gebhart/patrepeval huggingface dataset:
Man-Computer Graphics in Preliminary Ship Design (1973)

The Naval Ship Engineering Center through its Computer Aided Ship Design and Construction Office is working toward maximum effective use of computers in the Navy's ship design process. Many batch type analyses were developed but certain naval architectural problems, such as ship hull form creation and arrangements, cannot readily be handled by the computer without human intervention. Hence, interactive graphics developments were required. The existing interactive graphics programing languages were applicable only to the hardware for which they were written. To minimize conversion problems of inevitable hardware configuration changes, a portable interactive graphics language was developed and used. The active graphics programs described herein are under continuing development and in use for hull form generation, deck and bulkhead location, and topside and internal room arrangements. In their present form, they are applicable to early stage feasibility and preliminary design. The Integrated Ship Design System (ISDS) is being developed to allow communication of all types of design programs, including interactive graphics through a common data base; so that all applicable preliminary ship design tasks can be done within the computer environment.
cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line. (1995)

A human T lymphoid cell line, PEER, dies by apoptosis in the presence of PMA and calcium ionophore. A new gene, TINUR, was cloned from apoptotic PEER cells. The expression of the TINUR gene is induced within 1 h after the cross-linking of the T cell Ag receptor complex. TINUR belongs to the NGFI-B/nur77 family of the steroid receptor superfamily and is an orphan receptor. TINUR binds to the same DNA sequence as NGFI-B/nur77. We also propose that the NGFI-B/nur77 family can be classified into two subtypes.
Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo (2013)

Tumor necrosis factor alpha (TNF-α) plays a key role in inflammation, and its production and signaling contribute to many inflammatory related diseases. Recently, we discovered that selective activation of serotonin 5-HT2A receptors with the agonist (R)-DOI produces a super-potent blockade of proinflammatory markers in primary rat aortic smooth muscle cells. Here, we demonstrate that systemic administration of (R)-DOI can block the systemic effects of TNF-α in whole animal, with potent anti-inflammatory effects in the aortic arch and small intestine. This includes blockade of TNF-α-induced expression of pro-inflammatory cell adhesion (Icam-1, Vcam-1), cytokine (Il-6, IL-1b), and chemokine (Mcp-1, Cx3cl1) genes, and expression of VCAM-1 protein in the intestine. Further, systemic (R)-DOI also prevents the TNF-α-induced increase of circulating IL-6. Importantly, utilizing receptor selective antagonists, we have demonstrated that the mechanism underlying the systemic anti-inflammatory effects of (R)-DOI is activation of serotonin 5-HT2A receptors. Our results highlight a powerful new role for the serotonin 5-HT2A receptor in inflammatory processes, and indicate that agonism of serotonin receptors may represent an effective and novel approach to develop powerful small molecule therapeutics for inflammatory diseases and conditions such as atherosclerosis and inflammatory bowel disease.
The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle (1995)

Human immunodeficiency virus type 1 (HIV-1) infection causes profound immunological defects in afflicted patients. Various mechanisms have been proposed to account for the immune dysfunction in AIDS ultimately leading to loss of CD4+ T cells, including HIV-1 envelope-mediated syncytium formation, apoptosis, and cytokine modulation. Here we present results which suggest a novel hypothesis for T-cell dysfunction. We show, using HIV-1 bearing a novel cell surface reporter gene, that infected cells are unable to progress normally through the cell cycle and became arrested in the G2 + M phase. Furthermore, we identify the HIV-1 vpr gene product as being both necessary and sufficient for eliciting this cell cycle arrest. Cell cycle arrest induced by Vpr correlates with an increase in the hyperphosphorylated (inactive) form of the cyclin-dependent serine/threonine kinase CDC2, consistent with an arrest of cells at the boundary of G2 and M.
Evidence for Angiotensin-converting Enzyme 2 as a Therapeutic Target for the Prevention of Pulmonary Hypertension (2009)

