gebhart/patrepeval huggingface dataset:
The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series (2010)

Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic (1,2). Its prevalence is 0.1% (3). Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods (1). All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain (4) or occipital nerve stimulation (5). However, serious complications from brain surgery, including death, can occur (6). An Internet survey of 53 CH patients reported on claims that psilocybin is better at aborting acute attacks than either oxygen or sumatriptan and that LSD and psilocybin are both better at triggering and extending remission than standard drugs (7). However, due to hallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed within the most restrictive Schedule I of the Controlled Substances Act, which sanctions only limited research use. Although the hallucinogenic properties of LSD and psilocybin are undesirable from both regulatory and patient safety perspectives, it was unclear to us at the outset whether a non-hallucinogenic analog could also provide meaningful relief to CH patients. To address the question of whether the CH relief associated with these two structurally diverse compounds is related to the mechanisms triggering intoxication, we decided to investigate the efficacy of a nonhallucinogenic analog of LSD. LSD’s hallucinogenic effects are completely lost when the double bond in the D ring is saturated and with substitution at R2 (e.g. by bromination in 2-bromo-LSD) (BOL-148) (8). BOL-148 has been studied in volunteers (up to 20mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies concluded that BOL-148 is non-toxic and non-hallucinogenic. Only very mild side effects, if any, have been observed, when given in the dose range used in our project (30mg/kg/body weight) (9). No long-term behavioral or psychological effects from BOL-148 have been reported from past studies with more than 300 healthy, normal subjects (11), and 30mg BOL-148 administered daily over four to five weeks failed to alter active psychosis in chronically ill schizophrenic women (12).
Diaminobutane (DAB) Dendrimers Are Potent Binders of Oral Phosphate (2008)

Reduction of blood phosphorus is a critical component in the management of secondary hyperparathyroidism in chronic kidney disease patients. In addition to dialysis treatment and dietary phosphorus restriction, oral phosphate binders are often consumed with meals to reduce the availability of food phosphorus. Several oral phosphate binders are approved for use in chronic kidney disease patients, but all have practical limitations because of toxicity, poor efficacy, or high cost. Using an in vivo method to measure intestinal phosphate absorption in rats using radiolabeled phosphate, we found that first-, second-, third-, and fifth-generation diaminobutane dendrimer compounds, DAB-4-Cl, DAB-8-Cl, DAB-16-Cl, and DAB-64-Cl, respectively, drastically reduce the absorption of inorganic phosphate in a dose-dependent manner. To avoid complications of metabolic acidosis caused by hydrochloride salts, an acetate salt, DAB-9-AcOH, was prepared and shown to be equally effective at binding radiolabeled phosphate as DAB-8-Cl. DAB-8-AcOH was further shown to increase fecal phosphorus and decrease serum phosphorus in a dose-dependent manner when fed to rats. These data suggest that dendrimer compounds are of great potential use in the binding of food phosphate for the management of hyperparathyroidism secondary to chronic kidney disease.
Magnetization switching and tunneling magnetoresistance effects with synthetic antiferromagnet free layers consisting of amorphous CoFeSiB (2005)

MTJs with the synthetic antiferromagnetic (SAF) free layer consisting of CoFeSiB/Ru/CoFeSiB were prepared because a SAF structure can reduce the magnetostatic coupling. Magnetic switching and tunneling magnetoresistance (TMR) ratio of MTJs were investigated by experiment and by simulation. SAF structures show lower TMR ratio and coercivity (H/sub c/) than single free layer due to low net magnetic moment. The CoFeSiB SAF structure was found to have lower exchange energy.
Accuracy-configurable adder for approximate arithmetic designs (2012)

