Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxic Adaptation and Arsenic Trioxide Treatment in Small Cell Lung Carcinoma

Small cell lung carcinoma (SCLC) is a very aggressive solid tumor and is often widely metastasized by the time of diagnosis. Despite good response to the initial chemotherapy, SCLC cells often develop multidrug resistance to conventionally used chemotherapeutic drugs, which cause almost all SCLC tumors to relapse. The 5-year survival rate for patients with limited disease is around 20% while it is only a few percent for patients with a disseminating disease. Arsenic trioxide (As2O3) is one of the oldest medicines used for treatment of different diseases and it is today used as first-line treatment for patients with relapsed or refractory acute promyelocytic leukemia. Here, we demonstrate that As2O3 is cytotoxic to SCLC cells and xenotransplanted SCLC tumors at clinically relevant concentrations and the effect is also sustained at hypoxic conditions. Areas of low oxygen tensions, hypoxia, are a common characteristic in solid tumors and are associated with aggressive tumor behavior, treatment resistance and poor outcome in several tumor forms. In response to hypoxia, tumor cells induce a transcriptional shift which is mainly regulated by the transcription factors hypoxia-inducible factor (HIF)-1 and HIF-2. HIF proteins consist of two subunits, an oxygen-regulated α-subunit and a constitutively expressed β-subunit. Previous reports have shown that the transcription factors are differentially regulated over time; HIF-1 primarily mediates the acute hypoxic response, whereas HIF-2 dominates during more chronic phases of hypoxia. We found that SCLC tumor specimens and cells lack expression of HIF-2α protein while HIF-1α is expressed at both acute and prolonged hypoxia. In addition, SCLC cells have a high adaptive capacity to hypoxia including a high proliferation rate and low cell death, even though we demonstrated a modest induction of well-known hypoxia-driven genes. We further show that knockdown of HIF1A using siRNA or shRNA, is not significantly affecting the cell viability of cultured SCLC cells at moderate and severe hypoxia or tumor take and tumor growth in SCLC xenografts. We found that SCLC cells are dependent on glutamine metabolism for cell viability and proliferation, in a HIF-independent fashion. The SCLC cells used here are MYC and MYCL amplified and MYC overexpression is known to stimulate glutaminolysis and lipogenesis. In HIF1A repressed cells that overexpress MYC, genes involved in these pathways are further up-regulated at hypoxic conditions. Taken together, our data indicate that the adaptive capacity to hypoxia is partially HIF-independent in MYC amplified SCLC cells.
Diatoms as indicators of environmental change in lakes and ponds of the lowlands, Middle Hills and High Himalaya of Nepal

Kieselalgen wurden in verschiedenen Mikrohabitaten von Hochgebirgsseen in der Region von Gosainkunda, Langtang National Park, in Teichen und kleinen Seen des Kathmandu Tales im mittleren Bergland, und in Teichen der Region von Koshi Tappu im nepalesischen Tiefland untersucht. Temperatur, Leitfahigkeit und pH wurden vor Ort gemessen und Wasserproben fur die chemische Analyse von Kationen und Anionen entnommen. In Gosainkunda und im Kathmandu Tal wurden Proben des Oberflachenwassers, und in Koshi Tappu wurden Proben des Oberflachen- und des Interstitialwassers genommen. Gleichzeitig wurde eine Untersuchung des Habitatcharakters der Seen und Teiche bezuglich der Substratbeschaffenheit und der Gewasservegetation sowie der Uferregion bezuglich der Substratzusammensetzung, des Uferprofils, der terrestrischen Vegetation und der Landnutzung in unmittelbarer Umgebung durchgefuhrt. Die Kieselalgengemeinschaften der verschiedenen Mikrohabitate in Teichen und Seen aus drei Regionen Nepals unterschiedlichen Charakters sind gute Indikatoren fur Umweltveranderungen als Folge von landwirtschaftlicher Intensivierung, Industrialisierung und Verstadterung. Dieser Wandel wird sich in Zukunft beschleunigen mit zunehmender Beanspruchung von Wasserressourcen.
Search for

A search for highly electrically charged objects (HECOs) and magnetic monopoles is presented using 2.2 fb − 1 of p-p collision data taken at a centre of mass energy (E CM ) of 8 TeV by the MoEDAL detector during LHC’s Run-1. The data were collected using MoEDAL’s prototype Nuclear Track Detector array and the Trapping Detector array. The results are interpreted in terms of Drell-Yan pair production of stable HECO and monopole pairs with three spin hypotheses (0, 1/2 and 1). The search provides constraints on the direct production of magnetic monopoles carrying one to four Dirac magnetic charges (4 g D ) and with mass limits ranging from 590 GeV to 1 TeV. Additionally, mass limits are placed on HECOs with charge in the range 10 e to 180 e , where e is the charge of an electron, for masses between 30 GeV and 1 TeV.
THE IMPACT OF FISCAL DECENTRALIZATION ON CORRUPTION IN INDONESIA

