gebhart/patrepeval huggingface dataset:
2013 Alzheimer's disease facts and figures (2013)

This report provides information to increase understanding of the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, health expenditures and costs of care, and effect on caregivers and society in general. It also explores the roles and unique challenges of long-distance caregivers, as well as interventions that target those challenges. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million comprise the older onset AD population. Throughout the coming decades, the baby boom generation is projected to add about 10 million to the total number of people in the United States with AD. Today, someone in America develops AD every 68 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. AD is the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The number of deaths from AD as determined by official death certificates (83,494 in 2010) likely underrepresents the number of AD-related deaths in the United States. A projected 450,000 older Americans with AD will die in 2013, and a large proportion will die as a result of complications of AD. In 2012, more than 15 million family members and other unpaid caregivers provided an estimated 17.5 billion hours of care to people with AD and other dementias, a contribution valued at more than $216 billion. Medicare payments for services to beneficiaries age 65 years and older with AD and other dementias are three times as great as payments for beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2013 for health care, long-term care, and hospice services for people age 65 years and older with dementia are expected to be $203 billion (not including the contributions of unpaid caregivers). An estimated 2.3 million caregivers of people with AD and other dementias live at least 1 hour away from the care recipient. These "long-distance caregivers" face unique challenges, including difficulty in assessing the care recipient's true health condition and needs, high rates of family disagreement regarding caregiving decisions, and high out-of-pocket expenses for costs related to caregiving. Out-of-pocket costs for long-distance caregivers are almost twice as high as for local caregivers.
Emotion Dysregulation as a Core Feature of Borderline Personality Disorder (2009)

Borderline personality disorder (BPD) is a debilitating mental illness that affects approximately 1-2% of the general population. Researchers have increasingly come to view emotion dysregulation as a core feature of BPD. The present study examines the relationship between BPD symptomatology and emotion dysregulation using the Difficulties in Emotion Regulation Scale (DERS) in two college samples. BPD symptoms were assessed by self-report (MSI-BPD) in sample 1 and by semi-structured interview (SIDP-IV) in sample 2. Results suggest that emotion dysregulation accounts for unique variance in BPD even after controlling for traditional indicators of negative emotionality, including depression, anxiety, and negative affect. Findings support theories regarding the role of emotion dysregulation in BPD and provide directions for future research.
Neisserial TonB-dependent outer-membrane proteins: detection, regulation and distribution of three putative candidates identified from the genome sequences The GenBank accession number for the sequence of tdfH from meningococcal strain IR1074 reported in this paper is AF227418. (2001)

Computer searches were carried out of the gonococcal and meningococcal genome databases for previously unknown members of the TonB-dependent family (Tdf) of outer-membrane receptor proteins. Seven putative non-contiguous genes were found and three of these (identified in gonococcal strain FA1090) were chosen for further study. Consensus motif analysis of the peptide sequences was consistent with the three genes encoding TonB-dependent receptors. In view of the five previously characterized TonB-dependent proteins of pathogenic neisseriae, the putative genes were labelled tdfF, tdfG and tdfH. TdfF had homology with the siderophore receptors FpvA of Pseudomonas aeruginosa and FhuE of Escherichia coli, whereas TdfG and TdfH had homology with the haemophore receptor HasR of Serratia marcescens. The aim of this project was to characterize these proteins and determine their expression, regulation, distribution and surface exposure. Strain surveys of iron-stressed commensal and pathogenic neisseriae revealed that TdfF is unlikely to be expressed, TdfG is expressed by gonococci only and that TdfH is expressed by both meningococci and gonococci. Expression of TdfH was unaffected by iron availability. Susceptibility of TdfH to cleavage by proteases in live gonococci was consistent with surface exposure of this protein. TdfH may function as a TonB-dependent receptor for a non-iron nutrient source. Furthermore, TdfH is worthy of future investigation as a potential meningococcal vaccine candidate as it is a highly conserved, widely distributed and surface-exposed outer-membrane protein.
Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity levels (2010)

