RRID:AB_3711244

RRID:AB_10013382

AB_330248

AB_2534079

AB_2249358

AB_561053

AB_2798136

AB_2800199

AB_2534069

AB_10839118

AB_10013641

AB_2174466

AB_2160882

AB_477629

AB_2291558

AB_2128060

AB_10891442

RRID:AB_2307391

AB_10694415

RRID:AB_2338505

AB_3698765

AB_476749

plasmid_208049

Plasmid_213962

单体式与层次式如何取舍

Highlights can be created by clicking the

Filter Streams are special stream classes in Java that add extra functionality to existing input and output streams. They wrap another stream and process the data while it is being read or written.Filter streams enhance stream operations such as buffering, data conversion, and object serialization. They do not directly connect to a data source or destination; instead, they work on top of another stream

__________________

_______________

Monster - The Automatic

From an adult’s point of view, I was destructive and out of control, but as a child I didn’t think of it that way. I never wanted to destroy. I wanted to create.

I chose to have you because I wanted something to love and something that would love me unconditionally in return.”

한 가지를 제안

변비와 복통

다리 저림 증상

Several conclusions are generally true for all bonds

Discount bond

MD-1001 STGD1 44 c.6089G>A p.(Arg2030Gln) 47 c.6410G>A p.(Cys2137Tyr) - - - - - - - This study

Intersection of Stargardt Dystrophy and AIDS: A Case Report

Supplementary data. bjophthalmol-2018-312064supp004.pdf

Pt-75Mc.4539 + 2028C > Tp.[= ,Arg1514Leufs*36]c.2453G > Ap.(Gly818Glu)

