Miracle-dz/UniFAR-FTUs huggingface dataset:
The JAK inhibitor tofacitinib regulates synovitis through inhibition of interferon-γ and interleukin-17 production by human CD4+ T cells.

OBJECTIVE Tofacitinib (CP-690,550) is a novel JAK inhibitor that is currently in clinical trials for the treatment of rheumatoid arthritis (RA). The aim of this study was to examine the effects of tofacitinib in vitro and in vivo in RA, in order to elucidate the role of JAK in the disease process. METHODS CD4+ T cells, CD14+ monocytes, and synovial fibroblasts (SFs) were purified from the synovium and peripheral blood of patients with RA and were evaluated for the effect of tofacitinib on cytokine production and cell proliferation. For in vivo analysis, synovium and cartilage samples obtained from patients with RA were implanted in immunodeficient mice (SCID-HuRAg mice), and tofacitinib was administered via an osmotic minipump. RESULTS Tofacitinib treatment of CD4+ T cells originating from synovium and peripheral blood inhibited the production of interleukin-17 (IL-17) and interferon-γ (IFNγ) in a dose-dependent manner, affecting both proliferation and transcription, but had no effect on IL-6 and IL-8 production. Tofacitinib did not affect IL-6 and IL-8 production by RASFs and CD14+ monocytes. However, conditioned medium from CD4+ T cells cultured with tofacitinib inhibited IL-6 production by RASFs and IL-8 production by CD14+ monocytes. Treatment of SCID-HuRAg mice with tofacitinib decreased serum levels of human IL-6 and IL-8 and markedly suppressed invasion of synovial tissue into cartilage. CONCLUSION Tofacitinib directly suppressed the production of IL-17 and IFNγ and the proliferation of CD4+ T cells, resulting in inhibition of IL-6 production by RASFs and IL-8 production by CD14+ cells and decreased cartilage destruction. In CD4+ T cells, presumably Th1 and Th17 cells, JAK plays a crucial role in RA synovitis.
Changes in Photosynthetic Capacity and Photosynthetic Protein Pattern during Tomato Fruit Ripening.

Levels of polypeptides participating in the photosynthetic light and dark reactions have been measured during fruit ripening in tomato. Photosynthetic proteins were identified by Western blot analysis with heterologous antibodies. The concentrations of proteins of photosystem (PS) I (14 kilodaltons), of PSII (47-kilodalton reaction center protein, 32-kilodalton ;Q(B) binding' protein and light harvesting complex proteins), of the photosynthetic electron transport chain (ferredoxin-NADP-oxidoreductase and plastocyanin), and of the stroma (ribulose-1,5-bisphosphate carboxylase) decrease during the ripening process. The 32-kilodalton protein and plastocyanin were detectable in pericarp protein preparations of ripe tomato fruits. Absorbance difference spectrophotometry provided information on the relative concentrations of PSII and PSI reaction centers in leaf and green fruit tissue of tomato. These results indicate that green fruit pericarp of tomato is photosynthetically active. Photosynthetic activity decreases during chloroplast/chromoplast differentiation. This is consistent with changes that occur at the transcript level of photosynthesis-specific proteins during the differentiation process.
Replicated population divergence caused by localized coevolution? A test of three hypotheses in the red crossbill‐lodgepole pine system

Several lines of evidence support the hypothesis that local populations of red crossbills (Loxia curvirostra complex) enter into a predator‐prey arms race with lodgepole pine (Pinus contorta latifolia) in the absence of competing pine squirrels (Tamiasciurus hudsonicus). Nevertheless, the alternative hypotheses that neutral evolution or factors other than squirrels have caused crossbill population differentiation have not been thoroughly tested. We compared crossbill and pine cone morphology between island populations where squirrels are absent or present, and mainland sites where squirrels are present, in order to distinguish among these hypotheses. All comparisons supported an effect of squirrel absence, not island status, on crossbill and cone morphology. Hence our results provide further evidence that strong localized coevolutionary interactions in a geographic mosaic have driven adaptive population differentiation. In addition, vocal differentiation of crossbills was related to the absence of squirrels, but not to island status. As morphological and vocal differentiation is correlated with reproductive isolation in crossbills, the geographic mosaic of coevolution also seems to promote ecological speciation.
Automating URL Blacklist Generation with Similarity Search Approach

