gebhart/patrepeval huggingface dataset:
High tumor cell platelet‐derived growth factor receptor beta expression is associated with shorter survival in malignant pleural epithelioid mesothelioma (2021)

Malignant pleural mesothelioma (MPM) has a rich stromal component containing mesenchymal fibroblasts. However, the properties and interplay of MPM tumor cells and their surrounding stromal fibroblasts are poorly characterized. Our objective was to spatially profile known mesenchymal markers in both tumor cells and associated fibroblasts and correlate their expression with patient survival. The primary study cohort consisted of 74 MPM patients, including 16 patients who survived at least 60 months. We analyzed location-specific tissue expression of seven fibroblast markers in clinical samples using multiplexed fluorescence immunohistochemistry (mfIHC) and digital image analysis. Effect on survival was assessed using Cox regression analyses. The outcome measurement was all-cause mortality. Univariate analysis revealed that high expression of secreted protein acidic and cysteine rich (SPARC) and fibroblast activation protein in stromal cells was associated with shorter survival. Importantly, high expression of platelet-derived growth factor receptor beta (PDGFRB) in tumor cells, but not in stromal cells, was associated with shorter survival (hazard ratio [HR] = 1.02, p < 0.001). A multivariable survival analysis adjusted for clinical parameters and stromal mfIHC markers revealed that tumor cell PDGFRB and stromal SPARC remained independently associated with survival (HR = 1.01, 95% confidence interval [CI] = 1.00-1.03 and HR = 1.05, 95% CI = 1.00-1.11, respectively). The prognostic effect of PDGFRB was validated with an artificial intelligence-based analysis method and further externally validated in another cohort of 117 MPM patients. In external validation, high tumor cell PDGFRB expression associated with shorter survival, especially in the epithelioid subtype. Our findings suggest PDGFRB and SPARC as potential markers for risk stratification and as targets for therapy.
Three different 2,3-dihydroxybiphenyl-1,2-dioxygenase genes in the gram-positive polychlorobiphenyl-degrading bacterium Rhodococcus globerulus P6 (1993)

Rhodococcus globerulus P6 (previously designated Acinetobacter sp. strain P6, Arthrobacter sp. strain M5, and Corynebacterium sp. strain MB1) is able to degrade a wide range of polychlorinated biphenyl (PCB) congeners. The genetic and biochemical analyses of the PCB catabolic pathway reported here have revealed the existence of a PCB gene cluster--bphBC1D--and two further bphC genes--bphC2 and bphC3--that encode three narrow-substrate-specificity enzymes (2,3-dihydroxybiphenyl dioxygenases) that meta cleave the first aromatic ring. None of the bphC genes show by hybridization homology to each other or to bphC genes in other bacteria, and the three bphC gene products have different kinetic parameters and sensitivities to inactivation by 3-chlorocatechol. This suggests that there exists a wide diversity in PCB meta cleavage enzymes.
Chemical Synthesis and Structure of the Prokineticin Bv8 (2010)

Bv8, a 77-residue protein isolated from frogs, is the prototypic member of the prokineticin family of cytokines. Prokineticins (PKs) have only recently been identified in vertebrates (including humans), and they are believed to be involved in a number of key physiological processes, such as angiogenesis, neurogenesis, nociception, and tissue development. We used a combination of Boc solid-phase peptide synthesis, native chemical ligation, and in vitro protein folding to establish robust chemical access to this molecule. Synthetic Bv8 was obtained in good yield and exhibited full activity in a human neuroblastoma cell line and rat dorsal root ganglion (DRG) neurons. The 3D structure of the synthetic protein was determined by using NMR spectroscopy and it was found to be homologous with that of mamba intestinal toxin 1, which is the only other known prokineticin structure. Analysis of a truncated mutant lacking five residues at the N terminus that are critical for receptor binding and activation showed no perturbation to the core protein structure. Together with the functional data, this suggests that receptor binding is likely to be a highly cooperative process possibly involving major allosterically driven structural rearrangements. The facile and efficient synthesis presented here will enable preparation of unique chemical analogues of prokineticins, which should be powerful tools for modulating the structure and function of prokineticins and their receptors, and studying the many physiological processes that have been linked to them.
Potential health implications of water resources depletion and sewage discharges in the Republic of Macedonia (2016)

