Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina.

PURPOSE To study the physiological function of NR2E3 and possible molecular mechanisms underlying enhanced short-wavelength cone syndrome (ESCS) pathogenesis in developing human retina, and to compare its expression to that of Neural Retina Leucine zipper (NRL), a transcription factor essential for rod differentiation. METHODS Expression of NR2E3, a photoreceptor-specific orphan nuclear receptor, was examined in human retinas between fetal weeks (Fwk) 9 to 22 by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Both NR2E3 and NRL expression patterns were followed by immunocytochemistry. The human retina develops in a central to peripheral pattern, in which a protein may take weeks to be expressed throughout the entire retina. This allowed a detailed temporal analysis of NR2E3 and NRL expression. RESULTS NR2E3 expression was detected shortly after the appearance of NRL in putative immature rods on the foveal edge at Fwk 11.7. Expression of both markers was maintained in rod opsin expressing fetal photoreceptors. NR2E3 expression was not detected in either long/medium- or short-wavelength cones. Its absence from cones was also supported by the position of labeled nuclei deep in the outer nuclear layer, and by the absence of NR2E3 from the fovea. CONCLUSIONS A role for NR2E3 in the rod developmental pathway is suggested. The closely related expression patterns of NRL and NR2E3 supported an interactive function, where both transcription factors determine the rod fate and suppress immature rods from adopting the S-cone fate.
Involvement of norepinephrine and serotonin system in antidepressant-like effects of hederagenin in the rat model of unpredictable chronic mild stress-induced depression

Abstract Context: Previous studies from our laboratory indicated that both acute and subchronic administration of Fructus Akebiae (FAE) [the fruit of Akebiae quinata (Thunb.) Decne, (Lardizabalaceae)] produce antidepressant-like effects in animal depressive behavior tests. FAE contains approximately 70% of hederagenin (HG) as its main chemical component. Objective: This study compared the antidepressant ability of FAE with that of HG in mice and further investigated the antidepressant-like effects and potential mechanisms of HG in rats subjected to unpredictable chronic mild stress (UCMS). Materials and methods: Mice received FAE (50 mg/kg) and HG (20 mg/kg) once a day via intragastric administration (i.g.) for 3 weeks. The anxiolytic and antidepressant activities of FAE and HG were compared using elevated plus maze (EPM) and behavioral despair tests including tail suspension test (TST) and forced swimming test (FST), respectively. Antidepressant effects of HG (5 mg/kg) were assessed using the UCMS depressive rat model. Moreover, the levels of monoamine neurotransmitters and relevant gene expression in UCMS rats’ hippocampi were determined through high-performance liquid chromatography with electrochemical detection and real-time polymerase chain reaction techniques. Results: The results of our preliminary screening test suggest that HG at 20 mg/kg, while not FAE at 50 mg/kg, significantly decreased the immobility in both TST and FST compared with the vehicle group when administered chronically; however, there were no significant differences observed between the HG and the FAE group. Chronic administration of HG failed to significantly reverse the altered crossing and rearing behavioral performance, time spent in the open arm and closed entries in the EPM, even if they showed an increased tendency, but HG significantly increased the percent of sucrose preference in the sucrose preference test (SPT) and decreased the immobility time in the FST. HG showed that significant increases of norepinephrine and serotonin levels and exhibited a tendency to increase the expression of 5-hydroxytryptamine (serotonin) 1A receptor mRNA, and to significantly decrease the expression of the mRNA for the serotonin transporter (5-HTT). However, there were no significant differences in the expression of the brain-derived neurotrophic factor. Conclusion: These findings confirm the antidepressant-like effects of HG in a behavioral despair test and UCMS rat model, which may be associated with monoamine neurotransmitters and 5-HTT mRNA expression.
Qualitative analysis of skeletal myosin as substrate of Ca2+-activated neutral protease: comparison of filamentous and soluble, native, and L2- deficient myosin

