gebhart/patrepeval huggingface dataset:
ΔF508 CFTR protein expression in tissues from patients with cystic fibrosis (1999)

Heterologous expression of the cystic fibrosis transmembrane conductance regulator (CFTR) provided evidence that the major cystic fibrosis (CF) mutation DeltaF508 leads to defective protein folding in the endoplasmic reticulum, which prevents its processing and targeting to the cell surface. In this study, we investigated endogenous CFTR expression in skin biopsies and respiratory and intestinal tissue specimens from DeltaF508 homozygous and non-CF patients, using immunohistochemical and immunoblot analyses with a panel of CFTR antibodies. CFTR expression was detected at the luminal surface of reabsorptive sweat ducts and airway submucosal glands, at the apex of ciliated cells in pseudostratified respiratory epithelia and of isolated cells of the villi of duodenum and jejunum, and within intracellular compartments of intestinal goblet cells. In DeltaF508 homozygous patients, expression of the mutant protein proved to be tissue specific. Whereas DeltaF508 CFTR was undetectable in sweat glands, the expression in the respiratory and intestinal tracts could not be distinguished from the wild-type by signal intensity or localization. The tissue-specific variation of DeltaF508 CFTR expression from null to apparently normal amounts indicates that DeltaF508 CFTR maturation can be modulated and suggests that determinants other than CFTR mislocalization should play a role in DeltaF508 CF respiratory and intestinal disease.
Combination anti–CTLA-4 plus anti–PD-1 checkpoint blockade utilizes cellular mechanisms partially distinct from monotherapies (2019)

Immune checkpoint blockade therapy targets T cell-negative costimulatory molecules such as cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1). Combination anti-CTLA-4 and anti-PD-1 blockade therapy has enhanced efficacy, but it remains unclear through what mechanisms such effects are mediated. A critical question is whether combination therapy targets and modulates the same T cell populations as monotherapies. Using a mass cytometry-based systems approach, we comprehensively profiled the response of T cell populations to monotherapy and combination anti-CTLA-4 plus anti-PD-1 therapy in syngeneic murine tumors and clinical samples. Most effects of monotherapies were additive in the context of combination therapy; however, multiple combination therapy-specific effects were observed. Highly phenotypically exhausted cluster of differentiation 8 (CD8) T cells expand in frequency following anti-PD-1 monotherapy but not combination therapy, while activated terminally differentiated effector CD8 T cells expand only following combination therapy. Combination therapy also led to further increased frequency of T helper type 1 (Th1)-like CD4 effector T cells even though anti-PD-1 monotherapy is not sufficient to do so. Mass cytometry analyses of peripheral blood from melanoma patients treated with immune checkpoint blockade therapies similarly revealed mostly additive effects on the frequencies of T cell subsets along with unique modulation of terminally differentiated effector CD8 T cells by combination ipilimumab plus nivolumab therapy. Together, these findings indicate that dual blockade of CTLA-4 and PD-1 therapy is sufficient to induce unique cellular responses compared with either monotherapy.
Indicators of Estrus in Holstein Cows Housed in Tie Stalls (1986)

Fourteen lactating Holstein cows were observed between 40 and 150 d postpartum to identify physiological and behavioral changes associated with the day of estrus. Ovulation was predicted on 29 occasions from changes in concentrations of progesterone in milk. Estrus was detected by casual observation by the herdsperson 22 times, but only 13 were detected during a daily 30-min exercise period with an androgenized heifer. Morning milk yield and daily feed intake decreased on the day of estrus. Rectal temperature, afternoon milk yield, and number of changes in postural position during the previous night increased on the day of estrus. When an increase greater than one standard deviation from the within-cow mean was considered evidence of estrus, all measures indicated more false positives than true positives. A combination of elevated temperature, increased changes of postural position at night, and depressed feed intake accurately predicted estrus, but only on 6 occasions out of 29.
Emerging technologies to measure neighborhood conditions in public health: implications for interventions and next steps (2016)

