Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative activities of clavulanic acid, sulbactam, and tazobactam against clinically important beta-lactamases

Clavulanic acid, sulbactam, and tazobactam are inhibitors of a variety of plasmid-mediated beta-lactamases. However, inhibition data for these three inhibitors with a wide range of different plasmid-mediated beta-lactamases have not yet been compared under the same experimental conditions. A number of groups have inferred that clavulanic acid inhibits extended-spectrum TEM and SHV beta-lactamases, but inhibition data have rarely been published. In this study, the 50% inhibitory concentrations of these three beta-lactamase inhibitors for 35 plasmid-mediated beta-lactamases have been determined. Of these 35 beta-lactamases, 20 were extended-spectrum TEM- or SHV-derived beta-lactamases. The other 15 enzymes were conventional-spectrum beta-lactamases such as TEM-1 and SHV-1. Clavulanic acid was a more potent inhibitor than sulbactam for 32 of the 35 plasmid-mediated beta-lactamases tested. In particular, clavulanic acid was 60 and 580 times more potent than sulbactam against TEM-1 and SHV-1, respectively, currently the two most clinically prevalent gram-negative plasmid-mediated beta-lactamases. Statistical analysis of the data of the 50% inhibitory concentrations showed that clavulanic acid was 20 times more active overall than sulbactam against the conventional-spectrum enzymes. In addition, clavulanic acid was 14 times more potent than sulbactam at inhibiting the extended-spectrum enzymes. Tazobactam also showed significantly greater activity than sulbactam against the two groups of beta-lactamases. There were no significant differences between the overall activities of tazobactam and clavulanic acid against the extended-spectrum TEM and SHV enzymes and conventional-spectrum enzymes, although differences in their inhibition profiles were observed.
Protective effect of pyrrolidine dithiocarbamate on liver injury induced by intestinal ischemia-reperfusion in rats.

BACKGROUND The nuclear translocation of transcription factors may be a critical factor in the intracellular pathway involved in ischemia/reperfusion (I/R) injury. The aim of the study was to evaluate the role of nuclear factor-kappa B (NF-kappaB) in the pathogenesis of liver injury induced by intestinal ischemia/reperfusion (IIR) and to investigate the effect of pyrrolidine dithiocarbamate (PDTC) on this liver injury. METHODS Male Wistar rats were divided randomly into three experimental groups (8 rats in each): sham operation group (control group); intestinal/reperfusion group (I/R group): animals received 1-hour of intestinal ischemia and 2-hour reperfusion; and PDTC treatment group (PDTC group): animals that received I/R subject to PDTC treatment (100 mg/kg). The histological changes in the liver and intestine were observed, and the serum levels of tumor necrosis factor-alpha (TNF-alpha), alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver superoxide dismutase (SOD), and nitrite/nitrate (NO) were measured. The immunohistochemical expression and Western blot analysis of liver NF-kappaB and intercellular adhesion molecule-1 (ICAM-1) were observed. RESULTS IIR induced liver injury characterized by the histological changes of liver edema, hemorrhage, polymorphonuclear neutrophil (PMN) infiltration, and elevated serum levels of AST and ALT. The serum TNF-alpha level was significantly higher than that of the control group (P<0.01) and a high level of liver oxidant product was observed (P<0.01). These changes were parallel to the positive expression of NF-kappaB and ICAM-1. After the administration of PDTC, the histological changes after liver injury were improved; the levels of SOD and NO in the liver were elevated and reduced, respectively (P<0.01). The expressions of ICAM-1 and NF-kappaB in the liver were weakened (P<0.01). CONCLUSION NF-kappaB plays an important role in the pathogenesis of liver injury induced by IIR. PDTC, an agent known to inhibit the activation of NF-kappaB, can reduce and prevent this injury.
Biomechanical Analysis of Distal Biceps Tendon Repair Methods

