Miracle-dz/UniFAR-FTUs huggingface dataset:
Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses

Background Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CLpro), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection. Methodology/Principal Findings Here, we profiled the substrate specificities of 3CLpro from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19×8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CLpro prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CLpro from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CLpro prefers P4-Pro and SARS-CoV 3CLpro prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences ‘VARLQ↓SGF’ that can be cleaved efficiently by all 3CLpro with relative activity of 1.7 to 3.2, and ‘VPRLQ↓SGF’ that can be cleaved specifically by IBV 3CLpro with relative activity of 4.3. Conclusions/Significance The comprehensive substrate specificities of 3CLpro from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases.
Membrane/microtubule tip attachment complexes (TACs) allow the assembly dynamics of plus ends to push and pull membranes into tubulovesicular networks in interphase Xenopus egg extracts

We discovered by using high resolution video microscopy, that membranes become attached selectively to the growing plus ends of microtubules by membrane/microtubule tip attachment complexes (TACs) in interphase- arrested, undiluted, Xenopus egg extracts. Persistent plus end growth of stationary microtubules pushed the membranes into thin tubules and dragged them through the cytoplasm at the approximately 20 microns/min velocity typical of free plus ends. Membrane tubules also remained attached to plus ends when they switched to the shortening phase of dynamic instability at velocities typical of free ends, 50-60 microns/min. Over time, the membrane tubules contacted and fused with one another along their lengths, forming a polygonal network much like the distribution of ER in cells. Several components of the membrane networks formed by TACs were identified as ER by immunofluorescent staining using antibodies to ER-resident proteins. TAC motility was not inhibited by known inhibitors of microtubule motor activity, including 5 mM AMP-PNP, 250 microM orthovanadate, and ATP depletion. These results show that membrane/microtubule TACs enable polymerizing ends to push and depolymerizing ends to pull membranes into thin tubular extensions and networks at fast velocities.
Development of a Smartphone Application to Measure Physical Activity Using Sensor-Assisted Self-Report

Introduction: Despite the known advantages of objective physical activity monitors (e.g., accelerometers), these devices have high rates of non-wear, which leads to missing data. Objective activity monitors are also unable to capture valuable contextual information about behavior. Adolescents recruited into physical activity surveillance and intervention studies will increasingly have smartphones, which are miniature computers with built-in motion sensors. Methods: This paper describes the design and development of a smartphone application (“app”) called Mobile Teen that combines objective and self-report assessment strategies through (1) sensor-informed context-sensitive ecological momentary assessment (CS-EMA) and (2) sensor-assisted end-of-day recall. Results: The Mobile Teen app uses the mobile phone’s built-in motion sensor to automatically detect likely bouts of phone non-wear, sedentary behavior, and physical activity. The app then uses transitions between these inferred states to trigger CS-EMA self-report surveys measuring the type, purpose, and context of activity in real-time. The end of the day recall component of the Mobile Teen app allows users to interactively review and label their own physical activity data each evening using visual cues from automatically detected major activity transitions from the phone’s built-in motion sensors. Major activity transitions are identified by the app, which cues the user to label that “chunk,” or period, of time using activity categories. Conclusion: Sensor-driven CS-EMA and end-of-day recall smartphone apps can be used to augment physical activity data collected by objective activity monitors, filling in gaps during non-wear bouts and providing additional real-time data on environmental, social, and emotional correlates of behavior. Smartphone apps such as these have potential for affordable deployment in large-scale epidemiological and intervention studies.
Comparison of BTA stat and NMP22 Tests in the Detection of Bladder Cancer

