Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA

Bacterial pathogens deliver effector proteins with diverse biochemical activities into host cells, thereby modulating various host functions. Legionella pneumophila hijacks host vesicle trafficking to avoid phagosome–lysosome fusion, a mechanism that is dependent on the Legionella Dot/Icm type IV secretion system. SidM/DrrA, a Legionella type IV effector, is important for the interactions of Legionella-containing vacuoles with host endoplasmic reticulum–derived vesicles. SidM is the only known protein that catalyzes both the exchange of GDP for GTP and GDI displacement from small GTPase Rab1. We determined the crystal structures of SidM alone (residues 317–647) and SidM (residues 193–550) in complex with nucleotide-free WT Rab1. The SidM structure contains an N-terminal helical domain with a potential new function, a Rab1-activation domain, and a C-terminal phosphatidylinositol 4-phosphate–binding P4M domain. The Rab1-activation domain has extensive strong interactions mainly with Rab1 switch I and II regions that undergo substantial conformational changes on SidM binding. Mutations of switch-contacting residues in SidM attenuate both the nucleotide exchange and GDI displacement activities. Structural comparisons of Rab1 in the SidM complex with Rab1-GDP and Ypt1-GDP in the GDI complex identify key conformational changes that disrupt the nucleotide and GDI binding of Rab1. Further biochemical and structural analyses reveal a unique mechanism of coupled GDP release and GDI displacement likely triggered by the SidM-induced drastic displacement of switch I of Rab1.
Finding a role for leptin in the regulation of the Th17 response in experimental arthritis: comment on the article by Deng et al. Reply.

To the Editor: In a recent article, Deng et al (1) confirmed that leptin, a peptide hormone produced by adipose tissue, increases the Th17 response and contributes to disease progression in mice with collagen-induced arthritis (2). In vitro data also showed that leptin treatment significantly enhanced Th17 cell generation from naive CD4 T cells. Their interesting study provides valuable data on the role of leptin in the regulation of the Th17 response in experimental arthritis. Nevertheless, we advise caution with regard to the results of the study. First, the authors investigated whether leptin exerts any direct effect on Th17 cells in vitro. In order to differentiate Th17 cells, naive CD4 T cells from the spleens of mice were cultured with transforming growth factor (TGF ), interleukin-6 (IL-6), and IL-23 (1). However, whether Th17 differentiation requires TGF signaling is a matter of controversy. Several recent reports have shown that Th17 cell differentiation can occur in the absence of TGF (3,4). IL-1 signaling in combination with IL-6 and IL-23 is required for early murine Th17 differentiation, which can occur in the absence of TGF , suggesting that even IL-1 is a crucial cytokine for Th17 differentiation, whereas the addition of TGF may not be required. Second, the results of the study were partly based on IL-17–positive cells and IL-17 levels in vivo and in vitro, and the results may not offer much help for exploring the role of leptin in the regulation of the Th17 response in experimental arthritis. The results identify IL-17–producing CD4 Th17 cells as potential sources of IL-17, but a number of cell types other than Th17 can produce IL-17, including neutrophils, natural killer cells, natural killer T cells, and possibly others (5–7). Thus, it is necessary to carefully investigate the mechanism of leptin in the regulation of IL-17–producing cell responses in experimental arthritis. Overall, the data demonstrate a previously unreported function of leptin in regulating the Th17 response and exacerbating autoimmune arthritis, which may contribute to the improvement in treatment strategies for patients with rheumatoid arthritis. However, the real function of leptin in regulating Th17 cell differentiation remains partly unclear. In order to determine the exact mechanisms of leptin in regulating Th17 cell differentiation, further studies with a large sample size and increased power to detect a difference are required, especially in human systems.
Electrostatic‐Driven Exfoliation and Hybridization of 2D Nanomaterials

