Miracle-dz/UniFAR-FTUs huggingface dataset:
Inferring Signaling Pathway Topologies from Multiple Perturbation Measurements of Specific Biochemical Species

Bayesian inference–based modeling identifies the most likely paths through a signaling network. Picking the Right Path Signaling networks have become increasingly complex as large-scale analysis and experiments in multiple systems add new potential connections and players. Xu et al. present a mathematical approach to rank the possible paths through a signaling pathway and develop hypotheses that can be rationally tested. They call their approach BIBm for Bayesian inference–based modeling and apply BIBm to explore the signaling pathways by which epidermal growth factor (EGF) stimulates extracellular signal–regulated kinase (ERK). Using a limited set of biochemical experiments, the authors tested four models and found that the one that relied on two Raf family members ranked the highest. This model was then experimentally validated in two cell lines to show that both Raf-1 and B-Raf contribute to ERK activation in response to EGF. The specification of biological decisions by signaling pathways is encoded by the interplay between activation dynamics and network topologies. Although we can describe complex networks, we cannot easily determine which topology the cell actually uses to transduce a specific signal. Experimental testing of all plausible topologies is infeasible because of the combinatorially large number of experiments required to explore the complete hypothesis space. Here, we demonstrate that Bayesian inference–based modeling provides an approach to explore and constrain this hypothesis space, permitting the rational ranking of pathway models. Our approach can use measurements of a limited number of biochemical species when combined with multiple perturbations. As proof of concept, we examined the activation of the extracellular signal–regulated kinase (ERK) pathway by epidermal growth factor. The predicted and experimentally validated model shows that both Raf-1 and, unexpectedly, B-Raf are needed to fully activate ERK in two different cell lines. Thus, our formal methodology rationally infers evidentially supported pathway topologies even when a limited number of biochemical and kinetic measurements are available.
Carcinosarcoma of the Ovary: A Review

Carcinosarcoma of the ovary, also referred to as mixed mullerian tumor of the ovary, is a rare and aggressive tumor. This tumor type is unique in that it contains malignant epithelial and stromal elements. The average survival for a woman diagnosed with carcinosarcoma of the ovary is less than 2 years. Due to the rarity of this tumor, the optimal treatment for carcinosarcoma of the ovary has not been determined. We review the pathology, risk factors, and current treatment recommendations for carcinosarcoma of the ovary. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the participant should be better able to recall the existence of carcinosarcoma of the ovary, demonstrate that with rare tumors, analogous treatment regimens are used, and plan to refer patients with carcinosarcoma of the ovary to gynecologic oncologist for treatment.
Tumor Necrosis Factor α Mediates Lipopolysaccharide-Induced Microglial Toxicity to Developing Oligodendrocytes When Astrocytes Are Present

Reactive microglia and astrocytes are present in lesions of white matter disorders, such as periventricular leukomalacia and multiple sclerosis. However, it is not clear whether they are actively involved in the pathogenesis of these disorders. Previous studies demonstrated that microglia, but not astrocytes, are required for lipopolysaccharide (LPS)-induced selective killing of developing oligodendrocytes (preOLs) and that the toxicity is mediated by microglia-derived peroxynitrite. Here we report that, when astrocytes are present, the LPS-induced, microglia-dependent toxicity to preOLs is no longer mediated by peroxynitrite but instead by a mechanism dependent on tumor necrosis factor-α (TNFα) signaling. Blocking peroxynitrite formation with nitric oxide synthase (NOS) inhibitors or a decomposition catalyst did not prevent LPS-induced loss of preOLs in mixed glial cultures. PreOLs were highly vulnerable to peroxynitrite; however, the presence of astrocytes prevented the toxicity. Whereas LPS failed to kill preOLs in cocultures of microglia and preOLs deficient in inducible NOS (iNOS) or gp91phox, the catalytic subunit of the superoxide-generating NADPH oxidase, LPS caused a similar degree of preOL death in mixed glial cultures of wild-type, iNOS−/−, and gp91phox−/− mice. TNFα neutralizing antibody inhibited LPS toxicity, and addition of TNFα induced selective preOL injury in mixed glial cultures. Furthermore, disrupting the genes encoding TNFα or its receptors TNFR1/2 completely abolished the deleterious effect of LPS. Our results reveal that TNFα signaling, rather than peroxynitrite, is essential in LPS-triggered preOL death in an environment containing all major glial cell types and underscore the importance of intercellular communication in determining the mechanism underlying inflammatory preOL death.
Kericho CLinic-Based ART Diagnostic Evaluation (CLADE): Design, Accrual, and Baseline Characteristics of a Randomized Controlled Trial Conducted in Predominately Rural, District-Level, HIV Clinics of Kenya

