gebhart/patrepeval huggingface dataset:
The discovery of a new structural class of cyclin-dependent kinase inhibitors, aminoimidazo[1,2-<i>a</i>]pyridines (2004)

The protein kinase family represents an enormous opportunity for drug development. However, the current limitation in structural diversity of kinase inhibitors has complicated efforts to identify effective treatments of diseases that involve protein kinase signaling pathways. We have identified a new structural class of protein serine/threonine kinase inhibitors comprising an aminoimidazo[1,2-a]pyridine nucleus. In this report, we describe the first successful use of this class of aza-heterocycles to generate potent inhibitors of cyclin-dependent kinases that compete with ATP for binding to a catalytic subunit of the protein. Co-crystal structures of CDK2 in complex with lead compounds reveal a unique mode of binding. Using this knowledge, a structure-based design approach directed this chemical scaffold toward generating potent and selective CDK2 inhibitors, which selectively inhibited the CDK2-dependent phosphorylation of Rb and induced caspase-3-dependent apoptosis in HCT 116 tumor cells. The discovery of this new class of ATP-site-directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis for a new medicinal chemistry tool to be used in the search for effective treatments of cancer and other diseases that involve protein kinase signaling pathways.
Multitask Sequence-to-Sequence Models for Grapheme-to-Phoneme Conversion (2017)

Recently, neural sequence-to-sequence (Seq2Seq) models have been applied to the problem of grapheme-to-phoneme (G2P) conversion. These models offer a straightforward way of modeling the conversion by jointly learning the alignment and translation of input to output tokens in an end-to-end fashion. However, until now this approach did not show improved error rates on its own compared to traditional joint-sequence based n-gram models for G2P. In this paper, we investigate how multitask learning can improve the performance of Seq2Seq G2P models. A single Seq2Seq model is trained on multiple phoneme lexicon datasets containing multiple languages and phonetic alphabets. Although multi-language learning does not show improved error rates, combining standard datasets and crawled data with different phonetic alphabets of the same language shows promising error reductions on English and German Seq2Seq G2P conversion. Finally, combining Seq2seq G2P models with standard n-grams based models yields significant improvements over using either model alone.
IEEE 802.11ax Spatial Reuse Improvement: An Interference-Based Channel-Access Algorithm (2019)

Wi-Fi is the dominant way of connecting indoor mobile devices to the Internet. The main reason behind the huge adoption of this technology is the simplicity of the IEEE 802.11 protocols, which offer low-cost ownership and maintenance combined with the ability to provide high data rates to end users. The increasing demand in traffic volumes leads to the continuous deployment of access points (APs), resulting in densification of the IEEE 802.11 networks. This densification, instead of enhancing the efficiency of wireless local area networks (WLANs), degrades their overall performance due to cochannel interference between overlapped basic services sets (OBSSs). One of the main goals of the IEEE 802.11ax amendment now under development is to address the WLAN densification problem by improving spatial reuse (SR).
Preparation of Naturally Occurring a-Terthiophenes (2,2':5',2''-Terthiophenes) (1986)

A series of naturally occurring a-terthiophenes (2,2':5',2"-terthiophenes) were prepared using readily accessible bis[2-0x0-2-(2-thienyl)ethyl] sulfide as the starting material.Biological properties of a-terthiophene (2,2':5',Zt'-terthiophene) (la) and its -derivatives have attracted much attention.'Terthiophene la was first obtained -as a byproduct in the preparation of 2,~'-bithiopheneZ and later characterized in the petals of the yellow marigold ( T a g e t e s e r e c t a ) .3Other plants belonging to the family Compositae also contain la and its derivative^.^Especially a series
SPONDYLOLISTHESIS (1938)