These observations provide conceptual support that activation of ACE2 by a small molecule can be a therapeutically relevant approach for treating and controlling PH.
Fc Engineering to Improve the Function of Therapeutic Antibodies (2016)

Monoclonal antibodies are currently the most attractive therapeutic modality in a broad range of disease areas, including infectious diseases, autoimmune diseases, and oncology. Fc engineering is one attractive application to maximize the value or overcome the drawbacks of monoclonal antibodies for therapeutic use. With the Fc region, antibodies bind to several types of receptors, such as Fc gamma receptors, a complement receptor, and a neonatal Fc receptor. Through this interaction with the receptors, antibodies demonstrate unique functions, such as antibody-dependent cellular cytotoxicity, antibody- dependent cellular phagocytosis, complement dependent cytotoxicity, agonistic activity, and endosomal recycling. Fc engineering technology is conducted mainly to maximize the receptor-mediated functions of antibodies. Moreover, Fc engineering of the two heavy chains to facilitate heterodimerization is indispensable for generating IgG-like bispecific antibodies that are asymmetric. Fc engineering is also conducted to avoid the undesired properties, such as cytokine release and protease-mediated cleavage of the hinge region, of wild-type antibodies, as well as providing additional functions. Thus, Fc engineering technology is an attractive approach for maximizing the potency and convenience of therapeutic antibodies. This review will cover a variety of Fc engineering technologies that improve the functions of therapeutic antibodies.
Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold (2012)

Employing a structure-based strategy, we have designed a new class of potent small-molecule inhibitors of the anti-apoptotic proteins Bcl-2 and Bcl-xL. An initial lead compound with a new scaffold was designed based upon the crystal structure of Bcl-xL and U.S. Food and Drug Administration (FDA) approved drugs and was found to have an affinity of 100 μM for both Bcl-2 and Bcl-xL. Linking this weak lead to another weak-affinity fragment derived from Abbott's ABT-737 led to an improvement of the binding affinity by a factor of >10 000. Further optimization ultimately yielded compounds with subnanomolar binding affinities for both Bcl-2 and Bcl-xL and potent cellular activity. The best compound (21) binds to Bcl-xL and Bcl-2 with K(i) < 1 nM, inhibits cell growth in the H146 and H1417 small-cell lung cancer cell lines with IC(50) values of 60-90 nM, and induces robust cell death in the H146 cancer cell line at 30-100 nM.
Androgen receptor involvement in the progression of prostate cancer. (2003)

Since the growth of prostate cancer is androgen-sensitive, metastatic disease has been treated by hormonal therapy. Almost all prostate cancer patients initially respond to hormonal therapy, but the majority gradually develop resistance. The mechanism of the change in tumors from being androgen-responsive to androgen-unresponsive is generally explained by clonal selection, adaptation, an alternative pathway of signal transduction and androgen receptor (AR) involvement. Since androgen action is mediated by ARs, abnormalities in ARs are believed to play an important role in the progression of prostate cancer. Hyperactivated AR gene mutations have been detected in 20-30% of hormone-refractory tumors and functional analyses have demonstrated a wide responsiveness to estrogens, progesterone and anti-androgens as well as to androgens. The AR is highly amplified in 30% of patients with hormone-refractory prostate cancer that has been treated by castration without anti-androgens. Immunohistochemical studies of ARs in hormone-refractory prostate cancer specimens have shown that AR protein is down-regulated. DNA hypermethylation of the AR promoter region leading to AR down-regulation has been identified in 30% of hormone-refractory prostate cancers. The AR N-terminal domain in the LNCaP cell line model is activated by interleukin-6 via mitogen-activated protein kinase and single transducers and activators of transcription 3. Epidemiological observations have shown that short CAG repeats are more frequently associated with higher transactivational function in the African-American population, which may explain racial differences in the incidence of prostate cancer. Among Japanese, a short CAG repeat appears to predict a response to hormonal therapy, indicating a positive prognostic value and good prognosis at the metastatic stage of prostate cancer. Several co-factors between ARs and the transcriptional complex have been cloned and reports indicate that steroid receptor co-activator 1 is correlated with the hormone-refractory progression of prostate cancer. Thus, ARs plays an important role in the progression of prostate cancer. Based on the findings described above, genetic diagnosis and/or molecular-targeted therapy via AR pathways can be developed for hormone-refractory states.
Management of breast cancer with nanoparticle albumin-bound (nab)-paclitaxel combination regimens: A clinical review (2011)

