Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding the effect of controlling phosphorothioate chirality in the DNA gap on the potency and safety of gapmer antisense oligonucleotides

Abstract Therapeutic oligonucleotides are often modified using the phosphorothioate (PS) backbone modification which enhances stability from nuclease mediated degradation. However, substituting oxygen in the phosphodiester backbone with sulfur introduce chirality into the backbone such that a full PS 16-mer oligonucleotide is comprised of 215 distinct stereoisomers. As a result, the role of PS chirality on the performance of antisense oligonucleotides (ASOs) has been a subject of debate for over two decades. We carried out a systematic analysis to determine if controlling PS chirality in the DNA gap region can enhance the potency and safety of gapmer ASOs modified with high-affinity constrained Ethyl (cEt) nucleotides in the flanks. As part of this effort, we examined the effect of systematically controlling PS chirality on RNase H1 cleavage patterns, protein mislocalization phenotypes, activity and toxicity in cells and in mice. We found that while controlling PS chirality can dramatically modulate interactions with RNase H1 as evidenced by changes in RNA cleavage patterns, these were insufficient to improve the overall therapeutic profile. We also found that controlling PS chirality of only two PS linkages in the DNA gap was sufficient to modulate RNase H1 cleavage patterns and combining these designs with simple modifications such as 2′-OMe to the DNA gap resulted in dramatic improvements in therapeutic index. However, we were unable to demonstrate improved potency relative to the stereorandom parent ASO or improved safety over the 2′-OMe gap-modified stereorandom parent ASO. Overall, our work shows that while controlling PS chirality can modulate RNase H1 cleavage patterns, ASO sequence and design are the primary drivers which determine the pharmacological and toxicological properties of gapmer ASOs.
Primary Total Hip Arthroplasty in Patients 20 Years Old and Younger.

BACKGROUND Historically, total hip arthroplasty (THA) performed in patients ≤20 years old has been associated with poor survivorship because of bearing-surface wear with conventional polyethylene, acetabular loosening with cemented sockets, and liner fracture in ceramic-on-ceramic (CoC) THA. For this population, there is a paucity of data regarding outcomes of THAs performed with use of modern implants and bearing surfaces. The purpose of the present study was to examine the mid- to long-term outcomes of modern THA in patients ≤20 years old. METHODS Utilizing a single-institution, prospectively collected total joint registry, we retrospectively identified 91 primary THAs performed in 78 patients ≤20 years old from 1998 to 2016. The average patient age was 17 years (range, 11 to 20 years), and the average body mass index was 26 kg/m (range, 16 to 49 kg/m). Forty-eight THAs (53%) were performed in male patients, and 47 (52%) were performed on the right hip. Bearing surfaces included CoC (53 THAs, 58%), metal-on-highly cross-linked polyethylene (MoP; 28 THAs, 31%), and ceramic-on-highly cross-linked polyethylene (CoP; 10 THAs, 11%). Outcome measures included reoperations, revisions, complications, clinical outcome scores, and bearing-surface wear. RESULTS At an average follow-up of 8 years (range, 2 to 18 years), the average modified Harris hip score was 92 (range, 54 to 100), and 95% of patients reported feeling "much better" following the surgical procedure. Survivorship at 2, 5, and 10 years postoperatively was 96.7%, 96.7%, and 95.0% for reoperation; 98.9%, 98.9%, and 97.2% for revision; and 91.2%, 91.2%, and 89.5% for complications, respectively. The most common complications were instability (3 THAs, 3%), aseptic acetabular loosening (2 THAs, 2%), and postoperative foot drop (2 THAs, 2%). Linear articular wear averaged 0.019 mm/yr. There were no correlations between age, sex, body mass index, bearing surface, femoral head size, use of cement, or operative time and survivorship from complications, reoperations, or revisions. There were no differences in linear wear among CoC, CoP, and MoP bearing surfaces. CONCLUSIONS In patients ≤20 years old, THAs performed with use of modern implants exhibit excellent clinical outcome scores and survivorship at mid- to long-term follow-up. CoC, CoP, and MoP bearing surfaces have similar survivorship, clinical outcomes, and bearing-surface wear in this population. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
SMALL LEAF AND BUSHY1 controls organ size and lateral branching by modulating the stability of BIG SEEDS1 in Medicago truncatula

