Joyce Lai - Academia.edu (original) (raw)
Papers by Joyce Lai
EDULEARN Proceedings
Today's competitive global market demands that engineers possess "soft skills" in addition to tec... more Today's competitive global market demands that engineers possess "soft skills" in addition to technical skills. Currently, engineers learn leadership, teamwork, and management skills while working "soft skills the hard way". In order to meet the demands of this changing world, engineering programs in different universities are challenged to come up with innovative ways to teach classes so that graduates are prepared to take on the challenges twenty-first-century engineers face. Team-Based Learning (TBL) is an advancing teaching pedagogy that shifts instruction from a traditional lecture-based teaching paradigm to a structured learning sequence. TBL has shown to be effective in student academic success and retention; however, it may also aid in the development of soft skills required for the industry. This study focuses on 165 students who were enrolled in a freshman-level programming course in the Fall 2019. The students were all asked voluntarily to fill a "Soft Skills Survey" in the second week of the semester that consisted of 38 questions evaluating various categories of soft skills. At the end of the semester, the same survey was given and both were used to evaluate the effectiveness of TBL on students' soft skills. The conducted survey is designed to assess five overarching factors within the TBL framework: The first is how group work improves individual motivation; the second is how group work stimulates academic growth; the third is the individual student's creative and critical thinking skills; the fourth is the value of group work for their overall education; the last is confidence in their own academic skills. Traditionally, the effectiveness of TBL has been assessed through grades and numeric measures of performance; however, TBL was designed to both enhance learning as well as team collaboration and critical thinking skills. These two surveys were conducted to assess the "soft skills" outcome gains. Preliminary results for this study showed modest gains in critical thinking and external motivation. The results show that using TBL will organically enhance the students' soft skills.
EDULEARN Proceedings
A comparative study to show the effectiveness of Team-Based Learning (TBL) and Mixed Active-Tradi... more A comparative study to show the effectiveness of Team-Based Learning (TBL) and Mixed Active-Traditional (MATL) learning for an introductory programming course at Iowa State University is discussed in this paper. The introductory programming C course was offered to 46 students using TBL and 50 students using MATL, led by two different instructors who use the same course schedule and textbook. The students on both courses received the same number of lectures/labs during the semester. To be able to assess the two methodologies, the instructors deliver the same course contents. Still, they differ with the course delivery method. MATL utilizes maximum class time for traditional lectures with class activities, and the TBL utilizes the maximum class time for interactive group activities with mini-lectures. Homework, reading assignments, and the final exam results are compared to check both teaching methods' overall effectiveness. Although students were satisfied with both teaching methods, students' performances were better in TBL than the MATL.
Cancer Immunology Research
G protein-coupled receptors (GPCRs), a family of seven-transmembrane receptor proteins function a... more G protein-coupled receptors (GPCRs), a family of seven-transmembrane receptor proteins function as sensors transmitting extracellular signals into the cell and mediate a diverse range of ligand signaling, are proven to be successful drug targets. GPCRs and the associated downstream signaling pathways have been linked to a wide range of disease types such as cancer, inflammatory and immune disorders, as well as metabolic and neurological diseases. Antibodies are becoming an increasingly promising modality to target these receptors due to their unique properties, such as exquisite specificity, long half-life, and fewer side effects, and their improved pharmacokinetic and pharmacodynamic profiles compared to peptides and small molecules, which results from their more favorable biodistribution. To date, there are only two US Food and Drug Administration-approved GPCR antibody drugs, namely erenumab and mogamulizumab, and this highlights the challenges encountered in identifying function...
2020 IEEE International Conference on Teaching, Assessment, and Learning for Engineering (TALE)
The coronavirus disease (COVID-19) is a public health emergency of international concern. The spr... more The coronavirus disease (COVID-19) is a public health emergency of international concern. The spread of the virus all over the world sent billions of people into lockdown. In light of rising concerns, a growing number of universities across the globe and specifically in the United States have either postponed or canceled all campus events such as workshops, conferences, sports, and other activities. Universities took intensive measures to prevent and protect all students, faculty, and staff members from the highly infectious disease. This resulted in migrating all face-to-face courses into an online course. In this paper, the authors present the impact of COVID-19 on migrating a Team-based Learning C programming course from face-to-face to online delivery and its effect on student learning. The results section of this paper shows that the student learning curve was affected significantly by the sudden online delivery of the course.