SUMMARY Modern web users may encounter a browser security threat called drive-by-download attacks when surﬁng on the Internet. Drive-by-download attacks make use of exploit codes to take control of user’s web browser. Many web users do not take such underlying threats into account while clicking URLs. URL Blacklist is one of the practical approaches to thwarting browser-targeted attacks. However, URL Blacklist cannot cope with previously unseen malicious URLs. Therefore, to make a URL blacklist e ﬀ ective, it is crucial to keep the URLs updated. Given these observations, we propose a framework called automatic blacklist generator (AutoBLG) that automates the collection of new malicious URLs by starting from a given existing URL blacklist. The primary mechanism of AutoBLG is expanding the search space of web pages while reducing the amount of URLs to be analyzed by applying several pre-ﬁlters such as similarity search to accelerate the process of generating blacklists. AutoBLG consists of three primary components: URL expansion, URL ﬁltration, and URL veriﬁcation. Through extensive analysis using a high-performance web client honeypot, we demonstrate that AutoBLG can successfully discover new and previously unknown drive-by-download URLs from the vast web space. key words: drive-by-download, URL blacklist, search space, machine learning, web client honeypot
Relationship of Serum CA125 and Lipid-Associated Sialic Acid Tumor-Associated Antigen Levels to the Disease Status of Patients With Gynecologic Malignancies

Serum samples obtained from 133 patients with gynecologic malignancies were assayed for two tumor-associated antigen markers: CA125, an ovarian marker, and lipid-associated sialic acid, a nonspecific marker. In the patient population, there were 77 papillary serous and 19 unspecified ovarian adenocarcinomas, and 24 miscellaneous ovarian carcinomas. Thirteen patients had nonovarian malignancies. Sixty-nine percent (74 of 108) of the patients with known disease had abnormal CA125 levels, whereas only 32% (20 of 63) had abnormal lipid-associated sialic acid levels. Changes in CA125 serum levels reflected the disease status of the patients for whom there were serial serum samples. Normal levels of CA125 corresponded to no evidence of disease in 100% (six of six) surgically evaluated patients and 75% (30 of 40) of clinically evaluated patients. Changes in CA125 levels from normal to abnormal corresponded to disease progression in 80% (12 of 15) of the patients. Decreases in CA125 levels from abnormal to normal corresponded to complete clinical response in 55% (11 of 20), and partial clinical response in 45% (nine of 20). No such correlations were available for lipid-associated sialic acid antigen levels. For tumors that express CA125 antigen, serum levels appear to be a good marker for the extent of malignant gynecologic disease. Levels of CA125 that rose from normal to abnormal were usually associated with recurrent disease.
Energy and reserve dispatch in the integrated electricity market with sectional price offers

In this paper, we propose an integrated energy and reserve market. Two models for dispatching the energy and the reserve simultaneously with sectional offering prices are presented. The objective function of the first model is to minimize the payment, while the other model minimizes the cost. The uniform energy market price and the uniform reserve price are obtained. The dispatch models are formulated as a mixed integer non-linear programming (MINLP) optimization problem. The IEEE-30 bus system is used for the case study. The uniform prices of energy and spinning reserve are obtained and compared for the two models.
Supportive Care Considerations During Concurrent Chemoradiotherapy for Pancreatic Adenocarcinoma: Lessons Learned From Clinical Experience

Concurrent chemotherapy and radiotherapy (chemoradiotherapy) for the management of pancreatic adenocarcinoma in either adjuvant or locally regional advanced settings produces predictable acute toxicities that are proportional in severity to the intensity and type of systemic therapy and to the parameters of radiotherapy. In addition, relevant to the adjuvant setting, surgery for pancreatic cancer often produces physiologic alterations that may impact a patient’s ability to tolerate chemoradiotherapy. Failures to anticipate, monitor, and proactively manage the effects of surgery and toxicities of chemoradiotherapy can result in the need for unplanned treatment interruptions and/or inability to complete all planned therapy. In this review, complications of pancreatic cancer itself and of pancreatic resection as well as toxicities of chemoradiotherapy are delineated, and approaches to their management before, during, and after chemoradiotherapy are presented. Planning for the treatment of side effects before the anticancer therapy begins facilitates therapy administration and improves patient tolerance.
Pain in Pediatric Oncology: Do the Experiences of Children and Parents Differ from Those of Nurses and Physicians?

