Profile Of Candidates Research Articles

Rancangan Sistem Pendukung Keputusan Pemilihan Calon Pegawai Honorer Pemerintah Kabupaten Lamandau Menggunakan Metode Profile Matching

This study aims to design a Decision Support System (DSS) that implements the Profile Matchingmethod for the selection of honorary employees in the Lamandau District Government. The oftennon-systematic selection process results in less objective decisions, necessitating a system that canenhance effectiveness and transparency in decision-making. The Profile Matching method is usedto compare the profiles of candidates with predetermined criteria, leading to a fairer and moreaccurate selection process. Data were collected through interviews with relevant stakeholders inthe Lamandau District Government, which were then analyzed to identify appropriate selectioncriteria. The findings indicate that the application of DSS can reduce subjectivity and improveclarity in the evaluation process. Additionally, the designed computer-based system facilitatesfaster data processing and presents information in a more comprehensible manner. Thus, thisresearch is expected to make a significant contribution to the development of employee selectionsystems in local government and enhance the quality of human resources in public service. Theimplementation of information technology in DSS is anticipated to serve as a reference for futureresearch in decision-making and human resource management.

Thiazepine-based Hybrids as Promising Anti-colon Cancer Agents: Design, Synthesis, Computational and In Vitro Screening.

Novel thiazepine-based hybrids (9a-d) were designed and synthesized to create lead molecules with exceptional anti-colon cancer efficacy. Analytical methods, including IR, NMR, and HR-MS, characterized the synthesized compounds. The in vitro colorectal study was carried out to compare the biological activity of newly developed compounds with the computational data. The tested compounds induced cytotoxicity in HT-29 cells for both 24h and 48h in a dose-dependent manner. However, compound 9a induced cytotoxicity at much higher concentrations compared to the rest of the compounds. 9b and 9c caused 50% cell death (compared to the untreated cells) at a dose of ~ 50µM and 40 µM in case of 24-hour exposure, respectively. On the contrary, for 48h exposure, both 9b and 9c induced 50% cell death concerning untreated cells at a dose of around ~20 µM, whereas 9d exhibited 50% cell death at 5 µM in the case of 48 h exposure. In silico ADMET was also carried out to understand the pharmacokinetics and safety profiles of the drug candidates. We found some of the critical targets of these compounds, which eventually will be integral to exploring the mechanistic actions of these compounds in colon cancer.

Holistic in silico developability assessment of novel classes of small proteins using publicly available sequence-based predictors.

The development of novel therapeutic proteins is a lengthy and costly process, with an average attrition rate of 91% (Thomas et al. Clinical Development Success Rates and Contributing Factors 2011-2020, 2021). To increase the probability of success and ensure robust drug supply beyond approval, it is essential to assess the developability profile of new potential drug candidates as early and broadly as possible in development (Jain et al. MAbs, 2023. https://doi.org/10.1016/j.copbio.2011.06.002 ). Predicting these properties in silico is expected to be the next leap in innovation as it would enable significantly reduced development timelines combined with broader screens at lower costs. However, developing predictive algorithms typically requires substantial datasets generated under very defined conditions, a limiting factor especially for new classes of therapeutic proteins that hold immense clinical promise. Here we describe a strategy for assessing the developability of a novel class of small therapeutic Anticalin® proteins using machine learning in conjunction with a knowledge-driven approach. The knowledge-driven approach considers developability attributes such as aggregation propensity, charge variants, immunogenicity, specificity, thermal stability, hydrophobicity, and potential post-translational modifications, to calculate a holistic developability score. Based on sequence-derived descriptors as input parameters we established novel statistical models designed to predict the developability scores for Anticalin proteins. The best models yielded low root mean square errors across the entire dataset and were further validated by removing input data from individual screening campaigns and predicting developability scores for those drug candidates. The adoption of the described workflow will enable significantly streamlined preclinical development of Anticalin drug candidates and could potentially be applied to other therapeutic protein scaffolds.

Ribosomal translation of fluorinated non-canonical amino acids for de novo biologically active fluorinated macrocyclic peptides.