Adverse neighborhood conditions play an important role beyond individual characteristics. There is increasing interest in identifying specific characteristics of the social and built environments adversely affecting health outcomes. Most research has assessed aspects of such exposures via self-reported instruments or census data. Potential threats in the local environment may be subject to short-term changes that can only be measured with more nimble technology. The advent of new technologies may offer new opportunities to obtain geospatial data about neighborhoods that may circumvent the limitations of traditional data sources. This overview describes the utility, validity and reliability of selected emerging technologies to measure neighborhood conditions for public health applications. It also describes next steps for future research and opportunities for interventions. The paper presents an overview of the literature on measurement of the built and social environment in public health (Google Street View, webcams, crowdsourcing, remote sensing, social media, unmanned aerial vehicles, and lifespace) and location-based interventions. Emerging technologies such as Google Street View, social media, drones, webcams, and crowdsourcing may serve as effective and inexpensive tools to measure the ever-changing environment. Georeferenced social media responses may help identify where to target intervention activities, but also to passively evaluate their effectiveness. Future studies should measure exposure across key time points during the life-course as part of the exposome paradigm and integrate various types of data sources to measure environmental contexts. By harnessing these technologies, public health research can not only monitor populations and the environment, but intervene using novel strategies to improve the public health.
High-performance FPGA implementation of DES using a novel method for implementing the key schedule (2003)

A generic, parameterisable key scheduling core is presented, which can be utilised in pipelinable private-key encryption algorithms. The data encryption standard (DES) algorithm, which lends itself readily to pipelining, is utilised to exemplify this novel key scheduling method and the broader applicability of the method to other encryption algorithms is illustrated. The DES design is implemented on Xilinx Virtex FPGA technology. Utilising the novel method, a 16-stage pipelined DES design is achieved, which can run at an encryption rate of 3.87 Gbit/s. This result is among the fastest hardware implementations and is a factor 28 times faster than software implementations.
The Operating Room Environment as Affected by People and the Surgical Face Mask (1975)

The microbiological counts were determined in an operating room suite of 8 rooms and a hallway. The bacterial counts in an empty operating room jumped statistically from 13 CFU/ft2/hr (+/- 31) to 24.8 (+/- 58.8) when the doors were left open (people in the hallways) and 447.3 (+/- 186.7) when 5 people were introduced. The wearing of a surgical face mask had no effect upon the overall operating room environmental contamination and probably work only to redirect the projectile effect of talking and breathing. People are the major source of environmental contamination in the operating room.
Parasite: mining the structural information on the world-wide web (1998)

The World-Wide Web is potentially the world&apos;s largest knowledge base but only if new information retrieval techniques are developed to take advantage of its unique characteristics, particularly the semi-structured information within pages, across pages, and in page names. Because these types of structure are represented in such different ways, a large number of specialized tools have been required to gather structural information. I provide a relational database interface to the Web called Squeal, which encapsulates these different types of structure in a uniform manner, allowing the user to query the Web in Structured Query Language (SQL) as if it were a database. A novel &quot;just-in-time&quot; interpreter automatically retrieves information from the Web as implicitly demanded by user queries, a technique which could be applied not just to the Internet but to other sources of data too large to be precomputed into a database. The level of abstraction provided by Squeal allows the user to easily ...
A New Two-Dimensional Routing Algorithm (1982)

A new heuristic algorithm for two-dimensional routing utilizing two distinct layers is described. It is assumed that all terminals are on the boundary of a rectilinear routing region with or without cutout sections. Terminals on vertical boundary segments are assumed to be on one layer and those on horizontal boundary segments are on the other layer. This algorithm finds all possible paths with minimum corners for a net and then chooses one of those paths by considering path length, the likelihood of blocking nets not yet routed, the usage of vacant tracks, and the necessity of going through an area expected to be congested. A dynamic data structure is maintained. If h and v are the numbers of horizontal and vertical tracks, n is the number of nets, and t is the number of terminals, then the storage requirement is o(hv) and the time complexity is o((t-n)hv). For h=23, v=64, n=47, and t=130 the storage required is 60K bytes and cpu time is 16 seconds. This algorithm is implemented in the C language on a VAX 11/780 under the Berkeley Unix (FOOTNOTE: Unix is a trademark of Bell Laboratories.) Operating system, as part of the LTX layout system of the layout aids group at Bell Laboratories, Murray Hill.
Experimental Study on the Perception Characteristics of Haptic Texture by Multidimensional Scaling (2015)