Many studies in the field of haemophilia and other coagulation deficiencies require analyses of bleeding frequencies. In haemophilia, the association of bleeding frequency with factor VIII (FVIII) activity levels is known from experience, but significant results are lacking. Bleeding frequencies in haemophilia are highly skewed count data, with large proportions of zeros. Both the skewness and the high amount of zeros pose a problem for standard (linear) modelling techniques. This study investigated the optimal analysing strategy for bleeding data by using the association of residual clotting factor level and number of joint bleeds in moderate and mild patients treated on demand as example. In total, 433 patients with moderate (27%) and mild (73%) haemophilia A treated on demand were included in this study. One year of self-reported data on joint bleed frequency and baseline clotting factor activity were analysed using Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial distributions. Multivariate regression analysis using negative binomial distribution provided the optimum data analytical strategy. This model showed 18% reduction [Rate ratio (RR) 0.82; 95%confidence interval (CI) 0.77-0.86] of bleeding frequency with every IU dL(-1) increase in residual FVIII activity. The actual association is expected to be higher because of exclusion (30 out of 463 patients) of patients on prophylaxis (baseline FVIII levels 0.01-0.06 IU mL(-1)). The best way to analyse low frequency bleeding data is using a negative binomial distribution.
Combination chemotherapy and alpha-interferon in the treatment of Kaposi's sarcoma associated with acquired immune deficiency syndrome. (1988)

Thirteen men with a median age of 37 (range 28 to 46) years who had extensive Kaposi's sarcoma associated with acquired immune deficiency syndrome (AIDS) were treated with combination chemotherapy and alpha-interferon. Four patients had stage III disease and nine had stage IV disease (one with pulmonary and eight with gastrointestinal involvement). Treatment consisted of monthly courses of actinomycin D, 1 mg/m2, and vinblastine sulfate, 6 mg/m2, given intravenously on day 1, bleomycin, 10 mg/m2 given intravenously on days 1 and 8, and human lymphoblastoid (alpha-) interferon, 10 million U/m2 given subcutaneously three times a week for six doses starting on day 14. Forty-one treatment cycles (median 3, range 1 to 12) were administered. The median granulocyte and platelet counts on day 14 before the start of interferon therapy were 600 X 10(9)/L and 134 X 10(9)/L respectively; the counts did not fall further during interferon therapy. There was no difference in T-cell subsets, 2',5'-oligoadenylate synthetase level or results of blastogenesis studies after interferon therapy. Four patients required admission to hospital for neutropenia-associated fever. A complete response (of 24 weeks' duration) was seen in one patient and a partial response (of 14 to 44 weeks' duration) in four. One patient had a mixed response, with regression of skin involvement but progression of pulmonary disease. The median length of survival was 48 (range 4 to 143) weeks. Eleven patients died of progressive Kaposi's sarcoma, one of lymphoma and one of Pneumocystis carinii pneumonia. The results suggest that this form of therapy is not appropriate for patients with Kaposi's sarcoma associated with AIDS.
A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies (2008)

Most antibodies induced by HIV-1 are ineffective at preventing initiation or spread of infection because they are either nonneutralizing or narrowly isolate-specific. Rare, "broadly neutralizing" antibodies have been detected that recognize relatively conserved regions on the envelope glycoprotein. Using stringently characterized, homogeneous preparations of trimeric HIV-1 envelope protein in relevant conformations, we have analyzed the molecular mechanism of neutralization by two of these antibodies, 2F5 and 4E10. We find that their epitopes, in the membrane-proximal segment of the envelope protein ectodomain, are exposed only on a form designed to mimic an intermediate state during viral entry. These results help explain the rarity of 2F5- and 4E10-like antibody responses and suggest a strategy for eliciting them.
Discovery of a Practical Direct O2-Coupled Wacker Oxidation with Pd[(−)-sparteine]Cl2 (2006)

