Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational Methods for Inferring Transcriptome Dynamics

Joshua D. Welch: Computational Methods for Inferring Transcriptome Dynamics (Under the direction of Jan F. Prins) The sequencing of the human genome paved the way for a new type of medicine, in which a molecularlevel, cell-by-cell understanding of the genomic control system informs diagnosis and treatment. A key experimental approach for achieving such understanding is measuring gene expression dynamics across a range of cell types and biological conditions. The raw outputs of these experiments are millions of short DNA sequences, and computational methods are required to draw scientific conclusions from such experimental data. In this dissertation, I present computational methods to address some of the challenges involved in inferring dynamic transcriptome changes. My work focuses two types of challenges: (1) discovering important biological variation within a population of single cells and (2) robustly extracting information from sequencing reads. Three of the methods are designed to identify biologically relevant differences among a heterogenous mixture of cells. SingleSplice uses a statistical model to detect true biological variation in alternative splicing within a population of single cells. SLICER elucidates transcriptome changes during a sequential biological process by positing the process as a nonlinear manifold embedded in high-dimensional gene expression space. MATCHER uses manifold alignment to infer what multiple types of single cell measurements obtained from different individual cells would look like if they were performed simultaneously on the same cell. These methods gave insight into several important biological systems, including embryonic stem cells and cardiac fibroblasts undergoing reprogramming. To enable study of the pseudogene ceRNA effect, I developed a computational method for robustly computing pseudogene expression levels in the presence of high sequence similarity that confounds sequencing read alignment. AppEnD, an algorithm for detecting untemplated additions, allowed the study of transcript modifications during RNA degradation.
Interaction Between Ploidy, Breeding System, and Lineage Diversification

If particular traits consistently affect rates of speciation and extinction, broad macroevolutionary patterns can be understood as consequences of selection at high levels of the biological hierarchy. Identifying traits associated with diversification rate differences is complicated by the wide variety of characters under consideration and the statistical challenges of testing for associations from comparative phylogenetic data. Ploidy (diploid vs. polyploid states) and breeding system (self-incompatible vs. self-compatible states) have been repeatedly suggested as possible drivers of differential diversification. We investigate the connections of these traits, including their interaction, to speciation and extinction rates in Solanaceae. We show that the effect of ploidy on diversification can be largely explained by its correlation with breeding system and that additional unknown factors, alongside breeding system, influence diversification rates. These results are largely robust to allowing for diploidization. Finally, we find that the most common evolutionary pathway to polyploidy in Solanaceae occurs via direct breakdown of self-incompatibility by whole genome duplication, rather than indirectly via breakdown followed by polyploidization.
Zur Empirizität des „Ich denke“ in Kants Kritik der reinen Vernunft