Approximation can increase performance or reduce power consumption with a simplified or inaccurate circuit in application contexts where strict requirements are relaxed. For applications related to human senses, approximate arithmetic can be used to generate sufficient results rather than absolutely accurate results. Approximate design exploits a tradeoff of accuracy in computation versus performance and power. However, required accuracy varies according to applications, and 100% accurate results are still required in some situations. In this paper, we propose an accuracy-configurable approximate (ACA) adder for which the accuracy of results is configurable <u>during runtime.</u> Because of its configurability, the ACA adder can adaptively operate in both approximate (inaccurate) mode and accurate mode. The proposed adder can achieve significant throughput improvement and total power reduction over conventional adder designs. It can be used in accuracy-configurable applications, and improves the achievable tradeoff between performance/power and quality. The ACA adder achieves approximately 30% power reduction versus the conventional pipelined adder at the relaxed accuracy requirement.
Nanoporous framework materials interfaced with mechanical sensors for highly-sensitive chemical sensing. (2010)

We will describe how novel nanoporous framework materials (NFM) such as metal-organic frameworks (MOFs) can be interfaced with common mechanical sensors, such as surface acoustic wave (SAW), microcantilever array, and quartz crystal microbalance (QCM) devices, and subsequently be used to provide selectivity and sensitivity to a broad range of analytes including explosives, nerve agents, and volatile organic compounds (VOCs). NFM are highly ordered, crystalline materials with considerable synthetic flexibility resulting from the presence of both organic and inorganic components within their structure. Chemical detection using micro-electro-mechanical-systems (MEMS) devices (i.e. SAWs, microcantilevers) requires the use of recognition layers to impart selectivity. Unlike traditional organic polymers, which are dense, the nanoporosity and ultrahigh surface areas of NFM allow for greater analyte uptake and enhance transport into and out of the sensing layer. This enhancement over traditional coatings leads to improved response times and greater sensitivity, while their ordered structure allows chemical tuning to impart selectivity. We describe here experiments and modeling aimed at creating NFM layers tailored to the detection of water vapor, explosives, CWMD, and volatile organic compound (VOCs), and their integration with the surfaces of MEMS devices. Molecular simulation shows that a high degree of chemical selectivity is feasible. Formore » example, a suite of MOFs can select for strongly interacting organics (explosives, CWMD) vs. lighter volatile organics at trace concentrations. At higher gas pressures, the CWMD are deselected in favor of the volatile organics. We will also demonstrate the integration of various NFM on the surface of microcantiliver arrays, QCM crystals, and SAW devices, and describe new synthetic methods developed to improve the quality of NFM coatings. Finally, MOF-coated MEMS devices show how temperature changes can be tuned to improve response times, selectivity, and sensitivity.« less
Integral CFLs performance in table lamps (1997)

This paper focuses on performance variations associated with lamp geometry and distribution in portable table luminaires. If correctly retrofit with compact fluorescent lamps (CFLs), these high use fixtures produce significant energy savings, but if misused, these products could instead generate consumer dissatisfaction with CFLs. It is the authors assertion that the lumen distribution of the light source within the luminaires plays a critical role in total light output, fixture efficiency and efficacy, and, perhaps most importantly, perceived brightness. The authors studied nearly 30 different integral (screw-based) CFLs available on the market today in search of a lamp, or group of lamps, which work best in portable table luminaires. The findings conclusively indicate that horizontally oriented CFLs outperform all other types of CFLs in nearly every aspect.
Disentangling the activity-selectivity trade-off in catalytic conversion of syngas to light olefins (2023)

Breaking the trade-off between activity and selectivity has been a long-standing challenge in the field of catalysis. We demonstrate the importance of disentangling the target reaction from the secondary reactions for the case of direct syngas conversion to light olefins by incorporating germanium-substituted AlPO-18 within the framework of the metal oxide-zeolite (OXZEO) catalyst concept. The attenuated strength of the catalytically active Brønsted acid sites allows enhancing the targeted carbon-carbon coupling of ketene intermediates to form olefins by increasing the active site density while inhibiting secondary reactions that consume the olefins. Thus, a light-olefins selectivity of 83% among hydrocarbons and carbon monoxide conversion of 85% were obtained simultaneously, leading to an unprecedented light-olefins yield of 48% versus current reported light-olefins yields of ≤27%.
3<i>H</i>‐2,1,3‐benzolhiadiazine 2,2‐dioxide. A novel heterocyclic system (1979)