Milliscale, magnetically-controlled robots can be used for targeted blood clot removal. This meth... more Milliscale, magnetically-controlled robots can be used for targeted blood clot removal. This method may provide a more precise, less dangerous, and less invasive removal process than the current methods which utilize blood thinning medication and catheters. These robots have helical threads so that magnetically induced rotation will produce a propulsive force that is controlled by an external magnetic system. The speed at which the robots need to rotate in order to hover in place in human blood is called the hovering frequency, and was used as a measure of the efficiency of the robot designs. We developed a pipeline for simulated testing of the robots using Finite Element Methods and post-processing. The flow of blood around the robots when rotating at various frequencies was modeled with the Navier-Stokes equations and approximated using the penalty method. In post-processing, the simulations were evaluated by visualizing the interaction of flow lines with the design geometries, co...
2021 IEEE Sensors
Short non-coding RNAs, which are known as microRNAs (miRNAs), play a key role in fundamental cell... more Short non-coding RNAs, which are known as microRNAs (miRNAs), play a key role in fundamental cellular processes by post-transcription regulations. This paper reports a paper-based miRNA exponential amplification and detection system for rapid analysis of miRNAs. The paper-based sensor system consists of a silicone frame, glass microfiber pads for the storage of reaction reagents, a polyethersulfone flow channel for sample delivery, and two transparent and adhesive films to seal the glass microfiber pads inside reaction chambers. The results showed that the paper-based miRNA sensor can detect miRNA-223 with a concentration as low as 10 pM within one hour.
levels of telomerase activity and perceived coping and lower levels of proinflammatory cytokines,... more levels of telomerase activity and perceived coping and lower levels of proinflammatory cytokines, perceived stress, and Tiwari et al. BMC Complementary and Alternative Medicine 2014, 14:300
EDULEARN Proceedings, 2020
Team-Based Learning (TBL) is an evidence-based collaborative learning teaching strategy designed ... more Team-Based Learning (TBL) is an evidence-based collaborative learning teaching strategy designed around units of instruction, known as "modules" that are taught in a three-step cycle: preparation, inclass readiness assurance test (RAT), and application-focused exercise. The in-class RAT includes two subtests; individual RAT (iRAT) and team RAT (tRAT). In first-year programming classes, the instructors rely on the mini-lecture to deliver advanced concepts or present a programming exercise to the students. Meanwhile, most of the class time is consumed by the iRAT, tRAT, and application-focused exercise. This paper sheds light on an attempt to modify the conventional TBL approach by taking the iRAT outside the classroom and exploit its time to extend the mini-lecture time. This modification is achieved by the aid of an interactive online book, which ensures that the students finished their reading assignments before the class. Hence, the interactive book can allow us to take the iRAT outside the classroom, which will save at least 20% of the class time. The proposed approach was implemented to a class of 165 students in Fall 2019 and 47 students in Spring 2020, and the preliminary results show that the students finish each class reading assignment with an average percentage of 87%.
L'invention concerne des anticorps anti-PCSK9 qui se lient a un site de clivage de PCSK9 et l... more L'invention concerne des anticorps anti-PCSK9 qui se lient a un site de clivage de PCSK9 et leurs procedes d'utilisation.
BMJ, 2020
Flatfoot is a deformity associated with collapse of the medial longitudinal foot arch, valgus def... more Flatfoot is a deformity associated with collapse of the medial longitudinal foot arch, valgus deformity of the heel, and abduction of the forefoot. It is commonly encountered in primary care settings. The prevalence of flatfoot is estimated between 3% and 25% in the general population based on studies in healthy volunteers. 2 In 1989, Johnson and Strom created a three stage classification system for adult acquired flatfoot deformity. This was further modified by Myerson with the addition of a fourth stage in 1997 (table 1). Causes of flatfoot include posterior tibial tendon dysfunction, trauma, inflammatory arthritis, Charcot arthropathy, and congenital causes such as tarsal coalition. The most common cause in adults is posterior tibial tendon dysfunction. It is associated with obesity, diabetes mellitus, hypertension, trauma, and corticosteroid injections. The symptomatic flatfoot presents with medial arch pain and can affect gait. Untreated symptomatic flatfoot in the long term can become a rigid deformity, which will further affect the patient’s quality of life. Despite this, there are few publications or guidance for management of adult flatfoot in primary care. This article aims to give a systematic approach to manage a patient presenting with symptomatic flatfoot. What you should cover History What and where are the symptoms?