Summary Organ size is a major agronomic trait that determines grain yield and biomass production in crops. However, the molecular mechanisms controlling organ size, especially in legumes, are poorly understood. Using forward genetic approaches in a Tnt1 insertion mutant population of the model legume Medicago truncatula, we identified SMALL LEAF AND BUSHY1 (SLB1), which is required for the control of organ size and lateral branching. Loss of function of SLB1 led to reduced leaf and flower size but increased lateral branch formation in M. truncatula. SLB1 encodes an F‐box protein, an orthologue of Arabidopsis thaliana STERILE APETALA (SAP), that forms part of an SKP1/Cullin/F‐box E3 ubiquitin ligase complex. Biochemical and genetic analyses revealed that SLB1 controls M. truncatula organ growth and lateral branching by modulating the stability of BIG SEEDS1 (BS1). Moreover, the overexpression of SLB1 increased seed and leaf size in both M. truncatula and soybean (Glycine max), indicating functional conservation. Our findings revealed a novel mechanism by which SLB1 targets BS1 for degradation to regulate M. truncatula organ size and shoot branching, providing a new genetic tool for increasing seed yield and biomass production in crop and forage legumes.
Antibacterial Polyketides from Antarctica Sponge-Derived Fungus Penicillium sp. HDN151272

Three new polyketides, ketidocillinones A–C (1–3), were discovered from the extract of an Antarctica sponge-derived fungus Penicillium sp. HDN151272. All the structures were deduced by spectroscopic data, including NMR and HRESIMS. The absolute configuration of compound 3 was established by using ECD calculation. Compounds 1−3 can be slowly oxidized to quinone form when exposed to air. Ketidocillinones B and C (2 and 3) exhibited potent antibacterial activity against Pseudomonas aeurigenosa, Mycobacterium phlei, and MRCNS (methicillin-resistant coagulase-negative staphylococci) with MIC values ranging from 1.56 to 25.00 µg/mL.
Two new nor-sesquiterpenoids from Fusarium tricinctum, an endophytic fungus isolated from Ligusticum chuanxiong

Abstract As part of our search for compounds with cytotoxicity from endophytes of traditional Chinese medicines, two novel nor-sesquiterpenoids (1–2) with a new skeleton containing a tetrahydrofuran moiety were isolated form a rice medium of Fusarium tricinctum, an endophytic fungus isolated from the root of Ligusticum chuanxiong. The structures of these two previously undescribed compounds were elucidated by interpretation of the spectroscopic evidences including NMR correlations as well as MS data. The absolute configurations of these two compounds were confirmed by TD-DFT-ECD calculations. An MTT assay indicated that compound 1 exhibited moderate cytotoxic activity against MV4-11 with an IC50 value of 22.29 μM. Graphical Abstract
The Influence of Inflammation on Anemia in CKD Patients

Anemia is frequently observed in the course of chronic kidney disease (CKD) and it is associated with diminishing the quality of a patient’s life. It also enhances morbidity and mortality and hastens the CKD progression rate. Patients with CKD frequently suffer from a chronic inflammatory state which is related to a vast range of underlying factors. The results of studies have demonstrated that persistent inflammation may contribute to the variability in Hb levels and hyporesponsiveness to erythropoietin stimulating agents (ESA), which are frequently observed in CKD patients. The understanding of the impact of inflammatory cytokines on erythropoietin production and hepcidin synthesis will enable one to unravel the net of interactions of multiple factors involved in the pathogenesis of the anemia of chronic disease. It seems that anti-cytokine and anti-oxidative treatment strategies may be the future of pharmacological interventions aiming at the treatment of inflammation-associated hyporesponsiveness to ESA. The discovery of new therapeutic approaches towards the treatment of anemia in CKD patients has become highly awaited. The treatment of anemia with erythropoietin (EPO) was associated with great benefits for some patients but not all.
Single-Photon-Emissions-Computertomographie bei der Differentialdiagnose der Demenz

