Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Systems Biology Peer Review Process File Division of Labor by Dual Feedback Regulators Controls Jak2/stat5 Signaling over Broad Ligand Range Transaction Report

(Note: With the exception of the correction of typographical or spelling errors that could be a source of ambiguity, letters and reports are not edited. The original formatting of letters and referee reports may not be reflected in this compilation.) Thank you again for submitting your work to Molecular Systems Biology. We have now heard back from the three referees whom we asked to evaluate your manuscript. As you will see from the reports below, the referees find the topic of your study of potential interest. However, they raise substantial concerns on your work, which should be addressed in a major revision of the present work. The reviewers recognize the quality of the experimental work and the careful description of the model. However, they also express some important concerns with regard to the following points:-the physiological relevance of the postulated concerted roles of CIS and SOCS in controlling STAT5 over a broad range of Epo concentrations remains unclear. -the correlation between dynamical features of the system and apoptosis should be explored more systematically (reviewer #2 recommends PCA) rather than be restricted to the integral npSTAT response only. -some important discrepancies between model and experimental measurements should be clarified. NOTE: in addition to our capacity to host datasets in our supplementary in formation section, we provide a new functionality on our website, which allows readers to directly download the 'source data' associated with selected figure panels (eg <http://tinyurl.com/365zpej>), for the purpose of alternative visualization, re-analysis or integration with other data. These files are separate from the traditional supplementary information files and are directly linked to specific figure panels. In the case of this study, we would strongly encourage you to submit the relevant data files for the quantitative data displayed in the figures of this study. We provide below some general guidelines with regard to the format of such data tables.
Joint Optimization of Altitude and Transmission Direction in UAV-Based Two-Way Communication

Unmanned aerial vehicles (UAVs) can be used as flying base stations. When one-way communication is considered, either uplink or downlink, the system performance is limited by the strong co-channel interference that takes place over the UAV-ground channel. This letter considers two-way communication and takes advantage of the fact that the interference over ground–ground channel is likely lower than the one over the UAV-ground channel. This sets the stage for joint optimization of the user association, UAV altitude, and transmission direction, which is shown to lead to improved system throughput for a given known placement of the ground devices.
sclerosis Huntington ’ s disease Multiple sclerosis Spinal cord injuries Glaucoma / corneal injuries Diabetes Obesity Remyelination strategies Cancer Organ transplantation Immune system modulation Wound healing Cosmetic industry Maturation Survival Potential applications

Correspondence: Satish Srinivas Kitambi Department of Medical Biochemistry and Biophysics, Division of Molecular Neurobiology, Scheeles Väg 2, Karolinska Institutet, Stockholm, Sweden 17177 Tel +46 8 5248 7659 Fax +46 8 341 960 Email satish.kitambi@ki.se Abstract: The identification of normal and cancerous stem cells and the recent advances made in isolation and culture of stem cells have rapidly gained attention in the field of drug discovery and regenerative medicine. The prospect of performing screens aimed at proliferation, directed differentiation, and toxicity and efficacy studies using stem cells offers a reliable platform for the drug discovery process. Advances made in the generation of induced pluripotent stem cells from normal or diseased tissue serves as a platform to perform drug screens aimed at developing cell-based therapies against conditions like Parkinson’s disease and diabetes. This review discusses the application of stem cells and cancer stem cells in drug screening and their role in complementing, reducing, and replacing animal testing. In addition to this, target identification and major advances in the field of personalized medicine using induced pluripotent cells are also discussed.
Why formation rate of 3 nm particles depends linearly on sulphuric acid concentration

According to atmospheric observations new particle formation seems to be a function of sulphuric acid concentration to the power from one to two. The nucleation theorem then predicts that the critical cluster contains one to two sulphuric acid molecules. However, existing nucleation theories predicts that the power is more (or equal) than 5 2. Here we present an activation theory, which can explain the observed slope. In cluster activation the clusters containing one sulphuric acid molecule will activate for further growth due to heterogeneous nucleation, heterogeneous chemical reactions including polymerization or activation of soluble clusters. In the activation process organic vapours are typically needed as condensing agents. 10
Design, Synthesis and Anticonvulsant Activity of the Potent Adenosine Kinase Inhibitor GP3269