Das Hauptziel dieser Arbeit besteht darin, die Bedeutung des kantischen Satzes ‚Ich denke‘ als empirischer Satz zu erklaren. Dafur analysiere und interpretiere ich eine Stelle aus B422 f. Anm. der Kritik der reinen Vernunft, in der die These, das ‚Ich denke‘ sei ein empirischer Satz, auftaucht. Fur die Interpretation dieser Stelle werden zwei Lesarten, namlich [L1: Das analytische Implikat der Denkhandlung] und [L2: Die Abhangigkeit des Satzes „Ich denke“ von der empirischen Vorstellung] vorgestellt. Die Kernaussage der ersten Lesart ([L1]) besagt, dass der Satz ‚Ich denke‘ deswegen ein empirischer Satz sei, weil er eine Wahrnehmung meiner selbst ausdruckt. Die zweite Lesart ([L2]) bedeutet: Erst wenn das Mannigfaltige in der Anschauung gegeben ist, ist das ,Ich denke‘ tatig. Und letztlich zeige ich, dass die beiden Lesart sich folgendermasen vereinigen konnen: Der Satz ‚Ich denke‘ wird in dem Sinne als empirischer Satz betrachtet, dass die Handlung ‚Ich denke‘ immer mit den empirischen Vorstellungen stattfinden muss, wodurch das ‚Ich‘ sich im ,Ich bin‘ seiner selbst zugleich bewusst wird. The main objective of this dissertation is to clarify the meaning of Kant’s empirical statement ‘I think. ’ The difficulty of interpreting this ‘I think’ statement is already well-known in previous Kant-studies. In order to do this task, I analyze and interpret a passage from B422 note in Critique of Pure Reason where it is claimed that the ‘I think’ should be an empirical statement. For interpretation of this passage I propose two different approaches to it, namely grasping from it [L1: the analytic implication of thinking activity] or [L2: the dependence of the proposition ‘I think’ on empirical representations]. The former approach ([L1]) claims that the statement ‘I think’ should be an empirical statement, because it expresses a perception of my own self. The second approach ([L2]) rather implies: only when the manifold are given to intuition, the ‘I think’ will be activated. Finally, I show that these two approaches can be reconciled in the following way: the proposition ‘I think’ can be regarded as an empirical statement in the sense that the activity ‘I think’ should always arise together with empirical representations, whereby the ‘I’ cognizes itself simultaneously in its ‘I am. ’
No evidence for functional distinctions across fronto-temporal language regions in their temporal receptive windows

The “core language network” consists of left temporal and frontal regions that are selectively engaged in linguistic processing. Whereas the functional differences across these regions have long been debated, many accounts propose distinctions in terms of representational grain-size—e.g., words vs. sentences—or processing time-scale, i.e., operating on local linguistic features vs. larger spans of input. Indeed, the topography of language regions appears to overlap with a cortical hierarchy reported by Lerner et al. (2011) wherein mid-posterior temporal regions are sensitive to low-level features of speech, surrounding areas—to word-level information, and inferior frontal areas—to sentence-level information and beyond. However, the correspondence between the language network and this hierarchy of “temporal receptive windows” (TRWs) is difficult to establish because the precise anatomical locations of language regions vary across individuals. To directly test this correspondence, we first identified language regions in each participant with a task-based localizer, which confers high functional resolution to the study of TRWs (traditionally based on stereotactic coordinates); then, we characterized regional TRWs with the naturalistic story listening paradigm of Lerner et al. (2011), which augments task-based characterizations of the language network by more closely resembling comprehension “in the wild”. We find no region-by-TRW interactions across temporal and inferior frontal regions, which are all sensitive to both word-level and sentence-level information. Therefore, the language network as a whole constitutes a unique stage of information integration within a broader cortical hierarchy. Highlights Language regions are identified with task-based, participant-specific localization. A progressively scrambled naturalistic story probes regional processing timescales. Widespread sensitivity to scrambling at the timescales of both words and sentences. No processing timescale distinctions across temporal and inferior-frontal regions. These regions all occupy a common, unique stage in a broader processing hierarchy.
Energy landscape analysis of ecological communities elucidates the phase space of community assembly dynamics

Studies on historical contingency in community assembly frequently report the presence of alternative stable states as the result of different assembly sequences. If we can observe multiple assembly sequences and resulting community structure, these observations collectively inform the constraints on community assembly dynamics that emerge from various ecological processes. These observations would be a basis for predicting the outcome of assembly processes and understanding the mechanisms that shape species assemblage. However, empirical approaches such as invasion/removal experiments require enormous time and effort and are impossible in some cases. Here, we show that data on multispecies occurrences analyzed using a pairwise maximum entropy model and energy landscape analysis are capable of providing insights into the constraints on community assembly dynamics. This approach is a minimal theoretical framework to systematically and mechanistically study community assembly dynamics. Community assembly has a prominent role in shaping real world ecosystem organization. Our approach provides a new systemic paradigm for developing a predictive theory of community ecology and can have broad impact on ecological studies and its applications including regime shifts and ecosystem management.
PERFORMANCE COMPARISON OF HUFFMAN AND LZW DATA COMPRESSION FOR WIRELESS SENSOR NODE APPLICATION

