Miracle-dz/UniFAR-FTUs huggingface dataset:
PDGFRalpha- and c-kit-mutated gastrointestinal stromal tumours (GISTs) are characterized by distinctive histological and immunohistochemical features.

AIMS To study the immunohistochemical and histological features of 158 gastrointestinal stromal tumours (GISTs), consisting of 137 tumours with mutations in c-kit and platelet-derived growth factor receptor-alpha (PDGFRalpha) genes and 21 wt-GISTs. Additionally, we evaluated the localization of PDGFRalpha in the normal intestine. PDGFRalpha gene mutations were recently described in a subset of GISTs and it has been hypothesized that PDGFRalpha-mutated tumours represent a distinctive entity among GISTs. RESULTS PDGFRalpha was expressed in ganglion bodies of the myenteric plexus and in Schwann cells but not in interstitial cells of Cajal. In contrast to other GISTs, tumours with PDGFRalpha mutations had an epithelioid phenotype and multinuclear giant cells. Kit was down-regulated in PDGFRalpha-mutated GISTs and PDGFRalpha expression was decreased in c-kit mutated tumours. Dot-like staining of Kit and PDGFRalpha was associated very frequently with mutation within the respective gene. CONCLUSIONS Features of PDGFRalpha-mutated GISTs are multinuclear giant cells and dot-like staining for PDGFRalpha. In contrast, c-kit-mutated GISTs display a spindle cell phenotype and Kit-dots on immunohistochemistry. Our findings not only help to distinguish distinctive entities of GISTs using histological and immunhistochemical features, but also indicate that Kit and PDGFRalpha are differentially regulated in a subset of GISTs.
Predicting Case Volume from the Accumulating Elective Operating Room Schedule Facilitates Staffing Improvements

Background:Precise estimates of final operating room demand can only be made 1 or 2 days before the day of surgery, when it is harder to adjust staffing to match demand. The authors hypothesized that the accumulating elective schedule contains useful information for predicting final case demand sufficiently in advance to readily adjust staffing. Methods:The accumulated number of cases booked was recorded daily, from which a usable dataset comprising 146 consecutive surgical days (October 10, 2011 to May 7, 2012, after removing weekends and holidays), and each with 30 prior calendar days of booking history, was extracted. Case volume prediction was developed by extrapolation from estimates of the fraction of total cases booked each of the 30 preceding days, and averaging these with linear regression models, one for each of the 30 preceding days. Predictions were verified by comparison with actual volume. Results:The elective surgery schedule accumulated approximately three cases per day, settling at a mean ± SD final daily volume of 117 ± 12 cases. The model predicted final case counts within 8.27 cases as far in advance as 14 days before the day of surgery. In the last 7 days before the day of surgery, the model predicted the case count within seven cases 80% of the time. The model was replicated at another smaller hospital, with similar results. Conclusions:The developing elective schedule predicts final case volume weeks in advance. After implementation, overly high- or low-volume days are revealed in advance, allowing nursing, ancillary service, and anesthesia managers to proactively fine-tune staffing up or down to match demand.
Hyperforin, an Anti-Inflammatory Constituent from St. John's Wort, Inhibits Microsomal Prostaglandin E2 Synthase-1 and Suppresses Prostaglandin E2 Formation in vivo

