gebhart/patrepeval huggingface dataset:
Nonclinical Safety and Toxicokinetics of MnTnBuOE-2-PyP5+(BMX-001) (2016)

BMX-001, a manganese porphyrin that has anti-inflammatory, antioxidant, and antitumor properties, is being developed as a potential therapeutic for high-grade glioma (HGG) and head and neck (H&N) cancer. An IND has been opened for BMX-001 in the treatment of HGG (NCT02655601) and another is in preparation for H&N. The safety of BMX-001 has been evaluated in a battery of nonclinical Good Laboratory Practice (GLP)-compliant studies. Systemic toxicity has been evaluated using the intended cGMP product administered subcutaneously for periods of up to 5 weeks in both the mouse and the monkey and included toxicokinetic evaluations to characterize systemic exposure and tissue distribution and clearance of BMX-001. In additional GLP studies, BMX-001 was not irritating to the skin or eye and caused no changes in cardiac rate or rhythm or blood pressure. Mixed results for genotoxicity were seen with the weight of evidence indicating that BMX-001 poses no genotoxic risk in humans. In systemic mouse and monkey studies, loading/maintenance dose no observed adverse effect levels were 12/2 mg/kg/dose and 6/2 mg/kg/dose, respectively, with maintenance doses administered every 3 days after the initial loading dose. Systemic data were used to determine a Food and Drug Administration-approved safe starting dose for the initial clinical study in patients with HGG. BMX-001 was detected in analyzed tissues, including the brain, persisting well past the short plasma clearance period. The highest levels of BMX-001 were seen in the liver and kidneys, with amounts in these tissues returning to close to undetectable levels after a 2-week cessation of dosing.
IMMUNOASSAY OF ENDOGENOUS PLASMA INSULIN IN MAN (1960)

For years investigators have sought an assay for insulin which would combine virtually absolute specificity with a high degree of sensitivity, sufficiently exquisite for measurement of the minute insulin concentrations usually present in the circulation. Methods in use recently depend on the ability of insulin to exert an effect on the metabolism of glucose in vivo or in excised muscle or adipose tissue. Thus, the insulin concentration in plasma has been estimated: a) from the degree of hypoglycemia produced in hypophysectomized, adrenalectomized, alloxan-diabetic rats (1); b) from the augmentation of glucose uptake by isolated rat hemidiaphragm (2); or c) from the increased oxidation of glucose-1-C14 by the rat epididymal fat pad (3). Since there have been reports indicating the presence, in plasma, of inhibitors of insulin action (4) and of noninsulin substances capable of inducing an insulin-like effect (5,6), these procedures, while yielding interesting information regarding the effects of various plasmas on glucose metabolism in tissues, are of doubtful specificity for the measurement of insulin per se (5).
Aromatic nucleophilic substitution on Cr(CO)3-complexed halogenoarenes: a new synthesis of O-aryloximes and their cyclization to benzofurans (1985)

A. Alemagna, C. Baldoli, P. Del Buttero, E. Licandro and S. Maiorana, J. Chem. Soc., Chem. Commun., 1985, 417 DOI: 10.1039/C39850000417
Wnt signaling induces epithelial differentiation during cutaneous wound healing (2006)

These findings suggest that adult interfollicular epithelium is capable of responding to Wnt morphogenic signals necessary for restoring epithelial tissue patterning in the skin during wound repair.
Predictive log-synchronization (2006)