Background Prospective clinical trial data regarding routine HIV-1 viral load (VL) monitoring of antiretroviral therapy (ART) in non-research clinics of Sub-Saharan Africa are needed for policy makers. Methods CLinic-based ART Diagnostic Evaluation (CLADE) is a randomized, controlled trial (RCT) evaluating feasibility, superiority, and cost-effectiveness of routine VL vs. standard of care (clinical and immunological) monitoring in adults initiating dual nucleoside reverse transcriptase inhibitor (NRTI)+non-NRTI ART. Participants were randomized (1:1) at 7 predominately rural, non-research, district-level clinics of western Kenya. Descriptive statistics present accrual patterns and baseline cohort characteristics. Results Over 15 months, 820 adults enrolled at 7 sites with 86–152 enrolled per site. Monthly site enrollment ranged from 2–92 participants. Full (100%) informed consent compliance was independently documented. Half (49.9%) had HIV diagnosed through voluntary counseling and testing. Study arms were similar: mostly females (57.6%) aged 37.6 (SD = 9.0) years with low CD4 (166 [SD = 106]) cells/m3). Notable proportions had WHO Stage III or IV disease (28.7%), BMI <18.5 kg/m2 (23.1%), and a history of tuberculosis (5.6%) or were receiving tuberculosis treatment (8.2%) at ART initiation. In the routine VL arm, 407/409 (99.5%) received baseline VL (234,577 SD = 151,055 copies/ml). All participants received lamivudine; 49.8% started zidovudine followed by 38.4% stavudine and 11.8% tenofovir; and, 64.4% received nevirapine as nNRTI (35.6% efavirenz). Conclusions A RCT can be enrolled successfully in rural, non-research, resource limited, district-level clinics in western Kenya. Many adults presenting for ART have advanced HIV/AIDS, emphasizing the importance of universal HIV testing and linkage-to-care campaigns. Trial Registration ClinicalTrials.gov NCT01791556
Rethinking Wireless Internet with Smart Media

Third-generation mobile networks (3G) will support the end-to-end delivery of IP to wireless end-devices. The cost of this infrastructure and the moderate data-rates that can be expected have lead to proposals for a mixed 3G and wireless LAN (WLAN) approach. WLAN delivers much higher data-rates, currently up to 11 Mbps (IEEE 802.11b). Field trials with public WLAN extensions to Gigabit Ethernet networks show outdoor coverage of several hundred meters. Our previous work demonstrated smart delivery of multimedia involving agents running in the mobile, the access point, and the content provider. This allowed us to dynamically adapt both the application and network behavior (to each other) in order to meet the criteria for specific applications. In this paper, we extend this approach by adding service knowledge meta-data to the multimedia content (creating so-called Smart Media) to take advantage of the fact that for non real-time media content, which needs ample bandwidth to deliver, there does not need to be a coupling between transfer rate and playout rate. This approach enables the agent to further free resources for the delivery of streaming media to mobile users. In light of this approach, we propose novel network topologies with WLAN access using Smart Media Packets, for which we examine the minimal requirements for delivering the services.
Linear Degrees of Freedom of the $X$ -Channel With Delayed CSIT

We establish the degrees of freedom (DoF) of the two-user X-channel with delayed channel knowledge at transmitters [i.e., delayed channel state information at the transmitters (CSIT)], assuming linear coding strategies at the transmitters. We derive a new upper bound and characterize the linear DoF of this network to be 6/5. The converse builds upon our development of a general lemma that shows that, if two distributed transmitters employ linear strategies, the ratio of the dimensions of received linear subspaces at the two receivers cannot exceed 3/2, due to delayed CSIT. As a byproduct, we also apply this general lemma to the three-user interference channel with delayed CSIT, thereby deriving a new upper bound of 9/7 on its linear DoF. This is the first bound that captures the impact of delayed CSIT on the DoF of this network, under the assumption of linear encoding strategies.
Relevance in Information Systems Research: An Empirical Analysis