Although somewhat confusing and laborious, a detailed study of the human spine must be the basic factor in an understanding of certain of its clinical disorders. The one selected for discussion here is spondylolisthesis, a condition or anomaly formerly mentioned only as occurring in women because of its relation to maternal dystocia. Recent investigation has sought the cause of pain and disabilities affecting the lower part of the back, which result in difficulties in awarding compensation when the condition is directly associated with the traumas of occupation or when distress and restricted activity are chronically prolonged exclusive of a known trauma. In the course of this investigation the condition and its alleviation have become prominent in surgical research. The advent of high grade roentgenologic aid in the clinical study of the human spine has added to knowledge of the anatomic and pathologic character of these formerly obscure conditions affecting the
Novel insights into the genetics, biochemistry, and immunocytochemistry of the 30-kilodalton major extracellular protein of Mycobacterium tuberculosis (1996)

The 30/32-kDa complex of major secretory proteins are among the most important and intensively studied proteins of Mycobacterium tuberculosis. The proteins have been demonstrated to be immunoprotective and to play a central role in the physiology of the mycobacterium. In this study, we present a series of novel insights into this key protein complex arising out of a combination of genetic, biochemical, and immunocytochemical analyses. Our genetic analyses (i) indicate that the genes are arranged as separate transcription units, (ii) demonstrate that the mature 30-kDa protein of M. tuberculosis differs from the corresponding 30-kDa proteins of two strains of Mycobacterium bovis BCG by only 1 and 5 amino acids, (iii) suggest that expression of the proteins is regulated at the transcriptional level, and (iv) map the transcriptional start site of the 30-kDa protein gene. Our biochemical analyses provide evidence that (i) the 30-kDa protein and the two 32-kDa proteins (i.e., 32A and 32B) are secreted at a ratio of approximately 3:2:1, respectively, (ii) the proteins exist as monomers, (iii) the proteins are not posttranslationally modified by the addition of carbohydrates and lipids, (iv) the 30-kDa and 32A proteins contain one disulfide bridge, and (v) high-level expression and leader peptide processing are achievable in Escherichia coli. Our immunocytochemical analyses demonstrate that the 30/32-kDa complex is expressed in human monocytes and that the proteins are localized to the phagosomal space and the mycobacterial cell wall. These analyses fill important gaps in our knowledge of this critical protein complex of M. tuberculosis and, at the same time, raise new and fundamental questions regarding regulatory mechanisms that control coordinate expression of the proteins at a fixed ratio.
Switchable Selectivity during Oxidation of Anilines in a Ball Mill (2010)

A solvent-free method for the direct oxidation of anilines to the corresponding azo and azoxy homocoupling products by using a planetary ball mill was developed. Various oxidants and grinding auxiliaries were tested and a variety of substituted anilines were investigated. It was possible to form chemoselectively either azo, azoxy, or the nitro compounds from reaction of aromatic anilines. The selectivity of the solvent-free reaction is switchable by applying a combination of oxidant and grinding auxiliary. Furthermore, a comparison with other methods of energy input (microwave, classical heating, and ultrasound) highlighted the advantages of the ball mill approach and its high energy efficiency.
Purinergic 2Y <sub>1</sub> Receptor Stimulation Decreases Cerebral Edema and Reactive Gliosis in a Traumatic Brain Injury Model (2012)

Traumatic brain injury (TBI) is the leading cause of death and disability in children and young adults. Neuroprotective agents that may promote repair or counteract damage after injury do not currently exist. We recently reported that stimulation of the purinergic receptor subtype P2Y(1)R using 2-methylthioladenosine 5' diphosphate (2MeSADP) significantly reduced cytotoxic edema induced by photothrombosis. Here, we tested whether P2Y(1)R stimulation was neuroprotective after TBI. A controlled closed head injury model was established for mice using a pneumatic impact device. Brains were harvested at 1, 3, or 7 days post-injury and assayed for morphological changes by immunocytochemistry, Western blot analysis, and wet/dry weight. Cerebral edema and expression of both aquaporin type 4 and glial fibrillary acidic protein were increased at all time points examined. Immunocytochemical measurements in both cortical and hippocampal slices also revealed significant neuronal swelling and reactive gliosis. Treatment of mice with 2MeSADP (100 μM) or MRS2365 (100 μM) 30 min after trauma significantly reduced all post-injury symptoms of TBI including edema, neuronal swelling, reactive gliosis, and AQ4 expression. The neuroprotective effect was lost in IP(3)R2-/- mice treated with 2MeSADP. Immunocytochemical labeling of brain slices confirmed that P2Y(1)R expression was defined to cortical and hippocampal astrocytes, but not neurons. Taken together, the data show that stimulation of astrocytic P2Y(1)Rs significantly reduces brain injury after acute trauma and is mediated by the IP(3)-signaling pathway. We suggest that enhancing astrocyte mitochondrial metabolism offers a promising neuroprotective strategy for a broad range of brain injuries.
Template-Synthesized Nanotubes for Chemical Separations and Analysis (2002)

