gebhart/patrepeval huggingface dataset:
Dental Enamel Development: Proteinases and Their Enamel Matrix Substrates (2013)

This review focuses on recent discoveries and delves in detail about what is known about each of the proteins (amelogenin, ameloblastin, and enamelin) and proteinases (matrix metalloproteinase-20 and kallikrein-related peptidase-4) that are secreted into the enamel matrix. After an overview of enamel development, this review focuses on these enamel proteins by describing their nomenclature, tissue expression, functions, proteinase activation, and proteinase substrate specificity. These proteins and their respective null mice and human mutations are also evaluated to shed light on the mechanisms that cause nonsyndromic enamel malformations termed amelogenesis imperfecta. Pertinent controversies are addressed. For example, do any of these proteins have a critical function in addition to their role in enamel development? Does amelogenin initiate crystallite growth, does it inhibit crystallite growth in width and thickness, or does it do neither? Detailed examination of the null mouse literature provides unmistakable clues and/or answers to these questions, and this data is thoroughly analyzed. Striking conclusions from this analysis reveal that widely held paradigms of enamel formation are inadequate. The final section of this review weaves the recent data into a plausible new mechanism by which these enamel matrix proteins support and promote enamel development.
Absolute Sense of Twist of the C12C13 Bond of the Retinal Chromophore in Bovine Rhodopsin Based on Exciton‐Coupled CD Spectra of 11,12‐Dihydroretinal Analogues (1997)

Insight into the visual transduction process: Details on the structure of the retinal chromophore in rhodospin are crucial to understanding the visual transduction process on a molecular structural level. Exciton-coupled circular dichroism (CD) spectra of opsin-bound 11,12-dihydroretinals exhibit negative bisignate couplets, which indicate that the B and C planes are oriented as shown on the right.
Gene Therapy Strategies to Prevent Autoimmune Disorders (2002)

Autoimmunity accounts for a significant percentage of human disease and remains a challenging syndrome to treat. While systemic immunosuppression can be beneficial, the associated toxicity of the pharmacologic agents necessitates an antigen-specific approach to silence, eradicate or prevent the genesis of autoreactive immune cells. Gene therapy offers the possibility of providing precise antigen-targeted therapies, thereby sparing the patient the significant toxicity associated with lifelong commitment to chemical immunosuppressives. Gene-based therapies could include, but are not limited to the manipulation of immune networks of tolerance by antigen presenting cell engineering, pro-inflammatory cytokine blockade using soluble antagonists expressed from viral vectors as well as modulation of immune regulatory networks. The potential utility of gene therapy strategies promoting tolerance in two model autoimmune disorders, type I diabetes mellitus and rheumatoid arthritis are discussed in this review.
A monoclonal antibody against hinge-cleaved IgG restores effector function to proteolytically-inactivated IgGs in vitro and in vivo (2014)

We report a chimeric monoclonal antibody (mAb) directed to a neo-epitope that is exposed in the IgG lower hinge following proteolytic cleavage. The mAb, designated 2095-2, displays specificity for IdeS-generated F(ab')₂ fragments, but not for full-length IgG or for closely-related F(ab')₂ fragments generated with other proteases. A critical component of the specificity is provided by the C-terminal amino acid of the epitope corresponding to gly-236 in the IgG1 (also IgG4) hinge. By its ability to bind to IdeS-cleaved anti-CD20 mAb, mAb 2095-2 fully restored antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against WIL2-S cells to the otherwise inactive anti-CD20 IgG1 F(ab')₂ fragment. Similarly, 2095-2 reinstated ADCC against MDA-MB-231 cells to an anti-CD142 IgG1 F(ab')₂ fragment. mAb 2095-2 was also capable of eliciting both CDC and ADCC to IgG4 F(ab')₂ fragments, an IgG subclass that has weaker ADCC and CDC when intact relative to intact IgG1. The in vitro cell-based efficacy of 2095-2 was extended to the in vivo setting using platelets as a cell clearance surrogate. In a canine model, the co-administration of 2095-2 together with IdeS-generated, platelet-targeting anti-CD41/61 F(ab')₂ fragment not only restored platelet clearance, but did so at a rate and extent of clearance that exceeded that of intact anti-CD41/61 IgG at comparable concentrations. To further explore this unexpected amplification effect, we conducted a rat study in which 2095-2 was administered at a series of doses in combination with a fixed dose of anti-CD41/61 F(ab')₂ fragments. Again, the combination, at ratios as low as 1:10 (w/w) 2095-2 to F(ab')₂, proved more effective than the anti-CD41/61 IgG1 alone. These findings suggest a novel mechanism for enhancing antibody-mediated cell-killing effector functions with potential applications in pathologic settings such as tumors and acute infections where protease activity is abundant.
Configurable Architecture for System-Level Prototyping of High-Speed Embedded Wireless Communication Systems (2003)

