gebhart/patrepeval huggingface dataset:
Novel synthetic derivatives of the natural product berbamine inhibit Jak2/Stat3 signaling and induce apoptosis of human melanoma cells (2012)

Persistent Jak/Stat3 signal transduction plays a crucial role in tumorigenesis and immune development. Activated Jak/Stat3 signaling has been validated as a promising molecular target for cancer therapeutics discovery and development. Berbamine (BBM), a natural bis-benzylisoquinoline alkaloid, was identified from the traditional Chinese herbal medicine Berberis amurensis used for treatment of cancer patients. While BBM has been shown to have potent antitumor activities with low toxicity in various cancer types, the molecular mechanism of action of BBM remains largely unknown. Here, we determine the antitumor activities of 13 synthetic berbamine derivatives (BBMDs) against human solid tumor cells. BBMD3, which is the most potent in this series of novel BBMDs, exhibits over 6-fold increase in biological activity compared to natural BBM. Moreover, BBMD3, directly inhibits Jak2 autophosphorylation kinase activity in vitro with IC(50)0.69 μM. Autophosphorylation of Jak2 kinase at Tyr1007/1008 sites also was strongly inhibited in the range of 15 μM of BBMD3 in human melanoma cells at 4h after treatment. Following inhibition of autophosphorylation of Jak2, BBMD3 blocked constitutive activation of downstream Stat3 signaling in melanoma cells. BBMD3 also down-regulated expression of the Stat3 target proteins Mcl-1and Bcl-x(L), associated with induction of apoptosis. In sum, our findings demonstrate that the novel berbamine derivative BBMD3 is an inhibitor of the Jak2/Stat3 signaling pathway, providing evidence for a molecular mechanism whereby BBMD3 exerts at least in part the apoptosis of human melanoma cells. In addition, BBMD3 represents a promising lead compound for development of new therapeutics for cancer treatment.
ϒ production and nuclear modification at forward rapidity in Pb–Pb collisions at sNN=5.02TeV (2021)

The production of mesons in Pb-Pb collisions at a centre-of-mass energy per nucleon pair s NN = 5.02 TeV is measured with the muon spectrometer of the ALICE detector at the LHC. The yields as well as the nuclear modification factors are determined in the forward rapidity region 2.5 < y < 4.0, as a function of rapidity, transverse momentum and collision centrality. The results show that the production of the (1S) meson is suppressed by a factor of about three with respect to the production in protonproton collisions. For the first time, a significant signal for the (2S) meson is observed at forward rapidity, indicating a suppression stronger by about a factor 2-3 with respect to the ground state. The measurements are compared with transport, hydrodynamic, comover and statistical hadronisation model calculations.
Peptide Model of the Mutant Proinsulin Syndrome. II. Nascent Structure and Biological Implications (2022)

Toxic misfolding of proinsulin variants in β-cells defines a monogenic diabetes syndrome, designated <i>mutant INS-gene induced diabetes of the young</i> (MIDY). In our first study (previous article in this issue), we described a one-disulfide peptide model of a proinsulin folding intermediate and its use to study such variants. The mutations (Leu<sup>B15</sup>→Pro, Leu<sup>A16</sup>→Pro, and Phe<sup>B24</sup>→Ser) probe residues conserved among vertebrate insulins. In this companion study, we describe <sup>1</sup>H and <sup>1</sup>H-<sup>13</sup>C NMR studies of the peptides; key NMR resonance assignments were verified by synthetic <sup>13</sup>C-labeling. Parent spectra retain nativelike features in the neighborhood of the single disulfide bridge (cystine B19-A20), including secondary NMR chemical shifts and nonlocal nuclear Overhauser effects. This partial fold engages wild-type side chains Leu<sup>B15</sup>, Leu<sup>A16</sup> and Phe<sup>B24</sup> at the nexus of nativelike α-helices α<sub>1</sub> and α<sub>3</sub> (as defined in native proinsulin) and flanking β-strand (residues B24-B26). The variant peptides exhibit successive structural perturbations in order: parent (most organized) > Ser<sup>B24</sup> >> Pro<sup>A16</sup> > Pro<sup>B15</sup> (least organized). The same order pertains to (a) overall α-helix content as probed by circular dichroism, (b) synthetic yields of corresponding three-disulfide insulin analogs, and (c) ER stress induced in cell culture by corresponding mutant proinsulins. These findings suggest that this and related peptide models will provide a general platform for classification of MIDY mutations based on molecular mechanisms by which nascent disulfide pairing is impaired. We propose that the syndrome's variable phenotypic spectrum-onsets ranging from the neonatal period to later in childhood or adolescence-reflects structural features of respective folding intermediates.
AN INTEGRATED APPROACH TO MONITORING A FIELD TEST OF IN SITU CONTAMINANT DESTRUCTION (1998)

