Miracle-dz/UniFAR-FTUs huggingface dataset:
Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies

Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer to treat with overall 5‐year survival on the order of 50–60%. Therefore, predictive biomarkers for this disease would be valuable to provide more effective and individualized therapeutic approaches for these patients. While prognostic biomarkers such as p16 expression correlate with outcome; to date, no predictive biomarkers have been clinically validated for HNSCC. We generated xenografts in immunocompromised mice from six established HNSCC cell lines and evaluated response to cisplatin, cetuximab, and radiation. Tissue microarrays were constructed from pre‐ and posttreatment tumor samples derived from each xenograft experiment. Quantitative immunohistochemistry was performed using a semiautomated imaging and analysis platform to determine the relative expression of five potential predictive biomarkers: epidermal growth factor receptor (EGFR), phospho‐EGFR, phospho‐Akt, phospho‐ERK, and excision repair cross‐complementation group 1 (ERCC1). Biomarker levels were compared between xenografts that were sensitive versus resistant to a specific therapy utilizing a two‐sample t‐test with equal standard deviations. Indeed the xenografts displayed heterogeneous responses to each treatment, and we linked a number of baseline biomarker levels to response. This included low ERCC1 being associated with cisplatin sensitivity, low phospho‐Akt correlated with cetuximab sensitivity, and high total EGFR was related to radiation resistance. Overall, we developed a systematic approach to identifying predictive biomarkers and demonstrated several connections between biomarker levels and treatment response. Despite these promising initial results, this work requires additional preclinical validation, likely involving the use of patient‐derived xenografts, prior to moving into the clinical realm for confirmation among patients with HNSCC.
Import/export in digital rights management

The inherently controlled nature of digital rights management systems does little to promote inter-operability of systems provided by different vendors. In this paper, we consider import and export functionality by which multimedia protected by one digital rights management regime can be made available to a multimedia device that supports a different digital rights management regime, without compromising the protection afforded to the content under the original regime. We first identify specific issues to be addressed by developers of digital rights management import/export regimes and outline a variety of methods by which these regimes may be implemented. We then apply our observations to the specific example of import and export of content between the digital rights management regimes defined by the Motion Picture Exports Group and the Open Mobile Alliance.
Clinical and audiological features in auditory neuropathy.

OBJECTIVE To medically and audiologically characterize a population of children diagnosed as having auditory neuropathy (AN). STUDY DESIGN Retrospective medical chart review. SETTING/SUBJECTS We identified 22 patients from a pediatric otology clinic in a tertiary care pediatric hospital setting. RESULTS A genetic factor in AN is suggested by our identification of 3 families with 2 affected children and 2 other children with family histories that were positive for hearing loss. Clinical features common among our population included a history of hyperbilirubinemia (n = 11 [50%]), prematurity (n = 10 [45%]), ototoxic drug exposure (n = 9 [41%]), family history of hearing loss (n = 8 [36%]), neonatal ventilator dependence (n = 8 [36%]), and cerebral palsy (n = 2 [9%]). Full clinical and audiological data were available for 18 of the 22 children, including otoacoustic emissions, auditory brainstem responses with cochlear microphonics, and age-appropriate audiometric findings. Significantly, 9 of these 18 patients showed improvement in behavioral thresholds over time, indicating that a subset of children with AN may recover useful hearing levels. Also significant was the success of cochlear implantation in 4 children. CONCLUSIONS Management of AN in children requires serial clinical and audiometric evaluations, with a prominent role for behavioral testing. Prematurity, genetics, and hyperbilirubinemia appear to be significant factors in the development of AN; hyperbilirubinemia can be associated with spontaneous improvement of hearing thresholds. For those children not benefiting from amplification or FM systems, cochlear implantation remains a potentially successful method of habilitation.
Alcohol and Hepatitis C

