Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of the nuclear protein ‘cyclin’ in quiescent mouse 3T3 cells stimulated by serum and growth factors. Correlation with DNA synthesis.

The effect of serum and growth factors [platelet‐derived growth factor (PDGF), fibroblast growth factor (FGF)] on the synthesis of the nuclear protein cyclin and its correlation with DNA synthesis has been studied in quiescent mouse 3T3 cells by means of quantitative two‐dimensional gel electrophoresis. Serum must be present in the medium for at least 8‐12 h to induce maximal synthesis of cyclin (6‐ to 7‐fold increase compared with quiescent cells). The stimulation of cyclin synthesis is dose‐dependent and correlates directly with DNA synthesis. In addition, partially purified PDGF and FGF also induce cyclin and DNA synthesis in a coordinate way. Both growth factors, like serum, exhibit a similar lag phase to induce maximal cyclin (6‐ to 7‐fold) and DNA synthesis (90% of the cells). Pure PDGF at a concentration as low as 10 ng/ml has the same effect as 10% serum. The coordinate induction of cyclin and DNA synthesis can only be observed with growth factors that induce DNA synthesis. These results strengthen the notion that cyclin is an essential component of the events leading to DNA replication.
Topographic controls on shallow groundwater levels in a steep, prealpine catchment: When are the TWI assumptions valid?

Topographic indices like the Topographic Wetness Index (TWI) have been used to predict spatial patterns of average groundwater levels and to model the dynamics of the saturated zone during events (e.g., TOPMODEL). However, the assumptions underlying the use of the TWI in hydrological models, of which the most important is that groundwater level variation can be approximated by a series of steady state situations, are rarely tested. It is also not clear how well findings from existing hillslope studies on sites with transmissive soil can be transferred to entire catchments with less permeable soils. This study, therefore, evaluated the suitability of selected topographic indices to describe spatial groundwater level variations based on time series from 51 groundwater wells in a 20 ha catchment with low‐permeability soils in Switzerland. Results showed that median groundwater levels were correlated to slope, curvature, and TWI, but the strength of correlation depended on whether the indices characterized the local topography or the topography of the upslope contributing area. The correlation between TWI and groundwater levels was not constant over time but decreased at the beginning of rainfall events, indicating large spatial differences in groundwater responses, and increased after peak flow, when groundwater levels could be considered to be spatially in a steady state. Our findings indicate that topographic indices are useful to predict median groundwater levels in catchments with low‐permeability soils and that the TWI assumptions are best met when groundwater levels change slowly.
Regulation of the plasminogen activator inhibitor‐2 (PAI‐2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin

We investigate the regulation of plasminogen activator inhibitor‐2 (PAI‐2) in murine macrophages. PAI‐2 mRNA was inducible by bacterial lipopolysaccharide (LPS) in primary cells and macrophage‐like cell lines. Evidence is presented for a role for autocrine factors, including cyclooxygenase products but not the cytokines tumor necrosis factor α or interferon‐β (IFN‐β). PAI‐2 mRNA levels generally varied inversely from those of its target, urokinase‐type plasminogen activator (uPA), and the macrophage growth factor CSF‐1, which induces uPA, inhibited PAI‐2 expression in cells treated subsequently with LPS. Expression of PAI‐2 was distinct from that of other LPS‐inducible genes in terms of induction time course, LPS dose response, and sensitivity to co‐stimulation with IFN‐γ. Induction of PAI‐2 mRNA in subclones of the cell line RAW 264 was not uniform, reflecting heterogeneous expression in the parent line. The expression pattern of PAI‐2 is discussed in terms of a possible role in LPS‐induced pathology such as septicemia. J. Leukoc. Biol. 66: 172–182; 1999.
Healthcare utilization and cost of systemic lupus erythematosus in a US managed care health plan

