gebhart/patrepeval huggingface dataset:
Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling (2007)

During the hair cycle, follicle stem cells (SCs) residing in a specialized niche called the "bulge" undergo bouts of quiescence and activation to cyclically regenerate new hairs. Developmental studies have long implicated the canonical bone morphogenetic protein (BMP) pathway in hair follicle (HF) determination and differentiation, but how BMP signaling functions in the hair follicle SC niche remains unknown. Here, we use loss and gain of function studies to manipulate BMP signaling in the SC niche. We show that when the Bmpr1a gene is conditionally ablated, otherwise quiescent SCs are activated to proliferate, causing an expansion of the niche and loss of slow-cycling cells. Surprisingly, follicle SCs are not lost, however, but rather, they generate long-lived, tumor-like branches that express Sox4, Lhx2, and Sonic Hedgehog but fail to terminally differentiate to make hair. A key component of BMPR1A-deficient SCs is their elevated levels of both Lef1 and beta-catenin, which form a bipartite transcription complex required for initiation of the hair cycle. Although beta-catenin can be stabilized by Wnt signaling, we show that BMPR1A deficiency enhances beta-catenin stabilization in the niche through a pathway involving PTEN inhibition and PI3K/AKT activation. Conversely, sustained BMP signaling in the SC niche blocks activation and promotes premature hair follicle differentiation. Together, these studies reveal the importance of balancing BMP signaling in the SC niche.
The Effect of Low and High Temperature Anneals on the Hydrogen Content and Passivation of Si Surface Coated with SiO2 and SiN Films (1999)

A detailed comparison of the passivation quality and its dependence on the low and high temperature anneals is presented for various promising Si surface passivation schemes. The passivation schemes investigated in this study include: conventional furnace oxide (CFO), rapid thermal oxide (RTO), belt line oxide (BLO), plasma deposited oxide (PDO), SiN deposited by plasma enhanced chemical vapor deposition (PECVD), CFO/SiN, RTO/SiN, BLO/SiN, PDO/SiN, and RTO/PDO. Passivated low resistivity (1 Ω cm) p‐type silicon samples were subjected to three annealing treatments: (a) 400°C in forming gas (FGA), (b) 730°C in air, and (c) 850°C in air, to simulate heat‐treatments, which are typically used for contact anneal, front ohmic contacts, and back surface field formation, repectively, for screen printed silicon solar cells. It is found that the passivation quality of PDO, SiN, RTO, and CFO single layers improves significantly after the 400°C FGA and 730°C thermal cycles with RTO resulting in the lowest surface recombination velocities (Seff) of 154 and 405 cm/s, respectively. Silicon wafers coated with belt oxide (BLO and BLO/SiN) did not show any improvement in Seff, which remained at 5000 cm/s due to the inferior quality of BLO formed in compressed air. The oxide/nitride stack passivation is found to be far superior to single‐layer passivation resulting in Seff of 70 cm/s for the RTO/SiN scheme after the two high temperature anneals (850 and 730°C). The hydrogen concentration measurements by Fourier transform infrared spectroscopy show a greater decrease in the hydrogen content in the annealed RTO/SiN stack compared to the as‐deposited SiN single layer after the 730 and 850°C anneals. A combination of reduced hydrogen content and very low Seff in the RTO/SiN stack suggest that the release of hydrogen from SiN during the anneal further passivates the RTO/Si interface underneath. © 1999 The Electrochemical Society. All rights reserved.
Heart failure with preserved ejection fraction: present status and future directions (2019)