Although results of this review indicate that nab-paclitaxel may be an appropriate substitute for SBTs in combination regimens, additional research is required to confirm the place and cost effectiveness of these combinations before nab-paclitaxel could be recommended routinely in all settings.
Multivariate Determination of Glucose in Whole Blood Using Partial Least-Squares and Artificial Neural Networks Based on Mid-Infrared Spectroscopy (1993)

The infrared (IR) spectra of whole blood EDTA samples, in the range between 1500 and 750 cm −1 , obtained from the patient population of a general hospital, were used to compare different multivariate calibration techniques for quantitative glucose determination. Ninety-six spectra of whole undiluted blood samples with glucose concentration ranging between 44 and 291 mg/dL were used to create calibration models based on a combination of partial least-squares (PLS) and artificial neural network (ANN) methods. The prediction capabilities of these calibration models were evaluated by comparing their standard errors of prediction (SEP) with those obtained with the use of PLS and principal component regression (PCR) calibration models in an independent prediction set consisting of 31 blood samples. The optimal model based on the combined PLS-ANN produced smaller SEP values (15.6 mg/dL) compared with those produced with the use of either PLS (21.5 mg/dL) or PCR (24.0 mg/dL) methods. Our results revealed that the combined PLS-ANN models can better approximate the deviations from linearity in the relationship between spectral data and concentration, compared with either PLS or PCR models.
Guidance of rehabilitation at home in patients with laryngeal carcinoma (2014)

Objective To explore the effect and methods of the guidance of the rehabilitation at home in patients with laryngeal carcinoma.Methods 96 patients with laryngeal carcinoma were randomly divided into a control group and an intervention group,48 cases for each group.Both groups received routine nursing care and health education during hospitalization.In addition,after discharge,the intervention group received the guidance of rehabilitation at home,including the establishment of nursing intervention group,formulating the process of rehabilitation at home,formulating the individualized plan rehabilitation at home,training the patients,and helping the patients have command of the knowledge and/or technology of nutrition,exercise,airway protection and care,etc,were introduced the experience of no laryngeal tissue activity,demanded to re-visit the doctor regularly,followed up for 6 months.The abilities of rehabilitation at home and care of both groups were evaluated 1 week,3 months,and 6 months after discharge by self nursing ability scale.The postoperative tube-blocked times and re-hospitalization rates within 6 months because of complications were compared between the two groups.Results The scores of each dimension in the abilities of rehabilitation at home and care were higher in the intervention group than in the control group (P ＜ 0.05).Conclusions Guiding patients with laryngeal carcinoma rehabilitating at home can improve the patients' care ability,promote early rehabilitation,and improve the overall quality of life.

Key words: 
Home;  Nursing intervention;  Laryngeal carcinoma;  Rehabilitation nursing
cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity (2011)