Ca2+ -activated neutral protease (CAF) was capable of degrading myosin over a 200-fold range of protease concentrations. CAF selected the heavy chain of myosin, although either prolonged exposure to or high concentrations of the protease degraded the L1, but not the L2 or L3, light chains of myosin. The following results indicated that during the first hour of digestion, under conditions where native myosin was the substrate, CAF selected for the "head" region of the myosin heavy chain: (a) large heavy chain fragments of identical molecular weight were produced from filamentous and from soluble myosin; (b) light meromyosin was not a substrate; (c) agents known to bind to the head of myosin (actin, MgATP, and L2) had both a qualitative and quantitative effect on degradation; and (d) similar cleavage sites could be demonstrated for myosin and for heavy meromyosin (HMM) despite the fact that HMM was a much poorer substrate than myosin. This observation is interpreted as an indication that the conformation of myosin heavy chain is altered in the preparation of HMM. The principal cleavage sites on the heavy chain of myosin were 20,000, 35,000 and 50,000 D from the N-terminus, producing large fragments with molecular weights of 180,000, 165,000, and 150,000 which comprised a "nicked" species of myosin. This nicked species retained both normal solubility properties and normal hydrolytic activities. For this reason, it is concluded that "nicked myosin" is an important pathophysiological species.
An Analysis of the Alleged Skeletal Remains of Carin Göring

In 1991, treasure hunters found skeletal remains in an area close to the destroyed country residence of former Nazi leader Hermann Göring in northeastern Berlin. The remains, which were believed to belong to Carin Göring, who was buried at the site, were examined to determine whether it was possible to make a positive identification. The anthropological analysis showed that the remains come from an adult woman. The DNA analysis of several bone elements showed female sex, and a reference sample from Carin's son revealed mtDNA sequences identical to the remains. The profile has one nucleotide difference from the Cambridge reference sequence (rCRS), the common variant 263G. A database search resulted in a frequency of this mtDNA sequence of about 10% out of more than 7,000 European haplotypes. The mtDNA sequence found in the ulna, the cranium and the reference sample is, thus, very common among Europeans. Therefore, nuclear DNA analysis was attempted. The remains as well as a sample from Carin's son were successfully analysed for the three nuclear markers TH01, D7S820 and D8S1179. The nuclear DNA analysis of the two samples revealed one shared allele for each of the three markers, supporting a mother and son relationship. This genetic information together with anthropological and historical files provides an additional piece of circumstantial evidence in our efforts to identify the remains of Carin Göring.
Correlation of CDA, ERCC1, and XPD Polymorphisms with Response and Survival in Gemcitabine/Cisplatin–Treated Advanced Non–Small Cell Lung Cancer Patients

Purpose: Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in non–small cell lung cancer (NSCLC). Polymorphisms at the xeroderma pigmentosum group D (XPD), excision repair cross-complementing 1 (ERCC1), and cytidine deaminase (CDA) genes have been associated with alterations in enzymatic activity and may change sensitivity to the widely used cisplatin-gemcitabine regimen. Experimental Design: Analyses of CDA, XPD, and ERCC1 polymorphisms were done on blood samples of 65 chemotherapy-naïve, advanced NSCLC patients treated with cisplatin-gemcitabine. Furthermore, CDA enzymatic activity was evaluated by high-performance liquid chromatography analysis. Association between XPD Asp312Asn and Lys751Gln, ERCC1 C118T, and CDA Lys27Gln polymorphisms and response, clinical benefit, toxicity, time to progression (TTP), and overall survival (OS) was estimated using Pearson's χ2 tests, the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards model. Results: The CDA Lys27Lys polymorphism significantly correlated with better clinical benefit (P = 0.04) and grade ≥3 neutropenia and thrombocytopenia, as well as with longer TTP and OS (P = 0.006 and P = 0.002, respectively), whereas no significant associations were found among ERCC1 and XPD polymorphisms and both response and clinical outcome. Finally, the enzymatic activity assay showed a significant lower mean in subjects harboring the CDA Lys27Lys polymorphism. Conclusions: Our data suggested the role of CDA Lys27Lys polymorphism as a possible predictive marker of activity, toxicity, TTP, and OS in advanced NSCLC patients treated with cisplatin and gemcitabine. These results may be explained by the lower enzymatic activity associated with the Lys27Lys CDA and offer a potential new tool for treatment optimization.
Analisis Pola Persebaran Klorofil-a, Suhu Permukaan Laut, dan Arah Angin untuk Identifikasi Kawasan Upwelling secara Temporal Tahun 2003-2016 (Studi Kasus : Laut Halmahera)