Patients and Methods The protocol of the study adhered to the provisions of the Declaration of Helsinki. After informed consent was obtained, blood samples were taken and molecular analysis on the ABCA4 gene was performed as described by Maugeri et al. 14 The charts of patients with ABCA4 mutations who originally had received diagnoses of isolated or autosomal recessive CRD were reviewed. All patients originated from the University Medical Centre Nijmegen (Nijmegen, The Netherlands) and the University of Heidelberg (Heidelberg, Germany). In this study the diagnosis of CRD was based on the following criteria: initial symptoms of blurred central vision without a history of night blindness, impairment of color vision, and fundoscopic evidence of maculopathy without or with mild peripheral retinopathy. 3 4 5 7 8 In patients with recordable ERGs a cone–rod pattern of degeneration had to be present (i.e., the photopic b-wave impairment had to be greater than or equal to the scotopic b-wave amplitude impairment). Patients 9250 and 13163, who had nonrecordable ERGs, were included because their histories and clinical features were similar to those of other patients with cone–rod degeneration and they were believed to represent advanced cases of CRD. In addition to an ophthalmic examination, Goldmann kinetic perimetry routinely was performed using III-4-e and I-4-e isopters. Color vision was tested with the Ishihara and Panel D15 tests, except in patients 9369, 9378, and 10125, who were tested under conditions described earlier. 18 Because these patients were examined in two different clinics and ERGs were recorded over a long period, the methods, instrumentation, and analysis techniques of the electroretinography varied. The ERGs in patients 9369, 9378, 10125, and 11872 were performed as described by Thijssen et al. 19 The ERG method used in patients 9370, 9553, 9633, and 13163 was described by Alexandridis and Krastel. 20 The ERGs of the remaining patients (9250, 9371, and 9650) are of a more recent date and were performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards. 21 Fundus photographs were taken in most patients and some of the patients (9650, 9369, 9378, and 10125) also underwent fluorescein angiography.  Results The characteristics of 12 patients with ABCA4-associated retinal dystrophy resembling CRD are summarized in Table 1 . Most did not have affected family members, and therefore their retinal dystrophies could not be classified as autosomal dominant, autosomal recessive or X-linked. Four patients reported a brother or sister with subnormal vision. In view of the reputedly normal visual acuity of the parents and the molecular defects, the inheritance pattern of the gene defects in these patients (individuals 9303, 9369, 9553, and 13163) was classified as autosomal recessive.  The visual acuity of the patients did not exceed 20/200 and, on average, was much lower. With the exception of patient 9553, the age of onset was at or before the age of 12, and in each of the patients, blurred vision was the initial symptom. Night blindness did not occur except in patients 9378 and 10125, in the final stages of retinal degeneration. Evidence of maculopathy in the form of bull’s eye maculopathy or pigmentary changes was present in all the patients reported in this study (Fig. 1A) . The functional equivalent of the mainly centrally located retinal disease was a central scotoma, varying from 8° to more than 40°. In all but one patient, the scotoma was absolute. Only in patient 9378 was the central scotoma relative and surrounded by absolute scotomas. Fundoscopic evidence of early peripheral involvement of the retina was mild, and only in the later stages of the disease did peripheral changes characteristic of RP, such as narrowing of retinal vessels and bone spicula, occur in patients 9369 (Fig. 1B) and 10125. Similarly, mild constriction of the visual fields occurred only in two patients (9650 and 10125) and only in the advanced state. Color vision was tested in 10 patients. Six demonstrated a red–green defect, and in two of these (patients 11872 and 10125), it was accompanied by a blue-yellow defect. In the remaining four patients, color vision was so severely disturbed that the exact type of impairment could not be assessed.  The ERG recordings demonstrated degeneration of both rods and cones. When ERG responses could be elicited, the cones appeared to be affected as much as the rod photoreceptors and, in most of the patients, even more severely. The ERG responses in five patients progressively deteriorated until no photopic and scotopic responses could be recorded. In these patients, with exception of patients 9250 and 13163, ERG recordings of an earlier date were used in Table 1 . This applies to patient 9369, in whom an ERG was recorded at age 12 (all ERG responses had been nondetectable since the age of 21), patient 9378 at age 33 (all ERG responses at age 46 were nondetectable), and patient 10125 at age 8 (in 1998, at age 28, the ERG responses were no longer detectable). Recent ERG findings were not available for patients 9650 and 9371. Their ERGs were recorded in 1989 and 1985, respectively. The remaining ERG data were derived from ERG recordings performed in the past 4 years. Of patient 9371 only the ERG data in the left eye were available.  Two patients warrant a more detailed description, due to the unusual course of their retinal dystrophies. Patient 9378, at the age of 12, had blurred vision with fundoscopic evidence of irregular chorioretinal atrophy in the posterior pole. At that time, there were no peripheral abnormalities on ophthalmoscopy, and there was no history of night blindness. The ERG demonstrated an equal reduction of both cone- and rod-mediated responses. Later in life, however, fundoscopic changes developed that were characteristic of RP, and the patient reported a decrease in night vision. With fluorescein angiography partly confluent patches of chorioretinal atrophy were visible (Fig. 1C) .  The clinical picture of patient 10125 differed from that of the other patients, despite the mutation in the ABCA4 gene. Initially, disease in this patient was diagnosed as STGD because of the bull’s eye maculopathy, the granular pigment alterations in the macular area, and the pisciform flecks surrounding the posterior pole. At age 8 his visual acuity had decreased to 20/200 in both eyes. When he was referred to our clinic in 1998 at the age of 28, peripheral degeneration in the form of narrow retinal vessels and deposition of peripheral bone spicula had developed, in addition to the earlier described disease of the central retina. A fluorescein angiogram showed typical findings: a central small hypofluorescent spot enclosed by an ellipsoid—a markedly hyperfluorescent area that in turn was surrounded by hyperfluorescent dots against a dark background, most likely caused by obscuration of choroidal background fluorescence (Fig. 1D) . Early ERG recordings were not available, and the ERG tracings recorded at age 28 represent the final stage of the degenerative process, with absence of both cone and rod responses. This retinal dystrophy seemed to have evolved from STGD into more widespread retinal degeneration, resulting in loss of function of both rods and cones.  Discussion Progressive CRD is a clinically heterogeneous retinal disorder, but typical findings include reduced visual acuity, impairment of the central visual field, color vision deficits, and fundoscopic evidence of maculopathy, with no or few midperipheral retinal pigment deposits. 3 4 7 8 There is some dispute about typical ERG findings in CRD. Some state that the diagnosis of CRD must be based on the reduction or absence of cone responses in the presence of quantitatively less reduction in rod responses, whereas others state that an equal impairment of both photoreceptor systems, if accompanied by the characteristic features, suffices to justify the diagnosis of CRD. 3 7 8 22 Several propositions have been made in the past to classify cone–rod disorders. Some classification systems have focused on individual case reports and were based on nosologic aspects; others have made a distinction according to the various patterns of inheritance. 3 6 23 24 In recent studies, Szlyk et al. 7 and Yagasaki et al. 8 made use of full-field ERGs, dark adaptometry, and modified perimetric techniques to identify functionally distinct subtypes of CRD. Finally, over the past few years, a molecular genetic classification of CRD has emerged.  At the moment, four genes and three loci have been implicated in autosomal dominant CRD, whereas one X-linked locus has been described. 25 26 27 28 29 30 31 32 Thus far, two loci and one gene (ABCA4) have been associated with autosomal recessive CRD. 12 33 34 The genetic heterogeneity seen in CRD is matched by the range of the clinical findings attributed by various investigators to this type of retinal dystrophy.  Whatever the classification system used, some patients display retinal disorders that cannot be classified satisfactorily. Often, these retinal degenerations involve overlapping features. Krill et al. 5 reported that 9 of 45 patients with cone degenerations showed typical features associated with fundus flavimaculatus. Heckenlively 2 described 76 patients with cone–rod patterns on the ERG in whom retinal disease otherwise met the standard definition of RP (progressive peripheral visual field loss with ring scotoma). Alternatively, as seen in patient 10125 in this study, patients with STGD have been described who had progressive peripheral retinal degeneration with severe abnormalities in the ERG and electro-oculogram (EOG) later in life—a condition that has been described by Fishman 4 as secondary progressive cone–rod dysfunction.  