Here, direct and effective electrostatic‐driven exfoliation of tungsten trioxide (WO3) powder into atomically thin WO3 nanosheets is demonstrated for the first time. Experimental evidence together with theoretical simulations clearly reveal that the strong binding of bovine serum albumin (BSA) on the surface of WO3 via the protonation of NH2 groups in acidic conditions leads to the effective exfoliation of WO3 nanosheets under sonication. The exfoliated WO3 nanosheets have a greatly improved dispersity and stability due to surface‐protective function of BSA, and exhibit a better performance and unique advantages in applications such as visible‐light‐driven photocatalysis, high‐capacity adsorption, and fast electrochromics. Further, simultaneous exfoliation and hybridization of WO3 and MoS2 nanosheets are demonstrated to form hybrid WO3/MoS2 nanosheets through respective electrostatic and hydrophobic interaction processes. In addition, this electrostatic‐driven exfoliation strategy is applied to exfoliate ultrathin black‐phosphorus nanosheets from its bulk to exhibit a greatly improved stability due to the surface protection by BSA. Overall, the work presented not only presents a facile and effective route to fabricate 2D materials but also brings more opportunities to exploit unusual exotic and synergistic properties in resulting hybrid 2D materials for novel applications.
Rational Development of Neutral Aqueous Electrolytes for Zinc–Air Batteries

Abstract Neutral aqueous electrolytes have been shown to extend both the calendar life and cycling stability of secondary zinc–air batteries (ZABs). Despite this promise, there are currently no modeling studies investigating the performance of neutral ZABs. Traditional continuum models are numerically insufficient to simulate the dynamic behavior of these complex systems because of the rapid, orders‐of‐magnitude concentration shifts that occur. In this work, we present a novel framework for modeling the cell‐level performance of pH‐buffered aqueous electrolytes. We apply our model to conduct the first continuum‐scale simulation of secondary ZABs using aqueous ZnCl2–NH4Cl as electrolyte. We first use our model to interpret the results of two recent experimental studies of neutral ZABs, showing that the stability of the pH value is a significant factor in cell performance. We then optimize the composition of the electrolyte and the design of the cell considering factors including pH stability, final discharge product, and overall energy density. Our simulations predict that the effectiveness of the pH buffer is limited by slow mass transport and that chlorine‐containing solids may precipitate in addition to ZnO.
On the Effect of Selective Laser Melting Process Parameters on the Microstructure and Mechanical Properties of Al Alloys

Additive manufacturing (AM) offers customization of microstructure and mechanical properties of fabricated components according to the material selected, and process parameters applied. Selective laser melting (SLM) is the commonly used technique for processing high strength aluminum alloys. Selection of SLM process parameters could control the microstructure of parts and their mechanical properties. However, the process parameters limit and defects obtained inside the as-built parts present obstacles to customized part production. This study investigates the influence of SLM process parameters on the quality of as-built Al6061 and AlSi10Mg parts according to the mutual connection between the microstructure characteristics and mechanical properties. The microstructure of both materials was characterized for different parts processed over a wide range of SLM process parameters. The optimized SLM parameters were investigated to eliminate the internal microstructure defects. The behaviour of mechanical properties of parts was presented through regression models generated from the design of experiment (DOE) analysis for the results of hardness, ultimate tensile strength, and yield strength. A comparison between the results obtained and that reported in the literature is presented to illustrate the influence of process parameters, build environment, and powder characteristics on the quality of parts produced. The results obtained from this study could help to customize the part’s quality by satisfying their design requirements in addition to reducing the as-built defects which in turn reduce the amount of the post-processing needed.
Haptic interaction with global deformations