Fluorination has emerged as a promising strategy in medicinal chemistry to improve the pharmacological profiles of drug candidates. Similarly, incorporating fluorinated non-canonical amino acids into macrocyclic peptides expands chemical diversity and enhances their pharmacological properties, from improved metabolic stability to enhanced cell permeability and target interactions. However, only a limited number of fluorinated non-canonical amino acids, which are canonical amino acid analogs, have been incorporated into macrocyclic peptides by ribosomes for de novo construction and target-based screening of fluorinated macrocyclic peptides. In this study, we report the ribosomal translation of a series of distinct fluorinated non-canonical amino acids, including mono-to tri-fluorinated variants, as well as fluorinated l-amino acids, d-amino acids, β-amino acids, etc. This enabled the de novo discovery of fluorinated macrocyclic peptides with high affinity for EphA2, and particularly the identification of those exhibiting broad-spectrum activity against Gram-negative bacteria by targeting the BAM complex. This study not only expands the scope of ribosomally translatable fluorinated amino acids but also underscores the versatility of fluorinated macrocyclic peptides as potent therapeutic agents.

In Search of the Missing Link: Election Law Infractions and Candidate Sanctions

In contrast to the extensive literature on the determinants of campaign spending and its effect on candidates’ electoral performance, comparatively less literature exists on the legal and sanctioning characteristics of political finance systems. Though some contributions have analyzed and compared the institutional designs of these financing systems, limited literature has empirically examined infractions and sanctions of electoral laws, categorized as either a crime or a misdemeanor, by the candidates. Limited knowledge exists about the political and sociodemographic profile of candidates who commit such offenses or misdemeanors, a gap this study addresses by empirically analyzing electoral law infractions. Using the case of Chile and an unpublished database of infractions of 38,246 candidates in the local elections of 2008, 2012, and 2016, as well as the legislative elections of 2009, 2013, and 2017, we present four conclusions. First, only about one-fifth of candidates commit such infractions. Second, such infractions are more common during first-tier elections, especially in deputy and senatorial elections. Third, the candidates most likely to commit such infractions are independent candidates who compete in regions remote from large urban centers, especially in rural areas. Fourth, the rise in infractions is linked to a new law that more strictly regulates candidates’ campaign spending. The study enhances our understanding of the efficacy of political finance systems and the enforcement of electoral sanctions.

Cementless Total Knee Arthroplasty: A State-of-the-Art Review.

» The demographic profile of candidates for total knee arthroplasty (TKA) is shifting toward younger and more active individuals.» While cemented fixation remains the gold standard in TKA, the interest is growing in exploring cementless fixation as a potentially more durable alternative.» Advances in manufacturing technologies are enhancing the prospects for superior long-term biological fixation.» Current research indicates that intermediate to long-term outcomes of modern cementless TKA designs are comparable with traditional cemented designs.» The selection of appropriate patients is critical to the success of cementless fixation techniques in TKA.» There is a need for high-quality research to better understand the potential differences and relative benefits of cemented vs. cementless TKA systems.

The Impact of Social Media on Political Enthusiasm Study of the Young Generation in the General Election of Jekan Raya City, Palangka Raya City

General Election (Election) Young generation or millennials. General elections are a process to achieve integrity and legal authority which is carried out with the participation of candidates as well as the control process of the agency or field of supervision, to obtain legality by the public which is approved by the established law. Become an underlying part of democratic instruments. The general election indicator is community involvement and participation. This is with the involvement of young people or the millennial generation. The participation or involvement of young people or the millennial generation in general elections is very crucial because, apart from being large in number, these young people are also one of the nation's next generations. However, in terms of participation efforts and indications of what possibilities could have an impact on an outcome, it will certainly be influenced by the participation or involvement of young people. It needs to be identified so that in the future it can help their efforts regarding ways or procedures to take part in a correct election. This research was conducted in Jekan Raya Village, Palangkaraya City. The research findings illustrate that social media has a big influence on the millennial generation, especially in recognizing the profiles of candidates running for office.

SIGecom Job Market Candidate Profiles 2024

This is the ninth annual collection of profiles of the junior faculty job market candidates of the SIGecom community. The twenty seven candidates for 2024 are listed alphabetically and indexed by research areas that define the interests of the community. The candidates can be contacted individually, or collectively via the moderated mailing list ecom-candidates2024@acm.org. Shortly before publishing these candidate profiles, we received the shocking news that one of the candidates from this collection, Orestis Papadigenopoulos, unexpectedly passed away. Apart from a great researcher, Orestis was a very kind, pleasant, and fun person and will be sorely missed. His profile remains in this collection in his memory, despite his untimely passing.