The acylphloroglucinol hyperforin (Hyp) from St. John's wort possesses anti-inflammatory and anti-carcinogenic properties which were ascribed among others to the inhibition of 5-lipoxygenase. Here, we investigated whether Hyp also interferes with prostanoid generation in biological systems, particularly with key enzymes participating in prostaglandin (PG)E2 biosynthesis, i.e., cyclooxygenases (COX)-1/2 and microsomal PGE2 synthase (mPGES)-1 which play key roles in inflammation and tumorigenesis. Similar to the mPGES-1 inhibitors MK-886 and MD-52, Hyp significantly suppressed PGE2 formation in whole blood assays starting at 0.03–1 μM, whereas the concomitant generation of COX-derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid, thromboxane B2, and 6-keto PGF1α was not significantly suppressed up to 30 μM. In cell-free assays, Hyp efficiently blocked the conversion of PGH2 to PGE2 mediated by mPGES-1 (IC50 = 1 μM), and isolated COX enzymes were not (COX-2) or hardly (COX-1) suppressed. Intraperitoneal (i.p.) administration of Hyp (4 mg kg−1) to rats impaired exudate volume and leukocyte numbers in carrageenan-induced pleurisy associated with reduced PGE2 levels, and Hyp (given i.p.) inhibited carrageenan-induced mouse paw edema formation (ED50 = 1 mg kg−1) being superior over indomethacin (ED50 = 5 mg kg−1). We conclude that the suppression of PGE2 biosynthesis in vitro and in vivo by acting on mPGES-1 critically contributes to the anti-inflammatory efficiency of Hyp.
Efficacy of Imatinib in Aggressive Fibromatosis: Results of a Phase II Multicenter Sarcoma Alliance for Research through Collaboration (SARC) Trial

Purpose: Aggressive fibromatoses (AF; desmoid tumors) are rare clonal neoplastic proliferations of connective tissues that can be locally aggressive despite wide surgical resection and/or radiation therapy. The Sarcoma Alliance for Research through Collaboration (SARC) initiated a prospective phase II trial to investigate the outcome of patients treated with imatinib, a multiple tyrosine kinase inhibitor, in patients with AF, or 1 of 10 sarcoma subtypes. Here, we report specifically on the outcome of patients with AF as well as evaluations undertaken to examine the mechanism of imatinib. Experimental Design: Patients ≥10 years old with desmoid tumors that were not curable by surgical management or in whom curative surgery would lead to undesirable functional impairment were eligible. Imatinib was prescribed at 300 mg twice daily [body surface area (BSA) ≥ 1.5 m2], 200 mg twice daily (BSA = 1.0-1.49 m2), or 100 mg twice daily (BSA < 1.0 m2). Response outcomes at 2 and 4 months were assessed. Tissue specimens were analyzed by immunohistochemistry for expression of cKIT, platelet-derived growth factor receptor α (PDGFRα), PDGFRβ, AKT, PTEN, FKHR, and β-catenin. Tumor DNA was analyzed for PDGFRα exon 18 and APC mutations by allelic discrimination PCR. Results: Fifty-one patients were enrolled. The median number of prior regimens was 1. Kaplan-Meier estimates of 2- and 4-month progression-free survival rates were 94% and 88%, respectively, and 1-year progression-free survival was 66%. Objective response rate was 6% (3 of 51). Expression and polymorphisms of target proteins were identified in tissue samples, but no significant correlation with outcome was observed using the samples available. Conclusion: Imatinib may have a role in the management of unresectable or difficult to resect desmoid tumors. Clin Cancer Res; 16(19); 4884–91. ©2010 AACR.
Structural features of the herpes simplex virus alpha gene 4, 0, and 27 promoter-regulatory sequences which confer alpha regulation on chimeric thymidine kinase genes