This paper proposes predictive log-synchronization, an alternative paradigm to the software transactional memory approach for simplifying the design of concurrent data structures. Predictive log-synchronization simplifies concurrent programming and program verification by requiring programmers to write only specialized sequential code. This sequential code is then automatically transformed into a non-blocking concurrent program in which threads coordinate all data structure operations via a shared lock-controlled log. The non-blocking progress property is achieved by having threads that fail to acquire the lock predict the outcome of their operations by reading the log and state and computing the effect of these operations without modifying the actual data structure.Log-synchronization is founded on the belief (at this point unsubstantiated by statistical data) that in many concurrent data structures used in real-world applications, the ratio of high level operations that modify the structure to ones that simply read it, greatly favors read-only operations, and what's more, that many natural data structures have inherent sequential bottlenecks limiting the concurrency among operations that modify the structure. It follows that delegating all data structure modifications to a single lock-controlled thread at a time will not significantly harm the throughput of modifying operations. Moreover, as we show, it can boost read-only throughput by significantly reducing the overhead of coordination among concurrent operations, and provides a way to simplify concurrent data structures.Initial experimental testing using a Java-based implementation of predictive log-synchronization showed that a log-synchronized concurrent red-black tree is up to five times faster than a simple lock-based one. This paper presents our current understanding of the advantages, drawbacks, and scope of predictive log-synchronization.
Scanning the Future—Ultrasonography as a Reproductive Management Tool for Dairy Cattle (2002)

Application of transrectal real-time ultrasonography as a research tool to study bovine reproduction represents a technological breakthrough that has revolutionized our understanding of reproductive biology in cattle. The widespread adoption and use of ultrasonography for routine reproductive examinations of dairy cattle by bovine practitioners is the next contribution this technology will make to the dairy industry. Assessment of pregnancy status and fetal viability early postbreeding to identify cows that fail to conceive improves reproductive efficiency by decreasing the interval between artificial insemination services and increasing artificial insemination service rate. Early identification of cows carrying twin fetuses will allow for implementation of differential management strategies to abrogate negative effects of twinning during the periparturient period once such strategies have been developed. Ovarian and uterine pathologies not accurately detected via rectal palpation can easily be visualized by ultrasound, and appropriate therapies can be implemented. Determination of fetal sex in utero is useful when coupled with a management decision that justifies the expense of fetal sexing. Development of integrated reproductive management systems that combine ultrasound with new and existing reproductive technologies will further enhance the practical applications of ultrasonography. Development of Extension education programs to train bovine practitioners to use ultrasound for routine reproductive examinations is a critical step toward rapid implementation of this technology into the dairy industry.
XOMA 052, a potent, high-affinity monoclonal antibody for the treatment of IL-1β-mediated diseases (2011)

Interleukin-1β (IL-1β) is a potent mediator of inflammatory responses and plays a role in the differentiation of a number of lymphoid cells. In several inflammatory and autoimmune diseases, serum levels of IL-1β are elevated and correlate with disease development and severity. The central role of the IL-1 pathway in several diseases has been validated by inhibitors currently in clinical development or approved by the FDA. However, the need to effectively modulate IL-1β-mediated local inflammation with the systemic delivery of an efficacious, safe and convenient drug still exists. To meet these challenges, we developed XOMA 052 (gevokizumab), a potent anti-IL-1β neutralizing antibody that was designed in silico and humanized using Human Engineering™ technology. XOMA 052 has a 300 femtomolar binding affinity for human IL-1β and an in vitro potency in the low picomolar range. XOMA 052 binds to a unique IL-1β epitope where residues critical for binding have been identified. We have previously reported that XOMA 052 is efficacious in vivo in a diet-induced obesity mouse model thought to be driven by low levels of chronic inflammation. We report here that XOMA 052 also reduces acute inflammation in vivo, neutralizing the effect of exogenously administered human IL-1β and blocking peritonitis in a mouse model of acute gout. Based on its high potency, novel mechanism of action, long half-life, and high affinity, XOMA 052 provides a new strategy for the treatment of a number of inflammatory, autoimmune and metabolic diseases in which the role of IL-1β is central to pathogenesis.
Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging. (1978)

Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.
A human lymphocyte‐associated antigen involved in cell‐mediated lympholysis (1983)