The development of in situ thermal remediation techniques requires parallel development of techniques capable of monitoring the physical and chemical changes for purposes of process control. Recent research indicates that many common contaminants can be destroyed in situ by hydrous pyrolysis/oxidation (HPO), eliminating the need for costly surface treatment and disposal. Steam injection, combined with supplemental air, can create the conditions in which HP0 occurs. Field testing of this process, conducted in the summer of 1997, indicates rapid destruction of polycyclic aromatic hydrocarbons (PAHs). Previous work established a suite of underground geophysical imaging techniques capable of providing sufficient knowledge of the physical changes in the subsurface during thermal treatment at sufficient frequencies to be used to monitor and guide the heating and extraction processes. In this field test, electrical resistance tomography (ERT) and temperature measurements provided the primary information regarding the temporal and spatial distribution of the heated zones. Verifying the in situ chemical destruction posed new challenges. We developed field methods for sampling and analyzing hot water for contaminants, oxygen, intermediates and products of reaction. Since the addition of air or oxygen to the contaminated region is a critical aspect of HPO, noble gas tracers were used to identify fluids from different sources. The combination of physical monitoring with noble gas identification of the native and injected fluids and accurate fluid sampling resulted in an excellent temporal and spatial evaluation of the subsurface processes, from which the amount of in situ destruction occurring in the treated region could be quantified. The experimental field results constrain the destruction rates throughout the site, and enable site management to make accurate estimates of total in situ destruction based on the recovered carbon. As of October, 1998, over 400,000 kg (900,000 lb) of contaminant have been removed from the site; about 18% of this has been destroyed in situ.
Involvement of PatE, a Prophage-Encoded AraC-Like Regulator, in the Transcriptional Activation of Acid Resistance Pathways of Enterohemorrhagic Escherichia coli Strain EDL933 (2012)

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a lethal human intestinal pathogen that causes hemorrhagic colitis and the hemolytic-uremic syndrome. EHEC is transmitted by the fecal-oral route and has a lower infectious dose than most other enteric bacterial pathogens in that fewer than 100 CFU are able to cause disease. This low infectious dose has been attributed to the ability of EHEC to survive in the acidic environment of the human stomach. In silico analysis of the genome of EHEC O157:H7 strain EDL933 revealed a gene, patE, for a putative AraC-like regulatory protein within the prophage island, CP-933H. Transcriptional analysis in E. coli showed that the expression of patE is induced during stationary phase. Data from microarray assays demonstrated that PatE activates the transcription of genes encoding proteins of acid resistance pathways. In addition, PatE downregulated the expression of a number of genes encoding heat shock proteins and the type III secretion pathway of EDL933. Transcriptional analysis and electrophoretic mobility shift assays suggested that PatE also activates the transcription of the gene for the acid stress chaperone hdeA by binding to its promoter region. Finally, assays of acid tolerance showed that increasing the expression of PatE in EHEC greatly enhanced the ability of the bacteria to survive in different acidic environments. Together, these findings indicate that EHEC strain EDL933 carries a prophage-encoded regulatory system that contributes to acid resistance.
Streaming Gibbs Sampling for LDA Model (2016)