Broadband wireless technologies have the potential to provide integrated data and multimedia services in several niche areas. There is a growing need to develop high-performance communication systems that can satisfy high-end data processing requirements inherent in these technologies. The speed and complexity of these systems necessitates designers to break away from traditional architectures and design methodologies. A more comprehensive and demanding design and verification process including both hardware and software is required. Field-programmable gate arrays (FPGA) offer an attractive alternative to the low efficiency of Digital Signal Processor (DSP) based systems and low flexibility of Application Specific Integrated Circuits(ASIC). The availability of high-density, high-performance field-programmable gate arrays with several capabilities, like embedded memory and advanced routing, together with the adaptability that they offer make them highly desirable for developing hardware prototypes of communication systems. This thesis describes the development of a configurable architecture and FPGA-based design methodology used in the development of a Local Multipoint Distribution Service (LMDS) gateway for a disaster response network. The design of the gateway posed several challenges due to high data rates (120 Mbits/sec) and adaptive features like variable Forward Error Correction Coding and optional link-level retransmissions. The design decisions and simulation results of the verification process are discussed in detail. Finally, the aspects of testing and integration of the prototype in the overall system are discussed.
Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo (2011)

Our findings provide the first evidence of the existence of resident MSCs in the knee joint synovium that undergo proliferation and chondrogenic differentiation following injury in vivo.
Validation of a Five-Tier Cytodiagnostic System for Thyroid Fine Needle Aspiration Biopsies Using Cytohistologic Correlation (2006)

The data presented shows that the five diagnostic categories of thyroid FNAB are excellent at distinguishing benign from neoplastic thyroid nodules. Both the indeterminate and suspicious categories, while not statistically different from each other in predicting benign from neoplasia, are statistically different from obviously benign and obviously malignant categories. These results support the need for an indeterminate and/or suspicious category.
Flucytosine (1977)

Flucytosine is a systemic antifungal drug that is readily absorbed from the gastrointestinal tract. The most clearly documented therapeutic effect has been in cryptococcosis, candidiasis, and chromomycosis. An important limitation of the use of flucytosine in all three diseases has been drug resistance arising during therapy. The addition of low-dose, intravenous amphotericin B to flucytosine therapy of cryptococcosis has appeared to decrease the frequency of secondary flucytosine resistance. In addition, the two drugs have an additive or slightly synergistic effect against flucytosine susceptible isolates of Cryptococcus and Candida. The combination is probably the treatment of choice in cryptococcal meningitis and offers promise in the therapy of systemic candidiasis and nonmeningeal cryptococcosis.
Effect of sleep stage on interictal high‐frequency oscillations recorded from depth macroelectrodes in patients with focal epilepsy (2008)

Rates of HFOs recorded from depth macroelectrodes are highest in non-REM sleep. HFO properties were similar in stages N1-N2 and N3, suggesting that accurate sleep staging is not necessary. The spatial specificity of HFO, particularly fast ripples, was affected by sleep stage, suggesting that recordings excluding REM sleep and wakefulness provide a more reliable indicator of the SOZ.
Natalizumab update (2007)

Natalizumab offers an effective treatment option for patients with MS who have had an inadequate response to or are intolerant of alternative MS therapies. Because of its potential to increase the risk of PML, the risks and benefits should be carefully weighed before initiating natalizumab therapy in patients with MS. Natalizumab should not be used to treat Crohn's disease or any other unapproved indication until more postmarketing safety data are available.
Surface-Enhanced Raman Scattering (SERS) and Surface-Enhanced Resonance Raman Scattering (SERRS): A Review of Applications (2011)

