Miracle-dz/UniFAR-FTUs huggingface dataset:
Developing new diagnostic and therapeutic approaches in adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is an aggressive malignancy with high recurrence rates and poor response to chemotherapy. With this work, we have evaluated a potential new treatment target focusing on the mitochondrial NADPH generator Nicotinamide Nucleotide Transhydrogenase (NNT). NNT has a central role within the mitochondrial antioxidant pathways, which protect cells from oxidative stress. Our hypothesis was that NNT silencing will expose cells to cytotoxic levels of oxidative stress. We knocked down NNT transiently in NCJ-H295R ACC cells in vitro; this led to an increase in cellular oxidative stress and a strong cytotoxic and cytostatic effect. With stable NNT knockdown, we observed the emergence of a partially compensated phenotype over the course of time, with restored redox balance. Surprisingly, steroidogenesis was stimulated by transient NNT loss, challenging current perceptions about the impact of oxidative stress on steroidogenesis. In our clinical study, we evaluated a new diagnostic tool for biochemical detection of ACC recurrence. Serial post-operative urine samples were collected from a large cohort of patients who had undergone complete ACC resection. Standardised review of longitudinal steroid measurements resulted in detection of disease recurrence prior to or concurrently with imaging with high sensitivity in cases where a pre-operative steroid profile had been provided.
Gold nanosupplement in selective inhibition of methylglyoxal and key enzymes linked to diabetes

The non-enzymatic glycation of macromolecules resulting into advanced glycation end products (AGEs) that constituents lead secondary complication in diabetes. Currently, scientists are focusing on identifying a novel compound that possibly inhibits AGEs without affecting normal cellular function. So far a number of natural and synthetic compounds were reported. This study intended to evaluate the gold nanoparticles (GNPs) on carbohydrate digestive enzymes inhibition and methylglyoxal (MGO) trapping ability. Initially, GNPs were synthesised using Couroupita guianensis and characterised. Further, remarkable inhibition of α-amylase, and glucosidase was found through calorimetric techniques. In addition, the results concluded that GNPs limited the glucose uptake and lead to AGEs inhibition. Also, the mechanistic link behind this study illustrated as MGO inhibition will restrict further glycation of macromolecules, eventually control the complication progression. Collectively, GNPs have significant inhibition of digestive enzymes, MGO and AGEs on dose-dependent manner and metal coated polyphenols have an ideal therapeutic role in controlling diabetes and its complications.
Ornithobacterium rhinotracheale infection in red wattled lapwings (Vanellus indicus) in Pakistan - a case report.

Respiratory infections are of major concern in the poultry industry in Pakistan. Previously, wild birds have been reported to transmit respiratory infections. The Red Wattled Lapwing (RWL) is a wild bird prevalent in the Indus basin and the wetlands of Punjab, Pakistan. Out of total of eighteen RWL birds housed at Lahore Zoo, Pakistan, three birds died after showing signs of respiratory distress and paralysis, in August, 2014. Postmortem examination revealed air sacculitis and pneumonia. Microbiological examination revealed Ornithobacterium rhinotracheale (ORT) as the causative agent, which was later confirmed by Polymerase Chain Reaction (PCR). The isolate was found to be susceptible to amoxicillin, erythromycin, tetracycline and enrofloxacin, and resistant to gentamycin, neomycin and sulfamethoxazole/trimethoprim. All the remaining birds were treated with long acting tetracycline, and diseased birds eventually recovered. No further mortality was declared. This is the first report of its kind which demonstrates ORT infection in RWL in Punjab, Pakistan.
Mechanistic characterization of members of the amidohydrolase superfamily

