gebhart/patrepeval huggingface dataset:
Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2 (2001)

Trastuzumab increases the clinical benefit of first-line chemotherapy in metastatic breast cancer that overexpresses HER2.
A 2‐Year Clinical Evaluation of a Diphenylphosphorylazide‐Cross‐Linked Collagen Membrane for the Treatment of Buccal Gingival Recession (1998)

To retard collagen membrane enzymatic degradation and to increase its mechanical strength, the diphenylphosphorylazide (DPPA) technique has been demonstrated to achieve natural cross-links between peptide chains of collagen without leaving any foreign product in the cross-linked molecule. In the present prospective clinical trial, the potential of a DPPA-cross-linked type I bovine collagen membrane was evaluated in the healing of 15 buccal soft tissue recessions in 15 patients according to the biological concept of guided tissue regeneration. The recession decreased from 3.7 mm (SD 1.4) at baseline to 0.8 mm (SD 1.2) at 2 years postsurgery, corresponding to a mean root coverage of 82.2% (P <0.0001). Concurrently, the clinical attachment level decreased from 5.4 mm (SD 1.6) at baseline to 1.9 mm (SD 1.2) 2 years postsurgery, corresponding to an average clinical attachment gain of 3.5 mm (SD 1.3) (P <0.0001). The 2-year postsurgical width of the keratinized tissue was not significantly different from baseline values. More than half (53%) of the treated sites showed complete root coverage and about two-thirds (73%) of the total cases showed a 75% to 100% disappearance of the mucogingival defect. The present investigation demonstrated that the use of DPPA-cross-linked collagen membranes in the treatment of human buccal soft tissue recessions results in predictable amounts of root coverage and clinical attachment gain. Long-term randomization controlled clinical trials of this material are needed to fully evaluate its potential for treating periodontal recession.
Molecular cloning and characterization of murine interleukin-11. (1996)

Human interleukin-11 (IL-11) has been shown to have pleiotropic action on hematopoietic, hepatic, stromal, epithelial, neural, and osteoclast cells. In the present work, the murine IL-11 cDNA has been isolated from a fetal thymic cell line, and its structure and function compared with human IL-11. The murine protein was demonstrated to have identical actions on the proliferation of a murine plasmacytoma cell line, murine primitive bone marrow progenitor cells, and megakaryocyte precursors. The murine IL-11 protein was synthesized as a soluble thioredoxin-IL-11 fusion in Escherichia coli and the expression of murine IL-11 was examined by pulse-chase radiolabeling in COS cells. The chromosomal location of the murine IL-11 gene was assigned to the proximal arm of chromosome 7.
Identification of three novel peptides that inhibit CD40–CD154 interaction (2005)

The CD40–CD154 interaction is an attractive target for therapeutic intervention in various autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and myasthenia gravis. In this study, to develop a new disruption strategy of the CD40–CD154 interaction, we screened for peptides with inhibitory effects on such ligation. 2 × 1011 phage display libraries displaying liner peptides of 12-mer amino acids were screened by CD40-Ig binding assay and eight phages which expressed a different respective peptide (40BP-1 to -8) were able to specifically bind to CD40. Competitive inhibition analyses showed that 3 of the 8 peptides (40BP-N1-1 – APELPNMTPSWT; 40BP-N1-2 – APRPHTSYSPLP; and 40BP-N1-3 – GMTAPPPPRLTQ) blocked CD40–CD154 interaction when used at high concentrations. A consensus sequence (APxPPxxT) was conserved in these three peptides. These peptides may constitute a useful and novel strategy for the inhibition of the interaction between CD40 and CD154 molecules.
INFORMATION TECHNOLOGY OF COMMERCIAL VEHICLES IN THE JAPANESE PARCEL SERVICE BUSINESS (1992)

This paper describes a highly successful parcel door to door delivery service in Japan which involves the following components: a Takkyubin truck with technologically advanced design, truck information systems traffic control system, and digital driving pattern monitors.
In the complex family of heat stress transcription factors, HsfA1 has a unique role as master regulator of thermotolerance in tomato (2002)