The association of CRD and a dark choroid has also been described previously. 35 36 The atypical pattern of retinal degeneration with confluent patches of chorioretinal atrophy in patient 9378 resembles that in another previously described unrelated patient with CRD-like disease caused by mutations in ABCA4. 37 In the molecular genetic study by Maugeri et al., 14 in which 11 of the 12 patients with autosomal recessive CRD described in this study were analyzed, ABCA4 mutations were found in 13 of 20 unrelated patients, strongly suggesting that ABCA4 mutations are the major cause of this disorder. If this is true, the genetic heterogeneity in autosomal recessive CRD, compared with, for example, classic RP, is surprisingly low. Because autosomal recessive inheritance is believed to be the most frequent mode of inheritance of monogenic chorioretinal disorders, it is very possible that a large fraction of the patients with CRD who have been clinically studied previously carry ABCA4 mutations. In that case, the explanation for the high variability of the clinical findings in autosomal recessive CRD would not be genetic heterogeneity but rather the genotype–phenotype model for ABCA4. According to this model, there is an inverse relationship between the presumed residual ABCA4 function as an N-retinylidene-PE flippase and the severity of the disorder. 12 37 38 As a consequence, a continuum of phenotypes is to be expected, ranging from STGD to CRD to RP. Although this is probably a simplified representation of reality and needs corroboration by detailed biochemical studies of individual mutations, as described previously, this model explains why mutations in the ABCA4 gene could give rise to phenotypes that do not satisfy the standard classification of retinal dystrophies. 39   Two patients in this study may reflect borderline CRD phenotypes. Patient 9553 carries a combination of a mild (2588G>C) and severe ABCA4 mutation, which, according to the genotype–phenotype model described earlier, should be associated with STGD. We have previously discussed that most likely, one of the pathologic mutations has not yet been identified in this patient. 14 However, the age of onset in this patient (25 years) is relatively high, and although other features such as visual acuity, perimetry, and ERG findings are typical of CRD, this may indicate a relatively mild subtype. Another more convincing example of blending of ABCA4-associated phenotypes is patient 10125. The molecular findings in this patient have not yet been described elsewhere. He carries a severe splice site mutation (IVS30+1G→T) in combination with a nucleotide change leading to a stop codon at Gln1029. A patient with RP who was homozygous for the IVS30+1G→T mutation has been described, 12 whereas the Q1029X mutation has not been described. Both mutations can be considered to be null alleles. According to the proposed ABCA4 model, the clinical phenotype in patient 10125 should be RP. Instead, this patient exhibits a typical retinal dystrophy, which gradually progresses from STGD to a more widespread degeneration of photoreceptors in a cone–rod pattern later in life. At present, both rod and cone ERG responses are not detectable, indicative of a final stage similar to that in many patients with RP. Functional studies are necessary to clarify whether these specific ABCA4 mutations are responsible for the particular progression of the retinal degeneration in this patient, or whether other as yet unknown modifying factors play a role.  In this study we have described 12 unrelated patients with retinal dystrophy resembling CRD caused by mutations in the ABCA4 gene. In a previous study we described the ophthalmic features in five siblings with CRD-like retinal dystrophy who were carrying ABCA4 mutations. 37 From the clinical data of these patients and previous molecular studies in patients with autosomal recessive CRD, two important conclusions can be drawn. 12 14 First, the genetic basis of autosomal recessive CRD is less heterogeneous than was thought, based on the variability in clinical features, because mutations in the ABCA4 gene seems to be the major pathologic cause. Second, given the wide clinical spectrum of CRD-like phenotypes associated with ABCA4 mutations, detailed clinical subclassifications are difficult and may not be very useful.   Supported by the British Retinitis Pigmentosa Society, the Rotterdamse Vereniging Blindenbelangen, the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, the Stichting Blindenhulp, the Stichting de Drie Lichten, the Gelderse Blindenvereniging and the Landelijke Stichting voor Blinden en Slechtzienden and the Stichting voor Ooglijders.  Submitted for publication June 15, 2001; revised December 21, 2001; accepted January 2, 2002.  Commercial relationships policy: N.  The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.  Corresponding author: B. Jeroen Klevering, Department of Ophthalmology, University Medical Centre Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands; b.klevering@ohk.azn.nl. Table 1. View Table Patients with Cone–Rod Degeneration and ABCA4 MutationsTable 1. Patients with Cone–Rod Degeneration and ABCA4 Mutations Patient Sex Current Age (ys) ABCA4 Mutations* Visual Acuity Age of Onset (ys) Fundoscopy Color Vision Perimetry ERG Cone (μV), † ERG Rod (μV), † OD OS OD OS OD OS 9250 M 30 1622T→C; 3113C→T 194G→A CF CF 6 Pigment clumping in the macula NP Large central scotoma over 40° ND, ‡ ND, ‡ 9303 M 21 1622T→C; 3113C→T 20/400 20/400 7 Granular pigmentary changes in the macula Diffusely disturbed Central scotoma of 20° Severely decreased, § Severely decreased, § 9369 F 40 6601-6602deIAG LP LP 8 Irregular hypopigmentation, mainly in the posterior pole. In later stages: attenuated vessels and bone spicula temporal to the macula Red-green defect Central scotoma varying from 10–30° 65 (65%) 80 (80%), ∥ 140 (90%) 160 (nl), ∥ 9370 M 15 1622T→C; 3113C→T 20/200 20/200 7 Granular aspect of the macula NP Concentric central scotoma of 8° 10 (13%) 9 (13%), ¶ 29 (29%) 29 (23%), ¶ 9371 M 38 1622T→C; 3113C→T 1622T→C;3113C→T 20/400 20/400 10 Bull’s eye maculopathy Red-green defect Concentric central scotoma of 20° NP 29 (16%), ‡ NP 54 (30%), ‡ 9378 F 50 768G→T CF CF 12 Bull’s eye maculopathy, narrow vessels in periphery with mild granular changes of the pigment epithelium and confluent patches of chorioretinal atrophy Severely disturbed Large, absolute, paracentral scotomas, relative scotoma centrally 20 (20%) 30 (30%), ∥ 70 (47%) 90 (60%), ∥ 9553 F 45 2588G→C IVS35del-2→+2del4 20/400 20/400 25 Bull’s eye maculopathy. Peripheral diffuse motting of RPE Severely disturbed Large central scotoma over 40° 14 (14%) 19 (19%), ¶ 41 (41%) 24 (24%), ¶ 9633 M 22 1622T→C; 3113C→T 4469G→A 20/400 20/200 12 Atrophy of retinal pigment epithelium in posterior pole. Early stages of bull’s eye maculopathy Red-green defect Central scotoma of 20° 12 (16%) 12 (16%), ¶ 61 (62%) 39 (39%), ¶ 9650 F 20 3364G→A 20/400 20/400 5 Central granular aspect Red-green defect Large central scotoma of 30° and relative constriction of III-4 70 (39%) 106 (59%), ‡ 272 (nl) 115 (76%), ‡ 10125 M 30 IVS30+1G→T 3085C→T 20/200 20/200 8 Central hypopigmentation with dark surrounding, resembling bull’s eye. Later in life: peripheral changes characteristic of RP Severe red-green defect; mild blue-yellow defect Central scotoma of 10–15° with mild peripheral restriction 75 (75%) 80 (80%), ∥ 130 (87%) 140 (93%), ∥ 11872 M 30 634C→T 20/200 20/200 10 Bull’s eye pattern Severely disturbed; blue-yellow more than red-green Central scotoma of 25° 23 (23%) 35 (35%), ∥ 110 (73%) 95 (63%), ∥ 13163 M 15 1622T→C;3113C→T IVS36+1G→A 20/400 20/200 6 Granular aspect of retinal pigment epithelium in macula. Slightly pale optic disc Severely disturbed Central scotoma of 10–15,° no peripheral involvement ND, ¶ ND, ¶  CF, count fingers; LP, light perception; ND, not detectable; NP, not performed. *  Allele 1, first line; allele 2, second line. †  Between parentheses: percentage of the ERG value compared to the lower limit of the normality; normal ERG values are indicated nl. ‡  Minimal values for ERG recordings: 150 μV for the photopic ERG, 180 μV for the scotopic ERG. §  ERG performed with skin electrodes. ∥  Minimal values for ERG recordings: 100 μV for the photopic ERG, 150 μV for the scotopic ERG. ¶  Minimal values for ERG recordings: 99 μV for the photopic ERG, 75 μV for the scotopic ERG. Figure 1. View OriginalDownload Slide (A–D) Fundus photographs and fluorescein angiograms in eyes of patients with (atypical) CRD. (A) Patient 11872 with bull’s eye maculopathy. (B) Patient 9369, demonstrating CRD in the later stages with attenuation of the retinal arterioles and irregular pigmentation temporal to the macula. (C) Fluorescein angiograms in patient 9378 showing confluent patches of chorioretinal atrophy. (D) Patient 10125 with central hypofluorescence enclosed by an ellipsoid hyperfluorescent area. In the surrounding area, hyperfluorescent flecks are visible, and the choroidal background fluorescence seems blocked, as seen in STGD.