Mechanistic Characterization of Members of the Amidohydrolase Superfamily. (December 2006) Ricardo Martí Arbona, B.S., Universidad de Puerto Rico, at Río Piedras Chair of Advisory Committee: Dr. Frank M. Raushel The amidohydrolase superfamily is a functionally diverse group of enzymes found in every organism sequenced to date. The landmark for this superfamily is the conservation of a ( / )8-barrel structural fold. Isoaspartyl dipeptidase (IAD) from Escherichia coli catalyzes the hydrolytic cleavage of -aspartyl dipeptides. Structural studies of the wild-type enzyme demonstrate that the active site consists of a binuclear metal center. Bell-shaped pH-rate profiles are observed for all four metal-substituted forms of the wild-type enzyme and the site-directed mutants, E77Q and Y137F. Structural analysis of IAD with the bound substrate and site-directed mutagenesis shows the importance of the side chains of residues Glu-77, Tyr-137, Arg-169, Arg-233, Asp285, and Ser-289 in the substrate binding and hydrolysis. The reaction mechanism for the hydrolysis of dipeptides by IAD is initiated by the polarization of the amide bond via complexation to the -metal and the hydrogen bond to Tyr-137. Asp-385 participates in the activation of the bridging hydroxide for nucleophilic attack at the peptide carbon center. The lately protonated Asp-285 donates the proton to the -amino group of the leaving group, causing the collapse of the tetrahedral intermediate and cleavage of the carbon-nitrogen bond. N-formimino-L-glutamate iminohydrolase (HutF) from
Mechanisms of Regulation of Promyelocytic Leukemia (PML) Proteins by Epstein-Barr Nuclear Antigen 1 (EBNA1) and Ubiquitin Specific Protease 7 (USP7)

Promyelocytic leukemia (PML) nuclear bodies (NBs) are important nuclear structures that mediate tumour suppressive and antiviral functions. Epstein-Barr virus (EBV) has evolved mechanisms to disrupt these structures and abrogate their functions, through the EBNA1 protein. EBNA1-mediated PML NB disruption requires its interaction with two cellular proteins, CK2 and USP7, both of which negatively regulate PML in the absence of EBNA1. I determined that USP7-null cells have greatly increased PML NBs. I have demonstrated the importance of serine 393 of EBNA1, a phosphosite essential for the EBNA1-CK2 interaction. An S393A mutation abrogated the ability of EBNA1 to disrupt PML NBs, while a S393T mutation restored this ability. I have also determined that EBNA1 and USP7 can directly interact with PML proteins, primarily with PML IV. In summary, my data supports a model in which EBNA binds PML proteins directly and negatively regulates them through recruitment of
In vitro and in vivo evaluation of a Brucella putative hemagglutinin

Brucellosis, a zoonotic disease caused by Brucella spp. , presents both health and economic difficulties for livestock, wildlife, and humans. While brucellosis is nearly eradicated in the United States, the disease remains detrimental in many countries worldwide. Attempts to produce a safe and effective small ruminant vaccine have been met with limited success. The current vaccine for bovine brucellosis in the United States is B. abortus RB51. This strain transiently colonizes the host and induces a cell-mediated immune response. Levels of protection have not been demonstrated in goats and thus it is considered a relatively poor caprine vaccine that probably does not survive long enough in the tissues to produce a sufficient protective immune response. This study analyzes the possibility of using RB51 containing plasmid QAE for vaccination in goats. The plasmid QAE contains a gene region of DNA from B. melitensis 16M hypothesized to encode for a putative hemagglutinin that is believed to be a host specificity protein. The region E gene sequence is not present in any strain of B. abortus, including RB51. It is proposed that the addition of region E to RB51 will enhance survivability in the caprine host to the extent where an adequate protective immune response is elicited. The QAE plasmid was electroporated into B. abortus RB51 and screened using ampicillin resistance as a selective measure. Ten goats were conjunctivally inoculated with RB51-QAE, the modified strain, and ten goats received strain RB51 in the same manner as controls. Two goats from each group were euthanized and necropsied at weekly intervals for four weeks and again at 42 days. Tissues from these animals were
The effect of tick salivary proteins on innate immunity cells

Saliva of Ixodid ticks contains a whole array of pharmacologically active molecules with vasodilatory, antihemostatic, and immunomodulatory activities. This thesis focuses on two types of salivary proteins, serpins and cystatins, and their role in immunomodulation. These protease inhibitors are known to affect many biological functions. To better understand their role in tick saliva we examined their effect on dendritic cells and their ability to modulate the immune response after pathogen infection. As model pathogens, Borrelia spirochetes and tick-borne encephalitis virus were used.
A Filter Method for Improved Monitoring of Drosophila suzukii (Diptera: Drosophilidae) Larvae in Fruit