The clinical importance of heart failure with preserved ejection fraction (HFpEF) has recently become apparent. HFpEF refers to heart failure (HF) symptoms with normal or near-normal cardiac function on echocardiography. Common clinical features of HFpEF include diastolic dysfunction, reduced compliance, and ventricular hypokinesia. HFpEF differs from the better-known HF with reduced ejection fraction (HFrEF). Despite having a "preserved ejection fraction," patients with HFpEF have symptoms such as shortness of breath, excessive tiredness, and limited exercise capability. Furthermore, the mortality rate and cumulative survival rate are as severe in HFpEF as they are in HFrEF. While beta-blockers and renin-angiotensin-aldosterone system modulators can improve the survival rate in HFrEF, no known therapeutic agents show similar effectiveness in HFpEF. Researchers have examined molecular events in the development of HFpEF using small and middle-sized animal models. This review discusses HFpEF with regard to etiology and clinical features and introduces the use of mouse and other animal models of human HFpEF.
Intervention to train physicians in rural China on HIV/STI knowledge and risk reduction counseling: preliminary findings (2009)

We evaluated an intervention to train physicians in rural China on knowledge of HIV/STI prevention, diagnosis, treatment options, and HIV/STI behavioral risk reduction counseling. This paper reports preliminary findings related to feasibility and acceptability of the program. Using a pre-post design, 69 physicians were recruited from rural county hospitals and participated in a 10-day group training program, followed by two months of clinical fieldwork and two additional weeks of training. Physicians completed baseline and six-month assessments. Patients' cohorts, recruited from clinic waiting areas of participating physicians, completed baseline and six-month HIV/STI risk assessments. Physicians reported increased knowledge of HIV biology and pathology, epidemiology, host immune response, opportunisitic infection and syndromic management, antiretroviral therapy, risk reduction counseling, and stigma reduction following the training. Patients reported improved knowledge of HIV, reduced HIV stigma, higher rates of HIV testing, and improved condom use at follow-up. The findings suggest that training physicians on HIV/STI-related knowledge and risk reduction counseling is a promising strategy for reducing HIV/STI epidemics in rural China.
Bat Transmitted Rabies (1961)

Up to a few years ago, all the information one needed for a full understanding of rabies as a disease seemed to be readily available in most text-books. The rapidity with which changes in our concepts of this disease are now taking place, and the multiplicity of publications dealing with this disease both make frequent reviews desirable. Actually, bat-transmitted rabies created problems long before it was even recognized. A paralytic disease of epizoonotic proportions in horses, mules, and cattle in Brazil in 1908 was not even identified as rabies until three years after the outbreak started.
Further development of hydrogen bond functions for use in determining energetically favorable binding sites on molecules of known structure. 1. Ligand probe groups with the ability to form two hydrogen bonds (1993)

The directional properties of hydrogen bonds play a major role in determining the specificity of intermolecular interactions. An energy function which takes explicit account of these properties has been developed for use in the determination of energetically favorable ligand binding sites on molecules of known structure by the GRID method (Goodford, P.J.J. Med. Chem. 1985, 28, 849. Boobbyer, D.N.A.; Goodford, P.J.; McWhinnie, P.M.; Wade, R.C.J. Med. Chem. 1989, 32, 1083). In this method, the interaction energy between a target molecule and a small chemical group (a probe), which may be part of a larger ligand, was calculated using an energy function consisting of Lennard-Jones, electrostatic, and hydrogen bond terms. The latter term was a function of the length of the hydrogen bond, its orientation at the hydrogen-bonding atoms, and their chemical nature. We now describe hydrogen bond energy functions which take account of the spatial distribution of the hydrogen bonds made by probes with the ability to form two hydrogen bonds. These functions were designed so as to model the experimentally observed angular dependence of the hydrogen bonds. We also describe the procedure to locate the position and orientation of the probe at which the interaction energy is optimized. The use of this procedure is demonstrated by examples of biological and pharmacological interest which show that it can produce results that are consistent with other theoretical approaches and with experimental observations.
Substituting Disk Failure Avoidance for Redundancy in Wide Area Fault Tolerant Storage Systems (2012)

The primary mechanism for overcoming faults in modern storage systems is to introduce redundancy in the form of replication and/or error correcting codes. The costs of such redundancy in hardware, system availability and overall complexity can be substantial, depending on the number and pattern of faults that are handled. In this paper, we describe a system that seeks to use disk failure avoidance to reduce the need for costly redundancy by using adaptive heuristics that predict such failures. While a number of predictive factors such as hard drive utilization rate, age, SMART errors, and model can be used, the initial work we present here focuses on SMART errors. Our approach can predict where near term disk failures are more likely to occur, enabling proactive movement/replication of at-risk data, thus maintaining data integrity and availability. Our strategy can reduce costs due to redundant storage without compromising these important requirements.
Replication Stress, DNA Damage, Inflammatory Cytokines and Innate Immune Response (2020)

