gebhart/patrepeval huggingface dataset:
Enhancement of the Tumor Penetration of Monoclonal Antibody by Fusion of a Neuropilin-Targeting Peptide Improves the Antitumor Efficacy (2014)

The limited localization and penetration of monoclonal antibodies (mAb) into solid tumors restricts their antitumor efficacy. Here, we describe a solid tumor-targeting antibody with enhanced tumor penetration activity. We designed a 22-residue peptide (A22p), which was extracted from the C-terminal basic region of semaphorin 3A (Sema3A) but modified to have higher affinity with neuropilin receptors (NRP), and genetically fused it to the C-terminus of Fc of human immunoglobulin G1 via a 15-residue (G4S)3 linker, generating Fc-A22p, for the bivalent binding to NRPs. In contrast to Fc or the monovalent A22p peptide alone, Fc-A22p homed to tumor vessels and induced vascular permeability through VE-cadherin downregulation and penetrated tumor tissues by interacting with NRPs in mice bearing human tumor xenografts. We extended the Fc-A22p platform by generating mAb-A22p antibodies of two clinically approved solid tumor-targeting mAbs, the anti-EGF receptor mAb cetuximab (erbitux), and the anti-Her2 mAb trastuzumab (herceptin). The mAb-A22p antibodies retained the intrinsic antigen binding, natural Fc-like biophysical properties, and productivity in mammalian cell cultures, comparable with those of the parent mAbs. In mouse xenograft tumor models, the mAb-A22p antibodies more efficiently homed to tumor vessels and spread into the extravascular tumor parenchyma, which significantly enhanced antitumor efficacy compared with the parent mAbs. Our results suggest that mAb-A22p is a superior format for solid tumor-targeting antibodies due to its enhanced tumor tissue penetration and greater antitumor efficacy compared with conventional mAbs.
Aspergillus oryzae acid proteinase. Purification and properties, and formation of π-chymotrypsin (1975)

An acid proteinase from Aspergillus oryzae was isolated from a commercial powder by successive (NH4)2SO4 fractionation, acetone precipitation, and ion-exchange chromatography on phosphate- and DEAE-cellulose columns. The purified enzyme was found to be homogeneous by ultracentrifuge-sedimentation analysis (S20, W equal 3.63S), but electrofocusing in polyacrylamide gels and electrophoresis at pH 3.2 revealed that it consists of two very closely migrating bands. No difference in the amino acid composition and enzymic activities of the two partially separated bands could be detected, and it was concluded that the acid proteinase exists in two molecular forms. The enzyme activates bovine trypsinogen and chymotrypsinogen at pH 3.5 (the kappacat. and Km values at 35degrees C are 11.3S- minus 1, 0.10mM and 1.14S- minus 1, 0.18mM respectively). It hydrolyses the Phe-Phe bond of the synthetic pepsin substrates Z-His-Phe-Phe-OEt (kappacat. equal 1.65S- minus 1, Km equal 0.640mM at pH 3.5, 30degrees C) and Z-Ala-Ala-Phe-Phe-OPy4Pr (kappacat. equal 0.37S- minus 1, Km equal 0.037 mM at pH2.9, 39degrees C), where Z represents benzyloxycarbonyl and OPy4Pr represents 3-(4-pyridyl)-propyl 1-ester. Activation of bovine chymotrypsinogen results from the cleavage of the Arg(15)-Ile(16) bond in the zymogen. No other cleavages were observed. The use of A. oryzae proteinase provides a simple tool for the production of pi-chymotrypsin in good yield and purity.
272. N-substituted amino-acids. Part I. A new method of preparation of dimethylamino-acids (1950)

R. E. Bowman and H. H. Stroud, J. Chem. Soc., 1950, 1342 DOI: 10.1039/JR9500001342
Factors affecting the under-diagnosis of atypical ductal hyperplasia diagnosed by core needle biopsies – A 10-year retrospective study and review of the literature (2017)

We recommend excision in all patients with ADH diagnosed by CNB, especially in patients with suspicious mammographic features.
Sequential phosphorylation of the phosphoprotein of vesicular stomatitis virus by cellular and viral protein kinases is essential for transcription activation (1992)