Diagnosis and treatment of pain are central components in the care of children withcancer. The aim of the present study was to compare the viewpoints of children andparents with those of professionals, on different aspects of pain in children with cancer.Information was collected through questionnaires and interviews. In particular, wefocused on the extent and causes of pain, strategies to reduce procedural pain, painevaluation, and attitudes to pain treatment.We found that both families and professionals shared the opinion that pain was acommon symptom during different phases of cancer treatment but, surprisingly, profes-sionals regarded it as more frequent than families. The groups agreed that treatmentrelated pain is the most critical problem, followed by procedure and cancer relatedpain. Concerning strategies to decrease procedural pain, there was a high concordancein views between groups. Nurses and physicians more often claimed that failing paintreatment was associated with psychological factors such as high levels of anxiety inparents and children, loneliness, and lack of preparation. The self-report, according toboth parents and professionals, is a feasible procedure even in young children from 4years of age. Both groups asserted that parents were better in ascertaining the extent oftheir child's pain. In conclusion, although the families and professionals in this study have many com-parable views concerning pain in children with cancer, divergences also exist. Toacquire a more accurate picture of the situation we must focus on the views of the chil-dren first, and then those of parents and professionals. Atendency to overestimate theproblems was observed in professionals. Hopefully this reflects a keen awareness ofthe current situation.
Comparison of Results of TIPU Repair for Hypospadias with “Spongioplasty Alone” and “Spongioplasty with Dorsal Dartos Flap”

Objective: The aim of our study was to compare the results of tubularized plate urethroplasty with interposing healthy tissue spongioplasty alone and spongioplasty with dorsal dartos flap to assess the role of dartos flap in prevention of fistulae. Patients and Methods: A retrospective study was performed on 80 patients, aged 4 months to 27 years who underwent hypospadias repair using the Snodgrass technique. The patients were assigned to two groups. In group I (40 patients) the neourethra was covered with spongioplasty only, and in group II (40 patients) the neourethra was covered with spongioplasty plus dartos flap. Integrity of the urethral plate was maintained in all the cases. The ventral curvature & torsion was corrected by penile de-gloving, mobilization of the urethral plate and spongiosum and mobilization of the proximal urethra if needed. The results were analysed in view of complication rates. The average period of hospital stay was 7 days & fol- low-up varied from 8 months to 28 months with a mean of 14 months. Results: In group I, hypo- spadias were distal penile in 31 (77.5%), mid-penile in 4 (10%) and proximal/peno-scrotal in 5 (12.5%) patients. In group II, hypospadias were distal penile in 17 (42.5%), mid penile in 9 (22.5%) and proximal/peno-scrotal in 14 (35%) patients. Sixty five percent in group I and 80% in group II had ventral curvature but the difference was not statistically significant. Good functional results were achieved in 97.5% patients in group I and in 95% patients in group II which were statistically similar (p value—0.585). Urethral fistula was encountered in 2.5% in group I & in 2 cases (5%) in group II. Meatal stenosis was noted in 7.5% each in both groups, which responded to urethral dilatation. One patient in group II had complete disruption. There was no statistically significant difference in early and late complications in both groups (p value—0.812). Conclusions: Spongioplasty with healthy spongiosal tissue is strong enough and is effective waterproofing as an * Corresponding author.
On the hydrodynamic stability of curved premixed flames

2014 We propose a non-linear, model equation describing the dynamics of finite amplitude disturbances superimposed to a two-dimensional, weakly unstable, flame tip of parabolic shape. By showing that solutions of this equation admit a pole decomposition, we illustrate how the local curvature effects, non-linearity and the geometry-induced flame stretch compete with the hydrodynamic instability. Cases of stability, of metastability or leading to « sidecusping » are exhibited. For spatially-periodic disturbances, a non-linear analog to Zel’dovich et al.’s criterion (C. S. T. 24 (1980)) is obtained. The appearance of steady tip-splitting is also shown to be non-generic in the class of pole-decomposable solutions. J. Phys. France 50 (1989) 1069-1082 ler MAI 1989, Classification Physics Abstracts 47.20 47.70F
As a Definitive Choice of Treatment, Joint and Defect Spanning Multiplanar Tubular External Fixation in the Management of Pediatric Open Defective Supracondylar Humerus Fracture: A Case Report