Recent works regarding real texture perception demonstrate that physical factors such as stiffness and spatial period play a fundamental role in texture perception. This research used a multidimensional scaling (MDS) analysis to further characterize and quantify the effects of the simulation parameters on haptic texture rendering and perception. In a pilot experiment, 12 haptic texture samples were generated by using a 3-degrees-of-freedom (3-DOF) force-feedback device with varying spatial period, height, and stiffness coefficient parameter values. The subjects' perceptions of the virtual textures indicate that roughness, denseness, flatness and hardness are distinguishing characteristics of texture. In the main experiment, 19 participants rated the dissimilarities of the textures and estimated the magnitudes of their characteristics. The MDS method was used to recover the underlying perceptual space and reveal the significance of the space from the recorded data. The physical parameters and their combinations have significant effects on the perceptual characteristics. A regression model was used to quantitatively analyze the parameters and their effects on the perceptual characteristics. This paper is to illustrate that haptic texture perception based on force feedback can be modeled in two- or three-dimensional space and provide suggestions on improving perception-based haptic texture rendering.
Ghrelin stimulates neurogenesis in the dorsal motor nucleus of the vagus (2004)

Ghrelin, a gastric peptide hormone, has been reported to regulate growth hormone secretion and energy homeostasis. Here we show that ghrelin promotes neural proliferation in vivo and in vitro in the rat dorsal motor nucleus of the vagus (DMNV). Ghrelin receptor mRNA and immunoreactivity were detected in tissues from DMNV. Systemic administration of ghrelin (130 nmol kg(-1)) significantly increased 5-bromo-2'-deoxyuridine (BrdU) incorporation in the DMNV in adult rats with cervical vagotomy (BrdU positive cells; from 27 +/- 4 to 69 +/- 14 n = 5, P < 0.05). In vitro, exposure of cultured DMNV neurones to ghrelin significantly increased the percentage of BrdU incorporation into cells in both dose-dependent (10(-9) -10(-6)m), and time-dependent (6 h to 48 h) manners. Ghrelin significantly increased voltage-activated calcium currents in isolated single DMNV neurones from a mean maximal change of 141 +/- 26 pA to 227 +/- 37 pA. Upon removal of ghrelin, calcium currents slowly returned to baseline. Blocking L-type calcium channels by diltiazem (10 microm) significantly attenuated ghrelin-mediated increments in BrdU incorporation (n = 5, P < 0.05). Ghrelin acts directly on DMNV neurones to stimulate neurogenesis.
Complex mixtures of antibodies generated from a single production qualitatively and quantitatively evaluated by native Orbitrap mass spectrometry (2013)

Composite antibody mixtures designed to combat diseases present a new, rapidly emerging technology in the field of biopharmaceuticals. The combination of multiple antibodies can lead to increased effector response and limit the effect of escape variants that can propagate the disease. However, parallel development of analytical technologies is required to provide fast, thorough, accurate, and robust characterization of these mixtures. Here, we evaluate the utility of native mass spectrometry on an Orbitrap platform with high mass resolving power to characterize composite mixtures of up to 15 separate antibodies. With this technique, unambiguous identification of each antibody in the mixtures was achieved. Mass measurements of the intact antibodies varied 7 ppm on average, allowing highly reproducible identification and quantitation of each compound in these complex mixtures. We show that with the high mass-resolving power and robustness of this technology, high-resolution native mass spectrometry can be used efficiently even for batch-to batch characterization.
Amphotericin B enzyme-linked immunosorbent assay (1996)