The phosphoprotein (P) and the large protein (L) constitute the RNA-dependent RNA polymerase of vesicular stomatitis virus (VSV). We show that phosphate-free P protein expressed in bacteria is transcriptionally inactive when reconstituted with L protein and viral N-RNA template free of cellular protein kinase. Phosphorylation of P protein by a cellular kinase(s) was essential for transcription as well as for further phosphorylation by an L-associated kinase, the two kinases acting in a sequential (cascade) manner. Phosphate groups introduced by cell kinase were stable, whereas those due to L kinase underwent a turnover which was coupled to ongoing transcription. We present a model for the phosphorylation pathway of P protein and propose that continued phosphorylation and dephosphorylation of P protein may represent a transcriptional regulatory (on-off) switch of nonsegmented negative-strand RNA viruses.
Local Angiotensin II and Transforming Growth Factor-β1 in Renal Fibrosis of Rats (2000)

Studies have demonstrated that local angiotensin II (Ang II) generation is enhanced in repairing kidney and that ACE inhibition or AT(1) receptor blockade attenuates renal fibrosis. The localization of ACE and Ang II receptors and their relationship to collagen synthesis in the injured kidney, however, remain uncertain. Using a rat model of renal injury with subsequent fibrosis created with chronic elevations in circulating aldosterone (ALDO), we examined the distribution and binding density of ACE and Ang II receptors in repairing kidneys, as well as their anatomic relationship to transforming growth factor-beta1 (TGF-beta1) mRNA, type I collagen mRNA, collagen accumulation, and myofibroblasts. Two groups of animals (n=7 in each group) were studied: (1) normal rats served as controls, and (2) uninephrectomized rats received ALDO (0.75 microg/h SC) and 1% NaCl in drinking water for 6 weeks. Compared with control rats, in ALDO-treated rats we found (1) significantly (P<0.01) increased blood pressure, reduced plasma renin activity, and increased plasma creatinine levels, (2) diffuse fibrosis in both renal cortex and medulla, (3) abundant myofibroblasts at these sites of fibrosis, (4) significantly increased (P<0.01) binding density of ACE and Ang II receptors (60% AT(1), 40% AT(2)) at the sites of fibrosis, and (5) markedly increased (P<0.01) expression of TGF-beta1 and type I collagen mRNAs at these same sites. Thus, in this rat model of renal repair, the enhanced expression of ACE, Ang II receptors, and TGF-beta1 is associated with renal fibrosis. Ang II generated at the sites of repair appears to have autocrine/paracrine functions in the regulation of renal fibrous tissue formation alone or through its stimulation of TGF-beta1 synthesis.
Cetuximab Shows Activity in Colorectal Cancer Patients With Tumors That Do Not Express the Epidermal Growth Factor Receptor by Immunohistochemistry (2005)

Colorectal cancer patients with EGFR-negative tumors have the potential to respond to cetuximab-based therapies. EGFR analysis by current IHC techniques does not seem to have predictive value, and selection or exclusion of patients for cetuximab therapy on the basis of currently available EGFR IHC does not seem warranted.
P-Coding: Secure Network Coding against Eavesdropping Attacks (2010)

Though providing an intrinsic secrecy, network coding is still vulnerable to eavesdropping attacks, by which an adversary may compromise the confidentiality of message content. Existing studies mainly deal with eavesdroppers that can intercept a lim-ited number of packets. However, real scenarios often consist of more capable adversaries, e.g., global eavesdroppers, which can defeat these techniques. In this paper, we propose P-Coding, a novel security scheme against eavesdropping attacks in network coding. With the lightweight permutation encryption performed on each message and its coding vector, P-Coding can efficiently thwart global eavesdroppers in a transparent way. Moreover, P-Coding is also featured in scalability and robustness, which enable it to be integrated into practical network coded systems. Security analysis and simulation results demonstrate the efficacy and efficiency of the P-Coding scheme.
Impaired wound healing and angiogenesis in eNOS-deficient mice (1999)