The importance of instilling relevance for IT executives in IS research has been stressed by a number of scholars for the long term survival and growth of the IS discipline. Though there have been extended deliberations on the subject, to our knowledge, there has been no empirical analysis to examine the relevance of current IS research. In this study, we analyze the relevance of the 388 published academic articles in the three top IS journals: MIS Quarterly, Information Systems Research and Journal of Management Information Systems, for a five year period from 2000-2004, by examining their ‘fit’ with the ‘key issues for IT executives’ identified by the latest survey conducted by Society for Information Management (SIM) in the year 2003. Results from the empirical analysis reveal that the issue of relevance for IT executives is not being adequately addressed by the current IS research. Based on the results of analysis, we make recommendations for increasing the relevance of IS research. As a future research direction, we identify four top concerns of the IT executives, which have not been adequately researched. The four identified topics are IT and business alignment, IT strategic planning, security and privacy, and attracting, developing, and retaining IT professionals.
Effect of positive end-expiratory pressure on right ventricular function in humans.

The effect of positive end-expiratory pressure (PEEP) on right ventricular (RV) function in humans is complex. Previous studies have been limited in their interpretation by not defining either pericardial pressure (Ppc) or RV volumes. Accordingly, we measured RV volumes and pressures and Ppc as PEEP was increased from zero to 15 cm H2O in 12 patients after thoracotomy, using a pulmonary arterial catheter equipped with a rapid responding thermistor that allowed measurement of RV ejection fraction (ef), while Ppc was measured via a pericardial balloon catheter. RV end-diastolic volume (EDV) was estimated as the ratio of stroke volume (SV) to RVef, whereas RV end-systolic volume (ESV) was estimated as RV EDV-SV. Right atrial pressure (Pra) was defined as end-diastolic pressure, and pulmonary arterial pressures (Ppa), both peak and mean, were used as end-systolic pressures. PEEP increased Ppc, Pra, and lung compliance (Cl). Cardiac output also decreased but not significantly. Neither mean nor peak systolic Ppa, nor RVef was significantly altered by PEEP. There was no relation between either RV filling pressure (Pra-Ppc) and EDV or the change in RV filling pressure and EDV, although EDV varied significantly as PEEP varied for individuals (p less than 0.05). Similarly, there was no relation between Ppa and ESV when either mean or peak Ppa values relative to Ppc were used. The relations between EDV and both SV and RVef were weak (r = 0.54 and 0.55, respectively). RVef varied inversely with ESV (r = -0.77), although it showed no relation to transmural peak Ppa (r = 0.28). (ABSTRACT TRUNCATED AT 250 WORDS)
Quadrotor helicopter with tilting rotors: Modeling and simulation

Quadrotors have recently become a focus of research in Unmanned Aerial Vehicle (UAV) and flying robots applications. However, controlling the quadrotor dynamics is noticeably complex as the conventional quadrotor is underactuated. Some of the quadrotor motions are coupled with others which makes it impossible to achieve all the desired maneuvers. In this paper, a novel quadrotor design is proposed. The design increases the number of inputs from four in conventional quadrotors to twelve by allowing each rotor to tilt in two directions about its fixed frames. This addition aims to separate the quadrotor motions and give it more maneuverability and robustness. The model of the new design is introduced and several flights are simulated to show the superiority over conventional design.
Celleration: loss-resilient traffic redundancy elimination for cellular data