Streaming variational Bayes (SVB) is successful in learning LDA models in an online manner. However previous attempts toward developing online Monte-Carlo methods for LDA have little success, often by having much worse perplexity than their batch counterparts. We present a streaming Gibbs sampling (SGS) method, an online extension of the collapsed Gibbs sampling (CGS). Our empirical study shows that SGS can reach similar perplexity as CGS, much better than SVB. Our distributed version of SGS, DSGS, is much more scalable than SVB mainly because the updates' communication complexity is small.
Sulfates of the Refractory Metals: Crystal Structure and Thermal Behavior of Nb2O2(SO4)3, MoO2(SO4), WO(SO4)2, and Two Modifications of Re2O5(SO4)2 (2011)

The sulfates Nb(2)O(2)(SO(4))(3), MoO(2)(SO(4)), WO(SO(4))(2,) and two modifications of Re(2)O(5)(SO(4))(2) have been synthesized by the solvothermal reaction of NbCl(5), WOCl(4), Re(2)O(7)(H(2)O)(2), and MoO(3) with sulfuric acid/SO(3) mixtures at temperatures between 200 and 300 °C. Besides the X-ray crystal structure determination of all compounds, the thermal behavior was investigated using thermogravimetric studies. WO(SO(4))(2) (monoclinic, P2(1)/n, a = 7.453(1) Å, b = 11.8232(8) Å, c = 7.881(1) Å, β = 107.92(2)°, V = 660.7(1) Å(3), Z = 4) and both modifications of Re(2)O(5)(SO(4))(2) (I: orthorhombic, Pba2, a = 9.649(1) Å, b = 8.4260(8) Å, c = 5.9075(7) Å, V = 480.27(9) Å(3), Z = 2; II: orthorhombic, Pbcm, a = 7.1544(3) Å, b = 7.1619(3) Å, c = 16.8551(7) Å, V = 863.64(6) Å(3), Z = 4) are the first structurally characterized examples of tungsten and rhenium oxide sulfates. Their crystal structure contains layers of sulfate connected [W═O] moieties or [Re(2)O(5)] units, respectively. The cohesion between layers is realized through weak M-O contacts (343-380 pm). Nb(2)O(2)(SO(4))(3) (orthorhombic, Pna2(1), a = 9.9589(7) Å, b = 11.7983(7) Å, c = 8.6065(5) Å, V = 1011.3(1) Å(3), Z = 4) represents a new sulfate-richer niobium oxide sulfate. The crystal structure contains a three-dimensional network of sulfate connected [Nb═O] moieties. In MoO(2)(SO(4)) (monoclinic, I2/a, a = 8.5922(6) Å, b = 12.2951(6) Å, c = 25.671(2) Å, β = 94.567(9)°, V = 2703.4(3) Å(3), Z = 24) [MoO(2)] units are connected through sulfate ions to a three-dimensional network, which is pervaded by channels along [100] accommodating the terminal oxide ligands. In all compounds except WO(SO(4))(2), the metal ions are octahedrally coordinated by monodentate sulfate ions and oxide ligands forming short M═O bonds. In WO(SO(4))(2), the oxide ligand and two monodentate and two bidentate sulfate ions build a pentagonal bipyramid around W. The thermal stability of the sulfates decreases in the order Nb > Mo > W > Re; the residues formed during the decomposition are the corresponding oxides.
NMDA receptor modulators: an updated patent review (2013 – 2014) (2014)

The number of patents involving novel NMDA receptor modulators suggests a renewed interest in the NMDA receptor as a therapeutic target. Subunit-selective modulators continue to show promise, and the development of new subunit-selective NMDA receptor modulators appears poised for continued growth. Although a modest number of channel blocker patents were published, successful clinical outcomes involving ketamine have led to a resurgent interest in low-affinity channel blockers as therapeutics.
Proteins of vesicular stomatitis virus. V. Identification of a precursor to the phosphoprotein of Piry virus (1979)

A metabolic precursor to the major phosphoprotein of Piry virus (NSv) has been identified in extracts of Piry virus-infected L cells. The conversion of the precursor NSi to NSv occurs with a half-life of 20 min and is independent of continued protein synthesis. NSi has a greater electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than does the product NSv, suggesting an increase in molecular weight during maturation. The conversion is unaffected by cyclic AMP, cyclic GMP, or by theophilline and cordycepin. No decrease in isoelectric point of NSv relative to NSi was observed on isoelectric focusing acrylamide gels. These latter observations suggest that NSi and NSv do not differ in extent of phosphorylation. We also report, without further characterization, the identification of another phosphoprotein in Piry virus-infected cells having an electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis just slightly greater than the nucleocapsid N protein.
Flow cytometric measurement of fluorescence (Förster) resonance energy transfer from cyan fluorescent protein to yellow fluorescent protein using single‐laser excitation at 458 nm (2003)