Drosophila suzukii Matsumura (Diptera: Drosophilidae) has become a major economic pest of soft-skinned fruits since it was detected in North America in 2008. Control of this fly is achieved through insecticide sprays applied when ripening or ripe fruit are present. Monitoring to aid informed management decisions is challenging since trapping for adults is not a reliable indicator of potential or existing infestation in the fruit. Moreover, current larval monitoring techniques using brown sugar or salt solutions allow for visual detection of late-instar larvae, but they are time consuming and tend to miss smaller larvae. Here, we describe a method combining a salt solution, coffee filter, and microscope that can reliably and efficiently detect small and large larvae of D. suzukii in fruit samples. By sifting the sample liquid through an inexpensive coffee filter, larvae of all instars can be counted quickly and accurately. This method is 1.7 times faster than using a visual traybased method and can detect more larvae because first instar larvae can be detected. Growers can use this information to target insecticide sprays for curative control of small larvae, identify fields where the presence of larger larvae may indicate an unmarketable crop, or verify that no infestation exists and control programs are working. We provide images to support larval identification of this pest, and we expect this method will become an important component of rebuilding IPM programs in fruit crops affected by D. suzukii.
Extinction-free Census of AGNs in the AKARI/IRC North Ecliptic Pole Field from 23-band infrared photometry from Space Telescopes

In order to understand the interaction between the central black hole and the whole galaxy or their co-evolution history along with cosmic time, a complete census of active galactic nucleus (AGN) is crucial. However, AGNs are often missed in optical, UV, and soft X-ray observations since they could be obscured by gas and dust. A mid-infrared (MIR) survey supported by multiwavelength data is one of the best ways to find obscured AGN activities because it suffers less from extinction. Previous large IR photometric surveys, e.g. Wide field Infrared Survey Explorer and Spitzer, have gaps between the MIR filters. Therefore, star-forming galaxy-AGN diagnostics in the MIR were limited. The AKARI satellite has a unique continuous nine-band filter coverage in the near to MIR wavelengths. In this work, we take advantage of the state-of-the-art spectral energy distribution modelling software, cigale, to find AGNs in MIR. We found 126 AGNs in the North Ecliptic Pole-Wide field with this method. We also investigate the energy released from the AGN as a fraction of the total IR luminosity of a galaxy. We found that the AGN contribution is larger at higher redshifts for a given IR luminosity. With the upcoming deep IR surveys, e.g. JWST, we expect to find more AGNs with our method.
DiDi’s Machine Translation System for WMT2020

This paper describes the DiDi AI Labs’ submission to the WMT2020 news translation shared task. We participate in the translation direction of Chinese->English. In this direction, we use the Transformer as our baseline model and integrate several techniques for model enhancement, including data filtering, data selection, back-translation, fine-tuning, model ensembling, and re-ranking. As a result, our submission achieves a BLEU score of 36.6 in Chinese->English.
Learning Robust Algorithms for Online Allocation Problems Using Adversarial Training

We address the challenge of finding algorithms for online allocation (i.e. bipartite matching) using a machine learning approach. In this paper, we focus on the AdWords problem, which is a classical online budgeted matching problem of both theoretical and practical significance. In contrast to existing work, our goal is to accomplish algorithm design {\em tabula rasa}, i.e., without any human-provided insights or expert-tuned training data beyond specifying the objective and constraints of the optimization problem. We construct a framework based on insights and ideas from game theory, adversarial training and GANs Key to our approach is to generate adversarial examples that expose the weakness of any given algorithm. A unique challenge in our context is to generate complete examples from scratch rather than perturbing given examples and we demonstrate this can be accomplished for the Adwords problem. We use this framework to co-train an algorithm network and an adversarial network against each other until they converge to an equilibrium. This approach finds algorithms and adversarial examples that are consistent with known optimal results. Secondly, we address the question of robustness of the algorithm, namely can we design algorithms that are both strong under practical distributions, as well as exhibit robust performance against adversarial instances. To accomplish this, we train algorithm networks using a mixture of adversarial and practical distributions like power-laws; the resulting networks exhibit a smooth trade-off between the two input regimes.
Lipschitz continuity of probability kernels in the optimal transport framework