MD-0302 ABCA4 12 c.1622T>C p.Leu541Pro 42 c.5882G>A p.Gly1961Glu 17 Yes ABCR400

Whole exome sequencing identifies a novel splice-site mutation in IMPG2gene causing Stargardt-like juvenile macular dystrophy in a northIndian family

ABCA4-retinopathy

20/28/2/18/
female CRD c.1654 G>A
c.4363 T>C 35, 35 38,
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Disruption in Bruch membrane in patients with Stargardt disease

Modification of the PROM1 Disease Phenotype by a Mutation inABCA4

Identification of Novel Mutations in ABCA4 Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease

Sixteen patients from 13 families with signs of Stargardt macular dystrophy/fundus flavimaculatus and known mutations on both alleles of the ABCA4 gene (15 compound heterozygous, one homozygous) were characterized by clinical examination, fundus autofluorescence, psychophysics (color vision, kinetic and two-color dark- and light-adapted static threshold perimetry), and electrophysiology (Ganzfeld, multifocal ERG, EOG).

Unusual clinical phenotype of Stargardt disease

Patient 2

Additional file 2: All supplemental tables cited in the text. Enclosed data include data set meta-information, CAP scores for all drug-related genes, DRP scores for all drugs, CAP and DRP differences between populations, and a comparison between allele frequencies in the studied data set and CPIC guidelines. (XLSX 776 kb)13073_2017_502_MOESM2_ESM.xlsx (776K)GUID: B02AAF40-A613-411F-A471-357C45A33F82

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Screening of reported pathogenic variants in ABCA4 for Stargardt (STGD) The disease prevalence of STGD is estimated as 1 in 10000 individuals4. It has been estimated that about 70% of STGD patients carry variants in ABCA45. Therefore, this represents the scenario of a recessive disease with a relatively homogeneous genetic cause. We screened 945 reported pathogenic variants in ABCA4 genes collected in HGMD. Among them, 11 variants are likely benign, as their population AF in is higher than 0.7% (1/20000‾‾‾‾‾‾‾‾√)<math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="M11"><mrow><mrow><mo>(</mo><mrow><msqrt><mrow><mn>1</mn><mo>/</mo><mn>20000</mn></mrow></msqrt></mrow><mo>)</mo></mrow></mrow></math>, the cutoff based on STGD disease prevalence, therefore were excluded from further analysis. The remaining 934 variants were subjected to our test model. As a result, 26 variants with the AF in the range of 0.46% to 0.03% were identified as likely benign (Binomial test1, Bonferroni correction p-value ≤ 0.05/934 and test2 Bonferroni correction p-value > 0.05/934) (Figure 3A).

STGD-06

Double hyperautofluorescent ring on fundus autofluorescence in ABCA4

Did I leave the method to AI?

Could someone else read it and know when the job is finished?

oes my sentence describe a result, not an action?

Which result could you judge without first having to trust your own plan?

Did the one-sentence version use sources you did not name?

, “I saw what different paths my friendswent on, and I decided that I didn’t want to not go back to schoolat all.”

