Miracle-dz/UniFAR-FTUs huggingface dataset:
From Famine to Feast: Developing Early-Phase Combination Immunotherapy Trials Wisely

Not until the turn of this century has immunotherapy become a fundamental component of cancer treatment. While monotherapy with immune modulators, such as immune checkpoint inhibitors, provides a subset of patients with durable clinical benefit and possible cure, combination therapy offers the potential for antitumor activity in a greater number of patients. The field of immunology has provided us with a plethora of potential molecules and pathways to target. This abundance makes it impractical to empirically test all possible combinations efficiently. We recommend that potential immunotherapy combinations be chosen based on sound rationale and available data to address the mechanisms of primary and acquired immune resistance. Novel trial designs may increase the proportion of patients receiving potentially efficacious treatments and, at the same time, better define the balance of clinical activity and safety. We believe that implementing a strategic approach in the early development of immunotherapy combinations will expedite the delivery of more effective therapies with improved safety and durable outcomes. Clin Cancer Res; 23(17); 4980–91. ©2017 AACR. See all articles in this CCR Focus section, “Clinical Trial Design Considerations in the Immuno-oncology Era. ”
Brief review of the chicken Major Histocompatibility Complex: the genes, their distribution on chromosome 16, and their contributions to disease resistance

ABSTRACT Nearly all genes presently mapped to chicken chromosome 16 (GGA 16) have either a demonstrated role in immune responses or are considered to serve in immunity by reason of sequence homology with immune system genes defined in other species. The genes are best described in regional units. Among these, the best known is the polymorphic major histocompatibility complex-B (MHC-B ) region containing genes for classical peptide antigen presentation. Nearby MHC-B is a small region containing two CD1 genes, which encode molecules known to bind lipid antigens and which will likely be found in chickens to present lipids to specialized T cells, as occurs with CD1 molecules in other species. Another region is the MHC-Y region, separated from MHC-B by an intervening region of tandem repeats. Like MHC-B, MHC-Y is polymorphic. It contains specialized class I and class II genes and c-type lectin-like genes. Yet another region, separated from MHC-Y by the single nucleolar organizing region ( NOR ) in the chicken genome, contains olfactory receptor genes and scavenger receptor genes, which are also thought to contribute to immunity. The structure, distribution, linkages and patterns of polymorphism in these regions, suggest GGA 16 evolves as a microchromosome devoted to immune defense. Many GGA 16 genes are polymorphic and polygenic. At the moment most disease associations are at the haplotype level. Roles of individual MHC genes in disease resistance are documented in only a very few instances. Provided suitable experimental stocks persist, the availability of increasingly detailed maps of GGA 16 genes combined with new means for detecting genetic variability will lead to investigations defining the contributions of individual loci and more applications for immunogenetics in breeding healthy poultry.
Disparities in the utilization of high-volume hospitals for complex surgery.

CONTEXT Referral to high-volume hospitals has been recommended for operations with a demonstrated volume-outcome relationship. The characteristics of patients who receive care at low-volume hospitals may be different from those of patients who receive care at high-volume hospitals. These differences may limit their ability to access or receive care at a high-volume hospital. OBJECTIVE To identify patient characteristics associated with the use of high-volume hospitals, using California's Office of Statewide Health Planning and Development patient discharge database. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of Californians receiving the following inpatient operations from 2000 through 2004: elective abdominal aortic aneurysm repair, coronary artery bypass grafting, carotid endarterectomy, esophageal cancer resection, hip fracture repair, lung cancer resection, cardiac valve replacement, coronary angioplasty, pancreatic cancer resection, and total knee replacement. MAIN OUTCOME MEASURES Patient race/ethnicity and insurance status in high-volume (highest 20% of patients by mean annual volume) and in low-volume (lowest 20%) hospitals. RESULTS A total of 719,608 patients received 1 of the 10 operations. Overall, nonwhites, Medicaid patients, and uninsured patients were less likely to receive care at high-volume hospitals and more likely to receive care at low-volume hospitals when controlling for other patient-level characteristics. Blacks were significantly (P<.05) less likely than whites to receive care at high-volume hospitals for 6 of the 10 operations (relative risk [RR] range, 0.40-0.72), while Asians and Hispanics were significantly less likely to receive care at high-volume hospitals for 5 (RR range, 0.60-0.91) and 9 (RR range, 0.46-0.88), respectively. Medicaid patients were significantly less likely than Medicare patients to receive care at high-volume hospitals for 7 of the operations (RR range, 0.22-0.66), while uninsured patients were less likely to be treated at high-volume hospitals for 9 (RR range, 0.20-0.81). CONCLUSIONS There are substantial disparities in the characteristics of patients receiving care at high-volume hospitals. The interest in selective referral to high-volume hospitals should include explicit efforts to identify the patient and system factors required to reduce current inequities regarding their use.
Feeling softness on a hard touch panel using an electrostatic tactile texture display

This paper presents a method to deliver soft tactile textures on a hard touch panel, using an electrostatic tactile feedback display, which produces high-frequency frictional textures with extremely low-frequency friction stimuli. Through experiments involving several participants, we found that low frequency signals are effective at transmitting soft sensations. Although the underlying mechanism requires further study, this new perceptual effect may provide the touch panel industry with an attractive haptic advancement.
Changes in the gross morphological appearance of chicken and turkey blastoderms during preincubation storage.