Market Design Job Market Candidate Profiles 2024

Inspired by the SIGecom Exchanges' annual survey of job market candidates, 1 this is the fourth annual collection of profiles of the junior faculty job market candidates of the market design community. The eleven candidates are listed alphabetically. Along with information regarding the candidate's bio, job market paper, other representative papers, and short research summary, each profile also contains links to the candidate's homepage and CV. We dedicate this effort in memory of all the innocents who were murdered or otherwise harmed in the terrorist attack on Israel on Oct 7, and all the innocents who were killed or otherwise harmed in its ongoing aftermath, and with the hope that all those abducted---children, women, and men---will be back home by the end of this job market season.

Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug

GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound’s physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.

Advancing Drug Safety in Drug Development: Bridging Computational Predictions for Enhanced Toxicity Prediction.

The attrition rate of drugs in clinical trials is generally quite high, with estimates suggesting that approximately 90% of drugs fail to make it through the process. The identification of unexpected toxicity issues during preclinical stages is a significant factor contributing to this high rate of failure. These issues can have a major impact on the success of a drug and must be carefully considered throughout the development process. These late-stage rejections or withdrawals of drug candidates significantly increase the costs associated with drug development, particularly when toxicity is detected during clinical trials or after market release. Understanding drug-biological target interactions is essential for evaluating compound toxicity and safety, as well as predicting therapeutic effects and potential off-target effects that could lead to toxicity. This will enable scientists to predict and assess the safety profiles of drug candidates more accurately. Evaluation of toxicity and safety is a critical aspect of drug development, and biomolecules, particularly proteins, play vital roles in complex biological networks and often serve as targets for various chemicals. Therefore, a better understanding of these interactions is crucial for the advancement of drug development. The development of computational methods for evaluating protein-ligand interactions and predicting toxicity is emerging as a promising approach that adheres to the 3Rs principles (replace, reduce, and refine) and has garnered significant attention in recent years. In this review, we present a thorough examination of the latest breakthroughs in drug toxicity prediction, highlighting the significance of drug-target binding affinity in anticipating and mitigating possible adverse effects. In doing so, we aim to contribute to the development of more effective and secure drugs.

Creativity profile of biology teacher candidates: An exploratory study

Abstract: Creativity is one of the important skills that teachers must have today. Creativity can be defined as the human ability to generate new and valuable ideas. In addition, creativity is considered as a basic competency that needs to be possessed by students in higher education. The purpose of this study was to determine the creativity of prospective biology teachers and its relationship with students' knowledge mastery. For this purpose, a descriptive and correlational study was conducted on 13 biology pre-service students. The instrument used in this study was the Torrance creativity test based on 4 creativity indicators: fluency, flexibility, originality and elaboration. Descriptive and correlational analyses were conducted to identify students' creativity profiles and the relationship between students' creativity and their knowledge mastery. The results showed that there were three types of creativity owned by prospective biology teacher students, namely students with low (38.46%), medium (38.46%) and high (23, 07%) levels of creativity. The correlation test results show that concept mastery correlates with student creativity (r=0.3). The conclusion of this study is that prospective biology teacher students have different creativity, and there is a correlation between students' concept mastery and their creativity level so that there needs to be an effort from lecturers by designing learning strategies that can increase student creativity and concept mastery.

Target population for a selective cardiac myosin inhibitor in hypertrophic obstructive cardiomyopathy: Real-life estimation from the French register of hypertrophic cardiomyopathy (REMY)

BackgroundThe efficacy of current pharmacological therapies in hypertrophic cardiomyopathy is limited. A cardiac myosin inhibitor, mavacamten, has recently been approved as a first-in-class treatment for symptomatic hypertrophic obstructive cardiomyopathy. AimsTo assess the profile and burden of cardiac myosin inhibitor candidates in the hypertrophic cardiomyopathy prospective Register of hypertrophic cardiomyopathy (REMY) held by the French Society of Cardiology. MethodsData were collected at baseline and during follow-up from patients with hypertrophic cardiomyopathy enrolled in REMY by the three largest participating centres. ResultsAmong 1059 adults with hypertrophic cardiomyopathy, 461 (43.5%) had obstruction; 325 (30.7%) of these were also symptomatic, forming the “cardiac myosin inhibitor candidates” group. Baseline features of this group were: age 58±15years; male sex (n=196; 60.3%); diagnosis-to-inclusion delay 5 (1–12)years; maximum wall thickness 20±6mm; left ventricular ejection fraction 69±6%; family history of hypertrophic cardiomyopathy or sudden cardiac death (n=133; 40.9%); presence of a pathogenic sarcomere gene mutation (n=101; 31.1%); beta-blocker or verapamil treatment (n=304; 93.8%), combined with disopyramide (n=28; 8.7%); and eligibility for septal reduction therapy (n=96; 29%). At the end of a median follow-up of 66 (34–106) months, 319 (98.2%) were treated for obstruction (n=43 [13.2%] received disopyramide), 46 (14.2%) underwent septal reduction therapy and the all-cause mortality rate was 1.9/100 person-years (95% confidence interval 1.4–2.6) (46 deaths). Moreover, 41 (8.9%) patients from the initial hypertrophic obstructive cardiomyopathy group became eligible for a cardiac myosin inhibitor. ConclusionsIn this cohort of patients with hypertrophic cardiomyopathy selected from the REMY registry, one third were eligible for a cardiac myosin inhibitor.