Human lymphocyte function antigen (HLFA) is a cell surface protein defined by two monoclonal antibodies MHM23 and MHM24. It is present on both B and T lymphocytes but in greater amounts on the latter. Both antibodies precipitated antigen, from radiolabeled HSB-2 cells, which ran as two chains on sodium dodecyl sulfate polyacrylamide gel electrophoresis at 180 and 94 kDa. Neither antibody inhibited binding of the other, indicating that distinct epitopes were recognized. Both antibodies were shown to inhibit HLA-restricted lysis of influenza virus-infected and Epstein-Barr virus-transformed target cells by cytotoxic T lymphocytes. Blocking occurred at the level of the effector cells and in the presence of subsaturating concentrations of antibody. Both reagents also inhibited lysis of K562 cells, mediated by natural killer cells. These blocking effects differ from the inhibitory effects of monoclonal anti-HLA ABC and anti-suppressor cytotoxic T cell antibodies which inhibit only HLA-restricted lysis when present in saturating amounts. It is concluded therefore that HLFA is likely to be involved in the nonspecific adherence or lytic functions of killer cells rather than specific antigen recognition.
Characteristics and the nature of the low-frequency dielectric response in moderately concentrated KTaO3:Li (2001)

The temperature-frequency behaviour of the complex dielectric permittivity of K0.957Li0.043TaO3 (KLT) was studied in detail. Below 250 K a pronounced relaxation-type dielectric dispersion occurs with two wide temperature maxima shifted to lower temperatures increasing in magnitude as the alternating-current monitoring frequency decreases. The results obtained are analysed by using a theory proposed considering the coupling of the TO1 soft mode (TO standing for transverse optical) to two Li relaxation modes known in moderately concentrated KLT as π- and (π/2)-relaxations.
The Story of the Western Railroads (2010)

The Story of the Western Railroads by Robert E. Riegel is not for the romanticist… It is rather the account of an inch by inch, month by month conquest in the threefold field of politics, finance, and engineering… He writes without bias; he is strictly non-partisan whether he is writing of the capitalist, the politician, or the interested public.
The Role of Grp 78 in α2-Macroglobulin-induced Signal Transduction (2002)

The low density lipoprotein receptor-related protein (LRP) is a scavenger receptor that binds to many proteins, some of which trigger signal transduction. Receptor-recognized forms of alpha(2)-Macroglobulin (alpha(2)M*) bind to LRP, but the pattern of signal transduction differs significantly from that observed with other LRP ligands. For example, neither Ni(2+) nor the receptor-associated protein, which blocks binding of all known ligands to LRP, block alpha(2)M*-induced signal transduction. In the current study, we employed alpha(2)-macroglobulin (alpha(2)M)-agarose column chromatography to purify cell surface membrane binding proteins from 1-LN human prostate cancer cells and murine macrophages. The predominant binding protein purified from 1-LN prostate cancer cells was Grp 78 with small amounts of LRP, a fact that is consistent with our previous observations that there is little LRP present on the surface of these cells. The ratio of LRP:Grp 78 is much higher in macrophages. Flow cytometry was employed to demonstrate the presence of Grp 78 on the cell surface of 1-LN cells. Purified Grp 78 binds to alpha(2)M* with high affinity (K(d) approximately 150 pm). A monoclonal antibody directed against Grp 78 both abolished alpha(2)M*-induced signal transduction and co-precipitated LRP. Ligand blotting with alpha(2)M* showed binding to both Grp 78 and LRP heavy chains in these preparations. Use of RNA interference to silence LRP expression had no effect on alpha(2)M*-mediated signaling. We conclude that Grp 78 is essential for alpha(2)M*-induced signal transduction and that a "co-receptor" relationship exists with LRP like that seen with several other ligands and receptors such as the uPA/uPAR (urinary type plasminogen activator or urokinase/uPA receptor) system.
A Response Map for use with Nuclear Electric's Irradiated Fuel Transport Flask Emergency Plan (1991)

A response map to be used in the initial phase of Nuclear Electric's Emergency Plan for irradiated fuel transport has been produced. The Emergency Plan itself is outlined and the role of the map in identifying the most appropriate source of health physics expertise is described. With the recent change in Alert Centre the opportunity was taken to revise this map in order to improve its usefulness and confirm its accuracy. The revised map was prepared using route planning computer software to determine the boundaries of the response area of each Power Station and other agencies involved in the Emergency Plan. The potential for future development in emergency response is discussed, examining in particular the role of route finding and mapping software, including databases of specialist materials and equipment, and in-car systems to guide those attending the emergency.
Reflective-Type Phase Shifters for Multiple-Antenna Transceivers (2007)

