Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of Trop2 Promotes Carcinogenesis and Features of Epithelial to Mesenchymal Transition in Squamous Cell Carcinoma

Trop2, an oncogenic cell surface protein under investigation as a therapeutic target, is commonly overexpressed in several epithelial tumor types yet its function in tumor biology remains relatively unexplored. To investigate the role of Trop2 in epithelial carcinogenesis, we generated Trop2−/− mice, which are viable and possess a normal lifespan. Contrary to expectations, Trop2 loss fails to suppress keratinocyte transformation. Instead, ras-transformed Trop2−/− keratinocytes preferentially pass through an epithelial to mesenchymal transition (EMT) and form tumors with spindle cell histology. Furthermore, Trop2 loss renders Arf-null mice susceptible to the formation of biphasic sarcomatoid carcinomas containing both squamous and spindle cell components upon carcinogen exposure in an otherwise skin cancer–resistant strain (C57BL/6). Immortalized keratinocytes derived from Trop2−/−Arf−/− mice exhibit enhanced proliferative and migratory capacity as well as increased activation of mitogen-activated protein kinase and Src prior to transformation. The clinical relevance of these findings was supported by studying the molecular epidemiology of Trop2 in primary head and neck squamous cell carcinomas. This analysis revealed that Trop2 mRNA levels are decreased in a subset of tumors with features of EMT, and total loss of Trop2 protein expression is observed in the spindle cell component of sarcomatoid carcinomas. Therefore, while previous studies have emphasized the potential importance of Trop2 gain of function, these results uncover a role for Trop2 loss in tumorigenesis and the mesenchymal transdifferentiation observed in a subset of squamous cell carcinomas. Mol Cancer Res; 9(12); 1686–95. ©2011 AACR.
Functional inhibition of chemokine receptor CCR2 by dicer-substrate-siRNA prevents pain development

Background Accumulating evidence suggests that the C-C chemokine ligand 2 (CCL2, or monocyte chemoattractant protein 1) acts as a neuromodulator in the central nervous system through its binding to the C-C chemokine receptor 2 (CCR2). Notably, it is well established that the CCL2/CCR2 axis plays a key role in neuron-glia communication as well as in spinal nociceptive transmission. Gene silencing through RNA interference has recently emerged as a promising avenue in research and drug development, including therapeutic management of chronic pain. In the present study, we used 27-mer Dicer-substrate small interfering RNA (DsiRNA) targeting CCR2 and assessed their ability to reverse the nociceptive behaviors induced by spinal CCL2 injection or following intraplantar injection of complete Freund’s adjuvant. Results To this end, we first developed high-potency DsiRNAs designed to target different sequences distributed across the rat CCR2 (rCCR2) messenger RNA. For optimization, methyl groups were added to the two most potent DsiRNA candidates (Evader and M7 2′-O-methyl modified duplexes) in order to improve in vivo duplex stability and to reduce potential immunostimulatory activity. Our results demonstrated that all modified candidates formulated with the cell-penetrating peptide reagent Transductin showed strong RNAi activity following intrathecal delivery, exhibiting >50% rCCR2 knockdown in lumbar dorsal root ganglia. Accordingly, we found that these DsiRNA duplexes were able to reduce spinal microglia activation and were effective at blocking CCL2-induced mechanical hypersensitivity. Along with similar reductions of rCCR2 messenger RNA, both sequences and methylation patterns were similarly effective in inhibiting the CCL2 nociceptive action for the whole seven days testing period, compared to mismatch DsiRNA. DsiRNAs against CCR2 also reversed the hypernociceptive responses observed in the complete Freund’s adjuvant-induced inflammatory chronic pain model. Conclusion Altogether, these results validate CCR2 as a an appropriate molecular target for pain control and demonstrate that RNAi-based gene therapy represent an highly specific alternative to classical pharmacological approaches to treat central pathologies such as chronic pain.
Effect of relative humidity on the tribological performance and tribofilm characteristic of boundary lubricated systems with ZDDP containing oil; Part II: Numerical