cAMP and mTOR signalling pathways control a number of critical cellular processes including metabolism, protein synthesis, proliferation and cell survival and therefore understanding the signalling events which integrate these two signalling pathways is of particular interest. In this study, we show that the pharmacological elevation of [cAMP](i) in mouse embryonic fibroblasts (MEFs) and human embryonic kidney 293 (HEK293) cells inhibits mTORC1 activation via a PKA-dependent mechanism. Although the inhibitory effect of cAMP on mTOR could be mediated by impinging on signalling cascades (i.e. PKB, MAPK and AMPK) that inhibit TSC1/2, an upstream negative regulator of mTORC1, we show that cAMP inhibits mTORC1 in TSC2 knockout (TSC2(-/-)) MEFs. We also show that cAMP inhibits insulin and amino acid-stimulated mTORC1 activation independently of Rheb, Rag GTPases, TSC2, PKB, MAPK and AMPK, indicating that cAMP may act independently of known regulatory inputs into mTOR. Moreover, we show that the prolonged elevation in [cAMP](i) can also inhibit mTORC2. We provide evidence that this cAMP-dependent inhibition of mTORC1/2 is caused by the dissociation of mTORC1 and 2 and a reduction in mTOR catalytic activity, as determined by its auto-phosphorylation on Ser2481. Taken together, these results provide an important insight into how cAMP signals to mTOR and down-regulates its activity, which may lead to the identification of novel drug targets to inhibit mTOR that could be used for the treatment and prevention of human diseases such as cancer.
Analytical methods for dynamic simulation of non-penetrating rigid bodies (1989)

A method for analytically calculating the forces between systems of rigid bodies in resting (non-colliding) contact is presented. The systems of bodies may either be in motion or static equilibrium and adjacent bodies may touch at multiple points. The analytic formulation of the forces between bodies in non-colliding contact can be modified to deal with colliding bodies. Accordingly, an improved method for analytically calculating the forces between systems of rigid bodies in colliding contact is also presented. Both methods can be applied to systems with arbitrary holonomic geometric constraints, such as linked figures. The analytical formulations used treat both holonomic and non-holonomic constraints in a consistent manner.
Mixed-Ligand Coordination Species:  A Promising Approach for “Second-Generation” Drug Development (2006)

A series of crystalline mixed-ligand copper(II)−aspirinate coordination complexes have been synthesized, structurally characterized, and shown to exhibit a diverse range of pharmacologically relevant properties, such as bulk solubility, solubility ratio (Swo/Sow), and partition coefficient.
Handbook of Applied Cryptography (2018)

Cryptography, in particular public-key cryptography, has emerged in the last 20 years as an important discipline that is not only the subject of an enormous amount of research, but provides the foundation for information security in many applications. Standards are emerging to meet the demands for cryptographic protection in most areas of data communications. Public-key cryptographic techniques are now in widespread use, especially in the financial services industry, in the public sector, and by individuals for their personal privacy, such as in electronic mail. This Handbook will serve as a valuable reference for the novice as well as for the expert who needs a wider scope of coverage within the area of cryptography. It is a necessary and timely guide for professionals who practice the art of cryptography. The Handbook of Applied Cryptography provides a treatment that is multifunctional:It serves as an introduction to the more practical aspects of both conventional and public-key cryptographyIt is a valuable source of the latest techniques and algorithms for the serious practitionerIt provides an integrated treatment of the field, while still presenting each major topic as a self-contained unitIt provides a mathematical treatment to accompany practical discussionsIt contains enough abstraction to be a valuable reference for theoreticians while containing enough detail to actually allow implementation of the algorithms discussedNow in its third printing, this is the definitive cryptography reference that the novice as well as experienced developers, designers, researchers, engineers, computer scientists, and mathematicians alike will use.
The Chondrogenic Potential of Human Bone-Marrow-Derived Mesenchymal Progenitor Cells* (1998)