To assess the value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia SPECT and conventional computed tomography were performed in 77 patients (50 men, 27 women, mean age 59 [28-90] years) with dementia diagnosed by a battery of psychometric tests. In 13 out of 15 patients with dementia of Alzheimer type SPECT showed a typical Alzheimer pattern (bilateral parietotemporal perfusion defects). Both patients with dementia of Pick type had definite decreases in frontal perfusion. All 21 patients with dementia due to Huntington's chorea showed a typical pattern with absent perfusion of the head of the caudate nucleus, although in three of them conventional computed tomography didn't demonstrate complete atrophy of this structure. Out of 23 patients with multi-infarct dementia there were 17 with focal uptake deficits at various sites, while six displayed an Alzheimer pattern. In Korsakoff's syndrome (n = 11), Down's syndrome (n = 1), Fahr's syndrome (n = 2), senile chorea (n = 1) and HIV encephalopathy (n = 1) no typical distribution patterns were noted. Single photon emission computed tomography can make a contribution to the diagnosis and classification of primary degenerative dementias and can be used to differentiate them from other forms of dementia.
Impact of betaine as a feed additive on livestock performance, carcass characteristics and meat quality- a review

Betaine (trimethylglycine) is a nontoxic methylamine compound contains the amino acid glycine with three chemically reactive methyl groups. This review gives an overview of the roles of betaine as a feed additive on the performance, carcass, meat quality in livestock production. Biological functions of betaine are defined as an osmolyte, methyl donor, and carcass modifier. As an osmolyte, betaine regulates the cellular hydration status and alleviates osmotic stress. As a methyl donor, betaine plays an important role in methylation reactions. Therefore, betaine may partly replace other methyl donors such as choline and methionine in the diet. Betaine is also supposed to play a significant role in lipid metabolism and has lipotropic effects also participating in the protein synthesis. A review of the results of this study suggests that betaine supplementation was effective to improve the average daily gain significantly, increased feed consumption and improved efficiency of food utilization of ruminants and monogastric animals. Betaine has been characterized as a carcass modifier by increasing the lean carcass percentage and decrease fat percentage by reducing lipid deposition. In conclusion, this study implies that dietary betaine supplementation was efficacious on growth performance and carcass characteristics of livestock.
Significant Personal Networks of Patients who Underwent Cardiac Surgery1

The personal network established by the patient when facing the cardiac surgical process has a significant impact regarding patients’ recovery and rehabilitation. This qualitative study aimed to comprehend the relational dynamics of significant personal networks of patients who underwent cardiac surgery. Twelve post-surgical patients participated in the research. Data collection was carried out through semi-structured interviews and the Social Networks Map. Data analysis was based on Grounded Theory. Family was the most emphasized group mentioned by the participants. The predominant function of the members of the personal network of participants was emotional support, evidencing the relational competencies of the health care professionals. Results highlight actors who are generally invisible in processes of health care, but who are also responsible for it, evidencing the relevance of the relational dynamics of different subjects present in the cardiac surgery process, regarding health care actions that consider patients as protagonists of their treatment.
Automotive Real-Time Data Acquisition Using Wi-Fi Connected Embedded System

The advancement in embedded systems, which includes the mass deployment of internet-connected electronics, allows the concept of Internet of Things (IoT), to become a reality. This paper discusses one example of how an internet-connected embedded system is utilized in an automotive system. An Electronic Control Unit (ECU), which functions as a control unit in a fuel injection system, are equipped with Wi-Fi capability and installed on 110cc motorcycle. The ECU is connected to multiple sensors that is used by the ECU as part of control system, as well as giving raw data in real time to the server by using Wi-Fi as the communication medium. The server will accumulate data transmitted from ECU by using MQTT protocol, chosen due to its minimal data profile. The data can be visualized through web portal, or opened by any other web-enabled devices. The data collected may also be used later for any other purposes, such as On-Board Diagnostics (OBD) system, etc.
Analysis of the Effects of Relational Marketing Towards Tourist Satisfaction Level On Organizing a Tourism Event In South Sumatra Province