International Journal of Surgical Pathology, 2019
Counting intraepithelial lymphocytes (IELs) is a key part of the assessment of duodenal biopsies.... more Counting intraepithelial lymphocytes (IELs) is a key part of the assessment of duodenal biopsies. Immunohistochemistry (IHC) for CD3 can aid identification of lymphocytes in this context, but it is not evident that counts on hematoxylin and eosin (H&E) and CD3 are comparable. This study aimed to compare the IEL counts in duodenal biopsies using H&E stains and CD3 IHC, and to examine the interobserver variability. Thirty-five paired H&E and CD3 sections were reviewed by 6 pathologists who counted the number of IELs per 100 enterocytes. The counts were categorized into groups: normal (<25 lymphocytes), mildly raised (25-40 lymphocytes), and markedly raised (>40 lymphocytes). CD3 IHC was associated with significantly higher IEL counts than H&E. Four cases with normal H&E counts had raised counts with CD3. There was moderate agreement between observers for both H&E and CD3. Lack of concordance between CD3 and H&E IEL counts suggests that counts derived from the 2 methods may not b...
Hematology, 2017
Objectives: As thromboembolism (TE) continues to be one of the principal causes of death in obste... more Objectives: As thromboembolism (TE) continues to be one of the principal causes of death in obstetrical patients and as the postpartum period is associated with the highest risk for TE, we sought to determine the risk factors associated with TE following cesarean section (CS). Methods: A retrospective analysis of patients who had CS at a large tertiary referral center was conducted. Patients were identified through hospital medical records and were contacted approximately 1 year following their CS. Medical records and a questionnaire were used to identify features that were potentially associated with TE. Univariate analysis was used to determine the risk associated with these characteristics. Results: A total of 2206 patients had a CS, of which 1377 (62%) participated. Of the respondents, 137 patients received heparin (94% received a prophylactic dose, 6% received a therapeutic dose) and the remainder, 1233 patients, did not receive heparin. Seven patients (0.5%) developed a TE and 86% developed a TE within 7 days of CS. The odds ratio (OR) for TE for women with hypertension prior to pregnancy compared to patients who did not receive anticoagulation was 21.28 [95% confidence interval (CI) 4.64-90.13] and for patients who had varicose veins with superficial thrombophlebitis when compared to patients who had received heparin postpartum was 21.01 (95% CI 1.55-288.24). Discussion: Hypertension and the presence of varicose veins were associated with TE following CS. Larger cohort analyses are required to confirm these associations so that risk scores incorporating these characteristics may accurately predict the occurrence of TE.
The Faseb Journal, Apr 1, 2007
SSRN Electronic Journal, 2010
This study examines whether the abnormal performance of active Australian small-cap equity fund m... more This study examines whether the abnormal performance of active Australian small-cap equity fund managers is associated with broker recommendations. Our evidence supports the investment value of broker recommendations, showing significant abnormal returns (ARs) both pre-and post-broker recommendations. We find that when a factor-mimicking portfolio based on broker recommendations is added to a Carhart (1997) model, annual alphas are reduced by 48 basis points. Using transaction-level data, buy trades following broker recommendations earn significant cumulative ARs of 1.56 per cent after 60 days. Overall, we find that broker recommendations account for an economically significant component of alphas.
Proceedings of the National Academy of Sciences, 2013
Many important signaling pathways rely on multiple ligands. It is unclear if this is a mechanism ... more Many important signaling pathways rely on multiple ligands. It is unclear if this is a mechanism of safeguard via redundancy or if it serves other functional purposes. In this study, we report unique insight into this question by studying the activin receptor-like kinase 1 (ALK1) pathway. Despite its functional importance in vascular development, the physiological ligand or ligands for ALK1 remain to be determined. Using conventional knockout and specific antibodies against bone morphogenetic protein 9 (BMP9) or BMP10, we showed that BMP9 and BMP10 are the physiological, functionally equivalent ligands of ALK1 in vascular development. Timing of expression dictates the in vivo requisite role of each ligand, and concurrent expression results in redundancy. We generated mice ( Bmp10 9/9 ) in which the coding sequence of Bmp9 replaces that of Bmp10 . Surprisingly, analysis of Bmp10 9/9 mice demonstrated that BMP10 has an exclusive function in cardiac development, which cannot be substit...
Nature Immunology, 2011
Interleukin 17C (IL-17C) is a member of the IL-17 family that is selectively induced in epithelia... more Interleukin 17C (IL-17C) is a member of the IL-17 family that is selectively induced in epithelia by bacterial challenge and inflammatory stimuli. Here we show that IL-17C functioned in a unique autocrine manner, binding to a receptor complex consisting of the receptors IL-17RA and IL-17RE, which was preferentially expressed on tissue epithelial cells. IL-17C stimulated epithelial inflammatory responses, including the expression of proinflammatory cytokines, chemokines and antimicrobial peptides, which were similar to those induced by IL-17A and IL-17F. However, IL-17C was produced by distinct cellular sources, such as epithelial cells, in contrast to IL-17A, which was produced mainly by leukocytes, especially those of the T H 17 subset of helper T cells. Whereas IL-17C promoted inflammation in an imiquimod-induced skin-inflammation model, it exerted protective functions in dextran sodium sulfate-induced colitis. Thus, IL-17C is an essential autocrine cytokine that regulates innate epithelial immune responses.