Abstract OELLACHER (1872) reported the presence of vacuoles in the germinal area of incubated and unincubated infertile chicken eggs, observing that such vacuoles were absent in fertile eggs. According to Lecaillon (1910) segmentation in the infertile unincubated avian germ disc is restricted to its central portion and does not progress as far as in the fertile, unincubated egg. Furthermore, he found that incubating infertile eggs, or keeping them at room temperature for a time results in a rapid breakdown of the segmentation area. The vacuoles are characteristic not only of the germinal area of chicken eggs, but also those of the duck (Chappelier, 1912) and turkey (Kosin, 1951). Kosin (1944) observed that the presence of a varying number of large and small vacuoles both along the periphery and in the center of the blastodisc of unincubated chicken eggs in extreme cases gives its surface a reticular appearance. The normal blastoderm in …
Binding stability of peptides on major histocompatibility complex class I proteins: role of entropy and dynamics

Prediction of peptide binding on specific human leukocyte antigens (HLA) has long been studied with successful results. We herein describe the effects of entropy and dynamics by investigating the binding stabilities of 10 nanopeptides on various HLA Class I alleles using a theoretical model based on molecular dynamics simulations. The fluctuational entropies of the peptides are estimated over a temperature range of 310–460 K. The estimated entropies correlate well with experimental binding affinities of the peptides: peptides that have higher binding affinities have lower entropies compared to non-binders, which have significantly larger entropies. The computation of the entropies is based on a simple model that requires short molecular dynamics trajectories and allows for approximate but rapid determination. The paper draws attention to the long neglected dynamic aspects of peptide binding, and provides a fast computation scheme that allows for rapid scanning of large numbers of peptides on selected HLA antigens, which may be useful in defining the right peptides for personal immunotherapy.
Financing Capacity Investment Under Demand Uncertainty: An Optimal Contracting Approach

We study the capacity choice problem of a firm whose access to capital is hampered by financial frictions (i.e., moral hazard). The firm optimizes both its capacity investment under demand uncertainty and its sourcing of funds from a competitive investor. Ours is the first study of this problem to adopt an optimal contracting approach: feasible sources of funds are derived endogenously from fundamentals and include standard financial claims (debt, equity, convertible debt, etc.). Thus, in contrast to most of the literature on financing capacity investments, our results are robust to a change of financial contract. We characterize the optimal capacity level under optimal financing. First, we find conditions under which a feasible financial contract exists that leads to the first-best capacity. When no such contract exists, we find that under optimal financing, the choice of capacity sometimes exceeds strictly the efficient level. Furthermore, the firm invests more when its cash is low, and in some cases le.
A composite of a graphene oxide derivative as a novel sensing layer in an organic field-effect transistor

We report the fabrication of a gas sensor with an oleylamine-modified graphene oxide (OA-GO)/poly(9-9′-dioctyl-fluorene-co-bithiophene) (F8T2) composite as an active layer and demonstrate that it has better sensing ability than a comparable device with an F8T2-only active layer. OA-GO was chosen as the receptor material because of its enhanced interaction with gas analytes and its easy mixing with F8T2. OA-GO was synthesized by a simple condensation reaction between GO and oleylamine (9-octadecylamine), and characterized by Fourier transform infrared spectroscopy. The sensitivities of the gas sensors with respect to acetone and ethanol analytes were investigated by measuring the electrical parameters of the corresponding organic field effect transistor at room temperature. The sensitivity of the OA-GO/F8T2 composite device was up to 34 times that of the F8T2 device for the mobility change of acetone.
[Efficacy of analgesic and sedative treatments in children with mechanical ventilation in the pediatric intensive care unit].