Potential health implications of deficient sanitation infrastructure and reduced surface water flows due to climate change are examined in the case study of the Republic of Macedonia. Changes in surface water flows and wastewater discharges over the period 1955-2013 were analyzed to assess potential future surface water contamination trends. Simple model predictions indicated a decline in surface water hydrology over the last half century, which caused the surface waters in Macedonia to be frequently dominated by >50% of untreated sewage discharges. The surface water quality deterioration is further supported by an increasing trend in modeled biochemical oxygen demand trends, which correspond well with the scarce and intermittent water quality data that are available. Facilitated by the climate change trends, the increasing number of severe weather events is already triggering flooding of the sewage-dominated rivers into urban and non-urban areas. If efforts to develop a comprehensive sewage collection and treatment infrastructure are not implemented, such events have the potential to increase public health risks and cause epidemics, as in the 2015 case of a tularemia outbreak.
A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID ‐19 (2023)

Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.
Core-Stateless Forwarding With QoS Revisited: Decoupling Delay and Bandwidth Requirements (2020)

Network QoS, fairness and resource sharing control are not completely solved problems. Available solutions lack scalability due to maintaining flow state, require re-tuning if traffic changes, focus on a limited set of networking scenarios or require complex, centralized controllers and feedback loops. In this paper, we propose a core-stateless solution for closed network domains like access, enterprise and data center networks that handles resource sharing and provides guarantees for per-hop latency, independently. The proposed method enables controlled resource sharing by encoding the utility function of flows to Packet Value markings. This allows expressing resource sharing policies for all possible congestion situations, while operation is completely flow unaware inside the network. In addition, it also satisfies per-hop delay requirements for traffic flows independently. The separation of the delay requirements of the packets from their importance has not generally been possible by existing methods so far. The performance of the proposed method has thoroughly been analyzed by large number of simulations covering both static and dynamic scenarios and was implemented in a cloud-native virtual router implementing all the policies needed for a Broadband Network Gateway, showing good performance and better scalability than existing weighted queuing-based solutions.
The crystal structures of semi-synthetic aequorins (2002)

Lipoproteins modified by lipids are localized on the outer or inner membrane of Gram-negative bacteria depending on the sorting signal. Lol system (LolA, LolB and LolCDE complex) mediates translocation of the water-insoluble outer membrane lipoprotein across the periplasm. A periplasmic chaperone LolA and an outer membrane lipoprotein receptor LolB are members of Lol system. We determined crystal structures of LolA and LolB from E. coli at 1.65 and 1.90 resolution, respectively. Unexpected similarity on threedimensional structure indicates that these proteins work as pouches wrapping the hydrophobic lipids of the lipoprotein in common binding site. Significant differences between LolA and LolB also reveal structural basis of the ATP independent translocation mechanism of lipoproteins from LolA to LolB, LolA is a closed pouch with a lid made by alpha-helices covering hydrophobic cavity of the pouch. The closed form of LolA is stabilized by hydrogen bonds between -sheet and the -helical lid. The lid is open to bind the lipoprotein, and tends to expel the associated lipoprotein. ATP hydrolysis energy released in cytosol by the LolCDE complex is converted another energy form as unstable LolA-lipoprotein complex in periplasm. LolB is an open-lid pouch that can associate with the lipoprotein easily. The Lol system utilizes slightly but significant structural differences structures in order to transfer hydrophobic lipoproteins across the periplasm without any additional ATP energy.
The neuropathogenesis of HIV-1 infection (1999)