The Journal of Immunology, 2005
Journal of Cellular Physiology, 1996
Regulation of immune cell activation in lymphocyte-bearing human tissues is a pivotal host functi... more Regulation of immune cell activation in lymphocyte-bearing human tissues is a pivotal host function, and metabolites of arachidonic acid (prostaglandin E2 in particular) have been reported to serve this function at non-mucosal sites. However, it is unknown whether prostaglandin E2 is immunoregulatory for the large lymphocyte population in the lamina propria of intestine; whether low (nM) concentrations of prostaglandin E2 modulate immune responses occurring there; and whether adjacent inflammation per se abrogates prostaglandin E2's regulatory effects. To address these issues, intestine-derived lymphocytes and T hybridoma cells were assessed, T cell activation was monitored by release of independently quantitated lymphokines, and dose-response studies were performed over an 8-log prostaglandin E2 concentration range. IL-3 release by normal intestinal lamina propria mononuclear cells was reduced (up to 78%) in a dose-dependent manner by prostaglandin E2, when present in as low a concentration as 10(-10) M. PGE2 also inhibited (by > or = 60%) mucosal T lymphocytes' ability to destabilize the barrier function of human epithelial monolayers. Further, with an intestine-derived T lymphocyte hybridoma cell line, a prostaglandin E2 dose-dependent reduction in IL-3 and IL-2 (90 and 95%, respectively) was found; this was true for both mitogen- and antigen-driven T cell lymphokine release. Concomitant [3H] thymidine uptake studies suggested this was not due to a prostaglandin E2-induced reduction in T cell proliferation or viability. In contrast, cells from chronically inflamed intestinal mucosa were substantially less sensitive to prostaglandin E2, e.g., high concentrations (10(-6) M) of prostaglandin E2 inhibited IL-3 release by only 41%. We conclude that prostaglandin E2 in nM concentrations is an important modulator of cytokine release from T lymphocytes derived from the gastrointestinal tract, and it may play a central role in regulation of lamina propria immunocyte populations residing there.
Journal of Biological Chemistry, 2012
Background: Two forms of PCSK9, an intact and a furin cleaved form, circulate in blood. Results: ... more Background: Two forms of PCSK9, an intact and a furin cleaved form, circulate in blood. Results: Both forms, as highly purified recombinant proteins, are able to bind to and trigger degradation of LDL receptors and elevate serum cholesterol levels. Conclusion: Furin cleavage is not associated with a loss of PCSK9 polypeptides or a significant loss of function. Significance: LDL-c levels are controlled by both forms of PCSK9. Proprotein convertase subtilisin/kexin 9 (PCSK9) regulates plasma LDL cholesterol levels by regulating the degradation of LDL receptors. Another proprotein convertase, furin, cleaves PCSK9 at Arg 218-Gln 219 in the surface-exposed "218 loop." This cleaved form circulates in blood along with the intact form, albeit at lower concentrations. To gain a better understanding of how cleavage affects PCSK9 function, we produced recombinant furin-cleaved PCSK9 using antibody Ab-3D5, which binds the intact but not the cleaved 218 loop. Using Ab-3D5, we also produced highly purified hepsin-cleaved PCSK9. Hepsin cleaves PCSK9 at Arg 218-Gln 219 more efficiently than furin but also cleaves at Arg 215-Phe 216. Further analysis by size exclusion chromatography and mass spectrometry indicated that furin and hepsin produced an internal cleavage in the 218 loop without the loss of the N-terminal segment (Ser 153-Arg 218), which remained attached to the catalytic domain. Both furin-and hepsin-cleaved PCSK9 bound to LDL receptor with only 2-fold reduced affinity compared with intact PCSK9. Moreover, they reduced LDL receptor levels in HepG2 cells and in mouse liver with only moderately lower activity than intact PCSK9, consistent with the binding data. Single injection into mice of furincleaved PCSK9 resulted in significantly increased serum cholesterol levels, approaching the increase by intact PCSK9. These findings indicate that circulating furin-cleaved PCSK9 is able to regulate LDL receptor and serum cholesterol levels, although somewhat less efficiently than intact PCSK9. Therapeutic anti-PCSK9 approaches that neutralize both forms should be the most effective in preserving LDL receptors and in lowering plasma LDL cholesterol.