Infection with the hepatitis C virus (HCV) has become a leading cause of scarring of the liver (i.e., fibrosis) and cirrhosis in the United States. HCV-related cirrhosis (with its associated complications, such as liver cancer) is a major cause of death, although it develops slowly and occurs only in approximately one-third of HCV-infected patients. Alcohol can exacerbate HCV infection and the associated liver damage by causing oxidative stress and promoting fibrosis, thereby accelerating disease progression to cirrhosis. Furthermore, alcohol may exacerbate the side-effects associated with current antiviral treatment of HCV infection and impair the body’s immune defense against the virus. Of the HCV-infected people who do not consume alcohol, only a minority progresses to severe liver disease and requires antiviral treatment. Because alcohol potentiates the fibrosis- and cancer-inducing actions of HCV, alcoholics are particularly vulnerable to HCV infection and most in need of treatment.
TPK 1 Is a Vacuolar Ion Channel Different from the Slow-Vacuolar Cation Channel 1

TPK1 (formerly KCO1) is the founding member of the family of two-pore domain K channels in Arabidopsis (Arabidopsis thaliana), which originally was described following expression in Sf9 insect cells as a Caand voltage-dependent outwardly rectifying plasma membrane K channel. In plants, this channel has been shown by green fluorescent protein fusion to localize to the vacuolar membrane, which led to speculations that the TPK1 gene product would be a component of the nonselective, Ca and voltage-dependent slow-vacuolar (SV) cation channel found in many plants species. Using yeast (Saccharomyces cerevisiae) as an expression system for TPK1, we show functional expression of the channel in the vacuolar membrane. In isolated vacuoles of yeast yvc1 disruption mutants, the TPK1 gene product shows ion channel activity with some characteristics very similar to the SV-type channel. The open channel conductance of TPK1 in symmetrically 100 mM KCl is slightly asymmetric with roughly 40 pS at positive membrane voltages and 75 pS at negative voltages. Similar to the SV-type channel, TPK1 is activated by cytosolic Ca21, requiring micromolar concentration for activation. However, in contrast to the SV-type channel, TPK1 exhibits strong selectivity for K over Na, and its activity turned out to be independent of the membrane voltage over the range of680 mV. Our data clearly demonstrate that TPK1 is a voltage-independent, Ca-activated, K-selective ion channel in the vacuolar membrane that does not mediate SV-type ionic currents.
SoC TAM Design to Minimize Test Application Time

We propose a new test access mechanism(TAM) design to reduce the System-on-chip (SoC) test application time (TAT) under various hardware and power constraints. Prior works on TAM design focus on designing TAM architecture based on fixed cores parameters, which assumes unchanged internal scan chains and layout arrangement of cores, and therefore is unable to make effective use of SoC resources for testing purpose. Moreover, previous works on SoC test scheduling fail to incorporate the presented hardware and power constraints at once, which may render the testing result inapplicable. The proposed TAM design is tightly integrated with scan chain redesign and layout arrangement of individual core in SoC, and thus able to reduce the wiring complexity and to make effective use of TAM resources. Various hardware and power constraints are considered in this work, which are often ignored or partly addressed by previous SoC test scheduling work. Dynamic voltage and frequency scaling (DVFS) is adopted in test scheduling to minimize testing time. Both session-less and session-based scheduling are formulated in Mixed-integer linear programming. Experimental result of a set of ITC'02 benchmark shows up to 69% of reduction in test application time with the proposed TAM Design and DVFS scheduling.
Designing Collective Behavior in a Termite-Inspired Robot Construction Team