Mariella, for example, noted,“I didn’t have the best grades in high school, so I didn’t apply toany four- year colleges. I just thought it was a waste of time, sinceI knew that I wasn’t going anywhere real good. So that’s why I’mhere.”

Recent high school graduates, who represent the majority offirst- time community college students, tended to report that theyhad always assumed that college would be the immediate stepafter they finished high school.

well over two-thirds of first-time commu-nity college students enter with the express goal of attaining aneducational credential

students may be pursuing one of many possible goals, includ-ing transfer to a baccalaureate-granting college, certifi ca tion orlicensure in an occupation, exploration of possible career paths,avocational interests, or job- spe cific professional development.

the funda-mental character of the community college derives from the ideathat its doors are open to everyone.

Or as another student put it, “This islike high school with cigarettes.”

community colleges are heavilyin flu enced by the local and state contexts, and as a result thevariation extends across colleges as well.

one of the truisms aboutthe two- year sector is that its diversity when it comes to educa-tional missions, program offerings, and student population cre-ates a bewildering and contradictory set of policies and practiceswithin each college.

American higher education is due for reinvention, if it is to ad-dress the realities that apply to today’s students

my aim is toilluminate how college students understand their educationalpaths, what mismatches exist between their expectations andtheir professors’ expectations, and how some of the traditionalstructures and norms of higher education function as obstaclesto increased access and educational opportunity.

Thefirst of the three parts begins with an examination of students’goals, expectations, and orientation toward college.

we must uncoverstudents’ preconceptions and expectations and integrate thoseresults as we rethink course objectives and the means of accom-plishing them.

chang-ing from within requires a more comprehensive understandingof today’s college students and how to address their needs.

I contendthat accommodating the changing patterns of partici pa tion inhigher education will require orga ni za tional changes, and thatthese will benefit all college students at every level

multiple and conflicting expectations—among stu-dents and instructors—can easily lead to miscommunication inthe classroom and undermine the learning environment.

such knowledge requires awell- grounded understanding of students’ perspectives, expecta-tions, and behavior.

excellentteachers tend to assume that their students can learn at a highlevel, and that such teachers understand enough about how peo-ple learn to be able to support in-depth learning.

The other common approach is to tryto make the work easier, whether by slowing down, by break-ing the subject matter into discrete parts, or by assigning less.This strategy, however, risks focusing on low-level cognitive ob-jectives to the exclusion of higher-order thinking skills.

professors who view their stu-dents as underprepared for college tend to respond in one of twoways. One approach is to “maintain standards,” by continuingalong as usual

If a stu-dent’s style of partic i pa tion is different from the norm, for ex-ample, an instructor may believe that the student is not ascapable as the other students.

Sometimes the assumptions about appropriate socialbehavior and academic performance are class- or race- based,embodying norms and values that are not universally held oreven acknowledged.

Even in college classes, with students who have metentry- level requirements, professors lament students’ weak skillsand lack of preparation for the demands of college.

Professors were asking the class to analyze texts, butsome students were unprepared to do so, for their high schoolwork had familiarized them with summarizing and paraphras-ing, but nothing more.

I draw on interviews with more

than 120 students, conducted as part of four different researchproj ects

Being unprepared to meet certain expectations, however, is notthe same as being unable to meet them.

rooms in the 1970s, as working-class students resisted the ab-stract exercises that their professors devised.

Howard London, forinstance, observed the conflict inside community college class-

The most compelling evidence of this disjuncture emerges at theclassroom leve

The complications are perhapsmost evident at community colleges, where the diversity of stu-dents is most pronounced

Higher education’s exclusive beginnings have kept col-leges from adequately serving a greater proportion of thepopulation

My children are old enough so I can say, ‘It’s time forMom to do something she would really like.’

“A lot of people who come to thecommunity college—not half, but a lot of them—are here be-cause they don’t have the grades to get into a good college, andthe other people are here because they don’t have the money toget into a good college.

“I’ll be going here for a year and then trans-ferring to [the nearby university]. I thought it would be nice tosave a little money before I head off.”

“Really it was just finan cial. I got into severalout- of- state universities coming out of high school, but I couldn’tafford any of them. Even with academic scholarships they werestill too much money, because I have to pay for half of my owncollege

“I wanted an education,but I wasn’t ready to put forth the horsepower; I wasn’t ready toget serious about it.

In particular, he said, “I saw friends working at the pizzaplace—and I didn’t want to do that.”

“My friends had the ability to go straight into universitywithout worrying about paying. I didn’t. I lived on my own inhigh school, and so as soon as I graduated I needed to producemoney because I didn’t have any.”

For women who had left high school and started familiesyears earlier, attending college had not been part of the plan.

The three chapters take up themes that consistentlyemerged from those interviews, and provide the basis for under-standing the tensions and misunderstandings that occur insidecollege classrooms.

The explanation for the disparities lies in the fundamentalcontradiction between the elite origins of American higher edu-cation and current increased access for people previously ex-cluded.

How is it that the percentage of the popu-lation with college degrees has stayed the same over the past fourde cades

By contrast, other countries have increased their collegegraduation rates—in the case of Japan and Korea, by over 30

the number of college graduates has merely kept pace with theoverall population growth.

The Ameri-can system of providing higher education for the masses remainsan unfinished proj ect

it comprises the largest group ofdifferent types of accredited postsecondary institutions and con-stitutes the first stop for roughly half of today’s college students.In many states (thirty-five out of fifty

From this perspective, The College Fear Factor takes an un-conventional approach, focusing on the least selective and leastprestigious colleges in the country: community colleges

In a recent real-ity show, the preeminent role of the Vidal Sassoon Academy wasunderscored by its description as “the Harvard of hairdressing.