These results demonstrated the feasibility of flow cytometric detection of FRET signals from CFP to YFP by excitation with the 458-nm line from the tunable argon-ion laser. The method was as efficient as excitation with the krypton UV laser and therefore should make FRET a more generally available flow cytometric technique.
First proton minibeam radiation therapy treatment plan evaluation (2020)

Proton minibeam radiation therapy (pMBRT) is a novel dose delivery method based on spatial dose fractionation. pMBRT has been shown to be promising in terms of reduced side effects and superior tumour control in high-grade glioma-bearing rats compared to standard irradiation. These findings, together with the recent optimized implementation of pMBRT in a clinical pencil beam scanning system, have triggered reflection on the possible application to patient treatments. In this context, the present study was designed to conduct a first theoretical investigation of the clinical potential of this technique. For this purpose, a dedicated dose engine was developed and used to evaluate two clinically relevant patient treatment plans (high-grade glioma and meningioma). Treatment plans were compared with standard proton therapy plans assessed by means of a commercial treatment planning system (ECLIPSE-Varian Medical systems) and Monte Carlo simulations. A multislit brass collimator consisting of 0.4 mm wide slits separated by a centre-to-centre distance of 4 or 6 mm was placed between the nozzle and the patient to shape the planar minibeams. For each plan, spread-out Bragg peaks and homogeneous dose distributions (±7% dose variations) can be obtained in target volumes. The Peak-to-Valley Dose Ratios (PVDR) were evaluated between 9.2 and 12.8 at a depth of 20 mm for meningioma and glioma, respectively. Dose volume histograms (DVHs) for target volumes and organs at risk were quantitatively compared, resulting in a slightly better target homogeneity with standard PT than with pMBRT plans, but similar DVHs for deep-seated organs-at-risk and lower average dose for shallow organs. The proposed delivery method evaluated in this work opens the way to an effective treatment for radioresistant tumours and will support the design of future clinical research.
When the screen is not enough (2013)

The study of visual perception and higher order cognitive processes, such as memory, has been performed mainly in controlled experimental environments given by the researchers' laboratories. However, the laboratory environment experiments cannot capture naturalistic behaviours and are, therefore, a limited approximation to the behaviours in real conditions. To study how the environment affects behavioural studies we have performed an exploratory art experiment in the controlled environment of our laboratory and in the British Museum in London.
Microfluidics-mediated isothermal detection of enzyme activity at the single molecule level (2011)

Conventional analysis of enzymatic activity, often carried out on pools of cells, is blind to heterogeneity in the population. Here, we combine microfluidics with a previously developed isothermal rolling circle amplification-based assay to investigate multiple enzymatic activities in down to single cells. This microfluidics-meditated assay performs at very high sensitivity in picoliter incubators with small quantities of biological materials. Furthermore, we demonstrate the assay's capability of multiplexed detection of at least three enzyme activities at the single molecule level.
Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance (2020)

The efficacy of psychedelic-assisted therapies for mental disorders has been attributed to the lasting change from experiential avoidance to acceptance that these treatments appear to facilitate. This article presents a conceptual model that specifies potential psychological mechanisms underlying such change, and that shows substantial parallels between psychedelic therapy and cognitive behavioral therapy: We propose that in the carefully controlled context of psychedelic therapy as applied in contemporary clinical research, psychedelic-induced belief relaxation can increase motivation for acceptance <i>via</i> operant conditioning, thus engendering episodes of relatively avoidance-free exposure to greatly intensified private events. Under these unique learning conditions, relaxed avoidance-related beliefs can be exposed to corrective information and become revised accordingly, which may explain long-term increases in acceptance and corresponding reductions in psychopathology. Open research questions and implications for clinical practice are discussed.
Use of liquid chromatographic methods for gelatin differentiation in halal verification (2014)