Silver‐Enabled Cycloaddition of Bicyclobutanes with Isocyanides for the Synthesis of Polysubstituted 3‐Azabicyclo[3.1.1]heptanes

AbstractSynthesis of bicyclic scaffolds has emerged as an important research topic in modern drug development because they can serve as saturated bioisosters to enhance the physicochemical properties and metabolic profiles of drug candidates. Here we report a remarkably simple silver‐enabled strategy to access polysubstituted 3‐azabicyclo[3.1.1]heptanes in a single operation from readily accessible bicyclobutanes (BCBs) and isocyanides. The process is proposed to involve a formal (3+3)/(3+2)/retro‐(3+2) cycloaddition sequence. This novel protocol allows for rapid generation of molecular complexity from simple starting materials, and the products can be easily derivatized, further enriching the BCB cycloaddition chemistry and the growing set of valuable sp3‐rich bicyclic building blocks.

Silver-Enabled Cycloaddition of Bicyclobutanes with Isocyanides for the Synthesis of Polysubstituted 3-Azabicyclo[3.1.1]heptanes.

Synthesis of bicyclic scaffolds has emerged as an important research topic in modern drug development because they can serve as saturated bioisosters to enhance the physicochemical properties and metabolic profiles of drug candidates. Here we report a remarkably simple silver-enabled strategy to access polysubstituted 3-azabicyclo[3.1.1]heptanes in a single operation from readily accessible bicyclobutanes (BCBs) and isocyanides. The process is proposed to involve a formal (3+3)/(3+2)/retro-(3+2) cycloaddition sequence. This novel protocol allows for rapid generation of molecular complexity from simple starting materials, and the products can be easily derivatized, further enriching the BCB cycloaddition chemistry and the growing set of valuable sp3-rich bicyclic building blocks.

Some head starts are bigger than others: dynastic legacies and variation in candidate quality in Taiwan's local elections

Abstract Candidates from established political families are more likely to win than their non-dynastic counterparts because their political inheritance often includes significant advantages in resources and reputation. Yet dynastic candidates also bring their own set of experiences and qualities to the game. Is it the case that their individual characteristics can explain their electoral success, or is their success due to their family legacy? Theoretically, how and when are political resources transferred to the new generation? We examine these questions by looking at non-incumbent candidates in city and county council elections in Taiwan from 2009 to 2014, drawing on unique data on politicians' backgrounds. The profile of dynastic candidates differs from that of non-dynastic candidates: they are younger, have less electoral experience and list experience in different sorts of organizations and jobs. However, these differences are not what drives their electoral success; indeed, they tend to win despite these qualities rather than because of them. Even after controlling for candidate quality, dynastic status remains a powerful predictor, conveying roughly a 20 percentage point increase in the probability of winning. This suggests that while dynastic candidates accrue some of their advantage long before they run for office, a large part of the inheritance is transferred during the campaign.

Proposing a framework to quantify the potential impact of pharmacokinetic drug-drug interactions caused by a new drug candidate by using real world data about the target patient population.