HIV encephalitis is the common pathologic correlate of HIV-dementia (HAD). HIV-infected brain mononuclear phagocytes (MP) (macrophages and microglia) are reservoirs for persistent viral infection. When activated, MP contribute to neuronal damage. Such activated and virus-infected macrophages secrete cellular and viral factors, triggering neural destructive immune responses. Our Center's laboratories have begun to decipher the molecular and biochemical pathways for MP-mediated neuronal damage in HAD. This review will discuss the salient clinical and pathological features of HAD and highlight the recent advances made, by our scientists and elsewhere, in unraveling disease mechanisms, including the role of chemokines and their receptors in the neuropathogenesis of HIV-1 encephalitis.
ChemInform Abstract: Stable Carbocations. Part 285. 1‐Ferrocenyl‐1‐cyclopropyl Cation: The First Long‐Lived Cyclopropyl Cation. (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
An Evaluation of the Bending Stiffness of Various Tibia1 Fixation Methods (1987)

The relative stiffness of human tibial fixation by plaster casts, intramedullary rods, external fixators, and dynamic compression plates was compared to the stiffness of the intact tibia. Four-point bending was performed on each specimen, first intact, and then after sequential instrumentation, thus allowing each specimen to serve as its own control. The mean stiffnesses obtained for the bone-device complexes, as a percentage of the intact tibial stiffness, were 113 +/- 9% for the delta frame fixator, 57 +/- 14% for the dynamic compression plate, 28 +/- 2% for the unilateral external fixator (UEF) with stainless steel sidebar, 18 +/- 1% for the UEF with aluminum sidebar, 7 +/- 2% for the flexible intramedullary (IM) rods, and 6 +/- 2% for the cast. Even relatively flexible unilateral external fixators are much stiffer than cast or IM rod fixation, methods that usually lead to satisfactory union by secondary healing. If secondary union with callus formation is desirable, modifications of the external fixator may be necessary to provide more flexible fixation. This study may be one of the first attempts to quantitate the stiffness of tibial fixation in a standard cast and compare it with other devices.
On the Fading MIMO Dirty Paper Channel with Lattice Coding and Decoding (2016)

A multiple-input-multiple-output (MIMO) version of Costa's dirty paper channel is studied, where both the input signal and the state experience ergodic fading with channel state information at the receiver. An inner bound using lattice coding and decoding is derived and its gap to the point-to- point ergodic capacity is computed. Under Rayleigh fading, the gap is a constant that vanishes as the number of receive antennas increases, even at finite signal-to-noise ratio (SNR). This implies that under certain configurations the point-to- point capacity can be almost realized in the presence of fading dirt, similar to Costa's result for the non-fading scalar case. The proposed scheme is applied to a class of MIMO broadcast channels with receive channel state information. The scheme is compared to time sharing as well as a dirty paper scheme with non-causal channel state information at the transmitter. The lattice coding scheme is shown to outperform time sharing as well as achieve most of the region of the dirty paper scheme for the cases under study.
Microstructure and Mechanical Properties of the ZrC-Added Mo-Si-B Alloys Prepared by Arc-Melting (2015)

ZrC-added Mo-Si-B alloys were prepared by arc-melting. After heat-treatment at 1800℃ for 24 h, their density and elastic moduli were measured, and their microstructure was evaluated. Moreover, high-temperature compression tests at 1400℃ and four-point bending tests with a Chevron notch at room temperature were conducted to investigate their mechanical properties. The primary phase was Mo solid solution (Moss) or ZrC depending on Mo/ZrC compositional ratio. After the primary phase crystallization, Mo2B, Mo5SiB2 (T2), Moss+ZrC eutectic, Moss+T2 eutectic and/or Moss+Mo3Si+T2 eutectic were crystallized out during solidification. Mo2B and/or Mo3Si dissolved during the heat treatment in some alloys. The ZrC-added Mo-Si-B alloys had higher high-temperature strength compared with the ternary Mo-Si-B alloys even though ZrC-added Mo-Si-B alloys contained less volume fraction of the T2. Besides, the ZrC-added Mo-Si-B alloys exhibited better fracture toughness than that of ternary Mo-Si-B alloys, reaching 20.2 MPa(m)1/2. Therefore, this study found that ZrC plays a significant role in improving high-temperature strength and fracture toughness in Mo-Si-B alloys.
Sorption of flavour compounds by polyethylene terephthalate and copolyester films for food packaging (2023)