Complete and accurate DNA replication is essential to genome stability maintenance during cellular division. However, cells are routinely challenged by endogenous as well as exogenous agents that threaten DNA stability. DNA breaks and the activation of the DNA damage response (DDR) arising from endogenous replication stress have been observed at pre- or early stages of oncogenesis and senescence. Proper detection and signalling of DNA damage are essential for the autonomous cellular response in which the DDR regulates cell cycle progression and controls the repair machinery. In addition to this autonomous cellular response, replicative stress changes the cellular microenvironment, activating the innate immune response that enables the organism to protect itself against the proliferation of damaged cells. Thereby, the recent descriptions of the mechanisms of the pro-inflammatory response activation after replication stress, DNA damage and DDR defects constitute important conceptual novelties. Here, we review the links of replication, DNA damage and DDR defects to innate immunity activation by pro-inflammatory paracrine effects, highlighting the implications for human syndromes and immunotherapies.
Effects of Alterations in Auditory Feedback and Speech Rate on Stuttering Frequency (1993)

This study investigated the effects of altered auditory feedback on stuttering frequency during speech production at two different speech rates, Nine stutterers, who exhibited at least 5% dysfluency during a reading task, served as subjects. They read eight different passages (each 300 syllables in length) while receiving four conditions of auditory feedback: nonaltered, masking, delayed, and frequency altered. For each auditory feedback condition, subjects read at both a normal and a fast rate. Results indicated that stuttering frequency was significantly decreased during conditions of delayed and frequency altered auditory feedback at both speech rates (p < 0.05). These findings refute the notion that a slowed speech rate is necessary for fluency enhancement under conditions of altered auditory feedback. Considering previous research and the results of this study, it is proposed that there may be two interdependent factors that are responsible for fluency enhancement: alteration of auditory feedback and modification of speech production.
PandIX — Exchanging P&I diagram model data (2012)

The P&I diagram (P&ID) shows the product flow structure and the functionality of a process plant. These data are a central base of the downstream control engineering and maintenance processes. We present a model to store these data electronically. Furthermore, the model allows a simple, formal, and unambiguous exchange of P&ID information. It is a bridge between significant information gaps through the information flow between process plant engineering and control engineering. The model is designed in a simple, formal, and unambiguous way. It allows an explicit access to the structural and functional information of the plant. Via this access, the downstream engineering processes can be supported by automatic assistance functions and self-configuration tools. A PandIX model can be created via an XSL transformation, which creates a CAEX file out of a vendor-specific XML file.
PN offset planning in IS-95 based CDMA systems (2002)

PN offset planning in IS-95 based CDMA systems is systematically addressed in this paper. The minimum reuse distance for the same pilot PN offset is derived based on pilot signal strengths. The reuse distance is a function of receiver sensitivity, propagation path loss, system configuration, search window size and hand-off parameters. It is found that the required reuse distance decreases from six times of cell radius to one cell radius, when the path loss slope increases from 20 to 50 dB/decade. The minimum pilot offset interval between two adjacent base stations is a function of propagation delay spread, hand-off parameter settings and cell distance difference. The minimum pilot separation between two adjacent cell sites will increase when the hand-off area increases. Several PN offset aliasing cases in the CDMA system deployment are discussed. Pilot PN planning strategy is also addressed. System deployment demonstrates that the established criteria are sufficient to avoid the pilot PN offset ambiguity.
A method based on PCR for the construction of cDNA libraries and probes from small amounts of tissue. (1994)

A PCR-based method is described for the production of cDNA libraries and total cDNA probes from a few milligrams of tissue. Using a model system, we show how a PCR library and PCR probes can be used to identify genes expressed at different levels in two tissues. Small amounts of tissue derived from two plants, one infected with arabis mosaic virus and the other uninfected, were used to make a library and probes. This library and the probes were used to identify viral genes expressed only in the infected plant.
Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay (1989)

