Miracle-dz/UniFAR-FTUs huggingface dataset:
Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine

The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunochemotherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition; prolong chemotherapeutic plasma half-life (reduces administration frequency); minimize innocent exposure of normal tissues and healthy organ systems; and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunochemotherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between gemcitabine-equivalent concentrations of 10−12 M and 10−6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunochemotherapeutics. Results: Gemcitabine-(C4-amide)-[anti-EGFR], gemcitabine-(C4-amide)-[anti-HER2/neu] and the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] all had anti-neoplastic cytotoxic potency against mammary adenocarcinoma. Gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] produced progressive increases in anti-neoplastic cytotoxicity that were greatest between gemcitabine-equivalent concentrations of 10−9 M and 10−6 M. Dual simultaneous combinations of gemcitabine-(C4-amide)-[anti-EGFR] with gemcitabine-(C4-amide)-[anti-HER2/neu] produced levels of anti-neoplastic cytotoxicity intermediate between each of the individual covalent gemcitabine immunochemotherapeutics. Total anti-neoplastic cytotoxicity of the dual simultaneous combination of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) was substantially higher when formulated with [Se]-methylsele-nocysteine.
Dynamics of the Firing Probability of Noisy Integrate-and-Fire Neurons

Cortical neurons in vivo undergo a continuous bombardment due to synaptic activity, which acts as a major source of noise. Here, we investigate the effects of the noise filtering by synapses with various levels of realism on integrate-and-fire neuron dynamics. The noise input is modeled by white (for instantaneous synapses) or colored (for synapses with a finite relaxation time) noise. Analytical results for the modulation of firing probability in response to an oscillatory input current are obtained by expanding a Fokker-Planck equation for small parameters of the problemwhen both the amplitude of the modulation is small compared to the background firing rate and the synaptic time constant is small compared to the membrane time constant. We report here the detailed calculations showing that if a synaptic decay time constant is included in the synaptic current model, the firing-rate modulation of the neuron due to an oscillatory input remains finite in the high-frequency limit with no phase lag. In addition, we characterize the low-frequency behavior and the behavior of the high-frequency limit for intermediate decay times. We also characterize the effects of introducing a rise time to the synaptic currents and the presence of several synaptic receptors with different kinetics. In both cases, we determine, using numerical simulations, an effective decay time constant that describes the neuronal response completely.
Exchange Rates and Fiscal Adjustments: Evidence from the OECD and Implications for the EMU

Abstract This paper investigates whether monetary and exchange rate policies are important for the success of major fiscal adjustments. We assess their role controlling for other determinants of success identified in the literature, including the size and composition of the deficit cut, the level of public debt and the rate of economic growth. We find that successful adjustments are preceded by exchange rate depreciations. Empirically, a depreciation of the nominal effective exchange of one standard deviation of the sample mean in the two years before an adjustment increases the probability of success by 2 percentage points. The size and composition of the deficit cut are also important determinants of success: an increase of one standard deviation of the sample mean raises the probability of success by 3 and 4 percentage points, respectively. One implication of our results is that it may be more difficult to attain persistent fiscal adjustments within the Economic and Monetary Union of Europe, since the adoption of a single currency rules out the use of exchange rate policy among member countries.
Role of substrate concentration in mitosis and hyphal extension of Aspergillus.

The filamentous fungi Aspergillus oryzae and A. niger grow by apical extension of multinucleate hyphae that are subdivided into compartments by cross-walls called septa. Submerged cultivation, image analysis, and fluorescence microscopy were used to study the role of the carbon source on mitosis and hyphal extension in these fungi. In the two species of Aspergillus, the length of the apical compartment, the number of nuclei in the apical compartment, and the hyphal diameter were regulated in response to the surrounding glucose concentration. A long apical compartment with many nuclei was the result of a high glucose concentration, whereas a short apical compartment with few nuclei was the result of a low glucose concentration. This is the first study of the influence of glucose concentration on nuclear mitosis and septation in filamentous fungi grown submerged. In addition, this is the first time a model of the duplication cycle in higher filamentous fungi has been simulated.
Bauxite residue sinter phase transformations

Bauxite residue (BR) contains between 2 and 35 wt % aluminium (expressed as Al2O3). This aluminium is lost from Bayer process, primarily due to the formation of sodium containing desilication products (DSP), incomplete digestion of aluminium bearing minerals and in some cases early precipitation of gibbsite. The sintering process has been used commercially in the processing of high silica bauxites and could be used effectively for the recovery of aluminium and sodium values from bauxite residue (BR). In the sinter process BR is calcined with Na2CO3 to produce a soluble NaAlO2 product, while stabilising the silicates with CaO2. The recovery of this material is the first step in total BR valorisation. In this research, two distinct BRs’ are characterised before and after sintering. The mineralogy was quantified using XDB4,5. Key reaction equilibrium was considered using the Factsage thermodynamic modelling package5, contributing to the understanding of potential reaction pathways during sintering.
Eight-Shaped Hatching Increases the Risk of Inner Cell Mass Splitting in Extended Mouse Embryo Culture