Abstract The sorption of flavour compounds by PET and 15 copolyesters (PET copolymerized with isophthalic acid, adipic acid, sebacic acid, tetramethylene glycol, diethylene glycol, triethylene glycol and neopentyl glycol in the range of 5 to 18 mol%) was studied. Biaxially oriented films of each resin were immersed in aqueous solutions containing 37 types of flavour compounds for 4 weeks at 37°C. The amount of flavour compounds sorbed by the films was highly dependent on the copolymer composition. Among the tested films, the copolyester film containing 11 mol% sebacic acid exhibited the highest sorption of the 37 compounds, which was approximately 40 times that of PET. The copolyester film containing 11 mol% isophthalic acid exhibited the lowest sorption, approximately half that of PET. The relationship between sorption and the characteristic values of the polyester films was studied. Sorption was negatively correlated with the solubility parameter and density of the amorphous area and strongly negatively correlated with the glass transition temperature. It was concluded that the dynamic free volume involved in diffusion dominates the sorption of flavour compounds by copolyesters. The log P value and molecular size of the compounds had a strong effect on the sorption of individual flavour compounds by the films in aqueous solutions.
Attenuated renal response to dopaminergic drugs in spontaneously hypertensive rats. (1990)

Activation of renal dopamine-1 receptors decreases sodium transport. However, the spontaneously hypertensive rat retains sodium despite increased renal dopamine concentration. We tested the hypothesis that the abnormal sodium handling in spontaneously hypertensive rats (Okamoto-Aoki strain) is related to a decreased dopaminergic response by studying the effects of the intrarenal infusion of the dopamine-1 agonist SKF-38393 and the dopamine-1 antagonist SCH-23390 in hypertensive and in normotensive Wistar-Kyoto rats. Rats (9-16 weeks old) were studied with renal nerves intact under pentobarbital anesthesia (n = 5-6 in each group). Specificity of dopamine-1 effects of SKF-38393 was verified because its natriuretic effect was blocked in a dose-related manner by the dopamine-1 antagonist SCH-23390 (n = 5). Intrarenal but resulted in a dose-related natriuresis and diuresis in normotensive but not in hypertensive rats. Intrarenal arterial infusion of the dopamine-1 antagonist SCH-23390 alone induced an antinatriuresis, without affecting glomerular filtration rate, in normotensive but not in hypertensive rats. Addition of the dopamine-2 antagonist YM-09151 to the dopamine-1 antagonist infusion did not enhance the effect of the dopamine-1 antagonist. The lack of response to the dopamine-1 agonist or antagonist in hypertensive rats was not due to differences in renal dopamine-1 receptor density (1.3 +/- 0.3 pmol/mg protein for spontaneously hypertensive rats, n = 4; 1 +/- 0.2 for Wistar-Kyoto rats, n = 4) or affinity; distribution determined by autoradiography was also similar. The abnormal renal sodium handling in 9-16-week-old spontaneously hypertensive rats is in part due to decreased response distal to the dopamine-1 receptor.
Data from Integration of Distinct ShcA Signaling Complexes Promotes Breast Tumor Growth and Tyrosine Kinase Inhibitor Resistance (2023)