A role for nitric oxide (NO) in wound healing has been proposed; however, the absolute requirement of NO for wound healing in vivo and the contribution of endothelial NO synthase (eNOS) have not been determined. Experiments were carried out using eNOS gene knockout (KO) mice to determine the requirement for eNOS on wound closure and wound strength. Excisional wound closure was significantly delayed in the eNOS KO mice (29.4 +/- 2.2 days) compared with wild-type (WT) controls (20.2 +/- 0.4 days). At 10 days, incisional wound tensile strength demonstrated a 38% reduction in the eNOS KO mice. Because effective wound repair requires growth factor-stimulated angiogenesis, in vitro and in vivo angiogenesis assays were performed in the mice to assess the effects of eNOS deficiency on angiogenesis. Endothelial cell sprouting assays confirmed in vitro that eNOS is required for proper endothelial cell migration, proliferation, and differentiation. Aortic segments harvested from eNOS KO mice cultured with Matrigel demonstrated a significant reduction in endothelial cell sprouting and [(3)H]thymidine incorporation compared with WT mice at 5 days. Capillary ingrowth into subcutaneously implanted Matrigel plugs was significantly reduced in eNOS KO mice (2.67 +/- 0.33 vessels/plug) compared with WT mice (10.17 +/- 0.79 vessels/plug). These results clearly show that eNOS plays a significant role in facilitating wound repair and growth factor-stimulated angiogenesis.
Selectivity of binding of PEGs and PEG-like oligomers to anti-PEG antibodies induced by methoxyPEG-proteins (2013)

The use of methoxypoly(ethylene glycol) (mPEG) in PEG conjugates of proteins and non-protein therapeutic agents has led to the recognition that the polymer components of such conjugates can induce anti-PEG antibodies (anti-PEGs) that may accelerate the clearance and reduce the efficacy of the conjugates. Others have classified anti-PEGs as "methoxy-specific" or "backbone-specific". The results of our previous research on anti-PEGs in the sera of rabbits immunized with mPEG or hydroxyPEG (HO-PEG) conjugates of three unrelated proteins were consistent with that classification (Sherman, M.R., et al., 2012. Bioconjug. Chem. 23, 485-499). Enzyme-linked immunosorbent assays (ELISAs) were performed on rabbit antisera and rabbit monoclonal anti-PEGs with competitors including 10 kDa mPEG, 10 kDa PEG diol and six linear or cyclic oligomers of oxyethylene (CH2CH2O), with molecular weights of ca. 150-264 Da. Our results demonstrate that (1) the binding affinities of anti-mPEGs depend more on the backbone lengths of the polymers and the hydrophobicities of their end-groups than on their resemblance to the methoxy terminus of the immunogenic polymer; (2) anti-PEGs raised against HO-PEG-proteins are not directed against the terminal hydroxy group, but against the backbone; (3) rabbit anti-PEGs bind to and distinguish among PEG-like oligomers with as few as three oxyethylene groups; and (4) none of the monoclonal or polyclonal anti-PEGs was absolutely "methoxy-specific" or "backbone-specific", but displayed distinct relative selectivities. If these results are relevant to human immune responses, the clinical use of stable conjugates of HO-PEG with proteins and non-protein therapeutic agents would be expected to produce fewer and less intense immune responses than those induced by conjugates with mPEG or PEGs with larger alkoxy groups.
Effect of paclobutrazol on vegetative growth in citrus nursery trees (1989)

Two foliar sprays of paclobutrazol applied at four different concentrations, viz. 50,100, 200 and 500 mg a.i. l−1 on Citrus volkameriana (Ten. & Parq.) under greenhouse conditions, showed that concentrations of 100 mg l−1and above are suitable for reducing undesirable spindly growth of citrus rootstocks under crowded nursery conditions. Paclobutrazol at 200 and 500 mg l−1 resulted in the greatest growth check and there was no significant difference between these two treatments. At these higher concentrations, however, there seemed to be a residual effect on the subsequent growth of the scions. The growth check on the rootstock at 100 mg l−1 was significantly less than 200 and 500 mg l−1 but still of practical benefit to nurserymen, besides having no residual effect on the growing scions. The treatments did not cause any significant differences in stem diameter and bud take.
Tumorigenicity of human hematopoietic cell lines in athymic nude mice (1977)