Introduction: Although supracondylar fractures of the humerus are common in children, open fractures of are extremely rare injuries. Gustilo- Anderson Type-III fractures in the upper extremity are primarily associated with considerable bone loss resulting from high energy trauma. In this study, a case of open pediatric supracondylar humerus fracture treated by a joint and defect spanning multiplanar tubular external fixation is presented. Case Report: A boy aged 3 years suffered from a Gustilo-Anderson Type-IIIA supracondylar humerus fractures. There was no neurovascular compromise. Intravenous antibiotic regimen was introduced. A joint and defect spanning multiplanar tubular external fixation was employed within 4 h of the accident. After the operation, the patient was closely followed in the inpatients unit. The external fixator was removed in the 6th week of follow-up, and range of motion exercises was started. With the exception of limited flexion of the elbow in 12th month of follow-up, supination and pronation were full. At the 48th month follow-up, 120° of elbow flexion, full extension, and full forearm rotation were observed. Physical examination showed 15° change in carrying angle to cubitus varus; radiologic examination showed a slight varus angulation of the distal humerus, a decreased Baumann’s angle. The Mayo elbow performance score was 100 points. Conclusion: When taking into account the high remodeling capacity, healing potential, and greater resistance to joint stiffness in fractures of children, joint and external fixators appear as a viable definitive treatment in such cases.
Nonsynonymous Polymorphisms in Genes in the One-Carbon Metabolism Pathway and Associations with Colorectal Cancer

The Ala222Val single nucleotide polymorphism (SNP) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in one-carbon metabolism, has been associated with colorectal cancer risk. Many enzymes are involved in one-carbon metabolism, and SNPs in the corresponding genes may play a role in colorectal carcinogenesis. We examined 24 nonsynonymous SNPs in 13 genes involved in the one-carbon metabolism pathway in relation to the risk of colorectal cancer in a case-control study nested in the Nurses' Health Study and the Health Professionals Follow-up Study cohorts. Among 376 men and women with colorectal cancer and 849 controls, a reduced risk of colorectal cancer was observed for Val/Val versus Ala carriers of MTHFR Ala222Val [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.43-1.00]. An increased risk was suggested for the variant carrier genotypes versus homozygous wild-type for betaine hydroxymethyltransferase Arg239Gln (OR, 1.40; 95% CI, 1.07-1.83) and two linked SNPs in methionine synthase reductase, Ser284Thr (OR, 1.85; 95% CI, 1.05-3.27) and Arg415Cys (OR, 2.03; 95% CI, 1.15-3.56). The other SNPs were not associated with colorectal cancer risk. Also, none of the SNPs were associated with risk in subgroups of dietary methyl status or were jointly associated with colorectal cancer risk in combination with another SNP, except possibly SNPs in methionine synthase and transcobalamin II. However, these analyses of gene-diet interactions were limited in statistical power. Our results corroborate previous findings for MTHFR Ala222Val and suggest that other genes involved in one-carbon metabolism, particularly those that affect DNA methylation, may be associated with colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2408–17)
Hair Counts from Normal Scalp Biopsy in Taiwan