We generated transgenic tomato plants with altered expression of heat stress transcription factor HsfA1. Plants with 10-fold overexpression of HsfA1 (OE plants) were characterized by a single HsfA1 transgene cassette, whereas plants harboring a tandem inverted repeat of the cassette showed cosuppression (CS plants) by posttranscriptional silencing of the HsfA1 gene connected with formation of small interfering RNAs. Under normal growth conditions, major developmental parameters were similar for wild-type (WT), OE, and CS plants. However, CS plants and fruits were extremely sensitive to elevated temperatures, because heat stress-induced synthesis of chaperones and Hsfs was strongly reduced or lacking. Despite the complexity of the plant Hsf family with at least 17 members in tomato, HsfA1 has a unique function as master regulator for induced thermotolerance. Using transient reporter assays with mesophyll protoplasts from WT tomato, we demonstrated that plasmid-encoded HsfA1 and HsfA2 were well expressed. However, in CS protoplasts the cosuppression phenomenon was faithfully reproduced. Only transformation with HsfA2 expression plasmid led to normal expression of the transcription factor and reporter gene activation, whereas even high amounts of HsfA1 expression plasmids were silenced. Thermotolerance in CS protoplasts was restored by plasmid-borne HsfA2, resulting in expression of chaperones, thermoprotection of firefly luciferase, and assembly of heat stress granules.
Microheterogeneity of the oligosaccharides carried by the recombinant bovine lactoferrin expressed in Mamestra brassicae cells (1997)

The development of therapeutic glycoprotein production using the baculovirus expression system depends on the ability of insect cell lines to reproduce site specific mammalian-like N-glycans. A combination of 1H-NMR and mass spectrometry techniques (MALD-MS, ES-MS, and CID-MS-MS) allowed us to elucidate the N-linked oligosaccharides microheterogeneity on three different N-glycosylation sites, Asn233, Asn476, and Asn545, of a baculovirus-expressed recombinant bovine lactoferrin produced in Mamestra brassicae. Two families of N-glycan structures have been found: first, oligomannosidic glycans (Man[9-5]GlcNAc2) and secondly, short truncated partially fucosylated glycans (Man(3-2)[Fuc(0-1)]GlcNAc2). These results indicate that Mamestra brassicae cell line is not able to synthesize complex N-glycans, even if an alpha1,6-linked fucose residue is frequently present on the asparagine-bound N-acetylglucosamine residue of short truncated structures. Nevertheless, we have shown that Mamestra brassicae ensures the same N-glycosylation pattern as found on natural bovine lactoferrin showing the same distribution between complex and high-mannose type glycans on the different glycosylation sites. Sites which are naturally occupied by high-mannose glycans (Asn233 and Asn545) are substituted essentially by the same type of N-glycans in the recombinant counterpart, and the site Asn476,which carries sialylated complex type chains in the natural glycoprotein, is substituted by short, truncated, partially fucosylated chains in Mamestra brassicae-expressed bovine lactoferrin. These various results lead us to the conclusion that bovine lactoferrin is an interesting model to determine the potential of glycosylation of the baculovirus/insect cell expression systems.
Prolactin and the prolactin receptor: new targets of an old hormone (2004)

Prolactin (PRL) is one of a family of related hormones including growth hormone (GH) and placental lactogen (PL) that are hypothesized to have arisen from a common ancestral gene about 500 million years ago. Over 300 different functions of PRL have been reported, highlighting the importance of this pituitary hormone. PRL is also synthesized by a number of extra-pituitary tissues including the mammary gland and the uterus. Most of PRL's actions are mediated by the unmodified 23 kDa peptide, however, PRL may be modified post-translation, thereby altering its biological effects. PRL exerts these effects by binding to its receptor, a member of the class I cytokine receptor super-family. This activates a number of signaling pathways resulting in the transcription of genes necessary for the tissue specific changes induced by PRL. Mouse knockout models of the major forms of the PRL receptor have confirmed the importance of PRLs role in reproduction. Further knockout models have provided insight into the importance of PRL signaling intermediates and the advent of transcript profiling has allowed the elucidation of a number of PRL target genes.
Normal Fasting Plasma Glucose Levels and Type 2 Diabetes in Young Men (2005)