We have developed a new class of synthetic membranes that consist of a porous polymeric support that contains an ensemble of gold nanotubes that span the thickness of the support membrane. The support is a commercially-available microporous polycarbonate filter with cylindrical nanoscopic pores. The gold nanotubes are prepared by electroless deposition of Au onto the pore walls, that is, the pores acts as templates for the nanotubes. We have shown that by controlling the Au deposition time, Au nanotubes that have effective inside diameters of molecular dimensions (<1 nm) can be prepared. These nanotube membranes can be used to cleanly separate small molecules on the basis of molecular size. Furthermore, use of these membranes as a novel electrochemical sensor is also discussed. This new sensing scheme involves applying a constant potential across the Au nanotube membrane and measuring the drop in the transmembrane current upon the addition of the analyte. This paper reviews our recent progress on size-based based transport selectivity and sensor applications in this new class of membranes.
P/M PROCESSING AND CHARACTERIZATION OF CONTROLLED TRANSFORMATION TEMPERATURE NiTi (1982)

Double vacuum arc remelted NiTi ingots were vacuum induction remelted and subsequently atomized using a high-pressure gas stream. Powders were collected, loaded into cans, and hot isostatically pressed (HIP'ed). Prior to HIP'ing, powders of various known transformation temperatures (As), were precisely blended to achieve a desired intermediate transformation temperature (As). This intermediate As follows an empirical relationship which approximates a rule of mixtures based on weight fraction. As were measured using differential scanning calorimetry (DSC). Results for HIP'ed and high temperature annealed specimens indicate that this technique was accurate and reproducible for measuring the transformation temperature of smooth, nearly symmetrical DSC curves. DSC/DTA thermograms in the literature typically show a double peak exothermic-martensitic reaction which was different than the smooth peaks observed for the HIP'ed condition. The specific thermomechanical history performed on the P/M material resulted in the double peak exothermic reaction. To interpret the peaks, thermal arrest experiments were conducted on both exothermic peaks, the results of which clearly support the existence of a premartensitic reaction. Thermal arrest experiments were also performed to analyze incomplete thermal cycles on both heating and cooling. Thermal arrest of the martensite reaction resulted in reduced energy absorbed for completion of the austenite reaction. Conversely, martensite energy was reduced by an arrest of the austenite reaction. However, reheating the sample revealed that the arrest split the austenite reaction into two distinct peaks, the split occurring at the temperature of the prior thermal arrest. These results and results of additional DSC experiments serve to emphasize the influence of thermomechanical history on the kinetics and energetics of the SME transformation. The P/M blending process technique was found to result in unprecedented control of the As temperature. Scientific/engineering considerations justify P/M processing and mechanical blending as opposed to conventional cast/wrought processing to achieve accurate As temperatures.
POTENTIAL FOR BED SORES DUE TO HIGH PRESSURES : INFLUENCE OF BODY SITES, BODY POSITION, AND MATTRESS DESIGN (1993)

Pressures were measured on 10 subjects, supine and sitting, under six anatomical sites prone to bed sores on three different mattresses. Studied were the Clinifloat and Therarest specialist replacement mattresses, and a standard hospital mattress. Mean supine pressures were less than 5 kPa under four sites. Average supine buttock pressure was 2.93 kPa. Occiput and heel pressures were much higher than under other sites, being on average 2.6 and 4.5 times greater respectively than the mean buttock pressure. On sitting up, buttock pressure increased by a factor of 1.7 on average, to a level higher than the accepted capillary closing pressure. Measurements were consistent with mattress design, specific features of which can significantly affect pressure under certain sites.
Bone mineral density in patients with inflammatory bowel disease: A population‐based prospective two‐year follow‐up study (2004)