This study is to determine the effect of relational marketing on the level of tourist satisfaction with the organization of tourism events in South Sumatra Province. Relational marketing researched includes the variables of commitment, empathy, reciprocity, and trust. Data collection techniques used were interviews, questionnaires, and observations. The data analysis model used is multiple linear regression analysis with hypothesis testing carried out simultaneously and partially with the help of IBM SPSS Statistics 22 software. The study population was 925 foreign tourists who were or had participated in organizing tourism events in South Sumatra Province. Research on 174 samples shows the results that the independent variables consisting of commitment, empathy, reciprocity, and trust simultaneously have a very strong influence on the dependent variable level of tourist satisfaction. While partially, the study produced that there are two variables, namely empathy and trust which have a significant influence on the level of tourist satisfaction, where empathy is the most dominant variable. Keywords—tourism events, relational marketing, customer satisfaction levels.
Elicitation strategies of in-vitro cultures for the sustainable use of medicinal plants:

Medicinal plants are highly traded for its promising potential against different types of diseases includingcancers. Development of elicitation strategies for increased production of important anticancer compounds from invitro cultures of medicinal plants has proved very productive. For this purpose, different stresses are applied to invitro cultures to produce increased amounts of the compounds. For instance, cell cultures are produced via stemexplants in the Murashige & Skoog basal medium supplemented with different concentrations of plant growthregulators (PGRs). The extracts from samples are then subject to flavonoid and phenolic content assessment, antioxidantquantification and Chromatographic analysis. In our experiments, among the many PGRs, Thidiazuron (TDZ)triggered higher quantities of biomass and total flavonoid & phenolic content (191.03 μg quercetin/mg and 202.8 μggallic acid equivalent/ mg, respectively) through cell cultures of F. indica. Similarly, sucrose induced the maximumbiomass among the different carbon sources (fructose, glucose, maltose, and sucrose) given in different concentrationsto cell cultures of F. indica while glucose produced the maximum phenolic content followed by fructose whenharvested after 42 days. Manipulation in the supply of light to the cultures with a combined effect from other chemicals,a significant effect was seen on growth and secondary metabolism such that dark-grown cell cultures treatedwith Methyl Jasmonate (Me-J) gave the highest TPC. High-performance liquid chromatography analysis revealed anincreased quantity of secondary metabolites. In conclusion, cell cultures of F. indica treated with Thidiazuron andgrown in dark in the presence of glucose as a sugar source and Me-J as elicitor gives enhanced quantities of importantanticancer secondary metabolites.
Clinical Implications of a One-hand Versus Two-hand Technique in the Silfverskiöld Test for Gastrocnemius Equinus

Introduction Isolated gastrocnemius equinus contracture has been associated with several foot and ankle pathologies within the literature. The Silfverskiöld test is commonly used to identify isolated gastrocnemius contracture, however, the proper technique for performing the test has been scrutinized. The purpose of this study was to determine if there is a clinical significance in the ankle dorsiflexion that is obtained when the examination is performed incorrectly with a single hand versus the correct two-hand technique. Methods Thirty consecutive new patients with conditions associated with gastrocnemius equinus were included in the study. The Silfverskiöld test was performed with a two-hand technique and a single-hand technique. The amount of dorsiflexion obtained with the knee in full extension was measured and recorded using an extendable goniometer for each technique, with the arms aligned with the fifth metatarsal and fibular head. Results The average amount of dorsiflexion that was obtained with the two-hand technique with the knee in full extension was 76.3°±4.2°. When the one-hand technique was utilized the average amount of dorsiflexion obtained with the knee in full extension was 88.4°±4.2°. This was found to be statistically significant (p<0.01). Conclusion This study demonstrates that if the Silfverskiöld test is not performed correctly, the diagnosis of an isolated gastrocnemius contracture could be underappreciated. Accordingly, it may be important to perform the test with two hands in order to neutralize the hindfoot, midfoot, and forefoot, so that the dorsiflexion motion is through the tibiotalar joint alone.
TASTING GAZIANTEP: HOW LOCAL FOOD SHAPES SENSE OF PLACE