Background The 1-incision and 2-incision techniques are commonly used methods to repair a distal biceps rupture, and they differ in the location of reinsertion of tendon into bone. Hypothesis The native distal biceps brachii tendon inserts on the posterior-ulnar aspect of the bicipital tuberosity, which functions as a cam, increasing the tendon's moment arm during its principal action of forearm supination. Repair of the distal biceps tendon to the anterior aspect of the tuberosity compromises forearm supination due to absence of the bicipital tuberosity's cam effect. Study Design Controlled laboratory study. Methods Eleven matched pairs of fresh-frozen cadaveric upper extremities were prepared for repair of the distal biceps tendon using either anterior or posterior reattachment with transosseous suture fixation. Specimens were tested on a materials testing machine with intact distal biceps insertion and after repair. A load cell at the distal radial-ulnar joint measured resultant elbow flexion and forearm supination torque produced by 100-N force applied to the proximal aspect of the tendon. Results Although there was a trend (P = .104) toward loss of supination torque with the anterior reconstruction method, no significant differences in torque (0.80 vs 0.89 N·m) or flexion force (11.87 vs 12.07 N) were found between the anterior and posterior reconstruction techniques. Conclusion There is no statistically significant difference in flexion force or supination torque between the anterior and posterior reconstruction techniques. Clinical Relevance This study supports existing limited clinical data suggesting no functional differences exist between 2 common repair methods. Further biomechanical and clinical investigations directly comparing the results of distal biceps tendon repairs made to the anterior aspect versus the posterior aspect of the tuberosity are necessary to definitely determine if differences exist in resultant elbow flexion and forearm supination functions.
Mitigating impacts of water shortage on Egyptian agriculture: a catchment scale analysis

The impacts of water shortages on Egypt9s agriculture continues to receive widespread attention. Several mitigation schemes have been proposed to reduce the potential economic impact of supply reductions of the Nile9s waters into Egypt. This paper examines the economic consequences for the Egyptian agricultural economy of application of limited water markets to mitigate the impacts of potential water supply shortages. We address this aim by assembling detailed data on farm budgets, hydrology, institutions and culture in order to develop an integrated catchment framework for analyzing Egypt9s use of the Nile. The results of our policy analysis illustrate that a limited form of water trading is one institutionally flexible measure that can mitigate the impacts of water shortages. When water supplies flowing into Egypt are reduced by 10 and 20% per year, adopting limited water trading reduces national farm income losses by 32 and 33% per year, respectively, compared to income losses borne without trading. So water trading grows in importance as a measure to sustain farm income in the face of more severe water shortages. Our findings provide insight for Egyptian policymakers to enable examination of options to mitigate the economic impacts of water supply shortages resulting from drought, climate change, or renegotiated arrangements for sharing the Nile9s waters.
Contrasting patterns of neoplastic cell behaviour in long‐term culture of bone marrow from patients with acute leukaemia and myelodysplastic disorders

Summary. Alterations in neoplastic cell behaviour responsible for increased production of terminally‐differentiated granulocytes during long‐term culture of bone marrow in different categories of acute leukaemia and myelodysplasia have been investigated. An increase in neutrophils associated with transition to a morphological picture identical to normal control cultures occurred in 15 of 25 studies on acute leukaemia in contrast to one of six studies on myelodysplastic disorders. An abnormal neoplastic karyotype was employed as a marker for monitoring the course of the neoplastic cell population in 11 studies in which there was progression towards a normal pattern of differentiation. An increase in differentiation was shown by this means to represent increased maturation of cells of the neoplastic process in one study on a myelodysplastic disorder, demonstrating domination of proliferative activity in culture by all of the myelodysplastic disorders examined. Transition towards normal differentiation in nine studies on acute leukaemia, however, correlated with partial or complete replacement of the acute leukaemic cells by normal haemopoietic series in de novo acute leukaemia, and by Ph positive cells in blast crisis of CML. Conversion to morphologically and cytogenetically normal cell populations in five studies on de novo acute leukaemia occurred in four cases which failed to respond to remission‐induction therapy, suggesting the selective toxic effect capable of purging acute leukaemic cells from bone marrow operated by a mechanism which lacked cross‐resistance to currently‐employed cytotoxic agents.
Which Type of Trust Matters?: Interpersonal vs. Institutional vs. Political Trust