Higher fasting plasma glucose levels within the normoglycemic range constitute an independent risk factor for type 2 diabetes among young men, and such levels may help, along with body-mass index and triglyceride levels, to identify apparently healthy men at increased risk for diabetes.
Genetic Reclassification of Histologic Grade Delineates New Clinical Subtypes of Breast Cancer (2006)

Histologic grading of breast cancer defines morphologic subtypes informative of metastatic potential, although not without considerable interobserver disagreement and clinical heterogeneity particularly among the moderately differentiated grade 2 (G2) tumors. We posited that a gene expression signature capable of discerning tumors of grade 1 (G1) and grade 3 (G3) histology might provide a more objective measure of grade with prognostic benefit for patients with G2 disease. To this end, we studied the expression profiles of 347 primary invasive breast tumors analyzed on Affymetrix microarrays. Using class prediction algorithms, we identified 264 robust grade-associated markers, six of which could accurately classify G1 and G3 tumors, and separate G2 tumors into two highly discriminant classes (termed G2a and G2b genetic grades) with patient survival outcomes highly similar to those with G1 and G3 histology, respectively. Statistical analysis of conventional clinical variables further distinguished G2a and G2b subtypes from each other, but also from histologic G1 and G3 tumors. In multivariate analyses, genetic grade was consistently found to be an independent prognostic indicator of disease recurrence comparable with that of lymph node status and tumor size. When incorporated into the Nottingham prognostic index, genetic grade enhanced detection of patients with less harmful tumors, likely to benefit little from adjuvant therapy. Our findings show that a genetic grade signature can improve prognosis and therapeutic planning for breast cancer patients, and support the view that low- and high-grade disease, as defined genetically, reflect independent pathobiological entities rather than a continuum of cancer progression.
BotB (botulinum Toxin type B): Evaluation of safety and tolerability in botulinum toxin type A‐Resistant cervical dystonia patients (preliminary study) (1997)

Botulinum toxin (BTX) injection is considered the treatment of choice for patients with cervical dystonia (torticollis). We conducted a pilot, open-label, dose-escalation study with BTX type B in 12 patients who no longer responded clinically to injections with BTX type A. At the doses tested, BTX type B was safe and well tolerated without evidence of dose-limiting toxicity in this patient population. Mild-to-moderate adverse events generally resolved quickly and included asthenia, pain, nausea, dysphagia, hypertonia, and tremor. No serious adverse events or antibodies to type-B treatment were reported. Low-dosing-session (100-899 units) and high-dosing-session (900-1,500 units) groups were defined based on units administered per dosing session. Toronto Western Spasmodic Torticollis Rating Scale-Severity Scale (TWSTRS-Severity), Patient Analogue Pain Scale, and Physician and Patient Global Assessment Scales were measured during this study. The TWSTRS-Severity mean maximum percent improvement from baseline demonstrated a 9.9% versus 28.8% difference between the low-dose and high-dose groups, respectively. EFfectiveness was noted for the high-dose group on the Patient Analogue Pain Scale but not on the Global Assessment Scales.
Use of Stevia rebaudiana sweeteners in Japan (2001)

Worldwide, the most widespread use of Stevia rebaudiana sweeteners is in Japan. The leaves of S.
rebaudiana contain several sweet ent-kaurene glycosides inclusive of stevioside, rebaudiosides A, C, D, and
E, and dulcoside A, as shown in Figure 9.1 (Mosettig et al. 1963; Kohda et al. 1976; Sakamoto et al. 1977a;
1977b; Kobayashi et al. 1977). Since the latter half of the 1970s, extracts of the leaves of S. rebaudiana
have been employed as sweetening agents, taste modifiers, and sugar substitutes in the food industry in
Japan, and have been making slow but steady progress in their utilization and distribution. In Japan, sweettasting products from S. rebaudiana leaves are called simply ‘stevia sweeteners’ and have been
commercialized in three basic forms: (i) ‘stevia extract’; (ii) ‘sugar-transferred stevia extract’; and (iii)
‘rebaudioside A-enriched stevia extract’, which have been used in a variety of foods and beverages. This
chapter deals with the practical use of stevia sweeteners in Japan, referring to their developmental
background and sweetening properties relative to progress made in these uses. Information published
previously in the English language concerning this subject may be obtained from reviews by Bakal and
O’Brien Nabors (1985) and Kinghorn and Soejarto (1985).
Metabolic Mechanisms in Heart Failure (2007)