Relative humidity and the effect on tribochemistry and wear of boundary lubricated systems are examined experimentally in part one of this study. In part II of this study the tribofilm thickness and wear results obtained experimentally are used to develop a semi-deterministic approach to implement the effect of humidity in wear prediction of boundary lubrication for the first time. Two approaches were used for this purpose; firstly, a modification factor was found to be suitable for Archard’s wear equation to be able to account for the effect of relative humidity. This factor is found to be good for engineering designers to be able to predict the lifetime of machine parts. Secondly, the effect of humidity on the tribofilm growth on the surfaces was captured in the model and its effect on wear was tested based on a recent model developed by the authors. It is shown that, as expected, if the tribofilm growth is captured effectively, wear can be predicted. The prediction results were validated with the experimental results showing good agreement. Calibration of the tribochemical model at different levels of relative humidity suggest that the maximum tribofilm formation factor (h_max) is varying linearly with the humidity percentage. This led to the further development of the tribochemical model of the authors to adapt to the humid environments.
Driving Characteristics and Adaptive Cruise Control ? A Naturalistic Driving Study

With the increasing number of vehicles equipped with Adaptive Cruise Control (ACC), it becomes important to assess its impact on traffic flow efficiency, in particular with respect to capacity and queue discharge rate. Simulation studies and surveys suggest that ACC has both positive and negative effects on traffic flow, but empirical evidence on this topic is scarce. A naturalistic driving study has been conducted with 8 participants who drove their own ACC-equipped vehicle during their regular trips on freeways for a period of 4 to 5 weeks. We measured spacing, headway, speed, acceleration, lane use, and the number of lane changes, and compared these between ACC On and ACC Off in different traffic states, for a total of 48 hours of driving data. Results show that with ACC On, average spacing and headways were larger, whereas standard deviations were smaller. Larger headways can be assumed to reduce capacity, whereas more constant spacing, headway, speed, and acceleration indicate more stable traffic. With ACC On, drivers performed 36% fewer lane changes in saturated traffic, resulting in increased use of either the faster or the slower lane, depending on the driver. Furthermore we found that headways were smaller with ACC On than ACC Off when only selecting accelerations below -0.5m/s2 and above 0.5m/s2, which is the opposite of the overall finding. The latter result suggests that ACC has an important limitation: a lack of anticipation. On the other hand, the smaller headways with ACC On during acceleration indicate an increased queue discharge rate.
Root environment acidity as a regulatory factor in ammonium assimilation by the bean plant.

Previous experiments have revealed a much greater efficiency of ammonium utilization by bean plants (Phaseolus vulgaris L.) when the acidity of the ambient medium was maintained at near-neutral conditions with carbonates or hydroxides. The present investigation, in which (15)N-labeled ammonium was used, permitted an assessment of the origin of nitrogen in tissue nitrogen pools with and without acidity control (CaCO(3) treated and untreated, respectively) in the root environment. Control of acidity resulted in greater ammonium uptake and greater incorporation into the amino fraction, amide, and ethanol-insoluble nitrogen by the root tissue. These differences were clearly evident by the fifth day after ammonium nitrogen had been applied.Shoots of the untreated plants rapidly accumulated free ammonium and amino nitrogen. A substantial portion of both fractions came from pre-existing nitrogen in the plants, indicating significant protein degradation. No evidence was found for such degradation in the roots of the untreated plants or in either roots or shoots of CaCO(3) treated plants. The data indicate that control of ambient acidity in the root environment during ammonium absorption enhanced the conversion of entering ammonium to organic nitrogen compounds in the root tissue thereby restricting movement of free ammonium to shoots. Consequently, the detrimental effects of high ammonium concentrations in the leaves were largely prevented.
The cost of being valuable: predictors of extinction risk in marine invertebrates exploited as luxury seafood