Drug development teams must evaluate the risk/benefit profile of new drug candidates that perpetrate drug-drug interactions (DDIs). Real-world data (RWD) can inform this decision. The purpose of this study was to develop a predicted impact score for DDIs perpetrated by three hypothetical drug candidates via CYP3A, CYP2D6, or CYP2C9 in type 2 diabetes mellitus (T2DM), obesity, or migraine. Optum Market Clarity was analyzed to estimate use of CYP3A, CYP2D6, or CYP2C9 substrates classified in the University of Washington Drug Interaction Database as moderate sensitive, sensitive, narrow therapeutic index, or QT prolongation. Scoring was based on prevalence of exposure to victim substrates and characteristics (age, polypharmacy, duration of exposure, and number of prescribers) of those exposed. The study population of 14,163,271 adults included 1,579,054 with T2DM, 3,117,753 with obesity, and 410,436 with migraine. For T2DM, 71.3% used CYP3A substrates, 44.3% used CYP2D6 substrates, and 44.3% used CYP2C9 substrates. For obesity, 57.1% used CYP3A substrates, 34.6% used CYP2D6 substrates, and 31.0% used CYP2C9 substrates. For migraine, 64.1% used CYP3A substrates, 44.0% used CYP2D6 substrates, and 28.9% used CYP2C9 substrates. In our analyses, the predicted DDI impact scores were highest for DDIs involving CYP3A, followed by CYP2D6, and CYP2C9 substrates, and highest for T2DM, followed by migraine, and obesity. Insights from RWD can be used to estimate a predicted DDI impact score for pharmacokinetic DDIs perpetrated by new drug candidates currently in development. This score can inform the risk/benefit profile of new drug candidates in a target patient population.

Psychological Characteristics of Patients Undergoing Awake Craniotomy With Dexmedetomidine: A Retrospective Analysis

BACKGROUND AND OBJECTIVES: Only few studies have investigated the psychological profile of patient candidates for awake craniotomy (AC). The aim of this study was to describe the multidisciplinary clinical protocol adopted in our hospital and to retrospectively explore differences in psychological characteristic of 51 patients, analyzing association with the tolerability of the procedure. METHODS: During the preoperative neuropsychological assessment, the Pain Anxiety Symptoms Scale was administered to assess pain-related anxiety. Clinical characteristics and anesthesiological management were retrospectively recollected. The AC procedure was classified as “optimal” or “suboptimal” based on administration of rescue sedative midazolam doses because of psychomotor agitation or emotional distress in excess with respect to our anesthesiological protocol. RESULTS: The awake procedure was considered optimal in 33 cases (64.7% of total sample). General anesthesia was never required in our patients. No significant differences between optimal and suboptimal groups were found. No single variable was significant as a predictor of outcome on the univariate analysis, and no multivariate predictive model was possible. CONCLUSION: Although in our experience the Pain Anxiety Symptoms Scale score was not useful in identifying candidates for AC procedures, our multidisciplinary approach provided good results with respect to the tolerability of AC surgery. However, more studies are required to identify psychological profiles and preoperative possible warning signs to find the best course of surgery for each patient.

Profile and Social Assessment of Liver Transplant Candidates: A Retrospective Approach

Profile and Social Assessment of Liver Transplant Candidates: A Retrospective Approach

BioisoIdentifier: an online free tool to investigate local structural replacements from PDB

Within the realm of contemporary medicinal chemistry, bioisosteres are empirically used to enhance potency and selectivity, improve adsorption, distribution, metabolism, excretion and toxicity profiles of drug candidates. It is believed that bioisosteric know-how may help bypass granted patents or generate novel intellectual property for commercialization. Beside the synthetic expertise, the drug discovery process also depends on efficient in silico tools. We hereby present BioisoIdentifier (BII), a web server aiming to uncover bioisosteric information for specific fragment. Using the Protein Data Bank as source, and specific substructures that the user attempt to surrogate as input, BII tries to find suitable fragments that fit well within the local protein active site. BII is a powerful computational tool that offers the ligand design ideas for bioisosteric replacing. For the validation of BII, catechol is conceived as model fragment attempted to be replaced, and many ideas are successfully offered. These outputs are hierarchically grouped according to structural similarity, and clustered based on unsupervised machine learning algorithms. In summary, we constructed a user-friendly interface to enable the viewing of top-ranking molecules for further experimental exploration. This makes BII a highly valuable tool for drug discovery. The BII web server is freely available to researchers and can be accessed at http://www.aifordrugs.cn/index/. Scientific Contribution: By designing a more optimal computational process for mining bioisosteric replacements from the publicly accessible PDB database, then deployed on a web server for throughly free access for researchers. Additionally, machine learning methods are applied to cluster the bioisosteric replacements searched by the platform, making a scientific contribution to facilitate chemists’ selection of appropriate bioisosteric replacements. The number of bioisosteric replacements obtained using BII is significantly larger than the currently available platforms, which expanding the search space for effective local structural replacements.Graphical