Increased risk of monozygotic twinning (MZT) has been shown to be associated with assisted reproduction techniques, particularly blastocyst culture. Interestingly, inner cell mass (ICM) splitting in human ‘8’-shaped hatching blastocysts that resulted in MZT was reported. However, the underlying cause of MZT is not known. In this study, we investigated in a mouse model whether in vitro culture leads to ICM splitting and its association with hatching types. Blastocyst hatching was observed in: (i) in vivo developed blastocysts and (ii–iii) in vitro cultured blastocysts following in vivo or in vitro fertilization. We found that ‘8’-shaped hatching occurred with significantly higher frequency in the two groups of in vitro cultured blastocysts than in the group of in vivo developed blastocysts (24.4% and 20.4% versus 0.8%, respectively; n = 805, P < 0.01). Moreover, Oct4 immunofluorescence staining was performed to identify the ICM in the hatching and hatched blastocysts. Scattered and split distribution of ICM cells was observed around the small zona opening of ‘8’-shaped hatching blastocysts. This occurred at a high frequency in the in vitro cultured groups. Furthermore, we found more double OCT4-positive masses, suggestive of increased ICM splitting in ‘8’-shaped hatching and hatched blastocysts than in ‘U’-shaped hatching and hatched blastocysts (12.5% versus 1.9%, respectively; n = 838, P < 0.01). Therefore, our results demonstrate that extended in vitro culture can cause high frequencies of ‘8’-shaped hatching, and ‘8’-shaped hatching that may disturb ICM herniation leading to increased risk of ICM splitting in mouse blastocysts. These results may provide insights into the increased risk of human MZT after in vitro fertilization and blastocyst transfer.
Effectiveness of radiofrequency ablation for hepatocellular carcinomas larger than 3 cm in diameter.

HYPOTHESIS Radiofrequency ablation is a safe and effective treatment for hepatocellular carcinomas 3.1 to 8.0 cm in diameter. DESIGN Case series with prospective data collection. SETTING Tertiary referral center. PATIENTS Eighty-six patients with hepatocellular carcinoma treated with radiofrequency ablation from May 1, 2001, to December 31, 2002, were placed into categories of those with tumors 3 cm or smaller (group 1, n = 51) and those with tumors 3.1 to 8.0 cm (group 2, n = 35) in diameter. INTERVENTIONS Radiofrequency ablation was performed with a single or cluster cool-tip electrode. The choice of treatment route was based on tumor size and position. MAIN OUTCOME MEASURES Complication, treatment mortality, and complete ablation rates. RESULTS Radiofrequency ablation was performed percutaneously in 26 patients in group 1 and 9 patients in group 2, with laparoscopy in 2 patients in group 1 and 1 patient in group 2, and with open operation in 23 patients in group 1 and 25 patients in group 2. The complication rates were 12% and 17% in group 1 and group 2, respectively (P =.48); treatment mortality rates were 0% and 3%, respectively (P =.41). Complete ablation rates after a single session of ablation assessed by means of computed tomography 1 month after treatment were 94% and 91% in group 1 and group 2, respectively (P =.68). CONCLUSION Radiofrequency ablation is a safe and effective treatment for patients with hepatocellular carcinomas 3.1 to 8.0 cm in diameter.
Automatic OS Kernel TCB Reduction by Leveraging Compile-Time Configurability

The Linux kernel can be a threat to the dependability of systems because of its sheer size. A simple approach to produce smaller kernels is to manually configure the Linux kernel. However, the more than 11,000 configuration options available in recent Linux versions render this a demanding task. We report on designing and implementing the first automated generation of a workload-tailored kernel configuration and discuss the security gains such an approach offers in terms of reduction of the Trusted Computing Base (TCB) size. Our results show that the approach prevents the inclusion of 10% of functions known to be vulnerable in the past.
Functional Relations and Special Values of Mordell-tornheim Triple Zeta and L-functions

In this paper, we prove the existence of meromorphic continuation of certain triple zeta-functions of Lerch's type. Based on this result, we prove some functional relations for triple zeta and L-functions of the Mordell-Tornheim type. Using these functional relations, we prove new explicit evaluation formulas for special values of these functions. These can be regarded as triple analogues of known results for double zeta and L-functions.
The way to the pastures: how to reconcile community-based pasture management with mobility in agro-pastoral systems in the Naryn province of Kyrgyzstan