Abstract Human hematopoietic cell lines, which had been classified on the basis of studies on clonality, and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non‐neoplastic origin, and lymphoma, myeloma and leukemia lines of proven malignant origin, were tested for tumorigenic potential on subcutaneous transplantation to nude mice and for capacity to grow in semi‐solid medium in vitro Recently established LCL failed to grow both in nude mice and in agarose. In contrast, some of the LCL which had developed secondary chromosomal alterations during continuous cultivation for periods exceeding several years were tumorigenic and/or had the capacity to form colonies in agarose. Most lymphoma lines formed colonies in agarose and tumors in the mice. One of the two myeloma lines formed subcutaneous tumor which, however, showed no progressive growth. The other myeloma line failed to grow. Both myeloma lines, however, formed colonies in agarose. The myeloid leukemia line was tumorigenic while two of the three tested lymphocytic leukemia lines failed to grow in the mice. All leukemia lines formed colonies in agarose. We conclude from this study that: (1) Of the two types of Epstein‐Barr virus containing cell lines [LCL and Burkitt lymphoma (BL) lines], only BL lines were shown to form tumors when inoculated subcutaneously in nude mice and had the capacity to grow in agarose in vitro. This shows that EBV transformation per se does not necessarily render lymphocytes tumorigenic in nude mice. The capacity to form colonies in agarose is not acquired either. (2) Changes of the karyotype and several phenotypic characteristics which occur in the originally diploid LCL during prolonged cultivation in vitro may be accompanied by the acquisition of the potential to grow subcutaneously in nude mice and in agarose in vitro. (3) The inconsistency with regard to the capacity of some of the neoplastic cell lines to grow in nude mice or in agarose seems to underline that neither of the two tests is a reliable criterion for malignancy of human lymphoma, leukemia and myeloma cell lines.
Extractive Summarization of Call Transcripts (2022)

Automatic text summarization is one of the most challenging and interesting problems in natural language processing (NLP). Text summarization is the process of extracting the most important information from the text and presenting it concisely in fewer sentences. Call transcript involves textual description of a phone conversation between a customer (caller) and agent(s) (customer representatives). Call transcripts pose unique challenges that are not adequately addressed by most open-source automatic text summarizers, which are developed to summarize continuous texts such as articles and stories. This paper presents an indigenously developed method that combines topic modeling and sentence selection with punctuation restoration in condensing ill-punctuated or un-punctuated call transcripts to produce more readable summaries. This unique combination is what distinguishes the proposed summarizer from other text summarizers. Extensive testing, evaluation and comparisons, with an open-source, state-of-the-art extractive summarizer using three different pre-trained language models, have demonstrated the efficacy of this summarizer for call transcript summarization. The summaries generated by the proposed summarizer were shown to be more compelling and useful based on multiple criteria.
PD-1/PD-L1 blockade in cancer treatment: perspectives and issues (2016)

Recent studies showed that tumor cells 'edit' host immunity in several ways to evade immune defenses in the tumor microenvironment. This phenomenon is called "cancer immune escape." One of the most important components in this system is an immunosuppressive co-signal (immune checkpoint) mediated by the PD-1 receptor and its ligand, PD-L1. PD-1 is mainly expressed on activated T cells, whereas PD-L1 is expressed on several types of tumor cells. Preclinical studies have shown that inhibition of the interaction between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor activity. Several clinical trials of PD-1/PD-L1 signal-blockade agents have exhibited dramatic antitumor efficacy in patients with certain types of solid or hematological malignancies. In this review, we highlight recent clinical trials using anti-PD-1 or anti-PD-L1 antibodies against several types of malignancies, including a trial conducted in our department, and describe the clinical perspectives and issues regarding the PD-1/PD-L1 blockade in cancer treatment.
Load shedding in stream databases: a control-based approach (2006)

In Data Stream Management Systems (DSMSs), query processing has to meet various Quality-of-Service (QoS) requirements. In many data stream applications, processing delay is the most critical quality requirement since the value of query results decreases dramatically over time. The ability to remain within a desired level of delay is significantly hampered under situations of overloading, which are common in data stream systems. When overloaded, DSMSs employ load shedding in order to meet quality requirements and keep pace with the high rate of data arrivals. Data stream applications are extremely dynamic due to bursty data arrivals and time-varying data processing costs. Current approaches ignore system status information in decision-making and consequently are unable to achieve desired control of quality under dynamic load. In this paper, we present a quality management framework that leverages well studied feedback control techniques. We discuss the design and implementation of such a framework in a real DSMS - the Borealis stream manager. Our data management framework is built on the advantages of system identification and rigorous controller analysis. Experimental results show that our solution achieves significantly fewer QoS (delay) violations with the same or lower level of data loss, as compared to current strategies utilized in DSMSs. It is also robust and bears negligible computational overhead.
A chopped Hall sensor with small jitter and programmable "True Power-on" function (2005)