Abstract Objective: To assess healthcare resource utilization and costs in a cohort of US managed care patients with systemic lupus erythematosus (SLE). Methods: Claims data from a large managed care plan were used to identify patients of 18–64 years old with SLE-related claims from 2004–2005. Algorithms were developed to retrospectively categorize patients by disease severity and identify flare episodes by flare severity. Descriptive and multivariate analyses were performed to estimate healthcare resource utilization and costs over a 2-year period for the cohort overall and by disease and flare severity. Results: Among the 2990 patients in the study cohort, disease severity was mild in 789 (26.4%), moderate in 1558 (52.1%), and severe in 643 (21.5%). During the 2-year follow-up period, SLE patients utilized the following categories of care: office visit (99.7%), laboratory service (99.5%), outpatient hospital visit (76.0%), emergency room visit (45.6%), and inpatient hospital stay (26.4%). Mean total unadjusted healthcare cost per patient was $30,010 over the 2-year follow-up period, with medical and pharmacy costs comprising 76.5% and 23.5% of total expenditures, respectively. Additionally, 95.7% of patients had one or more flares, with a mean (SD) of 6.7 (3.6) flares during the 2-year follow-up period. The average unadjusted cost per mild, moderate, and severe flare, respectively, was $909, $1539, and $17,059, most of which was for medical cost rather than pharmacy cost. The frequency and cost of flares increased with disease severity. Limitations: The disease severity and flare severity algorithms were based upon managed care claims data; the algorithm was not verified clinically and may not be generalizable to other health plans. Conclusions: SLE is associated with high levels of healthcare utilization and costs in a managed care health plan. Inpatient hospital stays were the primary medical cost drivers, followed by physician office visits and outpatient hospital visits.
Bivalirudin (Angiomax) Use during Intracoronary Brachytherapy May Predispose to Acute Closure

We describe two cases of intracoronary vascular brachytherapy where bivalirudin (Angiomax), employed as an anticoagulant, led to abrupt vessel closure or threatened abrupt closure. Use of bivalirudin (Angiomax) during intracoronary brachytherapy may predispose to the formation of intracoronary thrombus, related to the reversible binding kinetics of the bivalirudin to thrombin, and resulting in recovery of thrombin functional activity during periods of prolonged stasis that occur during intracoronary brachytherapy. Intracoronary abciximab administration may be a useful strategy in resolving the acute closure, since abciximab administered early during the formation of thrombus has been shown to facilitate clot lysis.
Altered Expression of 15-Hydroxyprostaglandin Dehydrogenase in Tumor-Infiltrated CD11b Myeloid Cells: A Mechanism for Immune Evasion in Cancer

Many cancers are known to produce high amounts of PGE2, which is involved in both tumor progression and tumor-induced immune dysfunction. The key enzyme responsible for the biological inactivation of PGE2 in tissue is NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). It is well established that cancer cells frequently show down-regulated expression of 15-PGDH, which plays a major role in catabolism of the PGE2. Here we demonstrate that tumor-infiltrated CD11b cells are also deficient for the 15-PGDH gene. Targeted adenovirus-mediated delivery of 15-PGDH gene resulted in substantial inhibition of tumor growth in mice with implanted CT-26 colon carcinomas. PGDH-mediated antitumor effect was associated with attenuated tumor-induced immune suppression and substantially reduced secretion of immunosuppressive mediators and cytokines such as PGE2, IL-10, IL-13, and IL-6 by intratumoral CD11b cells. We show also that introduction of 15-PGDH gene in tumor tissue is sufficient to redirect the differentiation of intratumoral CD11b cells from immunosuppressive M2-oriented F4/80+ tumor-associated macrophages (TAM) into M1-oriented CD11c+ MHC class II-positive myeloid APCs. Notably, the administration of the 15-PGDH gene alone demonstrated a significant therapeutic effect promoting tumor eradication and long-term survival in 70% of mice with preestablished tumors. Surviving mice acquired antitumor T cell-mediated immune response. This study for the first time demonstrates an important role of the 15-PGDH in regulation of local antitumor immune response and highlights the potential to be implemented to enhance the efficacy of cancer therapy and immunotherapy.
Segmentation Matters: An Exploratory Study of Mobile Service Users