1.02倍にしかならなかったのはなぜか

疑問

実際にローカルHTTPサーバーで試すと

計算部分をExecutorへ切り出す方法もありますが、処理が各所に散らばっていると、どこで分けるか悩みます。

そこで、

毎秒1,000件で1コア分に達する計算です。

複数のイベントループで並列実行

コミュニティの

final T2T genome assembly

armston, 2002). A coach chooses observation and reflection when teachers have implement ed new practices within their own classrooms independently, are ready to examine their practice, want to reflect on the effectiveness of their teaching, want another set of eyes to help them enhance or refine their practice, or are focused on their own continuous improve- ment as professionals.

ctively observes the teaching practices and notes corresponding student behaviors.

Name: Laura Mason Date: Danan 4

Instead, they must feel prepared to respond to students at a moment’s notice.

Biological determinism holds that biological factors, and notsocial or environmental ones, are the real, main, or most signifi-cant cause of life-related phenomena.

Pretheory is problematic because it distorts research and knowl-edge. It equates testosterone to manhood/masculinity/maleness,despite the lack of empirical support for this and the presence oftestosterone in people of all gender/sexes (van Anders, 2013; vanAnders et al., 2011; van Anders & Watson, 2006).

Gender/sex is critical to social neuroendocrinology, because thepeople we study exist in evolved and socialized bodies and carryout behaviours that have evolutionary and sociocultural meaning.For example, a researcher might study testosterone and sexualdesire, but what desire involves is not universal. It can includedesire for erotic bodily pleasure as people typically presume, butalso for excitement, stress relief, feeling attractive, or more, all inways that are profoundly gendered (Chadwick, Burke, Goldey,Bell, et al., 2017; Chadwick, Burke, Goldey, & van Anders,2017).

Social neuroendocrinology explores dynamic hormone-behaviorassociations that are socially situated, and is especially useful as amodel for biobehavioral research with humans beyond binaries

ndeed, hormones are strikingly more malleablethan many social constructions, showing variability over the lifespan, days, seasons, and in response to exogenous cues that aresocial, environmental, and biochemical (Ellison, 2001; vanAnders, Goldey, et al., 2014).

Gender/sex refers to phenomena, features,and whole people where gender and sex intertwine, both could berelevant, and/or the two cannot be disentangled easily or at all, aswith whole women, men, and gender/sex-diverse people and manyaspects tied to them (van Anders, 2015; van Anders & Dunn,2009; see Figure 1). Understandings of ourselves and others arebased on a varying mix of cues that usually involve gender and sex(e.g., clothes, voice, hairstyles, facial structure).

ndeed, many sex differences in androgens and estro-gens are apparent and/or magnified only when all other sources ofvariation (like aging, diet, activity, social context, seasonality, timeof day) are held constant, leading to spurious assumptions that sexis the only or biggest source of variation (Hyde et al., 2019; vanAnders, Goldey, et al., 2014).

Accordingly, sex can be understood as biological/evolved, biomaterial, and/or bodily/physical aspects of organisms,individuals, or characteristics that can be classified as female, male,and/or sex diverse (building off of van Anders, 2015).

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Are typewriters becoming an elite hobby?

blood

F (t + Δt) − F (t)

5.149

0.1314

3.2

μ = eμ+σ2 /2 and σ2 = e2μ+σ2(eσ2− 1)

approach that is both more just and scientific, by offering biologicaldynamism, biological expansiveness/emergence, and biological con-textualism. These, in turn, help us to move beyond not just biolo-gisms, but related regressive ideologies that enact real harms topeople, groups, and hermeneutical justice or knowledge frameworks.ConclusionsHow can biobehavioral research move beyond binaries andbiologisms? In this article, I have laid out how concepts like gen-der/sex and methodological approaches like social neuroendocri-nolog

Biobehavioral research beyond biologisms offers a way to incor-porate biological parameters into psychological research beyond bio-logical determinism, reductionism, and essentialism. It offers an

Social neuroendocrinology and gender/sex can provide a usefulapproach to biobehavioral research because they offer some spe-cific ways to avoid biologism. But, like most of what I have dis-cussed in this paper, biologism is not just one thing. There arethree important and commonly discussed iterations of biologismand, moreover, three biological ways beyond them that I propose(see Figure 2).Biological determinism holds that biological factors, and notsocial or environmental ones, are the real, main, or most signifi-cant cause of life-related phenomena. It involves searching onlyfor biological causes and/or articulating explicitly or implicitlythat only biological causes matter.

The first involves “pretheory.” Pretheory refers to the cul-tural ideas that infuse scientific theory but go unrecognized,unstated, and untested; pretheory is quite literally pre (prior) totheory since theory is developed partially out of it (Lloyd, 1993).Pretheory is informed by social constructions—for example, howwe scientists study testosterone is influenced by cultural percep-tions of testosterone because these shape what we as scientiststhink about the hormone and what questions we think to ask about

Gender shapes and impacts what behaviours people engage in:competition is encouraged for men and punished for women, andespecially vice versa for nurturance. These aspects of gender canhave biomaterial consequences as per the S/P Theory, since com-petitive and nurturant behaviors are hormonally-salient (vanAnders et al., 2011). Gendered forms of engagement in competi-tive and nurturant behaviours might actually lead to differentiallevels of testosterone that overlap with gender/sex, which is why Ihave spoken of “gender?testosterone pathway” (van Anderset al., 2015). Research supports this, with evidence showing thatmany competitive behaviors increase testosterone and many nur-turant ones decrease it

Gender refers to sociocultural aspects of femininity, masculin-ity, and gender diversity, which can include minds, behavior,expression, appearance, people, relationships, structures, policies,laws, and cultures (van Anders, 2015). Accordingly, gender occursat many levels that are themselves interconnected and overlapping,such that gender is multifaceted and multiple, and can branch andcoincide. Gender shapes and constrains people’s behavior, withpractices and institutions rewarding those who meet genderexpectations and punishing those who violate them

He seemed to know us all, but he hadn’t the slightest what we were doing there, or where “there” might be—though he came up with several theories on that last point over the next two weeks, chief among them a wedding reception, a high-school poker game, and at one point, some kind of horrifyingly Kafkaesque holding cell.