A 10.5-GHz reflective-type phase shifter (RTPS) using resonant loads with L-match impedance transformation (RLT) is implemented in a 0.25-mum SiGe BiCMOS process. A 2.4-GHz RTPS with RLT loads is also integrated in 0.18-mum CMOS; it employs a negative resistance (NR) technique to reduce the loss by 5.9 dB compared to a conventional design that is also implemented. Several other 2.4-GHz reflective loads are fabricated in 0.18-mum CMOS including a Y-shaped dual RLT (DRLT). A transformation converts it from a Y-shape to a Delta-shape and enables use of the NR technique in an RTPS with DRLT loads, wherein the loss is reduced by 10 dB and the phase shift range is increased to over 360deg.
Overexpression of Pim-1 during progression of prostatic adenocarcinoma (2006)

Pim-1 expression is elevated in PIN and prostatic adenocarcinoma compared with benign prostatic epithelium. This finding suggests that upregulation of Pim-1 may play a role in prostatic neoplasia.
Research in Boron Neutron Capture Therapy at MIT LABA (1997)

A 4.1 MeV tandem electrostatic accelerator designed for research into Boron Neutron Capture Therapy (BNCT) has recently been installed in the MIT Laboratory for Accelerator Beam Applications (LABA). This accelerator uses a very high current switch mode high voltage power supply in conjunction with a multi-cusp negative ion source to supply the multimilliampere current required for clinical BNCT applications. A number of individual research projects aimed at evaluating the potential of this accelerator design as a hospital-based neutron source for radiation therapy of both tumors and rheumatoid arthritis are described here.
Data compression and database performance (2002)

Data compression is widely used in data management to save storage space and network bandwidth. The authors outline the performance improvements that can be achieved by exploiting data compression in query processing. The novel idea is to leave data in compressed state as long as possible, and to only uncompress data when absolutely necessary. They show that many query processing algorithms can manipulate compressed data just as well as decompressed data, and that processing compressed data can speed query processing by a factor much larger than the compression factor.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Three-dimensional imaging of drill core samples using synchrotron computed microtomography. Progress report, Year two (1994)

Fundamental theories of rock structure are limited by the absence of high resolution, pore level, three dimensional images which could be used for statistical analysis. The ability to produce such images in a non-destructive manner would also allow for repeated measurements of dynamic processes such as fluid motion which could be correlated to the medium properties. One aspect of this funded work is the production of cross sectional images of rock, drill core samples with one micron resolution. This work is being done by Keith Jones and Per Spanne of Brookhaven National Laboratory using beam lines X-17 and X-26 of the National Synchrotron Light Source. Jones`s annual report will provide a description of the progress in this area. The second aspect of this work is the geometrical and statistical analysis of the pore structure of the three dimensional images provided. This aspect is being carried out at SUNY-Stony Brook; we report here on the progress that has been accomplished to date. Year one I progress was discussed fully in the previous progress report (DOE/ER/14261-1). Year one effort focused on the problem of voxel-by-voxel pore/grain identification of the tomographic images (image filtering), and on analysis of the filtered images via 2-point correlation structure.
Immediate-Early Expression of a Recombinant Antigen by Modified Vaccinia Virus Ankara Breaks the Immunodominance of Strong Vector-Specific B8R Antigen in Acute and Memory CD8 T-Cell Responses (2010)