Only minor changes in BMD were observed in both CD and UC patients during a 2-year period. The multifactorial pathogenesis of bone loss in IBD makes it difficult to assess the importance of each single contributing factor. However, our results indicate that disease activity and corticosteriod therapy are involved in bone loss in CD patients.
A novel algorithm for real-time full screen capture system (2002)

We propose a novel system that can real-time capture and compress the full screen of PC into a video clip. It is real-time in that it can capture to 30 frames per second under the resolution of 1600 /spl times/ 1200 with true color. One application of this system is to produce a digital presentation clip for instruction or tutorial. Moreover, as the video clips can be streamed over Internet or intranet, they can be used for remote education or training. We believe this approach is clearer and more efficient than conventional text manual or handbook. As our system only captures the differences of successive snapshots instead of every single screen, it is more efficient and produces more compact clips than other existing systems. In addition, the compression algorithm adopted in our system is also described.
DM-GAN: Dynamic Memory Generative Adversarial Networks for Text-to-Image Synthesis (2019)

In this paper, we focus on generating realistic images from text descriptions. Current methods first generate an initial image with rough shape and color, and then refine the initial image to a high-resolution one. Most existing text-to-image synthesis methods have two main problems. (1) These methods depend heavily on the quality of the initial images. If the initial image is not well initialized, the following processes can hardly refine the image to a satisfactory quality. (2) Each word contributes a different level of importance when depicting different image contents, however, unchanged text representation is used in existing image refinement processes. In this paper, we propose the Dynamic Memory Generative Adversarial Network (DM-GAN) to generate high-quality images. The proposed method introduces a dynamic memory module to refine fuzzy image contents, when the initial images are not well generated. A memory writing gate is designed to select the important text information based on the initial image content, which enables our method to accurately generate images from the text description. We also utilize a response gate to adaptively fuse the information read from the memories and the image features. We evaluate the DM-GAN model on the Caltech-UCSD Birds 200 dataset and the Microsoft Common Objects in Context dataset. Experimental results demonstrate that our DM-GAN model performs favorably against the state-of-the-art approaches.
FromDaDy: Spreading Aircraft Trajectories Across Views to Support Iterative Queries (2009)

When displaying thousands of aircraft trajectories on a screen, the visualization is spoiled by a tangle of trails. The visual analysis is therefore difficult, especially if a specific class of trajectories in an erroneous dataset has to be studied. We designed FromDaDy, a trajectory visualization tool that tackles the difficulties of exploring the visualization of multiple trails. This multidimensional data exploration is based on scatterplots, brushing, pick and drop, juxtaposed views and rapid visual design. Users can organize the workspace composed of multiple juxtaposed views. They can define the visual configuration of the views by connecting data dimensions from the dataset to Bertin's visual variables. They can then brush trajectories, and with a pick and drop operation they can spread the brushed information across views. They can then repeat these interactions, until they extract a set of relevant data, thus formulating complex queries. Through two real-world scenarios, we show how FromDaDy supports iterative queries and the extraction of trajectories in a dataset that contains up to 5 million data.
Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration (2009)

Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged >or=65.
CRISPR/Cas9-mediated genome editing of splicing mutation causing congenital hearing loss (2019)