Local food is an integral part of the cultural heritage and tourist attraction of a destination. Local food may create peak experiences for a tourist. Taste and smell create lasting impressions and memories, shaping tourist experience and leading to an association between food and place. This paper aims to analyse the conditions of such an association. After a review of relevant literature, focus group interviews were conducted with participants who had visited Gaziantep. We have found out that while local food creates lasting impressions, unfamiliarity usually results in more memorable experiences, and participants who spent longer time in the city, with higher motivation and means to experience the local food expressed more vivid memories. Likely, complementary cultural heritage and accompanying visual elements create a more complete and memorable sensory experience as well as a stronger association. Lastly, time passed after the trip turned out to be insignificant on memorability.
Incorporation of Spirulina (Athrospira Platensis) in Traditional Egyptian Cookies as a Source of Natural Bioactive Molecules and Functional Ingredients: Enhancing Nutritional and Sensory Properties with Flavoring and Coloring Food Additives

Incorporation of Spirulina (Athrospira Platensis) in Traditional Egyptian Cookies as aSource of Natural Bioactive Molecules and Functional Ingredients: Enhancing Nutritional and Sensory Properties with Flavoring and Coloring Food Additives El Nakib DM, Ibrahim MM, Mahmoud NS, Abd El Rhman EN and Ghaly AE* Department of Agricultural Engineering, Faculty of Agriculture, Cairo University, Giza, Egypt
AI Safe Exploration: Reinforced learning with a blocker in unsafe environments

Artificial intelligence can be trained with a trial and error based approach. In an environment where a catastrophe can not be accepted a human overseer can be used, but this might lower the efficiency of the learning. The study includes implementation of an artifact meant to replace the human overseer when training an AI in simulated unsafe environments. The results of testing the implemented blocker shows that it can be used for avoiding catastrophes and finding a path to reach the goal in 17 out of 18 runs. The single failed execution shows that the implemented blocker is in need of improvement in terms of data efficiency. Shaping rewards solely to reduce number of steps and catastrophes for a reinforcement learning agent has been done successfully to some degree, but further steps can be taken to lower the number of catastrophes and steps. Keywords-Artificial intelligence; Reinforcement learning; Safe exploration; Blocker; Machine learning; Baby AI Game; Gym Mini Grid;
A New Methodology to Simulate Three-Dimensional Hydraulic Loads on a Vertical Breakwater along its Life Cycle

A new methodology has been defined to calculate three-dimensional loads (forces and moments) and hydraulic stability (sliding and overturning) on concrete caissons all along construction stages of their life cycle, from isolated caissons to the final operation phase. The study of wave loading on the caisson has been simulated using a coupling of two CFD (Computational Fluid Dynamics) models: the two-dimensional model IH2VOF and the three-dimensional model IHFOAM. In order to take into account the wave climate variability and uncertainties associated with all processes involved, the Monte-Carlo statistical technique has been used with a hybrid numerical simulation methodology. This new methodology allows for numerical optimization of computational costs and provides reliable results, because of the large number of cases simulated. The application of this methodology in a real study case is shown in this paper: the main vertical breakwater of Granadilla Port (Tenerife, Spain).
The Dark Side of Monetary Bonuses: Theory and Experimental Evidence

To incentivize workers and boost performance, firms often offer monetary bonuses for the achievement of production goals. Such bonuses appeal to two types of motivations of the worker. On the one hand, the existence of a goal, on its own, triggers an intrinsic motivation associated with the desire to not fall short of the goal. On the other hand, the money paid to achieve the goal constitutes an extrinsic motivation. This paper studies the possibility that these two effects are substitutes when workers set their own goals. We develop a theoretical model that predicts that if the worker is sufficiently loss averse and faces uncertainty about reaching a production goal, offering a monetary payment contingent on reaching such a goal is counterproductive. This is because under the presence of monetary bonuses, the loss averse worker prefers setting lower goals, which yield lower but more likely bonus payments. Lower goals, in turn, negatively affect subsequent performance. Results from a laboratory experiment corroborate this prediction. This paper highlights the limits of monetary bonuses as an effective incentive when workers are loss averse.