of vertices in an expression tree.
Metabolic Profiles in Obese Children and Adolescents with Insulin Resistance

BACKGROUND: In the past several decades, the increasing frequency of overweight and obese children and adolescents in the world has become a public health problem. It has contributed significantly to the already high tide of diabetes, cardiovascular and cerebrovascular diseases. AIM: To investigate the frequency of insulin resistance and to evaluate the metabolic profile of insulin resistant and non-insulin resistant obese children and adolescents. SUBJECTS AND METHODS: The study included 96 (45 boys, 51 girls) obese children and adolescents aged 4-17 years old (10.50 ± 2.87 years). Only participants with Body Mass Index ≥ 95 percentile were included. We analysed sera for fasting insulin levels (FI), fasting serum triglycerides (TG), total serum cholesterol (TC), fasting plasma glucose (FPG) and plasma glucose 2 hours after the performance of the oral glucose tolerance test (2-h G). Homeostatic model assessment for insulin resistance (HOMA-IR) index was calculated as fasting insulin concentration (microunits per millilitre) x fasting glucose concentration (millimolar)/22.5. The value of HOMA-IR above 3.16 was used as a cut-off value for both genders. RESULTS: Insulin resistance was determined in 58.33% of study participants. Insulin resistant participants had significantly higher level of 2-h G (p = 0.02), FI level (p = 0.000) as well as TG levels (p = 0.01), compared to non-insulin resistant group. Strikingly, 70.73% of the pubertal adolescents were insulin resistant in comparison to 49.09% of the preadolescents (p = 0.03). Significantly higher percentage of insulin-resistant participants were girls (p = 0.009). Moreover, a higher percentage of the girls (70.59%) than boys (44.44%) had HOMA-IR above 3.16 and had elevated FI levels (70.59% vs 48.89%). The difference in the frequency of insulin resistance among obese versus severely obese children and adolescents was not significant (p = 0.73, p > 0.05). Our study results also showed positive, but weak, correlation of HOMA-IR with age, FPG, TG and BMI of the participants (p < 0.05). CONCLUSION: Higher percentage of insulin-resistant participants was of female gender and was adolescents. In general, insulin resistant obese children and adolescents tend to have a worse metabolic profile in comparison to individuals without insulin resistance. It is of note that the highest insulin resistance was also linked with the highest concentrations of triglycerides.