OBJECTIVE To compare the efficacy and safety of different analgesic and sedative treatments in children with mechanical ventilation in the pediatric intensive care unit (PICU). METHODS Eighty children with mechanical ventilation in the PICU who needed analgesic and sedative treatments were equally and randomly divided into midazolam group and remifentanil+midazolam group. The sedative and analgesic effects were assessed using the Ramsay Scale and the Face, Legs, Activity, Cry and Consolability (FLACC) Scale. The following indices were recorded for the two groups: vital signs, ventilator parameters, organ function, total doses of remifentanil and midazolam, duration of mechanical ventilation, length of PICU stay, PICU cost, and incidence of adverse events. RESULTS Satisfactory sedation was achieved in the two groups, but the remifentanil+midazolam group had a significantly shorter time to analgesia and sedation than the midazolam group. The remifentanil+midazolam group had a significantly higher percentage of patients with grade 3-4 on the Ramsay Scale and a significantly lower dose of midazolam than the midazolam group (P<0.05). Both groups showed decreases in heart rate (HR), mean arterial pressure (MAP), and spontaneous breathing frequency (RRs) after treatment. However, the remifentanil+midazolam group had significantly greater decreases in HR at 3-24 hours after treatment and MAP and RRs at 3-12 hours after treatment than the midazolam group (P<0.05). Compared with the midazolam group, the remifentanil+midazolam group had significantly higher ventilator tidal volume and transcutaneous oxygen saturation at 6 and 12 hours after treatment and significantly lower end-tidal carbon dioxide partial pressure at 6 and 12 hours after treatment (P<0.05). The remifentanil+midazolam group had significantly shorter time to awake, extubation time, duration of mechanical ventilation, and length of PICU stay than the midazolam group (P<0.05). There were no significant differences in PICU cost, incidence of adverse events, and hepatic and renal functions before and after treatment between the two groups (P>0.05). Both groups showed a significant decrease in fasting blood glucose level after treatment (P<0.05). CONCLUSIONS For children with mechanical ventilation in the PICU, remifentanil+midazolam treatment can rapidly achieve analgesia and sedation, improve the effect of mechanical ventilation, and reduce the dose of sedative compared with midazolam alone, and is well tolerated.
The view from the other side: The border between controversial speech and harassment on Kotaku in Action

In this paper, we use mixed methods to study a controversial Internet site: The Kotaku in Action (KiA) subreddit. Members of KiA are part of GamerGate, a distributed social movement. We present an emic account of what takes place on KiA: who are they, what are their goals and beliefs, and what rules do they follow. Members of GamerGate in general and KiA in particular have often been accused of harassment. However, KiA site policies explicitly prohibit such behavior, and members insist that they have been falsely accused. Underlying the controversy over whether KiA supports harassment is a complex disagreement about what “harassment” is, and where to draw the line between freedom of expression and censorship. We propose a model that characterizes perceptions of controversial speech, dividing it into four categories: criticism, insult, public shaming, and harassment. We also discuss design solutions that address the challenges of moderating harassment without impinging on free speech, and communicating across different ideologies.
Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention

Abstract Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe and dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States, but currently are not available to civilians.
Asymptotic Analysis of Normalized SNR-Based Scheduling in Uplink Cellular Networks with Truncated Channel Inversion Power Control

This paper provides the signal-to-interference-plus-noise ratio (SINR) complimentary cumulative distribution function (CCDF) and average data rate of the normalized SNR-based scheduling in an uplink cellular network using stochastic geometry. The uplink analysis is essentially different from the downlink analysis in that the per-user transmit power control is performed and that the interferers are composed of at most one transmitting user in each cell other than the target cell. In addition, as the effect of multi-user diversity varies from cell to cell depending on the number of users involved in the scheduling, the distribution of the number of users is required to obtain the averaged performance of the scheduling. This paper derives the SINR CCDF relative to the typical scheduled user by focusing on two incompatible cases, where the scheduler selects a user from all the users in the corresponding Voronoi cell or does not select users near cell edges. In each case, the SINR CCDF is marginalized over the distribution of the number of users involved in the scheduling, which is asymptotically correct if the BS density is sufficiently large or small. Through the simulations, the accuracies of the analytical results are validated for both cases, and the scheduling gains are evaluated to confirm the multi-user diversity gain.
Effects of Time of Day on Age-Related Associative Deficits

Time of day is known to influence cognition differently across age groups, with young adults performing better later than earlier in the day and older adults showing the opposite pattern. Thus age-related deficits can be smaller when testing occurs in the morning compared with the afternoon/evening, particularly for tasks requiring executive/controlled/inhibitory processes. Stronger influences of time of day were therefore predicted on associative than on item recognition memory based on their differential requirements for demanding recollective (rather than familiarity) processes. In 2 experiments, participants were presented with unrelated word pairs and then tested on both item recognition (old/new item? ) and associative recognition (intact/recombined pair? ). In Experiment 1, young adults were tested either in the morning or in the evening; recognition memory was better when time of testing matched participants’ morningness-eveningness preferences, and more so for associative than for item memory. In Experiment 2, young and older adults (evening and morning types, respectively) were tested both in the morning and in the evening; again, recognition memory was better at participants’ preferred times of day, especially for associative memory. Consequently, age-related associative deficits varied considerably—indeed more than fourfold—from a nonsignificant 8% for testing in the morning to a substantial 35% for testing in the evening, suggesting that it is important to consider time of day effects in future studies of the associative deficit hypothesis.
Activation of β‐adrenergic receptors in rat visual cortex expands astrocytic processes and reduces extracellular space volume