Objective: This study aimed to compare the BTA (bladder tumour antigen) stat and urinary nuclear matrix protein (NMP22) test s in the detection of bladder cancer. Material and methods: The office-based qualitative BTA stat and the laboratory-based quantitative NMP22 tests were studied in the same urine samples obtained from 49 patients with a high suspicion of bladder cancer and 20 healthy subjects. Results: A tumour was identified in 36 patients after the cystoscopy. BTA stat demonstrated a sensitivity of 89%, which was superior to the sensitivity of 66.6% with the NMP22 test in detecting the bladder cancer (p < 0.02). The sensitivities for grade I tumours with BTA stat and NMP22 were 55.5% and 33.3%, respectively. The sensitivity of BTA stat was 100% for tumour categories except for the pTa and grade I tumours. No positive result was observed with both tests among the healthy subjects. The specificities for BTA stat and NMP22 were 78.7% and 69.6%, respectively. Conclusions: The BTA stat test was significantly more sensitive than the NMP22 test in the detection of bladder cancer. Although the sensitivity of BTA stat was not sufficient to replace cystoscopy, its ease and low cost may play a role in reducing the number of control cystoscopies, especially in patients with low risk of progression.
Neighborhood characteristics and change in depressive symptoms among older residents of New York City.

OBJECTIVES We investigated the relationship between the depressive symptoms of older adults over time and the characteristics of the neighborhoods in which they live. METHODS We surveyed a random sample of 1325 New York City residents aged 50 years or older in 2005 and conducted 808 follow-up interviews in 2007. We assessed the compositional characteristics of the respondents' neighborhoods at a census-tract level and determined the relationships between these characteristics and changes in respondents' depressive symptoms. RESULTS In multivariable models that adjusted for individual-level covariates including income, a range of neighborhood characteristics predicted worsening depressive symptoms. Factor analysis suggested that these characteristics operated in 3 clusters: neighborhood socioeconomic influences, residential stability, and racial/ethnic composition, with positive neighborhood socioeconomic influences being significantly protective against worsening symptoms. Life stressors, personality trait neuroticism, African American race, and daily baseline contact with social networks were also associated with worsening symptoms. CONCLUSIONS An older adult's neighborhood of residence is an important determinant of his or her mental health. Those making efforts to improve mental health among the elderly need to consider the role of residential context in improving or impairing mental health.
Activating HER2 mutations in HER2 gene amplification negative breast cancer.

UNLABELLED Data from 8 breast cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking HER2 gene amplification. To determine the phenotype of these mutations, we functionally characterized 13 HER2 mutations using in vitro kinase assays, protein structure analysis, cell culture, and xenograft experiments. Seven of these mutations are activating mutations, including G309A, D769H, D769Y, V777L, P780ins, V842I, and R896C. HER2 in-frame deletion 755-759, which is homologous to EGF receptor (EGFR) exon 19 in-frame deletions, had a neomorphic phenotype with increased phosphorylation of EGFR or HER3. L755S produced lapatinib resistance, but was not an activating mutation in our experimental systems. All of these mutations were sensitive to the irreversible kinase inhibitor, neratinib. These findings show that HER2 somatic mutation is an alternative mechanism to activate HER2 in breast cancer and they validate HER2 somatic mutations as drug targets for breast cancer treatment. SIGNIFICANCE We show that the majority of HER2 somatic mutations in breast cancer patients are activating mutations that likely drive tumorigenesis. Several patients had mutations that are resistant to the reversible HER2 inhibitor lapatinib, but are sensitive to the irreversible HER2 inhibitor, neratinib. Our results suggest that patients with HER2 mutation–positive breast cancers could benefit from existing HER2-targeted drugs.
Targeted molecular therapy of anaplastic thyroid carcinoma with AEE788

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies with a mean survival of only 6 months. The poor prognosis of patients with ATC reflects the current lack of curative therapeutic options and the need for development of novel therapeutic strategies. In this study, we report the results of a preclinical study of AEE788, a dual inhibitor of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, against ATC. AEE788 was able to inhibit the proliferation and induce apoptosis of ATC cell lines in vitro. Administration of AEE788, alone and in combination with paclitaxel, to athymic nude mice bearing s.c. ATC xenografts inhibited the growth of ATC xenografts by 44% and 69%, respectively, compared with the control group. Furthermore, tumors from mice treated with AEE788, alone and in combination with paclitaxel, showed increase in apoptosis of tumor cells by ∼6- and 8-fold, respectively, compared with the control group. The microvessel density within the ATC xenografts was decreased by >80% in the mice treated with AEE788 alone and in combination with paclitaxel compared with the control group. Lastly, immunofluorescence microscopy showed the inhibition of EGFR autophosphorylation on the tumor cells as well as the inhibition of VEGFR-2 autophosphorylation on tumor endothelium. Considering the fact that curative options seldom exist for patients with ATC, concurrent inhibition of EGFR and VEGFR tyrosine kinases seems to be a valid and promising anticancer strategy for these patients.
EnHTM: Exploiting Hardware Transaction Memory for Achieving Low-Cost Fault Tolerance