Efficient T-cell responses against recombinant antigens expressed by vaccinia virus vectors require expression of these antigens in the early phase of the virus replication cycle. The kinetics of recombinant gene expression in poxviruses are largely determined by the promoter chosen. We used the highly attenuated modified vaccinia virus Ankara (MVA) to determine the role of promoters in the induction of CD8 T-cell responses. We constructed MVA recombinants expressing either enhanced green fluorescent protein (EGFP) or chicken ovalbumin (OVA), each under the control of a hybrid early-late promoter (pHyb) containing five copies of a strong early element or the well-known early-late p7.5 or pS promoter for comparison. In primary or cultured cells, EGFP expression under the control of pHyb was detected within 30 min, as an immediate-early protein, and remained higher over the first 6 h of infection than p7.5- or pS-driven EGFP expression. Repeated immunizations of mice with recombinant MVA expressing OVA under the control of the pHyb promoter led to superior acute and memory CD8 T-cell responses compared to those to p7.5- and pS-driven OVA. Moreover, OVA expressed under the control of pHyb replaced the MVA-derived B8R protein as the immunodominant CD8 T-cell antigen after three or more immunizations. This is the first demonstration of an immediate-early neoantigen expressed by a poxviral vector resulting in superior induction of neoantigen-specific CD8 T-cell responses.
Gradation Curve of Aggregate using Digital Image Process (2010)

Shape conversion coefficient and equivalent diameter for changing 2D image to 3D image by the Digital Image Process(DIP) have been suggested and modified particle size distribution curve has been showed. Couple of aggregates, like two different marine aggregates and two different crushed stones, have been employed. The measured flatness ratios of each aggregate were 0.30, 0.36, 0.47 and 0.83, respectively. Also, the conversion shape coefficients of each aggregate were determinded as 0.77, 0.78, 0.84 and 0.92. The size of aggregate has been modified by multiplying the shape conversion coefficient and the aggregate size from DIP. The modified gradation curve with modified volume and weight of aggregate has been suggested. Within the limited test results, DIP is one of useful to get the particle shape of aggregate with limitation of measuring errors and to apply the particle distribution curve.
Damage control resuscitation in patients with severe traumatic hemorrhage (2016)

DCR can significantly improve outcomes in severely injured bleeding patients. After a review of the best available evidence, we recommend the use of a MT/DCR protocol in hospitals that manage such patients and recommend that the protocol target a high ratio of PLAS and PLT to RBC. This is best achieved by transfusing equal amounts of RBC, PLAS, and PLT during the early, empiric phase of resuscitation. We cannot recommend for or against the use of rVIIa based on the available evidence. Finally, we conditionally recommend the in-hospital use of TXA early in the management of severely injured bleeding patients.
Endothelin Receptor Antagonism Ameliorates Mast Cell Infiltration, Vascular Hypertrophy, and Epidermal Growth Factor Expression in Experimental Diabetes (2000)

Vascular hypertrophy, a feature of experimental and human diabetes, has been implicated in the pathogenesis of the microvascular and macrovascular complications of the disease. In the present study, we sought to examine the role of endogenous endothelin and its relation to vascular growth factors in the mediation of vascular hypertrophy in experimental diabetes and to examine the contribution of mast cells to this process. Vessel morphology, endothelin, growth factor gene expression, and matrix deposition were studied in the mesenteric arteries of control and streptozotocin-induced diabetic Sprague-Dawley rats treated with or without the dual endothelin(A/B) receptor antagonist bosentan (100 mg x kg(-1) x d(-1)) during a 3-week period. Compared with control animals, diabetic animals had significant increases in vessel weight, wall-to-lumen ratio, mast cell infiltration, extracellular matrix deposition, and gene expression of epidermal growth factor (EGF) and transforming growth factor-beta(1). In diabetic, but not control, vessels, not only were EGF mRNA and endothelin present in endothelial cells, but also their expression was observed in adventitial mast cells. Immunoreactive endothelin was present in the media of mesenteric vessels of diabetic, but not control, animals. Bosentan treatment significantly reduced mesenteric weight, wall-to-lumen ratio, mast cell infiltration, matrix deposition, and EGF mRNA but did not prevent the overexpression of transforming growth factor-beta(1) mRNA in diabetic rats. These findings suggest that endogenous endothelin and EGF may play a role in diabetes-induced vascular hypertrophy and that mast cells may be pathogenetically involved in this process.