Abstract The pyrrolopyrimidine nucleoside GP3269 (12) was shown to be a potent and selective inhibitor of human adenosine kinase (IC50 = 11 nM) and to exhibit anticonvulsant activity in rats after oral administration. Synthesis of GP3269 was accomplished in 4 steps from 4-chloro-5-iodopyrrolopyrimidine (9) and the protected 5-deoxy-1-α-chlororibose (8) using a base-catalyzed nucleoside coupling reaction and the Suzuki reaction to replace the 5-iodo substituent with phenyl.
Calcium and Integrin Binding Protein 1 (CIB1) Induces Myocardial Fibrosis in Myocardial Infarction via Regulating the PI3K/Akt Pathway RUNNING TITLE: CIB1 INVOLVES IN MYOCARDIAL INFARCTION

Myocardial infarction (MI) is a severe coronary artery disease resulted from substantial and sustained ischemia. Abnormal upregulation of calcium and integrin binding protein 1 (CIB1) has been found in several cardiovascular diseases. In this study, we established a mouse model of MI by permanent ligation of the left anterior descending coronary artery. CIB1 was upregulated in the heart of MI mice. Notably, CIB1 knockdown by intramuscular injection of lentivirus-mediated short hairpin RNA (shRNA) targeting Cib1 improved cardiac function and attenuated myocardial hypertrophy and infarct area in MI mice. MI-induced upregulation of α-SMA, vimentin, Collagen I, and Collagen III, which resulted in collagen production and myocardial fibrosis, were regressed by CIB1 silencing. In vitro , cardiac fibroblasts (CFs) isolated from mice were subjected to angiotensin II (Ang II) treatment. Inhibition of CIB1 downregulated the expression of α-SMA, vimentin, Collagen I, and Collagen III in Ang II-treated CFs. Moreover, CIB1 knockdown inhibited Ang II-induced phosphorylation of PI3K-p85 and Akt in CFs. The effect of CIB1 knockdown on Ang II-induced cellular injury was comparable to that of LY294002, a specific inhibitor of the PI3K/Akt pathway. We demonstrated that MI-induced cardiac hypertrophy, myocardial fibrosis, and cardiac dysfunction might be attributed to the upregulation of CIB1 in MI mice. Downregulation of CIB1 alleviated myocardial fibrosis and cardiac dysfunction by decreasing the expression of α-SMA, vimentin, Collagen I, and Collagen III via inhibiting the PI3K/Akt pathway. Therefore, CIB1 may be a potential target for MI treatment.
Pleura and Peritoneum

The peritoneum consists of a layer of mesothelial cells on a connective tissue base which is perfused with circulatory and lymphatic vessels. Total effective blood flow to the human peritoneum is estimated between 60 and 100 mL/min, representing 1–2% of the cardiac outflow. The parietal peritoneum accounts for about 30% of the peritoneal surface (anterior abdominal wall 4%) and is vascularized from the circumflex, iliac, lumbar, intercostal, and epigastric arteries, giving rise to a quadrangular network of large, parallel blood vessels and their perpendicular offshoots. Parietal vessels drain into the inferior vena cava. The visceral peritoneum accounts for 70% of the peritoneal surface and derives its blood supply from the three major arteries that supply the splanchnic organs, celiac and superior and inferior mesenteric. These vessels give rise to smaller arteries that anastomose extensively. The visceral peritoneum drains into the portal vein. Drugs absorbed are subject to firstpass hepatic metabolism. Peritoneal inflammation and cancer invasion induce neoangiogenesis, leading to the development of an important microvascular network. Anatomy of neovessels is abnormal and characterized by large size, varying diameter, convolution and blood extravasation. Neovessels have a defective ultrastructure: formation of large “mother vessels” requires degradation of venular and capillary basement membranes. Mother vessels give birth to numerous “daughter vessels”. Diffuse neoangiogenesis can be observed before appearance of macroscopic peritoneal metastasis. Multiplication of the peritoneal capillary surface by neoangiogenesis surface increases the part of cardiac outflow directed to the peritoneum.
Chemical Composition and Bioactivity of Salvadora persica Extracts against Some Potato Bacterial Pathogens