Although an increasing number of studies demonstrate the importance of trust in economic growth, they only focus on interpersonal trust. This paper considers various types of trust including interpersonal trust (i.e., trust in people), institutional trust (e.g., trust in the fair administration of justice, or trust in the protection of property rights), and political trust (e.g., trust in government or political parties), and investigates their impacts on growth. Using novel cross-country survey data, this paper finds that institutional trust is most robustly related to the economic growth in a cross-section of 46 countries. This paper also shows that there is a causal relationship between institutional trust and growth using panel data from those 46 countries. Hence, in contrast with the previous trust literature which focuses on trust in "people" as a "time-invariant cultural feature," this paper stresses trust in "social system" as an "institutions- dependent feature. "
Venous Ulcer: What Is New?

Summary: The pathophysiology of venous dermal abnormality in chronic venous ulcers is reflective of a complex interplay that involves sustained venous hypertension, inflammation, changes in the microcirculation, cytokine and matrix metalloproteinase activation, and altered cellular function. Red blood cells and macromolecules extravasate into the interstitium and activate endothelial cells. Endothelial expression of specific adhesion molecules recruits leukocytes and causes diapedesis of these cells into the dermal microvasculature, promoting an inflammatory response with activation of cytokines and proteinases. Altered cell function enhances a state of vulnerability in the surrounding tissues, initiating specific changes associated with venous disease. Ultimately, the persistent inflammatory-proteinase activity leads to advanced chronic venous insufficiency and ulcer formation. The mainstay of therapy in venous ulcer abnormality is correction of the underlying venous hypertension through compression therapy and/or surgery. Understanding the science involved in the pathophysiology of venous ulcer formation has led to the development of adjunctive treatment directed at the dysregulated molecular pathways. Randomized clinical trials are critical for determining the most effective evidence-based treatments for venous ulcer, and this review discusses important trials that have had a significant impact on venous ulcer healing. In addition, the authors have included subsections referred to as “Translational Implications for Therapy” in the basic science sections of the review to help bridge the basic science knowledge with clinical applications that may help to modulate the molecular abnormalities in the pathophysiologic cascade leading to venous ulcers.
Idiosyncratic Volatility, Measurement Frequency and Return Reversal

This paper examines whether the negative relation between idiosyncratic volatility and expected returns is due to stock return reversals as argued by Fu (2009) and Huang, Liu, Rhee and Zhang (2010). Controlling the return reversal effect, it shows that stocks with different past returns have different relations. The positive relation is mainly driven by stocks with low past returns, while the negative relation is result from stocks with high past returns. Additionally, the relation is very sensitive to the measurement frequency of idiosyncratic volatility, and the daily realized idiosyncratic volatility measure is a better proxy for the expected idiosyncratic volatility than the monthly measure. By employing an exponential generalized autoregressive conditional heteroskedascticity-in-mean (EGARCH-M) model, this paper finds a strong positive relation between time-varying risk premium and idiosyncratic volatility for portfolios containing stocks with low past returns and small portfolio, and a negative relation for growth portfolio.
Induction in vitro of primary cytotoxic T-lymphocyte responses with DNA encoding herpes simplex virus proteins

Vaccines which successfully protect against virus infections usually need to induce a broadly reactive immune response which includes the induction of cytotoxic T lymphocytes (CTL). In this study, we have used a convenient in vitro approach to investigate if plasmid DNAs encoding proteins of herpes simplex virus (HSV) are capable of inducing primary CD8+ CTL. Dendritic cells or macrophages were transfected with either plasmid DNA encoding glycoprotein B or DNA encoding the immediate-early protein ICP27. These antigen-presenting cells (APC) were then used to stimulate enriched populations of naive T cells in microcultures for 5 days in vitro. Antigen-specific CD8+ CTL which reacted both with specific protein-expressing targets and with syngeneic targets infected with HSV could be demonstrated. Dendritic cells, as APC, generated the maximal responses, but such cells needed to be transfected with DNA in the presence of a cationic lipid. However, macrophages could act as APC when they were exposed to purified DNA. HSV-primed splenocytes were also shown to generate specific CTL responses when they were stimulated with purified DNA encoding ICP27. The novel approach described in this paper promises to be extremely useful, since defining immunogenicity profiles and identifying epitopes on viral proteins should be easier and more convenient when working with DNA and investigating variables in vitro. This is particularly the case with complex viruses such as HSV, most of whose encoded proteins have yet to be isolated in sufficient quantity or purity to perform in vivo immunological studies.
mTORC1 signaling is essential for neurofibromatosis type I gene modulated osteogenic differentiation of BMSCs