Abstract In order to better understand the patho-physiologic role of granulocyte colony-stimulating factor (G-CSF), we estimated its serum levels in healthy persons and patients with various disorders, using a newly developed enzyme immunoassay (Motojima et al). In 49 of 56 normal healthy persons (88%), the levels were beneath the sensitivity of the assay (less than 30 pg/mL), while in the remaining seven healthy persons, the levels ranged from 33 to 163 pg/mL. On the other hand, nine of 11 patients (82%) with idiopathic aplastic anemia (AA), one patient with Fanconi's anemia, six of 12 patients (50%) with myelodysplastic syndrome (MDS), five of 12 patients (42%) with acute leukemia without any blast cells in the blood (M4: one, M5: one, L1: one, and L2: two), six of 18 patients (33%) with chronic myeloid leukemia (CML), one of two patients with chronic lymphoid leukemia (CLL), two of four patients with lung cancer, one patient with cyclic neutropenia, two of seven patients with malignant lymphoma, and four patients with acute infection had G-CSF levels ranging from 46 pg/mL to greater than 2,000 pg/mL. Interestingly, a reverse correlation between blood neutrophil count and serum G-CSF level was clearly demonstrated for aplastic anemia (r = -.8169, P less than .01). Moreover, it was found that the G-CSF level rose during the neutropenic phase of cyclic neutropenia and after chemotherapy or bone marrow transplantation (BMT) in three patients with leukemia; also high G-CSF levels were positively correlated to blood neutrophil counts in some cases of infectious disorders and lung cancer. The cellular sources and the mechanisms for production and secretion of circulating G-CSF were not investigated in this study, but the data presented here strongly indicate that G-CSF plays an important role as a circulating neutrophilopoietin.
Viral antigen mediated NKp46 activation of NK cells results in tumor rejection via NK-DC crosstalk (2012)

Natural killer (NK) cells play a critical role in antitumor immunity, their activation being regulated through NK cell receptors. Although the endogenous ligands for these receptors are largely unknown, viral ligands have been identified. We investigated the ability of an activating NK receptor ligand derived from the mumps virus, haemagglutinin-neuraminidase (HN) to enhance NK activation against tumor cells. HN-expressing B16.OVA tumor cells induced stronger activation of NK cells compared with B16.OVA cells and also promoted dendritic cell (DC) activation toward a DC1 phenotype, in vitro. Moreover, incubation of DCs, NK cells and HN-expressing B16-OVA cells further enhanced NK cell activation through the NK-DC crosstalk, in a cell-to-cell contact- and IL-12-dependent fashion. Immunization of mice with HN-expressing B16-OVA cells resulted in > 85% survival rate after subsequent challenge with parental B16 or B16.OVA tumor cells. Tumor rejection was dependent on both NK and CD8+ T cells but not on CD4+ T cells, demonstrating induction of an effective adaptive immune response through innate immune cell activation. Our data indicate the potential of using robust NK cell activation, which through the NK-DC crosstalk stimulates effective antitumor responses, providing an alternate vaccine strategy.
On the Synthesis of Sulfinyl Cyanides (1975)

Abstract m-Chloroperbenzoic acid oxidation of thiocyanates provides a synthetic route to sulfinyl cyanides (2). 1-Adamantane-sulfinyl cyanide (2c) is prepared more efficiently from the corresponding sulfinyl chloride and sodium cyanide.
Reduction of Compressor Stator Endwall Losses Through the Use of Bowed Stators (1995)