Potent antibacterial activities of solvent extracts (methanol:n-hexane) from the branch, leaf, and root-wood of Salvadora persica were examined against potato phytopathogenic bacteria, namely Pectobacterium carotovorum subsp. carotovorum, Dickeya solani, Ralostonia solanacerum, Enterobacter cloacae, and Bacillus pumilus. The main chemical constituents analyzed by gas chromatography–mass spectrometry (GC/MS) in the branch extracts were N-benzylbenzamide (71.08%), decane (3.17%), stigmasterol (3.17%), 9-desoxo-9-x-acetoxy-3,8,12-tri-O-acetylingol (2.33%), and β-sitosterol (2.15%). The main components in the leaf extracts were 2,6-dimethyl-N-(2-methyl-α-phenylbenzyl)aniline (28.65%), spiculesporic acid (13.60%), homo-γ-linolenic acid (12.63%), and methyl hexadecanoate (11.01%). The root-wood extracts contained, as primary parts, benzeneacetonitrile (71.47%), 4-aminocarbonyl-5-fluoro-1-α-D-ribofuranosyl-imidazole (10.99%), and benzylisothiocyanate (5.05%). The extracts from the root-wood showed moderate antibacterial activity against the potato bacterial pathogens, which was followed by leaf and branch extracts. The results suggested that S. persica plant extracts could be used as bioagents against potato soft and brown rot bacterial pathogens.
Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: a gynecologic oncology group study.

PURPOSE To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer. PATIENTS AND METHODS Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed. RESULTS In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%). CONCLUSION Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.
Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation

The gene expression pattern specified by an animal regulatory sequence is generally viewed as arising from the particular arrangement of transcription factor binding sites it contains. However, we demonstrate here that regulatory sequences whose binding sites have been almost completely rearranged can still produce identical outputs. We sequenced the even-skipped locus from six species of scavenger flies (Sepsidae) that are highly diverged from the model species Drosophila melanogaster, but share its basic patterns of developmental gene expression. Although there is little sequence similarity between the sepsid eve enhancers and their well-characterized D. melanogaster counterparts, the sepsid and Drosophila enhancers drive nearly identical expression patterns in transgenic D. melanogaster embryos. We conclude that the molecular machinery that connects regulatory sequences to the transcription apparatus is more flexible than previously appreciated. In exploring this diverse collection of sequences to identify the shared features that account for their similar functions, we found a small number of short (20–30 bp) sequences nearly perfectly conserved among the species. These highly conserved sequences are strongly enriched for pairs of overlapping or adjacent binding sites. Together, these observations suggest that the local arrangement of binding sites relative to each other is more important than their overall arrangement into larger units of cis-regulatory function.
Transforming Growth Factor- (cid:1) Inhibits Pulmonary Surfactant Protein B Gene Transcription through SMAD3 Interactions with NKX2.1 and HNF-3 Transcription Factors*