EDULEARN Proceedings
Today's competitive global market demands that engineers possess "soft skills" in addition to tec... more Today's competitive global market demands that engineers possess "soft skills" in addition to technical skills. Currently, engineers learn leadership, teamwork, and management skills while working "soft skills the hard way". In order to meet the demands of this changing world, engineering programs in different universities are challenged to come up with innovative ways to teach classes so that graduates are prepared to take on the challenges twenty-first-century engineers face. Team-Based Learning (TBL) is an advancing teaching pedagogy that shifts instruction from a traditional lecture-based teaching paradigm to a structured learning sequence. TBL has shown to be effective in student academic success and retention; however, it may also aid in the development of soft skills required for the industry. This study focuses on 165 students who were enrolled in a freshman-level programming course in the Fall 2019. The students were all asked voluntarily to fill a "Soft Skills Survey" in the second week of the semester that consisted of 38 questions evaluating various categories of soft skills. At the end of the semester, the same survey was given and both were used to evaluate the effectiveness of TBL on students' soft skills. The conducted survey is designed to assess five overarching factors within the TBL framework: The first is how group work improves individual motivation; the second is how group work stimulates academic growth; the third is the individual student's creative and critical thinking skills; the fourth is the value of group work for their overall education; the last is confidence in their own academic skills. Traditionally, the effectiveness of TBL has been assessed through grades and numeric measures of performance; however, TBL was designed to both enhance learning as well as team collaboration and critical thinking skills. These two surveys were conducted to assess the "soft skills" outcome gains. Preliminary results for this study showed modest gains in critical thinking and external motivation. The results show that using TBL will organically enhance the students' soft skills.
EDULEARN Proceedings
A comparative study to show the effectiveness of Team-Based Learning (TBL) and Mixed Active-Tradi... more A comparative study to show the effectiveness of Team-Based Learning (TBL) and Mixed Active-Traditional (MATL) learning for an introductory programming course at Iowa State University is discussed in this paper. The introductory programming C course was offered to 46 students using TBL and 50 students using MATL, led by two different instructors who use the same course schedule and textbook. The students on both courses received the same number of lectures/labs during the semester. To be able to assess the two methodologies, the instructors deliver the same course contents. Still, they differ with the course delivery method. MATL utilizes maximum class time for traditional lectures with class activities, and the TBL utilizes the maximum class time for interactive group activities with mini-lectures. Homework, reading assignments, and the final exam results are compared to check both teaching methods' overall effectiveness. Although students were satisfied with both teaching methods, students' performances were better in TBL than the MATL.
Cancer Immunology Research
G protein-coupled receptors (GPCRs), a family of seven-transmembrane receptor proteins function a... more G protein-coupled receptors (GPCRs), a family of seven-transmembrane receptor proteins function as sensors transmitting extracellular signals into the cell and mediate a diverse range of ligand signaling, are proven to be successful drug targets. GPCRs and the associated downstream signaling pathways have been linked to a wide range of disease types such as cancer, inflammatory and immune disorders, as well as metabolic and neurological diseases. Antibodies are becoming an increasingly promising modality to target these receptors due to their unique properties, such as exquisite specificity, long half-life, and fewer side effects, and their improved pharmacokinetic and pharmacodynamic profiles compared to peptides and small molecules, which results from their more favorable biodistribution. To date, there are only two US Food and Drug Administration-approved GPCR antibody drugs, namely erenumab and mogamulizumab, and this highlights the challenges encountered in identifying function...
2020 IEEE International Conference on Teaching, Assessment, and Learning for Engineering (TALE)
The coronavirus disease (COVID-19) is a public health emergency of international concern. The spr... more The coronavirus disease (COVID-19) is a public health emergency of international concern. The spread of the virus all over the world sent billions of people into lockdown. In light of rising concerns, a growing number of universities across the globe and specifically in the United States have either postponed or canceled all campus events such as workshops, conferences, sports, and other activities. Universities took intensive measures to prevent and protect all students, faculty, and staff members from the highly infectious disease. This resulted in migrating all face-to-face courses into an online course. In this paper, the authors present the impact of COVID-19 on migrating a Team-based Learning C programming course from face-to-face to online delivery and its effect on student learning. The results section of this paper shows that the student learning curve was affected significantly by the sudden online delivery of the course.