A wide diversity of gelatin sources that supported by the largest scale of porcine gelatin production in a global market has raised doubts among Muslim consumers towards gelatin-based ingredients products. The skepticism has been addressed through the implementation of food labelling regulations that require manufacturers to state the source of gelatin on the packaging. Since the application of halal certification is voluntary and not compulsory for industry players, hence it gives significant drawbacks. Without strictly monitoring and enforcement, the probability of contamination with non-halal materials during the production process and lacking of halal integrity particularly in the supply chain of raw materials may increase the number of masbooh and non-compliance products according to the Islamic law. Therefore, a trust on the halal products must be strengthened with the scientific evidence. This paper attempts to critically review on liquid chomatographic methods in determining the species origin of gelatin. It covers series of technological changes from a simple of high performance liquid chromatography (HPLC) to the system that coupled with mass spectrometry. A large similarity in amino acids profile and polypeptide sequences of the mammalian gelatin will be the main challenge in developing the analytical methods. Matrix interference in the gelatin-based products, adulteration and fraud in the mixed ingredients are an inevitable, hence it need to be tackled and solved. These analytical methods are expected to be used as tools to provide scientific evidences for halal verification on the gelatin-based products.
Supplementary Table 1 from A Pilot Clinical Study of Treatment Guided by Personalized Tumorgrafts in Patients with Advanced Cancer (2023)

Supplementary Table 1 from A Pilot Clinical Study of Treatment Guided by Personalized Tumorgrafts in Patients with Advanced Cancer
Free-Breathing Low-Field MRI of the Lungs Detects Functional Alterations Associated With Persistent Symptoms After COVID-19 Infection (2022)

Functional pulmonary examinations using free-breathing 0.55 T MRI with PREFUL analysis revealed potential quantitative markers of impaired lung function in patients with persistent symptoms after COVID-19 infection, potentially complementing morphologic imaging. Future work is needed to explore the translational relevance and clinical implication of these findings.
Anti-HIV-1 Activities of 1,3-Dioxolane Guanine and 2,6-Diaminopurine Dioxolane (1999)

DXG and its prodrug DAPD have been demonstrated to be effective inhibitors of HIV-1 in various cells. The EC50s for DXG were 0.032 microM in CBMCs and 0.05 microM in MT-4 cells, which were generally equipotent as 3TC. 3TC-resistant, but not AZT-resistant, HIV-1 had minimum diminished sensitivity to the compounds. Both DXG and DAPD were non-toxic to cells up to 500 microM.
Data from FcRL5 as a Target of Antibody–Drug Conjugates for the Treatment of Multiple Myeloma (2023)

&lt;div&gt;Abstract&lt;p&gt;Fc receptor-like 5 (FcRL5/FcRH5/IRTA2/CD307) is a surface protein expressed selectively on B cells and plasma cells. We found that FcRL5 was expressed at elevated levels on the surface of plasma cells from the bone marrow of patients diagnosed with multiple myeloma. This prevalence in multiple myeloma and narrow pattern of normal expression indicate that FcRL5 could be a target for antibody-based therapies for multiple myeloma, particularly antibody–drug conjugates (ADC), potent cytotoxic drugs linked to antibodies via specialized chemical linkers, where limited expression on normal tissues is a key component to their safety. We found that FcRL5 is internalized upon antibody binding, indicating that ADCs to FcRL5 could be effective. Indeed, we found that FcRL5 ADCs were efficacious &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; but the unconjugated antibody was not. The two most effective consisted of our anti-FcRL5 antibody conjugated through cysteines to monomethylauristatin E (MMAE) by a maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (MC-vcPAB) linker (anti-FcRL5-MC-vcPAB-MMAE) or conjugated via lysines to the maytansinoid DM4 through a disulfide linker (anti-FcRL5-SPDB-DM4). These two ADCs were highly effective &lt;i&gt;in vivo&lt;/i&gt; in combination with bortezomib or lenalidomide, drugs in use for the treatment of multiple myeloma. These data show that the FcRL5 ADCs described herein show promise as an effective treatment for multiple myeloma. &lt;i&gt;Mol Cancer Ther; 11(10); 2222–32. ©2012 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;