PER PREFIX FLEXIBLE METRIC FOR INTENT BASED ROUTING AND TRAFFIC ENGINEERING USING EIGRP

Routing protocols are typically designed to use a single-cost formula for all of a protocol\u27s routes. In some instances, a network administrator can adjust the cost formula of the Enhanced Interior Gateway Routing Protocol (EIGRP), but the protocol applies the formula uniformly to all prefixes, which can cause all applications to suffer from lower performance. In order to address such issues, techniques are presented herein through which a flexible metric can be applied that is isolated to prefixes. for example, the techniques presented herein provide for the reduced use of Virtual Private Network (VPN) routing & forwarding (VRF) instances on routers and ease network configuration as configurations provided in accordance with the techniques presented herein are only needed at prefix originators

Repurposing Thioridazine (TDZ) as an anti-inflammatory agent

Nuclear factor-kB (NF-kB) is a crucial transcription factor in the signal transduction cascade of the inflammatory signaling. Activation of NF-κB depends on the phosphorylation of IκBα by IκB kinase (IKKβ) followed by subsequent ubiquitination and degradation. This leads to the nuclear translocation of the p50- p65 subunits of NF-κB, and further triggers pro-inflammatory cytokine gene expression. Thus, in the need of a more effective therapy for the treatment of inflammatory diseases, specific inhibition of IKKβ represents a rational alternative strategy to the current therapies. A computer-aided drug identification protocol was followed to identify novel IKKβ inhibitors from a database of over 1500 Food and Drug Administration (FDA) drugs. The best scoring compounds were compared with the already known high-potency IKKβ inhibitors for their ability to bind and inhibit IKKβ by evaluating their docking energy. Finally, Thioridazinehydrochloride (TDZ), a potent antipsychotic drug against Schizophrenia was selected and its efficiency in inhibiting IκBα protein degradation and NF-κB activation was experimentally validated. Our study has demonstrated that TDZ blocks IκBα protein degradation and subsequent NF-κB activation to inhibit inflammation. Thus, it is a potential repurposed drug against inflammation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Interpreting Multivariate Time Series for an Organization Health Platform

Machine learning-based systems are rapidly becoming popular because it has been realized that machines are more efficient and effective than humans at performing certain tasks. Although machine learning algorithms are extremely popular, they are also very literal and undeviating. This has led to a huge research surge in the field of interpretability in machine learning to ensure that machine learning models are reliable, fair, and can be held liable for their decision-making process. Moreover, in most real-world problems just making predictions using machine learning algorithms only solves the problem partially. Time series is one of the most popular and important data types because of its dominant presence in the fields of business, economics, and engineering. Despite this, interpretability in time series is still relatively unexplored as compared to tabular, text, and image data. With the growing research in the field of interpretability in machine learning, there is also a pressing need to be able to quantify the quality of explanations produced after interpreting machine learning models. Due to this reason, evaluation of interpretability is extremely important. The evaluation of interpretability for models built on time series seems completely unexplored in research circles. This thesis work focused on achieving and evaluating model agnostic interpretability in a time series forecasting problem.  