Robots programmed with simple construction rules can work independently but collectively to build a complex structure. [Also see Perspective by Korb] Complex systems are characterized by many independent components whose low-level actions produce collective high-level results. Predicting high-level results given low-level rules is a key open challenge; the inverse problem, finding low-level rules that give specific outcomes, is in general still less understood. We present a multi-agent construction system inspired by mound-building termites, solving such an inverse problem. A user specifies a desired structure, and the system automatically generates low-level rules for independent climbing robots that guarantee production of that structure. Robots use only local sensing and coordinate their activity via the shared environment. We demonstrate the approach via a physical realization with three autonomous climbing robots limited to onboard sensing. This work advances the aim of engineering complex systems that achieve specific human-designed goals. Robot Rules In the case of mound-building termites, colonies comprising thousands of independently behaving insects build intricate structures, orders of magnitude larger than themselves, using indirect communication methods. In this process, known as stigmergy, local cues in the structure itself help to direct the workers. Werfel et al. (p. 754; see the Perspective by Korb) wanted to construct complex predetermined structures using autonomous robots. A successful system was designed so that for a given final structure, the robots followed basic rules or “structpaths” in order to complete the task.
Vertically-Suspended Environmental Enrichment Alters the Velocity Profiles of Circular Fish Rearing Tanks

The inclusion of vertically-suspended environmental enrichment in circular tanks has produced substantial benefits during fish rearing. This study examined the tank water velocity profiles of four different vertically-suspended structures (rod array, extended rod array, single angle array, double angle array) and a control (no environmental enrichment) at two incoming water velocities (18.3 cm/s and 54.9 cm/s) in 1.8-m diameter circular tanks. At both of the incoming water velocities, overall water velocities throughout the tank were significantly reduced with the addition of any environmental enrichment in comparison to the control. In addition, the overall water velocities in the double angle array were significantly lower than the other three enrichment treatments. The pattern of significant reductions in velocity with the use of any environmental enrichment, with further significant velocity reductions in the double angle treatment, was repeated when the data were combined for each sampling depth, radius from the center, and degree (circular arc). Although considerable variation in water velocity was observed at each specific sampling location with both incoming velocities, significantly lower velocities were observed at nearly every sampling location with the addition of any environmental enrichment to the circular tank. In addition, the double angle array consistently produced the lowest velocities among the environmental enrichment treatments. The changes in velocity profiles from vertically-suspended environmental enrichment may be at least partially-responsible for the frequently-observed improvements in fish growth.
Cooperative Caching for Financial Databases with Hot Spots

We measure the performance of several cooperative caching policies for a databas e with hot spots. The workload consists of queries and append-only update transactions, an d i modeled after a financial database of stock (historical) trading information. We show that cooperative caching is effective for this application. We show t at selecting the correct set of peer servers when servicing a cache miss is crucial to achieving high perfo rmance, and we demonstrate a greedy algorithm that performs close to optimal for this work load. We also evaluate several cache replacement policies and show that a 2 nd-chance algorithm performs best. In a 2 nd-chance algorithm, replaced pages are transferred to a peer server rather than being discarded. When a page is selected for replacement a 2nd time, the page is discarded. Our results can be applied in the design of “proxy” servers for databases or w eb servers where a layer of proxy servers are used to scale the system performance.
Circulating IgE in Patients with Ordinary and Crusted Scabies

Abstract Serum from seven patients with ordinary scabies and six with crusted scabies were screened by immunoblotting for IgE- and IgG-specific proteins in an extract of the mite, Sarcoptes scabiei variety canis. Sera from atopic individuals without sensitivity to house dust mites were used as controls. Serum from all of the patients with crusted scabies showed strong IgE binding to 11–21 and IgG binding to 1–7 scabies proteins. In contrast, three of the seven patients with ordinary scabies showed IgE binding to one to six scabies proteins, and their antibody binding was much weaker. Patients with crusted scabies had serum antibody that reacted with larger molecular weight proteins compared with patients with ordinary scabies. The results of this study indicate that patients with crusted scabies showed a pronounced IgE response to scabies mites, whereas patients with ordinary scabies did not.
Validated method for phytohormone quantification in plants