Wireless Sensor Networks (WSNs) are becoming important in today’s technology in helping monitoring our surrounding environment. However, wireless sensor nodes are powered by limited energy supply. To extend the lifetime of the device, energy consumption must be reduced. Data transmission is known to consume the largest amount of energy in a sensor node. Thus, one method to reduce the energy used is by compressing the data before transmitting it. This study analyses the performance of the Huffman and Lempel-Ziv Welch (LZW) algorithms when compressing data that are commonly used in WSN. From the experimental results, the Huffman algorithm gives a better performance when compared to the LZW algorithm for this type of data. The Huffman algorithm is able to reduce the data size by 43% on average, which is four times faster than the LZW algorithm.
Studi Laboratorium Siklus Hidup Anopheles vagus Pradewasa sebagai Vektor Filariasis dan Malaria di Provinsi Nusa Tenggara Timur

Anopheles vagus is one of the vectors that plays an essential role in malaria infection in East Nusa Tenggara, Indonesia. This vector’s density is related to population dynamics and the environment. The high population density is fluctuated according to the birth and death rate of the mosquitos on their life cycle. This is an observational study that employed a cross-sectional design aimed to identify the life cycle of pre-adult An. vagus mosquitos. The sample was collected from Manggarai Barat and Kupang regions. Sample was taken from around cattle’s cages between 6.00pm-12.00am and were the ones that have sucked cattle’s blood. Identification and colonization were conducted in Loka Litbangkes Waikabubak Laboratory. Data was collected through an hourly observation form and then analyzed descriptively. The results indicated that an adult An.vagus could produce 42-184 eggs each time it laid eggs with 79% hatching rate succeed. The life cycle of an An.vagus under a controlled environment in the laboratory was as following phases: egg (1-4 days), larvae (9-19 days), pupa (1-8 days). Anopheles vagus needed an average of 57.2 minutes to mate and 13 hours to suck blood after the mating process. The highest death rate (28.05%) occurred in instar IVof larvae stage. Pre-adult of An. vagus needed 11-31 days in with the environment that conditioned at 21.1°C and 74.3% humidity for their development,while the highest death rate observed at instar IV.
Mapping brain circuits : anatomy, connectivity and function

To decipher neural circuits anatomy is the central basis for all kinds of neurobiological studies. Here in this thesis, I will start with extensive overview of the current methods that have been intensively employed in labeling and mapping neurons and neuronal activities, including tracing techniques, imaging/recording systems and manipulation tools. This will be followed by the introduction of the two model systems that are being studied in this thesis. Specifically, the ultimate goal of this thesis is to examine the anatomical neural circuits of involving median prefrontal cortex and the serotonergic nuclei, by developing a standardized brain atlas for automatic processing and analyzing anatomical image data, which facilitate functional studies of the serotonergic neurons in rats. In paper I, we characterized the inputs to two major serotonergic nuclei using a retrograde trans-synaptic virus. We reconstructed a whole brain input map with customized software, and found previously undefined inputs. We also confirmed the existence of the functional connection from basal ganglia, lateral habenula, and prefrontal cortex to the raphe nuclei serotonergic neurons. In paper II, we developed a versatile interactive framework for automatic detection, registration, and analysis. In paper III, we characterized both the local and long-range inputs to four cell types in the mouse medial prefrontal cortex. A new viral strategy for tracing both local and long-range inputs at the same time was developed. We have confirmed the findings by other tracing techniques, and rebuilt our own connectivity map. In paper IV, we explored the roles of serotonergic neurons in impulsive behavior by manipulating and recording the neurons. In summary, we have developed new methods for neural circuitry study, added our knowledge of the serotonergic and median prefrontal cortex circuitry, and gained deeper insights of functional roles of serotonergic neurons. LIST OF SCIENTIFIC PAPERS I. Iskra Pollak Dorocic, Daniel Fürth, YANG XUAN, Yvonne Johansson, Laura Pozzi, Gilad Silberberg, Marie Carlén, Konstantinos Meletis A whole-brain atlas of inputs to serotonergic neurons of the dorsal and median raphe nuclei. Neuron, 2014, Volume 83, Issue 3, 663-678 II. Daniel Fürth, Thomas Vaissière, Ourania Tzortzi, YANG XUAN, Antje Märtin, Iakovos Lazaridis, Giada Spigolon, Gilberto Fisone, Raju Tomer, Karl Deisseroth, Marie Carlén, Courtney A. Miller, Gavin Rumbaugh & Konstantinos Meletis An interactive framework for whole-brain maps at cellular resolution Nature Neuroscience, 2018, 21, 139–149 III. YANG XUAN*/ Sofie Ährlund-Richter*, Hoseok Kim, Iskra Pollak Dorocic, Felix Wahl, Konstantinos Meletis, Marie Carlén. *) Equal contribution Manuscript IV. Xinming Wang*/ YANG XUAN*/ Hoseok Kim*, Iskra Pollak Dorocic, Daniel Kaping, Marc Parent, Konstantinos Meletis#, Marie Carlén# *) Equal contribution, #) corrsponding author Manuscript
Fish as food