Fault-tolerance has become an essential concern for processor designers due to increasing transient fault rates, even for the processors used in the mainstream computing. As the mainstream commodity market accepts only low-cost fault tolerance solutions, traditional high-end solutions are unacceptable due to their expensive overheads. This paper presents EnHTM, a hybrid software/hardware implemented low-cost fault tolerance solution for the serial programs running on commodity systems. EnHTM employs light-weight symptom-based mechanism to detect faults and recovers from faults using a minimally-modified Hardware Transactional Memory (HTM) which features lazy conflict detection, lazy data versioning. Compile-time analysis approach is also exploited to support larger transaction size, so that transient faults detected within long latency can be recovered. The evaluation experiment result shows that EnHTM can recover from 89.4%of catastrophic failures caused by transient faults, with a performance overhead of 2.6% in error-free executions on average.
Serum concentrations of IGF‐I, IGFBP‐3 and c‐peptide and risk of hyperplasia and cancer of the breast in postmenopausal women

Experimental evidence suggests that insulin and insulin‐related growth factors may play a role in breast pathology through their mitogenic and anti‐apoptotic effects on breast cells. Our objective was to assess the relationship between serum concentrations of insulin‐like growth factor‐I (IGF‐I), its major binding protein (IGFBP‐3), the ratio IGF‐I:IGFBP‐3, c‐peptide (a marker of insulin secretion) and the ratio c‐peptide:fructosamine (a marker of insulin resistance) and the risk of epithelial hyperplasia (an established breast cancer risk factor) and localized breast cancer among postmenopausal women. Study subjects were patients who provided serum before breast biopsy or mastectomy in 3 hospitals in Grand Rapids, MI between 1977 and 1987. Two case groups, 186 subjects with epithelial hyperplasia of the breast and 185 subjects with localized breast cancer, were compared to 159 subjects with nonproliferative breast changes that have not been associated with increased breast cancer risk. Serum concentrations of IGF‐I, IGFBP‐3 and the ratio IGF‐I:IGFBP‐3 were not related to risk of either hyperplasia or breast cancer. For women in the highest quartile of c‐peptide or of c‐peptide:fructosamine compared to those in the lowest quartile, the odds ratios (ORs) for hyperplasia were 3.0 (95% confidence interval [CI] 1.4–6.5) and 3.3 (95% CI 1.5–7.3), respectively (p trend = 0.02 and 0.02, respectively). The corresponding ORs for breast cancer were 1.5 (95% CI 0.7–3.0) and 1.6 (95% CI 0.8–3.2), respectively (p trend = 0.35 and 0.25, respectively). Our results suggest that insulin and insulin resistance may play a role in breast pathology in postmenopausal women. © 2003 Wiley‐Liss, Inc.
Oral Contraceptives Abolish Luteal Phase Exacerbation of Hyperglycemia in Type I Diabetes