&lt;div&gt;Abstract&lt;p&gt;The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (&lt;i&gt;SHC1&lt;/i&gt;) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTK), such as ErbB2, bind the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling. However, breast tumors also rely on the ShcA PTB domain to bind numerous negative regulators that limit activation of secondary mitogenic signaling networks. This study examines the role of PTB-independent ShcA pools in controlling breast tumor growth and resistance to tyrosine kinase inhibitors. We demonstrate that PTB-independent ShcA complexes predominately rely on the ShcA SH2 domain to activate multiple Src family kinases (SFK), including Src and Fyn, in ErbB2-positive breast cancers. Using genetic and pharmacologic approaches, we show that PTB-independent ShcA complexes augment mammary tumorigenesis by increasing the activity of the Src and Fyn tyrosine kinases in an SH2-dependent manner. This bifurcation of signaling complexes from distinct ShcA pools transduces non-redundant signals that integrate the AKT/mTOR and SFK pathways to cooperatively increase breast tumor growth and resistance to tyrosine kinase inhibitors, including lapatinib and PP2. This study mechanistically dissects how the interplay between diverse intracellular ShcA complexes impacts the tyrosine kinome to affect breast tumorigenesis.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Implications:&lt;/b&gt; The ShcA adaptor, within distinct signaling complexes, impacts tyrosine kinase signaling, breast tumor growth, and resistance to tyrosine kinase inhibitors. &lt;i&gt;Mol Cancer Res; 16(5); 894–908. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Analysis of the Pyrolytic Behaviour of Birch, Maple, and Rowan Leaves (2021)

A research study was conducted on the thermal behaviour of leaves of urban greenery (birch, maple, and rowan) and the products of their pyrolysis and extraction as assisted by microwaves. The obtained products of pyrolysis and extraction were investigated with the use of FT-IR and UV spectroscopies and XRD techniques. A contractive analysis of samples of chars, condensates, after-extraction residue, and extracts showed that the changes in structural-chemical parameters of leaves of different types of trees during pyrolysis and extraction take place in distinct ways. About 22% of material was removed from birch leaves during extraction, and more than 17% of material was extracted from maple and rowan leaves. It was determined that, during pyrolysis of after-extraction residue of leaves, many fewer PAH compounds with carbonyl groups along with alcohols and phenols are emitted than during pyrolysis of non-extracted leaves. Taking into account that pyrolysis is the first stage of combustion, a decrease in the amount of dangerous compounds in the volatile products of pyrolysis leads to a lower contribution of such compounds in combustion products. This indicates that leaves of urban greenery can be subjected to combustion after extraction, and the obtained extracts can be used as a source of phytochemicals and chemical reagents.
Conus Venoms - A Rich Source of Peptide-Based Therapeutics (2008)

Over two decades of research on venom peptides derived from cone snails ("conopeptides or conotoxins") has led to several compounds that have reached human clinical trials, most of them for the treatment of pain. Remarkably, none of the conopeptides in clinical development mediate analgesia through the opioid receptors, underlying the diverse and novel neuropharmacology evolved by Conus snails. These predatory animals produce an estimated approximately 100,000 distinct conotoxins, a vast majority yet to be discovered and characterized. The conopeptides studied to-date in animal models, have exhibited antinociceptive, antiepileptic, neuroprotective or cardioprotective activities. Screening results also suggest applications of conotoxins in cancer, neuromuscular and psychiatric disorders. Additional potentially important applications of conotoxin research are the discovery and validation of new therapeutic targets, also defining novel binding sites on already validated molecular targets. As the structural and functional diversity of conotoxins is being investigated, the Conus venoms continue to surprise with the plethora of neuropharmacological compounds and potential new therapeutics. This review summarizes recent efforts in the discovery of conopeptides, and their preclinical and clinical development.
On the Use of Optogenetics Wireless Systems in Modern Pathology: Opportunities and Challenges (2019)

Optogenetics tools and techniques are having a great attention lately. Thanks to these techniques, the understanding as well as the treatment of neurodegenerative diseases become more promising. In this work, we present an overview of the optogenetics approach as a tool used in the modern pathology to treat the neurodegenerative diseases. Moreover, the recent applications in modern pathology are presented as well as the wireless optogenetics techniques that ranges from infrared, high frequency, ultra high frequency and ultrasonic technologies. Finally, the challenges of the minimization of the systems as well as the issues related to patient risk are highlighted.