Neurofibromatosis type I (NF1), which is caused by mutations in the NF1 gene, is a common autosomal dominant genetic disease leading to skeletal abnormalities. Both NF1 gene and mammalian target of rapamycin complex 1 (mTORC1) signaling are associated with the osteogenic differentiation of bone marrow stem cells (BMSCs). In this study, we hypothesized that mTORC1 signaling is involved in NF1‐modulated osteoblast differentiation of BMSCs. Human BMSCs were cultured in an osteogenic induction medium. The expression of NF1 was either inhibited or overexpressed by transfecting NF1 with a specific small interfering RNA (siRNA) or pcDNA3.0 plasmid, respectively. In addition, an mTORC1 signaling inhibitor and agonist were used to investigate the effects of mTORC1 on NF1‐modulated osteogenic differentiation of BMSCs. The results indicated that inhibiting the expression of NF1 with siRNA significantly decreased the mRNA levels of NF1, whereas overexpressing the expression of NF1 with pcDNA3.0 plasmid significantly increased the mRNA levels of NF1 at days 3, 7, 14 and 21 after culture. We observed reduced osteogenic differentiation and cell proliferation in the NF1‐siRNA group and enhanced osteogenic differentiation and cell proliferation of BMSCs in the NF1‐pcDNA3.0 group. The activity of mTORC1 signaling (p‐mTORC1, p‐S6K1, and p‐4EBP1) was significantly upregulated in the NF1‐siRNA group and significantly inhibited in the NF1‐pcDNA3.0 group, 7 and 14 days after culture. The effects of NF1‐siRNA and NF1‐pcDNA3.0 on osteogenic differentiation of BMSCs and cell proliferation were reversed by mTORC1 inhibitor and agonist, respectively. In conclusion, NF1 modulates osteogenic differentiation and cell proliferation of human BMSCs and mTORC1 signaling is essential for this process.
Mechanisms of Plakoglobin-dependent Adhesion

Plakoglobin (PG) is a member of the Armadillo family of adhesion/signaling proteins that can be incorporated into both adherens junctions and desmosomes. Loss of PG results in defects in the mechanical integrity of heart and skin and decreased adhesive strength in keratinocyte cultures established from the skin of PG knock-out (PG-/-) mice, the latter of which cannot be compensated for by overexpressing the closely related β-catenin. In this study, we examined the mechanisms of PG-regulated adhesion in murine keratinocytes. Biochemical and morphological analyses indicated that junctional incorporation of desmosomal, but not adherens junction, components was impaired in PG-/- cells compared with PG+/- controls. Re-expression of PG, but not β-catenin, in PG-/- cells largely reversed these effects, indicating a key role for PG in desmosome assembly. Epidermal growth factor (EGF) receptor activation resulted in Tyr phosphorylation of PG, which was accompanied by a loss of desmoplakin from desmosomes and decreased adhesive strength following 18-h EGF treatment. Importantly, introduction of a phosphorylation-deficient PG mutant into PG null cells prevented the EGF receptor-dependent loss of desmoplakin from junctions, attenuating the effects of long term EGF treatment on cell adhesion. Therefore, PG is essential for maintaining and regulating adhesive strength in keratinocytes largely through its contributions to desmosome assembly and structure. As a target for modulation by EGF, regulation of PG-dependent adhesion may play an important role during wound healing and tumor metastasis.
Management research on disabilities: examining methodological challenges and possible solutions