For some time it has been recognized that postovulatory exacerbation of hyperglycemia contributes to the instability of diabetes in many women of reproductive age. It has been suggested that increasing plasma levels of progesterone and estrogen may induce insulin resistance and consequently lead to increased hyperglycemia during the luteal phase of the menstrual cycle. Due to the fact that menstrual cycles in a given woman may vary in length and that it takes patients several days on intermediate or long-acting insulin to achieve a steady state with regard to any dosage adjustment, it is difficult to design an insulin regimen that maintains euglycemia throughout the menstrual cycle in these labile patients. Recognition of this problem led to trying a nonsequential low estrogen contraceptive as adjunctive therapy in a 20-year old woman with insulin dependent diabetes mellitus. The patient consistently suffered an exacerbation of hyperglycemia after ovulation in each cycle, lasting until the onset of menses. On 1 occasion the patient developed frank diabetic ketoacidosis. For the first 2 cycles on Lo Ovral, the hyperglycemia was postponed from the 1st postovulatory day until day 18-19 of the cycle. It was reasoned that the serum estrogen and/or progestin level might be building cumulatively, and the oral contraceptives (OCs) were subsequently withdrawn at day 19 of the cycle rather than day 21. A maximum blood glucose level of 400 mg/dl was attained at day 19 and was treated with additional regular insulin. Levels in excess of 240 mg/dl did not recur during that cycle. The following cycle OC therapy was interrupted at day 18; no blood glucose level in excess of 240 mg/dl occurred that month. Hemoglobin A1c fell from a pre-OC treatment value of 12.4% to the current A1c of 9.7%. A modest increase in blood pressure has occurred, but this is easily managed with a 2 g sodium diet and 25 mg of hydrochlorothiazide daily. On the basis of this experience, a controlled trial is warranted of low dose estrogen nonsequential OCs in lean, nonsmoking, 18-30 year old women with insulin dependent diabetes mellitus with postovulatory hyperglycemia.
Predictors and prognosis of stent fracture after sirolimus-eluting stent implantation.

BACKGROUND Stent fracture is a cause of in-stent restenosis (ISR) after sirolimus-eluting stent (SES) implantation, so this study investigated the incidence, predictors and prognosis of stent fracture. METHODS AND RESULTS The 273 consecutive patients (364 lesions) after SES implantation and who had 6-9 month' scheduled follow-up coronary angiography (CAG) were divided into groups with and without stent fracture. Deltaangle was defined as the difference in the angle in the target lesion between diastole and systole before the procedure. The incidence of stent fracture was 4.9% (18 of 364 lesions). Deltaangle in the target lesion was larger in the fracture group (28.3 +/-11.5 degrees vs 12.3 +/-9.0 degrees , P<0.0001). Independent predictors of stent fracture were Deltaangle and total stent length. The rates of binary restenosis and target lesion revascularization (TLR) were higher in the fracture group (33% vs 4.0%, P=0.0002 and 28% vs 3.5%, P=0.0007, respectively). There were no major adverse cardiac events (MACE) in the fracture group during a mean 24-month follow-up after follow-up CAG. CONCLUSIONS Predictors of stent fracture were Deltaangle and total stent length. Although stent fracture was associated with ISR and TLR, it was not associated with MACE during long-term follow-up.
IBM Research Australia at LifeCLEF2014: Plant Identification Task

In this paper, we present the system and learning strategies that were applied by the IBM Research team to the plant identication task of LifeCLEF 2014. Plant identication is one of the most popular ne-grained categorization tasks. To ensure high classication accuracy, we have utilised strong visual features together with fusion of robust machine learning techniques. Our proposed system involves automatic delineation of the region of interest (e.g. plant's leaf, ower, etc.) in the given image, followed by extracting multiple complementary low level features. The features have been then encoded into the sophisticated Fisher Vector representation which enables accurate classication with
A randomized clinical trial comparing safety, clinical and parasitological response to artemether-lumefantrine and chlorproguanil-dapsone in treatment of uncomplicated malaria in pregnancy in Mulago hospital, Uganda.