Extinction risk has been linked to biological and anthropogenic variables. Prediction of extinction risk in valuable fauna may not follow mainstream drivers when species are exploited for international markets. We use results from an International Union for Conservation of Nature Red List assessment of extinction risk in all 377 known species of sea cucumber within the order Aspidochirotida, many of which are exploited worldwide as luxury seafood for Asian markets. Extinction risk was primarily driven by high market value, compounded by accessibility and familiarity (well known) in the marketplace. Extinction risk in marine animals often relates closely to body size and small geographical range but our study shows a clear exception. Conservation must not lose sight of common species, especially those of high value. Greater human population density and poorer economies in the geographical ranges of endangered species illustrate that anthropogenic variables can also predict extinction risks in marine animals. Local-level regulatory measures must prevent opportunistic exploitation of high-value species. Trade agreements, for example CITES, may aid conservation but will depend on international technical support to low-income tropical countries. The high proportion of data deficient species also stresses a need for research on the ecology and population demographics of unglamorous invertebrates.
New Generation Electron Beam Resists: A Review

The semiconductor industry has already entered the sub-10 nm region, which has led to the development of cutting-edge fabrication tools. However, there are other factors that hinder the best outcome of these tools, such as the substrate and resist materials, pre- and postfabrication processes, etc. Among the lithography techniques, electron beam lithography (EBL) is the prime choice when a job requires dimensions lower than 10–20 nm, since it can easily achieve such critical dimensions in reasonable time and effort. When obtaining pattern features in single nanometer regime, the resist material properties play an important role in determining the size. With this agenda in mind, many resists have been developed over the years suitable for attaining required resolution in lesser EBL writing time. This review article addresses the recent advancements made in EBL resists technology. It first describes the different lithography processes briefly and then progresses on to the parameters affecting the EBL fabric.
OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine over one year of treatment: Pooled results from the PREEMPT randomized clinical trial program

Background Chronic migraine (CM) is associated with high impact and reduced health-related quality of life (HRQoL). Methods Patients with CM from PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) were randomized (1:1) to receive onabotulinumtoxinA or placebo for two 12-week cycles in the double-blind (DB) phase, followed by three 12-week cycles of open-label (OL) onabotulinumtoxinA (onabotulinumtoxinA/onabotulinumtoxinA (O/O) and placebo/onabotulinumtoxinA (P/O) groups, respectively). HRQoL endpoints were assessed over 56 weeks using the Headache Impact Test (HIT-6) and the Migraine-Specific Quality of Life Questionnaire (MSQ). HIT-6 score reductions ≥2.3 and ≥5 denoted between-group minimally important difference and within-patient clinically meaningful response, respectively. Results A total of 1236 participants (O/O, n = 607; P/O, n = 629) participated in both phases. The DB phase showed significantly reduced HIT-6 and MSQ for onabotulinumtoxinA versus placebo (all p < 0.001). The OL phase showed significantly reduced HIT-6 for O/O versus P/O at weeks 28, 36, and 48, but not 56. All three MSQ domains showed improved HRQoL relative to baseline, but only the role restrictive domain showed a significant difference between O/O and P/O at week 56. Conclusions Benefits of onabotulinumtoxinA on HRQoL versus baseline persisted throughout the OL phase. Statistical superiority in favor of O/O was demonstrated for HIT-6 through 48 weeks and for MSQ (role restrictive) at 56 weeks.
Quantum criticality in a uniaxial organic ferroelectric

Tris-sarcosine calcium chloride (TSCC) is a highly uniaxial ferroelectric with a Curie temperature of approximately 130 K. By suppressing ferroelectricity with bromine substitution on the chlorine sites, pure single crystals were tuned through a ferroelectric quantum phase transition. The resulting quantum critical regime was investigated in detail and was found to persist up to temperatures of at least 30–40 K. The nature of long-range dipole interactions in uniaxial materials, which lead to non-analytical terms in the free-energy expansion in the polarization, predict a dielectric susceptibility varying as 1/T3close to the quantum critical point. Rather than this, we find that the dielectric susceptibility varies as 1/T2 as expected and observed in better known multi-axial systems. We explain this result by identifying the ultra-weak nature of the dipole moments in the TSCC family of crystals. Interestingly, we observe a shallow minimum in the inverse dielectric function at low temperatures close to the quantum critical point in paraelectric samples that may be attributed to the coupling of quantum polarization and strain fields. Finally, we present results of the heat capacity and electro-caloric effect and explain how the time dependence of the polarization in ferroelectrics and paraelectrics should be considered when making quantitative estimates of temperature changes induced by applied electric fields.
The Amide Local Anesthetic Lidocaine in Cancer Surgery—Potential Antimetastatic Effects and Preservation of Immune Cell Function? A Narrative Review

