gebhart/patrepeval huggingface dataset:
Broadband tuning (ΔE∼100 meV) of Alx Ga1−xAs quantum well heterostructure lasers with an external grating (1983)

Alx Ga1−xAs-GaAs quantum well heterostructure laser diodes are shown to be tunable over a 100-meV range when operated continuously (cw) at room temperature in an external cavity with a grating to control feedback. The gain profile of the n=1 and n′=1′ (electron-to-heavy hole and electron-to-light hole, e→hh and e→lh) transitions and the n=2 electron-to-heavy hole transitions are clearly outlined by the intensity profile of the selected laser lines. The partial homogeneous broadening of the gain profile agrees with rapid carrier relaxation in the well. The diodes contain a single 60–90-Å GaAs well and are grown by metalorganic chemical vapor deposition.
T-Cell Immunity to Infection with Dengue Virus in Humans (2014)

Dengue virus (DENV) is the etiologic agent of dengue fever, the most significant mosquito-borne viral disease in humans. Up to 400 million DENV infections occur every year, and severity can range from asymptomatic to an acute self-limiting febrile illness. In a small proportion of patients, the disease can exacerbate and progress to dengue hemorrhagic fever and/or dengue shock syndrome, characterized by severe vascular leakage, thrombocytopenia, and hemorrhagic manifestations. A unique challenge in vaccine development against DENV is the high degree of sequence variation, characteristically associated with RNA viruses. This is of particular relevance in the case of DENV since infection with one DENV serotype (primary infection) presumably affords life-long serotype-specific immunity but only partial and temporary immunity to other serotypes in secondary infection settings. The role of T cells in DENV infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing to severe disease. Our recent study has suggested an HLA-linked protective role for T cells. Herein, we will discuss the role of T cells in protection and pathogenesis from severe disease as well as the implications for vaccine design.
Early initiation of L‐dopa therapy enables stable development of executive function in tetrahydrobiopterin (BH4) deficiency (2007)

Executive function (EF) has been presumed to be mediated by the dopaminergic system in the prefrontal cortex. However, little is known about the early development of this function and the roles dopamine plays in it. Tetrahydrobiopterin (BH4) deficiencies are genetic disorders affecting catecholamine and serotonin biosynthesis which, if untreated, result in motor and cognitive symptoms including impairment of EF. A comprehensive neuropsychological test battery was administered to six participants with BH4 deficiency (four males, two females, mean Full-scale intelligence quotient [FIQ] 63.8 [SD 14.7]); all were on replacement therapy with L-dopa and BH4, but time of initiation of treatment varied. Age range (median) was 28 days to 41 years (2y 6mo) at initiation of treatment and 10 to 47 years (19y) at follow-up. On non-EF tests, performance agreed with those of IQ-matched controls (four males, two females; mean age 16y 6mo [SD 6mo]; mean FIQ 62.3 [SD 13.4]). On EF tests those who initiated treatment after 2 years 6 months of age performed poorly. In patients with BH4 deficiency, replacement therapy should be started in the first weeks or months of life. Patients diagnosed before the age of 2 years 6 months obtain normal EF, which suggests dopamine may play a critical role in ensuring stable development of EF in early life.
A Crawler-based Study of Spyware on the Web (2005)

Malicious spyware poses a significant threat to desktop security and integrity. This paper examines that threat from an Internet perspective. Using a crawler, we performed a large-scale, longitudinal study of the Web, sampling both executables and conventional Web pages for malicious objects. Our results show the extent of spyware content. For example, in a May 2005 crawl of 18 million URLs, we found spyware in 13.4% of the 21,200 executables we identified. At the same time, we found scripted “drive-by download” attacks in 5.9% of the Web pages we processed. Our analysis quantifies the density of spyware, the types of of threats, and the most dangerous Web zones in which spyware is likely to be encountered. We also show the frequency with which specific spyware programs were found in the content we crawled. Finally, we measured changes in the density of spyware over time; e.g., our October 2005 crawl saw a substantial reduction in the presence of drive-by download attacks, compared with those we detected in May.
Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of Fecal Microbiota Transplantation in Gastrointestinal Diseases (2016)