The use case discussed in this thesis work focused on finding a solution to a problem faced by a digital consultancy company. The digital consultancy wants to take a data-driven approach to understand the effect of various sales related activities in the company on the sales deals closed by the company. The solution involved framing the problem as a time series forecasting problem to predict the sales deals and interpreting the underlying forecasting model. The interpretability was achieved using two novel model agnostic interpretability techniques, Local interpretable model- agnostic explanations (LIME) and Shapley additive explanations (SHAP). The explanations produced after achieving interpretability were evaluated using human evaluation of interpretability. The results of the human evaluation studies clearly indicate that the explanations produced by LIME and SHAP greatly helped lay humans in understanding the predictions made by the machine learning model. The human evaluation study results also indicated that LIME and SHAP explanations were almost equally understandable with LIME performing better but with a very small margin. The work done during this project can easily be extended to any time series forecasting or classification scenario for achieving and evaluating interpretability. Furthermore, this work can offer a very good framework for achieving and evaluating interpretability in any machine learning-based regression or classification problem. Maskininlärningsbaserade system blir snabbt populära eftersom man har insett att maskiner är effektivare än människor när det gäller att utföra vissa uppgifter. Även om maskininlärningsalgoritmer är extremt populära, är de också mycket bokstavliga. Detta har lett till en enorm forskningsökning inom området tolkbarhet i maskininlärning för att säkerställa att maskininlärningsmodeller är tillförlitliga, rättvisa och kan hållas ansvariga för deras beslutsprocess. Dessutom löser problemet i de flesta verkliga problem bara att göra förutsägelser med maskininlärningsalgoritmer bara delvis. Tidsserier är en av de mest populära och viktiga datatyperna på grund av dess dominerande närvaro inom affärsverksamhet, ekonomi och teknik. Trots detta är tolkningsförmågan i tidsserier fortfarande relativt outforskad jämfört med tabell-, text- och bilddata. Med den växande forskningen inom området tolkbarhet inom maskininlärning finns det också ett stort behov av att kunna kvantifiera kvaliteten på förklaringar som produceras efter tolkning av maskininlärningsmodeller. Av denna anledning är utvärdering av tolkbarhet extremt viktig. Utvärderingen av tolkbarhet för modeller som bygger på tidsserier verkar helt outforskad i forskarkretsar. Detta uppsatsarbete fokuserar på att uppnå och utvärdera agnostisk modelltolkbarhet i ett tidsserieprognosproblem.  Fokus ligger i att hitta lösningen på ett problem som ett digitalt konsultföretag står inför som användningsfall. Det digitala konsultföretaget vill använda en datadriven metod för att förstå effekten av olika försäljningsrelaterade aktiviteter i företaget på de försäljningsavtal som företaget stänger. Lösningen innebar att inrama problemet som ett tidsserieprognosproblem för att förutsäga försäljningsavtalen och tolka den underliggande prognosmodellen. Tolkningsförmågan uppnåddes med hjälp av två nya tekniker för agnostisk tolkbarhet, lokala tolkbara modellagnostiska förklaringar (LIME) och Shapley additiva förklaringar (SHAP). Förklaringarna som producerats efter att ha uppnått tolkbarhet utvärderades med hjälp av mänsklig utvärdering av tolkbarhet. Resultaten av de mänskliga utvärderingsstudierna visar tydligt att de förklaringar som produceras av LIME och SHAP starkt hjälpte människor att förstå förutsägelserna från maskininlärningsmodellen. De mänskliga utvärderingsstudieresultaten visade också att LIME- och SHAP-förklaringar var nästan lika förståeliga med LIME som presterade bättre men med en mycket liten marginal. Arbetet som utförts under detta projekt kan enkelt utvidgas till alla tidsserieprognoser eller klassificeringsscenarier för att uppnå och utvärdera tolkbarhet. Dessutom kan detta arbete erbjuda en mycket bra ram för att uppnå och utvärdera tolkbarhet i alla maskininlärningsbaserade regressions- eller klassificeringsproblem