Surgical removal of the primary tumor in solid cancer is an essential component of the treatment. However, the perioperative period can paradoxically lead to an increased risk of cancer recurrence. A bimodal dynamics for early-stage breast cancer recurrence suggests a tumor dormancy-based model with a mastectomy-driven acceleration of the metastatic process and a crucial role of the immunosuppressive state during the perioperative period. Recent evidence suggests that anesthesia could also influence the progress of the disease. Local anesthetics (LAs) have long been used for their properties to block nociceptive input. They also exert anti-inflammatory capacities by modulating the liberation or signal propagation of inflammatory mediators. Interestingly, LAs can reduce viability and proliferation of many cancer cells in vitro as well. Additionally, retrospective clinical trials have suggested that regional anesthesia for cancer surgery (either with or without general anesthesia) might reduce the risk of recurrence. Lidocaine, a LA, which can be administered intravenously, is widely used in clinical practice for multimodal analgesia. It is associated with a morphine-sparing effect, reduced pain scores, and in major surgery probably also with a reduced incidence of postoperative ileus and length of hospital stay. Systemic delivery might therefore be efficient to target residual disease or reach cells able to form micrometastasis. Moreover, an in vitro study has shown that lidocaine could enhance the activity of natural killer (NK) cells. Due to their ability to recognize and kill tumor cells without the requirement of prior antigen exposure, NKs are the main actor of the innate immune system. However, several perioperative factors can reduce NK activity, such as stress, pain, opioids, or general anesthetics. Intravenous lidocaine as part of the perioperative anesthesia regimen would be of major interest for clinicians, as it might bear the potential to reduce the risk of cancer recurrence or progression patients undergoing cancer surgery. As a well-known pharmaceutical agent, lidocaine might therefore be a promising candidate for oncological drug repurposing. We urgently need clinical randomized trials assessing the protective effect of lidocaine on NKs function and against recurrence after cancer surgery to achieve a “proof of concept. ”
Unifying Framework for Fast Learning Rate of Non-Sparse Multiple Kernel Learning

In this paper, we give a new generalization error bound of Multiple Kernel Learning (MKL) for a general class of regularizations. Our main target in this paper is dense type regularizations including lp-MKL that imposes lp-mixed-norm regularization instead of l1-mixed-norm regularization. According to the recent numerical experiments, the sparse regularization does not necessarily show a good performance compared with dense type regularizations. Motivated by this fact, this paper gives a general theoretical tool to derive fast learning rates that is applicable to arbitrary mixed-norm-type regularizations in a unifying manner. As a by-product of our general result, we show a fast learning rate of lp-MKL that is tightest among existing bounds. We also show that our general learning rate achieves the minimax lower bound. Finally, we show that, when the complexities of candidate reproducing kernel Hilbert spaces are inhomogeneous, dense type regularization shows better learning rate compared with sparse l1 regularization.
Bone Morphogenetic Proteins and Cancer: Review of the Literature