Fecal microbiota transplantation (FMT), a process by which the normal gastrointestinal microbiota is restored, has demonstrated extraordinary cure rates for Clostridium difficile infection and low recurrence. The community of microorganisms within the human gut (or microbiota) is critical to health status and functions; therefore, together with the rise of FMT, the gastrointestinal microbiota has emerged as a 'virtual' organ with a level of complexity comparable to that of any other organ system and capable to compete with powerful known antibiotics for the treatment of several disorders. Although treatment protocols, donor selection, stool preparation and delivery methods varied widely, with a few reports following an identical protocol, FMT has diffused to other areas where the alterations of the gut microbiota ecology (or dysbiosis) have been theorized to play a causative role, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), among several other extra-intestinal disorders (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular diseases). FMT can be relatively simple to perform, but a number of challenges need to be overcome before this procedure is widely accepted in clinical practice, and currently, there is no consensus between the various gastrointestinal organizations and societies regarding the FMT procedure. In this article, we describe the modern high-throughput sequencing techniques to characterize the composition of gut microbiota and the potential for therapeutics by manipulating microbiota with FMT in several gastrointestinal disorders (C. difficile-associated diarrhea, IBD and IBS), with a look on the potential future directions of FMT.
Modeling spectral speech transitions using temporal decomposition techniques (2005)

ATAL [1] introduced a technique for decomposing speech into phone-length temporal events in terms of overlapping and interacting articulatory gestures. This paper reports on simplifications of this technique with applications to acoustic-phonetic synthesis. Spectral evolution is represented by time-indexed trajectories in the p-dimensional space of Log-Area Ratios <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">{y_{i}= \Ln ((1+k_{i})/(1-k_{i}))}</tex> where k <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">i</inf> are the reflection coefficients obtained from short-time stationary LPC analysis. The vocal tract configuration (spectral vector) associated with each interpolation function belongs to a finite set of articulatory targets (vector quantization code book). A set of speech segments ("polysons") has been encoded using this technique. It includes diphones, demi-syllables, and other units that are difficult to segment. Temporal decomposition using target spectra can break the complex encoding of these segments. In particular, coarticulation effects are analyticaiy explained and modeled. It is demonstrated that these new tools provide an adequate environment in our search for better rules in acoustic speech synthesis.
Porous Silicon Gas Sensors for Room Temperature Detection of Ammonia and Phosphine (2008)

Nanopore covered microporous porous silicon (PS) interfaces have been formed to provide an active scaffolding for the creation of rapidly responding, reversible, and sensitive, (&lt; 1ppm) PS gas sensors, operating at room temperature, and based on a uniquely formed highly efficient electrical contract to the nanopore covered microporous array. These sensors are modified on the basis of a general acid-base theory, introducing active nanoparticles to establish gas selectivity. NH3 and PH3 have been monitored well below the ppm level.
Severe hypophosphatasia due to mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. (2002)

Hypophosphatasia is a rare autosomal recessive inborn error of metabolism characterized by a defective bone mineralisation and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase activity. We report the characterisation of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutation in a patient affected by infantile hypophosphatasia. This boy was the first child of non affected, non related parents. At 1 month of age he presented with palsy of the left upper limb with hypotonia. Length was - 2SD. The anterior fontanel was large. There was a markedly decreased ossification of all bones. All limbs were shortened. Ultrasonographic examination of the kidneys showed nephrocalcinosis. Level of alkaline phosphatases was decreased in the child as well as in the parents. Bone density was decreased. At 2 years of age development was delayed. Weight was - 3,5 SD and OFC - 3SD. The child had craniosynostosis. Molecular studies showed 2 missense mutations, both in exon 6 of the TNSALP gene.
Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease. (1990)