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has ushered in a new era of gene therapy. In this study, we aimed to demonstrate precise CRISPR/Cas9-mediated genome editing of the splicing mutation c.919-2A > G in intron 7 of the SLC26A4 gene, which is the second most common causative gene of congenital hearing loss. We designed candidate single-guide RNAs (sgRNAs) aimed to direct the targeting of Staphylococcus aureus Cas9 to either exon 7 or exon 8 of SLC26A4. Several of the designed sgRNAs showed targeting activity, with average indel efficiencies ranging from approximately 14% to 25%. The usage of dual sgRNAs delivered both into Neuro2a cells and primary mouse embryonic fibroblasts resulted in the successful removal of large genomic fragments within the target locus. We subsequently evaluated genome editing in the presence of artificial donor templates to induce precise target modification via homology-directed repair. Using this approach, two different donor plasmids successfully introduced silent mutations within the c.919-2A region of Slc26a4 without evident off-target activities. Overall, these results indicate that CRISPR/Cas9-mediated correction of mutations in the Slc26a4 gene is a feasible therapeutic option for restoration of hearing loss.
Time Course Evolution of Ventilatory Responses to Inspiratory Unloading in Patients (1998)

Inspiratory muscle unloading decreases ventilatory drive. In this study, we examined the time course of this effect in patients with chronic obstructive pulmonary disease receiving two modes of ventilatory support: pressure support ventilation (PSV), during which each cycle was assisted, and biphasic positive airway pressure (BIPAP), set up in such a manner that one spontaneous breath took place between two consecutive pressure-assisted breaths. The first breath following the switch from spontaneous breathing to PSV was associated with an increase in tidal volume (VT) and a drop in mean transdiaphragmatic pressure (mean Pdi) and inspiratory work (WI) performed per liter but with unchanged values of esophageal occlusion pressure at 100 ms (Pes 0.1), diaphragmatic electrical activity (EMGdi), and WI performed by breath. The same phenomena were observed for the assisted breath of BIPAP as compared with the preceding spontaneous breath. During the subsequent breaths of PSV, Pes 0.1, EMGdi, and WI performed per breath decreased progressively up to the sixth to eighth breaths, and VT returned to pre-PSV values. We conclude that in patients with chronic obstructive pulmonary disease the decrease in ventilatory drive associated with PSV takes place from the first breath onwards but requires six to eight breaths to be fully achieved. During BIPAP, as a consequence of the kinetics of the PSV-induced downregulation of ventilatory drive, assisted breaths following spontaneous breaths are characterized by an enhanced inspiratory efficiency.
Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages (2010)

Tim-4 is a phosphatidylserine (PS) receptor that is expressed on various macrophage subsets. It mediates phagocytosis of apoptotic cells by peritoneal macrophages. The in vivo functions of Tim-4 in phagocytosis and immune responses, however, are still unclear. In this study, we show that Tim-4 quickly forms punctate caps on contact with apoptotic cells, in contrast to its normal diffused expression on the surface of phagocytes. Despite its expression in marginal zone and tingible body macrophages, Tim-4 deficiency only minimally affects outcomes of several acute immune challenges, including the trapping of apoptotic cells in the marginal zone, the clearance apoptotic cells by tingible body macrophages, and the formation of germinal centers and elicitation of antibody responses against sheep red blood cells (SRBCs). In addition, Tim-4(-/-) resident peritoneal macrophages (rPMs) phagocytose necrotic cells and other opsonized targets normally. However, their ability to bind and engulf apoptotic cells is significantly compromised both in vitro and in vivo. Most importantly, Tim-4 deficiency results in increased cellularity in the peritoneum. Resting rPMs produce higher TNF-alpha in culture. Their response to LPS, on the contrary, is dampened. Our data support an indispensible role of Tim-4 in maintaining the homeostasis of rPMs.
QUICKXPLAIN: preferred explanations and relaxations for over-constrained problems (2004)

Over-constrained problems can have an exponential number of conflicts, which explain the failure, and an exponential number of relaxations, which restore the consistency. A user of an interactive application, however, desires explanations and relaxations containing the most important constraints. To address this need, we define preferred explanations and relaxations based on user preferences between constraints and we compute them by a generic method which works for arbitrary CP, SAT, or DL solvers. We significantly accelerate the basic method by a divide-and-conquer strategy and thus provide the technological basis for the explanation facility of a principal industrial constraint programming tool, which is, for example, used in numerous configuration applications.
Applications for the femtosecond laser in corneal surgery (2007)

This review will examine the uses of the femtosecond laser in corneal surgery, as well as early results that have been reported.