Milliscale, magnetically-controlled robots can be used for targeted blood clot removal. This meth... more Milliscale, magnetically-controlled robots can be used for targeted blood clot removal. This method may provide a more precise, less dangerous, and less invasive removal process than the current methods which utilize blood thinning medication and catheters. These robots have helical threads so that magnetically induced rotation will produce a propulsive force that is controlled by an external magnetic system. The speed at which the robots need to rotate in order to hover in place in human blood is called the hovering frequency, and was used as a measure of the efficiency of the robot designs. We developed a pipeline for simulated testing of the robots using Finite Element Methods and post-processing. The flow of blood around the robots when rotating at various frequencies was modeled with the Navier-Stokes equations and approximated using the penalty method. In post-processing, the simulations were evaluated by visualizing the interaction of flow lines with the design geometries, co...
2021 IEEE Sensors
Short non-coding RNAs, which are known as microRNAs (miRNAs), play a key role in fundamental cell... more Short non-coding RNAs, which are known as microRNAs (miRNAs), play a key role in fundamental cellular processes by post-transcription regulations. This paper reports a paper-based miRNA exponential amplification and detection system for rapid analysis of miRNAs. The paper-based sensor system consists of a silicone frame, glass microfiber pads for the storage of reaction reagents, a polyethersulfone flow channel for sample delivery, and two transparent and adhesive films to seal the glass microfiber pads inside reaction chambers. The results showed that the paper-based miRNA sensor can detect miRNA-223 with a concentration as low as 10 pM within one hour.
levels of telomerase activity and perceived coping and lower levels of proinflammatory cytokines,... more levels of telomerase activity and perceived coping and lower levels of proinflammatory cytokines, perceived stress, and Tiwari et al. BMC Complementary and Alternative Medicine 2014, 14:300
EDULEARN Proceedings, 2020
Team-Based Learning (TBL) is an evidence-based collaborative learning teaching strategy designed ... more Team-Based Learning (TBL) is an evidence-based collaborative learning teaching strategy designed around units of instruction, known as "modules" that are taught in a three-step cycle: preparation, inclass readiness assurance test (RAT), and application-focused exercise. The in-class RAT includes two subtests; individual RAT (iRAT) and team RAT (tRAT). In first-year programming classes, the instructors rely on the mini-lecture to deliver advanced concepts or present a programming exercise to the students. Meanwhile, most of the class time is consumed by the iRAT, tRAT, and application-focused exercise. This paper sheds light on an attempt to modify the conventional TBL approach by taking the iRAT outside the classroom and exploit its time to extend the mini-lecture time. This modification is achieved by the aid of an interactive online book, which ensures that the students finished their reading assignments before the class. Hence, the interactive book can allow us to take the iRAT outside the classroom, which will save at least 20% of the class time. The proposed approach was implemented to a class of 165 students in Fall 2019 and 47 students in Spring 2020, and the preliminary results show that the students finish each class reading assignment with an average percentage of 87%.
L'invention concerne des anticorps anti-PCSK9 qui se lient a un site de clivage de PCSK9 et l... more L'invention concerne des anticorps anti-PCSK9 qui se lient a un site de clivage de PCSK9 et leurs procedes d'utilisation.
BMJ, 2020
Flatfoot is a deformity associated with collapse of the medial longitudinal foot arch, valgus def... more Flatfoot is a deformity associated with collapse of the medial longitudinal foot arch, valgus deformity of the heel, and abduction of the forefoot. It is commonly encountered in primary care settings. The prevalence of flatfoot is estimated between 3% and 25% in the general population based on studies in healthy volunteers. 2 In 1989, Johnson and Strom created a three stage classification system for adult acquired flatfoot deformity. This was further modified by Myerson with the addition of a fourth stage in 1997 (table 1). Causes of flatfoot include posterior tibial tendon dysfunction, trauma, inflammatory arthritis, Charcot arthropathy, and congenital causes such as tarsal coalition. The most common cause in adults is posterior tibial tendon dysfunction. It is associated with obesity, diabetes mellitus, hypertension, trauma, and corticosteroid injections. The symptomatic flatfoot presents with medial arch pain and can affect gait. Untreated symptomatic flatfoot in the long term can become a rigid deformity, which will further affect the patient’s quality of life. Despite this, there are few publications or guidance for management of adult flatfoot in primary care. This article aims to give a systematic approach to manage a patient presenting with symptomatic flatfoot. What you should cover History What and where are the symptoms?