Force feedback coupled with a real-time physically realistic graphic display provides a human operator with an artificial sense of presence in a virtual environment. Furthermore, it allows a human operator to interact with the virtual environment through "touch". We describe a haptic simulation system that allows a human operator to perform real-time interaction with soft 3D objects that go through large global deformations. We model and simulate such a global deformation using geometrically nonlinear finite element methods (FEM). We also introduce an efficient method that computes the force feedback, in real-time, by simulating the collision between the virtual "proxy" and the deformable object. To perceptually satisfy a human operator, haptics requires a much higher update frequency (at least 1000 Hz) than graphics. We update the graphics using full simulation and interpolate the fully simulated states at a higher frequency to render haptics. The interpolation is made possible by intentionally delaying the display (both graphics and haptics) by one full simulation cycle.
Representations of Knowledge in a Program for Solving Physics Problems

A computer p rogram w h i c h s o l v e s p h y s i c s p r o b lems s t a t e d i n E n g l i s h i s d e s c r i b e d i n terms o f t h e knowledge w h i c h i s used t o t r a n s f o r m one t y p e o f r e p r e s e n t a t i o n i n t o a n o t h e r . The E n g l i s h s e n t e n c e s o f t h e p r o b l e m s t a t e m e n t a re p r o g r e s s i v e l y t r a n s f o r m e d i n t o a s e m a n t i c n e t w o r k f o r m , a l a n g u a g e f r e e i n t e r n a l model o f t h e o b j e c t s i n t h e p r o b l e m and t h e i r a t t r i b u t e s and r e l a t i o n s h i p s , a s e t o f c a n o n i c a l o b j e c t f rames w h i c h i n t e r p r e t a c t u a l o b j e c t s as c a n o n i c a l o b j e c t s (such as a p o i n t mass) , a g e o m e t r i c m o d e l , a s e t of equat ions , and a p i c t u r e m o d e l . The g e n e r a l n o t i o n o f a c a n o n i c a l o b j e c t f r a m e , w h i c h a b s t r a c t s a s u b s e t o f t h e p r o p e r t i e s o f a n o b j e c t t o f o rm a r e p r e s e n t a t i o n o f a c a n o n i c a l o b j e c t whose i n t e r a c t i o n s w i t h r e l a t e d c a n o n i c a l o b j e c t s can b e f o r m a l l y m o d e l l e d , i s d i s c u s s e d as a method o f o r g a n i z i n g p r o b l e m s o l v i n g p r o g r a m s .
Performance of Textile and Apparel Companies Listed on the Warsaw Stock Exchange

The article presents the performance of textile and apparel companies listed on the Polish stock exchange from the market perspective based on a sample of financial data. The data are used to compute systematic risk measures (betas) for two different time intervals, to evaluate the risk of an equally weighted portfolio made up of the selected companies and to compare the portfolio’s Sharpe ratio with the broad market index and small companies’ index. To compare the selected companies’ stocks with the whole economy and non-public companies, DuPont analysis is employed. The research results indicate that the listed textile and apparel companies outperform non-public companies in terms of fundamental financial results as well as capital market investment results. The risk of individual stocks is usually relatively low. Also the portfolio of the selected companies has been found to have better investment properties compared with the general market and small stocks index in all years of analysis.
Synthesis of Polymer Inclusion Membranes based on Cellulose Triacetate for Recovery of Lanthanum(III) from Aqueous Solutions

Abstract Polymer inclusion membrane (PIM) containing cellulose triacetate (CTA) as a polymer matrix and 2-nitrophenyl octyl ether (NPOE) as a plasticizer was developed. This membrane also contained di(2-ethylhexyl)phosphoric acid (D2EHPA) and tributyl phosphate (TBP) as the carriers of metal ions. The facilitated transport of lanthanum(III) from aqueous nitrate(V) solutions across PIM was studied. It was observed that metal ions were transported from the source phase into 2M H2SO4 as the receiving phase. The transport through PIM with D2EHPA as the ion carrier was found as the more effective method of lanthanum(III) removal from the aqueous solution than transport through PIM with TBP as the ion carrier.
Electrocardiographic Comparison of Ventricular Premature Complexes during Exercise Test in Patients with CPVT and Healthy Subjects

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but highly malignant inherited arrhythmic disorder. Although a standardized exercise stress test (ST) is the most reliable way to diagnose CPVT, in 30% only single ventricular premature beats (VPCs) were recorded.
Intracameral bevacizumab in the treatment of neovascular glaucoma and exudative retinal detachment after brachytherapy in choroidal melanoma.