Interpreting Multivariate Time Series for an Organization Health Platform

Machine learning-based systems are rapidly becoming popular because it has been realized that machines are more efficient and effective than humans at performing certain tasks. Although machine learning algorithms are extremely popular, they are also very literal and undeviating. This has led to a huge research surge in the field of interpretability in machine learning to ensure that machine learning models are reliable, fair, and can be held liable for their decision-making process. Moreover, in most real-world problems just making predictions using machine learning algorithms only solves the problem partially. Time series is one of the most popular and important data types because of its dominant presence in the fields of business, economics, and engineering. Despite this, interpretability in time series is still relatively unexplored as compared to tabular, text, and image data. With the growing research in the field of interpretability in machine learning, there is also a pressing need to be able to quantify the quality of explanations produced after interpreting machine learning models. Due to this reason, evaluation of interpretability is extremely important. The evaluation of interpretability for models built on time series seems completely unexplored in research circles. This thesis work focused on achieving and evaluating model agnostic interpretability in a time series forecasting problem.  The use case discussed in this thesis work focused on finding a solution to a problem faced by a digital consultancy company. The digital consultancy wants to take a data-driven approach to understand the effect of various sales related activities in the company on the sales deals closed by the company. The solution involved framing the problem as a time series forecasting problem to predict the sales deals and interpreting the underlying forecasting model. The interpretability was achieved using two novel model agnostic interpretability techniques, Local interpretable model- agnostic explanations (LIME) and Shapley additive explanations (SHAP). The explanations produced after achieving interpretability were evaluated using human evaluation of interpretability. The results of the human evaluation studies clearly indicate that the explanations produced by LIME and SHAP greatly helped lay humans in understanding the predictions made by the machine learning model. The human evaluation study results also indicated that LIME and SHAP explanations were almost equally understandable with LIME performing better but with a very small margin. The work done during this project can easily be extended to any time series forecasting or classification scenario for achieving and evaluating interpretability. Furthermore, this work can offer a very good framework for achieving and evaluating interpretability in any machine learning-based regression or classification problem. Maskininlärningsbaserade system blir snabbt populära eftersom man har insett att maskiner är effektivare än människor när det gäller att utföra vissa uppgifter. Även om maskininlärningsalgoritmer är extremt populära, är de också mycket bokstavliga. Detta har lett till en enorm forskningsökning inom området tolkbarhet i maskininlärning för att säkerställa att maskininlärningsmodeller är tillförlitliga, rättvisa och kan hållas ansvariga för deras beslutsprocess. Dessutom löser problemet i de flesta verkliga problem bara att göra förutsägelser med maskininlärningsalgoritmer bara delvis. Tidsserier är en av de mest populära och viktiga datatyperna på grund av dess dominerande närvaro inom affärsverksamhet, ekonomi och teknik. Trots detta är tolkningsförmågan i tidsserier fortfarande relativt outforskad jämfört med tabell-, text- och bilddata. Med den växande forskningen inom området tolkbarhet inom maskininlärning finns det också ett stort behov av att kunna kvantifiera kvaliteten på förklaringar som produceras efter tolkning av maskininlärningsmodeller. Av denna anledning är utvärdering av tolkbarhet extremt viktig. Utvärderingen av tolkbarhet för modeller som bygger på tidsserier verkar helt outforskad i forskarkretsar. Detta uppsatsarbete fokuserar på att uppnå och utvärdera agnostisk modelltolkbarhet i ett tidsserieprognosproblem.  Fokus ligger i att hitta lösningen på ett problem som ett digitalt konsultföretag står inför som användningsfall. Det digitala konsultföretaget vill använda en datadriven metod för att förstå effekten av olika försäljningsrelaterade aktiviteter i företaget på de försäljningsavtal som företaget stänger. Lösningen innebar att inrama problemet som ett tidsserieprognosproblem för att förutsäga försäljningsavtalen och tolka den underliggande prognosmodellen. Tolkningsförmågan uppnåddes med hjälp av två nya tekniker för agnostisk tolkbarhet, lokala tolkbara modellagnostiska förklaringar (LIME) och Shapley additiva förklaringar (SHAP). Förklaringarna som producerats efter att ha uppnått tolkbarhet utvärderades med hjälp av mänsklig utvärdering av tolkbarhet. Resultaten av de mänskliga utvärderingsstudierna visar tydligt att de förklaringar som produceras av LIME och SHAP starkt hjälpte människor att förstå förutsägelserna från maskininlärningsmodellen. De mänskliga utvärderingsstudieresultaten visade också att LIME- och SHAP-förklaringar var nästan lika förståeliga med LIME som presterade bättre men med en mycket liten marginal. Arbetet som utförts under detta projekt kan enkelt utvidgas till alla tidsserieprognoser eller klassificeringsscenarier för att uppnå och utvärdera tolkbarhet. Dessutom kan detta arbete erbjuda en mycket bra ram för att uppnå och utvärdera tolkbarhet i alla maskininlärningsbaserade regressions- eller klassificeringsproblem

Interpreting Multivariate Time Series for an Organization Health Platform

Machine learning-based systems are rapidly becoming popular because it has been realized that machines are more efficient and effective than humans at performing certain tasks. Although machine learning algorithms are extremely popular, they are also very literal and undeviating. This has led to a huge research surge in the field of interpretability in machine learning to ensure that machine learning models are reliable, fair, and can be held liable for their decision-making process. Moreover, in most real-world problems just making predictions using machine learning algorithms only solves the problem partially. Time series is one of the most popular and important data types because of its dominant presence in the fields of business, economics, and engineering. Despite this, interpretability in time series is still relatively unexplored as compared to tabular, text, and image data. With the growing research in the field of interpretability in machine learning, there is also a pressing need to be able to quantify the quality of explanations produced after interpreting machine learning models. Due to this reason, evaluation of interpretability is extremely important. The evaluation of interpretability for models built on time series seems completely unexplored in research circles. This thesis work focused on achieving and evaluating model agnostic interpretability in a time series forecasting problem. The use case discussed in this thesis work focused on finding a solution to a problem faced by a digital consultancy company. The digital consultancy wants to take a data-driven approach to understand the effect of various sales related activities in the company on the sales deals closed by the company. The solution involved framing the problem as a time series forecasting problem to predict the sales deals and interpreting the underlying forecasting model. The interpretability was achieved using two novel model agnostic interpretability techniques, Local interpretable model- agnostic explanations (LIME) and Shapley additive explanations (SHAP). The explanations produced after achieving interpretability were evaluated using human evaluation of interpretability. The results of the human evaluation studies clearly indicate that the explanations produced by LIME and SHAP greatly helped lay humans in understanding the predictions made by the machine learning model. The human evaluation study results also indicated that LIME and SHAP explanations were almost equally understandable with LIME performing better but with a very small margin. The work done during this project can easily be extended to any time series forecasting or classification scenario for achieving and evaluating interpretability. Furthermore, this work can offer a very good framework for achieving and evaluating interpretability in any machine learning-based regression or classification problem