"This paper reports results of incorporating fish into IMPACT, a global model of food supply and demand that estimates market-clearing prices to 2020 for 32 commodities in 36 regions. It summarizes results for production, consumption, net exports and real price changes for 10 economic categories of fisheries items, disaggregated into 15 geographic regions of the world. Under the medium-variant scenario for the uncertain capture fisheries sectors, global production of food fish is projected to rise by 1.5% annually through 2020, with two-thirds of this from aquaculture, whose share in total food fish production rises to 41%. Global per capita fish consumption is projected to be 17.1 kg in 2020, with sensitivity analysis indicating a margin of 2 kg/capita either way based on extreme scenarios for capture and aquaculture. Most growth will occur in developing countries, which will account for 79% of food fish production in 2020. China's share of world production will continue to expand, while that of Japan, the EU, and former USSR will continue to contract. Real fish prices will rise 4 to 16% by 2020, while meat prices will fall 3%. Fishmeal and oil prices will rise 18%; use of these commodities will increasingly be concentrated in carnivorous aquaculture. Growing domestic demand will dampen fish exports from developing countries. Sensitivity analysis incorporating a very pessimistic view of capture fisheries leads to escalating food fish prices (+69% for high-value finfish) and soaring fishmeal prices (+134%), whereas an optimistic view of increased investment in aquaculture lowers real prices of low value food fish (-12%), and raises fishmeal prices (+42%). " Authors' Abstract
Dietary restriction and insulin‐like signalling pathways as adaptive plasticity: A synthesis and re‐evaluation

Dietary restriction (DR) under laboratory conditions generally extends life span and delays ageing across species as diverse as yeast, nematode worms, flies and mice, and is underpinned by taxonomically conserved physiological pathways, notably the insulin‐like signalling pathway (IIS). Despite growing excitement about the links between DR/IIS and ageing within biogerontology, our understanding of why the DR response and associated pathways evolved under natural selection remains controversial and limited. Here, we provide a brief overview of current understanding of the relationship between DR and IIS and ageing from modern biogerontology and go on to summarize the evidence that the IIS pathway integrates a range of important environmental cues including photoperiod, temperature and humidity, as well as nutrition. We go on to discuss the main existing evolutionary explanations for DR and argue that they are not mutually exclusive and are too nutrition‐focussed to fully explain the evolutionary origin of the IIS pathway. In the wild, environmental cues and pressures are dynamic and multivariate, and physiological pathways capable of integrating multiple predictive cues could be strongly favoured by natural selection. We hypothesize that the IIS and related pathways, such as mTOR, evolved to detect and integrate a wide range of environmental cues (not just diet) that are predictive of important selective pressures in the wild. Available evidence suggests the pathway is capable of triggering a range of phenotypic responses, depending on the cues provided, ranging from profound physiological remodelling (e.g. diapause, aestivation, hibernation) associated with promoting survival through challenging environments, to more subtle responses to acute, fine‐scale variation in the environment which may allow individuals to better match their level of reproductive investment to their conditions. We argue that the IIS pathway underpins important adaptive phenotypic plastic responses to a wide range of environmental inputs, of which diet is just one. A multi‐disciplinary approach combining perspectives and methods from biogerontology, cell biology, ecology and evolutionary biology will be essential to develop our understanding of the evolutionary origins of this pathway and the way natural selection and the environment have shaped variation in the IIS pathway's response to different environmental cues. A free Plain Language Summary can be found within the Supporting Information of this article.
Characterization and Potential Application of Blend of Passion Fruit Peel with Rice Flour in an Extruded Product for Fiber Enhancement