OBJECTIVEIn addition to their well-known osteogenic properties, bone morphogenetic proteins (BMPs) have developmental and regenerative roles that may impact tumorigenesis and promote tumor spread. Given that the most common site of tumor metastases to bone is the spine, determining whether BMPs can be linked to cancer is of particular relevance to surgeons treating primary or metastatic spinal disease. This article reviews the basic scientific and clinical background of BMPs and their potential role in promoting cancer. METHODSA literature review to identify studies relating to BMP and tumorigenesis was conducted. Databases evaluated included MEDLINE and EMBASE as well as the Cochrane Controlled Trials Register through 2008. RESULTSBone morphogenetic proteins are a diverse class of molecules belonging to the transforming growth factor-β superfamily that serve a variety of biologic functions. Bone morphogenetic proteins have critical roles in stem and progenitor cell biology as regulators of cellular expansion and differentiation. Transforming growth factor-β and related cell signaling pathways as well as stem and progenitor cell signaling have been linked to cancer. Multiple in vitro and in vivo studies suggest a significant role of BMPs in promoting tumorigenesis and metastasis. However, there are also comparable studies that imply that BMPs may have a negative effect on cancer. CONCLUSIONThere is no definitive association between BMPs and the promotion of tumorigenesis or metastasis. However, given the relatively large number of studies reporting a positive effect of BMPs on tumorigenesis or metastasis, the use of BMPs in patients with primary or metastatic spinal tumors should be carefully considered.
Provider Recommendation Mediates the Relationship Between Parental Human Papillomavirus (HPV) Vaccine Awareness and HPV Vaccine Initiation and Completion Among 13- to 17-Year-Old US Adolescent Children

Objectives. To examine the association between parental human papillomavirus (HPV) awareness and HPV vaccine initiation/completion based on 13- to 17-year-old US adolescent children and to explore whether these associations were mediated by provider recommendation. Methods. We used publicly available National Immunization Survey–Teen 2011 data (11 236 adolescent girls and 12 328 boys). Results. Weighted logistic regression analysis showed that parental HPV awareness and provider recommendation predicted HPV vaccine initiation and completion separately among both girls and boys, after adjusting for demographic and health care use variables. When provider recommendation and parental HPV awareness were entered in the model simultaneously, only provider recommendation was independently associated with HPV vaccine initiation and completion, demonstrating a mediation effect of provider recommendation. Conclusions. Future studies are needed to better understand why physicians may not provide a recommendation for the HPV vaccine as well as to identify strategies to improve providers’ ability to effectively communicate their recommendations.
Historical Reconstruction Reveals Recovery in Hawaiian Coral Reefs

Coral reef ecosystems are declining worldwide, yet regional differences in the trajectories, timing and extent of degradation highlight the need for in-depth regional case studies to understand the factors that contribute to either ecosystem sustainability or decline. We reconstructed social-ecological interactions in Hawaiian coral reef environments over 700 years using detailed datasets on ecological conditions, proximate anthropogenic stressor regimes and social change. Here we report previously undetected recovery periods in Hawaiian coral reefs, including a historical recovery in the MHI (∼AD 1400–1820) and an ongoing recovery in the NWHI (∼AD 1950–2009+). These recovery periods appear to be attributed to a complex set of changes in underlying social systems, which served to release reefs from direct anthropogenic stressor regimes. Recovery at the ecosystem level is associated with reductions in stressors over long time periods (decades+) and large spatial scales (>103 km2). Our results challenge conventional assumptions and reported findings that human impacts to ecosystems are cumulative and lead only to long-term trajectories of environmental decline. In contrast, recovery periods reveal that human societies have interacted sustainably with coral reef environments over long time periods, and that degraded ecosystems may still retain the adaptive capacity and resilience to recover from human impacts.
Autistic Traits in Children With and Without ADHD

OBJECTIVE: To assess the implications of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD) without a diagnosis of autism. METHODS: Participants were youth with (n = 242) and without (n = 227) ADHD and controls without ADHD in whom a diagnosis of autism was exclusionary. Assessment included measures of psychiatric, psychosocial, educational, and cognitive functioning. ATs were operationalized by using the withdrawn + social + thought problems T scores from the Child Behavior Checklist. RESULTS: A positive AT profile was significantly overrepresented among ADHD children versus controls (18% vs 0.87%; P < .001). ADHD children with the AT profile were significantly more impaired than control subjects in psychopathology, interpersonal, school, family, and cognitive domains. CONCLUSIONS: A substantial minority of ADHD children manifests ATs, and those exhibiting ATs have greater severity of illness and dysfunction.