Although neurohumoral antagonism has successfully reduced heart failure morbidity and mortality, the residual disability and death rate remains unacceptably high. Though abnormalities of myocardial metabolism are associated with heart failure, recent data suggest that heart failure may itself promote metabolic changes such as insulin resistance, in part through neurohumoral activation. A detrimental self-perpetuating cycle (heart failure --> altered metabolism --> heart failure) that promotes the progression of heart failure may thus be postulated. Accordingly, we review the cellular mechanisms and pathophysiology of altered metabolism and insulin resistance in heart failure. It is hypothesized that the ensuing detrimental myocardial energetic perturbations result from neurohumoral activation, increased adverse free fatty acid metabolism, decreased protective glucose metabolism, and in some cases insulin resistance. The result is depletion of myocardial ATP, phosphocreatine, and creatine kinase with decreased efficiency of mechanical work. On the basis of the mechanisms outlined, appropriate therapies to mitigate aberrant metabolism include intense neurohumoral antagonism, limitation of diuretics, correction of hypokalemia, exercise, and diet. We also discuss more novel mechanistic-based therapies to ameliorate metabolism and insulin resistance in heart failure. For example, metabolic modulators may optimize myocardial substrate utilization to improve cardiac function and exercise performance beyond standard care. The ultimate success of metabolic-based therapy will be manifest by its capacity further to lessen the residual mortality in heart failure.
Preparation and Characterization of Carbons from Coffee Residue: Adsorption of Salicylic Acid on the Prepared Carbons (2009)

Five activated carbons were prepared at 600 °C from coffee residue by chemical activation using ZnCl2. The effects of the impregnation ratio (ZnCl2/coffee residue) varying from (0 to 100) % on the physical and chemical characteristics were studied. Characterization of these samples was performed by using thermogravimetric analysis, scanning electron microscopy, Fourier transform infrared spectroscopy, and nitrogen adsorption−desorption isotherms at 77 K. Results showed that the microporosity (Vmic/Vtot) presented by the activated carbon at 25 % was more important with 95.70 %, while the other results indicated (92.33, 81.55, and 70.04) % for the rest of activated carbons prepared with activation ratios of (50, 75, and 100) %, respectively. Other physical and chemical characteristics such as pHPZC, apparent and real density, and so forth were also determined to complete the characterization. All of the prepared carbons were subjected to the adsorption of salicylic acid. The obtained results showed that the adsorption of salicylic acid is more effective onto activated carbon prepared with 25 % of ZnCl2 (AC 25 %). Consequently, the results of this study show that the coffee residue can be converted into activated carbon with desired characteristics by a judicious choice of activation ratio.
Pipes and filters: Modelling a software architecture through relations (2002)

Pipes and filters is a popular architecture which connects computational components (filters) through connectors (pipes) so that computations are performed in a stream like fashion. The data are transported through the pipes between filters, gradually transforming inputs to outputs. This kind of stream processing has been made popular through UNIX pipes that serially connect independent components for performing a sequence of tasks. We show in this paper how to foralize this architecture in terms of monads, hereby including relational specifications as special cases. The system is given through a directed acyclic graph the nodes of which carry the computational structure by being labelled with morphisms from the monad, and the edges provide the data for these operations. It is shown how fundamental compositional operations like combining pipes and filters, and refining a system by replacing simple parts through more elaborate ones, are supported through this construction. A notion of bisimular pipes and filters is introduced, it is shown that bisimilarity of components carries over to bisimilarity of entire systems.
Wireless Medical Sensor Networks in Emergency Response: Implementation and Pilot Results (2008)