A chopped Hall sensor for camshaft applications is presented which provides a programmable "True Power-on" switching level effective after the power-up phase. The proposed chopping technique and self-compensation methods for temperature drift and technology spread provide a correct output state immediately after power-on even at zero speed of the target wheel. The circuits improve the magnetic offsets from 5 to 10 mT to below 200 /spl mu/T in a bandwidth of 30 kHz and stabilize the spread of the magnetic switching points from 20% to <2% in a temperature range from -40/spl deg/C to 175/spl deg/C. The novel combination of chopping and enhanced digital self-calibration algorithm adjusts the magnetic switching point and improves phase accuracy to <0.5/spl deg/, independent of air gap variations between sensor and wheel. An end-of-line calibration for the customer is implemented using surface micromachined cavity fuses which offer a reliable function higher than 195/spl deg/C.
The Effect of Decalcified Bone Matrix on the Osteogenic Potential of Bone Marrow (1986)

Rabbit bone marrow cells were cultured in diffusion chambers with or without decalcified bone matrix. The chambers were assayed after 28 days for alkaline phosphatase activity, deoxyribonucleic acid (DNA), calcium, and phosphorus contents. Morphologically, marrow cells incubated with or without matrix differentiated to form bone and cartilage. With bone matrix, the calcium and phosphorus contents of chambers were significantly higher than control chambers. Alkaline phosphatase activity and DNA content were not influenced by inclusion of bone matrix. These results indicate that bone matrix constituents exert a stimulatory effect on bone formation from marrow cells. This osteogenic stimulation could be due to the influence of an osteoinductive factor and/or to stimulation of osteoprogenitor cells known to be present in the marrow.
In-Water Synthesis of Quinazolinones from 1,1-Dichloro-2-nitroethene and Anthranilamides (2016)

An efficient synthetic methodology was developed for direct formation of quinazolinones with 2-nitromethyl substituent via 1,1-dichloro-2-nitroethene and anthranilamides. This strategy provides an alternative for quinazolinones construction with merits of proceeding in water, easy purification, and no addition of catalysts.
Basic Principles of Hemostasis (2007)

The hemostatic system consists of blood vessels, platelets, and the plasma coagulation system including the fibrinolytic factors and their inhibitors. When a blood vessel is injured, three mechanisms operate locally at the site of injury to control bleeding: (1) vessel wall contraction, (2) platelet adhesion and aggregation (platelet plug formation), and (3) plasmatic coagulation to form a fibrin clot. All three mechanisms are essential for normal hemostasis. Abnormal bleeding usually results from defects in one or more of these three mechanisms. For a better understanding of the pathogenesis of pathological bleeding, it is customary to divide hemostasis into two stages (i.e., primary and secondary hemostasis). Primary hemostasis is the term used for the instantaneous plug formation upon injury of the vessel wall, which is achieved by vasoconstriction, platelet adhesion, and aggregation. The fibrin formation is not required for hemostasis at this stage. Primary hemostasis is, however, only temporarily effective. Hemorrhage may start again unless the secondary hemostasis reinforces the platelet plug by formation of a stable fibrin clot. Finally, mechanisms within the fibrinolytic system lead to a dissolution of the fibrin clot and to a restoration of normal blood flow.
Mobile Service Platform: A Middleware for Nomadic Mobile Service Provisioning (2006)

Ongoing miniaturization and power efficiency of mobile devices have led to widespread availability of devices that have an increasing amount of processing power and storage, and that support multiple wireless network interfaces connecting to various auxiliary devices and to the Internet. It is now feasible for a mobile device to host services and participate in a service discovery network. Roaming of a mobile device from one wireless network to another entails nomadic characteristics to the hosted services. We denote this class of services as nomadic mobile services. This paper discusses the requirements for nomadic mobile service provisioning and proposes the mobile service platform (MSP) as a supporting infrastructure and middleware which extends the service oriented architecture paradigm to the mobile device. The MSP design is based on the Jini surrogate architecture specification which enables devices that can not directly participate in a Jini network to join a Jini network with the aid of a third party. MSP consists of an HTTPInterconnect protocol to meet the specifications of Jini surrogate architecture and provides a custom set of APIs to develop and deploy a nomadic mobile service. This paper also presents case studies of MSP enabled services in diverse domains such as healthcare, robotics and positioning services. To conclude, we outline the need for a context-aware MSP