Previous studies have shown that herpes simplex virus genes form three groups, alpha, beta, and gamma, whose expression is coordinately regulated and sequentially ordered in a cascade fashion. Chimeric genes constructed by fusion of the coding and 5' nontranslated leader sequences of the thymidine kinase (TK) gene to the sequences upstream from the site of initiation of transcription of alpha genes 4 and 27 are regulated as alpha genes and are induced in cells converted to TK+ phenotype by infection with TK- virus. In alpha gene 4 (S. Mackem and B. Roizman, Proc. Natl. Acad. Sci. U.S.A. 79:4917-4921, 1982), both the promoter and the regulatory region are separable and movable. The promoter permits expression but not induction when fused to TK in the noncoding leader region of the gene. The regulator, when fused to the promoter of an expressible but noninducible portion of the natural beta TK, renders the gene inducible as an alpha gene; it consists of multiple regulatory units acting cumulatively. In this paper, we report on the precise site of initiation of transcription of alpha gene 0 within the inverted b sequences of the L component of viral DNA. We also report the following. (i) The chimeric gene consisting of the coding and 5' nontranslated leader regions of the TK gene fused to portions of the domain of alpha gene 0 extending largely upstream from the site of initiation of transcription of alpha gene 0 was regulated in the same fashion as the alpha 4- and alpha 27-TK chimeras. The regulatory region in the alpha gene 0 is largely upstream from nucleotide - 140. (ii) The promoter-regulatory regions of alpha genes 0, 4, and 27 share TATA sequences, A + T-rich (consensus) sequences occurring in regulating regions of alpha genes 0 and 4 in more than one copy, and multiple G + C-rich inverted repeats. The relation of these sequences to the function of the promoter-regulatory regions of the alpha genes is discussed.
Body Weight Alterations Under Early Corticosteroid Withdrawal and Chronic Corticosteroid Therapy with Modern Immunosuppression

Background. Weight gain is a known complication of corticosteroid maintenance therapy. The purpose of the present study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) with that observed under early (i.e., within 7 days posttransplant) corticosteroid withdrawal (CSWD) in renal-transplant recipients. Methods. Renal-transplant recipients who underwent early CSWD under four prospective, institutional review board-approved clinical trials were compared with a historic control group of patients receiving maintenance CCST. Results. One hundred sixty-nine patients with early CSWD were compared with 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 3, 6, and 12 months posttransplant. Race influenced weight gain because white CSWD patients demonstrated greater reductions in weight gain compared with African-American patients. Sex also influenced weight gain: women demonstrated a greater benefit from CSWD than did men. Corticosteroid rejection therapy in CSWD patients completely restored weight gain because these patients showed weight gains similar to the CCST group. Finally, pretransplant body mass index (BMI) also influenced weight gain because patients who were overweight (BMI 25–30) or obese (BMI>30) demonstrated a greater reduction in weight gain with CSWD than did patients of normal weight (BMI<25). Conclusions. Early CSWD minimizes weight gain in renal-transplant recipients. Women, whites, and patients with high pretransplant BMI had greater reductions in weight gain with early CSWD.
Adaptation of Habrobracon hebetor (Hymenoptera: Braconidae) to Rearing on Ephestia kuehniella (Lepidoptera: Pyralidae) and Helicoverpa armigera (Lepidoptera: Noctuidae)

Food characteristics strongly regulate digestive enzymatic activity of insects through direct influences on their midgut mechanisms. Insect performance is better on diets that contain nutrients in proportions that fit its digestive enzymes. Little is known about the influences of rearing history on parasitism success of Habrobracon hebetor Say. This research focused on the effect of nutrient regulation on survival, development, and parasitism of H. hebetor. Life history and digestive enzyme activity of fourth-stage larvae of H. hebetor were studied when reared on Ephestia kuehniella Zeller. This parasitoid was then introduced to Helicoverpa armigera (Hübner), and above-mentioned parameters were also studied in the first and fourth generations after transfer. In term of parasitism success, H. hebetor preferred E. kuehniella over He. armigera. When the first and fourth generations of He. armigera-reared H. hebetor were compared, the rearing history affected the life history and enzymatic activity of the parasitoid. A better performance of H. hebetor was achieved after it was reared on He. armigera for the four generations. Because, digestive α-amylase and general protease of the parasitoid were matched with the new host, it used reserve energy for a better performance. Thus, a better performance of H. hebetor could be obtained when the parasitoid was reared on its original host for at least four generations.
Development of Silicon Nanowire-Based NEMS Absolute Pressure Sensor Through Surface Micromachining