Efforts were directed to identify the specific mutations in the alpha-galactosidase A (alpha-Gal A) gene which cause Fabry disease in families of Japanese origin. By polymerase-chain-reaction-amplification of DNA from reverse-transcribed mRNA and genomic DNA, different point mutations were found in two unrelated Fabry hemizygotes. A hemizygote with classic disease manifestations and no detectable alpha-Gal A activity had a G-to-A transition in exon 1 (codon 44) which substituted a termination codon (TAG) for a tryptophan codon (TGG) and created an NheI restriction site. This point mutation would predict a truncated alpha-Gal A polypeptide, consistent with the observed absence of enzymatic activity and a classic Fabry phenotype. In an unrelated Japanese hemizygote who had an atypical clinical course characterized by late-onset cardiac involvement and significant residual alpha-Gal activity, a G-to-A transition in exon 6 (codon 301) resulted in the replacement of a glutamine for an arginine residue. This amino acid substitution apparently altered the properties of the enzyme such that sufficient enzymatic activity was retained to markedly alter the disease course. Identification of these mutations permitted accurate molecular heterozygote diagnosis in these families.
Monitoring Oral Anticoagulant Therapy with Point-of-Care Devices: Correlations and Caveats. (1997)

Utilization of point-of-care (POC) devices for monitoring patients receiving oral anticoagulant therapy is increasing. In this study, we compared three different POC devices with the clinical laboratory method of determining prothrombin times (PT) and the associated International Normalized Ratio (INR).

After approval by our Institutional Review Board, we obtained consent from and enrolled 40 consecutive patients. All patients had documented stabilization of their INR, and patients who had been taking coumadin <7 days were excluded. Whole-blood fingerstick samples were acquired by a single nurse practitioner (R.H.) and tested on the Coumatrak PT monitor (Boehringer Mannheim). Samples were then drawn from the patients by antecubital phlebotomy with a 20-gauge butterfly needle and syringe. The peripherally drawn whole blood was immediately (within 15 s of phlebotomy) tested on the Coumatrak and CoaguChek Plus (Boehringer Mannheim) monitors. The residual blood was then anticoagulated by placing into 32 g/L sodium citrate-containing tubes (Becton Dickinson), and the citrated whole blood was immediately tested on …
Androgen receptors in breast cancer (1984)

Androgen receptor assays have been performed on 1371 specimens of histologically confirmed primary and recurrent breast cancer. Forty-two patients who had received tamoxifen as treatment for advanced disease were assessed for objective response. Another 42 patients who had received chemotherapy were similarly studied. Patients with androgen receptor-negative tumors had a significantly poorer response rate to hormone therapy than those with receptor-positive tumors (P less than 0.05). This clinical correlation is supported by survival data of 1181 patients with primary breast cancer which showed that patients with androgen receptor-negative tumors had a highly significant trend toward shorter overall survival than those with receptor-positive tumors (P less than 0.001). Androgen receptor data added significantly to the information provided by estrogen receptor data both in terms of response to hormone treatment and survival.
Polymeric Photosensitizer Prodrugs for Photodynamic Therapy (2007)

A targeting strategy based on the selective enzyme-mediated activation of polymeric photosensitizer prodrugs (PPP) within pathological tissue has led to the development of agents with the dual ability to detect and treat cancer. Herein, a detailed study of a simple model system for these prodrugs is described. We prepared "first-generation" PPP by directly tethering the photosensitizer (PS) pheophorbide a to poly-(L)-lysine via epsilon amide links and observed that by increasing the number of PS on a polymer chain, energy transfer between PS units improved leading to better quenching efficiency. Fragmentation of the PPP backbone by trypsin digestion gave rise to a pronounced fluorescence increase and to more efficient generation of reactive oxygen species upon light irradiation. In vitro tests using the T-24 bladder carcinoma cell line and ex vivo experiments using mouse intestines illustrated the remarkable and selective ability of these PPP to fluoresce and induce phototoxicity upon enzymatic activation. This work elucidated the basic physicochemical parameters, such as water solubility and quenching/activation behavior, required for the future elaboration of more adaptable "second-generation" PPP, in which the PS is tethered to a proteolytically stable polymer backbone via enzyme-specific peptide linkers. This polymer architecture offers great flexibility to tailor make the PPP to target any pathological tissue known to over-express a specific enzyme.
Adult Schizophrenia Following Prenatal Exposure to an Influenza Epidemic (1988)