International Journal of Surgical Pathology, 2019
Counting intraepithelial lymphocytes (IELs) is a key part of the assessment of duodenal biopsies.... more Counting intraepithelial lymphocytes (IELs) is a key part of the assessment of duodenal biopsies. Immunohistochemistry (IHC) for CD3 can aid identification of lymphocytes in this context, but it is not evident that counts on hematoxylin and eosin (H&E) and CD3 are comparable. This study aimed to compare the IEL counts in duodenal biopsies using H&E stains and CD3 IHC, and to examine the interobserver variability. Thirty-five paired H&E and CD3 sections were reviewed by 6 pathologists who counted the number of IELs per 100 enterocytes. The counts were categorized into groups: normal (<25 lymphocytes), mildly raised (25-40 lymphocytes), and markedly raised (>40 lymphocytes). CD3 IHC was associated with significantly higher IEL counts than H&E. Four cases with normal H&E counts had raised counts with CD3. There was moderate agreement between observers for both H&E and CD3. Lack of concordance between CD3 and H&E IEL counts suggests that counts derived from the 2 methods may not b...
Hematology, 2017
Objectives: As thromboembolism (TE) continues to be one of the principal causes of death in obste... more Objectives: As thromboembolism (TE) continues to be one of the principal causes of death in obstetrical patients and as the postpartum period is associated with the highest risk for TE, we sought to determine the risk factors associated with TE following cesarean section (CS). Methods: A retrospective analysis of patients who had CS at a large tertiary referral center was conducted. Patients were identified through hospital medical records and were contacted approximately 1 year following their CS. Medical records and a questionnaire were used to identify features that were potentially associated with TE. Univariate analysis was used to determine the risk associated with these characteristics. Results: A total of 2206 patients had a CS, of which 1377 (62%) participated. Of the respondents, 137 patients received heparin (94% received a prophylactic dose, 6% received a therapeutic dose) and the remainder, 1233 patients, did not receive heparin. Seven patients (0.5%) developed a TE and 86% developed a TE within 7 days of CS. The odds ratio (OR) for TE for women with hypertension prior to pregnancy compared to patients who did not receive anticoagulation was 21.28 [95% confidence interval (CI) 4.64-90.13] and for patients who had varicose veins with superficial thrombophlebitis when compared to patients who had received heparin postpartum was 21.01 (95% CI 1.55-288.24). Discussion: Hypertension and the presence of varicose veins were associated with TE following CS. Larger cohort analyses are required to confirm these associations so that risk scores incorporating these characteristics may accurately predict the occurrence of TE.
The Faseb Journal, Apr 1, 2007
SSRN Electronic Journal, 2010
This study examines whether the abnormal performance of active Australian small-cap equity fund m... more This study examines whether the abnormal performance of active Australian small-cap equity fund managers is associated with broker recommendations. Our evidence supports the investment value of broker recommendations, showing significant abnormal returns (ARs) both pre-and post-broker recommendations. We find that when a factor-mimicking portfolio based on broker recommendations is added to a Carhart (1997) model, annual alphas are reduced by 48 basis points. Using transaction-level data, buy trades following broker recommendations earn significant cumulative ARs of 1.56 per cent after 60 days. Overall, we find that broker recommendations account for an economically significant component of alphas.
Proceedings of the National Academy of Sciences, 2013
Many important signaling pathways rely on multiple ligands. It is unclear if this is a mechanism ... more Many important signaling pathways rely on multiple ligands. It is unclear if this is a mechanism of safeguard via redundancy or if it serves other functional purposes. In this study, we report unique insight into this question by studying the activin receptor-like kinase 1 (ALK1) pathway. Despite its functional importance in vascular development, the physiological ligand or ligands for ALK1 remain to be determined. Using conventional knockout and specific antibodies against bone morphogenetic protein 9 (BMP9) or BMP10, we showed that BMP9 and BMP10 are the physiological, functionally equivalent ligands of ALK1 in vascular development. Timing of expression dictates the in vivo requisite role of each ligand, and concurrent expression results in redundancy. We generated mice ( Bmp10 9/9 ) in which the coding sequence of Bmp9 replaces that of Bmp10 . Surprisingly, analysis of Bmp10 9/9 mice demonstrated that BMP10 has an exclusive function in cardiac development, which cannot be substit...
Nature Immunology, 2011
Interleukin 17C (IL-17C) is a member of the IL-17 family that is selectively induced in epithelia... more Interleukin 17C (IL-17C) is a member of the IL-17 family that is selectively induced in epithelia by bacterial challenge and inflammatory stimuli. Here we show that IL-17C functioned in a unique autocrine manner, binding to a receptor complex consisting of the receptors IL-17RA and IL-17RE, which was preferentially expressed on tissue epithelial cells. IL-17C stimulated epithelial inflammatory responses, including the expression of proinflammatory cytokines, chemokines and antimicrobial peptides, which were similar to those induced by IL-17A and IL-17F. However, IL-17C was produced by distinct cellular sources, such as epithelial cells, in contrast to IL-17A, which was produced mainly by leukocytes, especially those of the T H 17 subset of helper T cells. Whereas IL-17C promoted inflammation in an imiquimod-induced skin-inflammation model, it exerted protective functions in dextran sodium sulfate-induced colitis. Thus, IL-17C is an essential autocrine cytokine that regulates innate epithelial immune responses.