The new community-based pasture management introduced in Kyrgyzstan at the municipality level in 2009 intended to renew long distance transhumance, which had been significantly reduced after the end of the Soviet Union. Kyrgyzstan is characterized by a mountainous geography and a long history of agro-pastoralism. In this paper we explore how the new formal management model influences the mobility of herds and households at the local level. The conceptual framework used for the analysis is based on the principles for the management of common-pool resources designed by Ostrom and reviewed by Cox. Because municipalities are not homogenous, different groups of stakeholders have different interests in mobility and different access to decision-making in the newly created community-based institution. The main result of this research is that, although the formal institution responsible for pasture management does not focus on participation and representation, informal pasture management groups develop their own mechanism to lobby their interests. Mobility meets the needs of the different groups, or at least actions to prompt mobility are not conducted at the expense of any group.
Do big athletes have big hearts? Impact of extreme anthropometry upon cardiac hypertrophy in professional male athletes

Aim Differentiating physiological cardiac hypertrophy from pathology is challenging when the athlete presents with extreme anthropometry. While upper normal limits exist for maximal left ventricular (LV) wall thickness (14 mm) and LV internal diameter in diastole (LVIDd, 65 mm), it is unknown if these limits are applicable to athletes with a body surface area (BSA) >2.3 m2. Purpose To investigate cardiac structure in professional male athletes with a BSA>2.3 m2, and to assess the validity of established upper normal limits for physiological cardiac hypertrophy. Methods 836 asymptomatic athletes without a family history of sudden death underwent ECG and echocardiographic screening. Athletes were grouped according to BSA (Group 1, BSA>2.3 m2, n=100; Group 2, 2–2.29 m2, n=244; Group 3, <1.99 m2, n=492). Results There was strong linear relationship between BSA and LV dimensions; yet no athlete with a normal ECG presented a maximal wall thickness and LVIDd greater than 13 and 65 mm, respectively. In Group 3 athletes, Black African ethnicity was associated with larger cardiac dimensions than either Caucasian or West Asian ethnicity. Three athletes were diagnosed with a cardiomyopathy (0.4% prevalence); with two athletes presenting a maximal wall thickness >13 mm, but in combination with an abnormal ECG suspicious of an inherited cardiac disease. Conclusion Regardless of extreme anthropometry, established upper limits for physiological cardiac hypertrophy of 14 mm for maximal wall thickness and 65 mm for LVIDd are clinically appropriate for all athletes. However, the abnormal ECG is key to diagnosis and guides follow-up, particularly when cardiac dimensions are within accepted limits.
Non-commutative path planning for tours with diversified attractions

Path planning is essential for all tour activities, including biking. In fact, path planning is a very classic and interesting topic that has attracted much attention due to the need for human movement. Depending on the nature of the problem, different solutions have been provided. Many of the solutions exhibit the characteristics of commutative properties; for example, the shortest path problem requires the solution to show the summation of the path weights to be the minimum for which the summation operation is commutative. However, there are situations where the evaluation function is non-commutative. This work considers the planning required for a sightseeing tour with diversified attractions. We formulate the path planning problem by defining a way to evaluate tour paths with various types of attractions and propose a scheme to solve the problem to increase customer satisfaction.
Impact of 6-Month Aerobic Exercise on Alzheimer's Symptoms

Little is known about how aerobic exercise affects Alzheimer’s disease (AD). The purpose of this pilot study was to test the impact of 6-month cycling on AD symptoms in community-dwelling older adults with mild-to-moderate AD, using a single-group, repeated-measures design (n = 26). AD symptoms were measured with the AD Assessment Scale–Cognitive (ADAS-Cog), Disability in AD (DAD), and Neuropsychiatric Inventory–Caregiver (NPI-Q) scales at baseline, 3 and 6 months. Data were analyzed using mixed linear models. The ADAS-Cog, DAD, and NPI-Q severity scores remained unchanged over the 6-month period, while caregiver distress decreased 40% (p < .05). We conclude that aerobic exercise may reduce AD symptoms and appears effective in decreasing caregiver distress. Further randomized controlled trials are needed to examine the effects of aerobic exercise in AD.
The Name-Your-Own-Price Channel in the Travel Industry: An Analytical Exploration