The discovery of a direct O2-coupled Wacker oxidation with use of balloon pressure of O2 and low catalyst loading is described. Use of (-)-sparteine as a ligand on Pd prevents olefin isomerization and leads to selective formation of methyl ketones from terminal olefins in good yields. Oxidation of enantiomerically enriched substrates is reported with no observed racemization.
Antitumor activity of a transforming growth factor alpha-Pseudomonas exotoxin fusion protein (TGF-alpha-PE40). (1991)

TGF-alpha-PE40 is a chimeric protein composed of transforming growth factor alpha (TGF-alpha) linked to a modified Pseudomonas toxin from which the cell recognition domain has been deleted (PE40). TGF-alpha-PE40 has been shown to have cytotoxic effects on human cancer cell lines that express the epidermal growth factor (EGF) receptor on their surface, and when given i.p., it prolongs the survival of nude mice bearing i.p. tumors. Because several normal tissues, including liver, express EGF receptors on their surfaces, it has not been clear that this agent can be used systemically to treat EGF receptor-bearing tumors. In this study, we have delivered TGF-alpha-PE40 for 7 days by continuous infusion through a miniosmotic pump placed in the peritoneal cavity of nude immunodeficient mice. Two different human cancer cell lines that express EGF receptors on their surface were implanted s.c. One was A431, an epidermoid carcinoma; the other was DU-145, a prostate carcinoma. By using this mode of continuous i.p. delivery, we were able to achieve a constant serum level of TGF-alpha-PE40 that was nontoxic to the mice and yet delayed the growth of both tumors implanted s.c. and caused partial regression of one. We conclude that it is possible to deliver TGF-alpha-PE40 systemically and achieve a therapeutic serum level in mice without major toxicity. Although side effects may be expected, this study establishes that there is a therapeutic window for this agent in the therapy of cancers with high numbers of EGF receptors.
VIP Neurotrophism in the Central Nervous System: Multiple Effectors and Identification of a Femtomolar‐Acting Neuroprotective Peptide (1998)

Vasoactive intestinal peptide has neurotrophic and growth-regulating properties. As in the case of many neurotrophic molecules, VIP also has neuroprotective properties, including the prevention of cell death associated with excitotoxicity (NMDA), beta-amyloid peptide, and gp120, the neurotoxic envelope protein from the human immunodeficiency virus. The neurotrophic and neuroprotective properties are mediated in part through the action of glial-derived substances released by VIP. These substance include cytokines, protease nexin I, and ADNF, a novel neuroprotective protein with structural similarities to heat-shock protein 60. Antiserum against ADNF produced neuronal cell death and an increase in apoptotic neurons in cell culture. A 14 amino acid peptide (ADNF-14) derived from ADNF has been discovered that mimics the survival-promoting action of the parent protein. These studies support the conclusion that VIP, PACAP, and associated molecules are both important regulators of neurodevelopment and strong candidates for therapeutic development for the treatment of neurodegenerative disease.
Design and analysis of synthetic carbon fixation pathways (2010)

Carbon fixation is the process by which CO(2) is incorporated into organic compounds. In modern agriculture in which water, light, and nutrients can be abundant, carbon fixation could become a significant growth-limiting factor. Hence, increasing the fixation rate is of major importance in the road toward sustainability in food and energy production. There have been recent attempts to improve the rate and specificity of Rubisco, the carboxylating enzyme operating in the Calvin-Benson cycle; however, they have achieved only limited success. Nature employs several alternative carbon fixation pathways, which prompted us to ask whether more efficient novel synthetic cycles could be devised. Using the entire repertoire of approximately 5,000 metabolic enzymes known to occur in nature, we computationally identified alternative carbon fixation pathways that combine existing metabolic building blocks from various organisms. We compared the natural and synthetic pathways based on physicochemical criteria that include kinetics, energetics, and topology. Our study suggests that some of the proposed synthetic pathways could have significant quantitative advantages over their natural counterparts, such as the overall kinetic rate. One such cycle, which is predicted to be two to three times faster than the Calvin-Benson cycle, employs the most effective carboxylating enzyme, phosphoenolpyruvate carboxylase, using the core of the naturally evolved C4 cycle. Although implementing such alternative cycles presents daunting challenges related to expression levels, activity, stability, localization, and regulation, we believe our findings suggest exciting avenues of exploration in the grand challenge of enhancing food and renewable fuel production via metabolic engineering and synthetic biology.
Speech coding using motion picture compression techniques (2003)