The Journal of Immunology, 2005
Journal of Cellular Physiology, 1996
Regulation of immune cell activation in lymphocyte-bearing human tissues is a pivotal host functi... more Regulation of immune cell activation in lymphocyte-bearing human tissues is a pivotal host function, and metabolites of arachidonic acid (prostaglandin E2 in particular) have been reported to serve this function at non-mucosal sites. However, it is unknown whether prostaglandin E2 is immunoregulatory for the large lymphocyte population in the lamina propria of intestine; whether low (nM) concentrations of prostaglandin E2 modulate immune responses occurring there; and whether adjacent inflammation per se abrogates prostaglandin E2's regulatory effects. To address these issues, intestine-derived lymphocytes and T hybridoma cells were assessed, T cell activation was monitored by release of independently quantitated lymphokines, and dose-response studies were performed over an 8-log prostaglandin E2 concentration range. IL-3 release by normal intestinal lamina propria mononuclear cells was reduced (up to 78%) in a dose-dependent manner by prostaglandin E2, when present in as low a concentration as 10(-10) M. PGE2 also inhibited (by > or = 60%) mucosal T lymphocytes' ability to destabilize the barrier function of human epithelial monolayers. Further, with an intestine-derived T lymphocyte hybridoma cell line, a prostaglandin E2 dose-dependent reduction in IL-3 and IL-2 (90 and 95%, respectively) was found; this was true for both mitogen- and antigen-driven T cell lymphokine release. Concomitant [3H] thymidine uptake studies suggested this was not due to a prostaglandin E2-induced reduction in T cell proliferation or viability. In contrast, cells from chronically inflamed intestinal mucosa were substantially less sensitive to prostaglandin E2, e.g., high concentrations (10(-6) M) of prostaglandin E2 inhibited IL-3 release by only 41%. We conclude that prostaglandin E2 in nM concentrations is an important modulator of cytokine release from T lymphocytes derived from the gastrointestinal tract, and it may play a central role in regulation of lamina propria immunocyte populations residing there.
Journal of Biological Chemistry, 2012
Background: Two forms of PCSK9, an intact and a furin cleaved form, circulate in blood. Results: ... more Background: Two forms of PCSK9, an intact and a furin cleaved form, circulate in blood. Results: Both forms, as highly purified recombinant proteins, are able to bind to and trigger degradation of LDL receptors and elevate serum cholesterol levels. Conclusion: Furin cleavage is not associated with a loss of PCSK9 polypeptides or a significant loss of function. Significance: LDL-c levels are controlled by both forms of PCSK9. Proprotein convertase subtilisin/kexin 9 (PCSK9) regulates plasma LDL cholesterol levels by regulating the degradation of LDL receptors. Another proprotein convertase, furin, cleaves PCSK9 at Arg 218-Gln 219 in the surface-exposed "218 loop." This cleaved form circulates in blood along with the intact form, albeit at lower concentrations. To gain a better understanding of how cleavage affects PCSK9 function, we produced recombinant furin-cleaved PCSK9 using antibody Ab-3D5, which binds the intact but not the cleaved 218 loop. Using Ab-3D5, we also produced highly purified hepsin-cleaved PCSK9. Hepsin cleaves PCSK9 at Arg 218-Gln 219 more efficiently than furin but also cleaves at Arg 215-Phe 216. Further analysis by size exclusion chromatography and mass spectrometry indicated that furin and hepsin produced an internal cleavage in the 218 loop without the loss of the N-terminal segment (Ser 153-Arg 218), which remained attached to the catalytic domain. Both furin-and hepsin-cleaved PCSK9 bound to LDL receptor with only 2-fold reduced affinity compared with intact PCSK9. Moreover, they reduced LDL receptor levels in HepG2 cells and in mouse liver with only moderately lower activity than intact PCSK9, consistent with the binding data. Single injection into mice of furincleaved PCSK9 resulted in significantly increased serum cholesterol levels, approaching the increase by intact PCSK9. These findings indicate that circulating furin-cleaved PCSK9 is able to regulate LDL receptor and serum cholesterol levels, although somewhat less efficiently than intact PCSK9. Therapeutic anti-PCSK9 approaches that neutralize both forms should be the most effective in preserving LDL receptors and in lowering plasma LDL cholesterol.