Name-your-own-price (NYOP) retailers, such as Priceline, offer an alternative distribution channel for service providers in the travel industry such as airlines, hotels, and car rental companies. Our research employs an analytical model to identify and understand key trade-offs driving the decision by a service provider to employ an NYOP channel, assuming that such a channel is available. This decision requires the existence of forces that counteract the adverse consequences of cannibalization of sales through traditional posted-price channels. Our analysis provides some insight into these forces. Contracting with the NYOP retailer facilitates market segmentation and price discrimination, and allows for disposal of excess capacity after meeting business travel demand. However, the cost of this flexibility is that the service provider can no longer credibly precommit to maintaining high prices when there is unsold capacity. Also, when contracting with an independent retailer, the service provider is unable to extract the entire revenue generated from NYOP consumers. A key insight from our model is that the rationale for contracting with an NYOP retailer is driven by the uncertainty in business travel demand, not the expectation of excess capacity. Indeed, all else equal, the larger the capacity, the less likely it is that contracting with an NYOP retailer is the right decision on the part of the service provider.
Experimental Study on Light Weight Concrete-Filled Steel Tubes

Tests on steel tubular columns of rectangular and circular sections filled with normal and lightweight concrete were performed to investigate the behavior of such columns under axial loadings. Comparison between normal and lightweight concrete filled steel columns for different column cross-sections using Euro Code 4 and BS 5400 codes was also conducted. The test results showed that both types of filled columns failed due to overall buckling; while hollow steel columns failed due to local buckling at the ends. According to these results, further interest was taken onto the replacement of normal concrete by lightweight concrete due to its low specific gravity and thermal conductivity.
A study of the glazing techniques and provenances of Tang
 sancai
 glazes using elemental and lead isotope analyses

This study discusses the elemental compositions and lead isotope ratios of Tang sancai glazes unearthed from the Huangpu kiln, Huangye kiln and two Tang sancai tomb sites. The various glazes feature distinct lead isotope ratios and trace element characteristics, which can be interpreted as evidence for the use of different lead ore deposits and siliceous raw materials in the glazes. This is a strong indication that lead isotopes combined with trace element analysis could be used as a viable approach for identifying the provenance of Tang sancai of unknown origin by linking them to kiln sites, This provenance technique could be significant in the interpretation of ancient ceramic trade and communication patterns. In this study, the provenance of several Tang sancai glazes of uncertain origin were determined using this method: some Tang sancai wares unearthed in Xi'an City were produced in the kiln near Luoyang City and then traded to Xi'an City, providing an idea of ancient Tang sancai ceramic trade routes
Circular Polarization from Gamma-Ray Burst Afterglows

We investigate the circular polarization (CP) from gamma-ray burst (GRB) afterglows. We show that a tangled magnetic field cannot generate CP without an ordered field, because there is always an oppositely directed field, so that no handedness exists. This implies that the observation of CP could be a useful probe of an ordered field, which carries valuable information on the GRB central engine. By solving the transfer equation of polarized radiation, we find that the CP reaches 1% at radio frequencies and 0.01% at optical for the forward shock and 10%-1% at radio and 0.1%-0.01% at optical for the reverse shock.
Identifying Recombination Hot Spots in the HIV-1 Genome

ABSTRACT HIV-1 infection is characterized by the rapid generation of genetic diversity that facilitates viral escape from immune selection and antiretroviral therapy. Despite recombination's crucial role in viral diversity and evolution, little is known about the genomic factors that influence recombination between highly similar genomes. In this study, we use a minimally modified full-length HIV-1 genome and high-throughput sequence analysis to study recombination in gag and pol in T cells. We find that recombination is favored at a number of recombination hot spots, where recombination occurs six times more frequently than at corresponding cold spots. Interestingly, these hot spots occur near important features of the HIV-1 genome but do not occur at sites immediately around protease inhibitor or reverse transcriptase inhibitor drug resistance mutations. We show that the recombination hot and cold spots are consistent across five blood donors and are independent of coreceptor-mediated entry. Finally, we check common experimental confounders and find that these are not driving the location of recombination hot spots. This is the first study to identify the location of recombination hot spots between two similar viral genomes with great statistical power and under conditions that closely reflect natural recombination events among HIV-1 quasispecies. IMPORTANCE The ability of HIV-1 to evade the immune system and antiretroviral therapy depends on genetic diversity within the viral quasispecies. Retroviral recombination is an important mechanism that helps to generate and maintain this genetic diversity, but little is known about how recombination rates vary within the HIV-1 genome. We measured recombination rates in gag and pol and identified recombination hot and cold spots, demonstrating that recombination is not random but depends on the underlying gene sequence. The strength and location of these recombination hot and cold spots can be used to improve models of viral dynamics and evolution, which will be useful for the design of robust antiretroviral therapies.