This letter reports on a nano-electro-mechanical system (NEMS) pressure sensor with p-doped silicon nanowires (average cross-sectional area ~100 nm2) as piezoresistive sensing elements. Taking advantage of surface micromachining, an absolute pressure-sensing device is developed using front-side isotropic etching. In contrast to the previously reported silicon nanowire (SiNW) pressure sensor processed with bulk micromachining through the backside deep reactive ion etching (DRIE), nonlinearity has been reduced to 0.31% (BFSL). In addition, the performance variations across the wafer have been significantly reduced to 6% in comparison with a 33% sensitivity fluctuation across the 8-inch wafer reported in our early work fabricated by a DRIE process. After front-side vacuum sealing, temperature-induced performance degradation has also been minimized. Moreover, the dramatic geometry downsizing (device footprint $\sim 385~\mu \text{m}^{\mathrm {\mathbf {2}}}$ ) validates the scalability of the SiNW-based NEMS sensor. With excellent uniformity, the SiNW-based sensor can be commercially manufactured on an 8-inch wafer at lower cost with high yield.
A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer

Purpose: Most high-grade serous ovarian cancer (HGSOC) patients develop recurrent disease after first-line treatment, frequently with fatal outcome. This work aims at studying the molecular biology of both primary and recurrent HGSOC. Experimental Design: Gene expression profiles of matched primary and recurrent fresh-frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. Clustering analyses and pairwise comparison of the profiles between matched samples and subsequent functional alignment were used for the identification of molecular characteristics of HGSOC. Results: Both primary and recurrent HGSOC samples presented predominant gene expression differences in their microenvironment, determined by a panel of genes covering all major pathways of immune activation together with a number of genes involved in the remodeling of extracellular matrix and adipose tissues. Stratifying tumor tissues into immune active and silent groups, we further discovered that although some recurrent tumors shared the same immune status as their primary counterparts, others switched the immune status, either from silent to active or active to silent. Interestingly, genes belonging to the B7-CD28 immune checkpoint family, known for their major role as negative regulators of the immune response, were overexpressed in the immune active tumors. Searching for potential tumor antigens, CEACAM21, a member of the carcinoembryonic antigen family, was found to be significantly overexpressed in immune active tissues in comparison with the silent ones. Conclusions: The results illustrate the complexity of the tumor microenvironment in HGSOC and reveal the molecular relationship between primary and recurrent tumors, which have multiple therapeutic implications. Clin Cancer Res; 23(24); 7621–32. ©2017 AACR.
Multiobjective bilevel optimization for production-distribution planning problems using hybrid genetic algorithm

Currently, the production-distribution planning problems are usually modeled as single-objective bilevel programming problems. However, many real world production-distribution planning problems involve several objectives simultaneously for decision makers at two different levels when the production and the distribution processes are considered. In this paper, a multiobjective bilevel production-distribution planning model with equilibrium between supply and demand is set up, in which the distribution company is the leader who controls the distributing process with the aims to minimize its overall cost, and the manufacturer is the follower who controls the production process with the aims to minimize its overall cost and storage cost. So in the proposed model, the leader has one objective and the follower has two objectives. To solve the model efficaciously, the lower level problem follower's problem is transformed into an equivalent single-objective programming problem by a weighted aggregation method. As a result, the multiobjective bilevel optimization problem is transformed into a single-objective bilevel optimization problem. To solve the transformed problem efficiently, a uniform design scheme is applied to generate some representative weight vectors and initial population. Thereafter, a uniform design based crossover and exponential mutation are designed, and a local search scheme is applied. Based on all these, a hybrid genetic algorithm is proposed. Finally, two real word problems are solved successfully by the proposed algorithm, and the effectiveness and efficiency of the proposed algorithm are also tested by other test problems.
Variability of Suspended Particle Properties Using Optical Measurements Within the Columbia River Estuary