Mesenchymal progenitor cells provide a source of cells for the repair of musculoskeletal tissue. However, in vitro models are needed to study the mechanisms of differentiation of progenitor cells. This study demonstrated the successful induction of in vitro chondrogenesis with human bone-marrow-derived osteochondral progenitor cells in a reliable and reproducible culture system. Human bone marrow was removed and fractionated, and adherent cell cultures were established. The cells were then passaged into an aggregate culture system in a serum-free medium. Initially, the cell aggregates contained type-I collagen and neither type-II nor type-X collagen was detected. Type-II collagen was typically detected in the matrix by the fifth day, with the immunoreactivity localized in the region of metachromatic staining. By the fourteenth day, type-II and type-X collagen were detected throughout the cell aggregates, except for an outer region of flattened, perichondrial-like cells in a matrix rich in type-I collagen. Aggrecan and link protein were detected in extracts of the cell aggregates, providing evidence that large aggregating proteoglycans of the type found in cartilaginous tissues had been synthesized by the newly differentiating chondrocytic cells; the small proteoglycans, biglycan and decorin, were also detected in extracts. Immunohistochemical staining with antibodies specific for chondroitin 4-sulfate and keratan sulfate demonstrated a uniform distribution of proteoglycans throughout the extracellular matrix of the cell aggregates. When the bone-marrow-derived cell preparations were passaged in monolayer culture as many as twenty times, with cells allowed to grow to confluence at each passage, the chondrogenic potential of the cells was maintained after each passage.
Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. (1993)

Malignant astrocytoma is the most common primary human brain tumor. Most astrocytomas express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could close an autocrine loop. It is not known whether these autocrine loops contribute to the transformed phenotype of astrocytoma cells or are incidental to that phenotype. Here we show that dominant-negative mutants of the PDGF ligand break the autocrine loop and revert the phenotype of BALB/c 3T3 cells transformed by the PDGF-A or PDGF-B (c-sis) gene. Then, we show that these mutants are selective in that they do not alter the phenotype of 3T3 cells transformed by an activated Ha-ras or v-src gene or by simian virus 40. Finally, we show that these mutants revert the transformed phenotype of two independent human astrocytoma cell lines. They have no effect on the growth of human medulloblastoma, bladder carcinoma, or colon carcinoma cell lines. These observations are consistent with the view that PDGF autocrine loops contribute to the transformed phenotype of at least some human astrocytomas.
Processing the nonstructural polyproteins of sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans (1989)

The processing of the Sindbis virus nonstructural polyprotein translated in vitro has been studied. When Sindbis virus genomic RNA was translated in a reticulocyte lysate, polyprotein P123 was cleaved efficiently to produce nsP1, nsP2, and nsP3. Inhibition of this processing by anti-nsP2 antibodies, but not by antibodies specific for nsP1, nsP3, or nsP4, suggested that the viral proteinase was present in nsP2. To localize the proteolytic activity more precisely, deletions were made in a full-length cDNA clone of Sindbis virus, and RNA was transcribed from these constructs with SP6 RNA polymerase and translated in vitro. Although virtually all of the nsP1, nsP3, and nsP4 sequences could be deleted without affecting processing, deletions in the N-terminal half of nsP2 led to aberrant processing, and deletions in the C-terminal half abolished proteolysis. However, inactive polyproteins containing the nsP2 deletions could be processed by exogenously supplied proteins translated from virion RNA, demonstrating that cleavage was virus specific and not due to a protease present in the reticulocyte lysate and that the deleted polyproteins still served as substrates for the enzyme. From these results and from experiments in which processing was studied at increasingly higher dilution, we have concluded the following: (i) the viral nonstructural proteinase is located in the C-terminal half of nsP2; (ii) in the P123 precursor the cleavage between nsP2 and nsP3 occurs efficiently as a bimolecular reaction (in trans) to remove nsP3, while the bond between nsP1 and nsP2 is cleaved inefficiently, but detectably, in trans, but no autoproteolysis of P123 was detected; (iii) once nsP3 has been removed, the bond between nsP1 and nsP2 in the P12 precursor is cleaved efficiently by autoproteolysis (in cis). This mode of processing leads to a slow rate of cleavage, particularly early in infection, suggesting that the polyproteins might play roles in virus RNA replication distinct from those of the cleaved products. A hypothesis is presented that the proteinase is a thiol protease related to papain.