ABSTRAK Indonesia merupakan negara kepulauan dengan wilayah laut yang luas dan memiliki sumber daya laut yang sangat potensial salah satunya ialah sumber daya perikanan. Laut Halmahera yang berbatasan langsung dengan Samudera Pasifik memiliki kondisi perairan yang dinamis. Agar kegiatan penangkapan ikan lebih optimal diperlukan teknologi yang tepat untuk menentukan lokasi potensial tempat berkumpulnya ikan salah satunya dengan menggunakan citra satelit Aqua MODIS untuk menentukan parameter upwelling (klorofil-a, dan suhu permukaan laut (SPL)), serta citra Quickscat untuk mendapatkan data arah dan kecepatan angin. Metode pengolahan yang digunakan pada penelitian ini menggunakan bahasa pemrograman ENVI IDL untuk mengolah data angin, SPL dan klorofil-a dari tahun 2003-2016 sehingga didapatkan nilai sebaran klorofil-a, SPL, dan angin secara klimatologi. Data klimatologi tersebut dianalisis secara spasial untuk melihat pola upwelling yang terjadi pada setiap musim. Selanjutnya dilakukan perhitungan kriteria upwelling untuk mengetahui kekuatan upwelling setiap bulannya. Selanjutnya dilakukan uji korelasi untuk mengetahui kekuatan hubungan antar parameter serta uji validasi untuk mendapatkan peta tematik sebaran klorofil-a dan SPL pada saat terjadi fenomena upwelling . Fenomena upwelling di Laut Halmahera terjadi pada musim timur yakni pada bulan Juni hingga Agustus dimana puncak upwelling terjadi pada bulan Agustus. Pada bulan tersebut kandungan klorofil-a mencapai 0,440 mg/m 3 , kecepatan angin sebesar 5,757 m/s dan suhu permukaan turun hingga mencapai 29,014 o C. Berdasarkan hasil uji korelasi diketahui bahwa antar parameter upwelling tersebut memiliki hubungan yang kuat. Klorofil-a dengan angin memiliki nilai korelasi sebesar 0,615 dan klorofil-a dengan SPL memiliki nilai korelasi sebesar -0,734.
Quality of life of Latina and Euro‐American women with ductal carcinoma in situ

Risk factors for psychosocial distress following a breast cancer diagnosis include younger age, history of depression, inadequate social support, and serious comorbid conditions. Although these quality of life (QOL) concerns have been studied in women with ductal carcinoma in situ (DCIS), Latina women have been understudied.
CD30 cell graphs of Hodgkin lymphoma are not scale-free - an image analysis approach

MOTIVATION Hodgkin lymphoma (HL) is a type of B-cell lymphoma. To diagnose the subtypes, biopsies are taken and immunostained. The slides are scanned to produce high-resolution digital whole slide images (WSI). Pathologists manually inspect the spatial distribution of cells, but little is known on the statistical properties of cell distributions in WSIs. Such properties would give valuable information for the construction of theoretical models that describe the invasion of malignant cells in the lymph node and the intercellular interactions. RESULTS In this work, we define and discuss HL cell graphs. We identify CD30(+) cells in HL WSIs, bringing together the fields of digital imaging and network analysis. We define special graphs based on the positions of the immunostained cells. We present an automatic analysis of complete WSIs to determine significant morphological and immunohistochemical features of HL cells and their spatial distribution in the lymph node tissue under three different medical conditions: lymphadenitis (LA) and two types of HL. We analyze the vertex degree distributions of CD30 cell graphs and compare them to a null model. CD30 cell graphs show higher vertex degrees than expected by a random unit disk graph, suggesting clustering of the cells. We found that a gamma distribution is suitable to model the vertex degree distributions of CD30 cell graphs, meaning that they are not scale-free. Moreover, we compare the graphs for LA and two subtypes of HL. LA and classical HL showed different vertex degree distributions. The vertex degree distributions of the two HL subtypes NScHL and mixed cellularity HL (MXcHL) were similar. AVAILABILITY AND IMPLEMENTATION The CellProfiler pipeline used for cell detection is available at https://sourceforge.net/projects/cellgraphs/. CONTACT ina.koch@bioinformatik.uni-frankfurt.de SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Behavioral Economics and Public Policy: A Pragmatic Perspective