This project demonstrates the feasibility of using cost- effective, flexible, and scalable sensor networks to address critical bottlenecks of the emergency response process. For years, emergency medical service providers conducted patient care by manually measuring vital signs, documenting assessments on paper, and communicating over handheld radios. When disasters occurred, the large numbers of casualties quickly and easily overwhelmed the responders. Collaboration with EMS and hospitals in the Baltimore Washington Metropolitan region prompted us to develop miTag (medical information tag), a cost- effective wireless sensor platform that automatically track patients throughout each step of the disaster response process, from disaster scenes, to ambulances, to hospitals. The miTag is a highly extensible platform that supports a variety of sensor add-ons - GPS, pulse oximetry, blood pressure, temperature, ECG - and relays data over a self-organizing wireless mesh network Scalability is the distinguishing characteristic of miTag: its wireless network scales across a wide range of network densities, from sparse hospital network deployments to very densely populated mass casualty sites. The miTag system is out-of-the-box operational and includes the following key technologies: 1) cost-effective sensor hardware, 2) self-organizing wireless network and 3) scalable server software that analyzes sensor data and delivers real-time updates to handheld devices and web portals. The system has evolved through multiple iterations of development and pilot deployments to become an effective patient monitoring solution. A pilot conducted with the Department of Homeland Security indicates miTags can increase the patient care capacity of responders in the field A pilot at Washington Hospital showed miTags are capable of reliably transmitting data inside radio-interference-rich critical care settings.
The Nell-1 Growth Factor Stimulates Bone Formation by Purified Human Perivascular Cells (2011)

The search for novel sources of stem cells other than bone marrow mesenchymal stem cells (MSCs) for bone regeneration and repair has been a critical endeavor. We previously established an effective protocol to homogeneously purify human pericytes from multiple fetal and adult tissues, including adipose, bone marrow, skeletal muscle, and pancreas, and identified pericytes as a primitive origin of human MSCs. In the present study, we further characterized the osteogenic potential of purified human pericytes combined with a novel osteoinductive growth factor, Nell-1. Purified pericytes grown on either standard culture ware or human cancellous bone chip (hCBC) scaffolds exhibited robust osteogenic differentiation in vitro. Using a nude mouse muscle pouch model, pericytes formed significant new bone in vivo as compared to scaffold alone (hCBC). Moreover, Nell-1 significantly increased pericyte osteogenic differentiation, both in vitro and in vivo. Interestingly, Nell-1 significantly induced pericyte proliferation and was observed to have pro-angiogenic effects, both in vitro and in vivo. These studies suggest that pericytes are a potential new cell source for future efforts in skeletal regenerative medicine, and that Nell-1 is a candidate growth factor able to induce pericyte osteogenic differentiation.
ChemInform Abstract: A Highly Efficient and Straightforward Stereoselective Synthesis of Novel Chiral α‐Acetylenic Ketones. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ROCK inhibition in models of neurodegeneration and its potential for clinical translation (2018)

Neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis are affecting a rapidly increasing population worldwide. While common pathomechanisms such as protein aggregation, axonal degeneration, dysfunction of protein clearing and an altered immune response have been characterized, no disease-modifying therapies have been developed so far. Interestingly, a significant involvement of the Rho kinase (ROCK) signaling pathway has been described in all of these mechanisms making it a promising target for new therapeutic approaches. In this article, we first review current knowledge of the involvement of ROCK in neurodegenerative disorders and the utility of its inhibition as a disease-modifying therapy in different neurodegenerative disorders. After a detailed description of the biochemical characteristics of ROCK and its molecular interactors, differences of ROCK-expression under physiological and pathological conditions are compared. Next, different pharmacological and molecular-genetic strategies to inhibit ROCK-function are discussed, focusing on pharmacological ROCK-inhibitors. The role of the ROCK-pathway in cellular processes that are central in neurodegenerative disorders pathology like axonal degeneration, autophagy, synaptic and glial function is explained in detail. Finally, all available data on ROCK-inhibition in different animal models of neurodegenerative disorders is reviewed and first approaches for translation into human patients are discussed. Taken together, there is now extensive evidence from preclinical studies in several neurodegenerative disorders that characterize ROCK as a promising drug target for further translational research in neurodegenerative disorders.