Surface-enhanced Raman scattering (SERS) and surface-enhanced resonance Raman scattering (SERRS) can provide positive identification of an analyte or an analyte mixture with high sensitivity and selectivity. Better understanding of the theory and advances in the understanding of the practice have led to the development of practical applications in which the unique advantages of SERS/SERRS have been used to provide effective solutions to difficult analytical problems. This review presents a basic theory and illustrates the way in which SERS/SERRS has been developed for practical use.
Glycerol Nucleoside Triphosphates:  Synthesis and Polymerase Substrate Activities (2006)

[Structure: see text] The synthesis of (S)-glycerol nucleoside triphosphates (gNTPs) and the analysis of their substrate activities for enzymatic polymerization is described. NTPs with simplified carbohydrate backbones such as the tNTPs (alpha-L-threose-NTPs) are polymerase substrates and offer the potential to create non-natural aptamer sequences with simplified backbones through enzymatic means. The acyclic (S)-GNA was modeled after the shortened alpha-threofuranosyl backbone. Here we describe the synthesis of (S)-glycerol NTPs and initial enzymatic testing of this further simplified nucleic acid backbone.
On aspects of indoor localization (2006)

One of the key issues of emerging mobile computing and robotics is to obtain knowledge of the position of persons, vehicles and objects in an indoor environment. In order to enable a pervasive coverage, this must be achieved at low cost. Due to the importance of this problem, numerous solutions have been proposed. In this thesis two important localization techniques are discussed and major improvements are developed to address their weaknesses. A common approach for the position estimation problem is hyperbolic localization. This method is based on time difference of arrival (TDOA) measurements of signals transmitted from the mobile unit, i.e. the unit that is to be located, to a set of fixed reference units. A key requirement of this technique is that the clocks of the reference devices are synchronized. Unfortunately, if electromagnetic signals are used that travel at the speed of light even a very small clock deviation results in a tremendous inaccuracy of the computed location. Therefore, a highly precise time measurement and synchronization is mandatory for these systems. However, clocks operating at the required resolution and precision are complex and thus expensive. In this thesis, a localization approach based on TDOA measurements that implies clock synchronization is proposed and discussed. It allows for the usage of low cost oscillators that operate at a moderate frequency in the order of 100 MHz. The impact of short and long term instabilities like jitter or clock drift are inherently delimited. The approach can be applied to radio or infrared as well as ultrasound based systems. The main advantage of this approach is that common synchronization mechanisms that require a significant amount of processing and/or hardware resources can be neglected. Hence, this method is well suited for applications where the mobile unit must be very low cost and thus, of low complexity. An alternative to hyperbolic localization is triangulation, which requires the measurement of angles among fixed reference units and the mobile target. In this work, an infrared detector array for angle of arrival measurement is presented. The array consists of multiple sensing elements that are orientated in different directions. First, the arrangement is described by a sampling system. However, it is shown that low cost integrated receivers yield various aberrations, and thus the sampling approach fails. Subsequently, a new approach named virtual filter interpolation is proposed and discussed. This approach can handle individual sensitivity characteristics of each sensor element and therefore outperforms the sampling approach. The proposed technique is qualified for extremely low cost localization, e.g. for robot navigation.
Synthesis and properties of a conformationally restricted spin-labeled analog of ATP and its interaction with myosin and skeletal muscle (1992)