In the context of a Finnish birth cohort, we tested the hypothesis that viral infection during the latter two thirds of fetal development would increase the risk of adult schizophrenic outcome. Psychiatric hospital diagnoses were recorded for all individuals in greater Helsinki who were fetuses during the 1957 type A2 influenza epidemic. Those exposed to the viral epidemic during their second trimester of fetal development were at elevated risk of being admitted to a psychiatric hospital with a diagnosis of schizophrenia. This was true for both males and females and independently in several psychiatric hospitals. The second-trimester effect was seen in the elevated proportion of schizophrenics among those admitted to a psychiatric hospital and also in higher rates of schizophrenia per 1000 live births in the city of Helsinki. The study has several limitations: (1) We have no direct evidence that the subjects actually suffered a viral infection. (2) The psychiatric data were obtained only for subjects up to the age of 26 years, 56 days. (3) The findings are based on hospital diagnoses. (4) The determination of stage of gestation at time of exposure to the epidemic is based on date of birth. The viral infection might have occurred outside the official epidemic window; the infant may have had a preterm or postterm delivery. These sources of error, however, should not serve to enhance the findings. The observed viral effect is interpreted as being one of many potential perturbations of gestation. We suggest that it is less the type than the timing of the disturbance during fetal neural development that is critical in determining risk for schizophrenia.
The developments and changes in the diagnostic criteria for Alzheimer disease (2015)

Alzheimer disease(AD) is the most common cause of dementia, and it has caused a huge economic burden to our country and other nations.Therefore, how to carry out an effective prevention and treatment strategy in the early stage of the disease, has become the key of the treatment of AD.In 1984, the National Institute of Neurological and Communicative Disorders and Stroke, and the Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) firstly announced.With the development of our understanding of AD as well as the new technologies coming out, the diagnostic criteria also develope significantly, such as the more emphasis on mild cognitive impairment(MCI) stage and putting the biomarkers into the diagnostic criteria.However, there are significant differences among diverse standards(e.g.IGW, NIA-AA, etc), so we summized this article reviewed the changes of the AD diagnostic criteria, and gave a detail discussion about them.


Key words: 
Alzheimer disease; Diagnostic criteria; Research progress
Expression Profiling by iAFLP: A PCR-Based Method for Genome-Wide Gene Expression Profiling (1999)

The availability of comprehensive sets of genes has prompted the researchers to carry out systematic collection of gene expression data. RT-PCR has the highest specificity and sensitivity for transcript detection among all available methods. Low throughput, especially when quantitative data are desired, has precluded RT-PCR from genome-wide application. Here we report a PCR-based expression profiling method, introduced amplified fragment length polymorphism (iAFLP), that has the same specificity and sensitivity as RT-PCR and a throughput level comparable to that of DNA-microarray hybridization. In this method, restricted ends of total cDNAs from six sources were ligated with adaptors having various length of short insertions to a common sequence (polymorphic adaptors). Amplification of a pool of these differentially adapted cDNAs with a gene-specific primer and an adaptor primer allows us to quantitate the abundance of any transcript in six mRNA sources. Using three different primer colors this technique allows quantitation of expression of 864 genes across six different sources per day with a single autosequencer, which is comparable to the throughput of microarray analysis in terms of number of genes x number of sources.
4-1BB (CD137) controls the clonal expansion and survival of CD8 T cellsin vivo but does not contribute to the development of cytotoxicity (2002)