Despite the penetration of mobile phones in the world the number of mobile services in actual use is-besides voice calls and SMS-rather few. In the study at hand, the authors describe users of mobile phones and mobile services and build the basis for segmentation of the consumer market based on a large random sample of the population. Selecting the correct segmentation base is one of the key steps in any segmentation procedure. The authors carried out life-style segmentation and found five segments-the skillful, the efficient, the trendy, the basic and the social-which offer a systematic description of the mobile consumers, and gives insight on how different users make use of mobile services. The findings are potentially important as mobile service providers do not appear to pay enough attention to consumer segments and the needs of the mobile service users.
Scrub typhus: an unrecognized threat in South India – clinical profile and predictors of mortality

Summary Scrub typhus is an important cause of acute undifferentiated febrile illnesses in the Indian subcontinent. Delay in diagnosis and in the initiation of appropriate treatment can result in severe complications such as acute respiratory distress syndrome (ARDS), septic shock and multisystem organ failure culminating in death. We conducted a prospective, observational study to delineate the clinical profile and predictors of mortality in scrub typhus in adults admitted to the medical wards of a tertiary care, referral hospital in South India over a one-year period. The case fatality rate in this study was 12.2%. Metabolic acidosis (odds ratio [OR] 6.1), ARDS (OR 3.6), altered sensorium (OR 3.6) and shock (OR 3.1) were independent predictors of mortality. It appears that scrub typhus has four possible overlapping clinical presentations: mild disease; respiratory predominant disease; central nervous system predominant disease (meningoencephalitis); or sepsis syndrome. Given the telltale presence of an eschar (evident in 45.5%), the characteristic clinical profile and the dramatic therapeutic response to a cheap, yet effective, drug such as doxycycline, medical practitioners in the region should have ample opportunity to reach an early diagnosis and initiate treatment which could, potentially, reduce the mortality and morbidity associated with scrub typhus.
In vitro and in vivo comparative toxicological study of a new preservative-free latanoprost formulation.

PURPOSE To compare in vitro, on the human reconstituted corneal epithelial SkinEthics model, and in vivo, using an acute rabbit toxicological model, the effects of a benzalkonium chloride (BAK)-preserved solution of latanoprost and a preservative-free (PF) latanoprost solution. METHODS In vitro, the three-dimensional (3D) reconstituted human corneal epithelia (HCE) were treated with PBS, BAK-latanoprost, PF-latanoprost, or 0.02% BAK for 24 hours followed or not followed by a 24 hour post incubation recovery period. Cellular viability was evaluated using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test at 24 hours and the apoptotic cells were counted using TUNEL labeling on frozen sections at 24 hours and 24 hours plus 24 hours. In vivo, rabbits received 50 μL of the same solutions, which were applied at 5 minute intervals a total of 15 times. Ocular surface toxicity was investigated using slit lamp biomicroscopy examination, conjunctival impression cytology (CIC), and corneal in vivo confocal microscopy (IVCM). Standard immunohistology also assessed inflammatory CD45-positive cells. RESULTS In vitro, BAK-latanoprost and 0.02% BAK induced significant apoptosis in the apical layers that correlated with the significant decrease of cell viability as assessed by the MTT test. PF-latanoprost slightly decreased cell viability and few apoptotic cells were found in the superficial layers, without reaching statistical significance compared with PBS. In vivo, clinical observation and IVCM images showed the lowest ocular surface toxicity with PBS and PF-latanoprost, while BAK-latanoprost and BAK induced abnormal corneoconjunctival aspects. PF-latanoprost showed the lowest CIC score, close to the PBS score and induced fewer CD45-positive cells in both the limbus and the conjunctiva compared with BAK and latanoprost, as assessed by immunohistology. CONCLUSIONS We confirm that rabbit corneoconjunctival surfaces presented better tolerance when treated with PF-latanoprost compared with the standard BAK-latanoprost preparation or the BAK solution.
Safety and efficacy of a new prophylactic tirofiban protocol without oral intraoperative antiplatelet therapy for endovascular treatment of ruptured intracranial aneurysms