Motion picture compression standards are well developed and widely used in multimedia applications. It could be very convenient to have only one coding algorithm implemented on a multimedia device which deals with video as well as audio and speech data. In this paper, we present a new approach to speech coding where we apply motion picture compression techniques to speech signals. An audio-to-video converter is proposed which prepares the speech or audio data to allow direct processing by a video coding algorithm (e.g. MPEG) and a video-to-audio converter which reconstructs the speech signal.
Management of metastatic HER2-positive breast cancer progression after adjuvant trastuzumab therapy – current evidence and future trends (2010)

Trastuzumab is now considered the standard of care for the adjuvant treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients, yet a sizable number of HER2-positive patients do not benefit from this treatment. For patients who progress on or after completion of adjuvant trastuzumab therapy, the standard of care is uncertain. Newer tyrosine kinase inhibitors and monoclonal antibodies are being evaluated in clinical trials for optimisation of treatment in this group. The interplay of HER2 and hormonal signalling pathways is being manipulated to see if response rates can be bettered. In this reveiw we explain the present role of the new molecules with a case scenario. The new anti-HER2 drugs have the potential to change clinical practise of targeting HER2 in the future. Better understanding of HER2 functions and interactions of different signalling pathways will be essential for optimal targetted therapies.
High-speed Curve25519 on 8-bit, 16-bit, and 32-bit microcontrollers. (2015)

Abstract This paper presents new speed records for 128-bit secure elliptic-curve Diffie-Hellman key-exchange soft-ware on three different popular microcontroller architectures. We consider a 255-bit curve proposed by Bernstein known as Curve25519, which has also been adopted by the IETF. We optimize the X25519 key-exchange protocol proposed by Bernstein in 2006 for AVR ATmega 8-bit microcontrollers, MSP430X 16-bit microcontrollers, and for ARM Cortex-M0 32-bit microcontrollers. Our software for the AVR takes only 13 900 397 cycles for the computation of a Diffie-Hellman shared secret, and is the first to perform this computation in less than a second if clocked at 16MHz for a security level of 128 bits. Our MSP430X software computes a shared secret in 5 301 792 cycles on MSP430X microcontrollers that have a 32-bit hardware multiplier and in 7 933 296 cycles on MSP430X microcontrollers that have a 16-bit multiplier. It thus outperforms previous constant-time ECDH software at the 128-bit security level on the MSP430X by more than a factor of 1.2 and 1.15, respectively. Our implementation on the Cortex-M0 runs in only 3 589 850 cycles and outperforms previous 128-bit secure ECDH software by a factor of 3.
PET (positron emission tomography) imaging of biomolecules using metal–DOTA complexes: a new collaborative challenge by chemists, biologists, and physicians for future diagnostics and exploration of in vivo dynamics (2008)

Recently, PET has been paid a great deal of attention as a non-invasive imaging method. In this review, the recent advances of PET using biomolecules, such as peptides, monoclonal antibodies, proteins, oligonucleotides, and glycoproteins will be described. So far, PET of biomolecules has been mainly used for diagnosis of cancers. The biomolecules have been conjugated with the DOTA ligand, labeled with radiometals as the beta+ emitter, and targeted to specific tumors, where they have enabled visualization of even small metastatic lesions, due to the high sensitivity of the PET scanners. Some of the biomolecules have been used not only for PET diagnosis, but also for radiotherapeutic treatments by simply changing the radiometals to beta(-) emitters. Collaborative work between chemists, biologists, and physicians will be important for the future of biomolecule-based targeting and diagnosis.
Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-kinase p110delta. (2003)