Brain extracellular space (ECS) is an interconnected channel that allows diffusion‐mediated transport of signaling molecules, metabolites, and drugs. We tested the hypothesis that β‐adrenergic receptor (βAR) activation impacts extracellular diffusion‐mediated transport of molecules through alterations in the morphology of astrocytes. Two structural parameters of ECS—volume fraction and tortuosity—govern extracellular diffusion. Volume fraction (α) is the volume of ECS relative to the total tissue volume. Tortuosity (λ) is a measure of the hindrance that molecules experience in the ECS, compared to a free medium. The real‐time iontophoretic (RTI) method revealed that treatment of acutely prepared visual cortical slices of adult female rats with a βAR agonist, DL‐isoproterenol (ISO), decreases α significantly, from 0.22 ± 0.03 (mean ± SD) for controls without agonist to 0.18 ± 0.03 with ISO, without altering λ (control: 1.64 ± 0.04; ISO: 1.63 ± 0.04). Electron microscopy revealed that the ISO treatment significantly increased the cytoplasmic area of astrocytic distal endings per unit area of neuropil by 54%. These findings show that norepinephrine decreases α, in part, through an increase in astrocytic volume following βAR activation. Norepinephrine is recognized to be released within the brain during the awake state and increase neurons’ signal‐to‐noise ratio through modulation of neurons’ biophysical properties. Our findings uncover a new mechanism for noradrenergic modulation of neuronal signals. Through astrocytic activation leading to a reduction of α, noradrenergic modulation increases extracellular concentration of neurotransmitters and neuromodulators, thereby facilitating neuronal interactions, especially during wakefulness. Synapse 70:307–316, 2016. © 2016 Wiley Periodicals, Inc.
Efficacy of a Fixed Combination of Tetracycline, Chloramphenicol, and Colistimethate Sodium for Treatment of Candida albicans Keratitis.

Purpose To evaluate the antifungal activity of a fixed antibiotic combination (AC) containing tetracycline (TET), chloramphenicol (CAF), and colistimethate sodium (CS). Methods In vitro: Candida ATCC and clinical strains were used. The minimum inhibitory concentrations (MICs) of AC and of each antibiotic were determined. Fluconazole (FLC) was tested for comparison. Time-killing curves of selected strains were performed. Ex vivo keratitis: corneas were injected intrastromally with the selected strains. After the injection, corneas were divided into groups of treatments: AC, FLC, or saline. Then, the tissues were analyzed for colony-forming units per gram (CFU/g). Propidium iodide (PI) and MitoTracker (MTR) staining were used to investigate the mode of action. Results Values of MIC required to inhibit the growth of 90% of organisms for the antibiotics alone were higher than FLC. However, their activity was enhanced when used in combination against Candida yeasts. Time-killing curves showed that at 24 hours, AC reduced the load of both strains of approximately 1 Log10 CFU/g compared with the initial inoculum (P < 0.0001). This effect was also significant versus FLC. In ex vivo, AC was effective in decreasing the loads of both strains by 4 Log10 CFU/g with respect to the control. Moreover, it showed higher activity than FLC against Candida albicans ATCC 10231 (1 Log10 CFU/g, P < 0.01 versus control). PI staining demonstrated that CS changed the membrane's permeability, whereas MTR staining demonstrated that TET or CAF altered mitochondrial function. The cells treated with AC and stained showed both effects. Conclusions In this study, AC showed antifungal efficacy versus Candida spp. ; this activity can be due to the synergistic effects of antibiotics in it.
Characterization of a cDNA sequence encoding the peroxisome proliferator activated receptor alpha in the chicken.

Peroxisome proliferator-activated receptors (PPAR) belong to the superfamily of the nuclear hormone receptors that play an important role in lipid homeostasis. A partial complementary deoxyribonucleic acid clone encoding a PPAR alpha from chicken liver was isolated and sequenced. Comparison with human, mouse, rat, and Xenopus PPAR alpha cDNA indicates a high degree of homology, especially at the level of the inferred peptide sequence (greater than 90%). The tissue pattern of expression indicates that PPAR alpha expression in the chicken is similar to that reported in other species, i.e., high expression levels in the liver, heart, and kidney, but also occurs in the lipogenic uropygial gland specific to birds.