Choroidal melanoma is the most common primary intraocular tumor in adults. Plaque brachytherapy is a common treatment option for medium-sized tumors. Radiation retinopathy and its sequellae, including neovascularization of the iris (NVI), neovascular glaucoma (NVG), and exudative retinal detachment (ERD), are among the known side effects of radiation treatment. NVI can develop as soon as 9 months after radiation (mean time of 27 months) and secondary NVG develops in up to 23% of eyes at 5 years. ERD occurs following plaque radiotherapy in up to 16% of patients. Treatment options for managing NVG secondary to brachytherapy include medical therapy, panretinal photocoagulation, cyclodestructive procedures, anti–vascular endothelial growth factor (VEGF) therapy, and, in some cases, enucleation. Typically, there are no specific treatments directed to ERDs in treated choroidal melanoma patients. Multiple reports have shown that intravitreal bevacizumab (Avastin, Genentech Inc, San Francisco, Calif.) an antiVEGF agent, reduces neovascular activity and vascular permeability in ocular tissues. Bevacizumab can be administered intravitreally or intracamerally to reduce NVI secondary to diabetes and other retinal vascular diseases. We report the use of intracameral bevacizumab in a patient with NVG and ERD following brachytherapy for a medium-sized choroidal melanoma. A 45-year-old woman was treated with iodine-125 (I-125) brachytherapy for a medium-sized choroidal melanoma (thickness of 6.8 mm, 10 mm at its largest diameter). There was no retinal detachment (RD) at the time of diagnosis. Fourteen months post treatment, a total ERD was noted despite local tumor control (4.26 mm thickness). Three months later, she developed a painful left eye and decreased visual acuity to no light perception (NLP). The intraocular pressure (IOP) was 50 mm Hg. Corneal edema was present, with 360° of NVI; the angle was open and neovascularization of the angle was noted. The tumor height was 4.35 mm by ultrasound. Maximum medical therapy was initiated to treat the elevated IOP. Panretinal photocoagulation could not be performed because of the extent of the RD. Bevacizumab (1.25 mg) was injected intracamerally since the intravitreal approach was deemed unsafe in the presence of an RD. One week post injection, the IOP was 36 mm Hg. On examination, there was regression of the iris and angle neovascularization, which was evident on iris angiography (Fig. 1). One month post injection, visual acuity remained NLP, IOP was 20 mm Hg, and some iris vessels were visible. Intracameral bevacizumab injections were repeated
The Bacterial Ecosystem of Mother’s Milk and Infant’s Mouth and Gut

The progressive building of the infants’ gut microbiota is pivotal for educating their immune system. Human breast milk is among the first sources of microbes for the assembly of the infant’s microbiota, but research struggles to give a demonstration for the origin of bacteria in milk. Aiming at contributing to the knowledge on assembly of the mother’s milk and infant’s microbiome, here we characterized the oral, gut and milk ecosystems in a homogeneous cohort of 36 healthy mother–infants pairs, by 16S rRNA next-generation sequencing. A limited number of operational taxonomic units (OTUs) was shared among the three ecosystems, including not only OTUs assigned to the well-known immune-modulating Bifidobacterium genus, but also specific Streptococcus and Staphylococcus OTUs, which were dominant in the infant’s mouth ecosystem. The high conservation of these OTUs among the three ecosystems seems to call for a worth exploring ecological role through targeted and/or culture-dependent techniques. Notwithstanding the limitations of a 16S rRNA gene-based molecular characterization, we might hypothesize that the baby’s mouth, being the transition point for the milk to reach the intestine, could play a role in both the gut microbiota assembly, via deglutition, and mother’s milk duct colonization, during suction.
Croatia’s EU Convergence Report: Reaching and Sustaining Higher Rates of Economic Growth / The World Bank, 2009