Our purpose was to develop and characterize an enzyme-linked immunosorbent assay (ELISA) which could measure the concentration of amphotericin B in serum. Amphotericin B was assayed by competition ELISA. Multiwell ELISA plates coated with amphotericin B (1.0 micrograms/ml) conjugated to bovine serum albumin were used to test replicates of serum samples spiked with amphotericin B. Purified rabbit polyclonal antibody against amphotericin B (1.4 micrograms/ml) was added subsequent to the instillation of samples spiked with unknown amounts of amphotericin B. Experiments were performed to test the sensitivity, specificity, precision, and accuracy of the assay. The ability to measure lipid-associated amphotericin B was also evaluated in preliminary studies. Analysis of reference samples containing amphotericin B yielded a traditional sigmoidal curve. The limits of detection were 0.15 to 156 micrograms/ml. The sensitivity of the assay was affected by light and temperature exposure. Assay specificity was altered only by the presence of nystatin, a polyene antifungal agent similar to amphotericin B. Intrarun (coefficient of variation = 3.0%) and interrun (coefficient of variation = 12.8%) coefficients of variation were calculated and were comparable to those in similar assays. The assay's correlation coefficient (r = 0.907) demonstrated a statistically significant correlation between the optical density of the sample and the concentration of drug in the sample. The amphotericin B ELISA's ease, precision, and overall accuracy suggest that this assay could be used for assessments of serum amphotericin B concentrations. Multiple research questions concerning the role of serum amphotericin B concentrations in toxicity and efficacy have gone unanswered because of the labor-intensive nature of the assays which have been available to date. The ability to easily and rapidly measure 40 duplicate samples containing amphotericin B should also prove to be a distinct advantage for clinical research or reference laboratories in addressing these questions.
Biodistribution and Pharmacokinetic Studies of Bone-Targeting <i>N</i>-(2-Hydroxypropyl)methacrylamide Copolymer−Alendronate Conjugates (2008)

The biodistribution and pharmacokinetics of bone-targeting N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-alendronate conjugates were evaluated following intravenous administration of radioiodinated conjugates to young healthy BALB/c mice. The synthesis of a polymerizable and cathepsin K cleavable alendronate derivative, N-methacryloylglycylglycylprolylnorleucylalendronate, enabled the preparation of HPMA copolymer-alendronate conjugates with varying composition. Using the RAFT (reversible addition-fragmentation chain transfer) polymerization technique, four conjugates with different molecular weight and alendronate content and two control HPMA copolymers (without alendronate) with different molecular weight were prepared. The results of biodistribution studies in mice demonstrated a strong binding capacity of alendronate-targeted HPMA copolymer conjugates to bone. Conjugates with low (1.5 mol%) alendronate content exhibited a similar bone deposition capacity as conjugates containing 8.5 mol % of alendronate. The molecular weight was an important factor in the biodistribution of the HPMA copolymer conjugates. More conjugate structures need to be evaluated, but the data suggest that medium molecular weights (50-100 kDa) might be effective drug carriers for bone delivery.
Discovery of HDAC Inhibitors That Lack an Active Site Zn<sup>2+</sup>-Binding Functional Group (2012)

Natural and synthetic histone deacetylase (HDAC) inhibitors generally derive their strong binding affinity and high potency from a key functional group that binds to the Zn(2+) ion within the enzyme active site. However, this feature is also thought to carry the potential liability of undesirable off-target interactions with other metalloenzymes. As a step toward mitigating this issue, here, we describe the design, synthesis, and structure-activity characterizations of cyclic α3β-tetrapeptide HDAC inhibitors that lack the presumed indispensable Zn(2+)-binding group. The lead compounds (e.g., 15 and 26) display good potency against class 1 HDACs and are active in tissue culture against various human cancer cell lines. Importantly, enzymological analysis of 26 indicates that the cyclic α3β-tetrapeptide is a fast-on/off competitive inhibitor of HDACs 1-3 with K i values of 49, 33, and 37 nM, respectively. Our proof of principle study supports the idea that novel classes of HDAC inhibitors, which interact at the active-site opening, but not with the active site Zn(2+), can have potential in drug design.
A decade with HTLV-I/HTLV-II: lesions in viral leukemogenesis. (1992)