In Bayesian statistics, a continuity property of the posterior distribution with respect to the observable variable is crucial as it expresses well-posedness, i.e., stability with respect to errors in the measurement of data. Essentially, this requires to analyze the continuity of a probability kernel or, equivalently, of a conditional probability distribution with respect to the conditioning variable. Here, we give general conditions for the Lipschitz continuity of probability kernels with respect to metric structures arising within the optimal transport framework, such as the Wasserstein metric. For dominated probability kernels over finite-dimensional spaces, we show Lipschitz continuity results with a Lipschitz constant enjoying explicit bounds in terms of Fisher-information functionals and weighted Poincare constants. We also provide results for kernels with moving support, for infinite-dimensional spaces and for non dominated kernels. We show applications to several problems in Bayesian statistics, such as approximation of posterior distributions by mixtures and posterior consistency.
Really Embedding Domain-Specific Languages into C++

Domain-specific languages (DSLs) are both pervasive and powerful, but remain difficult to integrate into large projects. As a result, while DSLs can bring distinct advantages in performance, reliability, and maintainability, their use often involves trading off other good software-engineering practices. In this paper, we describe an extension to the Clang C++ compiler to support syntax plugins, and we demonstrate how this mechanism allows making use of DSLs inside of a C++ code base without needing to separate the DSL source code from the surrounding C++ code.
An Involution on Semistandard Skyline Fillings

Non-attacking skyline fillings were used by Haglund, Haiman and Loehr to establish a combinatorial formula for nonsymmetric Macdonald polynomials. Semistandard skyline fillings are non-attacking skyline fillings with both major index and coinversion number equal to zero, which serve as a combinatorial model for key polynomials. In this paper, we construct an involution on semistandard skyline fillings. This involution can be viewed as a vast generalization of the classical Bender--Knuth involution. As an application, we obtain that semistandard skyline fillings are compatible with the Demazure operators, offering a new combinatorial proof that nonsymmetric Macdonald polynomials specialize to key polynomials.
Toward Evaluating Re-identification Risks in the Local Privacy Model

LDP (Local Differential Privacy) has recently attracted much attention as a metric of data privacy that prevents the inference of personal data from obfuscated data in the local model. However, there are scenarios in which the adversary needs to perform re-identification attacks to link the obfuscated data to users in this model. LDP can cause excessive obfuscation and destroy the utility in these scenarios, because it is not designed to directly prevent re-identification. In this paper, we propose a privacy metric which we call the PIE (Personal Information Entropy). The PIE is designed so that it directly prevents re-identification attacks in the local model. The PIE can also be used to compare the identifiability of personal data with the identifiability of biometric data such as a fingerprint and face. We analyze the relation between LDP and the PIE, and analyze the PIE and utility in distribution estimation for two obfuscation mechanisms providing LDP. Through experiments, we reveal the fact that a location trace is more identifiable than the best face matcher in the prize challenge. Then we also show that the PIE can be used to guarantee low re-identification risks for the local obfuscation mechanisms while keeping high utility.
Primes in geometric series and finite permutation groups

As a consequence of the classification of finite simple groups, the classification of permutation groups of prime degree is complete, apart from the question of when the natural degree $(q^n-1)/(q-1)$ of ${\rm L}_n(q)$ is prime. We present heuristic arguments and computational evidence to support a conjecture that for each prime $n\ge 3$ there are infinitely many primes of this form, even if one restricts to prime values of $q$.
The volumetric star formation law in nearby galaxies