The causes behind achieving different economic growth rates have been a major focus of economic research for a long time now, the result of which are various growth theories: from the Harrod-Domar model based on the capital accumulation to the modern, endogenous theories that emphasize the role of technological progress (Romer, 1986, 1990 ) and human capital (Lucas, 1988). It is well known that generators of growth differ among countries, and that the strategies applied will depend on country’s specific circumstances and constraints. Individual country potential in achieving higher rates of economic growth and development will primarily depend on its ability to improve the technology and capital used by workers: “Productivity isn’t everything, but in the long run it is almost everything” (Krugman, 1994). Thus, it is not surprising that the report whose review follows specifies total factor productivity (TFP) as critical and hitherto hidden potential for reaching higher rates of economic growth in Croatia. In addition, another important subject within the research of economic growth and development is the issue of convergence, i.e. whether there is a tendency of narrowing the real per capita income gap between rich and poor countries over the long run. There are two aspects of convergence offered in the literature: absolute or beta, and conditional or sigma convergence. Empirical distinction between the two was introduced by Barro and Sala-i-Martin (1995). While the first one assumes that there is a negative relation between initial level and growth rate of per capita income (i.e. the presumption that poorer economies will grow faster than the richer ones), according to the conditional convergence hypothesis, countries converge on different growth paths determined by their own labor force growth and technological progress (Gärtner, 2003). The concept of conditional convergence and the neo-classical growth model are also in the background of the analysis applied in the “Croatia’s EU Convergence Report: Reaching and Sustaining Higher Rates of Economic Growth”.
DPP4 in Diabetes

Dipeptidyl-peptidase 4 (DPP4) is a glycoprotein of 110 kDa, which is ubiquitously expressed on the surface of a variety of cells. This exopeptidase selectively cleaves N-terminal dipeptides from a variety of substrates, including cytokines, growth factors, neuropeptides, and the incretin hormones. Expression of DPP4 is substantially dysregulated in a variety of disease states including inflammation, cancer, obesity, and diabetes. Since the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP), are major regulators of post-prandial insulin secretion, inhibition of DPP4 by the gliptin family of drugs has gained considerable interest for the therapy of type 2 diabetic patients. In this review, we summarize the current knowledge on the DPP4–incretin axis and evaluate most recent findings on DPP4 inhibitors. Furthermore, DPP4 as a type II transmembrane protein is also known to be cleaved from the cell membrane involving different metalloproteases in a cell-type-specific manner. Circulating, soluble DPP4 has been identified as a new adipokine, which exerts both para- and endocrine effects. Recently, a novel receptor for soluble DPP4 has been identified, and data are accumulating that the adipokine-related effects of DPP4 may play an important role in the pathogenesis of cardiovascular disease. Importantly, circulating DPP4 is augmented in obese and type 2 diabetic subjects, and it may represent a molecular link between obesity and vascular dysfunction. A critical evaluation of the impact of circulating DPP4 is presented, and the potential role of DPP4 inhibition at this level is also discussed.
Novel Antibody-Based Proteins for Cancer Immunotherapy

The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value. Tumor burden, immune evasion, physiological resemblance, and cell plasticity are among the challenges that cancer therapy faces, and a number of antibody-based proteins are already available to deal with many of them. Some of these novel reagents have been shown to specifically increase apoptosis/cell death of tumor cells, recruit and activate immune effectors, and reveal synergistic effects not previously envisioned. In this review, we look into different approaches that have been followed during the past few years to produce these biologics and analyze their relative success, mainly in terms of their clinical performance. The use of antibody-based antitumor proteins, in combination with standard or novel therapies, is showing significant improvements in objective responses, suggesting that these reagents will become important components of the antineoplastic protocols of the future.