Abstract A new heterocyclic system, 3 H ‐2,1,3‐benzothiadiazine 2,2‐dioxide has been prepared via oxidation of the 3,4‐dihydro‐1 H ‐2,1, 3‐benzothiadiazine 2,2‐dioxides.
Synthesis and antiinflammatory and analgesic activity of 5-aroyl-6-(methylthio)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carboxylic acids and 1-methyl-4-(methylthio)-5-aroylpyrrole-2-acetic acids (1989)

5-Aroyl-6-(methylthio)-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1-carb oxylic acids and 1-methyl-4-(methylthio)-5-aroylpyrrole-2-acetic acids were synthesized and assayed as antiinflammatory and analgesic agents. The majority of these compounds exhibit a surprisingly low level of antiinflammatory activity (rat carrageenan paw) but have considerable potency as analgesics (mouse phenylquinone writing). For example, the p-tolyl-substituted bicyclic and monocyclic compounds 44 and 58 are 301 and 66 times more potent than aspirin (mouse writhing) but only 3.4 and 1.5 times more potent than phenylbutazone in the antiinflammatory screen (rat paw).
Therapeutic activity of modified U1 core spliceosomal particles (2016)

Modified U1 snRNAs bound to intronic sequences downstream of the 5' splice site correct exon skipping caused by different types of mutations. Here we evaluate the therapeutic activity and structural requirements of these exon-specific U1 snRNA (ExSpeU1) particles. In a severe spinal muscular atrophy, mouse model, ExSpeU1, introduced by germline transgenesis, increases SMN2 exon 7 inclusion, SMN protein production and extends life span. In vitro, RNA mutant analysis and silencing experiments show that while U1A protein is dispensable, the 70K and stem loop IV elements mediate most of the splicing rescue activity through improvement of exon and intron definition. Our findings indicate that precise engineering of the U1 core spliceosomal RNA particle has therapeutic potential in pathologies associated with exon-skipping mutations.
Selective Small Molecule Inhibitors of 12-Human Lipoxygenase (12-hLO) (2011)

Human lipoxygenases (hLOs) are distributed among a variety of tissues and cellular locations in the body, and they are part of the first committed step in a cascade of metabolic pathways. As such, hLOs are implicated in the onset of inflammatory diseases such as cancers, heart disease and asthmas, making them an ideal target for pharmaceutical intervention. The lipoxygenase platelet-type 12-(S)-hLO has been implicated in skin diseases, diabetes, platelet hemostasis, thrombosis and cancer. Despite the potential of 12-hLO as a therapeutic target, potent and selective inhibitors of the enzyme are lacking in the patent or public literature. To date, the only known modulators of 12-hLO are either weak inhibitors or promiscuous polyphenolic compounds that inhibit several of the closely related isoymes. In this report, we describe the development of small-molecule inhibitors that exhibit nanomolar potency against 12-hLO and >50-fold selectivity over the related lipoxygenases and cyclooxygneases. Kinetic experiments indicate that this chemotype is a non-competitive inhibitor that does not reduce the active site iron. Moreover, chiral HPLC separation of several of the racemic lead molecules revealed a strong preference for the (−)-enantiomer (IC50 ~ 0.4μM) compared to > 25μM for the (+)-enantiomer, indicating a fine degree of selectivity in the active site due to chiral geometry. The small molecule probe ML127 (CID-44460175) and its related analogs represent the most potent and selective 12-hLO inhibitors reported thus far.
Therapy with monoclonal antibody to interleukin 2 receptor spares suppressor T cells and prevents or reverses acute allograft rejection in rats. (1986)