BACKGROUND Horizontal scalp biopsy is a better method to use when evaluating hair disorders, but an accurate diagnosis requires quantitative data regarding normal hair counts to be used as a control, which are currently available only for Caucasians, African Americans, Koreans, and Iranians. OBJECTIVES To evaluate scalp hair counts in the Taiwanese population. METHODS Two 4‐mm punch biopsies were taken from clinically normal‐looking scalp skin of 31 patients who underwent scalp surgery for non‐hair‐loss disorders. Punch biopsy specimens were sectioned horizontally at the sebaceous gland level and the number of follicular units, terminal hairs including anagen and telogen hairs, and vellus hairs were counted and compared with other published data. The numbers of hairs were also compared between the sexes, different age groups, and different anatomical locations of the scalp. RESULTS The average counts of total hairs, terminal hairs, vellus hairs, and follicular units per 4‐mm punch scalp skin were 21.3, 20.5, 0.8, and 9.4, respectively. The mean ratio of anagen hair to telogen hair was 91.6:8.4 and of terminal hair to vellus hair was 25.3:1. The average density of hair follicles was 1.69 mm2. The mean counts of terminal hairs, total hairs, follicular units, and hair follicles/mm2 were significantly different between different age groups. CONCLUSION Differences in hair count parameters were recognized between different ethnic groups. Parameters of hair density established in the Taiwanese population will provide clinicians with useful reference data for the evaluation of hair disorders in Asians.
Sequence of epiphyseal union in a prehistoric Kentucky population from Indian Knoll.

THE time and order of epiphyseal union has been extensively studied during the past 35 years by means of both post-mortem examinations and roentgenographic methods. The result of these observations has been the establishment of a sequence of union that, in spite of not being definitely fixed, can be utilized in human identification, growth research, and clinical treatment. However, almost without exception, all of these studies have been of modern white populations, and data concerning this phenomenon in other racial groups are scarce. For this reason, the present study was undertaken. Dealing with a primitive, prehistoric series of American Indians from what is probably the largest racially homogeneous population in North America, it sets forth an age and order of union, within the limits imposed when dealing with undocumented material. This order of union is compared to other investigators' sequences and the similarities and differences noted.
The Proteasome Subunit Rpn8 Interacts with the Small Nucleolar RNA Protein (snoRNP) Assembly Protein Pih1 and Mediates Its Ubiquitin-independent Degradation in Saccharomyces cerevisiae*

Pih1 is a scaffold protein of the Rvb1-Rvb2-Tah1-Pih1 (R2TP) protein complex, which is conserved in fungi and animals. The chaperone-like activity of the R2TP complex has been implicated in the assembly of multiple protein complexes, such as the small nucleolar RNA protein complex. However, the mechanism of the R2TP complex activity in vivo and the assembly of the complex itself are still largely unknown. Pih1 is an unstable protein and tends to aggregate when expressed alone. The C-terminal fragment of Pih1 contains multiple destabilization factors and acts as a degron when fused to other proteins. In this study, we investigated Pih1 interactors and identified a specific interaction between Pih1 and the proteasome subunit Rpn8 in yeast Saccharomyces cerevisiae when HSP90 co-chaperone Tah1 is depleted. By analyzing truncation mutants, we identified that the C-terminal 30 amino acids of Rpn8 are sufficient for the binding to Pih1 C terminus. With in vitro and in vivo degradation assays, we showed that the Pih1 C-terminal fragment Pih1(282–344) is able to induce a ubiquitin-independent degradation of GFP. Additionally, we demonstrated that truncation of the Rpn8 C-terminal disordered region does not affect proteasome assembly but specifically inhibits the degradation of the GFP-Pih1(282–344) fusion protein in vivo and Pih1 in vitro. We propose that Pih1 is a ubiquitin-independent proteasome substrate, and the direct interaction with Rpn8 C terminus mediates its proteasomal degradation.
A neonatal case of congenital coronary artery fistula

Coronary artery fistulae (CAF) are rare forms of congenital heart disease with an incidence of one in 50 000 live births. The authors present the case of an asymptomatic neonate with a precordial murmur. Pre and postductal saturations, blood pressure and ECG were normal. Echocardiography revealed a large right coronary artery fistula to the right ventricle (4.5 mm). At 11 months, transcatheter occlusion of the fistula with a vascular plug was performed. A year on, the child was thriving, ECG and echocardiogram remained normal. CAF complications and symptoms (including aneurysm, myocardial ischaemia, angina, heart failure and dyspnoea) are commoner in older patients, so traditionally we intervene early. With increasing case reports of spontaneous closure of even large and symptomatic fistulae, management of especially asymptomatic children is unclear. Long-term complications of intervention also remain largely unknown. As such more information is required on the conditions natural history to better manage patients and counsel parents.