In this paper we present Celleration, a novel gateway-to-mobile Traffic Redundancy Elimination (TRE) system, designed for the new generation of data-intensive cellular networks. Cellular TRE needs to account for the mobile device's limited battery power and the characteristics of the cellular network such as users' mobility, high packet-loss and long round-trip delays. Celleration is based on a novel TRE technique, in which the cellular gateway observes the forwarded chunks to identify the beginning of a previously observed chunk chain, which in turn is used as a reliable predictor to multiple future chunks. These predictions establish an ad-hoc gateway-to-mobile TRE learning mechanism that leverages the gateway's history records and the user mobile device's cached content for an efficient TRE operation for both the backhaul and the wireless last-mile. We present a data analysis of captured cellular traffic from 130 cellular sites and a long-term study of a social network. Finally, we analyze Celleration redundancy elimination and performance under high packet loss.
Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=. 021, η2=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=. 028, η2=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=. 030, η2=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<. 01, adjusted r2=. 33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). Conclusions mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients.
Co–Teaching in Middle School Classrooms under Routine Conditions: Does the Instructional Experience Differ for Students with Disabilities in Co–Taught and Solo–Taught Classes?

Co–teaching is a popular strategy for implementing the inclusion of students with disabilities within secondary general education classrooms. However, we have little data regarding its effectiveness under routine conditions of educational practice. This study examined whether there was an “additive effect” of the special education teacher on the instructional experiences of students with disabilities as compared with the experiences of the same students taught by only the general education teacher under routine conditions. Observers used time sampling methods to document how students with disabilities spent their time in 11 middle school co–taught classes. Statistically significant differences were found for targeted students in terms of general education teacher interaction and individual instruction. General education teachers spent significantly less time with students with disabilities when the special education teacher was present. In addition, students with disabilities received significantly more individual instruction when the special education teacher was present. However, these differences were of limited practical significance.
Recent advancements in automatic speaker authentication

Verbal-information and fixed-phrase approaches for identifying a person via voice are ready for real-world applications. We focus exclusively on the use of voice for authentication applications and review advancements in this area. The technical components in speech recognition and verification systems are reviewed, and we then discuss a speech-verification system that utilizes stochastic matching to identify a person based on voice characteristics. We also discuss a verbal-information verification system that verifies identity through the content of the verbal information.
Differences in verbal behaviours of patients with and without emotional distress during primary care consultations

Background. In primary care consultations patients with emotional distress tend to give verbal cues or symptom reports with psychological or psychiatric contents. This study examined the cue behaviour defined not only by psychological, but also by medical, social and life episodes related contents in patients with and without emotional distress, recognized and not by their GP. The GP's verbal behaviour in relation to patients' cue emission was also investigated. Method. For the six participating GPs two groups of matched pairs of patients (N = 238) were created. The two groups comprised either patients considered by GPs as being without emotional distress or patients considered as emotionally distressed. Within each pair, one patient was a case (GHQ-12 score > 2) and the other was the matched control (GHQ-12 score < 3). The medical interviews with these patients were transcribed and classified according to the Verona Medical Interview Classification System (VR-MICS). Results. GHQ positive patients of both groups gave more cues in terms of total proportion than their matched controls (GHQ negative patients). The proportion of cues given by patients was related also to GP's verbal behaviour, increasing with closed psychosocial questions and decreasing with the use of active interview techniques. Attribution of emotional distress was more frequent when patients were high attenders and had a past psychiatric history. The content of cues changed in relation to GP's attribution: recognized patients gave more cues and more often with psychological content, patients not recognized as distressed gave mainly cues related to their lifestyle and life episodes. Conclusions. To improve the recognition of those emotionally distressed patients most likely to be missed GPs should increase their attention to cues related to life style and life episodes.
Diabetic ketoacidosis following pentamidine therapy in a patient with the acquired immunodeficiency syndrome.

cerning uterine penetration by an IUD. First, an initial workup with a plain film of the abdomen was misinterpreted and the intra-abdominal position of the IUD missed. This was probably due to a near-term gravid uterus. Second, the point when complete uterine perforation occurred is unknown, but it was presumably before her third child was conceived. Her uterus was most likely partially perforated with insertion of the device, and over the following two to three months complete perforation occurred. The periodic pain she experienced after that pregnancy was probably related to episodic exacerbation of chronic, low-grade inflammation in the mass surrounding the IUD. Third, as the gravid uterus grew, the inflammation surrounding the IUD eventually involved the appendix, and acute appendicitis developed. Finally, reexamination ofthe pelvis at cesarean section showed that the inflammatory mass had been replaced with dense adhesions that now included the right adnexa, which had previously been free ofthe pathologic process.