The debate about behavioral economics – the incorporation of insights from psychology into economics – is often framed as a question about the foundational assumptions of economic models. This paper presents a more pragmatic perspective on behavioral economics that focuses on its value for improving empirical predictions and policy decisions. I discuss three ways in which behavioral economics can contribute to public policy: by offering new policy tools, improving predictions about the effects of existing policies, and generating new welfare implications. I illustrate these contributions using applications to retirement savings, labor supply, and neighborhood choice. Behavioral models provide new tools to change behaviors such as savings rates and new counterfactuals to estimate the effects of policies such as income taxation. Behavioral models also provide new prescriptions for optimal policy that can be characterized in a non-paternalistic manner using methods analogous to those in neoclassical models. Model uncertainty does not justify using the neoclassical model; instead, it can provide a new rationale for using behavioral nudges. I conclude that incorporating behavioral features to the extent they help answer core economic questions may be more productive than viewing behavioral economics as a separate subfield that challenges the assumptions of neoclassical models.
Space and the persistence of male–killing endosymbionts in insect populations

Male–killing bacteria are bacteria that are transmitted vertically through the females of their insect hosts. They can distort the sex ratio of their hosts by killing infected male offspring. In nature, male–killing endosymbionts (male killers) often have a 100% efficient vertical transmission, and multiple male–killing bacteria infecting a single population are observed. We use different model formalisms to study these observations. In mean–field models a male killer with perfect transmission drives the host population to extinction, and coexistence between multiple male killers within one population is impossible; however, in spatially explicit models, both phenomena are readily observed. We show how the spatial pattern formation underlies these results. In the case of high transmission efficiencies, waves with a high density of male killers alternate with waves of mainly wild–type hosts. The male killers cause local extinction, but this creates an opportunity for uninfected hosts to re–invade these areas. Spatial pattern formation also creates an opportunity for two male killers to coexist within one population: different strains create spatial regions that are qualitatively different; these areas then serve as different niches, making coexistence possible.
Subtle neurologic compromise as a vulnerability factor for combat-related posttraumatic stress disorder: results of a twin study.

CONTEXT Previous studies have demonstrated subtle neurologic dysfunction in chronic posttraumatic stress disorder (PTSD) manifest as increased neurologic soft signs (NSSs). The origin of this dysfunction is undetermined. OBJECTIVE To resolve competing origins of increased NSSs in PTSD, namely, preexisting vulnerability factor vs acquired PTSD sign. DESIGN Case-control study of identical twins. SETTING A Veterans Affairs and academic medical center (ambulatory). PARTICIPANTS A convenience sample of male Vietnam veteran twins with (n = 25) and without (n = 24) PTSD and their combat-unexposed identical (monozygotic) co-twins. INTERVENTIONS Neurologic examination for 45 NSSs. MAIN OUTCOME MEASURE Average scores for 45 NSSs, each scored on an ordinal scale from 0 to 3, masked to diagnosis and combat exposure status. RESULTS There was a significant between-pair main effect of PTSD diagnosis (as determined in the combat-exposed twin) on average NSS score in the absence of a significant combat exposure main effect or diagnosis x exposure interaction. Combat veterans with PTSD had significantly higher NSS scores than combat veterans without PTSD. The "high-risk," unexposed co-twins of the former also had significantly higher NSS scores than the "low-risk," unexposed co-twins of the latter. This result could not be explained by age, number of potentially traumatic lifetime noncombat events, alcoholism, or the presence of a comorbid affective or anxiety disorder. The average NSS score in unexposed co-twins was not significantly associated with combat severity in combat-exposed twins. CONCLUSIONS These results replicate previous findings of increased NSSs in Vietnam combat veterans with PTSD. Furthermore, results from their combat-unexposed identical co-twins support the conclusion that subtle neurologic dysfunction in PTSD is not acquired along with the trauma or PTSD but rather represents an antecedent familial vulnerability factor for developing chronic PTSD on exposure to a traumatic event.
Recent immunomodulatory strategies in transplantation