4ms-400

Access to public Wi-Fi is increasingly seen as a must-have and expected amenity in buildings where the public is welcome

ConnectTO Program Update – July 2025

This means that access to government services, banking, medical appointments, social connections, and other digital tools is not evenly available to all residents

In RStudio, select Global Options from the Tools drop-down menu to make the following seven changes on three tabs.

x-analytics setup check, 2026-09-20 19:42 R 4.5.1 | RStudio 2026.06.1 | Darwin 25.6.0 | Git 2.39.5 Workspace: save never, restore false, history false (ok) Project: /Users/priya/Documents/x-analytics (ok) Folders: raw data figure session homework project-individual project-group (ok) Packages: 10 of 10 installed; xapir 0.1.0 (ok) STUDENT_DB_URL: set (ok) Class database: connected; post has 21,847 rows (ok)

'You! hypocrite lecteur!—mon semblable,—mon frère!'

Decision delay breakdown. We evaluate the impact of keyembedder model hyperparameters on decision delay. Amongthem, only the number of encoder layers and embedding sizehave an observable influence. Figure 16a and Figure 16bshow that the dominant contributor to decision delay is theinference time. Inference delay ranges from 2.2 ms to 23ms as the number of encoder layers increases from 2 to 32,and from 2.2 ms to 3.2 ms as the embedding size increasesfrom 8 to 256. For the default UNUM embedder configuration(4 encoder layers, 16 embedding size), the average decisiondelay is 2.68 ms (data collection: 38.95 ns, data movement:0.12 ms, tokenization: 0.01 ms, inference: 2.44 ms). Sinceboth Orca and Pensieve operate at coarse-grained timescalesfor control decisions, such a small added delay is acceptable

3kB - 96MB

Classical bibliographical databases have in general lostimportance compared with Internet search engines. It istoday an open question whether, for example, the tradi-tional thesaurus still has a role to fill in modern informa-tion retrieval (see Dextre Clarke and Vernau 2016). Hjør-land (2015a) argued however, that for serious scholarlypurposes it is important that users or intermediaries areable to control the search process. For such tasks, classi-cal databases seem to be the most advanced tools.

However, it is often difficult to reveal what kind of theo-retical assumption guide KOPs. Such processes are oftendone intuitively and some systems have been difficult to re-late to a theory.

Toronto’s Expanded Public Wi-Fi Strategy

Involuntary mental time travel into the future is often emotional (Barsics, Van der Linden, & D'Argembeau, 2016) and is perceived to help in decision‐making and action‐planning (D'Argembeau et al., 2011).

These studies consistently find that episodic memories contain greater sensory details and stronger feelings of traveling in time, whereas future thoughts have greater ratings of importance and emotional valence.

methods to discern the everyday frequency of episodic counterfactual thoughts have not been employed.

Past research has shown that mental time travel into the future is experienced frequently in everyday life (e.g. D'Argembeau, Renaud, & Van der Linden, 2011)

Keywords: episodic counterfactual thinking; episodic future thinking; episodic memory; mental time travel

To date, studies exploring the relationship of counterfactual thoughts with episodic memories and episodic future thoughts have focused mainly on voluntary mental time travel.

Digital Canopy

In This Section

He had touched death, but seemed to find life no less interesting for having done so.

put his mouth to a microphone in a garage in Lexington, Kentucky, and was electrocuted.

μ = αβ and σ2 = αβ2

igure 6.28: Gamma distributions

Executives: People who make business, economic, administrative, legal, governmental, or political decisions about the products.

Identifying what type of reader may be interested in your document will help you create an improved, more effective document.

Technical communication is the delivery of technical information to readers (or listeners or viewers) in a manner that is adapted to their needs, level of understanding, and background.