Phytohormones are long time known as important components of signaling cascades in plant development and plant responses to various abiotic and biotic challenges. Quantifications of phytohormone levels in plants are typically carried out using GC or LC-MS/MS systems, due to their high sensitivity, specificity, and the fact that not much sample preparation is needed. However, mass spectrometer-based analyses are often affected by the particular sample type (different matrices), extraction procedure, and experimental setups, i.e., the chromatographic separation system and/or mass spectrometer analyser (Triple-quadrupole, Iontrap, TOF, Orbitrap). For these reasons, a validated method is required in order to enable comparison of data that are generated in different laboratories, under different experimental set-ups, and in different matrices. So far, many phytohormone quantification studies were done using either QTRAP or Triple-quadrupole mass spectrometers. None of them was performed under the regime of a fully-validated method. Therefore, we developed and established such validated method for quantification of stress-related phytohormones such as jasmonates, abscisic acid, salicylic acid, IAA, in the model plant Arabidopsis thaliana and the fruit crop Citrus sinensis, using an Iontrap mass spectrometer. All parameters recommended by FDA (US Food and Drug Administration) or EMEA (European Medicines Evaluation Agency) for validation of analytical methods were evaluated: sensitivity, selectivity, repeatability and reproducibility (accuracy and precision).
Effective School Actions for Mitigating Seasonal Influenza Outbreaks in Niigata, Japan

Background Japan has implemented various school actions during seasonal influenza outbreaks since the 1950's under the School Health Law. However, the effective duration, extent, and timing of closures remain unresolved. Materials and Methods We conducted a retrospective study on the relationship between elementary class closures and influenza outbreak control during four consecutive influenza seasons from the 2004-2005 to 2007-2008 school years in Joetsu, Niigata, Japan. Among a total of 1,061 classes of 72 schools, 624 cases of influenza outbreaks were documented among 61 schools. Results Class closures were carried out in a total of 62 cases in response to influenza outbreak, which was defined as a student absentee rate of greater than 10% due to influenza or influenza-like illness. Of these cases, two-day class closures were conducted the day after reaching a 10% student absentee rate in 28 cases and other types of closures were initiated in 34 cases. A markedly higher number of outbreak cases ended within one week for two-day class closures compared to the other types of closures (82.1% vs. 20.6%, respectively). The significant association between two-day class closures and interruption of an outbreak within one week was confirmed using a multivariable model adjusted for the season, grade, day of the week of an outbreak start, and absentee rate on the day of an outbreak start (OR, 3.18; 95% CI, 1.12–9.07; p = 0.030). Conclusions Our results suggest that a two-day class closure carried out the day after reaching a 10% absentee rate is an effective approach for mitigating influenza outbreaks in elementary schools.
A General Projection Property for Distribution Families

Surjectivity of linear projections between distribution families with fixed mean and covariance (regardless of dimension) is re-derived by a new proof. We further extend this property to distribution families that respect additional constraints, such as symmetry, unimodality and log-concavity. By combining our results with classic univariate inequalities, we provide new worst-case analyses for natural risk criteria arising in classification, optimization, portfolio selection and Markov decision processes.
Activity energy expenditure and incident cognitive impairment in older adults.

BACKGROUND Studies suggest that physically active people have reduced risk of incident cognitive impairment in late life. However, these studies are limited by reliance on self-reports of physical activity, which only moderately correlate with objective measures and often exclude activity not readily quantifiable by frequency and duration. The objective of this study was to investigate the relationship between activity energy expenditure (AEE), an objective measure of total activity, and incidence of cognitive impairment. METHODS We calculated AEE as 90% of total energy expenditure (assessed during 2 weeks using doubly labeled water) minus resting metabolic rate (measured using indirect calorimetry) in 197 men and women (mean age, 74.8 years) who were free of mobility and cognitive impairments at study baseline (1998-1999). Cognitive function was assessed at baseline and 2 or 5 years later using the Modified Mini-Mental State Examination. Cognitive impairment was defined as a decline of at least 1.0 SD (9 points) between baseline and follow-up evaluations. RESULTS After adjustment for baseline Modified Mini-Mental State Examination scores, demographics, fat-free mass, sleep duration, self-reported health, and diabetes mellitus, older adults in the highest sex-specific tertile of AEE had lower odds of incident cognitive impairment than those in the lowest tertile (odds ratio, 0.09; 95% confidence interval, 0.01-0.79). There was also a significant dose response between AEE and incidence of cognitive impairment (P = .05 for trend over tertiles). CONCLUSIONS These findings indicate that greater AEE may be protective against cognitive impairment in a dose-response manner. The significance of overall activity in contrast to vigorous or light activity should be determined.
Kinetics of Nutrient Removal by Nano Zero‐Valent Iron under Different Biochemical Environments