Transforming growth factor- (cid:1) (TGF- (cid:1) ) represses surfactant protein B ( Sp-B ) gene transcription through a mechanism that remains unknown. A homeodomain and a forkhead transcription factor, NKX2.1 and HNF-3, re-spectively, are known activators of Sp-B transcription. Because SMADs are the effectors of TGF- (cid:1)(cid:2) induced gene activation, we examined the possibility that gene repression by TGF- (cid:1) may also occur through interactions of SMADs with NKX2.1 and HNF-3. We found that lung epithelial carcinoma H441 cells contain SMAD2/3 and -4, which localize to the nucleus in response to TGF- (cid:1) treatment. The activity of a transfected Sp-B pro-moter/reporter construct was reduced in a dose-depend-ent manner by TGF- (cid:1) . Cotransfection with a mutant, constitutively activated form of the Tgf- (cid:1) type I receptor repressed Sp-B promoter activity in the absence of TGF- (cid:1) ligand. Dominant negative mutants of Smads blocked the repressor activity of Assays— The human pulmo- nary epithelial cell lines NCI H441 and A549 (ATCC) and human cervical carcinoma cell line HeLa (ATCC) were maintained in RPMI medium 1640, F-12K nutrient mixture, and Dulbecco’s modified Eagle’s medium (Invitrogen), respectively, containing 10% fetal bovine serum and 1% penicillin-streptomycin. The mouse MLE15 cells were grown in culture according to the procedure described previously (27). All plas- mids used in transfection studies were purified on Qiagen columns (Qiagen). Transient transfection of H441 cells, A549 cells, and HeLa cells was performed with SuperFect or FuGENE 6 as described by the manufacturer (Qiagen and Roche Molecular Biochemicals). In brief, cells in 35-mm dishes at 60–80% confluence were transfected with 2.25 (cid:2) g of pSV- (cid:1) - gal (Promega), 2.25 (cid:2) g of test constructs, 2.25 (cid:2) g of trans-activator plasmids, and 15 (cid:2) l of transfectant. Cells were cultured for 6 h and then changed into regular medium with 10% serum. Cells were cultured for an additional 42 h in the presence or absence of human recombinant TGF- (cid:1) 1 (R&D Systems) and collected as described (Pro-mega). Supernatants of the cell extracts were used for the assay of (cid:1) -galactosidase and either chloramphenicol acetyltransferase or luciferase as described (Ref. 28; Promega). Plasmid Construction and Site-directed Mutagenesis— A 1.4-kilobase fragment of the human Sp-B promoter region ( (cid:1) 1040/ (cid:3) 431) (29) was cloned into pGL2 basic (Promega) and named SpB ( (cid:1) 1040/ (cid:3) 431 ). The fragment –140/ (cid:3) 431
The leukemogenic t ( 8 ; 21 ) fusion protein AML 1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes

The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes" (2008). Cell and Developmental Biology Publications and Presentations. 80. Introduction The most frequent target of chromosomal translocations in acute myeloid leukemia (AML) is the Runt-related transcription factor RUNX1/AML1, a key regulator of hematopoiesis (Setoguchi et al. directly regulates multiple distinct myeloid and lymphoid genes that are involved in hematopoietic lineage commitment (Huang et al. The protein contains an N-terminal DNA-binding domain (runt-homology domain) and a C-terminal regulatory domain that contains a nuclear-matrix-targeting signal (NMTS) and several context-dependent transcriptional activation or repression domains (Wheeler et al. Peterson et al., 2007a). AML1-ETO retains the DNA-binding function of the RUNX1/AML1 protein but does not contain the transactivation domain or the nuclear-matrix-targeting signal (NMTS) of RUNX1/AML1 (Zeng et al., 1997; McNeil et al., 1999). Previous studies have shown that exogenously expressed RUNX1/AML1 and AML1-ETO exhibit differential subnuclear targeting, which might be responsible in part for the aberrant function of the fusion protein (McNeil et al., 1999; Barseguian et
Proximal Mappings

We study differentiability properties and subdifferentiability properties of the Baire approximate and of the Moreau? Yosida approximate of a nonconvex function on a Banach space. These properties are intimately linked with exactness of the infimal convolution defining the approximation. When applied to indicator functions of possibly nonconvex subsets, our results yield existence of best approximations under subdifferentiability assumptions on the distance function and suitable smoothness assumptions on the space.
Efficacy and Safety of Biphasic Insulin Aspart 30/70 in Type 2 Diabetes Suboptimally Controlled on Oral Antidiabetic Therapy in Korea: A Multicenter, Open-Label, Single-Arm Study