This research is intended to examine the influence of fiscal decentralization on corruption case in Indonesia. Research population are regencies/municipalities throughout the province in Indonesia, employing secondary data from Dirjen Perimbangan Keuangan Pemerintah Daerah and Transparency International Indonesia (TIIndonesia) within the period of 2004, 2006, 2008, and 2010. Data analysis is conducted by using path analysis with AMOS program software. The results of this study indicate that, fiscal decentralization has a negative and significant effect on Corruption Perception Index (CPI). The higher the fiscal decentralization, the more higher the corruption is in Indonesia.
Genome-wide characterization of MLO family genes in bread wheat and Arabidopsis thaliana shed light on their role in growth and development, and resistance to powdery mildew, biotic and abiotic stresses

Powdery mildew (PM), caused by the fungus, Blumeria graminis tritici is a devastating and notorious disease that is prevalent across the globe and causes up to 62% of yield losses in wheat. The well-known 68 PM resistance loci (Pm1 -Pm68) are not long-lasting and break down when new races of pathogens interact with host plants. The editing of three known MLO genes through CRISPR/Cas9 has conferred resistance against PM. However, only seven MLO genes were known in wheat to date. Taking advantage of IWGSC Ref-seq v2.1 and using the gold-standard analysis pipeline that we have designed, we expanded this number to 47 and reported 40 additional potential CRISPR targets that can be used to develop PM resistance, disease resistance, and abiotic stress tolerance in wheat. We also performed phylogenetic, gene structure, and MOTIF analysis that indicated conserved evolutionary patterns, and the phylogenetic pattern was strongly supported by gene structure and MOTIF analysis. The gene duplication and evolution analysis showed that segmental duplications were prevalent and purifying selection operated during evolution. Comparative phylogenetic analysis with Arabidopsis thaliana and Brachypodium distachyon depicted that clade IV was exclusive for monocots. Finally, MLOs are expressed under powdery mildew, rusts, head blight, abiotic stresses, growth, and development thus TraesMLOs have a potential role in wheat under these conditions. Therefore, we hope that the MLO genes identified in this study will be edited through CRISPR/Cas9 or will be overexpressed to develop PM and disease-resistant and abiotic stress-tolerant wheat. Additionally, we performed most of the above-mentioned analyses for Arabidopsis thaliana, revised its numbers as compared to the TAIR database, and updated it outdated analysis performed in 2003.
Gene regulatory Networks Reveal Sex Difference in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively. Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data. We observe that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue, as well as in tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also uncovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database. These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.
Port-scanning resistance in Tor anonymity network

The Onion Router (Tor) is an anonymity network that allows users to perform web browsing and other internet activities anonymously. A Tor user's traffic is routed securely through several other Tor relays before making its way to its destination. No one except the final Tor router in this circuit knows what the final destination of users traffic is and each router in the circuit only knows about the previous and next router. Tor users get the list of Tor IP addresses from a dedicated server which lists most of the Tor routers. With this list they can create random circuits through the internet to route their traffic. Governments that censor the internet with country-wide firewalls want to block Tor, because it allows users to circumvent the censorship. China has begun blocking Tor by downloading the list of all public Tor IP addresses and blocking them. [1] There are still options for internet users in China to access the Tor network. One option is unpublished Tor relays whose internet addresses are shared via email and instant messenger instead of in a public directory like normal Tor relays. Since these unpublished routers cannot be easily downloaded in bulk like the published Tor routers, detecting and blocking unpublished routers is the obvious next step for China and other censoring nations. Currently it is possible to detect these unpublished Tor relays by running Tor and attempting to connect to every internet address on ports Tor commonly runs. If a computer responds as Tor would, you know it is running Tor and can thus block the internet address. In this paper I present and implement a protocol which decreases the ease of detection of these unpublished relays, by hiding them behind a web server to prevent this type of scanning.
Label-free 3-D molecular imaging of living tissues using Raman Spectral Projection Tomography