The synthesis is described of a spin-labeled analog of ATP, 2',3'-O-(1-oxy-2,2,6,6-tetramethyl-4-piperidylidene)adenosine 5'-triphosphate (SL-ATP). The spin-label moiety is attached by two bonds to the ribose ring as a spiroketal and hence has restricted conformational mobility relative to the ribose moiety of ATP. The synthesis proceeds via an acid-catalyzed addition of adenosine 5'-monophosphate to 1-acetoxy-4-methoxy-2,2,6,6-tetramethyl-1,2,5,6-tetrahydropyridine in acetonitrile. The spiroketal product is pyrophosphorylated, and alkaline hydrolysis with concomitant aerial oxidation gives the required product. The spin-labeled moiety probably takes up two rapidly interconverting conformations with respect to the ribose ring on the basis of the 1H NMR spectra of its precursors and related uridine derivatives [Alessi et al. (1991) J. Chem. Soc., Perkin Trans.1,2243-2247]. SL-ATP is a substrate for myosin and actomyosin with similar kinetic parameters to ATP during triphosphatase activity. SL-ATP supports muscle contraction and permits relaxation of permeabilized rabbit skeletal muscle fibers. SL-ADP is a substrate for yeast 3-phosphoglycerate kinase, thus permitting regeneration of SL-ATP from SL-ADP within muscle fibers. Electron paramagnetic resonance (EPR) studies of SL-ADP bound to myosin filaments and to myofibrils show a degree of nanosecond motion independent of that of the protein, which may be due to conformational flexibility of the ribose moiety of ATP bound to myosin's active site. This nanosecond motion is more restricted in myofibrils than in myosin filaments, suggesting that the binding of actin affects the ribose binding site in myosin. EPR studies on SL-ADP bound to rigor cross-bridges in muscle fiber bundles showed the nucleotide to be highly oriented with respect to the fiber axis.
[The assessment of breathing during sleep: a curiosity or clinical necessity?]. (2000)

The study of sleep, which initially focused on the neurophysiological mechanisms and cardiorespiratory function during the night, has shown the presence of sleep-related breathing disorders that epidemiological, pathophysiological and clinical data have indicated to be associated with increased cardiovascular morbidity and mortality: the obstructive sleep apnea syndrome (OSAS) and the central sleep apnea syndrome (CSAS). OSAS is a condition characterized by repetitive respiratory pauses due to the pharynx wall collapse, with a subsequent obstruction to the airflow. The hemodynamic consequences due to the markedly increased negative intrathoracic pressure (induced by the respiratory muscle effort towards the closed upper airways), the progressive hypercapnic hypoxemia and the arousal terminating the apneas, are the pathophysiological keys of the cardiovascular effects of OSAS and may explain the association between OSAS and the documented increase of cardiovascular morbidity and mortality. CSAS is a breathing disorder characterized by recurrent episodes of central hypopneas or apneas and hyperventilation which, is the classical form described by Cheyne and Stokes, show a crescendo-decrescendo pattern of respiration. Pathophysiological and epidemiological data clearly indicate the link between CSAS and heart failure, also showing a correlation between respiratory disorders and the severity of hemodynamic impairment. However, other mechanisms are involved in the genesis of CSAS in explaining the variable presence of CSAS independent of cardiac function and, more importantly, the impact of CSAS on poor prognosis in heart failure. In conclusion, the data available indicate the need to include screening for sleep-related breathing disorders in the evaluation of cardiac patients who are at risk for OSAS and, particularly, in patients with heart failure, who could really benefit from treatment of the respiratory disorder.
Temporally determinate disk access: an experimental approach (1997)

Disk drives are the most commonly used secondary storage devices in computer systems. The way operating systems access these devices leads to a wide range of variability in access time. In this paper we study the detailed temporal characteristics of disk drives. We describe a comprehensive set of experiments designed to build a model for the disk drive. Simulation is used to validate the model. This disk model will help design a device driver which can achieve a high degree of temporal determinacy. 1 Introduction During the recent years, disk drives have tremendously improved in terms of capacity, speed, reliability, and physical size. Even though several other secondary storage technologies have emerged, disk drives remain the dominant choice. However, the traditional method to access a disk has not changed. Applications send a read/write request with the proper disk address to an operating system process called the device driver. The application process requesting the disk service i...
The Physiological Role of Relaxin in the Pregnant Rat. II. The Influence of Relaxin on Uterine Contractile Activity* (1985)