v-erb-B is the principal transforming gene of avian erythroblastosis virus, a replication defective retrovirus that transforms erythroid and fibroblast cells in vitro and causes erythroleukemia and fibrosarcoma in vivo. We have used a recombinant murine retrovirus, based on the truncated genome of Moloney murine leukemia virus and containing a chimeric gag-v-erb-B gene, to determine the murine hematopoietic cells transformed by v-erb-B. Infection of day 16.5 murine embryonal cells in liquid culture with this virus resulted in the outgrowth of foci of loosely to non-adherent hematopoietic cells which grew in close association with an adherent monolayer. After several weeks in culture a clonal population of transformed pre-B-lymphocytes emerged from this transformation initiated, though still growth factor dependent, population. These transformed cells were growth factor independent, and were tumorigenic in syngeneic mice. The results indicate that although v-erb-B can initiate transformation of murine hematopoietic cells, additional events are required for establishment of the fully transformed growth factor independent, tumorigenic phenotype. This v-erb-B induced progression from growth factor dependence to independence provides an in vitro model system for analysing events involved in the initiation and maintenance of leukemia.
Requirement for the continual presence of lipopolysaccharide for production of tumor necrosis factor by thioglycollate‐induced peritoneal murine macrophages (1986)

This work demonstrates the need for the continued presence of lipopolysaccharide (LPS) for tumor necrosis factor (TNF) production by thioglycollate-induced peritoneal macrophages. Removal of LPS at any time resulted in the abrupt cessation of further TNF production. The readdition of LPS resulted in further production of TNF but the yield was limited to the amount that would have been produced had the LPS not been removed.
Vas deferens anastomosis: successful repair four years subsequent to bilateral vasectomy. (1938)

A case study of successful anastomosis of the vas 4 years after elective vasectomy is presented. The operation was recommended by reason of emotional depression due to the desire to father children. Anastomosis was accomplished by forcing the freshened, patent ends together with catgut. Live spermatozoa were present in the semen at follow-up examination. The patient's emotional condition improved considerably, and he has subsequently had normal offspring.
MPC‐based approximate dual controller by information matrix maximization (2012)

SUMMARY This paper proposes a method to approximate a dual controller by a computationally feasible algorithm. Dual control that optimally solves the problem of simultaneous control and identification of a system with uncertain parameters is known to be both analytically and computationally unsolvable. This paper proposes a multiple‐step active control algorithm that gives a suboptimal but tractable solution to the original dual control problem. The algorithm is based on model predictive control (MPC) and approximates persistent system excitation in terms of the increase of the lowest eigenvalue of the parameter estimate information matrix. The problem is formulated as a two‐phase optimization problem, where first an MPC solution is found and then the lowest eigenvalue of the information matrix is maximized in the next step within a given permitted input perturbation. Unlike similar methods, the proposed algorithm predicts the information matrix for more than one step of control, which makes it possible to uniformly excite the parameter space. The use of MPC in the first design phase instead of a cautious controller is justified by showing unfavorable properties of cautious control. The advantage of the multiple‐step prediction over single‐step prediction is shown by examples and simulations. The proposed algorithm is analyzed in terms of convergence and complexity, and stability issues are addressed. The formal proofs are included in the Appendix. Copyright © 2012 John Wiley & Sons, Ltd.
Phosphinsäure-induzierte Umkehr der Regioselektivität in der Pd-katalysierten Hydrophosphinylierung von Alkinen mit Ph2P(O)H (1998)

Ein Tropfen genügt zum Umschalten von Hydropalladierung auf Phosphinylpalladierung. Wird bei der Hydrophosphinylierung von Alkinen mit Diphenylphosphanoxid ein Tropfen Diphenylphosphinsäure zugegeben, so kehrt sich, wie unten gezeigt, die Regioselektivität um.
A direct comparison between terahertz time-domain spectroscopy and far-infrared Fourier transform spectroscopy (2001)

We perform a comprehensive comparison between terahertz (THz) time-domain spectroscopy and conventional far-infrared Fourier transform spectroscopy, including radiation source, detector, signal to noise ratio, bandwidth, availability, applications, and their own uniqueness. In terms of signal to noise ratio, THz time-domain spectroscopy is advantageous at low frequencies under 3 THz, while Fourier transform spectroscopy works better at frequencies above 5 THz. In addition, we provide a detailed discussion of the unique features of THz time-domain spectroscopy and its application to dynamic and time-resolved processes.