Despite preservation methods, surgical procedures, current immunosuppressive therapy regimens advances, organ transplantation is accompanied with a poor long-term survival and significant mortality. This has led to an increased interest to optimize outcomes while minimizing associated toxicity by using alternative methods for maintenance immunosuppression, organ rejection treatment, and monitoring of immunosuppression. Advance in long-standing allograft outcomes may depend on new drugs with novel mechanisms of action with minimal toxicity. Newer treatment techniques have been developed, including using novel stem cell-based therapies such as mesenchymal stem cells, phagosomes and exosomes. Immunoisolation techniques and salvage therapies, including photopheresis and total lymphoid irradiation have emerged as alternate therapeutic choices. The present review evaluates the recent clinical advances in immunosuppressive therapies for organ transplantation.
Ice cap erosion patterns from bedrock 10Be and 26Al, southeastern Tibetan Plateau

Quantifying glacial erosion contributes to our understanding of landscape evolution and topographic relief production in high altitude and high latitude areas. Combining in situ 10Be and 26Al analysis of bedrock, boulder, and river sand samples, geomorphological mapping, and field investigations, we examine glacial erosion patterns of former ice caps in the Shaluli Shan of the southeastern Tibetan Plateau. The general landform pattern shows a zonal pattern of landscape modification produced by ice caps of up to 4000 km2 during pre‐LGM (Last Glacial Maximum) glaciations, while the dating results and landforms on the plateau surface imply that the LGM ice cap further modified the scoured terrain into different zones. Modeled glacial erosion depth of 0–0.38 m per 100 ka bedrock sample located close to the western margin of the LGM ice cap, indicates limited erosion prior to LGM and Late Glacial moraine deposition. A strong erosion zone exists proximal to the LGM ice cap marginal zone, indicated by modeled glacial erosion depth >2.23 m per 100 ka from bedrock samples. Modeled glacial erosion depths of 0–1.77 m per 100 ka from samples collected along the edge of a central upland, confirm the presence of a zone of intermediate erosion in‐between the central upland and the strong erosion zone. Significant nuclide inheritance in river sand samples from basins on the scoured plateau surface also indicate restricted glacial erosion during the last glaciation. Our study, for the first time, shows clear evidence for preservation of glacial landforms formed during previous glaciations under non‐erosive ice on the Tibetan Plateau. As patterns of glacial erosion intensity are largely driven by the basal thermal regime, our results confirm earlier inferences from geomorphology for a concentric basal thermal pattern for the Haizishan ice cap during the LGM. © 2018 John Wiley & Sons, Ltd.
I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND Postoperative nausea and vomiting (PONV) remain significant clinical problems for patients, especially nausea. The D2-antagonist droperidol was popular for prophylaxis until safety concerns limited its use. In early testing, APD421 (amisulpride for i.v. injection), a D2/D3-antagonist, has shown promising antiemetic efficacy at very low doses. We conducted a randomized, double-blind, dose-finding study to investigate APD421 in PONV prophylaxis. METHODS Adult surgical patients with ≥2 Apfel risk factors for PONV undergoing surgery expected to last ≥1 h and receiving standard inhalation anaesthesia were randomized to receive placebo or one of three doses of APD421 (1, 5, or 20 mg) as a single i.v. administration at anaesthesia induction. The primary endpoint was PONV (vomiting/retching or antiemetic rescue) in the 24 h period after surgery. RESULTS Two hundred and fifteen patients received study drug, 92% female and 60% with ≥3 risk factors. Groups were well balanced for baseline characteristics and risk factors. The PONV incidence was 37/54 [69%; 90% confidence interval (CI), 57-79%] in the placebo group; 28/58 (48%; 90% CI, 37-60%) with 1 mg APD421 (P=0.048); 20/50 (40%; 90% CI, 28-53%) with 5 mg (P=0.006); and 30/53 (57%; 90% CI, 44-68%) with 20 mg (P>0.1). APD421 at 5 mg also significantly improved vomiting, rescue medication use, and nausea rates. The safety profile of APD421 was similar to that of placebo at all doses, with no significant central nervous system (CNS) or cardiac side-effects. CONCLUSIONS APD421 given i.v. before surgery is safe and effective at reducing PONV in moderate/high-risk adult surgical patients. The optimal dose tested was 5 mg.