BACKGROUND Malaria infection during pregnancy is a major public health problem. Due to increasing resistance to Chloroquine and Sulphadoxine/Pyrimethamine, the Ugandan national policy on malaria treatment was changed in 2005 to Artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. The policy recommends assessment of safety and efficacy of alternative drugs for treatment of uncomplicated malaria. We compared the efficacy and safety of Artemether-Lumefantrine (Coartem) and Chlorproguanil-Dapsone (Lapdap) in the management of uncomplicated malaria in pregnancy. METHODOLOGY We enrolled 110 pregnant women in the second and third trimester of pregnancy who presented to Mulago hospital, Uganda, with uncomplicated malaria. The study design was an open-label randomized clinical trial. Participants were randomized to receive either Artemether-Lumefantrine (Coartem 20 mg/120 mg) orally or Chlorproguanil-Dapsone (Lapdap) orally for 3 consecutive days. Primary endpoints were clinical and parasitological response assessed on days 0, 1, 2, 4, 7, 14 and 28. Adverse effects, clinical response (treatment failure) and parasitological response were compared. Analysis was by intention to treat. RESULTS Of the 100 women who completed the study, there was no statistically significant difference in clinical and parasitological response by Day 4. The mean fever clearance time 3.0 days with Lapdap versus 2.5 days with Coartem was comparable. Likewise, mean parasite clearance time of 2.4 and 2.2 days for Lapdap and Coartem respectively was comparable. The adverse effects were comparable between the two groups. CONCLUSION Artemether-Lumefantrine and Chlorproguanil-Dapsone have high and comparable cure rates and similar safety profiles when used for treatment of uncomplicated malaria in pregnancy.
Peningkatan Kualitas Pakan dan Perbaikan Manajemen Produksi di PeternakanSapi Potong Bago Mulyo, KecamatanGumuk MasKabupaten Jember

Limbah kulit edamame adalah salah satu sumber bahan pakan lokal asal limbah industri pertanian yang sangat potensial dan memberikan pula peluang besar dalam pengembangan bidang usaha peternakan ruminansia. Peluang tersebut dibidik oleh Kelompok Ternak Bago Mulyo selaku mitra melalui usaha penggemukan sapi potong. Namun demikian, hal tersebut terkendala oleh kondisi limbah kulit edamame yang sangat basah akibat proses pengolahan.Kondisi tersebut menyebabkan terjadinya pembusukan limbah kulit edamame dengan sangat cepat sehingga kualitasnya pun menurun, daya simpan berkurang, menurunkan nilai potensi dan ekonomisnya. Dampak negatif selanjutnya berupa penurunan produktivitas ternak menyebabkan kerugian pada peternak pengguna limbah kulit edamame yangsalah satunya adalah mitra. Solusi untuk menangani permasalahan tersebut adalah penerapan teknologi berupa peningkatan kualitas pakan berbasis limbah kulit edamame melalui aplikasi silase ransum komplit. Solusi tersebut diimplementasikan melalui kegiatan pengabdian kepada masyarakat dengan judul “Peningkatan Kualitas Pakan dan Perbaikan Manajemen Produksi di Peternakan Sapi Potong Bago Mulyo, Kecamatan Gumuk Mas Kabupaten Jember”. Pelaksanaan kegiatan dimulai pada Juli hingga November 2018 dan bertempat di Kelompok Ternak Bago Mulyo, Desa Bagorejo, Kecamatan Gumuk Mas, Kabupaten Jember. Seluruh kegiatan pengabdian kepada masyarakat yang terbagi menjadi tahap persiapan dan pemantapan, penyuluhan, koordinasi untuk pelatihan, pelatihan dan evaluasi kegiatan. Tim pelaksana dengan mitra mampu berkoordinasi dengan baik sehingga seluruh kegiatan dapat terakomodir dan berjalan dengan lancar. Mitra sangat antusias dalam mengikuti seluruh kegiatan dan banyak terjadi komunikasi 2 arah berupa diskusi-diskusi terkait teknologi penyimpanan maupun pengolahan pakan, formulasi dan pembuatan ransum komplit serta manajemen produksi melalui konsep efisiensi biaya, waktu dan tenaga dalam menjalankan peternakan sapi potong. Melalui kegiatan pengabdian ini, terjadi peningkatan kualitas pakan berbasis limbah kulit edamame dan perbaikan manajemen produksi pada peternakan sapi potong yang dikelola oleh mitra secara tidak langsung dan belum sepenuhnya terlihat nyata. Namun demikian, terjadi efektivitas proses dan efisiensi waktu, ruang, tenaga, maupun biaya dalam usaha penggemukan sapi potong yang dijalani. Aplikasi teknologi sederhana dapat menimbulkan dampak yang cukup besar dan sangat membantu mitra dalam proses usaha penggemukan sapi