Related to this, mononormativity presumes that pair bonds should be between two individuals only, marginalizing (a) people with partner number sexualities beyond one, as with those in multiple relationships, as well as (b) those who are single or not interested in being in relationships with other people, as with people who are Aromantic, single-by-choice, focused on sexual-erotic contacts only and more. Mononormativity and heteronormativity both reflect a sexual normativity, that people should be and/or should want to be sexual with someone else, marginalizing Asexual people. These normativities have meant that most human biobehavioral research on partnered sexuality/relationality has focused on biologically reductionist topics, for example, which hormones account for pair bonds or will promote monogamy over “promiscuity.” Biological expansiveness/emergence offers a different approach. In SCT, people can be understood to not be sexual and/or to not have desire to be sexual with others (van Anders, 2015), or to only be connected with others in erotic but not nurturant ways, all of which accords with many lived experiences. Or, for example, the S/P Theory starts with hormones but provides a rich model for approaching pair bonds (see Figure 3) TABLES AND FIGURESView larger image > in this page > in popup window| Thumbnail view> Download Powerpoint slide (.ppt) The downloadable content is an alternative presentation to the accessible web content and may not conform to WCAG 2.1 AA.Figure 3. Models of Pair Bonds by Partner Number Outside of Biologism, Binaries, and MononormativitiesNote. J and K are each in a “two-point pair bond” (i.e., one pair bond each that is with each other). L and N are in “embedded two-point pair bonds” with M, P, or Q (i.e., one pair bond each with a partner who has a pair bond with them and another/others). M is in a “multipoint pair bond” with L and N (i.e., M has multiple pair bonds who are each in a pair bond only with M). P and Q are in “embedded multipoint pair bonds” (i.e., they have multiple pair bonds, some of whom also have multiple pair bonds). Arrows represent the direction of the bond (in this case, all partners are pair bonded with each other; in other cases, someone might be pair bonded with a partner who is not pair bonded with them). These different forms of pair bonds may have implications for hormones specifically or biobehavioral research in general, as well as other psychological, relational, behavioural, and sociocultural aspects. Adapted from “The Steroid/Peptide Theory of Social Bonds: Integrating testosterone and peptide responses for classifying social behavioral contexts,” by S. M. van Anders, K. L. Goldey, and P. X. Kuo, 2011, Psychoneuroendocrinology, 36(9), pp. 1265–1275 (https://doi.org/10.1016/j.psyneuen.2011.06.001). Copyright 2011 by Elsevier. Adapted with permission. See the online article for the color version of this figure.Figure 3. Models of Pair Bonds by Partner Number Outside of Biologism, Binaries, and MononormativitiesNote. J and K are each in a “two-point pair bond” (i.e., one pair bond each that is with each other). L and N are in “embedded two-point pair bonds” with M, P, or Q (i.e., one pair bond each with a partner who has a pair bond with them and another/others). M is in a “multipoint pair bond” with L and N (i.e., M has multiple pair bonds who are each in a pair bond only with M). P and Q are in “embedded multipoint pair bonds” (i.e., they have multiple pair bonds, some of whom also have multiple pair bonds). Arrows represent the direction of the bond (in this case, all partners are pair bonded with each other; in other cases, someone might be pair bonded with a partner who is not pair bonded with them). These different forms of pair bonds may have implications for hormones specifically or biobehavioral research in general, as well as other psychological, relational, behavioural, and sociocultural aspects. Adapted from “The Steroid/Peptide Theory of Social Bonds: Integrating testosterone and peptide responses for classifying social behavioral contexts,” by S. M. van Anders, K. L. Goldey, and P. X. Kuo, 2011, Psychoneuroendocrinology, 36(9), pp. 1265–1275 (https://doi.org/10.1016/j.psyneuen.2011.06.001). Copyright 2011 by Elsevier. Adapted with permission. See the online article for the color version of this figure. that includes but goes well beyond “two-point” pair bonds to reflect the empirical reality of partner number sexual and relational diversity, for example, pair bonds that are “embedded two-point,” “multipoint,” and “embedded multipoint” as well as two-point (van Anders et al., 2011). Biobehavioral models can thus provide ways to think expansively about sexual and relational diversity, in ways that avoid marginalizing those on the sexual margins and instead recognizing that people with diverse partner number sexualities exist, and flourish.

Biologisms are problematic in and of themselves as described above but also because of their ties to other kinds of regressive ideologies including sexism, cisnormativity, heteronormativity, and mononormativity. Biobehavioral research beyond biologisms helps to address and attend to these. For example, biological contextualism can help provide scientific approaches beyond sexism, a usually biologically essentialist ideology that fits all people into men/boys or women/girls and marginalizes women/girls. Biological contextualism makes clear how seemingly innate differences can actually reflect varied social processes. Assumptions about female biology can make this point: there are higher rates of knee injuries among women/girls playing sports than among men/boys that are typically presumed to reflect innate “female biology.” But biological contextualism highlights how these injuries can actually reflect the physical embodiment of gender inequities in access to activity, open spaces, and sport itself (i.e., that these impact knee, bone, and muscle development)—and thus relate to key questions of gender in a biobehavioral research question (why do men/boys experience fewer of these knee injuries during sport than girls/women?; Parsons et al., 2021).

Moreover, because of gender norms, behaviours may be so common that they no longer even trigger hormonal responses due to acclimatization, physiological “tolerance” or habituation, or desensitization. For example, some evidence suggests that sexual thoughts are more likely to increase testosterone in women, and nurturance to decrease it in men (Goldey & van Anders, 2011, 2012), and this may reflect the very different kinds of socialization toward sexual thoughts (natural for men! dirty for women!) and stimuli (highly prevalent images of sexualized women). As such, engaging in the “same” behaviors can impact testosterone in differential ways given how gendered contexts can change the meaning or actions of the behaviors. Gender can thus have biomaterial impacts, modulating testosterone in acute, state-like ways. Whether we have high or low testosterone might at least partially depend, not just on our genetics but what we, as gendered beings, do.

Poor heart! he had helped to bury her, and knew it not.

We went on to a farmhouse that was yet standing

Christian to be seen, nor one house left standing.

Mr. Hoar,

Context: reasons for citing it, ways it is relevant to your research question, and how it relates to other sources

You can keep organized in a variety of ways. There are citation managers like Zotero and EndNote which can help generate citations and attach notes directly to the citation information and sources.

the first paragraph alludes to public debates on immigration policy. It suggests that it may not be right to stop people from coming into America, and it may not be wrong to cross the border, even illegally.

This study provides robust evidence for the effectivenessof AI-assisted pair programming in enhancing students’intrinsic motivation, reducing programming anxiety, andimproving programming performance.