Background The purpose of this study was to evaluate change in glycosylated hemoglobin (HbA1c), side effects, and quality of life (QOL) after a 16-week treatment period with Biphasic insulin aspart 30/70 (BIasp30) in patients with type 2 diabetes mellitus (T2DM) who had been suboptimally controlled with oral antidiabetic drugs (OADs). Methods The study consisted of a 4-week titration period when concurrent OAD(s) were replaced with BIasp30 and followed by a 12-week maintenance period. All patients completed the Diabetes Treatment Satisfaction Questionnaire at the beginning and the end of the trial. Hypoglycemic episodes were recorded by the patient throughout the trial. Results Sixty patients were included, of whom 55 patients (92%) completed the full 16-week treatment period. Seven-point blood glucose was significantly improved as compared with the baseline, except for the postlunch blood glucose level. HbA1c at the end of period was significantly improved from 9.2% to 8.2% (P<0.001). Eleven percent (n=6) of patients achieved HbA1c values ≤6.5% and 22% (n=12) of patients achieved <7.0%. There were 3.4 episodes/patients-year of minor hypoglycemia and 0.05 episodes/patients-year of major hypoglycemia. QOL showed significant changes only in the acceptability of high blood glucose category (P=0.003). Conclusion Treatment with once or twice daily BIasp30 may be an option for the patients with T2DM suboptimally controlled with OADs in Korea. However, considering the low number of patients achieving the HbA1c target and the high postlunch blood glucose levels, additional management with another modality may be required for optimal control.
Geometrical design of fractional PDμ controllers for linear time-invariant fractional-order systems with time delay

This article presents a simple procedure that allows a practical design of fractional – PD μ controllers for single-input single-output linear time-invariant fractional-order systems subject to a constant time delay. The methodology is based on a geometric approach, which provides practical guidelines to design stabilizing and non-fragile PDμ controllers. The simplicity of the proposed approach is illustrated by considering several numerical examples encountered in the control literature. Moreover, with the aim of showing the performance of the PDμ over a classical PD controller, both controllers were implemented at the end of the article in an experimental test-bench consisting a teleoperated robotic system.
Final response : Factors controlling Slope Environmental Lapse Rate ( SELR ) of temperature in the monsoon and cold-arid glacio-hydrological regimes of the Himalaya by Thayyen and

C1: We know very few information about the observational data used in this study. This paper cannot be published without more details on how are measured precipitation, temperature and moisture. The author should also detail the uncertainties associated with these observations. Does observations come from a specific Indian network? Or is this observational data collected specifically for this study? In addition, you should explain the possible uncertainties associated with this data, in particular those related to the difficulty to measure snowfall with rain gauges. Please refer to previous papers dealing with observational and modelling approaches showing that precipitation is potentially under-estimated in high altitude areas (e.g. Palazzi et al., 2013, Dimri et al. 2013). Ménégoz et al. (2013) estimated that that more than half of the total annual precipitation occurs as snowfall on average over a region located higher than 2500 m. a.s. l. at the border between Nepal and India. Shrestha et al. (2012) strongly corrected local measurements of precipitation considering snow depth and snow albedo measurements.
Geochronological Evidence of Pan-African Eclogites from the Central Menderes Massif, Turkey

The Menderes Massif in western Anatolia documents a complex geodynamic history from Precambrian to recent. Eclogitic relics found in metagabbros in the Precambrian basement were dated by the U/Pb method. The zircon age data from granulitic (coronitic) and eclogitic metagabbros is consistent with geological constraints as well as relative and radiometric ages of the host granulitic gneisses and augen gneisses. A Pan-African intrusion age (540 Ma) of the metagabbros and a shortly later eclogite facies event (530 Ma) are inferred. This scenario fits with the geodynamic evolution deduced form the acidic country rocks of the eclogitic metagabbros. Direct links between the Menderes Massif and Mozambique belt are obliterated by Alpine deformation. Nevertheless, the tectonic setting and age of the Menderes eclogites support a terminal collision of East and West Gondwana and the final suturing of the Mozambique Ocean during the Early Cambrian.
Television Coverage of the Middle East

This volume brings together original analyses about how the Middle East is depicted on U.S. television news. It analyzes some of the most intensely reported news stories of the past decade. Its revealing studies also show how broadcasting on Middle Ease issues has changed in recent years. These studies offer important and provocative findings regarding crucual issues in Middle East coverage.