Abstract Star formation laws are empirical relations between the cold gas (HI+H2) content of a galaxy and its star formation rate (SFR), being crucial for any model of galaxy formation and evolution. A well known example of such laws is the Schmidt-Kennicutt law, which is based on the projected surface densities. However, it has been long unclear whether a more fundamental relation exists between the intrinsic volume densities. By assuming the vertical hydrostatic equilibrium, we infer radial profiles for the thickness of gaseous discs in a sample of 23 local galaxies, and use these measurements to convert the observed surface densities of the gas and the SFR into the de-projected volume densities. We find a tight correlation linking these quantities, that we call the volumetric star formation law. This relation and its properties have crucial implications for our understanding of the physics of star formation.
Patterns of herders’ adaptation to changes in social–ecological systems across northern China’s grasslands over the past three decades

Understanding the changes in herders’ adaptation to environmental change can provide insight into humans’ adaptive mechanisms to different social–ecological systems, and is also important for the optimal management of grasslands. However, the existing and emerging patterns of herders’ adaptation to changes in social–ecological systems across different types of grasslands are poorly understood. This paper presents a systematic participatory investigation that was conducted to comprehensively understand herders’ adaptation in this context over the past three decades. Three counties in Inner Mongolia grasslands were selected as the case study sites, located in meadow steppe, typical steppe and desert steppe respectively. Our results indicate that herders’ perceptions partly fit with the reality of the actual changes. The majority of herders attributed their pasture’s quality degradation to reduced precipitation rather than overgrazing, a contradictory perception to previous scientific observations (overgrazing > climate change). Moreover, herders’ behaviour in relation to herbage storage and livestock structure had dramatically changed in terms of spatial and temporal patterns in Inner Mongolia, which benefited herders in production efficiency. Lambing time of sheep and goats occurred earlier than it did several decades ago across the three grassland types. This was attributed to a rise in temperature, increasing marketisation and developing infrastructure. In addition, there became evident a transformation in the animal husbandry production cycle from a two-year to one-year cycle. Our results highlighted that the transformation of herders’ behavioural strategies resulted from variations in spatial and temporal patterns of climate change, pasture degradation, new policies and marketisation in pastoral areas. These strategies can be seen as key mechanisms in long-term adaptation to changes in social–ecological systems, which benefit herders’ efficiency in grassland management.
Improved Approximation Algorithms for Stochastic-Matching Problems

We consider the Stochastic Matching problem, which is motivated by applications in kidney exchange and online dating. In this problem, we are given an undirected graph. Each edge is assigned a known, independent probability of existence and a positive weight (or profit). We must probe an edge to discover whether or not it exists. Each node is assigned a positive integer called a timeout (or a patience). On this random graph we are executing a process, which probes the edges one-by-one and gradually constructs a matching. The process is constrained in two ways. First, if a probed edge exists, it must be added irrevocably to the matching (the query-commit model). Second, the timeout of a node $v$ upper-bounds the number of edges incident to $v$ that can be probed. The goal is to maximize the expected weight of the constructed matching. For this problem, Bansal et al. (Algorithmica 2012) provided a $0.33$-approximation algorithm for bipartite graphs and a $0.25$-approximation for general graphs. We improve the approximation factors to $0.39$ and $0.269$, respectively. The main technical ingredient in our result is a novel way of probing edges according to a not-uniformly-random permutation. Patching this method with an algorithm that works best for large-probability edges (plus additional ideas) leads to our improved approximation factors.
An Efficient Ex Plant Sterilization Protocol for Reducing Microbial Contamination of Solanum tuberosum CV. ‘Kufri Jyoti for Establishing Micropropagation in Rainy Season

An efficient cost-effective disinfection method for initiation of micropropagation in rainy season for potato cultivar Kufri Joyti was developed. A comparison between UV-C irradiated and conventional surface sterilization procedure was performed using shoot tips (sprouted from tuber) as explants. Surface sterilized explants showed higher percentage of contamination in comparison to the explants exposed with UV-C prior to surface sterilization. However a poor viability rate and developmental deformities was observed with gradual exposure time. An efficient cost-effective disinfection method for initiation of micropropagation in rainy season for potato cultivar Kufri Joyti was developed. In this study optimization of a two stage sterilization process was developed (UVC irradiation for 5 min followed by 10 min surface sterilization) resulting most effective regime for maintaining low contamination and increase survival rate with better economic return.