The mouse hybridoma ART 18 monoclonal antibody (mAb), which binds to the rat interleukin 2 (IL-2) receptor, was studied for its effect on heterotopic cardiac allograft survival in two histoincompatible inbred rat strain combinations. Treatment with ART 18 mAb for 10 days after transplantation prolonged allograft survival in a dose-dependent fashion up to about 3 weeks (acute rejection normally occurs within 8 days). ART 18 mAb therapy started at 5 days after transplantation the time of major rejection activity) abrogated acute rejection and extended the survival to about 18 days. The dense cellular infiltrate noted histologically in acute rejection had virtually disappeared after ART 18 mAb treatment. Thus, IL-2 receptor-targeted therapy can be successfully used to prevent and/or treat acute rejection. When spleen cells from antibody-treated recipients bearing well-functioning allografts were adoptively transferred to normal untreated rats that received cardiac allografts 24 hr later, the survival of donor-specific, but not third-party, test cardiac allografts was prolonged significantly; this supports the idea that ART 18 mAb induced "sparing" of suppressor T lymphocytes. Combining infusion of ART 18 mAb with exogenous IL-2-rich conditioned medium produced the same effect as if the mAb alone had been administered, suggesting that an excess of IL-2 does not prevent binding of ART 18 mAb to IL-2 receptor-bearing cells in vivo. These results support the important role of the IL-2 receptor-bearing cells in the mechanism of allograft rejection; they may represent an important target for immunosuppression in clinical organ transplantation.
Input- and Output-Based Shared-Memory Crosspoint-Buffered Packet Switches for Multicast Traffic Switching and Replication (2008)

The incorporation of broadcast and multimedia- on-demand services are expected to increase multicast traffic in packet networks, and therefore in switches and routers. Combined input-crosspoint buffered (CICB) switches can provide high performance under uniform multicast traffic, however, at the expense of N <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> crosspoint buffers. In this paper, we introduce an output-based shared-memory crosspoint-buffered (O-SMCB) packet switch where the crosspoint buffers are shared by two outputs and use no speedup. The proposed switch provides high performance under admissible uniform and nonuniform multicast traffic models while using 50% of the memory used in CICB switches. Furthermore, the O-SMCB switch provides higher throughput than an SMCB switch with buffers shared by inputs, or I-SMCB, previously proposed, despite the strong similarities between the architectures of these two switches. In this paper, we study the performance of the O-SMCB switch under uniform and nonuniform multicast traffic models and compare it to the I-SMCB switch.
3D Ultrasonic Rangefinder on a Chip (2014)

An ultrasonic 3D rangefinder uses an array of AlN MEMS transducers and custom readout electronics to localize targets over a ±45° field of view up to 1 m away. The rms position error at 0.5 m range is 0.4 mm, 0.2 °, and 0.8 ° for the range, x-angle, and y-angle axes, respectively. The 0.18 μm CMOS ASIC comprises 10 independent channels with separate high voltage transmitters, readout amplifiers, and switched-capacitor bandpass ΣΔ ADCs with built-in continuous time anti-alias filtering. For a 1 m maximum range, power dissipation is 400 μW at 30 fps. For a 0.3 m maximum range, the power dissipation scales to 5 μW/ch at 10 fps.
Mechanisms and Refinements of PSCA Directed Antibody Therapy (2003)