The effectiveness of nano zero‐valent iron (NZVI; an average size of 55 nm at a concentration of 200 mg Fe/L) in nutrient removal was determined under anaerobic, anoxic, and aerobic conditions. Compared to the rate of reduction of nitrate nitrogen (‐N) to ammoniacal nitrogen ( ‐N) by NZVI alone, the presence of activated sludge increased the rate of complete reduction by 300%. About 31% of ‐N was converted to ‐N through NZVI‐facilitated dissimilatory nitrate reduction to ammonium, while 56% of ‐N was removed by heterotrophic denitrification. The presence of sludge reduced the rates of phosphorus removal by NZVI, with the first‐order reaction rate constants of 0.06/hour, 0.42/hour, and 0.18/hour under anaerobic, anoxic, and aerobic conditions, respectively. The highest phosphorus removal efficiency (95%) by NZVI was observed under anoxic abiotic conditions, whereas the efficiency dropped to 31% under anaerobic biotic conditions, which was attributed to significant sludge‐facilitated NZVI agglomeration.
Temperature sensor placement in thermal management systems for MPSoCs

Modern high-performance processors employ thermal management systems, which rely on accurate readings of on-die thermal sensors. Systematic tools for analysis and determination of best allocation and placement of thermal sensors is therefore a highly relevant problem. This paper proposes a novel technique for determining the placement of temperature sensors on complex Multi-Processor Systems-on-Chips (MPSoCs) floorplans. The proposed method first analyzes the observability of the system for all the possible sensor placement configurations. Minimum sensors placements ensuring the observability of the portion of the MPSoC system that is relevant to the designer are then compared with simulation-based data coming from a wide set of benchmarks. Pareto points identifying the best configurations are than stored. According to user designer needs the best configuration is selected and a specific location is assigned to each sensor. We compared the proposed method with state-of-the-art approaches [5], [6]. Results show a reduction up to 4.5× in the number of required sensors.
CO2-Driven Ocean Acidification Alters and Weakens Integrity of the Calcareous Tubes Produced by the Serpulid Tubeworm, Hydroides elegans

As a consequence of anthropogenic CO2-driven ocean acidification (OA), coastal waters are becoming increasingly challenging for calcifiers due to reductions in saturation states of calcium carbonate (CaCO3) minerals. The response of calcification rate is one of the most frequently investigated symptoms of OA. However, OA may also result in poor quality calcareous products through impaired calcification processes despite there being no observed change in calcification rate. The mineralogy and ultrastructure of the calcareous products under OA conditions may be altered, resulting in changes to the mechanical properties of calcified structures. Here, the warm water biofouling tubeworm, Hydroides elegans, was reared from larva to early juvenile stage at the aragonite saturation state (ΩA) for the current pCO2 level (ambient) and those predicted for the years 2050, 2100 and 2300. Composition, ultrastructure and mechanical strength of the calcareous tubes produced by those early juvenile tubeworms were examined using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and nanoindentation. Juvenile tubes were composed primarily of the highly soluble CaCO3 mineral form, aragonite. Tubes produced in seawater with aragonite saturation states near or below one had significantly higher proportions of the crystalline precursor, amorphous calcium carbonate (ACC) and the calcite/aragonite ratio dramatically increased. These alterations in tube mineralogy resulted in a holistic deterioration of the tube hardness and elasticity. Thus, in conditions where ΩA is near or below one, the aragonite-producing juvenile tubeworms may no longer be able to maintain the integrity of their calcification products, and may result in reduced survivorship due to the weakened tube protection.