Background Coil embolization of intracranial aneurysms is being increasingly used; however, thromboembolic events have become a major periprocedural complication. Objective To determine the safety and efficacy of prophylactic tirofiban in patients with ruptured intracranial aneurysms. Methods Tirofiban was administered as an intravenous bolus (8.0 μg/kg over 3 min) followed by a maintenance infusion (0.10 μg/kg/min) before stent deployment or after completion of single coiling. Dual oral antiplatelet therapy (loading doses) was overlapped with half the tirofiban dose 2 h before cessation of the tirofiban infusion. Cases of intracranial hemorrhage or thromboembolism were recorded. Results Tirofiban was prophylactically used in 221 patients, including 175 (79.19%) who underwent stent-assisted coiling and 46 (20.81%) who underwent single coiling, all in the setting of aneurysmal subarachnoid hemorrhage. Six (2.71%) cases of intracranial hemorrhage occurred, including four (1.81%) tirofiban-related cases and two (0.90%) antiplatelet therapy-related cases. There were two (0.90%) cases of fatal hemorrhage, one related to tirofiban and the other related to dual antiplatelet therapy. Thromboembolic events occurred in seven (3.17%) patients (6 stent-assisted embolization, 1 single coiling), of which one (0.45%) event occurred during stenting and six (2.72%) occurred during intravenous tirofiban maintenance. No thromboembolic events related to dual antiplatelet therapy were found. Conclusions Tirofiban bolus over 3 min followed by maintenance infusion appears to be a safe and efficient prophylactic protocol for the endovascular treatment of ruptured intracranial aneurysms and may be an alternative to intraoperative oral antiplatelet therapy, especially in the case of stent-assisted embolization.
Specific Role of Chk1 Phosphorylations in Cell Survival and Checkpoint Activation

ABSTRACT Chk1 is a multifunctional protein kinase that plays essential roles in cell survival and cell cycle checkpoints. Chk1 is phosphorylated at multiple sites by several protein kinases, but the precise effects of these phosphorylations are largely unknown. Using a knockout-knockin system, we examined the abilities of Chk1 mutants to reverse the defects of Chk1-null cells. Wild-type Chk1 could rescue all the defects of Chk1-null cells. Like endogenous Chk1, wild-type Chk1 localized in both the cytoplasm and the nucleus, and its centrosomal association was enhanced by DNA damage. The mutation at S345 resulted in mitotic catastrophe, impaired checkpoints, and loss of the ability to localize in the cytoplasm, but the mutant retained the ability to be released from chromatin upon encountering genotoxic stressors. In contrast, the mutation at S317 resulted in impaired checkpoints and loss of chromatin release upon encountering genotoxic stressors, but its mutant retained the abilities to prevent mitotic catastrophes and to localize in the cytoplasm, suggesting the distinct effects of these phosphorylations. The forced immobilization of S317A/S345A in centrosomes resulted in the prevention of apoptosis in the presence or absence of DNA damage. Thus, two-step phosphorylation of Chk1 at S317 and S345 appeared to be required for proper localization of Chk1 to centrosomes.
Numerical Terradynamic Simulation Group 1-2018 Characterizing permafrost active layer dynamics and sensitivity to landscape spatial heterogeneity in Alaska

An important feature of the Arctic is large spatial heterogeneity in active layer conditions, which is generally poorly represented by global models and can lead to large uncertainties in predicting regional ecosystem responses and climate feedbacks. In this study, we developed a spatially integrated modeling and analysis framework combining field observations, local-scale (∼ 50 m resolution) active layer thickness (ALT) and soil moisture maps derived from low-frequency (L+P-band) airborne radar measurements, and global satellite environmental observations to investigate the ALT sensitivity to recent climate trends and landscape heterogeneity in Alaska. Modeled ALT results show good correspondence with in situ measurements in higherpermafrost-probability (PP≥ 70 %) areas (n= 33;R = 0.60; mean bias= 1.58 cm; RMSE= 20.32 cm), but with larger uncertainty in sporadic and discontinuous permafrost areas. The model results also reveal widespread ALT deepening since 2001, with smaller ALT increases in northern Alaska (mean trend= 0.32± 1.18 cm yr−1) and much larger increases (> 3 cm yr−1) across interior and southern Alaska. The positive ALT trend coincides with regional warming and a longer snow-free season (R = 0.60± 0.32). A spatially integrated analysis of the radar retrievals and model sensitivity simulations demonstrated that uncertainty in the spatial and vertical distribution of soil organic carbon (SOC) was the largest factor affecting modeled ALT accuracy, while soil moisture played a secondary role. Potential improvements in characterizing SOC heterogeneity, including better spatial sampling of soil conditions and advances in remote sensing of SOC and soil moisture, will enable more accurate predictions of active layer conditions and refinement of the modeling framework across a larger domain.
Inducible and constitutive enhancer domains in the noncoding region of human papillomavirus type 18