Optical properties are used to understand the spatial and temporal variability of particle properties and distribution within the Columbia River Estuary, especially in the salinity transition zone and in the estuarine turbidity maximum region. Observations of optical properties in the Columbia River Estuary are consistent with the established model that the river water brings more organic, smaller particles into the estuary, where they ﬂocculate and settle into the salt wedge seaward of the density front. Large tidal currents resuspend mineral-rich, larger aggregates from the seabed, which accumulate at the density front. Optical proxies for particle size (beam attenuation exponent 𝛾 and backscattering exponent 𝛾 bb ) are compared to conventional measurements. The 𝛾 and 𝛾 bb are diﬀerent to the expected trend with Sauter mean diameter D s of suspended particles from low- to medium-salinity waters (LMW). D s increases in the LMW as does the 𝛾 derived from a WET Labs ac-9, which indicates that the particle population dominating the ac-9 is decreasing in size. The most likely explanation is that ﬂocculation acting at LMW transfers mass preferentially from medium-sized particles to large-sized particles that are out of the size range to which the ac-9 is most sensitive; 𝛾 bb shows no trend in the LMW. Since 𝛾 bb is a proxy of proportion of ﬁne particles versus large ﬂocs, the variation of 𝛾 bb may be insensitive to changes in the medium-sized particles. The overall results demonstrate that 𝛾 bb is a reliable proxy for changes in particle size in a stratiﬁed environment. from water samples require substantial time and labor, which has driven eﬀorts to develop indirect, yet accurate, alternative measurements of particle properties. In this study, we used optical instruments to measure particle variability within the Columbia River Estuary. The observations demonstrate that the river water delivered smaller, organic particles to the estuary, where they aggregated with one another and deposited to the seaﬂoor. Large tidal currents resuspended mineral-rich, larger aggregates from the seaﬂoor, and these aggregates accumulated in the region where river waters encountered coastal ocean waters that ﬂowed into the estuary. We observed that optical measurements related to particle size were diﬀerent from the expected trend in the transition zone between fresh, river water and salty, coastal water. This unexpected trend requires more study, but we propose that it was caused by preferential aggregation of medium-sized organic-rich particles into large particles. This process would aﬀect the processing of carbon, nutrients, and contaminants in estuaries.
Design principles for effective physics instruction: A case from physics and everyday thinking

Although several successful inquiry-based physics and physical science curricula have been developed, little has been published that describes the development of these curricula in terms of their basic design principles. We describe the research-based design principles used in the development of one such curriculum and how these principles are reflected in its pedagogical structure. A case study drawn from an early pilot implementation illustrates how the design principles play out in a practical classroom setting. Extensive evaluation has shown that this curriculum enhances students’ conceptual understanding and improves students’ attitudes about science.
Do UK television alcohol advertisements abide by the code of broadcast advertising rules regarding the portrayal of alcohol?

AIMS The aim of the study was to assess the extent to which members of the UK general public perceive television alcohol advertisements to comply with the regulatory code governing these: the Advertising Standards Authority Code of Broadcast Advertising (BCAP Code). The Code provides a general principle and 16 rules to prevent such adverts implying, condoning or encouraging immoderate, irresponsible or anti-social drinking. METHODS Quota sample of 373 adults, representative of the UK population aged 18-74 years in terms of age and gender, were recruited at a train station. Participants were shown one of seven advertisements that had been broadcast in the previous month on the two leading commercial television channels, and then completed a questionnaire with 40 statements representing the BCAP Code rules. RESULTS Overall, 75% of the participants rated the advertisements as breaching at least one rule from the BCAP Code. Breaches were observed for all the seven advertisements, ranging from 49 to 91% non-compliant. Rules regarding alcohol being presented as contributing to popularity or confidence, and implying that alcohol is capable of changing mood, physical condition, behaviour, or as nourishment, were seen as being breached by over 50% of participants. CONCLUSIONS A clear majority of the UK general public perceive alcohol advertisements to breach the BCAP Code, suggesting that the current regulatory system for UK television alcohol advertisements is inadequate.