Abstract : Prostate stem cell antigen is a cell surface protein expressed by a majority of localized, and metastatic prostate cancers. Our laboratory previously showed that a monoclonal antibody against PSCA, mAb 1GB, could inhibit the growth and metastasis of prostate cancers in immunodeficiency mice. The overall goal of this study was to determine the mechanism of action of this antibody, primarily whether it inhibited growth by recruiting the immune system or by direct crosslinking and signaling via the antigen on the cell surface. In addition, we proposed to test rational combination therapies to determine if we could improve upon the activity of the antibody itself. The major results reported here are that (1) the antibody 1GB inhibits tumor growth predominantly through an Fc independent mechanism of action, and (2) that combination therapies are context dependent. In some instances, castration synergized with antibody to prevent androgen independent tumor progression, while in others antibody promoted androgen independent progression. These results are directly relevant to the clinic as a humanized version of PSCA mAb 1GB generated by our laboratory nears application in the clinic.
Flat nonlinear optics: efficient frequency conversion in ultrathin nonlinear metasurfaces (2015)

We report highly-nonlinear ultra-thin metasurfaces based on coupling of modes in plasmonic nanoresonators with intersubband nonlinearities with phase-control of nonlinear optical response. Nonlinear susceptibility >106 pm/V and conversion efficiencies ~0.1% were measured for second-harmonic generation.
Robust Understanding in Multimodal Interfaces (2009)

Multimodal grammars provide an effective mechanism for quickly creating integration and understanding capabilities for interactive systems supporting simultaneous use of multiple input modalities. However, like other approaches based on hand-crafted grammars, multimodal grammars can be brittle with respect to unexpected, erroneous, or disfluent input. In this article, we show how the finite-state approach to multimodal language processing can be extended to support multimodal applications combining speech with complex freehand pen input, and evaluate the approach in the context of a multimodal conversational system (MATCH). We explore a range of different techniques for improving the robustness of multimodal integration and understanding. These include techniques for building effective language models for speech recognition when little or no multimodal training data is available, and techniques for robust multimodal understanding that draw on classification, machine translation, and sequence edit methods. We also explore the use of edit-based methods to overcome mismatches between the gesture stream and the speech stream.
Peptide Aptamers Targeting Mutant p53 Induce Apoptosis in Tumor Cells (2008)

Mutations in the p53 tumor suppressor gene frequently result in expression of p53 point mutants that accumulate in cancer cells and actively collaborate with tumor progression through the acquisition of novel properties. Interfering with mutant p53 functions may represent a valid alternative for blocking tumor growth and development of aggressive phenotypes. The interactions and activities of selected proteins can be specifically modulated by the binding of peptide aptamers (PA). In the present work, we isolated PAs able to interact more efficiently with p53 conformational mutants compared with wild-type p53. The interaction between mutant p53 and PAs was further characterized using molecular modeling. Transient expression of PAs was able to reduce the transactivation activity of mutant p53 and to induce apoptosis specifically in cells expressing mutant p53. These PAs could provide a potential strategy to inhibit the oncogenic functions of mutant p53 and improve mutant p53-targeted cancer therapies.
Novel Hyperbranched Dendron for Gene Transfer in Vitro and in Vivo (2004)

Novel hyperbranched dendron (HD) polymers were synthesized using a low molecular weight poly(ethyleneimine) core (BPEI). Using successive attachment of ethyleneimine moieties to the PEI core, the relative ratio of linear-to-branched structures was lowered from 1.17 to 0.70. We found that the more extensive branching of PEI enables the condensation of plasmid DNA into nanostructures with a size of 70−100 nm. The obtained complexes were stable at least for 3 weeks at 4 °C. The HD−DNA complexes prepared using secondary and tertiary amine-containing dendrons exerted a very low cytotoxicity in vitro during a coincubation with cells for 48 h. Using firefly luciferase as a marker of protein expression, we established that HD complexes were efficient in transfecting cells in the presence of serum. Under optimized conditions, the transfection activity at a nitrogen-to-phosphate (N/P) ratio of 6 was approximately six times higher than that of the commercially available polycationic transfection reagent. Bioluminescent imaging of in vivo gene expression using a luciferase reporter gene showed the increase of the signal in the liver and in submandibular lymph nodes in live mice. Our preliminary in vivo gene expression data demonstrates the potential of HD polymers as in vivo transfection agents that could be potentially useful for lymph node gene delivery.