The noncoding region of human papillomavirus type 18 (HPV-18) is shown to contain at least three enhancer elements. Two of these elements are responsive to papillomavirus-encoded trans-acting factors, and the third element functions as a constitutive enhancer, requiring only cellular factors for activity. The first enhancer (IE2) is located proximal to the E6 cap site and is responsive to papillomavirus E2 trans-activator. The second enhancer (IE6) is located approximately 500 base pairs upstream of the E6 cap site and is dependent upon the viral E6 gene product for function. A third enhancer (C) is located between 200 and 400 base pairs upstream of the E6 cap site and possesses a constitutive activity, requiring no HPV-18-encoded factors for function. The constitutive enhancer element exhibits some cell type preference for epithelial cell lines, but also functions in rodent fibroblast lines. Each of these enhancers manifests activity independent of the other elements and may reflect separate transcriptional control elements for different stages of the HPV-18 virus life cycle.
Cerebrospinal Fluid Leakage in Intracranial Hypotension Syndrome: Usefulness of Indirect Findings in Radionuclide Cisternography for Detection and Treatment Monitoring

Purpose: To evaluate indirect findings of cerebrospinal fluid (CSF) leakage on radionuclide cisternography and their changes after treatment. Materials and Methods: This study was approved by the hospital's institutional review board and informed consent was obtained before each examination. A total of 67 patients who were clinically suspected of spontaneous intracranial hypotension (SIH) syndrome underwent radionuclide cisternography, and 27 patients who had direct findings of CSF leakage on radionuclide cisternography were selected for this evaluation. They were 16 males and 11 females, aged between 26 and 58 years. Sequential images of radionuclide cisternography were acquired at 1, 3, 5, and 24 hours after injection. We assessed the presence or absence of 4 indirect findings; early visualization of bladder activity, no visualization of activity over the brain convexities, rapid disappearance of spinal activity, and abnormal visualization of the root sleeves. Changes of the direct and indirect findings after treatment were also evaluated in 14 patients who underwent epidural blood patch treatment. Results: Early visualization of bladder activity was found in all 27 patients. Seven of 27 (25.9%) patients showed no activity over the brain convexities. Rapid disappearance of spinal activity and abnormal root sleeve visualization were present in 2 (7.4%) and 5 (18.5%) patients, respectively. After epidural blood patch, both direct CSF leakage findings and indirect findings of early visualization of bladder activity had disappeared or improved in 12 of 14 patients (85.7%). The other indirect findings also disappeared after treatment in all cases. Conclusion: Indirect findings of radionuclide cisternography, especially early visualization of bladder activity, may be useful in the diagnosis and posttreatment follow-up of CSF leakage.
Linear birefringence measurements of the in vitro human cornea

This paper presents results of an in vitro investigation of the optical anisotropy of the human cornea. Computer controlled imaging polarimetry and the Jones formalism were used to investigate the distribution of the birefringence and the azimuth angle across the surface of 12 corneas taken from the corneal bank. Each map of the birefringence and the azimuth angle has no rotational symmetry and is different for each cornea. The minimal value of the birefringence always appears in the corneal centre and varies from 9 to 43° for different corneas. Birefringence of the cornea increases monotonically more than one order in the direction of the corneal periphery. Close to the centre of the cornea the azimuth angle is almost constant and varies significantly away from the optical part of the cornea.
Surgical Treatment of Acute Lateral Collateral Ligament and Posterolateral Corner Injuries

Early surgical treatment of injuries to the posterolateral corner of the knee is recommended to promote rehabilitation for normal function of the knee. To optimize the chance at primary repair, surgery should be performed within 2 weeks; otherwise, reconstruction is the most viable option. During operative treatment, each component of the posterolateral corner is assessed individually, with primary repair performed if amenable to repair. Additional techniques, such as augmentation, advancement, or reconstruction may be needed if the primary repair is tenuous or the tissues damaged.