In control intact rats (group C), the frequency of intrauterine pressure cycles (IUPC) declines steadily during pregnancy from 80-130 cycles/3 h on day 10 (D10) to 20-30 cycles/3 h on D20. The decline in frequency is due to increasingly prolonged periods of myometrial quiescence, which increase from 30-90 min/3 h on D10 to 120-150 min/3 h by D20. During the 24 h preceding labor, the frequency of IUPC remains at less than 15 cycles/h until 3 h prepartum, when there is an abrupt increase to 30 cycles/h. Ovariectomized pregnant animals treated with progesterone (P) and estrogen (E; group OPE) exhibit significantly greater frequency of IUPC and significantly lower incidence of myometrial quiescence than intact pregnant rats from D12 and for the remainder of pregnancy. Ovariectomized pregnant rats that received P, E, and porcine relaxin (R: group OPER) or P and porcine R only (group OPR) exhibited declining frequency of IUPC similar to that observed in group C animals. Group OPER rats exhibited prolonged periods of myometrial quiescence of similar duration to those observed in control intact rats. In group OPR animals, however, the periods of myometrial quiescence were considerably diminished during late pregnancy. Group OPER animals exhibited a pattern of myometrial activity during labor and postpartum similar to that of control animals. The results suggest an important role for R in the control of myometrial activity during the second half of pregnancy and parturition in the rat.
Random assignment multicenter phase II study of modified docetaxel, cisplatin, fluorouracil (mDCF) versus DCF with growth factor support (GCSF) in metastatic gastroesophageal adenocarcinoma (GE). (2010)

4014 Background: DCF is a standard first-line treatment for metastatic GE; however 80% experience grade 3-4 non-heme toxicity, and 30% febrile/neutropenia. We developed a modified DCF regimen with a goal to minimize toxicity without compromising efficacy. We report the initial results of an MSKCC Gastric Cancer Consortium random assignment phase II study evaluating mDCF and parent DCF with GCSF in advanced GE. Methods: Previously untreated metastatic GE patients were randomly assigned to Arm A, mDCF(D 40mg/m2, FU 400mg/m2, L 400mg/m2, FU 1000 mg/m2/day x2, C 40mg/m2 day 3 q14 days without GCSF) or Arm B, DCF(D 75 mg/m2, C 75 mg/m2, FU 750 mg/m2/d x5, with prophylactic GCSF q3 weeks). The primary endpoint is 6-month PFS, with 43% 6-month PFS as DCF historical control. Target accrual is 54 patients in each arm, with type I and II error at 0.1. An early stopping rule for toxicity is employed. Results: 72 evaluable patients from 10 centers have enrolled (Arm A, n=41; Arm B, n=31): median age 56 (31-76), KPS 90% (70-100%), M:F 60:17. Grade 3/4 attributable adverse events in the first 3-months for the first 30 patients in each arm are provided: Arm A—Any (57%), neutropenia (39%), febrile/neutropenia (6%), nausea/vomiting/dehydration (3%). Arm B—Any (73%), neutropenia (40%), febrile/neutropenia (17%), nausea/vomiting (20%). Toxicity-related hospitalizations: Arm A (30%, n=9), Arm B (53%, n=16). Arm B has met the early stopping rule for toxicity. Efficacy is shown in the Table. Conclusions: In this random assignment trial, despite the use of prophylactic GCSF, standard DCF is associated with unacceptable toxicity. Without compromising efficacy (median OS 15.1 months), modified DCF appears considerably more tolerable. Modified DCF is an appropriate three-drug regimen for further development in GE, including incorporation of targeted agents. Arm A—mDCF (n=41) Arm B—parent DCF+G (n=31) Liver/peritoneal disease 88% 88% Response rate 52% (33-71%) 34% (17-52 %) 6-month PFS (95%CI) 57% (37-73%) 57% (36-73 %) Time to treatment failure (median, range) 8.6 mo (5-14 mo) 7.1 mo (4-13 mo) Overall survival, median (95% CI) 15.1 mo (9-25 mo) 12.6 mo (8-18 mo) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
New Skull Turns Up in Northeast Africa (1996)

A new area for exploring human origins may be opening up. Three weeks ago, in the Danakil Desert of Eritrea, a team of Eritrean and Italian scientists unearthed a well-preserved hominid skull and other fossils dating to about 2 million years ago. Although the skull's precise identity is still shrouded in sand and stone, researchers think it could be Homo erectus; in any event, it is the first hominid found in the region.