The growth of suction surface corner separation in multistage compressor stators is shown to limit the pressure rise capability of core flow stator sections, which would otherwise remain unseparated at the same incident flow. Three dimensional CFD modeling of the stator flowfield has led to the development of “bowed” stator shapes which are predicted to substantially delay the onset of suction surface corner separation. Experimental testing of the bowed stator concept in the exit stator of a three–stage research compressor has confirmed the elimination of suction surface corer separation, the resulting reduction of the endwall loss, and the increase in pressure rise capability of the stator core sections due to the elimination of the radial growth of the corner separation region. Application of bowed stators in all three stator rows of the research compressor has provided more robust characteristics and substantially improved efficiency over the entire flow range.
Alumina: a cheap, active and selective catalyst for epoxidations with (aqueous) hydrogen peroxide (2001)

Chromatography alumina catalyses the epoxidation of alkenes with hydrogen peroxide under nearly anhydrous conditions. A variety of different aluminas show a similar catalytic behaviour. The hydrogen peroxide can be used as a preformed anhydrous solution in ethyl acetate, or it can be dried in situ by conducting the reaction under reflux with Dean–Stark water separation. The presence of a small amount of water in the reaction medium was shown to be of crucial importance.
Macrocyclic Inhibitors of Penicillopepsin. 3. Design, Synthesis, and Evaluation of an Inhibitor Bridged between P2 and P1‘ (1998)

Through application of a thorough design and modeling protocol, the macrocyclic peptidyl phosphonate 5 was derived from the bound structure of an acyclic inhibitor of penicillopepsin, 4, by linking the P1' and P2 side chains; the acyclic analogues 6 and 7 were also synthesized and evaluated for comparison. As observed for a related set of inhibitors, 1−3 [Meyer, J. H.; Bartlett, P. A. J. Am. Chem. Soc. 1998, 120, xxxx], the binding affinity at pH 4.5 was found to be inversely related to the degree of conformational flexibility across the series, 7 (Ki = 1300 nM), 6 (Ki = 42 nM), and 5 (Ki = 0.10 nM), although the differences are much greater. The structure of the macrocyclic ring of 5 in solution was determined by a combined NMR and molecular modeling method and found to correspond closely to the designed structure and to the backbone conformation of the original target, 4. The binding enhancement conveyed by the macrocyclic constraint corresponds to 0.9−1.4 kcal/mol/deg of rotational freedom lost, indicating what can be gained from this structure-based design strategy.
Non-vitamin K antagonist oral anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication adherence (2015)

Suboptimal medication adherence is a widespread problem in ambulatory care of chronic diseases, with deviations in either direction from the prescribed dosing regimen. For the non-vitamin K antagonist oral anticoagulants (NOACs), such deviations occur and can lead to bleeding or clotting, as suboptimal adherence involves temporary periods of either overdosing or underdosing. In this expert review, we discuss: (a) the proper definition of adherence in terms of its three elements: initiation, implementation, and discontinuation; (b) how adherence is reliably and accurately measured and (c) successfully enhanced, to achieve and maintain safe and effective levels of NOAC-based anticoagulation. We also discuss the comparative effects of prescribing the same total daily dose, given either once-daily or as half-strength twice-daily doses. Because NOACs have plasma half-lives of ∼12 h, the twice-daily dosing regimen is less prone than the once-daily dosing regimen to hazardously high peaks or hazardously low troughs in anticoagulant concentrations and associated actions. As in other fields of oral drug treatment, the continuity of drug action is greater with twice-daily than with once-daily dosing, despite the fact that a few more doses are skipped with twice-daily than with once-daily dosing. This paradox is explained by the disproportionately greater impact on drug action of skipping a once-daily than a twice-daily dose. Integration of these principles into real-world medication management is the next step in the improvement of oral anticoagulation.
GaN HEMT Potential for Low-Noise Highly Linear RF Applications (2008)

This paper presents a study of the capability of gallium-nitride (GaN) high-electron mobility transistors (HEMTs) to achieve low noise and high linearity performance. A packaged GaN HEMT was measured in a 50 - Omega system at 2 GHz. Noise figures slightly above 1.8 dB were achieved together with a record third-order intercept point of 54 dBm. The same configuration yields a maximum output power of 30 W, with 50% power-added efficiency. This combination of high power and low-noise performance allows the realization of highly linear low-noise amplifiers, which could significantly reduce protection and filter efforts at receiver inputs.