Class IA phosphoinositide 3'-kinases (PI3Ks) regulate many cellular processes downstream of tyrosine kinases and Ras. Despite a clear implication of PI3K in cancer, little is known about the distribution of the different PI3K isoforms in malignant cells. We screened a large panel of tissues and cell lines for expression of class IA PI3Ks, and document a ubiquitous expression of the p110alpha and p110beta isoforms but a variable and more restricted tissue distribution of the p110delta isoform. Originally found in WBCs, p110delta was also detected in some nonhematopoietic cell types especially those of breast or melanocytic origin, both in the untransformed and transformed state. Isoform-specific neutralization of PI3K isoforms in breast cancer cell lines (by PI3K antibody microinjection or a p110delta-selective pharmacological inhibitor) demonstrated that p110delta is the most important class IA PI3K in the regulation of epidermal growth factor-driven motility in vitro, controlling the directionality and, to a lesser extent, the speed of migration. In contrast, p110beta was required for the direction but not the speed of migration, whereas p110alpha did not impact on either of these parameters. These results show a nonredundant function of PI3K isoforms downstream of the epidermal growth factor receptor and indicate that the presence of p110delta may confer breast cancer cells with selective migratory capacities. The potential clinical implications of p110delta expression in non-WBC-derived tumors are discussed.
Biochemical and Metabolic Abnormalities in Articular Cartilage from Osteo-Arthritic Human Hips (1971)

For thirty-two areas of cartilage from nine osteo-arthritic and four "normal" femoral heads a histologic-histochemical grade was assigned as an index of severity of the osteo-arthritic process. The DNA and hexosamine concentrations were determined as indicators of cell density and polysaccharide content, respectively, and the incorporation rates of 3H-thymidine and 35SO4 were measured as indicators of synthesis of DNA and polysaccharide, respectively. From these data and the correlation analyses of them, the following information was derived: 1. Osteo-arthritis is a focal disease and there is considerable variation in the severity of the lesion on each osteo-arthritic femoral head. 2. There is excellent direct correlation between the severity of the process and the rates of DNA and polysaccharide synthesis. At a specific histologic-histochemical degree of "severity," however, the reparative mechanisms seem to "fail," and to decrease with advancing disease. 3. There is a significant inverse correlation between the severity of the process and the polysaccharide concentration, but there is no correlation between the cell density (as reflected by DNA levels) and the severity of the disease. 4. The cartilage covering osteophytes is less severely involved histologically and shows less diminution in the concentrations of polysaccharide. The synthesis of polysaccharide at these sites is increased as compared with that in non-osteophytic arthritic tissue. On the basis of these data, a scheme for the biochemical and metabolic response of cartilage to the chronic stress of osteo-arthritis is advanced.
Imaging Mitochondrial Organization in Living Primate Oocytes and Embryos using Multiphoton Microscopy (2003)

We employed multiphoton laser scanning microscopy (MPLSM) to image changes in mitochondrial distribution in living rhesus monkey embryos. This method of imaging does not impair development; thus, the same specimen can be visualized multiple times at various developmental stages. Not only does this increase the amount of information that can be gathered on a single specimen but it permits the correlation of early events with subsequent development in the same specimen. Here we demonstrate the utility of MPLSM for determining changes in mitochondrial organization at various developmental stages and show that rhesus zygotes possess a distinct accumulation of mitochondria between the pronuclei prior to syngamy. We present evidence that suggests that this pronuclear accumulation may be positively correlated with development to the blastocyst stage-in the same embryo-thereby illustrating how MPLSM can be used to correlate cellular dynamics of primate oocytes and early embryos with their developmental potential. Understanding the relationship between mitochondrial distribution and the subsequent development of mammalian embryos, particularly primates, will increase our ability to improve embryo culture technologies, including those used for human assisted reproduction.