By-products from the production of passion fruit juices can be a raw material for the formulation of foods with higher added value. Rice, characterized by being hypoallergenic and gluten-free, can be used with the passion fruit peel. The objective of this study was to prepare a precooked mixture by extrusion of rice flour (Rf) and passion fruit peel (Pfp) for the subsequent formulation of cookies with high fiber content and to determine the physicochemical, microbiological and sensorial characteristics of the flour and processed biscuits obtained. Experimental design of 20 treatments with (Pfp:Rf) percent ratios of 1.6/99.4, 5/95, 10/90, 15/85, and 18.4/81.6%; with moisture percentages of 14.64, 16, 18, 20 and 21.36%; and temperatures of 99.6, 120, 150, 180, and 200.4°C. The extrudates were characterized relative to the centesimal composition, dietary fiber, water absorption index (WAI), water solubility index (WSI), radial expansion index (REI), Ray-X diffraction (DRX), and microbiological stability. The results were subjected to analyses of variance and tests of comparisons of means (Tukey, p <0.05). Of three treatments, the best was chosen for use in obtaining the cookies. For ready-to-eat cookies, the formulation with 18.4% of Pfp flour showed 6.75% acceptability with the judges with an average score of 6.5, which is equivalent to I liked it slightly. For gluten-free cookies stored with microbiological stability for 120 days, the presence of microorganisms was not observed. From the technological point of view, the development of cookie formulations is a viable alternative for human consumption of precooked Pfp and Rf.
A Natural Impact: NK Cells at the Intersection of Cancer and HIV Disease

Despite efficient suppression of plasma viremia in people living with HIV (PLWH) on cART, evidence of HIV-induced immunosuppression remains, and normally benign and opportunistic pathogens become major sources of co-morbidities, including virus-induced cancers. In fact, cancer remains a primary cause of death even in virally suppressed PLWH. Natural killer (NK) cells provide rapid early responses to HIV infection, contribute substantially to disease modulation and vaccine protection, and are also major therapeutic targets for cancer immunotherapy. However, much like other lymphocyte populations, recent burgeoning evidence suggests that in chronic conditions like HIV, NK cells can become functionally exhausted with impaired cytotoxic function, altered cytokine production and impaired antibody-dependent cell-mediated cytotoxicity. Recent work suggests functional anergy is likely due to low-level ongoing virus replication, increased inflammatory cytokines, or increased presence of MHClow target cells. Indeed, HIV-induced loss of NK cell-mediated control of lytic EBV infection has been specifically shown to cause lymphoma and also increases replication of CMV. In this review, we will discuss current understanding of NK cell modulation of HIV disease, reciprocal exhaustion of NK cells, and how this may impact increased cancer incidences and prospects for NK cell-targeted immunotherapies. Finally, we will review the most recent evidence supporting adaptive functions of NK cells and highlight the potential of adaptive NK cells for cancer immunotherapy.