The ability to image tissues in three-dimensions (3-D) with label-free molecular contrast at mesoscale would be a valuable capability in biology and biomedicine. Here, we introduce Raman spectral projection tomography (RSPT) for volumetric molecular imaging with sub-millimeter spatial resolution. We have developed a RSPT imaging instrument capable of providing 3-D molecular contrast in transparent and semi-transparent samples. A computational pipeline for multivariate reconstruction was established to extract label-free spatial molecular information from Raman projection data. We demonstrate imaging and visualization of phantoms of various complex shapes with label-free molecular contrast. Finally, we apply RSPT as a novel tool for imaging of molecular gradients and extracellular matrix heterogeneities in fixed and live tissue-engineered constructs and explanted native tissues. RSPT imaging opens new possibilities for label-free molecular monitoring of tissues.
Engineering antigen-specific tolerance to an artificial protein hydrogel

Artificial protein hydrogels are an emerging class of biomaterials with numerous prospective applications in tissue engineering and regenerative medicine. These materials are likely to be immunogenic due their frequent incorporation of novel amino acid sequence domains, which often serve a functional role within the material itself. We engineered injectable “self” and “non-self” artificial protein hydrogels which were predicted to have divergent immune outcomes in vivo on the basis of their primary amino acid sequence. Following implantation in mouse, the non-self gels raised significantly higher anti-gel antibody titers than the corresponding self gels. Prophylactic administration of a fusion antibody targeting the non-self hydrogel epitopes to DEC-205, an endocytic receptor involved in Treg induction, fully suppressed the elevated antibody titer against the non-self gels. These results suggest that the clinical immune response to artificial protein biomaterials, including those that contain highly antigenic sequence domains, can be tuned through the induction of antigen-specific tolerance.
Multi-exponential DNA Residence Behaviors of Transcription Factors Under The Discrete Affinity Model

The transcription process is regulated by temporal interactions of transcription factors with DNA. In the last decade, computational and experimental studies revealed the residence times of transcription factors on DNA correlate with transcriptional output. Biochemical studies suggest that transcription factors exhibit bi-exponential dynamics, attributed to the binary affinity model composed of nonspecific and specific protein-DNA bindings. Recently, transcription factor residence times were shown to display a power-law pattern implicating proteinDNA affinity levels are rather continuous. Elucidating the underlying mechanisms of transcription factor residence distributions, beyond protein-DNA interaction strength, is crucial to construct a more complete understanding of transcriptional regulation. Here, by using molecular dynamics simulations of DNA and dimeric proteins, we demonstrate residence time behaviors of generic homodimeric transcription factors follow a multi-exponential pattern even with single and binary affinity levels between DNA and proteins, indicating the existence of emergent behavior. Our simulations reveal that DNA-protein clusters of various sizes contribute to this multi-exponential behavior. These findings add another layer to transcriptional regulation and, consequently, to gene expression by connecting protein concentration, DNA-protein clusters, and DNA residence times of transcription factors.
Variability in the phytoplankton response to upwelling across an iron limitation mosaic within the California Current System

Coastal upwelling currents such as the California Current System (CCS) comprise some of the most productive biological systems on the planet. Diatoms, a distinct taxon of phytoplankton, dominate these upwelling events in part due to their rapid response to nutrient entrainment. In this region, they may also be limited by the micronutrient iron (Fe), an important trace element primarily involved in photosynthesis and nitrogen assimilation. The mechanisms behind how diatoms physiologically acclimate to the different stages of the upwelling conveyor belt cycle with respect to Fe limitation remains largely uncharacterized. Here, we explore their physiological and metatranscriptomic response to the upwelling cycle with respect to the Fe limitation mosaic that exists in the CCS. Subsurface, natural plankton assemblages that would potentially seed surface blooms were examined over wide and narrow shelf regions. The initial biomass and physiological state of the phytoplankton community had a large impact on the overall response to simulated upwelling. Following on-deck incubation under varying Fe physiological states, our results suggest that diatoms quickly dominated the blooms by “frontloading” nitrogen assimilation genes prior to upwelling. However, diatoms subjected to induced Fe limitation exhibited reductions in carbon and nitrogen uptake and decreasing biomass accumulation. Simultaneously, they exhibited a distinct gene expression response which included increased expression of Fe-starvation induced proteins and decreased expression of nitrogen assimilation and photosynthesis genes. These findings may have significant implications for upwelling events in future oceans, where changes in ocean conditions are projected to amplify the gradient of Fe limitation in coastal upwelling regions.
A Genetically Encoded Actuator Selectively Boosts L-type Calcium Channels in Diverse Physiological Settings