4-1BB is expressed on activated T cells. We analyzed the role of 4-1BB during the CD8 T cell response of OT-I TCR-transgenic T cells to ovalbumin. In vitro, blocking 4-1BB during peptide presentation reduced proliferation of naive CD8 T cells, but did not affect the generation of CTL. Using an in vivo adoptive transfer model, clonal expansion of CD8 T cells to whole protein in adjuvant was significantly reduced when 4-1BB was blocked, with 50-70% fewer CD8 T cells accumulating. This was due to a reduction in T cell division and to enhanced apoptosis of CD8 T cells that had undergone many divisions. T cells generated in the absence of 4-1BB were impaired in their ability to secrete IFN-gamma whereas CTL activity of the T cells that survived was unaffected. These findings demonstrate that 4-1BB contributes to clonal expansion, survival, and development of Tc1 cells when protein antigen is encountered by primary CD8 T cells in an inflammatory environment in vivo.
in vivo inhibition of PC‐3 human androgen‐independent prostate cancer by a targeted cytotoxic bombesin analogue, AN‐215 (2000)

The effectiveness of chemotherapy targeted to bombesin (BN) receptors was evaluated in nude mice bearing PC-3 human androgen-independent prostate cancers. Cytotoxic BN analogue AN-215, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to BN-like carrier peptide RC-3094, was injected i.v. at 150 nmol/kg on days 1, 11 and 21. After treatment with AN-215, tumor volume was 69% (p < 0.01) smaller than that in controls and tumor doubling time was extended from 8.5 ± 0.7 days to 20.3 ± 3.5 days (p < 0.05). Cytotoxic radical AN-201, carrier RC-3094 and their unconjugated mixture administered at the same dosage were ineffective. The mortality rate was 12.5% in the AN-201 group and 16.7% in the group treated with the mixture, but no deaths occurred in mice receiving AN-215. Because the ester bond linking AN-201 to the carrier molecule is hydrolyzed much faster in mouse serum than in human serum, in the second experiment we investigated the tolerance to AN-215 and its effect in nude mice bearing PC-3 tumors after pharmacological inhibition of serum carboxylesterases. Two applications of AN-201 at 200 nmol/kg were lethal, whereas no mortality was observed after 4 injections of AN-215 at the same dose. Administration of 200 nmol/kg AN-215 on days 1, 7, 17 and 26 again produced 69% tumor inhibition. BN receptors on membranes of PC-3 tumors were detected by 125I-[Tyr4]BN binding, and expression of mRNA for BRS-3 and GRP-R subtypes was also found. AN-215 showed a high affinity to PC-3 tumors, displacing the radioligand at an IC50 of 12.95 ± 0.35 nM. Because BN receptors are present on primary and metastatic prostate cancer, targeted chemotherapy with AN-215 might benefit patients with advanced prostatic carcinoma who relapsed androgen ablation. Int. J. Cancer 88:652–657, 2000. © 2000 Wiley-Liss, Inc.
Interventions for atopic dermatitis in dogs: a systematic review of randomized controlled trials (2010)

The objective of this systematic review, which was performed following the guidelines of the Cochrane collaboration, was to assess the effects of interventions for treatment of atopic dermatitis (AD) in dogs. Citations identified from three databases (MEDLINE, Thomson's Science Citation Index Expanded and CAB Abstracts) and trials published by December 2007 were selected. Proceedings books from the major veterinary dermatology international congresses were hand searched for relevant citations. The authors selected randomized controlled trials (RCTs), published from January 1980 to December 2007, which reported the efficacy of topical or systemic interventions for treatment or prevention of canine AD. Studies had to report assessments of either pruritus or skin lesions, or both. Studies were selected and data extracted by two reviewers, with discrepancies resolved by a third arbitrator. Missing data were requested from study authors of recently published trials. Pooling of results and meta-analyses were performed for studies reporting similar interventions and outcome measures. A total of 49 RCTs were selected, which had enrolled 2126 dogs. This review found some evidence of efficacy of topical tacrolimus (3 RCTs), topical triamcinolone (1), oral glucocorticoids (5), oral ciclosporin (6), subcutaneous recombinant gamma-interferon (1) and subcutaneous allergen-specific immunotherapy (3) to decrease pruritus and/or skin lesions of AD in dogs. One high-quality RCT showed that an oral essential fatty acid supplement could reduce prednisolone consumption by approximately half. Additional RCTs of high design quality must be performed to remedy previous flaws and to test interventions for prevention of flares of this disease.