Providing companies and managers with knowledge about the inclusion of people with disabilities in the workplace is important since they often face significant obstacles such as discrimination and high unemployment rates. Poor workplace inclusion also has detrimental effects for companies, such as discrimination litigation, untapped personnel resources and missed business opportunities. Yet, empirical research on the topic of disability is extremely limited, especially in top-tier management journals. Although this shortcoming in research has often been mentioned by scholars, few explanations for it have been put forward. I propose that specific methodological challenges for quantitative research in the field are an important contributor to this shortcoming. In this paper, I identify and outline specific challenges through expert interviews, identify underlying issues and provide first suggestions on how to address these. The goal is to help increase the number of high-quality research studies in the organizational sciences and thereby advance our knowledge of the inclusion of people with disabilities in the workplace.
Extending a spherical robot for dealing with irregular surfaces: a sea urchin-like robot

Spherical robots provide an exploration platform that enables the access to inaccessible or dangerous places to people. These robots are also capable of hiding their components inside themselves, protecting in that way their integrity. Even though these robots are capable of moving over irregular surfaces, they face difficulties when moving over surfaces with hollows, stairs, or slopes. We propose a sea urchin-like robot, a spherical robot equipped with retractable devices within its body. This robot overcomes some disadvantages of spherical robots, concerning namely locomotion over irregular surfaces. The robot is capable of moving over irregular surfaces with hollows up to of its diameter, a significant gain to the known constraint of objects and hollows of of their diameter that traditional spherical robots are able to deal with. The main contribution of this work is a model of a flexible vehicle able to traverse irregular surfaces required in remote sensing missions. Graphical Abstract
The role of storage capacity in coping with intra- and inter-annual water variability in large river basins

Societies and economies are challenged by variable water supplies. Water storage infrastructure, on a range of scales, can help to mitigate hydrological variability. This study uses a water balance model to investigate how storage capacity can improve water security in the world’s 403 most important river basins, by substituting water from wet months to dry months. We construct a new water balance model for 676 ‘basin-country units’ (BCUs), which simulates runoff, water use (from surface and groundwater), evaporation and trans-boundary discharges. When hydrological variability and net withdrawals are taken into account, along with existing storage capacity, we find risks of water shortages in the Indian subcontinent, Northern China, Spain, the West of the US, Australia and several basins in Africa. Dividing basins into BCUs enabled assessment of upstream dependency in transboundary rivers. Including Environmental Water Requirements into the model, we find that in many basins in India, Northern China, South Africa, the US West Coast, the East of Brazil, Spain and in the Murray basin in Australia human water demand leads to over-abstraction of water resources important to the ecosystem. Then, a Sequent Peak Analysis is conducted to estimate how much storage would be needed to satisfy human water demand whilst not jeopardizing environmental flows. The results are consistent with the water balance model in that basins in India, Northern China, Western Australia, Spain, the US West Coast and several basins in Africa would need more storage to mitigate water supply variability and to meet water demand.
AN ALMA DISK MASS FOR THE CANDIDATE PROTOPLANETARY COMPANION TO FW TAU

We present ALMA observations of the FW Tau system, a close binary pair of M5 stars with a wide-orbit (300 AU projected separation) substellar companion. The companion is extremely faint and red in the optical and near-infrared, but boasts a weak far-infrared excess and optical/near-infrared emission lines indicative of a primordial accretion disk of gas and dust. The component-resolved 1.3 mm continuum emission is found to be associated only with the companion, with a flux (1.78 ± 0.03 mJy) that indicates a dust mass of 1–2 M⊕. While this mass reservoir is insufficient to form a giant planet, it is more than sufficient to produce an analog of the Kepler-42 exoplanetary system or the Galilean satellites. The mass and geometry of the disk-bearing FW Tau companion remains unclear. Near-infrared spectroscopy shows deep water bands that indicate a spectral type later than M5, but substantial veiling prevents a more accurate determination of the effective temperature (and hence mass). Both a disk-bearing “planetary-mass” companion seen in direct light or a brown dwarf tertiary viewed in light scattered by an edge-on disk or envelope remain possibilities.