L-type Ca2+ channels (CaV1.2/1.3) convey influx of calcium ions (Ca2+) that orchestrate a bevy of biological responses including muscle contraction and gene transcription. Deficits in CaV1 function play a vital role in cardiac and neurodevelopmental disorders. Yet conventional pharmacological approaches to upregulate CaV1 are limited, as excessive Ca2+ influx leads to cytotoxicity. Here, we develop a genetically encoded enhancer of CaV1.2/1.3 channels (GeeC) to manipulate Ca2+ entry in distinct physiological settings. Specifically, we functionalized a nanobody that targets the CaV macromolecular complex by attaching a minimal effector domain from a CaV enhancer—leucine rich repeat containing protein 10 (Lrrc10). In cardiomyocytes, GeeC evoked a 3-fold increase in L-type current amplitude. In neurons, GeeC augmented excitation-transcription (E-T) coupling. In all, GeeC represents a powerful strategy to boost CaV1.2/1.3 function in distinct physiological settings and, in so doing, lays the groundwork to illuminate new insights on neuronal and cardiac physiology and disease.
A Tale of Two Cultures: Comparing Interpersonal Information Disclosure Norms on Twitter

We present an exploration of cultural norms surrounding online disclosure of information about one's interpersonal relationships (such as information about family members, colleagues, friends, or lovers) on Twitter. The literature identifies the cultural dimension of individualism versus collectivism as being a major determinant of offline communication differences in terms of emotion, topic, and content disclosed. We decided to study whether such differences also occur online in context of Twitter when comparing tweets posted in an individualistic (U.S.) versus a collectivist (India) society. We collected more than 2 million tweets posted in the U.S. and India over a 3 month period which contain interpersonal relationship keywords. A card-sort study was used to develop this culturally-sensitive saturated taxonomy of keywords that represent interpersonal relationships (e.g., ma, mom, mother). Then we developed a high-accuracy interpersonal disclosure detector based on dependency-parsing (F1-score: 86%) to identify when the words refer to a personal relationship of the poster (e.g., "my mom" as opposed to "a mom"). This allowed us to identify the 400K+ tweets in our data set which actually disclose information about the poster's interpersonal relationships. We used a mixed methods approach to analyze these tweets (e.g., comparing the amount of joy expressed about one's family) and found differences in emotion, topic, and content disclosed between tweets from the U.S. versus India. Our analysis also reveals how a combination of qualitative and quantitative methods are needed to uncover these differences; Using just one or the other can be misleading. This study extends the prior literature on Multi-Party Privacy and provides guidance for researchers and designers of culturally-sensitive systems.
Large‐scale sea level, thermocline, and wind variations in the Indonesian throughflow region

The Indonesian throughflow is presumed to be driven by a sea level gradient from the Pacific to the Indian Ocean. Deep throughflow transport may also be driven by a steric gradient between the two basins. The sea level gradient, in turn, is thought to be maintained by the differing wind patterns in the two basins: monsoonal in the Indian Ocean and trades in the western equatorial Pacific. In the interaction between sea level, wind stress, and thermocline depth as identified from historical measurements, we find (1) over the Indian, Indonesian, and equatorial Pacific basins and specifically within the throughflow region, sea level, and thermocline seasonal variations are negatively correlated (sea level rise corresponding to thermocline deepening) and sea level and meridional wind stress are also correlated; (2) the expected strong seasonal gradients in sea level through the eastern throughflow region (near the island of Timor) are found, though without an accompanying thermocline depth gradient; (3) seasonal convergence in baroclinic, upper ocean throughflow transport previously identified [Meyers et al., 1995] in the Timor Sea is associated with changes in sea level as well as upper ocean dynamic height at annual period but not at semiannual; (4) interannual variability explains more of the sea level variance in the eastern throughflow region than is explained by seasonal harmonics; however, there does not appear to be a strong interannual signal in the sea level gradient to drive fluctuations in the upper ocean throughflow. We hypothesize that seasonal variability in the upper layer throughflow and interannual variability in the deep throughflow are the predominant results of the complex interaction of forcing mechanisms.
Cross-technology Communication between Visible Light and Battery-free RFIDs

The ubiquity of illumination facilities enables the versatile development of Visible Light Communication (VLC). VLC-based research achieved high-speed wireless access and decimeter-level indoor localization with complex equipment. However, it is still unclear whether the VLC is applicable for widely-used battery-free Internet-of-Things nodes, e.g., passive RFIDs. This paper proposes LightSign, the first cross-technology system that enables passive RFID tags to receive visible light messages. LightSign is compatible with commercial protocols, transparent to routine RFID communications, and invisible to human eyes. We propose a pseudo-timing instruction to achieve microsecond-level light switching to modulate the VLC message. To make it perceptible to passive RFIDs, we design an augmented RFID tag and prove its effectiveness theoretically and experimentally. With only one reply from an augmented tag, LightSign can decode 100-bit-long VLC messages. We evaluate LightSign in real industry environments and test its performance with two use cases. The results show that LightSign achieves up to 99.2% decoding accuracy in varying scenarios.